R. v. Smith Transcripts Volume 4

Court of Appeal CA040556
COURT OF APPEAL ON APPEAL FROM THE SUPREME COURT OF BRITISH COLUMBIA, FROM THE ACQUITTAL OF THE HONOURABLE MR. JUSTICE JOHNSTON, PRONOUNCED ON THE 10TH DAY OF JANUARY 2013.
REGINA
APPELLANT
v. OWEN EDWARD SMITH

RESPONDENT
TRANSCRIPT
Volume 4 (Pages 537 - 716)
Public Prosecution Service of Canada 900 - 840 Howe Street Vancouver, B.C. V6Z 2S9 Phone: (604) 775-7475 Fax: (604) 666-1599 Solicitors for the Appellant Kirk Tousaw 1135 Fisher Road Cobble Hill, B.C. V0R 1L4 Phone: (604) 836-1420 Solicitor for the Respondent
W. Paul Riley Counsel
Kirk I. Tousaw Counsel
J.C. WordAssist Ltd.

Head Office Toll Free 1-888-811-9882 Nanaimo Branch Office 250-754-7822
149345-2 Victoria Registry
In the Supreme Court of British Columbia

(BEFORE THE HONOURABLE MR. JUSTICE JOHNSTON) Victoria, B.C. January 16, 17, 18, 19, 20, 23, 24, 25, 26, 2012 February 1, 6, 7, 8, 27, 28, 29, 2012 March 1, 2012 April 13, 2012 January 10, 2013 REGINA v. OWEN EDWARD SMITH
PROCEEDINGS AT TRIAL
Crown Counsel:
P. Eccles K. Guest K. Tousaw
Defence Counsel:
Document1
J.C. WordAssist Ltd.

