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O’Shaughnessy’s • Spring 2004 —11—

A Handy List for Doctors and Patients

Which Conditions Are Treatable With Cannabis?

The historic medical marijuana initiative passed by California vot- Harper CE. Effects of smoked marijuana in
experimentally induced asthma. Am Rev
ers in 1996 authorizes physicians to approve the use of cannabis “ in Respir Dis 1975;112(3):377-86.
the treatment of cancer, anorexia, AIDS, chronic pain, spasticity, glau- 5. Williams SJ, Hartley JP, Graham JD.
coma, arthritis, migraine, or any other illness for which marijuana pro- Bronchodilator effect of delta1-tetrahydro-
cannabinol administered by aerosol of asth-
vides relief.” matic patients. Thorax 1976;31(6):720-3.
Californians’ understanding that cannabis is a remarkably versatile 6. Pertwee RG, Ross RA. Cannabinoid
medicine has been confirmed in recent years by researchers throughout receptors and their ligands. Prostaglandins
Leukot Essent Fatty Acids 2002;66(2-3):101-
the world. GW Pharmaceuticals, the British company that is develop- 21.
ing cannabis-plant extracts to be marketed by Bayer, identifies the fol- 7. Tashkin DP. Respiratory risks from
lowing conditions as likely targets for its products. marijuana smoking. In: Grotenhermen F,
Russo E, editors. Cannabis and cannabinoids:
Pharmacology, toxicology and therapeutic
AIDS Wasting Syndrome 7. Abrams DI, Hilton JF, Leiser RJ, Shade References
potential. Binghamton, NY: Haworth Press;
AIDS (Acquired Immune Deficiency SB, Elbeik TA, Aweeka FT, et al. Short-term 1. Russo EB. Role of cannabis and can-
effects of cannabinoids in patients with HIV- 8. Tashkin DP, Simmons MS, Sherrill DL,
Syndrome) wasting syndrome was a very nabinoids in pain management. In: Weiner
Coulson AH. Heavy habitual marijuana
frequent complication of HIV infection 1 infection. A randomized, placebo-con- RS, editor. Pain management: A practical
trolled clinical trial. Ann Intern Med smoking does not cause an accelerated de-
prior to the advent of protease-inhibitor guide for clinicians. 6th ed. Boca Raton, FL:
cline in FEV1 with age. Am J Respir Crit
drugs (1), and has been associated with 2003;139:258-266. CRC Press; 2002. p. 357-375. http://
major weight loss and cachexia, serving
to further debilitate its victims, already Arthritis 2. Marcandier M. Treatise on hemp.
weakened by immune system failure and Arthritis refers to a large group of dis- London: T. Becket and P.A. de Hondt; 1764.
opportunistic infections. Cannabis has orders that affect joints and soft tissues 3. Malfait AM, Gallily R, Sumariwalla PF,
been a frequently employed alternative to produce chronic pain. The two most Malik AS, Andreakos E, Mechoulam R, et al.
medicine for the condition, particularly common forms are osteoarthritis (OA), The nonpsychoactive cannabis constituent
in the USA (2), because of its reported a disease of aging and wear and tear) and cannabidiol is an oral anti-arthritic therapeu-
benefits on appetite and amelioration of rheumatoid arthritis (RA), a common tic in murine collagen-induced arthritis. Proc
other AIDS symptoms. In the rest of the autoimmune disorder producing joint Natl Acad Sci U S A 2000;97(17):9561-6.
world, where such medications are sel- pain, swelling and deformity. Cannabis
dom affordable, AIDS wasting remains may represent a new treatment option in Asthma
a common problem to the extent that it both categories.
The use of cannabis in asthma dates Care Med 1997;155(1):141-8.
is known in Africa as ‘slim disease’ (3). Cannabis has been employed to treat
to the traditional medicine of India (1), 9. Gieringer D. Why marijuana smoke
In a randomized trial (4) in AIDS pa- musculoskeletal pain for at least 4000
but was also rediscovered in Western harm reduction? Bulletin of the
tients, THC significantly improved ap- years, dating to the Ancient Assyrians
medicine in the 19th century (2, 3). Multidisciplinary Association for Psyche-
petite and nausea in comparison with (1). Marcandier’s 1758 work, Traité du
Although it may seem counter-intui- delic Studies 1996;6(64-66).
placebo. There were also trends towards Chanvre (2) is of particular interest be- 10. Gieringer DH. Cannabis “vaporiza-
tive, cannabis cigarettes such as those
improved mood and weight gain. Un- cause European cannabis of that time tion”: A promising strategy for smoke harm
marketed by Grimault & Cie to treat
wanted effects were generally mild or was fibre hemp that would be devoid of reduction. Journal of Cannabis Therapeutics
asthma were popularly utilized for their
moderate in intensity. The possible ben- THC, but rich in cannabidiol (CBD). 2001;1(3-4):(in press).
bronchodilatory effects. Studies in the
efit of cannabis in AIDS made it one of 11. Gieringer D, St. Laurent J, Goodrich
1970s confirmed this benefit of cannabis S. Cannabis vaporizer combines efficient de-
the lead indications for such treatment The role of CBD as an anti- (4), and in one study (5), inhaled THC livery of THC with effective suppression Of
in the judgment of the American Insti-
tute of Medicine in their study (5).
inflammatory and immunomo- produced an increase in FEV1 (forced pyrolytic compounds. Journal of Cannabis
dulatory agent has been of expiratory volume in 1 second) after one Therapeutics 2004;4(1):In Press.