Head Office Toll Free 1-888-811-9882 Victoria Office 250-477-8080
INDEX
VOLUME 1 PROCEEDINGS AT TRIAL - JANUARY 16, 2012 Proceedings .......................................................................................................... 1 WITNESSES FOR THE CROWN COLIN BREWSTER ................................................................................ 12 EXAMINATION IN CHIEF ON VOIR DIRE BY MR. ECCLES: ................. 12 CROSS-EXAMINATION ON VOIR DIRE BY MR. TOUSAW: .................. 35 WITNESSES FOR THE ACCUSED LEON EDWARD SMITH .......................................................................... 42 EXAMINATION IN CHIEF ON VOIR DIRE BY MR. TOUSAW: ............... 43 PROCEEDINGS AT TRIAL - JANUARY 17, 2012 Proceedings ........................................................................................................ 76 WITNESSES FOR THE ACCUSED LEON EDWARD SMITH .......................................................................... 80 EXAMINATION IN CHIEF ON VOIR DIRE BY MR. TOUSAW: ............... 80 CROSS-EXAMINATION ON VOIR DIRE BY MR. ECCLES: ................. 140 PROCEEDINGS AT TRIAL - JANUARY 18, 2012 Proceedings ...................................................................................................... 156 VOLUME 2 PROCEEDINGS AT TRIAL - JANUARY 19, 2012 Proceedings ...................................................................................................... 157 WITNESSES FOR THE ACCUSED LEON EDWARD SMITH ........................................................................ 158 CROSS-EXAM ON VOIR DIRE BY MR. ECCLES, CONTINUING: ....... 158 RE-EXAMINATION ON VOIR DIRE BY MR. TOUSAW:........................ 212 GAYLE QUIN ......................................................................................... 217 EXAMINATION IN CHIEF ON VOIR DIRE BY MR. TOUSAW: ............. 218
ii
PROCEEDINGS AT TRIAL - JANUARY 20, 2012 Proceedings ...................................................................................................... 233 WITNESSES FOR THE ACCUSED GAYLE QUIN ......................................................................................... 242 EXAM IN CHIEF ON VOIR DIRE BY MR. TOUSAW, CONTINUING: ... 243 CROSS-EXAMINATION ON VOIR DIRE BY MR. ECCLES: ................. 270 PROCEEDINGS AT TRIAL - JANUARY 23, 2012 Proceedings ...................................................................................................... 288 WITNESSES FOR THE ACCUSED DAVID PATE ......................................................................................... 288 EXAMINATION IN CHIEF ON VOIR DIRE BY MR. TOUSAW: ............. 291 VOLUME 3 PROCEEDINGS AT TRIAL - JANUARY 24, 2012 Proceedings ...................................................................................................... 352 WITNESSES FOR THE ACCUSED DAVID PATE ......................................................................................... 352 EXAM IN CHIEF ON VOIR DIRE BY MR. TOUSAW, CONTINUING: ... 352 CROSS-EXAMINATION ON VOIR DIRE BY MR. ECCLES: ................. 356 RE-EXAMINATION ON VOIR DIRE BY MR. TOUSAW:........................ 429 PROCEEDINGS AT TRIAL - JANUARY 25, 2012 Proceedings ...................................................................................................... 435 WITNESSES FOR THE ACCUSED SANDRA LARGE .................................................................................. 435 EXAMINATION IN CHIEF ON VOIR DIRE BY MR. TOUSAW: ............. 435 CROSS-EXAMINATION ON VOIR DIRE BY MS. GUEST: ................... 459 GIOCONDA HERMAN ........................................................................... 471 EXAMINATION IN CHIEF ON VOIR DIRE BY MR. TOUSAW: ............. 471 PROCEEDINGS AT TRIAL - JANUARY 26, 2012 Proceedings ...................................................................................................... 495
iii
WITNESSES FOR THE ACCUSED GIOCONDA HERMAN ........................................................................... 495 EXAM IN CHIEF ON VOIR DIRE BY MR. TOUSAW, CONTINUING: ... 495 CROSS-EXAMINATION ON VOIR DIRE BY MR. ECCLES: ................. 499 RUTH ARTHURS................................................................................... 511 EXAMINATION IN CHIEF ON VOIR DIRE BY MR. TOUSAW: ............. 511 CROSS-EXAMINATION ON VOIR DIRE BY MS. GUEST: ................... 524 PROCEEDINGS AT TRIAL - FEBRUARY 1, 2012 Proceedings ...................................................................................................... 532 VOLUME 4 PROCEEDINGS AT TRIAL - FEBRUARY 6, 2012 Proceedings ...................................................................................................... 537 WITNESSES FOR THE CROWN HANAN ABRAMOVICI .......................................................................... 539 EXAMINATION IN CHIEF ON VOIR DIRE BY MR. ECCLES: ............... 539 CROSS-EXAMINATION ON VOIR DIRE BY MR. TOUSAW: ................ 556 PROCEEDINGS AT TRIAL - FEBRUARY 7, 2012 Proceedings ...................................................................................................... 619 WITNESSES FOR THE CROWN HANAN ABRAMOVICI .......................................................................... 619 CROSS-EXAM BY MR. TOUSAW ON VOIR DIRE, CONTINUING: ...... 619 VOLUME 5 PROCEEDINGS AT TRIAL - FEBRUARY 8, 2012 Proceedings ...................................................................................................... 717 WITNESSES FOR THE CROWN HANAN ABRAMOVICI .......................................................................... 717 CROSS-EXAM BY MR. TOUSAW ON VOIR DIRE, CONTINUING: ...... 717 RE-EXAMINATION BY MR. ECCLES ON VOIR DIRE: ......................... 738
iv
PROCEEDINGS AT TRIAL - FEBRUARY 27, 2012 Proceedings ...................................................................................................... 783 PROCEEDINGS AT TRIAL - FEBRUARY 28, 2012 Proceedings ...................................................................................................... 784 PROCEEDINGS AT TRIAL - FEBRUARY 29, 2012 Proceedings ...................................................................................................... 785 PROCEEDINGS AT TRIAL - MARCH 1, 2012 Proceedings ...................................................................................................... 786 PROCEEDINGS AT TRIAL - APRIL 13, 2012 Proceedings ...................................................................................................... 787 PROCEEDINGS AT TRIAL - JANUARY 10, 2013 Proceedings ...................................................................................................... 791
EXHIBITS
EXHIBITS ON VOIR DIRE EXHIBIT 1: Admissions filed January 16, 2012 ............................................. 3 EXHIBIT 1-A: Amended Admissions filed January 17, 2012 ........................... 76 EXHIBIT 2: Crown's Book of Photographs ................................................... 14 EXHIBIT 3: Victoria Police Department Exhibit Flow Chart .......................... 17 EXHIBIT 4.1: Original Analyst Report No. 09 14838 V ................................... 30 EXHIBIT 4.2: Original Analyst Report No. 09 14835 V ................................... 30 EXHIBIT 4.3: Original Analyst Report No. 09 14839 V ................................... 30 EXHIBIT 4.4: Original Analyst Report No. 09 14803 V ................................... 30 EXHIBIT 4.5: Original Analyst Report No. 09 14804 V ................................... 30 EXHIBIT 4.6: Original Analyst Report No. 09 14805 V ................................... 30 EXHIBIT 4.7: Original Analyst Report No. 09 14806 V ................................... 30 EXHIBIT 4.8: Original Analyst Report No. 09 14807 V ................................... 30 EXHIBIT 4.9: Original Analyst Report No. 09 14808 V ................................... 30 EXHIBIT 4.10: Original Analyst Report No 09 14809 V .................................... 30
EXHIBIT 4.11: EXHIBIT 4.12: EXHIBIT 4.13: EXHIBIT 4.14: EXHIBIT 4.15: EXHIBIT 4.16: EXHIBIT 4.17: EXHIBIT 4.18: EXHIBIT 4.19: EXHIBIT 4.20: EXHIBIT 4.21: EXHIBIT 4.22: EXHIBIT 4.23: EXHIBIT 4.24: EXHIBIT 4.25: EXHIBIT 4.26: EXHIBIT 4.27: EXHIBIT 4.28: EXHIBIT 4.29: EXHIBIT 4.30: EXHIBIT 4.31: EXHIBIT 4.32: EXHIBIT 4.33: EXHIBIT 4.34: EXHIBIT 4.35: EXHIBIT 4.36: EXHIBIT 4.37: EXHIBIT 4.38: EXHIBIT 4.39: EXHIBIT 4.40: EXHIBIT 4.41: EXHIBIT 5: EXHIBIT 6: EXHIBIT 7: EXHIBIT 8: EXHIBIT 9: EXHIBIT 10:
Original Analyst Report No. 09 14810 V ................................... 31 Original Analyst Report No. 09 14811 V ................................... 31 Original Analyst Report No. 09 14812 V ................................... 31 Original Analyst Report No. 09 14813 V ................................... 31 Original Analyst Report No. 09 14814 V ................................... 31 Original Analyst Report No. 09 14815 V ................................... 31 Original Analyst Report No. 09 14816 V ................................... 31 Original Analyst Report No. 09 14817 V ................................... 31 Original Analyst Report No. 09 14818 V ................................... 31 Original Analyst Report No. 09 14819 V ................................... 31 Original Analyst Report No. 09 14820 V ................................... 31 Original Analyst Report No. 09 14821 V ................................... 31 Original Analyst Report No. 09 14822 V ................................... 31 Original Analyst Report No. 09 14823 V ................................... 31 Original Analyst Report No. 09 14824 V ................................... 31 Original Analyst Report No. 09 14825 V ................................... 31 Original Analyst Report No. 09 14826 V ................................... 32 Original Analyst Report No 09 14827 V .................................... 32 Original Analyst Report No. 09 14828 V ................................... 32 Original Analyst Report No. 09 14829 V ................................... 32 Original Analyst Report No. 09 14830 V ................................... 32 Original Analyst Report No. 09 14831 V ................................... 32 Original Analyst Report No. 09 14832 V ................................... 32 Original Analyst Report No. 09 14833 V ................................... 32 Original Analyst Report No. 09 14834 V ................................... 32 Original Analyst Report No. 09 14836 V ................................... 32 Original Analyst Report No. 09 14837 V ................................... 32 Original Analyst Report No. 09 14840 V ................................... 32 Original Analyst Report No. 09 14841 V ................................... 32 Original Analyst Report No. 09 14842 V ................................... 32 Original Analyst Report No. 09 14843 V ................................... 32 DVD containing scene video images......................................... 34 City of Victoria Proclamation "International Medical Marijuana Day" ........................................................................................ 112 Letter from Office of the Mayor of Victoria, B.C. to Tony Clement dated March 20, 2006 ............................................... 116 Letter to Leon Smith from Susan Fletcher, July 27, 2005 ....... 117 Letter from Leon "Ted" Smith to Susan Fletcher dated January 4, 2006 ...................................................................... 119 Letter to Ujjal Dosanjh from Leon "Ted" Smith dated February 3, 2005 ..................................................................... 121
vi
EXHIBIT 11: EXHIBIT 12: EXHIBIT 13: EXHIBIT 14: EXHIBIT 15: EXHIBIT 16:
EXHIBIT 17: EXHIBIT 18: EXHIBIT 19: EXHIBIT 20: EXHIBIT 21: EXHIBIT 22: EXHIBIT 23: EXHIBIT 24: EXHIBIT 25: EXHIBIT 26: EXHIBIT 27: EXHIBIT 28: EXHIBIT 29:
EXHIBIT 30:
EXHIBIT 31: EXHIBIT 32:
Letter to Leon Smith from Beth Pieterson, dated February 24, 2006 ................................................................... 124 Letter to Tony Clement from Leon "Ted" Smith dated August 1, 2006 ........................................................................ 128 Letter to Leon Smith from Susan Russell dated September 26, 2006................................................................ 130 Letter to Tony Clement from Leon "Ted" Smith dated January 3, 2007 ...................................................................... 133 Letter to Leon "Ted" Smith from Ronald Denault dated 2008-06-03.............................................................................. 137 Letter to Tony Clement on International Hempology 101 Society letterhead dated December 4, 2007 (was Exhibit B for identification) ...................................................................... 139 Cannabis Buyers' Club of Canada informational pamphlet ..... 176 Cannabis Buyers' Club of Canada - Medicinal Cannabis Recipe Book............................................................................ 258 Breast imaging report - exam date 18-Apr-2011 ..................... 260 Histopathology Report for Gayle Quin..................................... 261 Prescription sheet from Dr. Roland Graham dated November 28, 1997................................................................. 261 Urine Toxic Metals report of Dr. Peter Nunn dated August 12, 2002 ...................................................................... 262 Letter from Dr. Kristen Bovee dated January 6, 2012 ............. 266 Package of documents including original affidavit of Dr. Pate, curriculum vitae, list of publications and two studies ............... 290 Colour photograph of close-up depicting female flower of cannabis plant ......................................................................... 301 Macro colour photograph of close-up of leaf surface .............. 302 Macro photograph depicting isolated trichomes ...................... 319 1 page photocopy of prescriptions prescribed to Sandra Large ....................................................................................... 455 5-page document from St. Joseph's Health Care entitled, "Regional Evaluation Centre Multidisciplinary Health Care Assessment ............................................................................ 472 Document from St. Joseph's Health Care, Regional Evaluation Centre Multidisciplinary Health Care Assessment - Final.................................................................. 476 Copy of report from St. Joseph's Health Care dated March 28, 2002 ....................................................................... 476 3-page letter dated May 7, 2004 addressed to Dr. Patricia Morley-Forster ......................................................................... 478
vii
EXHIBIT 33: EXHIBIT 34: EXHIBIT 35: EXHIBIT 36: EXHIBIT 37: EXHIBIT 38: EXHIBIT 39: EXHIBIT 40: EXHIBIT 41:
EXHIBIT 42: EXHIBIT 43: EXHIBIT 44:
1-page copy of document from London Health Services dated July 22, 2004 ................................................................. 484 1-page document from Vancouver Island Health Authority dated May 6, 2009 .................................................................. 485 3-page copy of fax dated May 11, 2005 from Dr. Laurence Jerome Re: Gina Herman ....................................................... 487 1-page document of Prescription Authorization Request printed on January 20, 2012 re Herman, Gioconda ................ 488 4-page copy of document entitled Form B1 ............................ 493 Copy of letter from Dr. Grimwood to Mr. Brooks re Ruth Ann Arthurs dated April 15, 2010 ................................................... 515 1-page copy of assessment form for Life Mark Physiotherapy re Ruth Arthurs dated March 17, 2010 ............ 517 Affidavit of Hanan Abramovici ................................................ 556 "Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain" ................................................................ 721 "Adverse effects of medicinal cannabinoids: a systematic review" .................................................................................... 726 Large cerlox bound volume, affidavit of Eric Ormsby .............. 755 Curriculum vitae of Eric Ormsby ............................................. 765
EXHIBITS FOR IDENTIFICATION ON VOIR DIRE EXHIBIT A: Cannabis Buyers' Club of Canada, Product Guide ................. 102 EXHIBIT B: Letter to Tony Clement on International Hempology 101 Society letterhead dated December 4, 2007 ........................... 136 EXHIBIT C: Binder of Health Canada MMAR information .......................... 194 EXHIBIT D: Affidavit of Dr. Harold Kalant sworn April 3, 2008 ................... 412
RULINGS
Plea ...................................................................................................................... 2 Ruling re re Ban on Publication .......................................................................... 10 Order re Exclusion of Witnesses......................................................................... 11 Ruling re admissibility of document .................................................................. 100 Ruling re admissibility of document .................................................................. 115 Ruling re admissibility of document .................................................................. 119 Ruling re admissibility of question on re-examination ....................................... 214 Ruling re Qualification of Witness re Pate ........................................................ 291
viii
[RULING RE ADJOURNMENT APPLICATION] ............................................... 533 Ruling re Qualification of Witness re Abramovici .............................................. 538 Ruling on Voir Dire ............................................................................................ 787 Ruling on Voir Dire ............................................................................................ 788 Re-Election ....................................................................................................... 791 Plea .................................................................................................................. 794 Reasons for Judgment re Acquittal ................................................................... 795
537 Proceedings
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Victoria, B.C. February 6, 2012 THE CLERK: Calling the matter of Her Majesty the Queen against Owen Edward Smith, My Lord. MR. ECCLES: May it please the court, Peter Eccles, E-c-c-l-e-s, appearing for the Federal Crown in this matter. MS. GUEST: My Lord, K. Guest, G-u-e-s-t, on behalf of the Federal Crown as well. THE COURT: Thank you. MR. TOUSAW: My Lord Tousaw, T-o-u-s-a-w, first initial K. I appear for Mr. Smith, who is present in the back of the courtroom. THE COURT: All right. Thank you. Mr. Eccles. MR. ECCLES: Thank you, My Lord. The Crown now asks to call Dr. Hanan Abramovici and will be seeking to qualify Dr. Abramovici as an expert witness, able to assist the court by offering opinion evidence in the following areas, and I've had the clerk hand to Your Lordship a copy of Dr. Abramovici's report with Tab C removed and references to Tab C in the body of the report have been redlined out. I will be seeking to qualify Dr. Abramovici in the areas -- the following three areas. First, cannabis, its pharmacology, its absorption and its distribution in the body on ingestion. Secondly, the pharmacological actions of cannabinoids and cannabis and the therapeutic and adverse effects that can be a consequence of its use. THE COURT: All right. Slow down. Give me that one again. MR. ECCLES: I'm sorry, My Lord. The pharmacological actions of cannabis -- cannabinoids, sorry, and cannabis and the therapeutic and adverse effects that can be a consequence of its use. And finally, the medicinal aspect of cannabinoids. THE COURT: Is there an issue over Dr. Abramovici's qualifications to give opinions in these areas, Mr. Tousaw? MR. TOUSAW: No, My Lord. Any issues the defence has goes to weight. THE COURT: All right. Thank you. Is his CV attached? MR. ECCLES: Yes it is, My Lord. His CV is at Tab B.
538 Proceedings
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Tab A is a list of the references that Dr. Abramovici makes within the body of his report. Tab B is his CV. THE COURT: I'm satisfied, having reviewed Dr. Abramovici's curriculum vitae that by training, education and experience, he is qualified to give opinions on the areas in which he is tendered and that is on cannabis, including its pharmacology, absorption and distribution in the human body; the pharmacological actions of cannabis or cannabinoids and its therapeutic and adverse effects; and finally, the medicinal aspects of cannabis or cannabinoids. MR. TOUSAW: My Lord, I only rise to clarify my friend's indication that he's redlined some of the paragraphs of Dr. Hanan Abramovici's report and I just want to make sure we're working from the same set of documents because what I have is the one that does not have redlining. MR. ECCLES: For my friend's ease of reference, it's all paragraph 4 and paragraph 5, in their entirety I've redlined out. In addition, at paragraph 40, I've redlined out the reference, the first portion of paragraph 40 at paragraphs 15 to 20 of his affidavit, attached to his -- hereto as Exhibit C. Paragraph 40 will now read: Dr. Kalant speaks to the quality issues that would have to be addressed before marihuana should be used as therapeutic agents. I concur with his views as expressed in these paragraphs which I reproduce below for ease of reference. MR. TOUSAW: My Lord, the only issue is that my understanding was that we would not be -- my friend would not be making reference to the Dr. Kalant material or incorporating it by reference. I expect that that problem could be solved simply by removing all of the preface of paragraph 40 and simply saying I hold the following views. But it seems a bit problematic to leave in the reference to Dr. Kalant in this affidavit. THE COURT: If I simply read it as, "These are my opinions," although he's expressed it as adopting something that's not before me.
539 Proceedings
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
MR. THE MR. MR.
TOUSAW: Yes. Yes. COURT: Problem solved. TOUSAW: The accused is satisfied with that. ECCLES: And I do propose to clarify that with Dr. Abramovici once he's on the stand, My Lord. THE COURT: Yes. MR. ECCLES: I'd now call Dr. Abramovici. THE CLERK: Will you be swearing on the Bible? HANAN ABRAMOVICI: No. HANAN ABRAMOVICI a witness called for the Crown, affirmed. THE CLERK: Please state your full name and spell your last name for the record. A My first name is Hanan, H-a-n-a-n. Last name Abramovici, A-b-r-a-m-o-v-i-c-i. THE COURT: You may be seated, Dr. Abramovici. A Thank you. EXAMINATION IN CHIEF ON VOIR DIRE BY MR. ECCLES: Q A Q A Q Dr. Abramovici, the doctorate you hold is a PhD, correct? That is correct. You don't have an MD or a medical doctorate, your specialty is neuroscience in particular, correct? That's correct. I understand that you embarked on your education initially at McGill University in Montreal where you graduated with a Bachelor of Science in Physiology in 1997, is that correct? Correct. What was it that you studied in the course of your Bachelor of Science in Physiology, what does that cover? It's covers multiple -- multiple disciplines, anatomy, physiology, biochemistry, chemistry. All the life sciences. And I understand when you finished your Bachelor of Science in Physiology, you then went on to do a Masters in Pharmacology, correct? That's correct. During my -- I would just like to clarify that during my Bachelor of Science in Physiology, I also took courses in pharmacology and that was -- I had an interest in pharmacology
A Q A Q A
540 VOIR DIRE Hanan Abramovici (for Crown) in chief by Mr. Eccles
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
from that point on and I went to pursue a Masters in Pharmacology at the University of Toronto. Q And I understand you took -- completed your Masters in 1999, correct? A That's correct. Q You graduated in June, you defended your thesis is December? A Yes. Q December of '99 or the December before graduation? A December of '99. Q And what was your Masters in, what was your area of study? A It was studying N-Acetyltransferases which are -THE COURT: Sorry. Could you speak up, sir, I can't hear that. A Sure. Sorry. My apologies. My area of study in my masters was N-Acetyltransferases and drug metabolism. MR. ECCLES: Q Now, what is N-Acetyl -- I won't try the second word. A N-Acetyltransferases. Those are enzymes that are found in the liver that are involved in a variety of drug metabolic -- or drug metabolism. Q And in sort of terms that a lawyer like me can understand, is this drug mechanisms? You're studying drug mechanisms and how they work? A During my Masters? Q Yes. A I was studying, in a broader sense, how substances that are absorbed by the body are metabolized or transformed by the body. Q And I understand once you obtained your Masters in Pharmacology, you pursued further studies and ultimately obtaining your PhD in Neuroscience from the University of Ottawa, correct? A That's correct. Q And referring to your CV which is at tab -- do you have a copy of our report in front of you? A Sorry. What tab is it at? Q Tab B. And I just -A Yes. Q -- wanted to clarify something. You've broken down your CV into languages. Your areas of expertise is covered by your CV which are molecular and cellular biology; protein biochemistry, pharmacology, physiology,
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q
A Q A
A Q A Q A Q A
neuroscience and drug abuse research, correct? Yes. And then under the heading professional experience, from 2002 to 2010 -- or sorry, from 02-2010, February 2010 until now and still, you're the Senior Scientific Information Officer, Office of Research and Surveillance Controlled Substance and Tobacco Director at Healthy Environments and Consumer Safety Branch of Health Canada, correct? Correct. And prior to that, just looking at the second page of your CV, your Bachelor of Science in Physiology at McGill is '94 to '97. Your Masters of Science is '97 to 2000. And then as I understand it, from August 2000 to August 2001, you were employed at Promega Corporation, Madison, Wisconsin, correct? Yes. What is Promega Corporation? Promega Corporation is an American biotechnology company that generates or produces chemical agents for life science research, specifically in the areas of molecular biology and protein biochemistry. And under the description we have here, "Provided internal and external scientists with scientific guidance, technical support and troubleshooting expertise to help them solve a wide range of experimental problems." You acted as a liaison between customers in the business development groups, communicating customer concerns and ideas to departments that could address them, correct? That is correct. And you participated in the launching of new products, analyzing product value, benefits, drawbacks, potential pitfalls and problems? Yes. What -- you've described the products, what -what is that? I have no idea what you meant? What are the products, you mean? Yes. These are -- these are reagents such as enzymes or proteins or other chemical agents that are used by research scientists in universities and in industry to address problems in molecular biology, research and life science research. These are the tools that scientists use to answer the questions -- life science researchers use to
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q A Q A Q A
Q A
Q A
Q A Q A Q
answer the questions that they pose. And you worked there for one year? That is correct. And then you went on to do -- commence your postdoctoral studies? My doctoral studies. Doctoral -- sorry. Your doctoral at U of Ottawa? That's right. And your doctorate is in neuroscience. Was that your particular area of study or was that just who supervised you? I was -- I was in the Department of Neuroscience. My professor, my supervising professor was appointed to the Department of Neuroscience and I carried out research that was related to neuroscience but I also covered other areas as well. Now, research in relation to -- what is the nature of research in the neuroscience field that you were doing? I was looking at principally the molecular mechanisms underlying a particular neurological or neurophysiological disorder known as Duchenne's muscular dystrophy. What was the nature of the work you were doing? What were you looking for? We were trying to understand the molecular mechanisms, in other words, what is going on inside the cells of the -- of the disease -- or the diseased cells or the conditions. We were trying to understand what's going wrong with the molecular mechanisms inside those tissues or cells in order to eventually get an answer to eventually develop a therapy to help patients with Duchenne muscular dystrophy. Was the bulk of your work on your doctorate, your post-doctorate, your PhD, was that laboratory work, library work? The bulk of my scientific career, graduate and post -- graduate and postgraduate was laboratory based research. Now, Health Canada, how did you end up working there? I was hired at Health Canada based on my qualifications. Those were knowledge in the area of pharmacology, physiology and neuroscience. And what is it that you -- what is your job at
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q
Q A
Health Canada? Are you in a lab or are you -well, I'll back up. Promega Corporation, were you in the lab or were you liaising with scientists, research groups, customers, were you the buffer between the pure science and the customer, or were you the pure science? I had multiple roles in my job there. Principally, I didn't work in a lab but I did occasionally work in the lab at Promega to address certain questions or concerns that were posed by customers of the company but my job there was mostly an office -an office job or an office position, discussing experimental problems or questions that customers of Promega Corporation had. And at Health Canada, your current duties there, are you primarily in a lab or are you a mix of lab and non lab work, or what -- what is it that you do there? My position at Health Canada is office based. I don't do any laboratory research and my function is to collect, analyze and summarize the scientific and medical information on controlled substances and drugs of abuse. And amongst the controlled drugs and substances of abuse that you gather information, is cannabis one of those? Yes. Now, I understand, returning to your report, your affidavit there, Tab G of the affidavit is a document that's available on the Health Canada website entitled Information for Health Care Professionals. And at the bottom of the page on Tab G, date of latest version September 2010. Did you have any part to play in the creation of this document in the course of your professional employment? I did. When I began working at Health Canada, one of my projects was to update the Information for Health Care Professionals marihuana document. That was posted on the website, on the Health Canada website and so the document in Tab G is a document that I wrote. And I updated it, based on the information that was previously there, made it up to date. Did you have a previous document to work from, or was this reinventing the wheel from scratch? There was a document that I worked from but I felt
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q
that it was necessary to rework most of the document. And if we look to the back of the document, there seem to be 476 footnotes or references set out with -- as the reference list at the end of the document, correct? Correct. And then if we read the actual document itself, there will be reference numbers after various sentences within the document in brackets. Are those references to the reference list? Yes. So for example, just taking one off the top, page 7 of the document under the heading pharmacokinetics-pharmacodynamic relationships. The first sentence reads: The temporal relationship between plasma concentrations of THC and the associated psychotropic, cognitive and motor effects is unclear. And then there's a reference to 93 and 94. And if we look at the list of references, at 93 and 94 we have a study by Cone and Heustis (1993) Relating blood concentrations of tetrahydrocannabinol and metabolites to pharmacologic effects and time of marijuana usage. The publication is the Therapeutic Drug Monitor and then there's a reference. And at 94 is Harder and Rietbrock, Concentration-effect relationship of Delta-9-tetrahydrocannabiol and prediction of psychotropic effects after smoking marijuana, and a journal reference, International Journal of Clinical Pharmacology Therapy, I believe, is that right? And Therapeutics. Therapeutics, and then the reference. So if the reader wants to check the statement they can, I take it, go get that article and double check it, is that correct? Yes. Four hundred and seventy-six references. Do you have to check every one of those references before you footnoted them? Yes.
A Q
A Q A
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q
A Q A Q
A Q A Q
A Q A Q A Q A Q
Was this a time-consuming process? Very. How long did it take you to -- to get the document into the format we see it in, in the -- on the web or at Appendix G? How much time did you actually have to spend to write this thing? If I remember correctly, probably about three months full-time. And that's five days a week, 40 hour week? Yes. Weekends sometimes as well. Now, returning to your CV, I take it that would be an example of what you do as the Senior Scientific Information Officer at Health Canada, that's one example? Yes. One example. Do you assist or provide advice or summarize and disseminate within Health Canada information on other drugs that are abused? Yes, if required. Prior to your work at Health Canada, during your Bachelor of Science, your Masters or your PhD studies, had you done clinical or laboratory work with cannabis or its derivatives? No. Did your specific knowledge of cannabis and derivatives, was that something you began to develop when you worked at Health Canada? Yes. And thats when your focus on that area began? Yes. Bringing to bear your previous education? Yes. What was the goal of the Information for Health Care Practitioners, what were you -- or Health Care Professionals, I should say, what were you trying to create with that document? The purpose of this document is to provide, as much as possible, the complete knowledge of the scientific and medical literature on cannabis and cannabinoids to health care professionals, but this document can also be used by scientists and the public as it is available on the Health Canada website. Now, turning to your actual report, you were asked by Health Canada to assist in this case by providing a written report dealing with the report or replying to a report prepared by a Dr. David W.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q
A Q
A Q A Q A
Q A Q A Q A Q
Pate, correct? Correct. And in the course of reviewing and responding to Dr. Pate's report, you had available to you the report itself and that was made available to you on January the 19th of this year, correct? I believe so, yes. And then if we turn to your actual written report, the response to the report of Dr. Pate starts at paragraph 3 and just for ease of reading the report, is it fair to say you've gone through Dr. Pate's report and responded to specific assertions that he makes? Yes. So for example, paragraph 8, the term therapeutically -- therapeutically active compounds used by Dr. Pate at paragraphs 9 and 10, you've commented regarding the use of that phrase as being perhaps inappropriate because there are two sides to the coin? That's correct. There are two sides to the coin. What's the flipside of therapeutic? The flipside would be the adverse effects of these substances. And what would the adverse effects be that are -from your review of the literature? There are a broad range of adverse effects, those can include anxiety, panic attacks, hallucinations, paranoia, altered perception, effect on cognition, psychomotor impairment impairing driving, operating complex machinery, vomiting, headaches. Most of those effects, I believe, are summarized in my affidavit in paragraph 41. So that's disorientation -That's right. -- confusion, dizziness? What's ataxia? Lack of coordination. So basically being klutzy? Yes. Anxiety, agitation, increased heart rate, low blood pressure, euphoria, depression, hallucinations, paranoia, psychosis dependence, psychomotor impairment. It's a general phrase. What's covered under psychomotor impairment? Psychomotor impairment generally means inability to coordinate between cognitive processes and
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q A Q A Q A Q A
A Q A Q A Q
motor processes. An example of that would be driving a car, operating complex machinery, operating a plane, riding a bike. Those are examples of psychomotor impairment. And then cognitive impairment is simply -- impairs the ability to think sometimes? That's correct. And some of these effects in recreational users from the literature you've read, I take it, are not considered adverse, they're what is desired? In some cases. For medical use, why would these be a problem? These would be a problem because -- are you talking about the effects listed there -Yes. -- in their -The effects listed at paragraph 41. There's quite a list but -Right. Well, they would be undesired for medical purposes, if you want to improve your health you wouldn't want to experience any of these adverse effects because you may be experiencing some of these -- some of these effects or other disorders in the first place, so you wouldn't want to exacerbate your condition. Now, returning to your report, that's, you know, paragraph 8 as an example. Paragraph 9 you refer to the where glandular -- active compounds are secreted only in the glandular trichomes and you've set out the research in Dr. Pate's publication at paragraph 9, is that correct? Yes, correct. And in paragraph 10 you comment on several cannabinoids, the actual number is more than 70, seven zero, correct? Correct. So several is a imprecise phrase, fair to say? Yes. Paragraph 12, you comment -- of your paragraph, on paragraph 14 of Dr. Pate's: Terpenes may very well augment these effects. -- and when referring to so-called medical effects of cannabinoids and you refer to this statement as being speculative. Were you able to find any literature, any clinical trials, any studies, even
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
anecdotal to support that assertion that terpenes may very well augment the effects of cannabinoids or cannabis? I think that statement is anecdotal in nature. There are no scientific studies or clinical trials that I know of that have demonstrated that terpenes augment these effects. At paragraph 13 you comment on Dr. Pate's assertion at paragraph 15: Different strains are reputed to produce different effects on the patient, depending on the individual and condition. Again, you couldn't find any scientific studies to support this assertion? There are no scientific studies that I know of that support that assertion. And the same for your comments at paragraph 14 as to Dr. Pate's comments at paragraph 16 of his report? Yes. And the same for paragraph 17 of Dr. Pate's report that: Various compounds can produce synergistic effects. Any one compound in isolation may not provide the full spectrum of medical benefits sought by the patient. And were you able to find any literature to support that? No. As a hypothesis to explore through research, does that appear a viable hypothesis to explore? I think it would be an interesting hypothesis to explore if I was a research scientist in the field. Paragraph 21 of your report at page 5, you reference -- Dr. Pate refers to glandular trichomes in relation to female plants but the glandular trichomes can also be found in male plants on the leaves and not just on the flowers, and then you cite Dr. Pate's study -- Dr. Pate's publication: Roots contain trace amounts. Stocks,
A Q A Q
A Q A Q
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
branches and twigs have greater quantities, although not as much as leaf material. Vegetative leaf contains varying quantities, depending on its position on the plant. Lower leaves possessing less, upper ones more. Is that -- from your review of the literature, does Dr. Pate's description there accord with the balance and the bulk of the testing of cannabis for distribution -- distribution of the trichomes? A Yes. Q And then at paragraph 22, 23, you reference some of the difficulties with the petrochemical or ether -- petroleum ether technique for extraction of resin from glandular trichomes and that there are significant risks? A Yes, there are significant risks associated with this extraction process. Q And you've cited some articles relating to extensive burning suffered by individuals who are caught in fires that can result from these sort of extraction processes? A That's correct. Q Paragraph 24 of your report, commenting on Dr. Pate's paragraphs 24 and 25, you describe Dr. Pate from -- while not stating so directly, impliedly claims the plant matter can contain a variety of harmful or unwanted compounds which may include heavy metals, fertilizer residue, pesticides, molds and insect remnants, while the glandular trichomes are somehow spared from such contamination. Were you able to find any research anywhere to suggest that glandular trichomes would not be contaminated if the plant matter itself was? MR. TOUSAW: My Lord, at this point I'm going to rise to object to that question and in particular, that paragraph. It appears to me to be a paragraph relating to botany and/or the growth of the cannabis plant and not one related to pharmacology or any areas that this expert has been qualified in. MR. ECCLES: In my respectful submission, My Lord, the expert is qualified in pharmacology, absorption and distribution of cannabis, the pharmacological actions of cannabinoids and cannabis, therapeutic
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
and adverse effects that can be a consequence of its use. That would include the ingestion through cannabis of whatever is in the plant material that creates a potential adverse effect. It doesn't -in my respectful submission, it doesn't require a botany degree. It requires the knowledge of pharmacology, which is not confined to purely chemically produced matter. It includes natural products that have pharmacological actions. MR. TOUSAW: My Lord, I think what the witness says here at paragraph 24 is: Since heavy metals and fertilizers are usually found in the soil and absorbed by the plant.... -- to me, that's a botanical statement: ...it seems unlikely that the glandular trichomes would not contain any of these substances. Besides being speculative, and it is purely a speculative comment, again, that's about the botany of the plant and what's happening in the plant. It has nothing to do with what's absorbed by the human body. THE COURT: It seems to me the defence has a point. That Dr. Abramovici's qualifications relating to absorption and the rest of it are focused on the human bodies dealing with the various chemical substances and that this opinion does stray into the field of botany. Some of it may be common sense but some of it does require the expertise of a botanist and/or the knowledge of how plants deal with and extract from the soil those compounds and substances that they either rely upon to grow or take up accidentally or coincidentally. I think that does go beyond Dr. Abramovici's qualifications. MR. ECCLES: Certainly, My Lord. Q Then I'll move on to paragraph 25. You comment on Dr. Pate's statement in his report at para 26 that plant matter may be contraindicated for persons with gastrointestinal conditions. Were you able to find any scientific literature, clinical trials or studies to support that sort of an assertion?
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
No. Just turning to paragraph 35 at page 8, you comment on Dr. Pate's report: An added benefit is the elimination of psychoactive side effects through topical administration. You comment there's simply no scientific evidence to support these claims. Some evidence to suggest the contrary and then you set out studies you've reviewed in the course of your review of the literature and you have a study by Touitou in '87, Valiveti in 2004, Izzo in 2009 and Cichewicz in 2005. Are these studies that are also contained within the materials you prepared as health -- guide for health care practitioners? Some of them may be. I'm not sure if all of them are there. And transdermal delivery, what is transdermal delivery method? Transdermal delivery refers to the transport of drugs across the skin. What are the general methods of transdermal delivery of a therapeutic compound to an individual? Well, generally speaking, when we refer to transdermal delivery we're talking about a patch would could be applied to the skin in order to deliver the drug into the body. Like a nicotine patch? That's correct. What about transdermal delivery by infusing olive oil and then rubbing the olive oil onto the skin with cannabinoids in particular or cannabis? Sorry. Can you clarify the question? Well, a patch, a transdermal patch is one method of delivery. What about delivering through simply cannabis infused olive oil? You could apply the oil to the skin and it would penetrate into the skin. Any further? From what I've seen in the literature, using that method, most of the cannabinoids would be trapped in the skin. Now, turning to paragraph 40 at page 9 of your report, you -- just so we're clear, I take it you
A Q A Q A
Q A Q A Q A Q A Q
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q
A Q
were provided some material with these particular paragraphs in it describing the quality issues that need to be addressed before marihuana products should be used as therapeutic agents and I just want to be clear I -- I understand what you're saying here. Are you agreeing with and adopting paragraphs 15, 16, 17, 18, 19 and 20 of -- and only those paragraphs in paragraph 40, that's all your adopting? I'm adopting those opinions, yes. And those are -- you share the same opinion, in other words? I do, yes. And finally, at paragraph 42 that, in essence, is a conclusion to the section that we've just dealt with and the continuation of the thought set out at paragraph 41 above, correct? Yes. Very little scientific and medical information regarding additional adverse effects (in addition to the effects of cannabinoids themselves) that could be related to products derived from marihuana such as oils, ointments or baked goods. And you make: ...non-standardized production methods -- et cetera, et cetera. All of these are concerns in relation to any therapeutic product offered for sale to the public, is that fair to say? That's fair to say, yes. And then finally, in your conclusions you make reference to Sativex and in your report at Tab D you produced and included the current product monograph for Sativex? Yes. And Sativex is what? Sativex is an oral mucosal spray that is composed of botanical extracts from two different strains of cannabis sativa, one which contains high THC, another one contains high CBD and they're mixed in equal proportions. And you comment at paragraph 43 that the product
A Q
A Q A
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
is -- Sativex is -This product is well-characterized and its composition is known and stable from batch-to- batch. These same rigorous criteria also apply to other marketed cannabinoid-based pharmaceutical products such as Marinol and Cesamet? A Q A Yes. What are Marinol and Cesamet? Marinol -- Marinol is a synthetic Delta-9-THC, which is dissolved in sesame oil in a capsule and it's administered to patients who suffer from HIV/AIDS associated anorexia-cachexia and I believe also suffer from nausea and vomiting. And Nabilone is a synthetic derivative of Delta-9-THC. It's structure is slightly different and I believe that it's also used as an antinauseant in the clinic. And in your -- the report that's been presented, you've included the product monograph for Marinol as Tab E, correct? Yes. And that monograph is lengthy, 29 pages, 31 apparently in total. Thirty-one in total. And under Tab E as well you have the monograph for Cesamet or Nabilone, correct? Which is at the back of the tab. Yes. That's correct. And these product monographs, what are they? What's their purpose? The purpose of a product monograph is to give health care professionals and -- mostly health care professionals, can be used by the public as well, but the intended purpose is for physicians to be informed about the pharmacological and clinical aspects of the drug in question. The monograph summarizes the pharmacology, mechanism of action, clinical trials, adverse effects, dosing. All the information that would be required by a physician in order to be able to prescribe to a patient this particular drug. Have you had an opportunity in preparing to give evidence in these proceedings to take a look at the Cannabis Buyers Club of Canada, Medicinal Cannabis Recipe Book?
Q A Q
A Q A
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
MR. ECCLES: Perhaps Dr. Abramovici could have Exhibit 18, please. MR. TOUSAW: My Lord, while the clerk is getting that, I did not notice any references in the report of Dr. Abramovici to that exhibit or any opinions expressed upon that exhibit and therefore, at this point, I rise to object because I don't have any notes that this witness is going to speak to this exhibit. THE COURT: He hasn't been asked for an opinion about the exhibit yet. MR. TOUSAW: That's true. I suspect my friend's going in that direction but I wanted to make my objection before we got there. THE COURT: All right. Well, I'll hear the objection when we get to an objectionable question. MR. ECCLES: Q Dr. Abramovici, you're familiar from reading product monographs from your work on your Masters and your doctorate and your work at Health Canada with the process required to obtain approval of a therapeutic product, correct? A In general, yes. Q And the monographs for Cesamet, Nabilone and Marinol reflect the steps taken to satisfy those criteria? A Yes. Q Have you had the opportunity to look through the recipe book for Cannabis Buyers Club of Canada, Exhibit 18? A I haven't looked at the recipe book. I'm looking at it now but I have looked at their product -product. What page? Q To you knowledge, have any of the products, baked or edible or topical products, ointments or the like, been through the sort of testing and procedures required to generate a product monograph such as that for Cesamet or Marinol or Nabilone? MR. TOUSAW: My Lord, I'm going to object. It's outside of the scope of this witness' qualification. It's an area in which he hasn't been tendered as an expert and it's an area in which the accused has not been provided notice that this witness would be testifying. THE COURT: What he's being asked is does he know of any literature indicating that the products
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
MR.
THE MR. MR. Q
A Q A Q
A Q A Q A MR. THE MR. MR. MR. MR. THE THE
offered by the club have been through the testing, clinical trial or approval processes. Where is the opinion in that? TOUSAW: I did not hear my friend say -- ask if he was aware of any literature. He asked if he was aware that they'd gone through it sufficient to meet the standards for therapeutic drugs in Canada. COURT: Is that an issue? TOUSAW: I don't believe it to be an issue but... ECCLES: Well, if it's not in issue, I won't waste the court's time with it, My Lord, and I'll move on. At paragraphs 44, 45, and 46, you've set out in your report your conclusions regarding the report of Dr. Pate and the assertions set out therein, is that correct? That's correct. Now, you swore this document before a notary public in and for the province of Ontario on the 26th day of January 2012, correct? Yes. This document, pages 1 through 11, paragraphs 6 through 46 and in particular, 7 through 46, set out your response to the expert opinion of Dr. Pate, based on your review of the literature and the citations and references you provided in your report, correct? Yes. The report sets out your opinion in these areas and it continues to be your opinion today? Yes. You stand by your report? I do. ECCLES: Thank you, My Lord. Those are my questions in direct. COURT: Cross-examination. TOUSAW: Yes, My Lord. Just as a preliminary matter, is my friend intending to seek to introduce this report -ECCLES: Oh. Yes. TOUSAW: -- as an exhibit in these proceedings? ECCLES: That would be the logical next step, My Lord. I'd ask that be marked as Exhibit number -I'm not sure what number we're at. COURT: What number are we at, Mr. Clerk? CLERK: Forty, My Lord.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
THE COURT:
Exhibit 40. EXHIBIT 40 (on voir dire): Hanan Abramovici Affidavit of
MR. ECCLES: Thank you, My Lord. I thank my friend for reminding me. THE COURT: Yes. THE CLERK: I do not have a copy of the report, My Lord, to mark as an exhibit. MR. ECCLES: My Lord, if the copy Your Lordship has, has not been marked by Your Lordship -THE COURT: It has been. MR. ECCLES: Then on the break I will crack the spine on this one and pull out Exhibit C, or I can hand it up now and one way or the other, it just -- it takes a few minutes to get that much paper out. THE COURT: And has the redlining been done in the affidavit itself in that copy? MR. ECCLES: Yes, it has, My Lord. MR. TOUSAW: I'm content with Exhibit C remaining in the document and just not to be considered by the court. THE COURT: All right. We can mark that one, Mr. Clerk, on the basis that Tab C does not form part of the exhibit and is not in evidence. THE CLERK: Yes, My Lord. MR. TOUSAW: Thank you, My Lord. CROSS-EXAMINATION ON VOIR DIRE BY MR. TOUSAW: Q A Q Dr. Abramovici, am I saying your name properly? Abramovici. Abramovici. I take it from a review of your CV and the questions that my friend has asked you this morning that you have not yourself conducted any laboratory work with cannabis or cannabinoids? That is correct. You have not, in the course of your career either as an undergraduate, graduate, a student with Promega or with Health Canada, with the exception of the Information for Health Care Practitioners document, published any papers on cannabis or cannabinoids? That's correct. You have not received, in the course of your educational training, any specialized training in
A Q
A Q
557 VOIR DIRE Hanan Abramovici (for Crown) cross-exam by Mr. Tousaw
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q
A Q A Q A Q A Q A Q A Q A Q
A Q A Q A Q
cannabis or cannabinoids? That's correct. Whilst a student, either a undergraduate student, a graduate student or a postdoctoral student, did you have any classes specific to cannabis or cannabinoids? I did not. I note from your curriculum vitae at page 8, that you are -- under professional memberships, that you are a member of the -- something called the International Cannabis Research Society, are you? I believe it's the International Cannabinoid Research Society. Yes. Thank you. And you are a member of that society? I am, yes. And for how long have you been a member of that society? I believe for about a year or so. Safe to say that you joined that society after taking work with Health Canada? You are correct. Have you attended any of the conferences of the International Cannabinoid Research Society? I have. Was this the most recent conference in I think North Carolina? No. I believe it was in Pheasant Run, near Chicago. And you attended that conference? I did. And the International Cannabinoid Research Society, that's an international society, essentially of professionals devoted to the research of cannabis and cannabinoids, correct? That's correct. It's an internationally known and well-recognized organization? Very much so. You would consider it to be a reputable organization? I would. And it's -- is it fair to say that it is the primary international organization, perhaps the only international organization devoted to cannabinoid research? I think it's the most reputable one, the best
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q
A Q
A Q A Q A Q A Q
A Q A Q
known one, yes. And I note in -- starting at page 6 of your curriculum vitae that you've given a number of conference abstracts and you've been an invited presenter, continuing on page 7, at a number of seminars. Have you ever presented any conference abstract or given any presentation on cannabis or cannabinoids? I have not. And did you, at the most recent International Cannabinoid Research Society conference, did you submit any papers, posters or anything of the like? I haven't, no. You were in attendance essentially as an interested participant to hear what others are saying about the state of research in this area, is that fair? That's fair. You are aware, I take it -- fair to say that your first real professional experience with the issue of cannabis or cannabinoids came when you joined Health Canada and were hired by them to act as their Senior Scientific Information Officer? That's correct. And is that the position you held in December 2010 and continue to hold? I believe that I began working there in February of 2010. February 2010? Yes. And was that as a Senior Scientific Information Officer, correct? That's right. At page 1 of your curriculum vitae, Exhibit D -well, Exhibit 40 in these proceedings, there's a number of -- in italics under the title Senior Scientific Information Officer there's a number italicized subheadings. I take it that's simply a breakdown of the organizational hierarchy at Health Canada? You are correct. Do you now or have you ever worked in the medical marihuana access division at Health Canada? I have not. Do you now or have you ever -- do you, as part of your role as a Senior Scientific Information
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q A Q A Q
A Q A Q
A Q A Q A Q A Q A Q
Officer, do you consult with members of the medical marihuana access division at Health Canada? Yes, occasionally. Do you have any involvement in the processing, approval or issuance of authorizations to possess dried marihuana by that subgroup of Health Canada? Absolutely not. Have you ever had the occasion to review applications by patients to possess or produce marihuana for medical purposes? Never. You are aware that Health Canada does accept and process applications by residents of Canada for authorizations to possess dried marihuana? Yes, I'm aware. And you're aware that Health Canada issues, under the auspices of the Marihuana Medical Access Regulations, authorizations to possess dried marihuana, correct? Correct. That Health Canada issues authorizations to produce marihuana for medical purposes under those same regulations, correct? That's correct. You are -- with respect to the Information for Health Care Professionals document, when did you commence your work updating the prior version of that document? I believe I began it in June of 2010. May or June. I don't remember exactly but it was sometime in the early summer. So a few months after you began working for Health Canada? That's right. And you were asked to do that, I take it, by your superiors at Health Canada? I was. Was that Ms. Desjardins? Correct. And you had conversations with her and others in your division, I take it, about the work that you were to perform? I spoke with her about it, yes. She asked me to update the document. Were you provided any terms of reference or any guidance on what you should do to update that
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q A Q A Q A Q A Q A
A Q A Q
document? The Information for Health Care Professionals document dealing with marihuana follows a format similar to that of a drug product monograph. That is the format that I used. And did the prior version follow that similar format? It did. I take it in the process of updating the Information for Health Care Professionals document, you first read the old version, correct? I did. And you read the studies that were referenced in the older version? Yes. And then I take it you began a process of educating yourself on where the science had gone since that first document, is that fair to say? Yes, it's fair to say. And what was the process that you undertook to educate yourself about -- about where the science had gone since the earlier version? I think it's a process that every scientist uses and that is to consult the online medical and scientific literature found in PubMed. And PubMed is an online database of both abstracts of published research and occasionally full text articles of that research? I would say that most of the time you have the full text available and the abstract -- the abstracts are provided as a quick snapshot and then you have the option of downloading the article, the full article, yes. And when you go to PubMed, say you do a search on cannabinoids, you'll see a number of hits, for lack of a better term, is that right? A number of references in their database? Yes. And then you'll click on -- click on a paper, the abstract will pop up, is that correct? That's correct. And then there'll be a link to a full text version somewhere on the -- on the webpage or, alternatively, perhaps a link to the publisher of the paper's website so that you can go there and try to find the version, correct? Yeah. That's correct.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q
Q A Q A Q
A Q
A Q A Q A Q
A Q A
There are occasionally fees charged for obtaining those studies, is that correct? That's correct. And did you have occasion to, in the course of your research and updating the Health Canada professionals document need occasion to -- Health Canada had to pay for some of those studies, is that right, or were you provided some sort of PubMed login and that sort of gave you full text access? There are -- there are two avenues. A lot of the papers are available free of charge and there are papers that are not available but you have to pay a fee for and Health Canada, I believe, has a library type of agreement with many of these publishers to be provided most of these journals for a fee. I dont know how much they pay but certainly they have to pay something. Sort of a by subscription -Yes. -- type arrangements? Correct. Lawyers would be familiar with that through Lexus Nexus or Lexlaw or something like that. I guess I don't expect you to answer that, you're not a lawyer. I don't know. And so you -- you conduct your PubMed and database search and there is many thousands if not tens of thousands of studies on cannabis and cannabinoids that have been published that are referenced in PubMed, is that right? Yes. Do you happen to recall whether the number was closer to 50,000 or 5,000? I couldn't tell you. I don't know. A large number. A lot? A lot. Was there a process you then undertook to make a determination of which of those you're going to read, because I assume you didn't read all of the articles cited in PubMed about cannabinoids, correct? That would take a very long time to do. Yes. I'm somewhat familiar. Yeah. I began by looking at review papers which
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q
summarize much of the scientific literature out there and then narrowed the search down from that point on. And when you say review paper, what do you mean when you say that? Review papers are papers that are essentially summaries of the peer-reviewed scientific and medical literature. In a sense, the document that you put together, the Information for Health Care Professionals is a sort of review paper, is it not?
Q A Q
It's a summary of the literature on cannabis and -- on -- on the -- it's a summary of the peer-reviewed scientific and medical literature on cannabis and cannabinoids. And so you -- you start with these review papers, you read those, yeah? Yes. You then make a determination of whether or not you're going to then go to the actual source material and read those materials as well, is that correct?
That's correct.
Q A
And what guides your thinking in that process? What -- what is it that triggers you to go to the secondary material or I guess it would be the primary material that's cited in the review paper and then read that? I think the -- the decision is governed by what the mandate of the Information for Health Care Professionals document is and that is to collect and summarize, as much as possible, the relevant literature on cannabis and cannabinoids, medical and scientific literature. And so I tried to be as thorough as possible in that regard. And when you say the relevant literature, I mean, relevance is a -- is occasionally a very subjective determination, is it not? Can be but, you know, when you're looking at the review literature, that's also, you know, subjective as well. It depends what, you know, the person who's doing the review thinks is important but if you get enough opinions in the medical and scientific literature and you go by that. There's some weight attached to, for example,
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q
A Q A Q
A Q
A Q A
the fact that a number of different authors have pointed to a particular study or a particular set of circumstances that -- that then merit some further consideration, correct? Yeah. I would say that's correct. It's a quantitative analysis in some senses. Thirty or 40 people that are respected peer-reviewed researchers have cited this particular article, it's got some relevance, let me go back and read the actual article itself, correct? Yes. Were you provided by your superiors or anyone else at Health Canada with some guidance as to what ought to govern your relevance determinations? No. I based that on my scientific knowledge and experience. So that was your decision? Yeah. And I take it in -- in producing the Information for Health Care Professionals document you, on behalf of Health Canada, are attempting to be as accurate and complete as possible in both what you're saying and what you're including because you know that the document is going to be relied upon by -- and indeed, is intended to be relied upon by physicians and possible patients. Is that a fair summary? Yes. In the Information for Health Care Professionals document, there are studies that fit into the realm of what I'll call clinical studies, is that -- is that fair? Fair. And clinical studies are -- well, let me ask you what you -- when I say clinical studies, what does that mean to you? A clinical study to me is a scientific or a medical research study which follows a very predetermined and thorough methodology that's followed, I would say, all over the world, to answer a particular question, research or medical question and this study is carried on in humans.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q
A Q A Q A
A Q A Q
A Q
Also included in the Information for Health Care Professionals document are reports of lab studies, work that's done in the laboratory, correct? Yes. Correct. And that would be work done by research scientists on, for instance, Delta-9-tetrahydrocannabinol, one of the active compounds in cannabis, correct? Yes. Correct. Also referenced in the Information for Health Care Professionals document are studies or reports of case studies. Reports of things that have, for lack of a better term, happened out in the real world that someone's noticed, remarked upon and written about, is that fair to say? Yes. And there are in the Information for Health Care documents references to what I call anecdotal evidence, is that fair to say? That's fair to say. And when I say anecdotal evidence, what do you -- what do you mean -- what does that term mean to you? Anecdotal evidence is evidence that's not supported by the scientific or medical literature. It's somebody -- it could be something that somebody said offhand or, you know, just put it down on paper, or word of mouth. And anecdotal evidence can then, of course, be supported by either lab work or clinical studies subsequent to the anecdotal report, is that -- is that a fair process? It could be supported or it could be refuted. Fair to say either thing could happen? Yes. And that is dependent upon the ability or desire or an individual researcher, clinician, to actually follow up on the story and do the work? I would imagine. It would be the case that if any particular researchers -- a researcher didn't follow up on anecdotal evidence, didn't do the work, there wouldn't be any clinical work published
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
on that particular -- on that particular characteristic, is that fair to say? I believe so. That doesn't, of course, mean that the anecdotal reports are wrong or incorrect in any way. Similarly, it doesn't mean that they are correct or accurate in any way, it just means the work hasn't been done?
That's right.
One path of drug development is an anecdotal reports suggests a potential benefit, lab work is then done, analyze whether there is a scientific basis for a mechanism of action that produces that benefit and then potentially clinical work is subsequently done to try to verify the hypothesis developed in the lab, in actual practice. Is that a fair description of a process that a drug could go through? A One process. Q There are others? A There are others, yes. Q For example, a research scientist in a laboratory could have a hypothesis, find a mechanism of action that seems to support that hypothesis, do some lab study to try to determine whether or not what that scientist thinks is going to happen is actually happening. Is that fair to say? A Yes. Q It's fair to say that the three types of reporting that I've identified, anecdotal, lab work, clinical work, all three types of reports can have value but they have different levels of value, really depending on the person evaluating the work, is that fair? A I would say that, generally speaking, laboratory studies and clinical studies are more reliable than anecdotal evidence. Q But that's not to say that anecdotal evidence has no value? A I would -- I would question its value as a scientist. Q But again, that's not to say that it has no value? A You're correct. MR. TOUSAW: My Lord, I note the time.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
THE COURT:
All right.
We'll take 15 minutes.
(PROCEEDINGS ADJOURNED FOR MORNING RECESS) (PROCEEDINGS RECONVENED) HANAN ABRAMOVICI, recalled. MR. TOUSAW: Thank you, My Lord.
CROSS-EXAM ON VOIR DIRE BY MR. TOUSAW, CONTINUING: Q Doctor, just before the break I was asking you about three different types of evidence, anecdotal evidence, evidence derived from lab studies and evidence derived from clinical reports, and I guess what I was getting at is the value of the evidence really can depend on the perspective of the person looking at the evidence, can't it? And by way of a concrete example, let's say you have a patient, someone suffering from a medical condition, call it chronic pain, and that patient, that individual hears from other individuals well, for my rheumatoid arthritis pain I use Aspirin, or I use Tylenol, and the person hearing that information, that's anecdotal information, right? Yes. Now, the person hearing that says oh, well, I've never tried Tylenol for -- for my arthritis pain. I'm going to go try some Tylenol. Does so and finds it to be effective. That anecdotal evidence had some fairly significant value to that particular individual receiving it, correct? I would disagree with that because one doesn't take into account there the -- an effect called the placebo effect and that is that people are suggestible. And so if I say that this Aspirin worked for me and it made my headache go away, then the person I'm talking to gets it into their head that it might work for them. So there's a strong psychological factor and that's well-known. And so that's why clinical trials incorporate placebo controls to control for that psychological variable. But from the perspective of the person who doesn't have the headache anymore after taking the Aspirin, there's value to that experience whether it's caused by the placebo effect or caused by the
A Q
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q
A Q
A Q
A Q
mechanism of action of the Aspirin. There's value to that individual, isn't there? There may be value to the individual but it says nothing about the therapeutic value of the drug that was taken. No. And that's the point I'm trying to get at, is the perspective of whether the evidence has value has a lot to do with who's receiving the information. The patient may either not care or not, frankly, understand the mechanism of action of a particular therapeutic compound, whereas a lab scientist might, but the person takes the drug and gets the relief and the person is happy to achieve that relief, correct? The person taking the drug could also experience adverse effects taking that drug which the other person didn't experience. Undoubtedly, and that would go into their own personal evaluation of the value of the evidence that they've taken in but, nevertheless, there's value to that individual in having the opportunity to try something and it works for them and say they don't experience adverse effects. That's a valuable situation for somebody that's trying to deal with a headache, right? Maybe. Well, if someone has a headache and they want the headache to be gone and not experience the pain from the headache and they achieve that without any adverse effects, that's a benefit to that person, isn't it? Yeah. Similarly, a lab scientist, for example, may be very well-satisfied with demonstrating that that individual's hypothesis of a mechanism of action of a compound is demonstrated in the lab but may not particularly care that there's anecdotal reports that support or contradict that and may not particularly care whether or not it's established in clinical practice. They've had an idea, they proved the idea in the lab, they're happy with that. That's fair to say, isn't it? I'm not really sure I understand your question. Well, for example, similar to the patient who experiences the symptom relief and either doesn't understand or doesn't bother to go look at the product monograph, I take it -- my guess would be
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q
A Q A Q A Q A Q
A Q A
most people don't look at product monographs, but be that as it may, the lab scientist who has a hypothesis, for example, that CB -- Delta-9-THC has some analgesic effect and they go and they do some lab work with rats or something like that and they demonstrate some analgesic effect, they're happy to have that result. They're satisfied with the work they've done. Whether or not it moves on to clinical practice, they may or may not care about that, isn't that right? Yeah. That's true. It depends on your perspective, fair to say? I guess so. I'm not really sure what you're asking but... Well, the -- and just to sort of circle back to the placebo effect, the placebo effect is a very common effect in all therapeutic compounds, isn't it? Most. Pharmaceutical drugs can create a placebo effect, correct? They can. Your doctor, or you go to your -But it's controlled for. Yes. In clinical trials it's controlled for? That's right. When a patient goes to the allopathic physician says, you know, I'm suffering from chronic pain in my back. The physician says here, try Oxycontin, for example. Whether the Oxycontin works for that particular patient may be a result of either the mechanism of action of the Oxycontin or it may be the placebo effect, isn't that correct? Chances are it's actually a real effect because the placebo -- it's been tested in clinical trials so there is a chance that it's -- it's a real effect as opposed to a placebo effect, but we can't rule it out. Similarly -- well, it is the case, is it not, that there are some persons for whom a drug like Oxycontin may not produce analgesic effect, correct? Potentially, yes. But they may yet experience analgesic effect because people are suggestible, as you said, correct? Yes.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q
A Q
A Q A Q A Q A Q
A Q A
And again, from the perspective of the patient, absent some adverse effects, they're getting the relief they're looking for, they're happy, isn't that fair to say? That would be fair to say. The clinical trial work that we talked about is a means of determining efficacy and safety of a particular medicine or compound. Is that a fair description of clinical work? That's a fair description. It is not, of course, a guarantee of safety of that particular compound because effects when a drug is made widely available to the population may be different from those in a clinical trial setting, correct? That's correct. And there have been, of course, many cases, or at least some cases, where prescription drugs have gone through the clinical trial process, been approved for marketing to the population and later fairly significant negative events occur, correct? Yeah. That's correct. One perhaps famous example is Cox-2 inhibitor known as Vioxx. Are you familiar with that? Generally speaking I'm familiar with it. My understanding is that Vioxx went through -it's a non-steroidal anti-inflammatory drug, is that correct? I believe so, yes. Used in the treatment of inflammatory conditions and pain such as arthritis, correct? I think so. And Vioxx, ultimately, after going through the clinical trial process, being marketed as a pharmaceutical substance in Canada and elsewhere, killed a couple of hundred thousand people, isn't that correct? I wouldn't comment on the numbers, I don't know. A lot of people died though, you're aware of that? I don't know that a lot of people died. I don't know what a lot is. I don't know. I know that there were adverse reactions reported. I can't give you a number. I don't know. Fair enough. Coming back to your review of the -your updating of the Information for Health Canada, Information for Health Care Professionals document for your employer Health
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q A Q A Q
A Q A Q
A Q A Q A Q A Q
Canada, you conducted -- I take it you conducted your review of the literature as you said using PubMed, reading the summaries of the existing literature and then identifying the primary documents cited in those summaries that are worthy of further exploration. Is that a fair description of the process? I would say that I tried to be as thorough as possible and explore all of the literature that I could have access to, that I had time to read, primary sources and reviews included. You could -- well, you said you spent about three months full-time work on this project, is that fair? Approximately, yes. You could easily have spent three years reading all the literature out there on cannabis cannabinoids, correct? I don't know about three years but maybe a couple more months. There's a lot of it? There's a lot, yes. And I take it that you, after reading the summaries that you've identified, you did go and read some of those primary source documents cited in the summaries, correct? I did. And ultimately, you make a judgment call on which to include in your updated document, correct? Yes. And there are approximately -- well, there are 476 citations in the updated version of the Information for Health Care Professionals, correct? Yes. And I take it you've read all of those 476 cited documents? Probably almost all or all. Well, I -- I want to be a little specific here. Have you read them all or have you not read them all? I think I've read them all, yes. You wouldn't want to include a document -- a citation to a document you hadn't read in -- in the Information for Health Care Professionals? That's right. People are going to rely on that?
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q A Q
A Q A
Q A Q A Q
A Q A Q A Q
Mm-hmm. And your employer is obviously employing you to do that work -Correct. -- and you want to do your work to the best of your ability? Yes. You mentioned, upon the inception of that project, reviewing the old informational document and I think you said when my friend was asking you some questions that you felt that it was necessary to rework most of the document, is that correct? That's correct. Why did you feel it was necessary to rework most of the old document? Because I felt that the old document was organized in a way that I would have not necessarily organized it in and the way that certain statements were made or phrases put, I would have put them differently. Some of the sources were, you know -- you know, there was a certain amount of advancement in the field and I felt it needed to be updated. So there were different issues there. Research in this field, it's fair to say, is developing, correct? Yeah. That's fair to say. And is it fair to say also that research in the field of particularly cannabinoids is developing exponentially? I would say it's developing quite rapidly, yes. There's a lot of work being done in this area currently because it is, in terms of medicine or ecology, a relatively new area of scientific exploration, the science of cannabinoids themselves? The science of cannabinoids, yes. And that's because of the fairly recent discovery of the CB1 receptors and then the CB2 receptor system in the human body? Yes. And again, the fairly recent isolation of certain of the primary cannabinoids, delta-9-THC, CBD, CBC, CBN, fairly recently isolated in the lab? I wouldnt say they're fairly recently. Those were isolated in '60s and '70s. And it was the use -- it was the discovery, really
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q A Q
A Q A Q
A Q
A Q A Q
of the receptor systems and the endogenous cannabinoids that really sparked the surge in interest in doing work in this field, at least in the lab? Yeah. We've covered, in questions, about the Health Canada document that you updated. You reviewed the literature, your review of summaries of the literature, your review of some of the primary source documents. What else did you do beyond that in your work on the project itself? I believe that is all that I did. I looked at the -- I relied on the peer-reviewed scientific and medical literature to create this document. Did you have any personal communications with any of the researchers that have published any of the papers? No. Did you have any conversations with any of your colleagues at the International Cannabinoid Research Society about your work and the studies that you were reviewing? No. Whilst you were doing the project, were you a member of the ICRS or did you join that subsequent? I'm trying to remember. I think I joined afterwards, yeah. In preparing to give your -- in preparing the draft of your report, Exhibit 40 in these proceedings, and testify today in these proceedings, when did you first learn of the existence of this litigation? I believe it was -- I think it was essentially when I was provided the expert report of Dr. David Pate. But prior to receiving the Pate report, you were not aware that there was a Constitutional Question Act application involving edible, topical cannabis products? No. No. And who advised you that you might be a witness in these proceedings? I believe it was our legal counsel, I think. In your preparation to -- well, when you were provided with the affidavit of Dr. Pate on January 19th, at that point did you know that you would be
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q A Q A Q A Q A Q A Q A
Q A Q A Q A Q A
testifying in these proceedings? Not exactly, no. You knew it was a possibility? Potentially, yeah. That's why you had the affidavit? Yeah. And in preparation for drafting your report, I take it you reviewed the Pate affidavit, yes? Yes, I did. You reviewed an affidavit of Dr. Harold Kalant, correct? I did. You reviewed the two studies attached to Dr. Pate's affidavit, authored primarily by a Dr. Ethan Russo? Yes. And are you familiar with Dr. Russo? Yes. He is a well-respected researcher in the field of cannabinoids, correct? I don't know if he's necessarily a well-respected researcher. He works for a pharmaceutical company so he does do research on cannabinoids but I don't think that he publishes primary -- you know, primary source research papers. He is employed by GW Pharmaceuticals. His employment by GW Pharmaceuticals, do you consider that to be a -- a fact that compromises the validity of any work that he might undertake? Yes. Because he has potentially an interest in promoting, or at least supporting, the product that his employer has up, correct? Yes. People tend to, as a general rule, want to please their employers, correct? You could say that. And that's true of scientists as well as not scientists, correct? I think that's a general statement. If you're an academic researcher, you're working for yourself mostly, you know. I don't know if you want to please the university. Sometimes research findings are not necessarily -- don't necessarily go in the grain of what the research institution's mandate is, so I think it's a broad statement to make.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q A Q A Q A
Q A Q A
Q A Q
A Q A Q
So depending on the individual situation, there may or may not be influences that effect their perspective on research, for example? You could say that. And so Dr. Russo's perspective on the research may be influenced by the fact that he's employed by GW Pharmaceuticals? Yes. And GW Pharmaceuticals has an interest in a particular set of circumstances or realities, correct? Yes. You're aware that Dr. Russo is the current secretary of the International Cannabinoid Research Society? Possibly. I don't know exactly the make up of the board of directors or organization at the moment. It changes from time to time so I don't know what the latest change is. Did you have occasion to meet or hear any work presented by Dr. Russo at the last ICRS conference? Yes. And what was he presenting on? I can't remember exactly but I think it was on Sativex. I think actually it was on Sativex and adverse reactions and potential new products coming down the pipeline. Something like that. And Sativex is the drug that you described earlier in your testimony. It's manufactured by GW Pharmaceuticals, correct? Yes, correct. Have you reviewed any of the books that Dr. Russo has edited on the field -- in the area of medicinal applications of cannabis or cannabinoids? Possibly. Sitting here today, you don't know if you have or not? I don't remember off the top of my head if I have or not. Other than reviewing Dr. Pate's affidavit, Dr. Kalant's affidavit and the studies published by Dr. Russo, what else did you review in preparing to either draft your report or give your testimony today? Sorry. Can you repeat the question? Sorry.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q A Q A Q
A Q A Q A Q A Q A Q A Q A Q A Q A Q A Q A
Other than the Pate, Kalant and Russo material, what did you review in preparing either your report or for your testimony today? I believe I used the Information for Health Care Professionals and the papers that were included in my affidavit. And those papers are listed at Tab A of Exhibit 40 in these proceedings, under the boldface heading "References"? Yes. And did you read each of the papers listed under the boldface heading "References" in preparing to give your testimony today? Yes. Did you discuss either these papers, Dr. Pate, Dr. Kalant or the Russo material with anyone at Health Canada in preparation for giving your testimony today? No. Did you receive any directions from anyone at Health Canada with respect to your report or the testimony you're going to give today I did. I discussed -- sorry. I discussed my affidavit with my director at one point, yes. Was that Ms. Desjardins? Yes. That's correct. And did you provide a copy to her? Yes, I did. And did she have comments to make on it? Very few. Did you alter your report in any way based on those comments? Did I alter my report -- no, not really. Well, no and not really are different answers. No. Did you prepare any draft copies of your report in -- in preparation to give your testimony today? I may have, yes. And would that differ from the affidavit that you've provided that's been marked as Exhibit 40 in these proceedings? Yes. And who, if anyone, did you share those draft copies with? I shared it with my director. Anyone else? Legal counsel.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q A Q A
Q A Q A Q
A Q A Q A Q A
Q A
And you said your director had some comments, very few, but those comments did not result, I take it, in any alteration to the draft of your report, is that correct? I'm trying to remember now, sorry. It was a very, very busy week for me that week. Take your time. Thank you. She -- yeah. She had -- she had some comments on -- on my affidavit, yes. And -- and as a result of those comments, did you make any changes to your affidavit? Yes, I did. And what were those changes? Those changes were -- I would say those changes were probably paragraphs -- the last few paragraphs in the conclusions. Those were as a result of my discussions with Dr. Desjardins. So when you say the last few paragraphs in the conclusions, you're referring to paragraphs 43 through 46 of your affidavit? Yes. And in terms of substance, what did the draft say that's different from what the final report says? I believe those paragraphs were not in my original draft. They were added subsequent to my discussions with Dr. Desjardins. And so paragraphs 43 through 46, your conclusions, did not appear in your original draft affidavit but just to be clear, they were added after Dr. Desjardins, your superior at Health Canada, provided you with comments, correct? That's correct. And what was the substance of her comments? Those were her comments. The conclusions were her comments? The conclusions came from my discussions with Dr. Desjardins. I don't mean to be obtuse but what did she say, what were her comments and how are those reflected in this final draft? I think these were -- I'm trying to remember. Oh, I think I remember what -- okay. So these -- I think we had traded back and forth the -- my original affidavit and these were paragraphs that she had put into the document. So just to be clear -I -- I believe. I --
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q A Q
A Q
A Q
A Q A Q
A Q A Q A Q
A Q
Okay. I'm pretty -That's your memory of the event? That's my memory of the event, yes. Okay. And so just to be clear, paragraphs 43 through 46 of your affidavit were, in essence, authored by your superior, Dr. Desjardins, and then you incorporated them into the final version of the affidavit? That's correct. You indicate that you shared copies of a draft of this affidavit with legal counsel. I take it that's not my friend Mr. Eccles here, but that's someone at Health Canada? That's correct. And without entering into the substance of what legal counsel said to you, did you make any changes to the document as a result of those conversations? No. In terms of the specific facts of this case, had anyone given you a synopsis essentially of what the case is about? Briefly, yes. And if that was legal counsel I don't want inquire into the substance of that conversation so I'll just ask you, was that legal counsel or was that someone else? No, it was legal counsel. And you understand that Mr. Owen Smith is charged with simple possession of cannabis? I believe so, yes. And you understand he's also charged with possession for the purpose of trafficking in tetrahydrocannabinol? Yes. And do you understand that that charge arises based on an analysis by Health Canada of the contents of cookies and oils seized by police during the execution of a search warrant? I'm sorry. Can you repeat that again? Do you understand that the charge of possession for the purpose of trafficking tetrahydrocannabinol arises as a result of analysis by Health Canada determining that THC was present in cookies and oils seized by police? I guess so, yes.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q
MR.
MR. MR.
THE MR.
THE MR.
THE MR. THE A
You understand that Mr. Smith was essentially operating a bakery in an apartment, is that your understanding? That's my understanding. Do you understand whether or not there was any qualitative analysis conducted -- excuse me, quantitative analysis conducted on the cookies or the oils? ECCLES: I'm going to object, My Lord, on the basis of relevance and quantitative versus qualitative analysis is not an area the Crown has tendered Dr. Abramovici as an expert in. TOUSAW: I'm not seeking his opinion. Just whether or not he has an understanding, My Lord, of whether a quantitative analysis was conducted. ECCLES: Then I'll object on the basis of relevance. If my friend isn't seeking an opinion from the doctor, how is this relevant to the opinion he is seeking? In my respectful submission, it's not -COURT: It doesn't have to be relevant to anything he said so far. He's here and he's available for cross-examination generally, is he not? ECCLES: Within areas of relevance to the evidence he can provide the court, My Lord, yes. In my respectful submission, this isn't relevant to anything the -- the witness can offer by way of opinion or has offered by way of opinion or in any other capacity. COURT: Well, if it's relevant to any of the issues in the voir dire, can't he speak to it if he knows the answer? ECCLES: Well, the difficulty from the Crown's perspective, My Lord, is we maintain it's not relevant to any issue in this voir dire, as framed? COURT: What's the relevance? TOUSAW: My Lord, I'll have to ask that the witness be excused at this juncture so I can explain. COURT: All right. Dr. Abramovici, could you step out into the hallway just briefly. We'll try not to keep you out there too long. Thank you. (WITNESS STOOD DOWN)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
[DISCUSSIONS BETWEEN COURT AND COUNSEL 12:07:38 TO 12:26:35 P.M.] HANAN ABRAMOVICI recalled. THE COURT: Do you remember the question?
CROSS-EXAM ON VOIR DIRE BY MR. TOUSAW, CONTINUING: Q Are you aware, Doctor, of whether or not any quantitative analysis was performed on the products seized from Mr. Owen Smith by the police in this case? A No. Q It is -- and by quantitative analysis, I want to make sure we both understand what I mean by that. I mean amounts of a particular substance in the sample being tested? A No, I'm not aware. Q You are familiar with, I take it, methods of extracting the cannabinoids and other compounds from plant material into oils, yes? A Generally speaking, yes. Q And you're familiar with methods of extracting the cannabinoids and other compounds in the cannabis plant into alcohol? A That's one of the ways in which it's done, yes. Q And you speak in your report of extraction methods using butane, correct? A Petroleum ether, I believe. Q Each of these methods of extraction will yield an end product that is -- has a differing quantitative level of the active ingredients, cannabinoids -- let's just focus on cannabinoids. You will have a different level of quantity of THC, for example, in an oil extraction than you will in a petroleum ether extraction, correct? A Potentially. Q Same question with respect to other cannabinoids. You will potentially have differing quantitative levels of those substances in the end product, depending on your method of extraction, correct? A I would assume so, yes. MR. TOUSAW: My Lord, I note the time. THE COURT: All right. Two o'clock.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
(WITNESS STOOD DOWN) (PROCEEDINGS ADJOURNED FOR NOON RECESS) (PROCEEDINGS RECONVENED) HANAN ABRAMOVICI, recalled. MR. TOUSAW: Thank you, My Lord.
CROSS-EXAM ON VOIR DIRE BY MR. TOUSAW, CONTINUING: Q Doctor, just before we broke for lunch we were discussing methods of extracting the cannabinoids and terpenes from the cannabis plant into oils, alcohol or by ether extraction. Other than the studies that you've referenced in your affidavit, do you have any independent knowledge of the extraction processes used to -- that we've discussed? A I do not. Q Earlier when discussing your role at Health Canada, you indicated that, generally speaking, you provide advice to Health Canada on drugs of abuse, is that a fair summary? A Yes, and controlled substances. Q And by the -- does that include prescription drugs? A No, not generally. Q You are aware, however, that it is the case that prescription drugs, such as opiates, can be and are abused in Canada? A Certainly. Q And that, for example, people with addictions to opiates can attempt to buy more prescription drugs than they are necessarily entitled to by double doctoring or attempting to fill multiple prescriptions, things of that nature? A Yes. Q And that others perhaps without addiction issues will occasionally attend at physicians' offices in an attempt to get prescriptions filled in order to divert these prescription drugs to the illegal marketplace? A Possibly. MR. TOUSAW: Can we have the witness' -- Exhibit 40 put before the witness. THE CLERK: Yes. The binding is coming a little
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
undone. A Thank you. MR. TOUSAW: Q I don't know what the other materials you have on the desk in front of you are. I'm not going to be making reference to them but if you need a place to put Exhibit 40, you can clear them away. A It's okay. Q At -- at paragraph 7 of Exhibit 40 -A Sorry. Which tab is this? Q The affidavit itself. A Oh, my affidavit. Yes. Sorry. Yes. Q Well, actually, let me back up. Let's go to paragraph 6. At paragraph 6 you indicate that: Despite the clear gaps in the scientific basis for the use of marihuana for medical purposes, as a result of the 2000 Ontario Court of Appeal Parker decision, the MMARs were promulgated to provide a mechanism for legal access to possessing marihuana for medical purposes (only the plant material). I take it that statement is not something that you came across in your review of the scientific literature around cannabis and cannabinoids? A You are correct. Q That -- where did you gain the knowledge that underlines what you say in paragraph 6? A That paragraph -- that knowledge came from legal -- I think legal services. THE COURT: Sorry. From where? A From -- from our legal services. THE COURT: Thank you. MR. TOUSAW: Q And your reference to "clear gaps in scientific basis," is that a reference to the knowledge as it existed in 2000 or the knowledge as it exists today? A No. 2000. Q 2000. And the knowledge in that area, use of marihuana for medical purposes, has expanded considerably since 2000, correct? A I wouldn't say it has expanded considerably. Q Would you say it's expanded? A I would say it's gained some ground, a modest amount.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q
A Q A Q A Q A
Q A Q
You are aware from your review of the scientific literature that, at least in terms of anecdotal evidence, marihuana has been reported to be used for medical purposes for hundreds if not thousands of years? There is a historical record, yes. A fairly lengthy historical record? I can't really comment. I'm not familiar with the entire history of cannabis for medical purposes. In parens, in paragraph 6, in the parenthetical statement you say, "Only the plant material." I'm wondering what specifically you mean by plant material in that paragraph? I believe those were in reference to dried marihuana. And when you say dried marihuana, what are you referring to? Dried marihuana as in what part of the plant, is that what your question is? Yeah. I'm trying to get a sense of what you mean when you say dried marihuana. What I mean is the -- in flowering heads, the leaves. And this is primarily the female marihuana plant, correct? I don't know if there's a distinction between, in this case, female or male. Both plants can yield cannabinoids. The female yielding more than the male but both plants can yield. And that's because the greatest concentration of cannabinoids, excuse me, are found on the flowering heads, the buds colloquially, of the female marihuana plant, correct? The greatest concentration but cannabinoids can be found in the rest of the plant as well. It depends -- it depends on which particular strain of the plant or variant. Some have more, some have less. It depends. There's a variety. In the literature, in some cases, male and female plants are reported to have equal amounts of cannabinoids. It is the case then that there are different strains or what perhaps a botanist might call different chemotypes of marihuana, correct? Potentially. The -- for example, a particular sample of marihuana from a particular plant may have a high
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q
A Q
A Q
A Q A Q
A Q A Q A Q
level of THC contained in the resin glands, correct? Yes. And another sample from another plant may have a lower level of THC but a higher level of say CBD contained in the resin glands, correct? Yes. And I think that's what you referred to earlier when you were describing Sativex. The process by which it's made is GW Pharmaceuticals has a high THC strain and a high CBD strain and they combine the two to make their extract, correct? Yes. And you'd agree, wouldn't you, that assuming that CBD, for example, has some kind of modulating effect on, for example, the psychoactive properties of THC, that you're going to experience different things ingesting marihuana that's high TH -- low CBD versus high THC, high CBD -- or high CBD low THC? I don't think that's very well-established. Whether or not it's well-established, you'd agree with the principle underlying that in that if CBD has a modulating effect on, for example, the psychoactive effects of THC, the more CBD in your particular sample, the more modulating effect you're going to have and, therefore, you'll experience a different level of psycho-activity. That principle is sound, is it not? It's hypothetical. I can't really comment on it. Potentially. Paragraph 7 of your affidavit -Mm-hmm. -- you indicate that you were provided on January 19, 2012, with Dr. Pate's expert report but the concluding sense is that you've had limited time to review it. Do you see that? Yeah. Have you gone back over the report since you swore this affidavit on January 26th, 2012? Yes. And accordingly, you've had more time to consider it, is that accurate? You can say so, yes. And have your -- you haven't changed or altered your conclusions or responses to Dr. Pate's report in that intervening period?
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q A Q A Q A
Q A Q A Q A Q A Q A Q A Q A Q
No. At paragraph 8 you reference Dr. Pate's report at paragraphs 9 and 10 and the use of the term "therapeutically active compounds" and you say that essentially that's an inappropriate term to use because there aren't just therapeutic effects but there may be adverse effects as well, is that correct? Yes. That's correct. And then you prefer the term pharmacologically active in that context, is that correct? Yes. And what does that term, pharmacologically active, mean to you? It means that it can have -- that particular substance or substances can have different effects on a biological system. That's the -- that's the extent of what that term means to you? Pharmacologically active means that they have potentially a action on a particular biological system, yes. It could be good, it could be bad, it could be nothing, you know -- well, nothing would be not pharmacologically active but it could have a good or a bad effect. And so that term, pharmacologically active is the same term that you would apply to any prescription drug, for example? Yes. Indeed, that term would have applicability to things we may not ordinarily think of as drugs, food products, for example? Yes, potentially. Because they have effects on the biological system, correct? Yes. And prescription drugs, for example opiates, have analgesic effects, correct? Yes. And they also are responsible for some adverse effects, correct? Correct. And those effects can include addiction, correct? Yes. Overdose death, correct? Yes. Constipation, correct?
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q
Q A Q
Yes. Often those adverse effects are referred to as side effects, is that fair to say? Yes. Would it be fair to define side effects as essentially effects produced by a particular substance that are unwanted by the person ingesting the substance? Yes. And essentially, it's fair to say all drugs have target effects, the effects that you're seeking to achieve, correct? Yes. And side effects, effects that may be produced by that drug, but you're not seeking to achieve those? Yes. Possible adverse side effects can vary in severity, correct? Yes. And they can vary in frequency of occurrence, correct? Yes. Some side effects are more common than others, correct? Yes. Drugs that produce frequent and severe negative side effects don't get very popular, do they? That depends. Can you provide an example of a drug that has frequent and severe negative side effects but is in popular use? I would qualify that statement by saying it depends on the dosage. It depends on the dose of which you're ingesting the drug. If you take higher doses, you get more side effects. If you take lower doses, you may get less side effects, so it's hard to really make a broad statement, I think. And depending on dosages you may, in fact, achieve no side effects but still achieve the targeted effect, correct? Yes. A drug which at -- call it a common dosage that produces frequent and severe negative side effects does not typically gain general usage in a population?
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
Q A Q A Q
A Q
A Q
Correct. And so no matter how good a painkiller a particular drug may be, if it's killing half the people that take it, it's not going to be used very much? I would just back up a second and say in the case of a chemotherapeutic agent, for example, at a particular dose people may experience very severe side effects but they may also advance the course of the treatment. So it may not be a pleasant experience but, you know -But it may be a necessary one? It may be necessary, yeah. So -Occasionally, to achieve the target effect, you have to bear the side effects? Occasionally. At paragraph 9 of your affidavit you speak to Dr. Pate's statement which is at paragraph 9 of his report, and I understand his report is attached at -- well, to your affidavit Exhibit 40 in these proceedings as Tab F, is that accurate? Yes. And you take some issue with what you say is an implied statement of Dr. Pate's paragraph 9 that the active compounds are secreted only in the glandular trichomes found in the flowers of the cannabis plant. He doesn't actually say that at paragraph 9 but you imply that from what he has said at paragraph 9 of his affidavit? Well, it was my interpretation that he was saying it was exclusively or predominantly found there, so I just wanted to clarify that point. And at paragraph 9 of Dr. Pate's affidavit, attached to Exhibit 40 as Tab F, he says [as read in]: The primary therapeutically active compounds founds in cannabis are secreted by the plant in the glandular trichomes that are found in their highest population concentration on the [indiscernible], i.e., outer surface, of unfertilized female flowers.
A Q
You see that sentence? Mm-hmm. It is the case, is it not, that those glandular trichomes are found in their highest population
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q A Q A Q A Q A Q
A Q
concentration on the outer surfaces of unfertilized female flowers, that's an accurate statement, isn't it? I would say that it is, yes. Your -- your disagreement comes from the implication that perhaps, by exclusion, Dr. Pate is saying but nowhere else? Mm-hmm. Fair? Mm-hmm. For the court reporter's benefit you have to say -Yes. -- yes or no. I'm sorry. It happens constantly. Were you provided with notes or a transcript of Dr. Pate's evidence in these proceedings? No. And so if Dr. Pate testified on the witness stand essentially to the fact that trichomes appear throughout the plant but there's more of them towards the top of the plant in the unfertilized female flowers and there's less of them sort of as you go down the plant or away from the light, you wouldn't take issue with that statement, would you? Not necessarily, no. At paragraph 10 of your affidavit you -- well, let me back up. At paragraph 10 of Dr. Pate's affidavit he says: The two primary therapeutically active compounds found in the resin are essentially THC and CBD, plus associated minor cannabinoids and terpenes. You don't take issue with that statement, other than the use of the term "therapeutically active", correct? That's correct. And you similarly don't take issue with the statement made at paragraph 11 of Dr. Pate's affidavit that within each category of compounds there may indeed be several to many particular chemical species? That's correct.
A Q
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q
So it's a complex plant? Very. And he says at paragraph 12 of his affidavit: By way of example there are at least dozens of terpenes and several cannabinoids found in the resin contained within the glandular trichomes.
A Q A Q
A Q A Q A Q
A Q A Q A Q
A Q A Q
You see that, correct? Yes. And that's accurate, isn't it? Other than -Other than the issue of several cannabinoids. There's more than several. Yes. And you -- you, at paragraph 10 of your affidavit, you do take issue with the use of the term "several cannabinoids" and you say, citing a 2005 study, that there are, in fact, more than 70 reported cannabinoids, correct? Yes. And that was from a 2005 study. Yes. In your review of 2010 of the literature, are you aware of whether or not there are now, in fact, in excess of 80 reported cannabinoids? I'm not aware that there are 80. I'm aware of 70. And in your review of the literature, did you become aware that there, in fact, have now been more than 100 cannabinoids identified in the cannabis plant? The number keeps rising. It does keep rising, doesn't it? It does. I haven't seen that figure but I'll take your word for it. It wouldn't surprise you? I would have to see it in the literature, yeah. But the process of knowledge of this particular plant begins with the identification of one or two cannabinoids, THC, CBD, and there's progressively more and more and more identified, is that fair to say? Well, that's been the case. It's not necessarily assumed. It may not go on forever. Probably won't go on forever. Probably won't. That -- that figure, 70 or 80 or 100 or whatever
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q A Q A Q
A Q A Q A Q
A Q A Q A Q
it is, that represents all the cannabinoids ever found in all the plants ever studied in any quantity whatsoever by all the researchers in the history of researching this plant, that's fair to say, isn't it? I would say that -- we're talking about phytocannabinoids here? Yes. Right. Yes. So clarify that. In the plant. In the -- in the plant. Yes. But my statement is fair. That number is -it's an agglomeration of discoveries by a number of scientists, studying a number of different cannabis plants and finding all of these different cannabinoids which all may or not -- may or may not be present in any one particular plant? Possibly. Outside the scope of your knowledge? A little bit, yes. That's fair. That's stretching there. At paragraph 11 of you affidavit you suggest that Dr. Pate's statement at paragraph 14 of his report to the effect that, the medical effects of cannabinoids have been well-documented, is an overbroad statement and you say it's because the term medical is unclear. The statement doesn't refer to therapeutic or adverse effects, nor is it specific as to which medical effects have been well-documented. Those are your critiques of Dr. Pate's terminology? Yes. In principle, yes. There is, however, a long history of at least anecdotal reports suggesting that there are medical benefits to the marihuana plant? There are. There are also many reports saying that there are psychotropic effects as well, so -Absolutely. History of medical effects, history of some adverse effects, that's in the literature you've reviewed, correct? Yes. You don't -- putting aside for a moment the risk benefit analysis, one of the risks of using cannabis or cannabinoids outweighs the potential
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A
Q A Q A Q
A Q A Q
A Q A Q A Q
benefits that one is seeking, you don't deny that cannabis has medical value, do you? I don't deny that it has medical value -- or therapeutic value. I don't like the word medical very much. What's -- what's your issue with the term medical? Well, I think it's a -- it's a semantic issue. Medical can mean therapeutic or adverse. Medicinal, I think, leans more towards a therapeutic aspect of the term. I find medical a little too murky. If we take it that Dr. Pate is, by using the term medical, meaning some positive therapeutic effect -I understand. -- it's true that cannabis has some -- putting aside again the risk benefit analysis, some positive therapeutic value? Yes. And indeed, the document, the Information for Health Care Professionals document that you updated for Health Canada, references dozens if not hundreds of studies attesting to the therapeutic benefit of cannabis or cannabinoids? I would say more the issue of cannabinoids rather than cannabis. The cannabinoids, the compounds, have been more extensively studied in the laboratory than the plant itself, correct? Yes. And that's unsurprising as laboratory work is typically involved in dealing with compounds as opposed to dealing with whole plant materials, that's fair to say? Yes. Yes. Similarly, the clinical work on cannabis and cannabinoids has been -- it does exist for the whole plant, correct? Yes. But there's more studies, clinical studies at least, that have been conducted on compounds as opposed to the whole plant itself, correct? Yes. And of course, the impetus for clinical studies can come from a variety of factors but certainly include the desire of a particular pharmaceutical company to bring a product to market and thereby
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q A Q
A Q A Q A Q
make a profit on it, fair to say? Yes. And indeed there's been, at least over the last several decades, some difficulty in doing clinical trial work with whole plant cannabis because of its prohibited status, that's fair to say, isn't it? Yes. It's an illegal plant? Yes. You also -- well, let me back up. At paragraph 13 of Dr. Pate's report, it's at Tab F of Exhibit 40, you don't take issue with the statements made by Dr. Pate at paragraph 13? Sorry. Which -- which paragraph are you referring to? Paragraph 13 of Dr. Pate's affidavit. Oh, his affidavit. Yes. I agree with his statement. At paragraph 14, we've already discussed the first sentence. The second sentence is: Terpenes may well augment these effects. And you speak to that statement and respond to that statement at paragraph 12 of your affidavit, correct? Yes. And you say, essentially, that's a speculative statement? Yes. And indeed, Dr. Pate says "may very well", indicating that it's not a certainty, it's a possibility, correct? It's a possibility. And you don't deny that there's a possibility that terpenes may have some either enhancing or modulating effect on the role of cannabinoids in a therapeutic application? That's a -- that's a possibility, correct? Those studies have not been carried out so it's hard to comment. It is clear, however, that as you say, terpene content, types of terpenes, vary widely amongst different cannabis varieties, correct? Where do you see that?
A Q A Q A Q
A Q A
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q A Q A Q A Q
At paragraph 12 of your affidavit, the fourth sentencing beginning -That's -- well, I think that's from the reference by Hillig. Yes. And that's the Hillig study conducted in 2004, correct? Mm-hmm. Yes. And that is a study that you reviewed in conducting your literature review? Yes. And you found it to be a credible study? I assume because you've referenced it in your affidavit, you find it to have some value, correct? I find it to have some value, yes. And just reading from the abstract of the Hillig study which is titled the A chemotaxonomic analysis of terpenoid variation of Cannabis, the last sentence of the abstract reads: Cultivars of the two drug biotypes may exhibit distinctive medicinal properties due to significant differences in terpenoid composition.
Do you recall that from your reading? A No, I don't recall it but -MR. TOUSAW: My Lord, may I -THE COURT: Of course. MR. TOUSAW: Q Read the abstract there on page 1. A Mm-hmm. I don't disagree with this hypothesis but it's a hypothesis. Q It is -- it is the case, however, that terpenes do have, independently of cannabinoids, have been demonstrated to have some therapeutic effect, isn't that the case? A They've been demonstrated to have some kind of pharmacological effect on laboratory animals. Q And that pharmacological effect can include positive therapeutic effects, correct? A That would have to be established in more detail. Q There are -- in your literature review, in updating the Health Canada document, did you specifically research the issue of terpenes? A I didn't specifically research the issue of terpenes. Q And you don't, sitting here today, have an
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q
A Q A Q
independent laboratory or clinical or academic based knowledge on the effects of terpenes? I do not. That's outside of your field of expertise? It is. It is the case, however, as you say in paragraph 12, that there is a wide variation of terpenes amongst different cannabis varieties. That's -that's an accurate statement, correct? I would imagine that based on the literature there is -- that that's true. And in fact, you say that at paragraph 12 of your affidavit, that it's been reported at least. It's been reported, yes. You say also at paragraph 12: The notion that terpenes may also modify or enhance physiological effects of cannabinoids, Russo (2003), is more a matter of conjecture since very few, if any, studies of animals and humans exist to support this hypothesis. Are you aware of any studies that support that hypothesis? No. And is Health Canada currently engaged in doing any studies to support refute that hypothesis? Not that I know of. You're aware that at the inception of the Marihuana Medical Access Regulation program in 2001, one of the primary components of the program was a research component, correct? I know that research was a component. It's no longer a component, correct? That's correct. At paragraph 13 of your affidavit you refer to paragraph 15 of Dr. Pate's report and you take issue with the last sentence of his paragraph 15 which begins: Different strains are reputed to produce differing effects.
A Q A Q
A Q A Q
A Q
Correct? Mm-hmm. I take it --
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q
Yes. -- you don't take issue with the first two sentences of paragraph 15? I don't take issue with it. And your issue with the last sentence that: Different strains are reputed to produce differing effects on the patient depending on the individual and condition. -- is that that is a speculative statement, correct? It's anecdotal. There are anecdotal reports from patients of differing effects and different efficacies based on the strain-B symptom, correct? From what I hear, yes. And not just from what you hear, there is -- there are those anecdotal reports in the literature, in the literature that you reviewed in putting together the Information for Health Care Professionals document, correct? Yes. And again, to the extent that either terpenes or the various cannabinoids have modulating, enhancing, agonistic, antagonistic effects on each other, it makes sense that they would produce different effects in someone consuming that compound, isn't that right? Well, that's assuming that they do have antagonistic or agonistic effects. They may not. Well, it's clear that, for example, CBD -- well, let's define a couple of terms. There's agonists, correct? Yes. And what's an agonist? An agonist is something that produces an effect. And so if we describe something as a CB2 receptor agonist, what does that mean? It means it activates the CB2 receptor, it turns it on. And if something is a CB2 receptor antagonist, it turns it off, correct? It would block the action of an agonist. And the literature is clear that cannabinoids, CBD for example, can act as an agonist or an antagonist of different receptors, turning them on
A Q A Q
A Q
A Q A Q A Q A Q A Q
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q A Q
A Q
A Q
A Q
and off as you say, and potentially blocking the effect of THC. It's clear that there is a pharmacological process going on with the receptors where CBD could be an agonist, THC is an antagonist of that particular receptor. Something is happening there, correct? What is happening is actually unclear. CBD doesn't act very well at CB1 or CB2 receptors. But it has an effect? Sometimes it has an effect. And the concept of synergistic effects amongst compounds, that's not a foreign concept of pharmacological experience, is it? No. It's not a foreign concept. In fact, it's really the basis, for instance, of drug contraindications, is that one particular compound may enhance, modulate or detract from the effects of another compound. That happens all the time, doesn't it? Yes. So these -- these are not principles at least that are created out of whole cloth. They're principles that apply, generally speaking, to drugs, fair? Yes. And so what Dr. Pate says at paragraph 15 of his report, describing this anecdotal evidence and what patients report describing this anecdotal evidence of differential effect based on strain, that's not outside of what we were just talking about. The concepts, at least, of synergistic effect or modulating effect, that's not outside of those concepts. It fits within the parameter of those -- those concepts which are not specific cannabis but, in fact, applicable to many drugs? It doesn't fall outside the concepts but it hasn't been conclusively demonstrated in any way. At paragraph 14 of your affidavit, you make reference to paragraph 16 of Dr. Pate's report and you take issue with his suggestion that these differing effects that he describes are probably due to varying amounts and ratios of therapeutically active compounds. Your quibble with that, I take it, is that again it's speculative. It hasn't been demonstrated in the lab to your satisfaction, correct? I don't think it's been demonstrated in the lab to
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q
A Q A
A Q
A Q
many scientists' satisfaction, not just mine. And it's -- and that's the -- that's the basis of your disagreement with Dr. Pate's statement, is that there is -- well, you say little to no scientific evidence supporting that claim, correct? Yes. And you suggest that one possible explanation is the placebo effect that we talked about earlier, correct? Yes. And so that would be Person A is using a particular strain of cannabis for -- to deal with their nausea and they tell Person B well, this strain, call it Mountain Jam, works great for your nausea -- works great for my nausea, so Person B tries it and lo and behold it works great for their nausea too. That could be the placebo effect? Yes. Or it might not be the placebo effect. That's fair, isn't it? We just don't know. We don't know but there are experimental studies that suggest that the principle component modulating that effect is THC. There have been some studies done and would argue against the notion that there are other components that modulate the effect. Are you aware of any studies that suggest that a particular ratio of, for example, THC and CBD in -- in a therapeutic application is more efficacious than, for example, THC standing alone? Sorry. Can you repeat the question? Are you aware of any studies that suggest or demonstrate that a -- for example, a THC, CBD mix is more efficacious for a particular symptom or condition than THC standing alone? I'm not really aware of much evidence to that effect. I can't recall but nothing jumps out at me right away. It is the case, however, that -- well, it would fit within the concept of synergistic effects between compounds that if -- that if there are these enhancing effects between compound A and compound B and somebody takes a pill that's got 90 percent compound A and 10 percent compound B, someone else takes a pill that's 50/50, that that
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q A Q
A Q A Q A Q
would produce different effects on the individuals. That fits within the general principle of synergistic effects, right? Yes. At paragraph 15 of your affidavit, you -- you speak to paragraph 17 of Dr. Pate's report. You quote what he says there regarding the various compounds producing synergistic effects and your -- your dispute with that, again, same -same issue as the last two paragraphs. That's a speculative statement and you're unaware of scientific literature supporting that statement, correct? Yes. That's correct. But again, it's -- it's not outside of the general concept of synergistic effects but it's applicable to a number of different drugs, correct? That's correct. At paragraph 16 of your report, you speak to Dr. Pate's report at paragraph 18 and you -- at paragraph 18 of Dr. Pate's report, he incorporates and attaches two articles. One written by an Ethan Russo and a John McPartland, Cannabis and Cannabis Extracts: Greater Than the Sum of Their Parts? published in the Journal of Cannabis Therapeutics and another Cannabis Therapeutics -and also published in Cannabis Therapeutics and HIV/AIDS. And the secondary article being Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects, published in the British Journal of Pharmacology. Do you see that -Yes. -- at Dr. Pate's affidavit? Mm-hmm. Yes. And you take some issue with the scientific value of those two articles, correct? Yes. And your first point of departure from the value of those articles is that they are essentially broad literature reviews that summarize findings obtained by other investigators from studies carried out in laboratories under controlled conditions which have little, if anything, to do with the clinical context. That's a point of disagreement that you have with the value of those studies, correct?
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q A Q
A Q A Q A Q
A Q A
In this context, yes. And you say that conclusions that he gleaned from the papers are limited and narrow therefore, is that fair? In this context, yes. And essentially, a literature review is a compilation and synthesis of pre-existing work, correct? Yes. A scientist, for example Dr. Russo, would go, perhaps perform a PubMed search, find studies dealing with entourage effect -- or cannabis entourage effect, read them and then summarize them in his paper. Is that fair to say? It's fair to say. And in your view, that's essentially what Dr. Russo has done in those two articles? He may have evaluated the value of those papers during the course of his analysis. I can't speak for exactly what he did -Sure. -- but, yeah. He read the literature and made a summary of it. And there's nothing particularly scientifically unsound about compiling evidence from multiple sources and extrapolating from that evidence in that manner? There's nothing unsound about that, is there? There's nothing unsound about it as long as you couch the conclusions in the appropriate terms so that the reader is made aware of the context. And what types of terms would you expect to then see to make the reader aware of that context? There are certain terms that we use as scientists which raise certain caveats about, you know, the nature of those studies and the conclusions that can be drawn. We have a certain kind of language that we use. There is many -- there are many different phrases that we use to raise awareness. You know, to bring the awareness to the reader that, you know, this is a hypothesis, this hasn't been proven or it's only been proven in animals and not in humans. It's only been shown in such circumstances and not other circumstances. Those are the kind of statements that we use. And is it your opinion, having reviewed Dr. Russo's two studies, that he fails to use that
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q A Q
A Q
appropriate language to couch his conclusions? It's perhaps not so much the issue with Dr. Russo's conclusions as much as they are incorporated in Dr. Pate's report, which he says that he believes that this is true and Dr. Russo says it's a hypothesis. So, you know, he says it in his abstract, phytocannabinoid-terpenoid synergy, if proven. So he's saying that, you know, this is not -- this is hypothetical. This is in the realm of a hypothesis and so there's no concrete evidence that that's the case. Well, let's be fair to Dr. Pate. At paragraph 18 he does say this is because the effects, both positive and negative of the primary active ingredients, may be enhanced or medicated by secondary compounds. He -- he's careful to say it's not proven, fair? Okay. And he doesn't -- at least I don't see anywhere in paragraph 18 Dr. Pate saying anything other than he's attaching and incorporating those opinions. He's not saying and oh, by the way, they are true, accurate, any of those kinds of things. Just attaching and incorporating them. Well, in paragraph 17 he has -- he says, "It has been suggested and my opinion is correct." So he is supporting the hypothesis that could produce synergistic effects. And in paragraph 18, he incorporates the two papers and he's not just incorporating the positive stuff, he's incorporating the whole paper? Yes. And the reader can go to that paper and draw their own conclusions, correct? Yes. And your -- at paragraph 16 of your affidavit, you -- you say that Dr. Russo has summarized findings from investigators from studies carried out in laboratories under controlled conditions that have little, if anything, to do with the clinical context. It is the case, it is not, that laboratory work would typically precede clinical work in the development of drugs or drug compounds? That's correct. You have a hypothesis, you test it in the
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q
A Q
A Q
A Q A Q
laboratory, you find out if there's a mechanism of action to support your hypothesis and then it moves down the chain and possibly someone conducts clinical work? Yes. And whether or not the clinical work has been conducted is dependent on a number of factors, many of which may be absolutely irrelevant to whether or not the lab hypothesis is valid but may include such things as, is there funding to do the clinical work; is there somebody willing to pay the bill for doing the clinical work; is there a desire to do the clinical work, is there a valid product to bring to market; those considerations which are extraneous to, does the hypothesis we developed in the lab play out in the clinical setting, correct? Yes. The fact that no -- that clinical studies have not been conducted to validate the lab work does not, in and of itself, invalidate the lab work or the hypothesis being tested in the lab, correct? That's correct. You say at paragraph 17 of your affidavit that scientific value or importance of research papers published in the scientific/medical literature is often judged by what you describe as an "impact factor" and then you define that term as a measure of the number of times the paper published in the previous few years have been cited in the scientific literature, is that right? I believe so. That's one definition of an impact factor, yes. And if a paper is cited lots and lots and lots and lots of times, clearly it has greater impact in the field than a paper that has never been cited, correct? Generally speaking, yes. That's not to say, of course, that a paper that's never cited has no value, it just hasn't been cited, correct? That's correct. And the concepts expressed in a paper that's never been cited, their worth may have nothing at all do with whether or not that paper is ever cited again. There may be a number of other intervening factors that determine whether or not that paper
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q A Q A Q A Q A
Q A Q A
Q A Q A Q
is cited, correct? Possibly, but one would have to ask why that paper has never been cited. And you say at paragraph 18 that the Journal of Cannabis Therapeutics, which is, I take it, the journal that the first article, Cannabis and Cannabis Extracts: Greater Than the Sum of Their Parts?, that was published -- it was co-published in the Journal of Cannabis Therapeutics, correct? I believe so, yes. Yes. And also published, according to at least Dr. Pate, in Cannabis Therapeutics and HIV/AIDS, edited by Ethan Russo, correct? I believe that's the case. Are you aware of what Cannabis Therapeutics and HIV/AIDS is? No. And so you don't speak to that particular -- the impact factor of that particular publication, you don't know what it is? No. The Journal of Cannabis Therapeutics, at least, you indicate has no reported impact factor. How do you -- how do you find that out? Usually that information is available on the website of the journal, or it can be gained -- or gleaned from other sources such as the Institute for Scientific Information or other agencies like Reuters. And how specifically with respect to the Journal of Cannabis Therapeutics did you come to the conclusion that it has no reported impact factor? I went to their website and I did not see an impact factor posted on the website. And that website still exists? I think I got that from the International Association of Cannabinoid Medicines, which was the association, I believe, that supported the Journal of Cannabis Therapeutics. And that journal ceased publication in 2004, correct? Yeah. That's my understanding. Did you attempt to determine impact factor of the Journal of Cannabis Therapeutics by virtue of going to any of these other sources you say? No, I didn't. So it's possible that it has an impact factor,
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q
A Q A Q A Q A Q A Q
A Q A Q
A Q A Q
it's just not listed on its website? Very possible. You just don't know? I don't know. You compare the Journal of Cannabis Therapeutics at paragraph 18 of your affidavit, you contrast it to the New England Journal of Medicine, which you say has an impact factor 53.48, correct? Yes. And is that from the New England Journal of Medicine website? It is. The New England Journal of Medicine is -- my understanding, it's not specific to one particular area of medicine, is it? That's correct, it's not. So unlike the Journal of Cannabis Therapeutics, the New England Journal of Medicine has a much broader scope, correct? Yes. And journals with a broader scope are going to be cited more than journals with a narrow scope, correct? Yes. And that could be one explanation for the differential impact factors, the New England Journal of Medicine covers all kinds of different areas, correct? Yes. Not just cannabis therapeutics. The same applies to the Lancet, which you also reference at paragraph 18? Yes. Did you attempt to determine whether or not Dr. Russo's and Dr. McPartland's article, Cannabis and Cannabis Extracts: Greater Than the Sum of Their Parts? as an individual article had a particular impact factor? No. So that individual article may well have been cited in the literature somewhere but you don't know if it has or hasn't? That's right. And if it has been cited in the literature elsewhere, that would increase, at least according to the reason that you put here in your affidavit in paragraphs 17 and 18, that would increase its
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
scientific value, would it not? Possibly. It depends how -- it depends again on how the impact factor is calculated. Q Well, at least if you're determining impact factor in the way that you define it at paragraph 17, number of times papers published have been cited, if it's been cited a number of times, that increases its impact factor, correct? A Under this definition. MR. TOUSAW: My Lord, I note the time. THE COURT: All right. We'll take 15 minutes. A (WITNESS STOOD DOWN) (PROCEEDINGS ADJOURNED FOR AFTERNOON RECESS) (PROCEEDINGS RECONVENED) HANAN ABRAMOVICI, recalled. MR. TOUSAW: Thank you, My Lord.
CROSS-EXAM ON VOIR DIRE BY MR. TOUSAW, CONTINUING: Q Doctor, just before the break we were discussing the impact factor of various publications and in particular, your affidavit at paragraph 19 in which you indicate that Dr. Russo, one of the authors of the 2003 article that we're discussing, was also an editor of the Journal of Cannabis Therapeutics. You see that at paragraph 19? Yes. And you say this would call into question the so-called peer-reviewed process for this paper. Do you have, sitting here today, any evidence that would suggest that the paper was not peer-reviewed? No, I don't have any evidence that it was not peer-reviewed. It's a fairly serious accusation to suggest that an editor of a journal is labelling papers as peer-reviewed when, in fact, they're not peer-reviewed, isn't it? My concern here was that since he was the editor of the journal, that that could cause a conflict of interest. That's what I meant to say by that paragraph, actually. So you don't -- when you say "so-called
A Q
A Q
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q
A Q
A Q
A Q
A Q
peer-reviewed process for this paper," you dont mean to suggest that it was not peer-reviewed, you don't know? I don't know. You do say that, "Peer-review is a benchmark by which research is evaluated." That's accurate, correct? Yes. And you go on to critique the journal that you "believe was published by the International Association of Cannabinoid Medicines, a body which," you say, "has a vested interest in promotion of cannabis and cannabinoids as therapeutics." I take it that you're suggesting in that comment that there may be some editorial or journalistic bias because the publisher has an interest in the subject matter, a vested interest in the subject matter, correct? That is correct. And that's similar to what we talked about this morning, vis--vis researchers, scientists employed by GW Pharmaceuticals, for example, have an interest of promoting the work of GW Pharmaceuticals, correct? Yes. That's correct. That's, of course, not exclusive to Dr. Russo but that's a problem, if you will, that -- that exists throughout scientific work, scientific endeavour. As we talked about this morning, your -- other than, as you said, the academic fields or your tenured professors at universities, if you're employed by somebody you have a vested interest in your employer's views of a particular topic being accepted? Yes. Dr. Russo, as a researcher/publisher in this field, if it were to come up, for example, that he was claiming that certain articles were peer-reviewed when, in fact, they were not, that could have fairly serious repercussions for his career as a scientist, couldn't it? Yes. Do you have any evidence, specific evidence, suggesting that the International Association of Cannabinoid Medicines had a influence in either the content of -- well, influence in the content of the Russo article, the 2003 Russo, McPartland
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q A Q A Q
A Q
A Q A Q A Q A Q
A Q A
article? I don't have any solid evidence. Other than what you've put in your affidavit here, you don't have any evidence at all either way, correct? I don't. It was just a concern. And with respect to Dr. McPartland, are you familiar with any of John McPartland's work? Generally speaking, familiar. Not very familiar. I've seen his name on a few publications. He's published in the field, correct? I think so. Yes, he has. The second paper incorporated into Dr. Pate's affidavit titled Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects, that was published in 2011 in the British Journal of Pharmacology, is that correct? Yes. That's correct. And the British Journal of Pharmacology, I take it -- well, let me ask. Did you attempt to determine the impact factor of the British Journal of Pharmacology? I didn't. Fair to say that it's a fairly well-respected and reputable journal? I would say so. It's likely to have a fairly high impact factor, correct? Higher, yes. But you don't know precisely what it is because you didn't look? I did not look. Now, you say at paragraph 20 of your affidavit that -- you quote from Dr. Russo's article. Indeed, you highlight, if proven -phytocannabinoid-terpenoid synergy, "if proven" increases the likelihood that, and you've added the emphases on "if proven" and you say that the author is implying that the possible synergy is not established and purely hypothetical, correct? Yes. That's your interpretation of at least that sentence appearing in the article, correct? That's my interpretation of that sentence. Dr. Russo speaks to that further in the article and the conclusions with regards to the kind of work that would be needed to establish such a
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q
hypothesis. And of course, hypothetical is not -- is not the same as nonexistent, correct? In other words, hypothetical is a tentative explanation based on observations that may not yet have been demonstrated by experiment. Is that a fair definition? I guess so. At paragraph 21 of your affidavit you make reference to paragraph 19 of Dr. Pate's affidavit. Yeah. Paragraph 10 of Dr. Pate's affidavit reads: The glandular trichomes containing these chemical compounds can be isolated from the female flowers, thus eliminating most of the plant matter in the final product. And your -- your dispute with what Dr. Pate says is essentially glandular trichomes are not just in the female flowers, correct? That's correct. But you don't have any -- I take it you don't disagree with -- other than what we've just discussed, you don't disagree with Dr. Pate's statement that, in fact, you can isolate the glandular trichomes and eliminate most of the non-trichome plant matter in that final product, correct? I would assume that you can. I've never attempted the process myself, so I can't tell you whether or not it's possible but I would imagine that it is possible. And you have no reason to dispute Dr. Pate's statement therefore? That's correct. The glandular trichomes themselves, they're -they're part of the plant, correct? They are on top of the plant, on the leaf surface. They project from the leaf -- or from the plant material. And they're connected to the plant? They are connected to the plant. They're a part of the plant? Yes. Much like a leaf from the plant is part of the plant, correct?
A Q
Q A Q A Q A Q A Q
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q
A Q
A Q A Q
A Q A Q A Q A Q
Yes. And when you snap a leaf off the plant, is that, in your view, no longer part of the plant? Well, it's not part of the plant anymore if you've taken it off the plant. The dried flowers, for example, of a female cannabis plant, when you snip them off the top of the plant, are they still part of the plant or not part of the plant any longer, in your view? Well, I'm not really sure I understand your question. That's fair. When the plant is growing -- you know, a live plant is growing, it hasn't been harvested, everything attached to the plant is part of the plant, correct? Yes. Cut the plant down, just above the roots, the things still attached to it, they're still part of the plant, correct? At that stage, yes. And if you snip a bud off the top of the plant, for example, it's no longer connected to the plant itself but the buds are still part of the plant, correct? Yes. And the trichomes on those buds are still part of the plant, correct? Yes. Similarly, if you yank a leaf off, it's no longer connected to the main body of the plant but it's still part of the plant? Yes. It's still a plant part? Yes. It all depends on how you phrase the question. Fair enough. Fair enough. The -- at paragraph 20 -- at paragraph 20 of Dr. Pate's report he speaks to a variety of methods for isolating the glandular trichomes and he speaks to micro pore screens, he speaks to emersion in water and straining through fine mesh and suggests and says that these processes result in the removal of the trichomes from most of the other plant matter but they leave the resin still housed within the glandular trichomes. You don't have any dispute with what Dr. Pate says at paragraph 20 of his affidavit?
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q
Q A Q
A Q A Q
Q A Q
I don't have any dispute with it because, once again, I'm not familiar with those procedures so I can't really comment on them. Outside of your realm of expertise? Outside of my realm of expertise. At paragraph 21 of Dr. Pate's affidavit he speaks to extraction by hand, by soaking in fat or alcohol and by straining out plant debris. Again, is that outside the realm of your expertise? It's outside the realm of my expertise but I don't dispute extraction into fat and alcohol and other organic solvents. It's what I've seen in the literature. It's being done, fair to say? Yes. Similarly, there's a discussion of the use of petrochemical solvents and you speak to that in paragraphs 22 and 23 of your report, citing some studies, suggesting, well, this extraction procedure at least is common, can be quite dangerous. Is that fair to say? That's my understanding, yes. And that's your understanding based on the literature that you've reviewed and cited in your report, correct? Yes. I take it you're unaware of whether or not it's possible to use pure, unadulterated ethanol which can safely be evaporated at room temperature and which poses no explosive risk if done with proper ventilation? You don't know about that process, fair to say? What I would say is that all those liquids are flammable liquids, ethanol, methanol, acetone, butane, petroleum -- petroleum ether, those are all, of varying degrees, flammable liquids. So there can be dangers associated with the extraction using those solvents. And similarly, the process can be conducted safely given proper procedures, proper setting, correct? If the appropriate safeguards are taken then I would assume that the risk is decreased. Not necessarily eliminated but decreased. And certainly, as you note, there are accidents that happen when people are using some of the petrochemical solvents to extract resin from cannabis, explosions and burns, correct?
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q
A Q
A Q A Q
That's my understanding, yes. And that's happening currently under the regulatory scheme in place. In other words, under essentially the prohibition of cannabis, modified only by the MMRA in Canada, correct? It happens. And it's happening despite the fact that there's a law in place that says you can't possess this material and you can't make these extractions, correct? I say it happens during that process and can happen. At paragraph 23 -- well, at paragraph 22 of Dr. Pate's affidavit he speaks to terminology used to describe what's remaining after certain of these extraction processes. I take it you don't have any quibble with what Dr. Pate says at paragraph 22? I don't have any quibble but again, some of those terms are outside of my area of expertise. You've heard the term hash, correct? Yes, I have. And you understand that to be essentially the concentrated resin heads from the female marihuana plant absent the rest of the plant matter, fair to say? Yes. Have you heard the term bubble hash? No. Have you heard the term keef? No. And you understand that people do extract glandular trichome heads, the resin, into cooking oil or butter -Yes. -- and call that cannabis butter or cannabis oil? Yes. And hash oil, that's typically what results after the solvent extraction method, correct? Yes. And you're aware that that particular product can be smoked? Yes. Whereas the cannabis butter and the cannabis cooking oil, nobody is smoking butter or olive oil, correct? Not that I know of.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q
A Q
A Q A
Q A Q A Q
A Q
A Q A Q A Q
You haven't come across that in the literature? I haven't. Fair enough. Paragraph 23 of Dr. Pate's affidavit speaks to the point of these processes being to capture the trichomes and their contents, the resin, for lack of a precise term, while removing the plant matter and other by-products remaining in the plant matter following harvest. You don't have any dispute with what Dr. Pate says there? No. At paragraph 24, Dr. Pate says the plant matter itself is not a desired therapeutic component except as a vehicle for carrying for the resin prior to and during the act of pyrolysis and smoke inhalation. Do you see that first sentence? I do. Do you have any -- I take it you don't disagree that the plant matter itself is not a desired therapeutic component? I don't disagree with it but I don't know that the plant matter itself has ever been studied for possible therapeutic purposes, so it could, very hypothetically, have a therapeutic purpose, we just don't know. We don't know? I don't know. But at least in the literature -That's right. -- you're unaware of any studies, anecdotal reports, that once you've separated out the resins that the remaining cellulous plant matter has a pharmacological effect? Not that I've seen. Plant cellulous, however, does have some pharmacological effect in that if you ingest it, it can produce biological effects in the system, correct? I don't know that it can produce biological effects in the system, per se. I don't know what those biological effects could be. Outside of the realm of your expertise? I would say that it's fibre and fibre can be a bulking agent. Right. That it has any particular pharmacological properties, I don't know. At paragraph 25 -- I won't ask that. At
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q A Q
A Q A Q A Q A Q
A Q
paragraph -- at paragraph 26 of Dr. Pate's report, Dr. Pate says, in part, plant matter is composed of non-digestible cellulous. Do you have any dispute with that portion of the sentence? No. Dr. Pate further says that that is not harmful but it may be contraindicated for persons with gastrointestinal conditions. At paragraph 25 of your affidavit you take issue with that statement and specifically, you indicate that Dr. Pate does not specify the conditions to which he is referring, nor does he provide evidentiary support for the claim and you say in the absence of such information, you simply can't agree with that statement, correct? Yeah. That's right. You don't have any studies that you're independently aware of that refute that statement, correct? Not really, but I don't recall having seen that cellulous is contraindicated for people with gastrointestinal disorders. But independently, in terms of your professional experience, academic experience, you're unaware of any studies refuting the proposition that cellulous may be contraindicated for persons with gastrointestinal conditions? Yeah. Just don't know? I don't know. It is the case that in addition to the glandular trichomes, the cannabis plant has non-glandular trichomes, correct? That's correct. And that those non-glandular trichomes -- well, Dr. Pate called them silicified non-glandular trichomes. Is that a term you've heard before? I've seen it here and there, yes. And those non-glandular trichomes would not themselves contain any of the pharmacologically active ingredients, THC, CBD, the terpenes, any of those things, correct? As far as I understand they would not contain those substances. And if I put to you that in Dr. Pate's direct testimony he suggested that, though silicified, non-glandular trichomes are potentially a plant
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q A Q
A Q
A Q A Q A Q
A Q
defence mechanism in that they're abrasive to predators, you're unaware of any information that would contradict that claim, or at least it's outside of your realm of expertise. It strays into botany. Is that fair to say? I would say it's outside of my area of expertise. At paragraph 28 of Dr. Pate's report, he indicates that the glandular trichomes themselves are not a desired therapeutic component except as a vehicle for carrying the resin prior to and during the act of extraction, and I'll just stop there. Dr. Pate is correct when he says the trichome itself isn't, you would say pharmacologically active, he would say therapeutically active, but the trichome itself is not the desired compound. It's the material inside the trichome, it's the THC, the CBD, the terpenes, correct? I would agree. And so much like the buds carry the glandular trichomes, the glandular trichomes carry the resin, fair to say? That's fair to say. And you're unaware of any studies that suggest that trichome heads themselves, as opposed to the resin inside them, have therapeutic -- or therapeutic or pharmacologically active properties? I haven't seen anything in the literature to that effect. The -- it is the case that the resins contained in the glandular trichomes are extracted into fat, you agree with that, correct? They're extractable into fat? Yeah, they are extractable -They're fat soluble, correct? Yes, they are. They're extractable into alcohol, they're alcohol soluble, correct? Yes. And you take issue with Dr. Pate's use of the term fatty bodily fluids because you say there's no mention of which fatty bodily fluids or how they would be used to extract the resin, correct? Yeah. I found the construction of the sentence a little unusual. If -- well, for example, if one were to ingest -ingest a cookie, a cannabis infused cookie that's
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q A Q
A Q
made with a cannabis infused butter, the resin is extracted into the oil, goes into the body, there are fatty bodily fluids within the gut, correct? There wouldn't be any fatty bodily fluids in your gut, that I am aware of. There is a -- there are fatty fluids in bile or are you not aware of that? In bile, yes. Yeah. And at some point, if you eat something it'll come into contact with bile in the gastrointestinal system? Yes, it could. Yes. And so to the extent that you have glandular trichomes that you've ingested come into contact with the bile, which is a fatty bodily fluid, that -- the resin inside the glandular trichomes could be extracted into that -- that bile, that fatty bodily fluid because the resin is fat soluble, it comes into contact with fat, it's therefore extracted into the fat. Is that fair? That's one situation which could happen in the body, yes. At paragraph 29 of Dr. Pate's affidavit he describes a number of processes by which one can ingest the active compounds of cannabis. Subparagraph (a) he speaks to inhalation which he describes as a high temperature process by which the plant matter or the trichomes themselves are heated to the point of ignition and you inhale the smoke. You're familiar with that process, correct? Yes. And that is -- that's smoking, correct? Yes. Well, for the first part it's smoking, yes. The first part is smoking. Yeah. That's -- the material is ignited. Now -- it's now burning and then you inhale it and you're smoking a joint, for example? Mm-hmm. Yes. You also are aware that there's a process called vaporization -Yes. -- correct? Yes. And that's a process Dr. Pate describes as a low temperature process which heats the plant matter
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q A Q
A Q
A Q
A Q
A Q
to the point at which the active ingredients vaporize and become airborne which is then inhaled. Other than the term low temperature, you don't dispute that that's what vaporization is, correct? I don't dispute it. Your difficulty with Dr. Pate's description of that process is that, according to you, it's not a low temperature process but it's a lower temperature process compared to pyrolysis burning, for example? Yes. And that vaporization temperature is typically between 180 and 195 degrees Celsius, correct? Generally. I take it the remainder of paragraph 29 of Dr. Pate's affidavit in which he describes oral ingestion, topicals and transmucosal, you don't speak to that at paragraph 27 of your affidavit. I take it you don't disagree with what Dr. Pate has said in (b), (c) and (d) of his paragraph 29? That's correct. I don't disagree. At paragraph 30 of Dr. Pate's report he indicates the various modes of ingestion carry with them different risks and benefits. You don't disagree with that, correct? I don't disagree. And he goes on to say he's going to focus on oral versus -- oral or topical versus inhalation. He's not expressing any opinion there, just sort of setting the stage for the remainder, is that fair? Yes. At paragraph 31 of Dr. Pate's affidavit, he speaks to a benefit of orally ingesting cannabis based medicine arising from people suffering from gastrointestinal conditions such as Crohn's disease or irritable bowel syndrome and that for those individuals, oral ingestion allows for the application of therapeutic compounds directly to the site of pathogenicity. You take issue with that claim, the implied claim from this paragraph, that oral ingestion is more beneficial than inhalation for persons suffering from gastrointestinal conditions. You take issue with that implied claim, correct? I do. Because, as you say, you're aware -- you're
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q A Q A
Q A
A Q A Q
unaware of scientific evidence supporting that implied claim, correct? That's correct. There are other issues as well. It is the case, however, that oral ingestion of cannabis-based medicines does allow for application of the therapeutic compounds directly to the site of pathogenicity. You don't disagree with that being a mechanism of action that's occurring when somebody eats cannabis as opposed to smoking it? I disagree with that, actually. You say that the compounds are not being directly applied to the site of pathogenicity by being eaten? That's correct. Can you explain your disagreement there? Yeah, I can because in some of these disorders, the site of pathogenicity may be far away from where the cannabinoids are absorbed and so if the cannabinoids are absorbed into the bloodstream before they hit the site of pathogenicity, then -then that wouldn't happen. You wouldn't get the drug in contact with the site of pathogenicity. Where is the site of pathogenicity, in your understanding, for a condition like irritable bowel syndrome? Well, I think that it can be in the bowel at certain -- at different points in the bowel. In Crohn's disease it can be at several different points in the digestive system. And so, you know, it would really depend on where the site of pathogenicity is. It's possible to have the site of pathogenicity being in your colon, but most of the agent would be absorbed way before it hits the colon. Well, let's focus on that for a moment. If the site of pathogenicity is in your colon, you say most of the agents are absorbed prior to getting to the colon, correct? Yes. Not all are, however? The vast majority. Ninety to 95 percent. And I note that you don't have a citation for that in your -- at least at paragraph 28 of your report or, it appears, at paragraph 29 of your report. Do you have any specific study in mind that suggests --
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q A Q
A Q A
Q A Q A Q
A Q
A Q
I don't have a specific study in mind but I think it's very evident from the literature that orally absorbed cannabinoids undergo an extensive hepatic first pass effect and that occurs way before it gets to the colon. That occurs where? I think it occurs in the small bowel. But sitting here now, you can't point to a particular study that suggests that? I can't think of a particular study off the top of my head, no. Inhaled cannabis, inhaled marihuana, the compounds are not going to -- other than within the system itself, the compounds are not going to be applied directly to, for example, the colon? That's correct. At all, isn't that correct? Well, I wouldn't say not at all. I wouldn't say that they are necessarily concentrated in the colon. The cannabinoids might be found all over the body, including the colon but not exclusively the colon. And that's because even in the method of inhaling, it gets into the bloodstream, the blood goes throughout the body? That's right. Some gastrointestinal conditions are specific to the gut, for example, the stomach. Is that fair to say? Yes. And in that instance, if one is applying cannabinoids through oral ingestion, they go into the gut, there's going to be some direct application to the site of pathogenicity, correct? Theoretically, yes. The concept itself of application -- the concept itself, application of therapeutic compounds directly to the site of pathogenicity, that is not a concept, at least, that you dispute? No. It's the basis behind, for example, topical antibiotics being -- being put on the site that you have the irritation or the possible infection, you want to put it there first because there's no particular point of taking a systemic dose when a topical dose will do the job, correct? Yes. That's correct.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q
A Q A Q A Q
A Q A Q A Q
A Q A Q A
Q A
And that's not specific to cannabis. That's a general principle of pharmacological application? Yes. You indicate at paragraph 28 of your affidavit that most patients suffering from IBS, such as Crohn's, report smoking cannabis rather than consuming it orally, correct? From what I've seen in the literature, yes. And smoking cannabis is the primary mode of ingestion, period, correct? From what I understand from the literature, yes. Most people smoke it, correct? That's what I understand, yes. And so it stands to reasons that persons with any conditions, including irritable bowel syndrome, most of those people are going to be smoking cannabis rather than ingesting it orally, correct? I would assume. And as a by-product of the smoking process, there is going to be the inhalation of some unwanted compounds, correct? That is correct. Compounds that may be damaging to human health, correct? Yes. That's correct. The fact that most people smoke cannabis, even most people with an inflammatory bowel disease such as Crohn's, smoke cannabis as opposed to orally ingesting it, that's not necessarily probative of whether or not smoking it is more beneficial than eating it, correct? Sorry. Can you rephrase the question or -Yes. -- restate the question. The fact that most people smoke cannabis as opposed to eating it, is not proof that smoking it is more efficacious than eating it, correct? In and of itself, no, but one of the drawbacks of oral ingestion is that you get a -- the absorption process is variable and it's unreliable and it's erratic and people might not want that. They might want to have a more rapid and a better way of controlling their exposure to the -- to this drug rather than orally ingesting it. And that's a concept known as self-titration, correct? Yes.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46
Q A Q
It's a fairly common concept in medicine, correct? Yes. It's common not just with cannabis but with pharmaceutical prescription drugs as well, correct? A With some, yes. Q You go to your doctor complaining of pain. Your doctor gives you a prescription for a painkiller, says take one, see if it works for your pain. You go back the next day, that's not working. The doctor says well, try two tomorrow. In effect, you're in a feedback loop in which you're adjusting the titration of your dosage, based on whether or not you're achieving the desired effect, correct? A Yes. MR. TOUSAW: My Lord, I note the time. THE COURT: Yes. Ten o'clock tomorrow morning. MR. TOUSAW: Thank you. (WITNESS STOOD DOWN) (PROCEEDINGS ADJOURNED TO FEBRUARY 7, 2012, AT 10 A.M.) Transcriber: S. Hutchinson
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Victoria, B.C. February 7, 2012 THE CLERK: In the Supreme Court of British Columbia this Tuesday, the 7th day of February 2012, calling the matter of Her Majesty the Queen against Owen Edward Smith, My Lord. MR. ECCLES: My Lord, for the Crown, Peter Eccles, E-cc-l-e-s, and with me as my co-counsel is Ms. Kristina Guest. THE COURT: I dont think counsel need to introduce themselves every morning. By now I can recognize you. MR. ECCLES: Thank you, My Lord. MR. TOUSAW: Thank you, My Lord. THE CLERK: Remind the witness, My Lord? THE COURT: Yes, please. THE CLERK: Witness, having been previously affirmed, I remind you, you are still under affirmation. HANAN ABRAMOVICI recalled, warned. THE CLERK: Please state your full name and spell your last name for the record. A The first name Hanan, H-a-n-a-n, last name Abramovici, A-b-r-a-m-o-v-i-c-i. MR. TOUSAW: Thank you, My Lord. CROSS-EXAM BY MR. TOUSAW ON VOIR DIRE, CONTINUING: Q Dr. Abramovici, between the time that you left the stand yesterday afternoon and you taking the stand this morning did you discuss your testimony or the substance of this case with anyone? I did not. Did you communicate with anyone in any way about this case about the substance of your testimony? I did not. When we broke yesterday afternoon we were talking about the concept of self-titration; do you recall that conversation? Yes. The -- and I think we had established that the concept of self-titration is a fairly common one in medicine; is that a fair assessment? Its a fair assessment, yes.
A Q A Q A Q A
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q A Q
A Q
A Q
A Q
And that concept of self-titration occurs with oral pharmaceutical drugs, including cannabis based drugs and non-cannabis based drugs, correct? It can occur not just by oral but by other methods as well. But it does occur with oral, yes? It does occur with oral, but its much more difficult to achieve by oral so it occurs less often, I would imagine. And thats because of, at least with respect to cannabis or cannabinoids, the -- what you describe as the erratic -- slow and erratic uptake into the system, correct? Yes. It creates -- would it be fair to suggest it creates -- the oral ingestion say of a cannabis cookie would create a need for a longer feedback? In other words, if an individual smokes cannabis, they will feel the effects fairly quickly, and therefore can make a fairly quick determination as to whether or not they should smoke more cannabis, correct? In that respect, yes. And with oral ingestion of cannabis, cannabinoids that period of time between the ingestion of the compounds and the feeling of the effect or the non-feeling of the desired effect, thats a longer time though, correct? Yes. And so it would require one to, for example, perhaps eat a quarter of a cannabis-infused cookie, wait an hour or two, see if the effects been produced, see if there are any negative side effects being produced, make a determination as to whether or not one should ingest more in order to achieve the desired effect. Is that a fair description of a self-titration process for oral cannabinoids? Its a fair description, but I would add one more thing is that you dont know how much youre ingesting. You dont know the concentration, the amount, and so you could be ingesting a lot on your first bite, and ingesting a lot less on other bites or vice versa, so self-titration is made even more difficult because you dont know how much youre actually taking in. And if one does ingest more of say a cannabis
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A
A Q A Q
cookie than necessary to achieve the desired effect, one can experience some of the side effects that we described earlier, the euphoric effects, dizziness, potentially delusions, hallucinations in higher concentrations, correct? That depends on the -- that depends on the person, right. Some people may experience those effects at low dosages, some people may experience them at higher dosages, and often its the window between a therapeutic index and the adverse effects can be narrow. And thats true not just of cannabis-based substances, but thats also true of many other prescription drugs, correct? Its true of some prescription drugs, not -not -- not a lot. Some -- some prescription drugs, I cant tell you off the top of my head which ones, but... It would be good advice to someone considering eating, for example, a cannabis-based cookie, that they ought to eat just a little bit, see what happens, and then if theyre not achieving the desired effect, and theyre not experiencing any negative side effects, perhaps eat a little bit more the next time to try to achieve those effects? That would be reasonable advice to give somebody, wouldnt it? You dont really know what youre ingesting, so you would have -- it would be a pretty -- it would be a -- a bit of a lottery, I think. But you dont -- you dont actually -You -- you -- you would --- you dont actually know whether or not that last statement is true, correct? I mean, you dont know whether or not the person knows what theyre ingesting or not? Well, I think in the case of a cannabis cookie, if you compare it to medication containing a cannabinoids like Marinol, you know exactly how much youre getting, so you can figure out a dose far more easily than you can with a cannabis cookie. But at least with respect to the cannabis cookies, for example, at issue in this case, you dont have any idea sitting here today how much or how little THC, CBD or any other active components were in those cookies, correct?
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q
A Q A Q
A Q
I dont know. It would vary. It could vary from cookie to cookie, batch to batch, product to product, day to day, week to week. I wouldnt know. And you dont know whether or not, for example, the people producing the cookies are engaged in testing them for potency or anything like that? You dont know whether theyre doing that or not, do you? Not that I know of. And you dont know whether the members of the Cannabis Buyers Club of Canada, who are using the cookies, are aware of the contents of those cookies or at least the contents of the -- the quantitative amounts of the active ingredients? You dont know whether they do or dont know whats in them? I dont know if they do know or they dont know. Are you aware of whether or not Health Canada makes available to persons authorized to possess marihuana the ability to test either their marihuana or marihuana-derivatives in any of Health Canadas labs or quantities or amounts of the active ingredients? I know that the cannabis that Health Canada supplies goes through rigorous quality control process, and the can -- the THC level and the levels of other cannabinoids are measured, as well as the levels of other contaminants, and I think its a pretty standard process, and that information is available to the public. Yes. But you dont know -- do you know whether or not Health Canada makes available the ability for persons with an authorization to possess dried marihuana or produced marihuana the ability to test that marihuana for quantitative levels of THC, CBD or the other active ingredients? I do not. Would it surprise you to learn that that is not something provided by Health Canada? No, it wouldnt surprise me. And Health Canada of course, in addition, Health Canada has a contract with Prairie Plant Systems that produces the marihuana that you just described, correct? Thats correct. And that is sold to persons with an authorization
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q A Q
A Q A Q A Q A Q
A Q
A Q A Q A Q
to possess, thats correct, right? Yes. And that is a gamma irradiated product, in other words its gone through a gamma irradiation process before its sold to the public, correct? It is for safety purposes. Are you aware of any studies demonstrating the safety of gamma irradiation of inhaled products? Im not aware of either safety or not safety, but a lot of -- a lot of things are gamma irradiated. But Health Canada hasnt conducted any testing that youre aware or of that youve produced in your information for healthcare professionals on the issue of whether or not gamma irradiation is a safe process for an inhaled medical product? Health Canada hasnt done that testing, have they? Not that I know of. Im not aware that theres a health risk with gamma irradiated products. You dont know one way or another, do you? Well, Ive never seen anything that would suggest that there would be. Is that something youve looked for? Ive never come across it. Its not something youve looked for, is it? Not specifically, no. And in review -- in preparing the Information for Healthcare Professionals document you didnt look for studies on whether or not gamma irradiation on smoke products is safe or unsafe, did you? Gamma irradiation of cannabis is a process thats employed by other companies as well. But you, in reviewing and putting together your review of the literature in updating the Health Canada you didnt perform a search for whether or not gamma irradiation has been studied on marihuana and whether or not its safe for the public to consume it after its been gamma irradiated? You didnt do that research, did you? No, I did not do that research. Irradiation of a material does create changes in the material thats being irradiated, correct? Yes, it can. And thats the point, isnt it, of this, youre attempting to kill pathogens by using irradiation to do so, thats correct, isnt it? Yes. And that can produce changes in not just pathogens
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q A Q A
A Q
A Q A Q
A Q
but the other active compounds that are present in the product, thats correct, isnt it? Yes. With respect to self-titration, it is the case, is it not, that a product like Marinol in the product monograph talks about self-titration, speaks to the issue of beginning with a smaller dose and then increasing the dosage if one isnt achieving the desired effect, correct? I believe thats correct. And thats good advice, isnt it? I would say that its sensible advice, but at least you know what youre starting off with, yes. If you read the product monograph, correct? Well, the physician is the one who would be reading the product monograph, and they would be the one prescribing the drug to the patient as they do for all their -- all other drugs. And the physician is the one in terms of people that have an authorization to possess thats signed the forms that Health Canada requires in order to issue that authorization, thats correct? Thats correct. And you dont know sitting here today whether or not any particular physician before prescribing Marinol has actually gone to the product monograph and read? You dont know whether thats the case or not, do you? I cant speak for physicians. One hopes that theyve done that, but we dont know? One -- one -- one hopes that they take the necessary measures when theyre treating patients to the best of their abilities. And ultimately the patient goes home with a prescription, and whether the patient takes one tablet, one capsule, or two or three or ten or 40 really is a decision of the patient, not a decision of the physician, correct? Yes, thats correct. Early -- late in the afternoon yesterday we talked about something called the first-pass effect and the -- the way THC and the other active compounds in cannabis or cannabinoids are metabolised, and I want to focus in on the issue of, lets take a hypothetical, eating a cannabis cookie. Now, a cannabis cookie, you eat it, you chew it up and
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q
Q A Q A Q A Q A Q
swallow it. Some of the active compounds are going to be absorbed through the mouth, correct, in the process of chewing? Possibly. I dont know that thats established. And theyll go into the stomach and begin to be digested, correct? Yes. What happens after that in terms of metabolism of -- and lets just focus on THC, what happens after one chews it up in the stomach in terms of metabolism of THC? Well, I believe the THC begins to be degraded in the stomach along with the rest of the material, the food material. It then passes into the small intestine where it gets mixed with some enzymes released by the pancreas and the liver, and it begins to be absorbed in the small intestine. In fact, most of the absorption occurs -- of nutrients occurs in the small intestine at different points, and from there the nutrients are absorbed by the portal vein, and then they go into the liver where those nutrients are -- undergo a series of metabolic reactions in the liver, and then from there the nutrients, metabolites or compounds are then distributed to the rest of the body through the circulation, and then the remnants of the food get passed into the -- into the colon from where water is mostly reabsorbed into the body and it passes through the colon to the other side. And the remaining remnants are excreted either in the urine or in the feces, correct? Yeah, thats correct. And in fact some THC, for example, remains present and is excreted in both the urine and the feces, correct? Thats correct. You used the term nutrients. Does that also include the active compounds in the cannabinoids and other compounds? When Im talking about nutrients Im talking about generally in digestion, so it could be carbohydrates, proteins, fats, vitamins, minerals. And so just focusing on cannabinoids -Right. -- we have a degradation in the stomach as a product of digestion, passing into the small
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
Q A
A Q A Q A Q
intestine, mixing with enzymes, then theres the beginning of the what you called the absorption process where most nutrients are absorbed. Does that also include, for example, THC? Is most of the THC absorbed in the small intestine? I believe it is, yes. And then the remaining THC thats not absorbed by the small intestine, that then passes through into the large intestine, the colon, and then it is excreted, correct? Well, the first-pass effect of THC is 90 to 95 percent, so whatever that is, five or ten percent of whatever was not broken down in the stomach to begin with, so were getting it to a small percentage. I would assume that that small percentage then goes on into down into the colon and further on. And are you aware of studies suggesting that combining the intake of cannabinoids with food mitigated or minimizes the first-pass effect? I cant think of studies off the top of my head, but some of them there might be something that minimizes the first-pass effect or enhances the first-pass effect. I would say that foods in general can have an effect on the -- on the bioavailability of any compound. And so its certainly possible, at least in your understanding of the physiological processes, that intaking cannabinoids with food might in fact minimize the first-pass effect, therefore leaving more of the cannabinoids present in the matter thats being passed through the small intestine into the large intestine and into the colon and then excreted? Thats a hypothesis. But its not contrary to your understanding of physiology? I havent seen any evidence in the literature that is the case, so I have to hypothesize there or... Youre aware that, for example, Crohns Disease can manifest in the digestive track anywhere from the mouth to the anus, correct? Thats my understanding, yes. And so from the individuals experiencing Crohns Disease as a result of lesions in the stomach, for example, the cannabinoids that are being digested in the stomach could very well be being applied to
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q A Q A
Q A Q A Q A Q A Q A Q
A Q
those lesions prior to the first-pass effect, which you say primarily occurs after absorption in the small intestine, correct? Thats a possibility. Its never been demonstrated. Similarly, if one is experiencing Crohns Disease in the small intestine itself, it stands to reason that the cannabinoids which are being absorbed through the small intestine and then passed into the liver are being applied to the site of pathogenicity because thats in the small intestine? That makes sense, doesnt it? Yeah, I would just like to make a clarification here regarding the word pathogenicity. Sure. Its actually incorrect to use that term in this context -Okay. -- because pathogenicity refers to pathogens such as bacteria or viruses. I dont think this is the case for Inflammatory Bowel Disease or for Irritable Bowel Syndrome. Im -- Im not a doctor, so lets assume that when I said pathogenicity what Im referring to is the site of whatever it is youre trying to treat. Pathology. Pathology, thank you. Right. But -- but I just want to say that that was -- that you -- that term was used in Dr. Pates report. Yes. And its incorrect. Okay. You understood him to mean pathology and not pathogenicity when he was using the term, correct? I understood, but it was not correct. Okay. The meaning, however, semantically incorrect, the meaning was -- was clear to you in your reading of it? I connected the dots, yes. You did connect the dots. Now, with respect to the metabolism of orally ingested cannabinoids, it is your testimony that the uptake, systemic uptake is slow and erratic, correct? Yes. And that is a function of the first-pass effect, correct?
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q
A Q
A Q
Q A Q
A Q
In part. Its a function of the fact that people are different, and different things happen to different people, different effects occur in different people with the same medicine, correct? Yes. It is the case, however, that oral ingestion of cannabinoids result in a -- a longer -- a longer period of activity in the system, correct, longer than smoking? Yes. Thats not a -- not a good use of a comparative, theres nothing to compare it to. So my understanding is that when you smoke, for example, cannabis you have a fairly high spike in systemic levels followed by a fairly rapid decline as the -- as the cannabinoids are metabolized by the system. Is that a fair description of what occurs? For THC, yes. Okay. Whereas if youre orally ingesting it, you might have slow and erratic uptake, but youre going to reach a plateau, and its going to stay at that level for a longer period of time before it drops off? Sometimes in some people it can go up and be a plateau for awhile, and then it can actually go higher after awhile as well, and it can drop. Its quite erratic. And thats because different people react to medicines in different ways, correct? In -- in some respects, yes. It is the case, however, that, for example, someone wanting to consume cannabinoids for chronic pain, theyre in pain all day long, and lets assume a certain systemic concentration of cannabinoids provides them with an analgesic, it is the case that in order to maintain that level, that systemic level by smoking, one would have to smoke repeatedly because of the spike and drop off. Thats a fair statement, isnt it? If the person is experiencing pain, then they would have to smoke again, yes. To continue to treat that pain. On the other hand, if theyre orally ingesting cannabinoids, it is the case that because of that plateau, because of that longer period of activity in the system,
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q A Q A Q A Q
A Q A Q
A Q
they may be able to take one Marinol capsule in the morning to achieve that effect for a number of hours, perhaps take another later in the day or before they go to bed, but theyre not going to necessarily have to pop a Marinol capsule every hour to achieve the effect that theyre seeking, the pain relieving effect that theyre seeking, correct? I would just like to make a clarification here. I think were -- were using the term cannabinoids rather loosely. I think we could only speak about THC. I dont want to make a generalization and say cannabinoids. This is THC were talking about. Thats fair. Lets talk about THC -All right. -- particularly with Marinol since its just THC. Since it is THC, thats right. Yes. Pretend I use THC instead of cannabinoids. Okay. The concept Ive described makes sense, correct? Yes. And its also the case that if one is taking -intaking THC orally and achieving that long plateau or, as you say, perhaps a long plateau and a higher plateau, one may supplement the amount of THC in the system by smoking, but one would need to smoke less to achieve that particular concentration thats achieving the desired effect, correct? Possibly. I dont know that thats necessarily been established clinically. It makes sense in science, though, doesnt it? Can you repeat the question? Well, let me give you a hypothetical example. An individual suffering from chronic pain, in order to achieve an analgesic effect from the pain simply by smoking is smoking a joint every hour. Mm-hmm. That same person who eats a cookie in the morning may in fact have to smoke significantly less cannabis over the course of the day in order to achieve that same analgesic effect because therell already be a systemic load of, for example, THC in the system at a certain level, and therefore the smoking could get to the -- you know, even if the -- even if the cookie isnt
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q
A Q
Q A Q A Q A Q
quite at the level at which the analgesic effect is occurring, you dont need to smoke as much to bring the systemic level over that -- that effective point? Does my question make sense? Well, if youve already got quite a bit of cannabinoids or THC, in this case, in your system, you may overdose on it. Yes, but that wasnt my question, was it. My question was conceptually you could be smoking less because youve already got a load of THC in your system from the oral ingestion of the cookie in the morning? Potentially. And if I suggested to you that witnesses in this proceeding have testified to precisely that, to the fact that if they eat a cannabis cookie in the morning, they need to smoke much less cannabis over the course of the day to achieve the desired effect, that while that may not be shown clinically, its certainly consistent with your understanding of the science, correct? Yes. And of course by ingesting less -- by smoking less, one is reducing the amount of damage one does to the system thats caused by pyrolysis by the smoking act itself, correct? Yes. I would add one has the option of also vaporizing, which diminishes the number of byproducts that are given off by smoking. That option also exists. For people that have the ability to obtain a vaporizer, correct? Yes. These are not necessarily cheap devices to purchase, correct? I dont know if theyre cheap or not. I know the option exists. It would not surprise you to learn that, for instance, a Volcano Vaporizer costs somewhere in the neighbourhood of $600, would it? I cant comment. I dont know. It is the case, however, that putting aside the prospect of vaporization for a moment, generally speaking if we can have persons consume less cannabis by smoking and therefore do less damage to their system as a result of the act of smoking, thats a benefit to their health, isnt it?
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q A Q
Yes. Returning to Exhibit 40 in these proceedings, your affidavit -Mm-hmm. -- Id like to bring you back to paragraph 28 -Mm-hmm. -- and we had a discussion about paragraph 28 for Crohns Disease. Ill actually take you to paragraph 29. In paragraph 29 you actually discuss something you mentioned a little earlier about a concern of oral ingestion being potential for overdoses. I want to make sure Im clear of what youre saying in your second sentence in paragraph 29. You say [as read in]: In addition, since the cannabinoid concentration in hash oil has been reported to vary widely, and since hash oil is not subjected to rigorous quality assurance procedures to establish the concentration of cannabinoids, there is the potential for overdosing.
A Q A
Q A Q A Q A Q A Q A
Do you see that? Yes. What do you mean by the term hash oil in that sentence? Im talking about the oil thats produced as a result of extraction in organic solvents or alcohol or ether or -- but it can also apply to any -- not just hash oil but cannabis butter or cannabis oil which contains high concentrations of THC. And Marinol, correct, it can apply to Marinol as well, correct? It can apply to Marinol, yes. And it can apply to Cesamet as well, correct, and -Yes. -- other prescriptions? Yes. And it can apply to Sativex as well, cant it? Yes, it can. An overdose in this context means essentially intaking more than necessary to achieve the desired result, correct? Yes.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q A Q A Q A Q A Q A Q A Q A Q A Q A
Q A Q A
Q A
And the effects of overdose can vary widely depending on dose, correct? Yes. And depending on the individuals particular susceptibility to the compounds, correct? Yes, their experience with it, their susceptibility to it. Yes. Tolerance of it? Their tolerance, that goes with their experience generally. And the effect of overdose, generally speaking the primary effects of overdose of THC in this context can be dizziness, correct? At low doses, yes. A dry mouth, correct? Yes. A euphoria, the high thats associated with recreational smoking of cannabis, correct? Yes. Anxiety? Certainly. Potentially delusions, correct? Yes. Hallucinations, correct? Yes. And those effects are generally speaking transient effects that pass with time as the amount of cannabinoids in your system decreases, correct? I wouldnt say that its a function of as the cannabinoid concentration decreases in your system. Its as a function of biochemical changes which occur in your body as a result of prolonged exposure to these cannabinoids -And those effects, however --- or to THC. -- those overdose effects are transient. They diminish with time, correct? In some people they do. In others they -- they may not, and thats one of the reasons why some people find these medications intolerable because the effects dont go away. Are you suggesting that the effects never go away? It depends how long you use it and -- and how much you take, and it depends on the person. Some people develop tolerance to some of the effects, and other people develop a tolerance to other of the -- tolerance is a very complex subject.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q A Q A Q
A Q A Q A Q A Q A Q
A Q A Q A Q A Q A Q
Yes. If you cease intaking the compounds, the effects are going to diminish, correct? I mean, youre not going to have dry mouth for the rest of your life -No, thats correct. -- if you take Marinol? Thats correct. Youre not going to be dizzy forever? Thats right. Its going to go away? It will. And by and large upwards of 95 percent of negative effects associated with the intake of cannabis or cannabinoids are non-serious? Theyre not lifethreatening, correct? Theyre not life-threatening necessarily -They --- but they can -Theyre not --- but they can be serious. Theyre -- but the majority of them are not; isnt that correct? Theres quite a few that are quite serious. But the majority of them are not; isnt that correct? I cant say if the majority are or the majority arent. Are you aware of any studies conducted suggesting that somewhere between 90 and 95 percent of the negative adverse reaction to cannabis or cannabinoids are non-serious? I cant think of off the top of my head. It also depends on what the definition of non-serious is. Certainly one is not going to overdose to the point of death on cannabis or cannabinoids, correct? I agree with you on that one. And its -But thats only one definition of serious. It -- it certainly is serious, however? Its very serious, yes. And in contrast there are a number of prescription pharmaceuticals in which one of the effects of overdose is death; isnt that correct? Thats correct. Indeed the effect of overdose on aspirin can be death; isnt that correct?
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q A
Q A Q
A Q A Q A Q A Q A
Q A Q A Q
Thats correct. And aspirin is the over-the-counter remedy sold at Pharmasave, for example, and available to anyone, correct? Thats correct. You would not characterize dizziness as a serious adverse reaction, would you? I would consider it an adverse reaction, but if youre driving a car and youre dizzy and you have an accident because of that, that could be a serious consequence. Absolutely, and of course dizziness is a byproduct of a number of pharmaceutical substances, not just cannabis, correct? Thats correct. And so its appropriate to indicate to somebody, Well, if youre taking this particular medicine, you probably shouldnt operate heavy machinery, correct? Yes. But absent the circumstance that you described, a bit of dizziness is generally speaking not considered a serious adverse effect, correct? No. Or a bit of dry mouth is not considered a serious adverse effect, correct? I agree, right. Or a bit of euphoria is unlikely to be considered a serious negative adverse effect, correct? That depends on the person. Some people can find euphoria quite unpleasant if theyre not used to it. But again its up to the -- its -- thats something that the individual determines after experiencing that effect, correct? Yeah, but clinical studies, there -- there is evidence in the clinical literature that patients who experience euphoria find it unpleasant and withdraw from the study. Some people dont want to get high, for lack of a better word? Yeah, thats right. And thats true of not just cannabis and cannabisbased medicines, thats true of other pharmaceutical medications as well, isnt it? Some. And its certainly true of Marinol, correct?
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q A Q
Yes. Its certainly true of Sativex, correct? Yes. Its true of dried marihuana consumed by inhalation, correct? Yes. At paragraph 30 of your affidavit, Exhibit 40 in these proceedings, you suggest that theres no scientific evidence of which youre aware to support the implied claim by Dr. Pate that oral ingestion of cannabis-based medicines: ... can be more effective and require lesser dosages, and thus ameliorating potential unwanted side effects.
A Q
A Q A Q
A Q A Q
Do you see that -- do you see that paragraph? I do, but it was in reference to, I think, a particular paragraph of Dr. Pates affidavit. Yes, I -- my guess, because you dont reference it, is that youre referring to paragraph 32 of Dr. Pates affidavit, or paragraph 31? Its paragraph -- the last sentence of paragraph 31 -There --- is what youre applying it to, correct? Yes, thats right, Im applying to that. Yes. And then you go on to discuss the individualization of dosing and the reliance on self-titration, which weve talked about, and you talk about self-titration through smoking, and weve discussed that self-titration can occur not just through smoking but through other means of ingestion? [No audible response]. With respect to what Dr. Pate says immediately above the sentence that youre responding to -Mm-hmm. -- he says [as read in]: Good pharmaceutical practise dictates the use of a minimum effective drug amount and a treatment as close to the site of pathogenicity...
A Q
But lets call it -Pathology. -- pathology:
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
... as possible. A And you agree with that statement, dont you? I would agree that, you know, its probably a good idea to use the smallest amount of drug directly to the site of action to minimize unwanted side effects. I would agree with that, as a scientist, yes. Okay. And at paragraph 32 of Dr. Pates affidavit he says: Another benefit of oral ingestion is that it produces longer lasting therapeutic effects than inhalation. Weve discussed that with respect to the plateau issue. You dont dispute that that is an accurate statement and that oral ingestion produces longer lasting effects than inhalation, correct? I would just qualify that statement and say that it also produces longer lasting adverse effects. And similarly with smoked marihuana produces adverse effects, but theyre -- theyre shorter lasting because of the drop, the quick drop? They are shorter lasting, yes. Dr. Pate then says: Inhalation tends to produce spikes in the systemic load of the active compounds which quickly fall to low levels... You agree with that portion of the sentence that Ive just read? Well, they fall quickly to low levels compared to oral ingestion. Were still talking a matter of hours, not minutes. And we know that the high from smoking cannabis can last from minutes to hours, depending on the individual and the dose, correct? Yes. Dr. Pate goes on to say: ... resulting in elevating patient blood levels with more of the active compounds than necessary while making the effect of these compounds more transient.
A Q A Q
A Q A Q
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
That -- that concept we talked about a little earlier, but you agree with that concept, dont you? I would actually agree and disagree with it. There are certain issues that I take with that statement, especially the part where we say -where he says, Im sorry: ... resulting in elevating patient blood levels with more of the active compounds than necessary... What is more than necessary? The therapeutic effects and the adverse effects can be very close together, so, you know, to say that youre getting more -- to say that youre -- youre -- youre overloading the system more by inhalation than you are by oral ingestion is not really the case. Well, if you require, for example, 10 nanograms per kilogram of THC in your system to achieve an analgesic effect, and smoking cannabis produces 70 to 80 nanograms per kilogram of systemic load, youre intaken more than necessary to achieve the desired therapeutic effect, havent you? Well, you could achieve the same result by ingesting. You could -- you know, you may -- you may need ten nanograms per mil plasma concentration to achieve an antiemetic effect, and thats the same -- at ten nanograms per mil you may feel high as well. Yes, but that wasnt my question, was it? My question was if you require ten nanograms per mil to achieve the therapeutic effect that you desire, and you smoke cannabis and that puts your systemic level at 70 or 80 or 90 nanograms per mil, youve taken more than necessary, correct? Yeah, but you can take more than necessary by oral ingestion as well. I -- I appreciate that thats your position. It is the case, however, that oral ingestion tends to produce systemic levels in terms of nanograms per mil of cannabinoids than smoking, doesnt it? Generally speaking, yes. And occasionally thats on an order of magnitude, lesser, in that, for example, you could eat a cannabis cookie, dependant on the count -- the consistency of that cookie, that produces seven to
A Q
A Q
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q A
Q A Q
A Q
A Q A Q
ten nanograms per mil systemic load of THC, whereas smoking even low potency cannabis of one to three percent tends to produce a significantly greater, 50/60/70 nanograms per mil, systemic load of THC; isnt that the case? That depends on the potency of the cannabis, how much you smoke, you can get lower levels as well. But even low potency cannabis, one to three percent cannabis produces concentrations of THC in a system in the neighbourhood of 70 nanograms per mil? Oh, I wouldnt -- I wouldnt say that right off the top of my head like that. I dont -- I dont -- you know, I -- I -Sitting here today, you dont know one way or another? I would have to do the math on that to tell you. It depends how much you smoke and it depends on the potency. It depends on a lot of different things. Theres a lot of variables? There are variables, yes. And you talk about, in fact, at least the Information for Healthcare Professionals document discusses in the dosing section relative amounts of cannabis in the -- in the load after smoking, after oral ingestion, thats in the document for healthcare professionals, correct? Yes. And well return to that later this afternoon. It is the case, however, that direct delivery of cannabinoids to the site of action would make Dr. Pates statement that your produced at -reproduced at paragraph 30 of your affidavit to the effect that oral ingestion can be more effective and require lesser dosage, thus ameliorating potential unwanted side effects, direct application to the site of pathology is going to support that statement of Dr. Pate, isnt it? Its a hypothetical statement. But if youre applying directly to the site, youre going to require less, arent you? Potentially. Potentially. Youd have to determine that experimentally. At paragraph 31 of your affidavit you speak to psychotropic effect or high from marihuana
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q
A Q A Q
A Q
A Q
A Q
occurring more quickly when smoked rather than taken by the oral route, which is the reason smoking appears to be the preferred route of administration by most people. Do you see that? Mm-hmm, yes. That would be consistent with people whose goal is the high, correct? It can be, yes. And if your goal is not the high, it doesnt make sense that your referred route of administration is the route that gives you the high more quickly. Youre actually not going to want that, are you? You may need higher levels to treat certain conditions like pain. And as with any medicine, sometimes you have to take the good with the bad or the bad with the good? One way of looking at it. Well, as you discussed yesterday when referenced to, for example, in therapy treatment, if you want the benefit, youre going to have to suffer through the consequences, even if theyre very, very severe, as in the case of chemotherapy, correct? Yes. It is, at least hypothetically, possible to have -- to intake sufficient cannabis orally in treating gastrointestinal problems to have a therapeutic effect but no psychoactive effects, correct? Thats hypothetically possible? Hypothetically, yes. And if persons have testified in this proceeding that, for example, if they eat a cookie in the morning and they can achieve some analgesic effect for their pain but not achieve any psychoactive effect, thats a possible situation, correct? Thats a possible situation. There are other effects of ingesting cannabinoids that are not psychotropic but that effect brain function over the long-term, and that might not be felt for a long time. As with any -- as with many prescription pharmaceuticals, if youre going to be taking them for a long time, you may have effects that dont manifest for a long time, correct? Eventually, yes. So, for instance, something like Vioxx that we
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q
A Q A Q A Q
A Q A Q
talked about yesterday, you may take that medicine, that drug for a period of time achieving the affect that youre seeking to achieve, but down the line it manifests in heart attacks and death, correct? Sure. We know at least with respect to cannabis/cannabinoids that one of the outcomes of chronic use is not going to be that it kills you, correct? Generally speaking. Youre not aware of any studies in conducting your review of the literature suggesting that anyone has died as a direct cause of the intake of cannabis, correct? Not as a direct cause, but they could have died as an indirect cause. It could cause them impairment, they may have an accident. Absolutely, and thats the case for any medical substance that causes impairment, correct? Yes. Its not unique to cannabis or cannabinoids in any way, is it? No, its not unique to cannabis or cannabinoids. And what one does in those circumstances is one provides a warning that says its probably not a good idea to drive after taking this medicine, correct? One would hope so. And that is -- again its going to be up to the individual taking the medicine whether to follow that advice or not, isnt it? Yes. At paragraph 32 of your affidavit you say: Its inaccurate to imply that only inhalation results in blood levels with more active compounds than necessary as indicated at paragraph 32 of Dr. Pates report. Dr. Pate doesnt actually say that only inhalation results in blood levels with more of the active compound than necessary? He doesnt say that at paragraph 32 or anywhere in his affidavit, does he? He says in paragraph 32:
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Inhalation tends to produce spikes in systemic load resulting in elevating patient blood levels with more of the active compounds than necessary while making the effect of these compounds more transient. Q Yes, but he doesnt say anywhere in paragraph 32 that inhalation results: ... that only inhalation results in blood levels with more of the active compounds than necessary... He doesnt say that in paragraph 32 or anywhere in his affidavit, does he? That he says that only inhalation? Yes. Not directly, no, he doesnt say that. Thats your inference for -- thats an inference that you take from reading what he said, but thats not something that he actually says? It was an inference based on what I had read in paragraph 31, the last sentence where he says: This provides the benefit of direct requiring less dosages... Q I had made an inference on that. And of course the rest of that sentence is that: ... can be more effective and require lesser dosages. Its not a definitive statement. Its in fact a qualified statement, correct? Yes. Not having had the benefit of hearing Dr. Pates testimony or seeing any transcripts, it wouldnt surprise you to hear that Dr. Pate, on the stand, described the possibility of overdose on oral ingestion, that wouldnt surprise you to hear that, would it? No. Because anybody with a familiarity with the subject matter that has a reasonable grounding of science is going to understand that thats the case, correct?
A Q A Q A
A Q
A Q
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q A Q
I hope so. And if Dr. Pate testified on the stand, well, if you eat too much of the cookie, for example, you may be, I think his quote was along for the ride, youre going to experience these unwanted side effects until they dissipate, correct? Yes. And that would be an accurate statement based on what youve said in your affidavit, correct? Yes. At paragraph 33 of your affidavit, you speak to -well, let me just back up. At paragraph 32 of Dr. Pates affidavit, which is tab F to Exhibit 40 in these proceedings, halfway down he speaks to: Oral ingestion, by contrast, provides a plateau of longer and more stable systemic load of therapeutic agents. And we discussed that, and then he says: This eliminates the need to repeatedly ingest the medicine at short intervals in order to achieve continuous therapeutic benefits. Thats consistent with what we talked about earlier with the need, for example, for somebody with chronic pain that smokes repeatedly in order to achieve the desired effect, whereas with oral ingestion because of that long plateau you may not need to do that, correct? It would also depend on the condition that were talking about. Higher systemic load of the cannabinoid THC may be required and unachievable by oral ingestion. And thats the case with all medicines. It may well be that you have to take so much to achieve the desired effect that youre getting the negative effects whether you want them or not, correct? Yes. Dr. Pate goes on to say: It also allows for the treatment to continue during sleeping hours. You dont disagree with that statement, correct?
A Q
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
No, I dont disagree with it. For somebody suffering, for example, with chronic pain, using cannabis to treat that pain or cannabinoids to treat that pain, it is -- it would be, at best, inconvenient to have to wake up every hour/hour and a half to smoke cannabis in order to manage that pain. That person may well prefer to eat a cookie before going to bed to achieve a longer lasting effect whilst theyre sleeping. That makes sense from a patient perspective, doesnt it? A Yes. Q And if patients in these proceedings testified to precisely that, that they ate a cookie before going to bed so that they could have a good nights sleep, they had a pretty good nights sleep without having to wake up to treat that pain, and thats consistent with the science, you dont have any disagreement with that patients experience, do you? A I wont disagree with a patients experience. Its their experience. Q And its consistent with what weve just discussed in terms of the effect of the plateau and the oral ingestion of cannabinoids, its consistent with that, isnt it? A In principle, yes. MR. TOUSAW: My Lord, I note the time. THE COURT: Yes. Well take 15 minutes. (WITNESS STOOD DOWN) (PROCEEDINGS ADJOURNED FOR MORNING RECESS) (PROCEEDINGS RECONVENED) MR. TOUSAW: Thank you, My Lord. HANAN ABRAMOVICI, recalled. CROSS-EXAM BY MR. TOUSAW ON VOIR DIRE, CONTINUING: Q At paragraph 33 of your affidavit, Exhibit 40 in these proceedings, Doctor, you speak to Dr. Pates report at paragraph 36 in which he provides an example that: Inhalation would be preferable to oral
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
ingestion to treat acute pain and other symptoms associated with migraine headaches. Lets put aside for a moment your comments on the what you say is the dearth of scientific evidence to suggest that cannabis is an effective treatment for migraine headache. The concept expressed in that paragraph by Dr. Pate that inhalation is preferable to oral ingestion to treat acute pain, you dont disagree with that concept, do you? I disagree with it somewhat because very few scientific studies or clinical studies support the use of cannabis or cannabinoids for treating acute pain. Its been more convincingly shown that it has a benefit in neuropathic pain, which is more a chronic disorder. But you dont dispute that there are many studies that stand for the proposition that THC produces an analgesic effect, correct? There are studies that suggest that THC produces an analgesic effect. And analgesia is painkilling? Yeah, but theres different types. Different types of pain? Theres different types of pain, yes. It makes sense, however, that concept that if one is treating an acute condition, inhalation, youre going to want -- youre going to want the delivery of the pharmacologically active compounds quickly, conditions acute, you want to deal with it as quickly as possible, correct? Yes. At paragraph 35 -- or at paragraph 34 of your affidavit you indicate that youre: ... unaware of any scientific evidence supporting a claim that topical administration is in any way effective for inflammatory skin conditions or chronic pain of the joints as claimed at paragraph 37 of Dr. Pates affidavit. That you stand by that statement, youre unaware of any scientific evidence supporting the claim that topical administration is effective for inflammatory skin conditions? Thats correct, yes.
Q A Q A Q A Q
A Q
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q A Q A Q A Q A Q A Q A
Q A
Q A Q A Q A Q A Q A
And you note that there are some cases of contact urticaria. Thats correct. Did I say that right? Yes. Thats sort of a skin rash, correct? Its -- its a rash, yes. Rash and hives? Yes. Sort of an allergic reaction, correct? Yes. And thats contact with cannabis flowers, the -the plant itself and the growing plant itself, correct? It could also be the resin as well. Yes. The case report, however, deals with exposure to cannabis flowers, correct? There are two reports there, and I dont remember which one is which exactly. Id have to look at them, but I think that in one of the cases there was potentially an animal study, and the other one it was a case study. Yes. And I think in one of those studies there was, I -- if I recall correctly, they looked at the resin or -- Id have to look at the -- the studies to be -- to really to tell you. The -I do -- its -- its -- its the cannabin -- its the allergy to the cannabinoid. Yes. Its not to the -- its not to the plant material. Its to the cannabinoid. Yes, its -- people are allergic to things and sometimes you get rashes when you touch things youre allergic to, correct? Yeah. And not in -- in the human study there was a transient effect, it went away upon cessation of exposure, correct? Upon cessation of exposure, yeah. If youre allergic to something and you dont come in contact with it, you dont have a reaction, correct? Unless -- unless you come across something thats cross-reactive to that, then, you know, you could have an allergic reaction.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q A Q
A Q A Q A Q A Q
A Q
A Q
That case report of contact urticaria, thats the only one in humans that youre aware of, correct? Im aware of that only study. However, in the Marinol monograph, allergic hypersensitivity to THC is noted as a hyprous [phonetic] effect. People are allergic to different things and if youre allergic to something, you can have an adverse reaction to it, correct? Yeah, but it confirms the case study. Right. And Dr. Pate doesnt speak to, at paragraph 37 or anywhere in his affidavit, allergic reactions caused with negative at all, does he? No. And its clear that at least the lab science demonstrates that THC and CBD are antiinflammatories, correct? Laboratory evidence, yes. So with respect to -It would depend on the dose, of course. Well, we can just establish that just about everything is dose-dependent, correct? Generally speaking, yes. At paragraph 35 of your affidavit you speak to studies involving the transdermal delivery of Delta-8-THC, and you say that Dr. Pate is incorrect to suggest that, essentially, topical administration eliminates psychoactive side effects; do you see that? Mm-hmm. Are you aware of case studies, clinical evidence suggesting that topical administration of THC or C -- Delta 8, Delta 9 THC produces the high, the psychoactive side effect? No. The studies that you site, in fact what you say is, at paragraph 35: Transdermal delivery of Delta-8-THC, a compound highly related to Delta-9-THC, gave rise to detectable plasma levels of this cannabinoid for over 24 hours in an animal study.
A Q
Correct? Correct. That doesnt say anything about whether or not
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
there was a psychoactive effect produced in the animal or humans, correct? Thats correct. You go on to say: Another study carried out on animals demonstrated that transdermal administration of Delta-8-THC was also associated with detectable levels of Delta-8-THC in the blood plasma within 1.4 hours, and this concentration was maintained for at least 48 hours.
A Q A
Q A Q A Q A
Do you see that? I do. And again that doesnt speak to psychoactive effect, that just speaks to detectable levels of Delta-8-THC in the blood plasma, correct? Thats correct, but the levels of Delta-8-THC that were found in the blood plasma were, I think. in the order of four or five nanograms per mil or greater, and those could have psychoactive effects in the human, but this was a laboratory study in animals. I think the point here also in addition to the psychotomimetic issue was that it -- that the cannabinoid Delta-H -- Delta-8-THC applied to the skin does enter the systemic circulation. Yes, and Dr. Pate doesnt, at paragraph 38 -- or 37 of his affidavit, doesnt claim the contrary, does he? I dont -- I dont believe that he does. Right. So -Im just going to -- Im just going to check, sir. This was -Oh, please do. Please do. Well, he does say: A full systemic treatment to obtain a localized therapeutic benefit is not administered. But the animal study suggests that you can have systemic levels of the cannabinoid. Detectable levels within the blood? Yes. And so you could potentially get full systemic treatment, and thats one of the rationales from developing many years ago the
Q A
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q A Q
A Q A
Q A Q
A Q A Q A Q A Q
patch containing THC -Yes. -- was to allow delivery of -To the system? To the system, yes. Yes. And you, in your direct testimony when my friend was asking you questions, indicated that when he was asking about applying oil to the skin and whether that would penetrate the skin, and I think you said, from what youve seen in the literature, most of the cannabinoids would be trapped in the skin, correct? Yeah, I would like to qualify that statement. Mm. Most of the cannabinoids would be trapped in the skin it would be a reservoir, but the THC would eventually get into the systemic circulation, and thats supported by those studies. And there are CB -- there are cannabinoid receptors in the skin, correct? There are cannabinoid receptors in the skin, yes. And so if youre applying the cannabinoids to the skin and its -- most of its being trapped in the skin or at least theres a reservoir in the skin when youve got a skin inflammation, hypothetically at least, it stands to reason that there could be therapeutic effect from the topical application, correct? Hypothetically, yes. And at least in lab studies its clear that THC and CBD do produce anti-inflammatory effect, correct? Yes, but not on -- not necessarily on the skin. That hasnt been demonstrated, to my knowledge. And in terms of your critique of Dr. Pate, your references are to animal studies, not human studies, correct? Thats right. And theyre animal studies in lab, not clinical studies, correct? Thats right. And so at least in terms of your paragraph 35, youre prepared to rely on those laboratory studies, the non-human studies as a support for the basis for your opinion, correct? In this case, yes. The -- in some of those studies they met -- they compared the skin
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q
A Q
A Q A
properties of the animal to the skin properties of a human, and found them to be quite similar. And so as weve discussed, at least hypothetically, the lab studies in the animals could be translated to possible effect in humans, correct? Yes. And thats true not just of the studies that youve cited here to refute Dr. Pate, but thats also true of the studies that weve been referencing throughout the last day and a half in which youve taken some issue as to whether or not lab studies are necessarily translatable into clinical effects or application in humans, correct? Certainly. The same criticisms apply to both your reliance on these studies and reliance on other studies when there havent been some clinical documentation of whats trying to be proven [indiscernible], thats right, isnt it? Well, in the case of the systemic availability of THC by topical application, its hypothetical that it would happen in a human, but the evidence -there is evidence there that it does get into the systemic circulation, having the skin properties quite similar. And similarly in some of the other examples that weve discussed yesterday and today and which Ive indicated theres, at least in the lab, some hypotheses that are supported by the science and the mechanism, the same critiques that youve applied to those hypotheses may well apply to these hypotheses, correct? Certainly. And are you aware of studies in which tests have been -- in which theyve attempted to -scientists have attempted to determine what blood concentration of THC is necessary to produce a psychoactive effect? Generally, yes. And do you happen to recall, sitting here today, what that blood concentration is? I know that generally speaking a concentration of five nanograms per mil to 10 nanograms per mil has been associated with a blood alcohol level of 0.05 percent, which is considered in some areas to be
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q A Q
legally impaired, and higher levels thereof can cause psychoactive effects. And thats reproduced, those studies and that information is reproduced in the Information for Healthcare Professionals, Doctor, correct? Yeah, that -- that part is. Yeah, and other -and other -- yeah, theres information on that in the -- in the -- in the document, yes. At paragraph 36 of your affidavit you are responding to Dr. Pates materials at paragraph 38, point (d) of his report. Mm-hmm. And Im going to take you to paragraph 38 of Dr. Pates report, and at -- this is at page 11, the first subheading is (a): A cannabis plant is harvested for medicinal resin compounds found in the side glandular trichomes of the plant. With respect to attempts to seek a medical benefit from a cannabis plant, thats a true statement, isnt it? That -- thats -Yes. -- the cannabis plant is harvested for those resin compounds that are found in the glandular trichomes of the plant, correct? Well, thats the part of the plant that produces the cannabinoids and terpenoids, so -Those are the pharmacological active compounds, correct? Yes. So you dont dispute subheading (a)? I dont dispute it as its written, but it can also be harvested for recreational purposes as well, not just for medicinal purposes. And -- and clearly it is done so? Yes, it is. In quite vast amounts here in Canada, correct? I would imagine, yes. There are millions of Canadians that have consumed cannabis for recreational purposes; isnt that true? Yes. There are potentially tens or hundreds of millions that have consumed cannabis for recreational purposes worldwide, correct?
A Q A Q A Q A Q A Q A Q A Q
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q
A Q A Q A Q A Q
I would imagine, yes. Its fair to say that in the context of consuming cannabis, either for medical or recreational purposes, that its quite likely that in the order of billions of doses of cannabis have been ingested by humans over the course of our history with this planet. Isnt that accurate? Lots, yes. Quite possible that more, other than perhaps alcohol or tobacco, more cannabis has been ingested by humans for over the course of our history with this planet than just about any other substance used for recreational purposes, correct? I cant comment on that. I dont know. Do you have any sense of the number of Canadians who report using marihuana for medical purposes? I dont remember what the last figure is. Would it have been in the neighbourhood of 500 or more? I think its more than 500. More than 10,000? I cant recall the last number. Probably, possibly. Are you familiar with a 2006 publication known as the Canadian Addiction Survey? Yes, I am. Are you -Im vaguely familiar with it, yes. Are you familiar with the suggestion, at least in self-reporting, that there are somewhere in the neighbourhood of a million Canadians that selfreport using marihuana for medical purposes? Those are self-reports, yeah. Are you familiar with that number? It sounds somewhat familiar, yes. It rings a bell somewhere? It rings a bell. Are you familiar with The Report of the Senate Special Committee on Cannabis published in 2002? I read it awhile ago. I dont remember the -- all the details of it. Do you recall that the estimate that the Senate Committee used in writing its chapter on therapeutic use of cannabis was that there was somewhere in the neighbourhood of 400,000 Canadians that consumed marihuana for medical purposes?
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q
A Q
Possibly, but those are self-reports. The accuracy of those reports can be debated. It wouldnt surprise you to learn that somewhere between 400,000 and a million Canadians selfreport the use of cannabis for medical purposes, would it? I cant comment. I dont know. There are studies published that speak to the percentage of persons with particular conditions that self-report the use of cannabis for medical purposes, correct? Yes, I think so. Paragraph 38 (d) of Dr. Pates report reads: There is no medical utility to the dried plant matter.
A Q
You dont dispute that statement, do you? No, I dont dispute it. At paragraph (c) Dr. Pate opines that: In essence, the plant is no more than a carrier for the glandular trichomes which are themselves the manufacturing site and reservoir for the resin which contains the cannabinoids and terpenes.
A Q
A Q
A Q
You dont dispute that statement, do you? No, I dont dispute it. Its (d), you take issue with (d) subheading (d) of paragraph 38 of Dr. Pates report, and you speak of that at paragraph 36 of your report, correct? Yep. And the issue you take with Dr. Pates conclusion is not so much with his opinion but that it leaves out, in your view, the fact that there are also negative effects associated with oral ingestion or smoking of cannabis or hash oil since the oil also contains a psychoactive cannabinoid Delta-9-THC, correct? I would say the consumption of THC in any shape or form would correspond to that. There could be minor to serious effects. And Dr. Pate doesnt say otherwise at paragraph (d) of his report or elsewhere in his affidavit, correct?
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q A Q A Q
A Q A Q
I dont think so. Okay. So youre not disputing what he says at (d), youre qualifying it by adding to it that, in your view, there are also negative effects, correct, to -I -- I would --- to --- I would just -- I would just add that -- no, I wont, so I stand with my statement that I made earlier. When you say -- when you use the term hash oil in the second sentence of paragraph 36 of your affidavit -Mm-hmm, yes. -- or smoking of cannabis or hash oil, are you referring to the solvent extracted hash oil which is ingested by smoking or are you referring to olive oil extracts and those kinds of things? No, oral ingestion was for cannabis oils -Yes. -- and smoking hash oil. And similarly in your next full sentence you again use the term hash oil when you say: ... which may be found in an even higher concentration in hash oil compared to marihuana. There youre referring to the solvent extract hash oil, correct? Yes. When one extracts -- if one takes, for example, a gram of cannabis bud and grinds it up and extracts it into five ounces of olive oil, the concentration of Delta-9-THC and the other cannabinoids, terpenes in the oil is going to be less the concentration in the bud, correct? Sorry, say that again? Assume an individual takes a gram of 10 percent THC cannabis, and that 10 percent THC is the measure by weight, correct, the 10 percent refers to dry weight, does it? Ten percent refers to the amount of THC per gram amount of substance, yeah. Okay. So you have your 10 percent THC by weight bud, you grind that up, you put it into five ounces of olive oil, you let it soak, the oils
A Q
A Q
A Q
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q A Q
A Q A Q A Q A Q A Q
A Q
A Q
extract the resins from the glandular trichomes, you then strain it through a cheesecloth and youre left with an oil, five ounces or slightly less of oil with a certain concentration of THC. We may not know exactly what it is, but its going to be a lesser concentration of THC than was found in the bud itself, correct? Well, the -- I dont -- I dont think so. That doesnt make intuitive sense to me, but, you know, I think youre -Well, the --- you can -- you can get concentrations of hash oil that are 30/40/50, it depends, percent THC in the oil, in the hash oil. And youre speaking now of the solvent extracted hash oil, correct? Yes. Im speaking of olive oil, five ounces of olive oil into which a gram of 10 percent THC has been added and extracted. The concentration of Delta9-THC in the olive oil is going to be less than the concentration when it was in the bud simply because concentration is a function of a ratio of weight, correct? Yeah, but youre comparing weight to volume here. Yes, but theres a -- theres a weight to the oil, too. Its not -There is, but youd have to --- [inaudible/low voice]. -- multiply it by the density. And if you do that the result is going to be a concentration in the oil that is less than the concentration in the bud, isnt there? I dont know. But it stands to reason, doesnt it? I dont know. Have you ever seen quantitative test results for -- well, let me -- let me back up. Youve mentioned that you can have hash oil thats 50/60/70 percent THC, correct? Thats been reported, yes. And thats because, when youre extracting with the solvent, youre actually concentrating and refining the amount of the resins by weight in the finished product, correct? Yes. So youre getting rid of the dry weight of the
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q A Q A Q
A Q A Q A Q A Q A Q
bud, youre concentrating down the resins into -and then youre evaporating out the solvent, and really what youre left with is as puree resin as you can get through that process, correct? Yes. Thats not whats happening when youre extracting in olive oil, in fact quite the opposite is happening. Youre extracting into a greater volume, and youre not evaporating out the olive oil, youre leaving it in place, correct? Mm-hmm, yes. So it stands to reason, doesnt it, that its going to have a lesser concentration as opposed to a greater concentration; isnt that true? It would depend on the volume of olive oil that youre using. If youre using a microgram of olive oil, then thats going to change the ratio, correct? If you use less olive oil, the concentration will be much higher, and if you use a large amount of olive oil the concentration will be lower. And at a certain point you reach what I guess Id call a point of absurdity because youre not physically able to extract a gram of dried marihuana into a few drops of olive oil. Thats just not possible? You are correct, its not possible. You need a certain volume of olive oil in order to just undertake the process, correct? You might be extracting some little bit, but its not -Yes, but its -- its not going to be very powerful. Thats correct, isnt it? I dont know, but -It stands to reason --- you know --- that its not going to be very powerful, correct? That stands to reason, doesnt it? Possibly. The statement at paragraph -- well, with respect to (d), you speak to at paragraph 36 of your affidavit the negative effects associated with oral ingestion of Delta-9-THC, and you say these include well known adverse physical and psychotropic effects associated with the consumption of Delta-9-THC. Those are the negative effects that we discussed early in your
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A
Q A Q A Q A Q
A Q
A Q A Q
A Q A Q
testimony, correct, the dizziness, the -- the other possible negatives, correct, and that you speak to in your affidavit? This is my paragraph 36, my -- my 36? Your paragraph 36, yes. Mm-hmm. Yes. I would just add one other item to that is that anything thats found on the trichome itself, a contaminant, an impurity, could also be transferred to the butter or the hash oil, and so in addition to the psychotropic, adverse psychotropic or adverse physiological effects, there would all -- there could also be adverse health effects based on what exactly it is that youre extracting into that product. And in order to be extracted into the oil it would have to be there first of all, correct? Yeah, it would have to -- yeah, it would have to be in there in the first place. You can purchase, of course, by prescription, Marinol, which is a synthetic 100 percent THC in sesame oil and ingest it orally, correct? Yes. And thats an approved drug product in Canada? It is. Dr. Pate, at (d) indicates there are negative effects with ingesting the plant matter, and you quality that by saying, well, theres also negative effects to ingesting cannabinoids? Yes. Having one set of negative effects associated with cannabinoids doesnt mean that its medically irrelevant, but theres another set of negative effects to ingesting the plant matter, correct? No. Your goal would be to minimize the negatives in either case, correct? Yeah, you would want to minimize negatives. And so to the extent that you can eliminate the negatives associated with smoking or ingesting a plant matter it would be appropriate to do so, correct? Yes. I would just add one other thing, which is that hash oil is often smoked -Okay. -- so -But were not speaking now of hash oil, were speaking of oral ingestion or --
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q
A Q
A Q
Mm-hmm. -- topical administration of say an olive oil extract. If you can minimize the plant matter, you -- the negative effects associated with plant matter, you should do that, shouldnt you? If there are negative effects associated with the plant matter, yes. In terms of the active compounds, as we discussed before, if you want the positives youre seeking to experience, you have to accept the possible negatives to experience those, correct? Its a risk/benefit analysis. And so similarly if you want the pain relief provided by prescription opiate based narcotics, you have to accept the potential negative side effects which include addiction and overdose death, correct? Yes. At (e) of paragraph 38 of Dr. Pates report, Dr. Pate indicates that: Ingesting the resin by means of smoking would be less harmful to the patient than smoking the dried plant matter which bears the resin because (a) less would be consumed to achieve the desired therapeutic effect, and (b) the pyrolysis products of unwanted bulk plant material would not be inhaled.
A Q A Q A Q A Q A
You dont disagree with that statement, do you? I have some issues with it because, as I was mentioning just a moment ago, people often smoke hash oil by placing a drop of it on a cigarette -Yes. -- and so they would be smoking -Tobacco. -- tobacco -Yes. -- with the hash oil, and thats not very good or -No, but absent doing that, you dont have any disagreement with what Dr. Pates saying here in (e). It stands to reason? It stands to reason in principle, and I will just add one more thing which is when youre smoking anything, whether its plant -- plant matter or an oil, you also run the risk of inhaling other
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
substances. If theres a solvent that hasnt been properly or completely evaporated, or a contaminant or -- you would be inhaling that as well, and so theres a health -- could be a health risk associated with that as well. And Dr. Pate actually speaks to that in his affidavit, doesnt he, earlier in his affidavit when he discusses the possibility that by smoking the plant matter youre inhaling contaminants that you dont want that could have negative side effect. You agree with that? Yes. Youre aware that, with respect to hash oil, there are smoking devices available that allow one to smoke that hash oil without putting it on the end of a cigarette, correct? Yes, Im aware of that. And hash oil, too, could be vaporized, correct? It could, yes. And by doing so you would minimize some of the unwanted side effects associated with the act of pyrolysis, correct? I would imagine so, yes. Its something you dont just imagine so, in fact -Yes. -- you testified to that earlier, didnt you? Yes. Yes. Paragraph 38 of your affidavit speaks to paragraph 38(f) of Dr. Pates affidavit. Can I just say one other thing, please? Sure. With regards to point (e) -Yes. -- if youre smoking something thats more concentrated, then you can get higher levels of the THC in the bloodstream, and so the chances of experiencing an adverse -- adverse psychological or physiological effect can be greater. And again the concept of self-titration comes into play, one could take a small pop of a more highly concentrated substance, and just in the way you self-titrate with plant matter, you can selftitrate with the oil as well, correct? You can, but if you have a more concentrated form, you know, its -- your -- your risk of experiencing adverse physiological and
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q
A Q
psychotropic effects is much greater. And similarly if you simply extract the resin by means of dry sifting, which Dr. Pate talks about early in his affidavit, rubbing the plant matter on the screen and collecting the -- the trichomes that fall through the screen, thats a more highly concentrated form of the active ingredients than the plant matter, correct? Well, youre enriching for that, yes. Yes. And so you are able to, if you self-titrate properly, youre able to actually smoke less of that resin than you would have to smoke of the plant matter bearing the resin in order to achieve the desired effect. Thats accurate, isnt it? Its accurate, but it leaves the room for increased abuse of the substance because youll have more available, its more concentrated. And the same concept applies to prescription pharmaceuticals, there are different levels of concentrations in opiate-based painkillers, and the ones with higher concentrations are more susceptible to abuse than the ones with lower concentrations, correct? Thats correct. Returning to paragraph 38 of Dr. Pates affidavit you speak to at paragraph 38 of your affidavit, you say: Theres no scientific evidence to substantiate Dr. Pates claim of ingesting the resin compound in the form of baked goods being for some conditions significantly more effective than other routes of administration. Youre not aware of any evidence refuting that claim, are you? Im not aware of any evidence in the scientific and medical literature. And the concepts that we discussed earlier with respect to dose plateau and application to the site of action, those concepts, those hypotheses you call them, if correct, support Dr. Pates statement that, at least for some conditions, people can grain great efficacy from baked goods than they can from smoking, for example? Well, the way that its written makes it sound as
A Q
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q A Q
A Q A Q A Q
if its a fact, and it hasnt been shown clinically that that is true. Anecdotally, some people report greater effectiveness from oral products than from smoking, correct? Possibly. I dont know. Youre not aware one way or another, is that -Its anecdotal information, and I dont know. At paragraph 40 of your affidavit you incorporate a number of views that had been previously expressed by Dr. Kalant, which youve now incorporated as your own views, correct? Correct. These are concepts, at least paragraphs 15, 16 and 17, that generally speaking apply to pharmaceutical substances, correct? Yes. Youre aware that there are therapeutically active herbal substances that are available for sale in Canada? Theyre governed under other rules. Theyre governed under something called Natural Health Products Regulations, correct? I believe so, yes. Do you have any familiarity with that Regulation? I do not. You havent had occasion to review it in the course of your work with Health Canada? I have not. The statements made -- do you have any experience in your work with Health Canada or otherwise with the process of taking pharmaceutical products to market? I do not. And do you have experience with the Food and Drugs Act under which various food and drug products are regulated? No, not really. I dont deal with that information. Its not part of your job description? No, its not. At paragraph 40(18) you say that the: Marihuana Medical Access Regulations in effect permit authorized persons in Canada to cultivate marihuana for personal medical use without having to comply with any quality
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
standard which normally apply to pharmaceutical products using cannabis. A Q A Q A Q Do you see that? Yes. The MMAR do not require, for example, a personal producer of cannabis to produce in any particular way, correct? I dont know that they have to produce in a particular way or not to grow their plant. They dont impose any quality standards on Canadians whatsoever; isnt that correct? With the exception of the dried marihuana thats provided by Health Canada, no. But with respect to what you say at paragraph -subparagraph (18), the MMAR permit authorized persons in Canada to cultivate marihuana for personal medical use without having to comply with any quality standard, the MMAR do not contain any quality standards for cultivation of marihuana, correct? Not that I know of. Are you aware of whether the MMAR contain any recordkeeping requirements on either a person or a designated producer? I dont know. Are you aware of whether or not previous iterations of the MMAR imposed recordkeeping requirements on a person or designated producers cultivating marihuana? I cant answer that question. I dont know. Are you aware of whether or not Health Canada provides to persons issued an authorization to possess dried marihuana or a licence to cultivate marihuana for personal or for designated production any advice or information on proper cultivation processes to be used in cultivating the product? I cant comment. I dont know. Are you aware of whether or not Health Canada supplies persons holding an authorization to possess with suggestions about quality standards that should or could apply to their cultivation of marihuana for personal medical use? I cant comment. I dont know. Is it a fair statement to say you dont have a great deal of familiarity with the Marihuana
A Q A Q
A Q
A Q
A Q
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Medical Access Regulations? I dont work in that division. Its not part of your job description? No. And I think you testified yesterday that you occasionally but rarely consult with people in that division? If they need scientific information from me, yes. And is that something thats a regular part of your work with Health Canada? It depends. Sometimes yes, sometimes no. When was the last time someone in the Medical Marihuana Access Division consulted with you for scientific information? I dont know, probably a month or two ago. And what was the subject matter of that discussion? I cant recall, to be honest. Its been a very busy few months, so... I can imagine. At paragraph 42 of your affidavit, Exhibit 40 in these proceedings, you indicate that: ... there is very little scientific or medical information regarding additional adverse effects friends i.e. in addition to the effects of cannabinoids themselves on friends that could be related to products derived from marihuana such as oils, ointments or baked goods. There is likely a wide variety of non-standardized production methods for these products, as well as source materials, friends, e.g. varying THC levels and varying levels of contamination [indiscernible/rapid speech] added ingredients... Again your parenthetical is: ... to prepare ointments or baked goods, and storage conditions that could influence the quality and safety of final products. Youre using in those sentences that Ive just quoted what we described yesterday as careful language, could might maybe. Thats accurate, isnt it?
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q
Yes. And thats because you dont, yourself, know whether or not thats occurring or not occurring, do you? I dont know. I dont go out and investigate such things, no. Okay. And in -- you say: In the absence of good quality control manufacturing products -- manufacturing practices, the likelihood is high that composition, including THC levels and quality of these products will vary from one batch to the next, which creates an additional level of uncertainty regarding their effects. Also, unless valid laboratory analysis are performed on the product, it is not possible to determine whether and how the cannabinoids that were present in the source material may have been chemically modified, whether byproducts or contaminants are present in the final products, and in such cases what the effects these could have on the consumer or worse, on the patient. Again, careful language because we dont know, do we, whats happening? Thats right. And youre not aware, yourself, of any adverse -any reports of adverse effects related to the products at issue in this case that are produced by Mr. Smith for the Cannabis Buyers Club of Canada, are you? I am not. Many of the problems that you identify as possibilities are related to -- well, some of these -- some of these problems that you speak about -- of in this paragraph can arise in any food products; possibly contamination, possibility of unsafe food practices, that can arise in any food product, not just food products containing cannabinoids, correct? Well, theres a difference, I think, in that the food -- the food industry is highly regulated. There are rules and regulations, you know, in place to protect Canadians. And Health Canada has not --
A Q
A Q
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
MR. ECCLES: Perhaps my friend can allow the witness to complete his answer, please, My Lord? MR. TOUSAW: Oh, I thought -- I thought -MR. ECCLES: He wasnt finished. MR. TOUSAW: -- he had. I apologize. Q I thought youd finished. Please go ahead. A There are -- there -- there are rules and regulations in Canada governing the production, manufacturing, and associated processes regarding foods and drugs, and those are designed to protect Canadians, so I dont know that there are similar standards for cannabis. Q And as far as youre aware, the Marihuana Medical Access Regulations do not contain any such standards for the -- for the production of cannabis-based products, correct? A Not that I know of. They may, but I dont know the MMAR that well. Q And in fact one of the regulatory schemes that exists to govern the manufacturing process of, for example, herbal products is the Natural Health Products Regulations, isnt it? A I believe so, yes. Q And are -- you sitting there today, are you aware that, but for an exclusion clause in the Natural Health Products Regulations which excludes substances listed in the Controlled Drugs and Substances Act, that the Natural Health Products Regulations would in fact apply to the cannabis plant and its derivatives? A I cant comment because I dont know. Q Assuming that Im correct in my suggesting that Natural Health Products Regulations governs manufacture of natural health products and imposes quality controls on manufacturing of natural health products, and then but for an exclusion it would apply to cannabis, if that were the case, then there would be a regulatory scheme in place to protect Canadians that applies to cannabis products, cannabis-derived products, correct? A I dont want to speculate. Q It is within the purview of Health Canada to license laboratories for the purpose of testing products produced by Canadians with authorizations to possess dried marihuana, correct? A I dont know. Q It is your testimony, however, that, as you just
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q THE MR. THE MR. MR. THE A
said, that Canada has a number of rules and regulations that govern the manufacture of both food and drug products, and that those exist to protect Canadians, correct? Yes. And it is the case that the governments regulatory choices in these areas are the reason that those regulations do not apply to cannabis and cannabiday -- cannabis and cannabis-based products that are produced by licence first, thats correct? I dont know. I cant comment. At paragraph 43 of your affidavit you speak to Sativex, which weve discussed, a product of G.W. Pharmaceuticals -COURT: Havent we established that he doesnt speak to paragraph 43 -TOUSAW: Oh, youre right. COURT: -- at all and somebody else has spoken to paragraph 43? TOUSAW: Youre right, My Lord. ECCLES: Well, My Lord, perhaps we could excuse the witness because thats a matter I wish to address in the absence of the witness? COURT: Dr. Abramovici, could you step out into the hallway, but dont go too far? I will, thank you. (WITNESS STOOD DOWN)
MR. ECCLES: My Lord, in my respectful submission, the witness in his direct examination confirmed and clarified several paragraphs in the material, and in final questions under direct confirmed that he had read the entire affidavit, it reflected his views, and he stands by it. Whether or not those are views shared by the Director of the department is, in my respectful submission, not sufficient to simply delete them from all consideration. They do not become inadmissible or improperly before the court on that basis. THE COURT: Has he said these are his opinions? I thought all he said was I didnt draft that. MR. ECCLES: He has said, My Lord, that, when I took him through the affidavit and the conclusions, This is my opinion, and I stand by it. I specifically asked him two questions in that area.
666 VOIR DIRE Proceedings
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
THE
MR.
THE MR. THE MR.
Rather than go through every single paragraph Is this your opinion, do you stand by it? Is this your opinion, do you stand by it? I asked him at the conclusion of direct examination, towards the end of his questions You have read the entire document. This is your opinion, and you do stand by it? and he agreed, Yes, I do stand by the opinion and conclusions. He confirmed all. And in my respectful submission, if there is confusion in this area from re-examination -- from crossexamination, it is an appropriate area for the Crown to re-examine in, if Your Lordship has no note of that exchange. COURT: Well, I have a recollection, no particular note of the exchange, but I must say that when I heard that question, what I heard was him confirming the opinions that he expressed in his affidavit, but I did not take it necessarily as he having adopted those opinions stated by his supervisor in paragraphs 43 to the end. I simply and, perhaps incorrectly, Mr. Eccles, filtered out your omnibus question, those portions of the opinions that he disavowed in the sense of saying I had nothing to do with drafting this. Now, I -ECCLES: It may be, My Lord, this is a matter Ill have to address in re-examination, subject to my friends objections because there was a specific reason I asked those questions, and the specific reason is paragraph 41. I addressed 41 specifically because of the concern raised in that hes adopting Dr. Kalants opinion. I then asked him at the conclusion of the questioning whether he stands by the opinions expressed in his report, including the conclusions, and he said, Yes, I do. COURT: I dont remember the including the conclusions, but -ECCLES: I did take him to those, My Lord. COURT: Well, I -ECCLES: I wasnt aware of those being drafted and put into his affidavit, and then he swore to them. Thats the other difficulty, My Lord, which is that, regardless of who drafted those particular affidavits and inserted them into this witness affidavit, he swore to the entirety of the contents, including the conclusions.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
THE COURT: Well, I agree its a difficulty. MR. ECCLES: Yes, and my concern, My Lord, is if my friend is going to abandon the line of questioning on the understanding that those paragraphs are not before the court, that, in my respectful submission, is inappropriate because, in my respectful submission, they are properly before the court based on blanket questions, call them what we will, but the questions asked of the witness Have you read this report? Is it your report? Do you stand by the opinions in your report? He wasnt specifically asked by me, And did somebody else provide you information over and above that of Dr. Kalant, which youve adopted in your report? I wasnt aware that Ms. Desjardins, who was his direct supervisor, as I understand it, Dr. Suzanne Desjardins, the Director, had assisted in drafting those paragraphs and then having adopted -THE COURT: Well, she did more than assist. She added them to his report. MR. ECCLES: Yes, My Lord, and then he swore it. THE COURT: Yes. MR. ECCLES: And then -THE COURT: And thats a problem. MR. ECCLES: Well, with the greatest of respect, My Lord, it doesnt make it inadmissible or improperly before the court. If an expert is provided assistance by another expert, is given a summation, reads it, agrees to it and then swears to it. If my friend is going to abandon all questioning in that area, then my friend may have a difficulty when the Crown re-examines should Your Lordship permit it. Thats my concern, and thats why I wish to address it in the absence of the witness. THE COURT: Well, I suppose then what I ought to do is to hear Mr. Tousaws cross-examination on paragraphs 43 and on, well deal with the reexamination issue if it arises, but you have my own view of what I can or should make of paragraphs 43 on based on the evidence as I understand it to be at this point, and that is that, bearing in mind that had I known when this report was tendered that Ms. Desjardins had drafted paragraphs 43 through 46, I may not have
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
MR.
THE
MR. THE MR. THE
MR. THE MR.
THE
MR.
admitted those at all because of the clear law that joint or corporate opinions ought not to be admitted into evidence. TOUSAW: And where Your Lordship and I, and perhaps my friend and I will part company is as to whether or not Ms. Desjardins drafting those, producing them to the expert who then reviews them and says, Yeah, I agree with that, and swears to it, is a joint or corporate opinion. COURT: Well, if I had evidence that that is what happened, and I do not recall that that is the evidence, I recall an omnibus question, Do you stand by your opinions? -TOUSAW: Expressed in your -COURT: -- and he said, Yes. TOUSAW: -- report. COURT: Expressed in your report, and 43 and onward are not his opinions expressed in his report. At least thats the flavour I have from his evidence so far. They are the opinions of Ms. Desjardins added to his report as his supervisor. Now, thats what Ive got so far. Maybe I have misapprehended the evidence. Somebody may be able to or may want to order a transcript of that portion of the evidence, but thats the impression I have. So what Ive got is this man saying, in effect, My opinion ends at 42, Ms. Desjardins added the rest of it, and for some reason he then swore it. Where am I? ECCLES: And that may be a matter for reexamination, My Lord. COURT: Yes. ECCLES: But that was not my understanding of the question I asked, and it was the -- the result I was hoping what Your Lordship refers to as an omnibus question would avoid. COURT: Yes, well, it didnt get past, at least over that hump with me, but it probably is something now youre going to want to try to pursue in re-examination. Mr. Tousaw might want to cross-examine on it since he has Dr. Abramovici here, and try to force him to defend Ms. Desjardins opinions. ECCLES: And that is a matter that -- my concern, My Lord, was that my friend, it sounded like he was simply abandoning an area, and I wanted to flag the court and --
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
THE COURT: Yes. MR. ECCLES: -- for my friend this is an issue that may well arise -THE COURT: All right. MR. ECCLES: -- and I wouldnt want my friend to be caught by surprise at the end of the day. THE COURT: Can we have Dr. Abramovici back? THE SHERIFF: Yes, My Lord. HANAN ABRAMOVICI recalled. MR. TOUSAW: My Lord, while the witness is coming in, I note the time. It may be useful for me to take the lunch break a little early so that I can both turn my mind to the issue that weve just discussed and I will be embarking in the afternoon session on a new line of questioning using the Information for Healthcare Professionals document, but perhaps it does -THE COURT: Well, all right. MR. ECCLES: -- make sense to interrupt. THE COURT: Im sorry to bring you back, Dr. Abramovici -A No. THE COURT: -- but it looks like were taking an early lunch. A Very well. THE COURT: Two oclock. MR. TOUSAW: Thank you, My Lord. THE CLERK: Order in court. MR. ECCLES: Should I -- may I have your permission to tell -- I know, thats why Im saying it -THE CLERK: Just hold on a moment. MR. ECCLES: -- while its still running. Can I suggest to my witness he rearrange his flight for tomorrow? MR. TOUSAW: Yes, I think... (WITNESS STOOD DOWN) (PROCEEDINGS ADJOURNED FOR NOON RECESS) (PROCEEDINGS RECONVENED) HANAN ABRAMOVICI, recalled.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
MR. TOUSAW: Thank you, My Lord. If the witness could be provided with Exhibit 40, please? THE CLERK: Thank you. Exhibit 40. A Thank you. CROSS-EXAM BY MR. TOUSAW ON VOIR DIRE, CONTINUING: Q A Q Doctor, over the lunch break did you have the occasion to discuss your testimony or communicate about the substance of your testimony with anyone? No. Im going to take you to paragraph 37 of your affidavit in which you describe literature suggesting a positive association between cannabis use and the development of psychosis, particularly in people susceptible to psychotic disorders, as well as in adolescence. Do you see that paragraph? I do. There are not -- is it fair to say that there is -- there continues to be some gaps in the knowledge regarding the relationship between cannabis use and the development of psychosis such that it would not be appropriate to say that the use of cannabis is a -- is -- that the use of cannabis as a matter of fact causes the inception of psychosis in persons that are not pre -already predisposed to it? I would say that there is good evidence that, from clinical studies and epidemiological studies that suggest an increased risk of developing psychosis among people who are not susceptible or not genetically predisposed or not particularly -well, not particularly susceptible, but there is an even, I think, a stronger risk of developing psychosis following the use of cannabis or THC in people who are susceptible. Because of this potential risk it would be, and in fact there is a warning in the product monographs of Sativex and Marinol to the effect that use of those products if contraindicated in persons who have a history of schizophrenia, for example? Yes. And if I were to say to you that the Cannabis Buyers Club of Canada does not allow membership in that organization for purposes of people seeking to treat mental illnesses with cannabis,
A Q
A Q
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A
A Q
that would be -- that would be an appropriate response to -- it may not be the complete response, but it would be an unappropriate [sic] response to these potential risks, correct? Somewhat. I -- to my knowledge, the Cannabis Buyers Club of Canada has no real way of knowing whether or not these people have an underlying mental disorder or history. Theyre not doctors, medical doctors, that I know of, and so I dont think, you know, while -- while a cautionary statement or a prohibition of joining the club if youve got a diagnosed mental disorder is good, for those who have no diagnosed mental disorder but may suffer from subclinical symptoms, I dont think they would be in a position to make that decision. Similarly a physician seeing someone complaining of arthritic pain and that individual does not report any history of schizophrenia or other mental illness, and that physicians unaware of that history, assuming theres no prior relationship, correct? Well, I think physicians generally do a work-up on a patient to find out their history, physical and mental condition, et cetera, et cetera. Its part of the medical file, as far as I know. They ask the questions, and of course they depend on the individual to give honest answers, correct? I think their questions are generally followed up by physical examination as well as laboratory tests. Its not just the questioning. Its the overall evaluation of the patient. Youre not suggesting that a person who attends at a walk-in clinic for purposes of seeking a prescription to deal with arthritic pain is going to be put through a battery of tests to determine whether or not they have underlying schizophrenia, are you? I dont know. I cant comment on that. It is the case that the dosage of THC, for example, is going to be an important factor, both dosage and duration of use is going to be an important factor in whether or not a person whos at risk of developing, for example, schizophrenia may have psychotic episodes precipitated by the use of cannabis-based medicines, correct? Thats my understanding that the increase in risk
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
appears to be dependent on dose and duration of use, frequency of use. The studies that you -- the comments that you make at paragraph 37, the second paragraph -- the second sentence, my apologies, beginning with: Controlled clinical studies carried out in those with no history of psychotic disorders reported the manifestation of transient schizophrenia-like symptoms induced by the administration of Delta-9-THC.
A Q A Q A Q
A Q
A Q
Do you see that sentence? I do. And the word transient, I take it, means the symptoms manifested and then went away, correct? Yes. Thats what transient means. Similarly, the use of transient in the next sentence again symptoms manifested and then went away, correct? Yes. You are aware that there has been both an increase in usage rates at a population level, as well as an increase in potency of what Ill call street marihuana available to the population over the last 20 to 30 years, correct? Thats my understanding, yes. And are you aware of any epidemiological or population-based studies that demonstrate a significant uptick in the rates of schizophrenia in the population over that same time period? What I am aware of is the studies that Ive included, and those studies summarize the literature by doing a meta-analysis, and the -their conclusions are that there is an increased risk of developing psychosis among individuals who may not have a predisposition to the disorder as a function of usage and frequency -- dosage and frequency of use -- dose response. But in response to my question, youre unaware of any studies suggesting or demonstrating that theres been an uptick or an increase in the rates of schizophrenia in the general population that would track the increase in both potency and use rates of cannabis in the general population? No, Im not aware. At tab G to Exhibit 40 appears a document entitled
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Information for Healthcare Professionals, and that is the -- that is the document that weve been discussing yesterday and today that you updated as part of your role with Health Canada, correct? A Yes, thats correct. Q And this is dated September 2010, correct? A Yes. Q Since September of 2010 have you had the occasion to update yourself on the literature in the area? A I think so, yes. Q And have you correspondingly updated this document, the last version of which was in September 2010? A Im working on that, yes. Q Youre currently working on that now? A I have been working on it, yes. Q Do you have an estimated completion date for that work? A Id say probably the next few months. Q And you mentioned in your earlier testimony that you were working 40 hours a week for about three months or more, for about three months to complete this update, it appears in your affidavit. I take it youre not solely working in the next update of this monograph, correct? A Thats correct. Q During that period of time that you were producing the September 10 -- 2010 version, that work was your primary job responsibility for Health Canada? A It was a significant part of my workload, yes. Q And are you working 40 hours a week and sometimes weekends updating the Information for Healthcare Professionals document now? A Not so much now, no. Q Theres less urgency to completing that update? A No, I wouldnt say theres less urgency, but the information hasnt changed in a -- I dont -- I -I dont feel like I have to do as much work as I did initially. Q Do you recall the date of the version, the prior version of the Information for Healthcare Professionals document? A It was dated 2003. Q I am going to hand you a one-page printout -A Yes. MR. TOUSAW: I just want to make sure Im giving the right copy to my friend.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q A Q A Q A Q A Q A Q
Q A Q
A Q A Q
Im going to hand you a one-page printout which is a printout from a search in PubMed for the term cannabinoid. Do you recognize that? I recognize that its cannabinoid, you know, you put in the key word cannabinoid in PubMed and got a paper. And this was --- got -- got -- got a, sorry, search -- search results. And these are what the search results look like when you do a search on PubMed for a particular term, correct? Yes. And youll note at the right of that theres a [indiscernible] results [indiscernible] -Mm-hmm. -- 14,647; do you see that? I do, yes. That would be consistent with their being 14,647 hits, if you will, for that particular term in the PubMed database, correct? Yes. And is that type of search the type of search that you did when conducting -- at least one of the types of searches I assume that you did when conducting your work in updating the Information for Healthcare Professionals? Well, the problem with doing a search in this fashion is that, if you search a very broad term, youre going to have to look through a lot of papers -Yes. -- so typically when I do my searches I narrow down the search. Okay. So youre not just searching for cannabinoid, youll use other terms to try to restrict the number of hits that youre getting, correct? Yes. And there are filters that you can run in the PubMed database that allow you to reduce the number of hits, correct? Yes. And there are filters in the PubMed database that allow you to filter your results by, for example, the number of free full text documents that PubMed has in its database, correct?
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q
A Q A Q
A Q A Q A Q A Q A Q
A Q
A Q
I believe so, yes. Ill just hand you another document, the same search, filter your -- filter your results as free full text, and we see that the hits have reduced from 14,647 to 3,139, correct? Sure. And thats consistent with filtering the search for -- you get less articles because less of the full text articles are available in the database, correct? Certainly. Theres another filter that PubMed helpfully provides called a review filter. Are you aware of that filter? I am, yes. And that then filters your results not by the number of free full text articles that one has in the database, but by the number of articles that PubMed has listed as review articles, correct? Yes, I believe so. And review articles are articles that review the existing literature on the topic. You talked about that yesterday, correct? Thats right. Is that the type of search that you conducted when updating the September 2010 document? One of the many -Okay. -- different types of searches, yes. Yes. Undoubtedly you spent a lot of time putting different key words and filtering searches in different ways? Yes. But thats one way that PubMed gives you an opportunity to say Im interested in review literature, at least this is the stuff thats been identified as review literature, correct? Certainly. And you can search by date. Ill hand you the last piece of paper, which is a PubMed search for the same term cannabinoid, but its a date restriction commencing 30th of September 2010 in terms of the date of publication, and the number of hits that come up are 1,587; do you see that? I do. You dont have any reason to dispute that since September of 2010 theres 1,587 new articles
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q A Q A Q A Q
containing the term cannabinoid in the PubMed database? I dont. As we talked about yesterday, this is an area in which the science continues to evolve, correct? Yes. Ill ask you to direct your attention to Exhibit G of Exhibit 40 in these proceedings, tab G, and turn to Section 1.1. Yes. And we had a series of numbered sections corresponding to the table of contents, correct? Yes. And Section 1.1 is Chemistry -- or 1.0 is Chemistry and 1.1 is Composition, correct? Yes. And the second full sentence of that paragraph reads [as read in]: Although leaves and flowering tops of cannabis plants yield more than 60 different vital cannabinoids, the major active components are Delta-9 tetrahydrocannabinol, Delta-9-THC, THC, cannabinol, CBN, and cannabidiol CBD.
A Q
A Q
A Q A Q
Do you see that? I do. So at the time that you updated your research, the number of phytocannabinoids was 60, and youve now said in your affidavit 70 and perhaps theres even more that have been identified, correct? Yes. And of course at paragraph 10 of your affidavit you critique Dr. Pate for using the term several and indicate that theres more than -- more than 70, correct? Yes. Under 1.2, Other Ingredients, you discuss the potential ingredients in marihuana smoke, correct? Yes. And you say in that section that: Marihuana smoke contains many of the same carcinogenic chemicals found in tobacco smoke.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
Yes. And you go on to say that: Differences in smoking techniques are reported to result in a threefold higher levels of tar and fivefold higher levels of carbon monoxide being retained in the lungs during cannabis smoking as compared to tobacco smoking.
A Q A Q A Q
Correct? Yes. And that -- well, these are things obviously that people that are consuming cannabinoids would want to minimize, correct? Yes. Those are -- those are harmful things to human health, correct? Yes. You go on to talk about, in the last sentence after parenthetical 10, the last three sentences that: Ammonia in mainstream marihuana smoke is twentyfold greater than tobacco smoke, oxides of nitrogen and hydrogen cyanide were fives times higher than those in tobacco smoke, but the carbon monoxide was significantly lower in mainstream marihuana smoke under most smoking conditions.
A Q
A Q A Q
You see that, right? Yes. And of course youre going to want to minimize your intake of ammonia, oxides of nitrogen and hydrogen cyanide because those are harmful to human health, correct? Yes. One way to minimize the intake of those compounds is to not smoke, correct? Agreed. If you turn to 2.0, Clinical Pharmacology, theres a discussion of -- and Ill take your attention to, at the very bottom of page 1 a sentence, the last sentence, its a partial sentence that begins, Most tissues contain. Do you see that?
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q
Yes. Here youre talking about tissues within the human body, correct? Thats right. And youre indicating that: Most tissues contain a functional endocannabinoid system which consists of the cannabinoid receptors CB1 or CB2. The endocannabinoids anandamide AEA and 2arachidonoylglycerol 2AG and their ... And you put in quotes: ... entourage compounds which modulate endocannabinoid activity and endocannabinoid synthesizing in degrading enzymes.
A Q A
A Q A Q
Do you see that? I do. When you use the term entourage compounds, what do you mean by that? That those are lipid species that are found in the -- in the cells along with the endocannabinoids, and they are thought to modulate the activity of the endocannabinoid system. Much in the same way that, for example, Dr. Russo hypothesizes that some of the phytocannabinoids or that some of the terpenes may modulate phytocannabinoid activity in the human body, correct? Yes. Its a similar concept? Yes. And you go on to say in the next paragraph that: Much of the pharmacodynamic information on marihuana refers to the effects of the major constituent THC which has activity at both the CB receptors but whose psychoactive effects are mediated by the CB1 receptor.
A Q
Do you see that? I do. And thats because the principle focus of research, at least until recently, was on THC both in the laboratory setting and in the clinical
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
setting, correct? Thats correct. The next sentence reads: On the other hand, CBD, cannabidiol, lacks detectable psychoactivity but displays high potency as an antagonist of CB1, CB2 receptor agonists and affects the activity of a significant number of other targets, including ion channels, receptors and enzymes.
A Q A Q
Do you see that? I do. And so CBD is not at least a detectable psychoactive substance, correct? Thats correct. You go on to discuss that: The results from pre-clinical studies suggests CBD has anti-inflammatory, analgesic, antipsychotic, anti-ischemic, anxiolytic and anti-epileptic effects.
A Q A Q A Q A
Q A Q A Q
Do you see that sentence? I do. And thats an accurate review of the pre-clinical literature, correct? Yes. What is anti-ischemic? Anti-ischemic -Thank you. At least you knew what I was talking about. I knew, yes. An example of ischemia would be blockage of blood flow to an organ, so lets say something that happens during a stroke or vasospasm, the organ in question is lacking blood flow for a certain period of time. Thats ischemia, so anti-ischemia would be the opposite of that. Reducing the blockage? Thats right. And anxiolytic, as I understand it, is antianxiety. Is that fair to say? Yes, I would think it would be fair to say. Yes. You go on to discuss CBN, another of the phytocannabinoids, as a product of Delta-9-THC
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
oxidization as 10 percent of the activity of Delta-9-THC. You indicate that: Its effects are not well studied but that it appears to have some immunosuppressive properties... And go on to say: CBG... A Q Thats another phytocannabinoid, correct? Yes. ... is a partial CB1/2 receptor agonist and may have some anti-inflammatory and analgesic properties. A Q Correct? Yes, I believe so. Skipping a sentence and moving on to, However, your conclusion, or at least what you draw from these studies is: However, the results from these in vitro and animal studies point to potential therapeutic indications such as psychosis, epilepsy, anxiety, sleep disturbances, neurodegeneration, cerebral and myocardial... A Q Ischemia. ... ischemia, inflammation, pain and immune responses, emisis, food intake, type 1 Diabetes, osteogenesis and cancer. A Q A Q Correct? Thats right. Those are quite promising therapeutic applications, arent they? Those are avenues of research, yes. And that research would then, one hopes, be conducted clinically so that we can determine whether or not the promising areas of research actually turn into medicines that assist human health, correct? Yes.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q A Q
A Q A Q A Q A Q
And of course as we discussed yesterday that would require some organization or individual undertaking to do the clinical study work, correct? Yes. And currently Health Canada is not undertaking any of the clinical study work in this area, correct? No, but there are companies that are. And those are private companies seeking to bring drug products to the market, correct? Yes. Theres a table commencing on page 3 in which you -- theres another chart essentially of the pharmacologic actions of cannabis in humans. When you refer to cannabis at the top of table 1, and thats on page 3, are you referring to cannabis the plant or cannabis and cannabinoids? Its cannabis and THC. Cannabis and THC? Yes. Okay. And so you list a series of body systems and effects, and then provide some detail of those effects, correct? Yes. By way of example, in terms of a central nervous system effect, you have listed analgesic, painkilling essentially, right? Yes. And you indicate: ... similar in potency to codeine but by a different pharmacological mechanism.
A Q A Q A Q A Q
Correct? Yes. In this case it was THC. It was -- it was THC. THC is similar in potency to codeine -Yeah. -- but it -- but it works differently in the body? Yes. And my understanding is that, unlike codeine, for example, THC doesnt depress respiratory activity, correct? Thats correct. And that obviously one would not want to depress respiratory activity in excess because that can lead to inability to breathe and death, correct?
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q
Thats right. Slightly down from that theres a listing of tolerance? Yes. And its again with respect to THC: Humans can develop tolerance to the behavioural and somatic effects, including the high.
A Q A Q A Q A
Q A Q A Q
A Q
Correct. Yes, with chronic use. Yes. And so after awhile, if youre using this THC at least quite regularly the psychoactive effects may well diminish or indeed go away completely? For some people, yes. It depends on how often you use it, how much you use. Your own sensitivity to it? Your own sensitivity, yes. Turning the page, Section 2.2 refers to Pharmacokinetics. What does the term pharmacokinetics mean? Pharmacokinetics is essentially the discipline in pharmacology that looks at the distribution or essentially how -- how drugs behave in the body as a function of time, concentration. How theyre absorbed, metabolised, spread throughout the body, those kinds of things? Yeah, so absorption, distribution, metabolism -Okay. -- as a function of time, as a function of dose, yes. And so under Absorption, 2.2.1, broken down into subheadings of Smoked Cannabis, Vaporized Cannabis Oral THC and on the next page Buccal THC Rectal THC and Topical THC, and those are the different methods by which one can absorb THC, for example? Yes. And with respect to smoked cannabis, there -- the last -- the last sentence of the section on absorption speaks to -- well, it says: Smoking cannabis containing 1.64% THC (mean dose 13.0... Is that milligrams?
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
Yes. milligrams THC) resulted in mean peak THC plasma levels of 77 nanogram per mil...
...
A Q A Q A Q A Q A Q
A Q A Q A Q A
Q A Q A
Is that correct? Yes, thats correct. Thats a fairly low -- fairly low THC content for dried marihuana, correct? Yes. By -- by at least todays street standards? Thats right. And its an order of, well, 12 to 13 percent of the THC content of the marihuana currently sold by Health Canada, correct? Yes. And that low potency -- is it fair to call that a low potency cannabis? Yes. So if I say low potency cannabis, that type of low potency cannabis, smoking that 1.64 percent THC, according to this study that you brought puts THC plasma levels in the blood at 77 nanograms per mil? Thats an average. On average? On average. There could be some people had a lot lower and some people had a lot higher. Well, thats what averages are, arent they? Thats right. Right. It is possible that in that study, and I dont recall because there are so many studies, that they may have measured or not measured the THC level, THCA level in there, and so they may have underestimated. The potency might actually be more than recorded. I dont recall. The potency of the THC or the potency of the -- or the amount in the system? The amount in the cigarette -The amount in the cigarette. -- thats -- thats converted to THC, so although it says there 1.64 percent, saying its a low potency, its possible. I dont recall because theres so many papers that -Yes. Well, that would have been a useful fact to put into the monograph if in fact the numbers
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q
inaccurate, wouldnt it? Thats true, and in my review of it I cant recall if I updated that or not. That is consistent -But -- but that would be something that I would be updating, yes. Yes. So lets read the sentence just above that: Standardised cigarettes have been developed by the National Institute on Drug Abuse (NIDA), and the relationships among cannabis THC content, dose administered and resultant plasma levels have been investigated.
A Q A Q A Q A Q
Correct? Yes. And NIDA is a United States based organization? Yes. And having now read that sentence does that jog your memory about whether or not the 1.64 percent THC was an accurate figure? Oh, possibly, yes. Its been widely reported that the NIDA cannabis is quite low potency, correct? Yes. As we go to 2.1.3, Oral THC, and this Information for Healthcare Professionals on the website of Health Canada the first sentence is: THC can be absorbed orally by ingestion of foods containing cannabis (butters, oils, brownies, cookies [and friends]), teas prepared from leaves and flowering tops, or through ingestion of capsules containing THC or THC analogues.
A Q A Q
Do you see that? I do. And thats an accurate statement in terms of whats available out there and how people are orally consuming THC, correct? As far as I understand it, yes. If you drop down to about halfway through the paragraph, the sentence begins with Tea: Tea made from dried cannabis flowering tops (19.1% THCA, 0.6% THC) has been documented,
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
but the bioavailability of THC from such teas is likely to be smaller than that achieved by smoking ... A Q Do you see that? Yes. And 19.1 percent THCA, 0.6 percent THC, on first blush, one would look at the THC number and say, well, thats quite low potency, but thats simply because the THCA has not been decarboxylated? Thats correct. And thus transforming the THC, correct? Thats right. Its actually quite a potent -- quite a potent cannabis if that 19.1 percent THCA is all converted into THC in that heating, that decarboxylizing process? Yes. The next sentence is that: Only 10-20% of synthetic THC (dronabinol, Marinol ...) administered in capsules with sesame oil enters the systemic circulation indicating extensive first-pass metabolism... A Q A Q You agree with that statement? I do, yes. And thats what we talked about earlier, correct? Yes. Right. The psychotropic effect or "high" occurs more quickly by the smoking than the oral route... And here is where this language actually appears in your affidavit. Yes. ... which has been characterized by Iversen ... as the reason "smoking is the preferred route of cannabis for many people". Thats actually a quote thats reproduced in your affidavit, correct? It is, yes. No information is given in that paragraph at least about the nanograms per mil levels of THC in the
A Q A Q
A Q
A Q
A Q
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q A Q A Q
system following consumption of any of these methods; is that correct? Thats correct, yeah, theres no information there. Yes. But you do talk about, as we discussed earlier today, what you described as the slow and unreliable absorption from oral dose in the chocolate cookie, and that the differential peak plasmas with mult -- potentially multiple peaks, correct? Yes. Dropping down to 2.2.1.4 on the next page, Buccal THC, thats in the mouth, correct? Yes. So thats the -- how one would ingest Sativex, by spraying in the mouth, correct, or the cheek? Thats right, yes. Yes. And here you indicate that: Following a single buccal administration of Sativex... Which you describe as four sprays of Delta-9-THC and CBD totaling -- you have -- the number is in milligrams: ... peak plasma concentrations of both THC and CBD typically occur within two to four hours.
A Q A Q
Correct? Yes. And thats a fairly -- thats quite a bit longer than peak plasmas concentrations occur when smoking, correct? Yes. And in fact you go on to say that: When administered bucally, blood levels of THC and other cannabinoids are lower than [what is] ... achieved by inhalation of the same dose ... because the absorption is slower, redistribution into fatty tissue is rapid... And there is some first-pass effect presumably because some of the spray is actually swallowed
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q
A Q A Q
and then taken in through the liver. Yes. And dropping down to 2.2.1.6, Topical THC, you speak to the issue of cannabinoids being highly hydrophobic, scared of water, they dont go through water very well? Thats right. And so therefore going through the skin, the aqueous layer of the skin which has quite a bit of water, actually limits the absorption of THC administered topically, correct? It does, but there are other ways of THC to get in. To penetrate the aqueous layer? Yes, through the -- I think through the hair shafts and some glands. Yes. Yes. You say: No clinical studies on the absorption of cannabis containing ointments, creams or lotions exist. However, some research has been carried out on transdermal delivery of synthetic and natural cannabinoids. And here you talk about the Delta-8-THC, thats the studies that you referred to in your affidavit? Thats right. And in fact this information is reproduced in your affidavit, correct? It is, yes. The last sentence indicates that: Mean steady-state plasma concentration of Delta-8-THC was 4.4 nanograms per mil within 1.4 hours, and that was maintained for at least 48 hours...
A Q A Q
A Q A Q A Q
Correct? Yes. That is 4.4 nanograms per mil, substantially less systemic load of THC than was achieved by smoking even the low potency dried marihuana, correct? Yes. 4.4 as compared to 77 nanograms per mil, correct? Yes. Yes. You further indicate that CBD and CBN, the
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q A Q
A Q A Q
A Q A Q
A Q A Q A Q
permeability of those two cannabinoids is in fact tenfold higher than Delta-8-THC, correct? Thats whats written there, yes. So its reasonable to think that if ones putting a whole plant of cannabis extract on the skin, it may well be that ones absorbing more of the CBD and CBN than in fact the THC, correct, depending on concentrations in the initial -It would depend on the --- in the initial --- concentration in the -- in the topical ointment or cream, yes. Yes. And at least if the concentration of THC is less than ten times higher than the concentration of CBD, for example, you may well be achieving more of a systemic load of CBD than THC, correct? Yes. I should just say these are animal studies. Yes. Yes, that -It might be different in humans. Well, this is information thats at least put out here for healthcare professionals who presumably are going to look at this document or at least potentially going to look at this document because a human being has come in and has sought perhaps an authorization to possess dried marihuana, correct? Sorry, can you repeat the question? Well, people go to their doctors and they seek authorizations to possess dried marihuana, correct? Yes. And doctors can contact Health Canada or can go on the Health Canada website, and this is the information thats really designed for them to look at so that they can make a determination as to whether or not it might be an appropriate treatment modality for that particular patient, correct? Yes, but they would have to look at the reference. Theres no recommendation there. No, no, no recommendation, but thats the point of this document, its for healthcare professionals? The point is -- the point is to inform healthcare professionals -Yes. -- on the science of cannabis and cannabinoids. Absolutely, and possibly the public because it is
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q
A Q A Q A Q A Q
A Q
A Q
A Q
A Q
available online, correct? Yes. Dropping down to the next section, with is Metabolism, 2.2.3, and the subheading 2.2.3.1, My Lord, thats on page 6 towards the bottom, you have a section for inhalation? Yes. And that discusses the plasma values of 11-hydroxy THC, thats a by-product of THC thats sort of -thats post-absorption of THC, correct? Its a metabolite of THC? Its a metabolite of THC, yes. And you indicate that it appears rapidly and peaks shortly after THC, approximately 15 minutes after the start of smoking, correct? Yes. And thats what we talked about earlier with sort of the quick acting effect, quick onset of action, correct, thats consistent -Yes. -- with that discussion? Yes. Oral, under the section Oral, 2.2.3.2 theres an indication that the concentration of both parent drug and metabolite, so THC and the 11hydroxy THC, peak at approximately two to four hours after oral dosing and decline over several days. Thats accurate, isnt it? Yes. And thats consistent with what we talked about earlier today this idea that you can have sort of longer lasting effect from oral dosing because it stays in the system for longer than smoking does, correct? Yes. Theres no section, no metabolism section for topical application of THC in this paper. Is that simply because theres no research that youre able to find on that topic? I dont -- I dont think I had found any research on that topic, so I didnt put anything in there. And in terms of your updating of this Healthcare Professionals document for the next iteration, have you found anything speaking to the metabolism of topical THC? I cant recall, to be honest. Did you do any searching on PubMed or otherwise
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q A Q A Q
A Q A Q
for metabolism of topical THC in preparation for giving your testimony here today? No, I dont think so. Did you do any PubMed searches at all specifically in preparation for your giving testimony yesterday and today in these proceedings? Yes, at some point. Yes. And did you find information during those searches thats not present in the Information for Healthcare Professionals document? Well, like I said, Im working on updating the document, so there will be more information available, yes. Well, at least with specific reference to drafting your affidavit -Yes. -- for these proceedings, is there information in your affidavit that does not also appear in the medical marihuana monogram Information for Healthcare Professionals? Sorry, is there information in my affidavit? Is there information that supports the facts and opinions in your affidavit that does not appear in the medical marihuana monogram? I -- I cant recall. I dont know. The next section, 2.2.4, is Excretion, and here you indicate, as we talked about: THC levels in [blood] plasma decrease rapidly after cessation of smoking.
A Q
Correct? Yes. And that: Mean THC plasma concentrations are approximately 60 and 20 percent of peak concentrations 15 and 30 minutes post-smoking respectively ... and are below 5 nanograms per mil 2 hours after smoking.
A Q
Correct? Yes. And so at least consistent with the -- what we talked about earlier, the 4.4 nanograms per mil thats a result of oral ingestion, about two hours after smoking, the plasma levels of THC, mean
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q
A Q
plasma concentrations of THC are approximately that same amount, correct? Sorry, I think the 4.4 was topical, not oral. Was topical, yes. Sorry. Thank you for that. Topical. Sorry, can you repeat the question because I -The plasma concentration, post-smoking, about two hours post-smoking, is roughly equivalent to the plasma concentration of the topical administration, correct? Yes. You go on to talk about the fact that you can detect the THC for quite awhile after smoking, and then the last -- the final paragraph under Excretion discusses: Following inhalation (or intravenous administration), elimination of THC and its metabolites occurs via the feces (65%) and the urine (20%). And that: After five days, 80% to 90% of the total dose is excreted. And you go on to say: Similarly, following oral doses, THC and its metabolites are excreted in both feces and urine... And thats what we talked about before lunch, goes through the system, and like just about everything we ingest, eventually comes out and is excreted in feces and urine, if its not used by the body, correct? Yes. I would just -- I would just want to say one thing that, for the excretion, talking about THC levels, thats Delta-9-THC, and for the 4.4 nanograms per mil its Delta-8-THC. Yes. For the topical administration it was the -Yes, for the topical. -- Delta-8-THC? Its Delta-8 versus Delta-9, yes. The next section, 2.3, is titled Pharmacokinetic/Pharmacodynamic Relationships.
Q A Q A Q
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q A Q A Q
This is a relationship between the way the body processes the compounds and what actually is happening when the body processes the compounds; is that fair? Thats fair. And the first sentence indicates that fundamentally its just unclear the relationship between plasma concentrations of the THC and essentially the psychotropic, cognitive and motor effects. Something is happening there, there is a temporal relationship, its unclear precisely what it is, correct? Yes. And the high wears off, were not maybe necessarily sure why or how it wears off. Is that fair to say? Thats fair to say for that and for the other functions as well. Yes. And thats -The pharmacokinetics and pharmacodynamics of THC are very complex. Yes. The second paragraph indicates that: Target THC plasma concentrations have been ... [developed] based on the subjective "high" response that may or may not be related to the potential therapeutic applications. And the next sentence is: Various pharmacodynamic models provide steady-state blood plasma concentration estimates in the range of 7-29 nanograms per mil THC ... for the production of a 50 percent maximal subjective "high" effect...
A Q A
Q A
Do you see that sentence? I do. What does that mean? That means that you need a range, again its very variable for different people across the population, but you would need a concentration of seven to 29 or 30 nanograms per mil to get a half of a high. Its difficult to quantify what half a high is? Well, you know, people who are -- I guess people
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
Q A
Q A Q
who have a lot of experience can say, Wow, this is the -- the highest Ive ever -- Ive ever experienced or the strongest effect Ive ever had, and, you know, you can -- you can use a scale and say, Well, this is half or this is, you know, zero. It can be an analog scale. It could be a subjective report. That seven to 29 nanograms per mil THC, thats somewhere between a little under twice the amount in the system up to about six times, seven times the amount in the system, at least, thats reflected in the Delta-8-THC systemic concentrations achieved through topical, correct? Yes. That tends to suggest that, at least from the studies that are referenced here, that it is unlikely that topical administration, at least Delta-8-THC is producing a -- more than a 50 percent maximal subjective high, correct? Well, it would all depend on how much topical you had put on, and in the sentence afterwards, serum concentrations between 7 and 10 have been compared to a blood-alcohol concentration of 0.05 percent, so if were saying that its 4.4 nanograms per mil topically and here were saying that being 7 to be impaired, then were not that far away. Well, were about a little -- a little bit, about 60 percent? Yeah, but again it all depends on how much youve put on. If you put a lot of the topical cream on you, and its high potency, then maybe your blood -- blood THC levels may be high. You might be able to get there? You could. It all depends. The next sentence after what you just read reads: Simulation of multiple dosing with a 1 percent THC cigarette containing 9 milligrams THC yielded a maximal "high" at about 45 minutes after dosing, declining to 50 percent of peak at about 100 minutes ... [after] smoking... And then you go on to indicate that: A dosing interval of 1 hour with this dose would give a "continuous high" and the
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
recovery after the last dose would be 150 minutes. The peak THC plasma concentration during this dosage is estimated at about 70 nanograms per mil and the steady-state THC plasma concentration at 50 percent of the maximum "high" effect ... at about 30 nanograms per mil... A Q Correct? Yes. If Im interpreting that correctly, smoking a one percent THC cigarette, which I think we can categorize as a low potency THC cigarette, results in peak THC plasma again of about 70 nanograms per mil, thats consistent with whats said earlier in the document which found closer to 77 nanograms per mil for a 1.6 percent THC cigarette, correct? Yes. And again thats of an order of magnitude larger than whats achieved by at least the studies on the Delta-8-THC suggesting 4.4 nanograms per mil? Yes. And here we see an indication that -COURT: Mr. Tousaw -TOUSAW: Yes. COURT: -- what does all of that mean? TOUSAW: Well, let me ask this question. What all that means, Id suggest to you, Doctor, is that its awfully difficult to get high from topical administration, isnt it? Youre just not achieving the kind of blood concentrations, at least in the studies youve referenced, that are necessary or that result from smoking even very, very low potency marihuana cigarettes? Thats correct, isnt it? I would dispute that. You may not get the levels that you get from smoking, but you may get levels that can have an effect, and that was one of the reasons why topical type transdermal patches were considered because they -- the scientists at the time had wanted to reach levels in the blood of five to ten or more nanograms per mil of THC for therapeutic purposes, and thats what they were designing those topical applications for. Well, for therapeutic purposes, but were talking about psychoactive effect, which is different -Well --
A Q A Q THE MR. THE MR. Q
Q A
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q A Q A
Q A Q A Q A Q A Q A Q A
Q A Q A Q A Q
-- from therapeutic purposes, isnt it? Ah, that depends. You know, you can have -people can experience a high at low levels, at lower levels. Different for different people? Different for different people, but that doesnt mean that they wont experience that high. But if youre seeking therapeutic effect, youre seeking pain relief, for example, youre not necessarily seeking to get high, correct? Youre not, and some people withdraw from clinical studies because at therapeutic doses they experience euphoria and other unpleasant effects, and thats why they -- and at -- theyre at therapeutic doses theyre experiencing those recreational effects. Yes, and they dont like it? No, they dont. Thats not the goal? Thats right. At least for those people? Thats correct. Those dropout rates are pretty low, though, arent they? Oh, I dont know about that. You dont know one way or another? I dont think theyre that low. More than 50 percent? I cant tell you, but its -- but one of the problems with studying cannabis and cannabinoids for therapeutic purposes is that the clinical trials are small and theres a high dropout rate. More than 40 percent? I cant tell you, but I -More than 30 percent? I dont want to put a number on it, but its -its up there. You dont mind guessing that its up there, that it might be high, but you dont want to put a number on it. Is that whats happening? Mr. Tousaw, I dont know. The next section is under Dosing, 3.0, and thats at page 8, My Lord, you indicate that dosing schedules, precise dosing schedules for cannabis simply havent been established, and thats because of a whole bunch of factors that weve talked about, but there are some rough
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
dosing guidelines, correct? Yes. And you say in that section: Besides smoking and vaporization, marihuana is known to be consumed in baked goods such as cookies or brownies...
A Q
Correct? Yes. ... or drunk as teas or infusions.
A Q
Correct? Yes. And again you speak of dosing by oral being slow and erratic, and dosages less well established. You go on to discuss: Other forms of preparation reported in the lay literature include cannabis-based butters, oils, compresses, creams, ointments, and tinctures...
A Q A Q
Correct? Yes. And again little or no dosing information exists there, correct? Yes. The final sentence in that paragraph is: Patients with no prior experience with marihuana and initiating marihuana therapy for the first time are cautioned to begin at a very low dose and to stop therapy if unacceptable or undesirable side effects occur.
A Q A Q
Correct? Yes, correct. And thats the process of self-titration that weve discussed earlier in your testimony? Thats right. And thats what Health Canada is saying to the public and to healthcare professionals is an appropriate way for patients with no prior experience to begin their marihuana therapy, to
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
start at a low dose and work their way up? Yes. And thats good advice, isnt it? I think thats the only advice one can give -And its -- and its --- at this stage. -- and its good advice, whether it comes from Health Canada or whether it comes from an employee of the Cannabis Buyers of Canada, correct? A I guess in this case, yes. Q And a member of the public reading this sees that information, and there isnt a process by which they can then inquire of you, for example, the author of this document, What do you mean by that? How does that work? They just -- they can sort of read it, and -- and either discuss it with someone who may know or figure it out on their own -- on their own, correct? A Yes. Q A physician reading this section on dosing or a member of the public reading this section on dosing who, for example, has an authorization to possess dried marihuana, is being told that these are known ways of consumption, right; cookies, brownies, teas, infusions, butters, oils, compresses, creams, tinctures, ointments. Reading that, youre going to see this is the way people ingest THC, correct? A Yes. Q Health Canada doesnt indicate here or anywhere in this document that the preparation by someone with an authorization to possess dried marihuana of a cannabis-based butter is actually an unlawful act? They dont say that anywhere in this document, do they? A No, this is not a legal document. MR. TOUSAW: My Lord, I note the time. THE COURT: All right. Fifteen minutes. A Q A Q A Q (WITNESS STOOD DOWN) (PROCEEDINGS ADJOURNED FOR AFTERNOON RECESS) (PROCEEDINGS RECONVENED) MR. TOUSAW: Yes, My Lord. HANAN ABRAMOVICI, recalled.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
CROSS-EXAM BY MR. TOUSAW ON VOIR DIRE, CONTINUING: Q Doctor, were at page 8 of tab, I believe its E -- or, sorry, tab F -- G -- tab G to Exhibit 40 in these proceedings, and just at the bottom of the page continues on about dosing, and talks about the nanograms per mil of THC in the blood of a 3.55 percent THC joint, and after smoking the whole joint or almost all of the joint, the concentration is 1. -- 162 nanograms per mil, and thats consistent with a study youve read, and that reports the studies accurately, correct? I believe so, yes. Okay. The next page, 3.2, Section 3.2 on Oral talks about -- they talk about the absorption of Marinol, and that the 10 milligram dose of Marinol yields a mean peak plasma of 7.88 nanograms per mil, correct? I think thats probably 20 milligrams per day yields -Yes, its the -- 10 milligram b.i.d. dose of Marinol, whats the b.i.d. stand for? Bis In Die, twice a day. Twice a day, okay. So twice a day youll have peak plasma 7.88 nanograms per mil, and then a chocolate cookie containing about the same amount of total THC resulted in peak plasma between 4.4 and 11 nanograms per mil, correct? Yes. The next section on page 9, section 4, Purported Indications in Clinical Use, and you go on to talk about a number of symptoms and conditions in this section, correct? Thats correct. Rather than take you through each and every one, Ill just ask you, generally speaking, under each of these sections, for example, 4.1 Nausea and Vomiting, what youve done is youre reproduced, to the best of your ability, the existing science or the existing science that you reviewed on the issue of nausea and vomiting in cannabis or cannabinoids, correct? Yes. And this is your view or the view of Health Canada expressed through your document on the possible indications and clinical use of cannabis and cannabinoid therapy for these various conditions,
A Q
A Q A Q
A Q
A Q
A Q
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
correct? Yes. And so we have Nausea and Vomiting, we have Wasting Syndrome at 4.2, a loss of appetite also at 4.2, and Ill just draw your attention to a couple of portions. As I say, I dont want to take you through each and every one. Youve essentially said that this is -- these are your views or at least the views of the science, as youve expressed them on the indications of usages of cannabis and cannabinoids to treat these particular conditions, correct? The information presented in -- in this section is a summary of the pre-clinical and clinical studies that have been carried out on cannabis and cannabinoids for these medical conditions. At the bottom of page 11, the last paragraph, the first sentence reads: Generally speaking orally administered cannabinoids are well tolerated.
A Q A Q A Q
Correct? According to those reviews, yes -Okay. -- or those papers, yes. And you have no reason to disagree with that statement with respect of those papers and what they report, correct? Thats correct. Similarly at 4.3.2 the last sentence, and this is on page 11, My Lord, again summarizing these particular studies: In either case, dronabinol was well tolerated with few side effects.
Correct? THE COURT: Im sorry, where are you reading from? MR. TOUSAW: 4.3.2, My Lord, that appears at the top of page 12. THE COURT: Oh, all right. MR. TOUSAW: Its the last sentence. A Can I just back up one second? Q Yes. A When we were talking about Generally speaking orally administered cannabinoids are well
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q A Q A Q A Q A Q
A Q
tolerated on page 11 -Yes. -- that was in reference to studies of MS. Yes. Yes. That particular condition -Yes. -- its under multiple sclerosis. Yes. Its in reference to multiple sclerosis? Thats correct. Similarly in 4.3.2 speaking about dronabinol being used for amyotrophic lateral sclerosis, correct? Yes. And so I think we can take it for granted that when youre expressing the results of these studies in any particular subheading, those studies talk about that particular condition, correct? Thats correct. And you speak of the use of cannabis/cannabinoids in spinal cord injury, in epilepsy at 4.4, in pain and thats broken down into a number of different categories. 4.5.1 is cancer pain, and the second sentence reads: Two randomized, double-blind, placebocontrolled studies... And Ill just pause there to say thats the kind of gold standard study that ones looking for in the clinical -- in the clinical field, correct? Yes, thats correct. And that the results of those studies: ... suggested [that] oral THC (dronabinol [and] Marinol...) provided an analgesic effect in patients suffering from moderate to severe continuous pain due to advanced cancer.
A Q
A Q
Correct? Yes. It talks about the dosing that those folks were taking, and at the top of page 13, the first full sentence reads: The 10 mg THC dose was well tolerated and, despite its sedative effect, appeared to have
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
mild analgesic potential. The 20 mg THC dose induced somnolence... A Q Tiredness, yes? Yes, sleepiness. Sleepiness: ... dizziness, ataxia, and blurred vision. A Q Correct? Yes. And there was some extreme anxiety. Now, these are consistent with the side effects that you -that youve discussed earlier in your testimony, correct? Yes. Non-cancer Pain at 4.5.2, and I just want to focus here on the second sentence under 4.5.2, thats on page 13, My Lord: The anti-nociceptive... A Q Nociceptive. ... nociceptive efficacy of cannabinoids has been unequivocally demonstrated in several animal models of inflammatory and neuropathic pain. That term that I butchered means a reduction in sensitivity to painful stimuli, correct? Yes. And so at least with these studies theyre concluding, in terms of non-cancer pain, its, in animal models at least, been unequivocally demonstrated that cannabinoids reduce sensitivity to pain? In animal models. Yes. And much like for some of the negative effects of cannabis that weve talked about appearing in animal models, those positive effects may or may not appear in clinical studies if those clinical studies are in fact ever performed, correct? Yes. Theres tremendous, and I dont want to use an adjective, but there is anecdotal evidence that
A Q
A Q
A Q
A Q
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
people are using cannabinoids, cannabis and cannabinoids to treat non-cancer pain and chronic pain arising from a variety of conditions, correct? Yes. You go on to talk about, at the bottom of page 13, Post-Operative Pain, Neuropathic Pain, and here again the second full paragraph theres a suggestion that at least: Short-term clinical studies suggest cannabinoids are moderately effective in reducing intractable central or peripheral neuropathic pain of various etiologies in individuals already receiving analgesic drugs... Side effects comparable to existing treatments, including dizziness, ataxia, feeling of intoxication and various other side effects, and I just want to focus in comparable to existing treatments. Thats comparable to existing noncannabis treatments, correct? Yes. In other words, what theyre saying is similar side effects with the cannabinoids and the analgesic drugs these folks are already taking, correct? Yes. And then again we see titration discussed when you write: These effects may be minimized by employing low doses that are gradually escalated.
A Q
A Q
A Q
A Q
Correct? Yes. Again Im not going to read all of these to you, but you go on to speak at 4.5.2.3 of rheumatoid arthritis, and the use of Sativex in a preliminary study. Arthritis is, to your knowledge, a Category 1 condition under the MMAR? I think so, yes. And your understanding, I take it, is that Category 1 is a condition for which theres no consultation with a specialist required. One can obtain an authorization to possess based solely on
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
consultation with -- with ones physician, general practitioner, correct? Thats my understanding, yes. And you go on to speak about headache and fibromyalgia, and then under the fibromyalgia, and this is at page 15, My Lord, the first bold-faced heading, 4.5.2.5, you discuss: A randomized, double-blind, placebocontrolled trial of nabilone... Again, kind of gold standard of clinical trials that we talked about before: ... showed statistically significant improvements in a subjective measure of pain relief and anxiety as well as on scores on the fibromyalgia impact questionnaire after 4 weeks of treatment...
A Q A Q
A Q A Q
Correct? Yes. And theres no significant changes in the number of tender points, and no lasting benefit when the treatments discontinued, correct? Yes. And so that clinical trial shows essentially that nabilone is providing at least the people in this study with some improvements in at least their subjective measurements of pain? Thats correct. Thats self-reported pain? Thats right. And you go on to discuss other diseases and symptoms, talking about movement disorders, dystonia, Huntingtons disease, and here in terms of Huntingtons disease on page 15, the third sentence youre discussing animal models and suggesting that the endocannabinoid system may have a role to play in Huntingtons disease, and you go on to say that that potential role, the findings, together with the well-known protective properties of cannabinoid-related compounds suggests that cannabinoids might help delay or arrest the development of the disease but, as you say, theres little clinical evidence because theres so few clinical trials, correct?
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q
A Q
A Q
A Q
A Q
A Q A Q
Yes, thats true. It suggests a need for more research, correct? Yes. And thats going to be true not just with Huntingtons disease, but thats true of a whole -- well, perhaps all but certainly a number of the conditions that are listed in this document, more research needs to be done? We need more knowledge on these topics, correct? Yes. And you go on to discuss Parkinsons, Tourettes Syndrome at page 16, and again if you focus on Tourettes Syndrome, some promise in cannabinoid treatments, THC treatments, and particularly with respect to Tourettes, again another randomized, double-blind, placebo-controlled crossover trial, and this is of oral doses of THC, showed some plasma concentration, I take it thats THC plasma concentration related? Yes, I believe so. Yes. Yes. Improvements in control of motor and vocal ticks and obsessive compulsive behaviour with no serious side effects, although transient mild side effects, headache, nausea, ataxia, fatigue and anxiety were noted in five of the 12 patients, correct? Yes. And by way of contrast to what are described as healthy marihuana users, the five milligram, ten milligram doses of THC did not cause cognitive impairment, correct? Yes. And there was a follow-up, a randomized, doubleblind, placebo-controlled follow-up for that same group, and compared to placebo they reported a significant difference in tick reduction with no detrimental effects on neuropsychological performance during or after treatment, correct? Yes, thats what it says there. And there are limitations in terms of sample size and those kinds of things, but again more research needs to be done? Yes. Glaucoma, again another area in which theres some clear evidence of decreased intraocular pressure as a result of cannabinoid treatment, and that you say at the third sentence:
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Smoking or eating cannabis has been shown to reduce intraocular pressure but these means of delivery have serious drawbacks including short duration of cannabinoid action (3-4 hours) and unwanted physical and psychotropic effects... Thats the same kind of issues that we described perhaps at this point repeatedly now over the course of the day, theres an issue with onset of action, theres an issue with side effects, but if you want the benefit, you may have to -- you may have to deal with those side effects, correct? For glaucoma there are alterative treatments, yes. And thats true for a variety of different conditions, theres alternative treatments that one can turn to, which themselves may or may not have side effects that are wanted or unwanted, correct? Thats true. You discuss asthma and hypertension, psychiatric disorders at the bottom of page 17, and in the last full sentence of page 17 reads: On the other hand, preliminary evidence suggests that cannabidiol (CBD) may have anti-psychotic ... and anxiolytic ... activity. The reference there suggests that CBD, at least, divorced from THC may be anti-psychotic and antianxiety, correct? Yes, I think those -- that was from the -potentially a -- actually, I dont remember. Just hang on. And so here we run into this issue of, in fact, THC, which has potentially pro-psychotic and proanxiety activity, and CBD are contained in the same plant may colloquially butt heads in the body and may be producing differential effects. It is some suggestion that if one compound has a proanxiety activity, one compound has an anti-anxiety activity, they may modulate the effects of each other, correct? That would depend on the dose of each compound. As with everything dose-dependency, different people, all of those factors will apply generally
A Q
A Q
A Q
A Q
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q
A Q
A Q A Q
speaking to cannabis and all medicines, really? Well, yeah, I think in the case of cannabidiol, those effects are usually seen in very high doses, doses which would not normally be seen generally speaking in, I think, street marihuana or most strains of cannabis. Dose -- and the marihuana sold by Health Canada is not particularly high in CBD, correct? Thats correct. And in fact its the case, is it not, that CBD has essentially been bred out of marihuana, the street marihuana, for example, because its unwanted because, in terms of recreational marihuana use, one wants the THC content because thats whats producing the euphoria or the high that recreational users are looking for, correct? Thats correct. You go on to talk about Alzheimers disease, and this is at page 18 at 4.6.6, and dementia. Again theres a reference to the last two or three full sentences double-blind, placebo-controlled crossover studies of five milligrams dronabinol daily associated with decreased in disturbed behaviour, but that there were some adverse reactions; fatigue, sleepiness, euphoria in those patients, and that in an open-label pilot study of six patients suggests an even dose of dronabinol reduces nocturnal motor activity and agitation in those who are severely demented, correct? Yes. And another promising avenue of research, but one in which more work is necessary, yes? It would be up to the researcher to decide, yes. 4.6.7 talks about inflammation, and the first sentence, excuse me, reads that: The ability of cannabinoids to suppress the production of pro-inflammatory cytokines and chemokines has been well-documented and may have therapeutic applications in diseases with an underlying inflammatory component...
A Q
Correct? [No audible response]. So my understanding of pro-inflammatory conditions such as psoriasis, such as Crohns disease, such as some forms of arthritis, such as psoriatic
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
Q A Q A Q A Q
A Q
arthritis, that those are what are known are proinflammatory conditions, correct? Well, those are inflammatory conditions. Yes. Whats happening is your bodys producing an inflammation, an inflammatory response, and then, because of the inflammation effect antibodies and are sort of attacking your own body because of that inflammation, correct, or thats producing the inflammation? Is that a fair laymens description of whats going on in pro-inflammatory conditions? Well, I dont necessarily know about antibodies. Theres a whole host of different chemical reactions and biochemical reactions that are occurring there that produce an inflammatory response. And one of those is that theres an increased production of these pro-inflammatory cytokines and chemokines, correct? Yes. And so if you suppress that production, you then suppress the inflammation, correct? Yes. Thats the theory? Thats the theory. Yes. You discuss IBS, IBD, inflammatory bowel disease, and inflammatory skin diseases such as dermatitis, psoriasis, pruritus. Pruritus is itching basically, correct? Yes. Yes. And at the bottom of -- well, let me back up to the Crohns disease, the second to last full sentence reads: Pre-clinical experiments in animal models of IBD suggest cannabinoids and endocannabinoids may limit intestinal inflammation via activation of CB receptors...
A Q
A Q
Correct? Yes. And those will be CB receptors that are in the areas of inflammation, in the gut, in the intestine, colon and other areas of inflammation, correct? Yes. And so at paragraph 28 of your affidavit in which
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q A Q
you say that theres no scientific evidence that you know of supporting the implied claim in Dr. Pates report that oral ingestion of cannabisbased medicines are therefore more beneficial than inhalation for those suffering from gastrointestinal conditions, theres a scientific basis for thinking that providing cannabinoids to the receptors in the area that is the source of the inflammation, for example in Crohns disease, has the potential to treat that inflammation at its source, correct? Yes, I guess you could make that inference, except in the animal models they didnt treat the animals orally. Well, the science there, it makes sense, doesnt it? I mean, it fits with the pharmacological principle of direct application to the site of action, it fits with the idea that if the receptors are in that area are the ones that need to have what Dr. Pate described, I guess, as the key in the lock, the cannabinoids put into the receptors, it makes sense that thats going to potentially be effective in treating those inflammatory conditions, correct? Its a possibility. And there is scientific evidence that at least supports that hypothesis, correct? Yes. Inflammatory skin disease, and the last full sentence reads: Thus, it is possible that cannabinoids have therapeutic value in the treatment of certain inflammatory skin conditions (such as psoriasis, pruritus, and dermatitis)...
A Q A Q A Q A Q
And again further research is required, correct? Yes. And the next sentence beginning with On the other hand, thats where you talk about the case reports of contact urticaria, correct? Yes. And thats at paragraph 34 of your affidavit? Yes. And its a direct quote, in fact? Yes. But you dont reproduce the preceding sentence
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
that Ive just read: Thus, it is possible that cannabinoids have therapeutic value in the treatment of certain inflammatory skin conditions ... You dont repeat -- you dont reproduce that sentence in your affidavit, do you? Well, this was in reference to HU210, which is different from phytocannabinoids. Its a -- but it is a -- HU210 is a synthetic cannabinoid receptor agonist, correct? Its a very, very strong one, yes. Yes. Nevertheless, that sentence, Thus, it is possible that cannabinoids have therapeutic value, that sentence is not reproduced at paragraph 34 of your affidavit? Thats correct. Just the following sentence starting with On the other hand, correct? Thats correct. You go on to discuss bladder dysfunction, antineoplastic properties. Anti-neoplastic properties, thats -- those are properties that could be seen to inhibit tumour growth, correct? Yes. And so this -- this section on anti-neoplastic properties discusses the results from in vitro in animal studies that suggests cannabinoids, endocannabinoids inhibit tumour growth, and the progression of several types of cancer, including glioma, glioblastoma, multiforme, breast, prostate, thyroid, colon carcinoma, leukemia, lymphoid tumours, correct? Yes. So theres some indication that cannabinoids may be useful in the treatment of and indeed in the inhibition of the progression of cancer, correct? Well, the studies, again its a matter of dose. It appears that at low doses cannabinoids such as THC actually promote cancer, and in high doses it would be inhibit in pre-clinical models. And the next paragraph actually reports a clinical study of using THC to treat cancer, essentially nine patients who had failed conventional treatments, surgical and radiation therapy, but -and their tumours were progressing, were treated
A Q A Q
A Q A Q
A Q
A Q A
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q A Q A Q
A Q
with THC intracranially, correct? Yes. They were injected with THC into the -- into the cranium, into the skull or -I think it was, yes, in the -- actually intratumourally, in the tumour. The THC was injected right into the tumour itself? Thats correct. And glioblastoma multiforme, thats a form of brain cancer; is that right? Thats right. They treated these nine patients for a median duration of 15 days, there was an unclear effect on patient survival, although the doses were well tolerated, but at least in vitro THC inhibited the proliferation, so inhibited the growth of cancer cells, tumour cells isolated from their glioblastoma, and actually decreased the viability of those -- of those tumour cells? It made it more likely that the tumour cells would die, correct? Yes, but that was at very high doses. Yes. The last sentence reads: A more recent in vitro study suggests that CBD enhances the inhibitory effects of THC on human glioblastoma cell proliferation and survival... Thats a suggestion that CBD is actually having an synergistic and enhancing effect on THCs, a potential treatment, potential use to inhibit cancer proliferation and cancer cells continuing to live in the system, correct? In this in vitro model, yes. Again, another -- quite a promising development obviously in the treatment of cancer, but one that requires further clinical work, correct? Yes. The next section at page 19 is Contraindications. Here you list a number of different contraindications, comparing it to Sativex and Marinol contraindications, anybody under 18, people hypersensitive to cannabinoids or to smoking. Ill pause and just ask that the contraindication to people hypersensitive to smoking are -- is really only applicable to people
A Q A Q
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q
A Q A Q A Q
A Q A Q A Q
that are going to ingest it by smoking, correct? Not necessarily. Not necessarily. Hypersensitivity to any cannabinoid, so it could be -Or to smoking? Yes. Yes, so Im just focus -- asking you to focus on hypersensitivity to smoking, thats only applicable to people that are going to smoke it, right? I mean, its -- you dont have to worry about hypersensitivity of smoking if your mode of ingestion is, for example, oral or topical, correct? No, but youd have to worry about hypersensitivity to the cannabinoid if -Clearly. Thats not the question Im asking you though. Im asking about hypersensitivity to smoking. Yes. Yes. Thats for people that are going to smoke? Yes. And so, for example, somebody with emphysema they dont want to -- you dont want them smoking dried marihuana to treat, for instance, if they had emphysema and fibromyalgia, pain from fibromyalgia, they shouldnt be smoking. If they have emphysema, its contraindicated, correct? Thats correct. For those people, an oral mode of ingestion would be superior to smoking because of that contraindication? It would be an alternative, yes. A superior alternative because, if you have emphysema, as weve just established, you dont want to be smoking, correct? Well, you wouldnt want to be smoking, no. There are warnings given at 6.1, I wont take you through them, but those are warnings as a result of your research that youve put in this document, and theres -- the next section is Precautions. And in particular Ill take you to 7.3 Drug Interactions, and you speak of clinically -- the most clinically significant interaction occurring when cannabis is taken with CNS, central nervous system, depressant drugs such as sedatives, hypnotics or alcohol, correct? Yes.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
Q A Q A Q A Q A Q
You dont want to use marihuana and alcohol in combination, correct? No, but you wouldnt necessarily want to use marihuana and powerful sedatives or hypnotics either. Yes, and you dont want to use alcohol with powerful sedatives or hypnotics either? Thats correct. And you dont want to use alcohol in combination with opiate-based painkillers either, correct? Thats right. Because theyre all central nervous system depressants? Thats right. Under Adverse Effects, 8.0 on page 21, My Lord, section 8.1 talks about carcinogenesis and mutagenesis, and the first sentence reads: While there are many cellular and molecular studies that provide strong evidence that smoked marihuana is carcinogenic ... the epidemiological evidence of a link between marihuana use and cancer is still inconclusive. The point thats being made there is that when youre smoking marihuana, as we talked about earlier in the section on smoking in this document, youre intaking substances that we know are carcinogenic substances, ammonias and tars and things of that nature, correct? Yes. But the evidence, at least the epidemiological evidence has not established a link between actually using marihuana and the subsequent development of cancer, correct? Thats my understanding. By contrast with tobacco, where we know the act of smoking tobacco, you intake carcinogens, and we also know that smoking tobacco is epidemiologically linked to the later development of cancer, correct? Yes. Theres a possibility that the failure to find this link between intake of marihuana and the subsequent development of cancer may well be because, as we discussed earlier, THC and CBD may
A Q
A Q
A Q
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
A Q A Q
A Q A Q A Q
have anti-tumour properties that inhibit cancer cell growth and proliferation, correct? Thats one possible explanation. We know, by contrast, or let me ask, do you know by contrast whether nicotine, the active -- one of the active ingredients in tobacco, is -- actually promotes tumour proliferation and growth? I dont know. Part of your role with Health Canada focusing on drugs of abuse does not include tobacco? No. At 8.2 we talk about respiratory tract issues, and mucosal biopsy specimens that are taken from chronic marihuana smokers who reported smoking only marihuana, you say showed a number of histopathologic changes, and I wont try to pronounce all those words, but stuff that you dont want to see in the lungs of people, right; basal cell hyperplasia, stratification. These are negatives, arent they? Yes. And you would want to minimize these negatives because these are things that you dont want developing in your lungs, correct? Thats correct. And one way to minimize those negatives is to not smoke, correct? Yes. Dropping down on page 23, 8.7 Central Nervous System here you say: The most frequently reported adverse [effects] ... with cannabinoids involve the central nervous system. And that: Commonly encountered CNS events in controlled clinical trials with [marihuana] ... and Sativex ... are intoxication...
MR. MR. MR. MR. Q
ECCLES: TOUSAW: ECCLES: TOUSAW:
It says Marinol and Sativex. Did I not say that? You said marihuana and Sativex. Oh, thank you.
Marinol... and Sativex... include drowsiness,
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
dizziness and transient impairment of sensory and perceptual functions... A Q A Q A Q Correct? Yes. And again these are effects that are discontinued upon cessation of use, correct? Yes. And theyre dose dependent, yes? Yes. A "high"... Which is defined as: ... (easy laughing, elation, [and] heightened awareness) from Marinol... was reported in 24 percent of the patients receiving it as an antiemetic and in 8 percent of patients receiving it as an appetite stimulant... A Q A Q A Q Correct? In that study, yes. In that study, and thats part of -- and the dizziness, in terms of Sativex, dizziness is the most common intoxication effect, correct? Report, yeah. Its reported initially in 35 percent of patients titrating their dose, reported incidents of the effect of long-term use is 25 percent, correct? Thats right. So the dizziness drops off as one, I guess, becomes accustomed to either titrating in a more appropriate manner or develops a tolerance to the dizziness? Some tolerance because its still 25 percent. Its still there for some patients, correct? Yeah. All other intoxication-like effects are reported by less than 5 percent of users (with the exception of ... [sleepiness] 7 percent) [of users]... A Q Correct? Thats for Sativex, yes. Thats for Sativex, and Sativex is the THC/CBD
A Q A Q
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q
extract along with some of the other constituent components of cannabis? Thats correct. The last section, My Lord, and this will conclude my questions on this particular -- I do note the time, but I only have one or two questions on this particular document, is Overdose/Toxicity at page 25, and the third sentence reads: The estimated human lethal dose of intravenous THC is 30...
A Q
A Q A Q A Q A Q
Is that milligrams per kilogram? Yes. Or 2,100 milligrams per 70 kilograms. Just in terms of trying to understand how that relates to nanograms per mil, the systemic load of -- of THC from smoking, its on an order of magnitude greater, correct? Yes. Many thousands of times greater? Its pretty high. Its pretty high. Youd have to -- and this is intravenous THC, correct, this is injected THC right into the bloodstream? Thats right. Is it fair to say its essentially impossible to consume a lethal dose of THC with humans? Yes. The -- you go on to say that: Cannabis often produces unwanted physical effects... And weve talked about these: ... dizziness, sedation, intoxication, clumsiness, dry mouth, lowered blood pressure... The next sentence reads: These adverse effects are generally tolerable and not unlike those seen with other medications... Thats a fair statement, isnt it? You have --
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47
A Q A Q
Yes. -- to speak aloud. Im sorry, yes. Yes. There are rare acute complications...
THE COURT: But just as a matter of interest, what would be the likelihood that you would disagree with your own statement? Not high, I gather. MR. TOUSAW: Q And there are rare acute complications, and you indicate that those: ... rare acute complications (such as panic attacks, psychosis, convulsions ...) that present to the Emergency Department can be managed with conservative measures... Thats what you say there at the end of that sentence? A Thats correct. MR. TOUSAW: Thank you, My Lord. I note the time. THE COURT: All right. Ten oclock tomorrow morning. (WITNESS STOOD DOWN) (PROCEEDINGS ADJOURNED TO FEBRUARY 8, 2012, AT 10 A.M.)
Transcriber:
C. Peart

R. v. Smith Transcripts Volume 4

Diunggah oleh

Informasi Dokumen

Hak Cipta

Format Tersedia

Bagikan dokumen Ini

Bagikan atau Tanam Dokumen

Opsi Berbagi

Apakah menurut Anda dokumen ini bermanfaat?

Apakah konten ini tidak pantas?

Hak Cipta:

Format Tersedia

R. v. Smith Transcripts Volume 4

Diunggah oleh

Hak Cipta:

Format Tersedia

Court of Appeal CA040556

v. OWEN EDWARD SMITH

W. Paul Riley Counsel

Kirk I. Tousaw Counsel

J.C. WordAssist Ltd.

149345-2 Victoria Registry

In the Supreme Court of British Columbia

P. Eccles K. Guest K. Tousaw

J.C. WordAssist Ltd.

EXHIBIT 31: EXHIBIT 32:

EXHIBIT 42: EXHIBIT 43: EXHIBIT 44:

MR. THE MR. MR.

THE MR. MR. Q

A Q A Q A MR. THE MR. MR. MR. MR. THE THE

Exhibit 40. EXHIBIT 40 (on voir dire): Hanan Abramovici Affidavit of

We'll take 15 minutes.

THE MR. THE A

Correct? Mm-hmm. I take it --

But lets call it -Pathology. -- pathology:

Correct? Correct. That doesnt say anything about whether or not

A Q THE MR. THE MR. MR. THE A

666 VOIR DIRE Proceedings

THE MR. THE MR.

667 VOIR DIRE Proceedings

668 VOIR DIRE Proceedings

MR. THE MR. THE

MR. THE MR.

669 VOIR DIRE Proceedings

A Q A Q THE MR. THE MR. Q

Correct? Yes. ... or drunk as teas or infusions.

MR. MR. MR. MR. Q

ECCLES: TOUSAW: ECCLES: TOUSAW:

Marinol... and Sativex... include drowsiness,

Anda mungkin juga menyukai