A safety study was carried out in HIV
hour that was equal to that of salbutamol. 12. Whittle BA, Guy GW, Robson P.
positive patients to assess whether oral great interest. It has now been demonstrated that Prospects for new cannabis-based prescrip-
THC or smoked cannabis would produce tion medicines. Journal of Cannabis Thera-
endocannabinoids regulate broncho-di-
immunological damage in patients on Very recently, the role of CBD as an peutics 2001;1(3-4):183-205.
lation and constriction (reviewed (6)).
protease-inhibitor medication (6). No anti-inflammatory and immunomo- 13. Whittle BA, Guy GW. Development
Problems remain with the concept,
problems were noted with HIV viral dulatory agent potentially useful in treat- of cannabis-based medicines; risk, benefit
however. Almost no modern authorities and serendipity. In: Whittle BA, Guy GW,
loads or CD4 cell counts. The study was ing autoimmune conditions has been of feel that asthmatics should smoke can- Robson P, editors. Medicinal uses of cannabis
subsequently published in expanded great interest. Malfait et al. (3) explored nabis for asthma (7), although it seems and cannabinoids. London: Pharmaceutical
form (7), and some weight gain was also
that even chronic usage may not lead to Press; 2003.
observed in THC and cannabis-treated
emphysematous degeneration (8). Use of 14. Whittle BA, Guy GW, Robson P.
subjects as compared to controls. Cannabis and cannabinoids as medicines.
THC inhalation in isolation, however,
It is likely that cannabis-based medi- London: Pharmaceutical Press; 2003.
has been proved to induce cough and
cine extracts will have some consider- 15. McPartland JM, Russo EB. Cannabis
lung irritation even without concomitant
able contribution to offer in future clini- and cannabis extracts: Greater than the sum
cal trials in HIV/AIDS. of their parts? Journal of Cannabis Therapeu-
Modern research has turned to alter- tics 2001;1(3-4):103-132.
References native delivery systems. One, that of can-
1. Bayer R. Medicinal uses of marijuana nabis vapourisation, may be applicable McPartland-Russo-JCANT-1-3-4-2001.pdf
[letter; comment]. Ann Intern Med (9-11), but to date, potential carcinogens 16. Falk AA, Hagberg MT, Lof AE,
1997;127(12):1134; discussion 1135. in tobacco smoke have not been totally Wigaeus-Hjelm EM, Wang ZP. Uptake, dis-
2. Sidney S. Marijuana use in HIV-posi- eliminated. The development of whole tribution and elimination of alpha-pinene in
tive and AIDS patients: Results of a an anony- cannabis extract inhalers, as currently man after exposure by inhalation. Scand J
mous mail survey. Journal of Cannabis being researched by GW Pharmaceuti- Work Environ Health 1990;16(5):372-8.
Therapeutics 2001;1(3-4):35-43r. cals (12-14) may offer advantages. Cer-
3. Russo EB. Cannabis therapeutics in
tainly, there is rationale behind inclusion Crohn’s Disease/
HIV/AIDS. Binghamton, NY: Haworth its effect in a mouse model of rheuma-
Press; 2001. of cannabis terpenoids, that have addi- InflammatoryBowel Disease
toid arthritis, and discovered that it ar-
4. Beal JE, Olson R, Laubenstein L, Mo- tional anti-inflammatory properties in Crohn’s disease and ulcerative coli-
rested progression of the disease and
rales JO, Bellman P, Yangco B, Lefkowitz their own right (15), especially pinene, tis are chronic, inflammatory conditions
protected joints against severe damage.
L, Plasse T, Shepard KV (1995). Dronabinol of the gastrointestinal tract of autoim-
CBD also blocked the release of tissue that also demonstrates a bronchodilatory
as a treatment for anorexia associated with mune origin. While ulcerative colitis
necrosis factor-alpha (TNF-a), a key tar- benefit (16). Further research is clearly
weight loss in patients with AIDS. Journal preferentially affects the colon and lower
of Pain & Symptom Management, 10, 89-97 get in modern approaches to RA treat- required.
small intestine, Crohn’s disease may af-
5. Joy JE, Watson SJ, Benson JA, Jr. ment. These effects alongside anti-in- References
1. Nadkarni KM. Indian materia medica. fect any portion of the GI tract. Both are
Marijuana and medicine: Assessing the sci- flammatory and analgesic benefits of
3rd ed. Bombay: Popular Prakashan; 1976. associated with tissue ulceration, bleed-
ence base. Washington, DC: Institute of CBD and THC may represent a novel
Medicine; 1999. 2. McMeens RR. Report of the Ohio State ing, cramping, diarrhoea, weight loss,
approach to this difficult clinical prob-
6. Bredt BM, Higuera-Alhino D, Shade Medical Committee on Cannabis indica . and the possibility of bowel obstruction
SB, Hebert SJ, McCune JM, Abrams DI. White Sulphur Springs, OH: Ohio State with a resulting need for surgery. (1)
Clinical studies of GW’s cannabis Medical Society; 1860 June12-14, 1860.
Short-term effects of cannabinoids on im- A recent epidemiological study (2)
based medicine extracts containing THC 3. Mattison JB. Cannabis indica as an
mune phenotype and function in HIV-1-in- has examined the burden of gastrointes-
fected patients. J Clin Pharmacol 2002;42(11
and CBD are currently in Phase II trials anodyne and hypnotic. St. Louis Medical and tinal diseases in UK patients and found
Suppl):82S-89S. in RA patients. Surgical Journal 1891;61:265-271.
that both diseases are becoming more
4. Tashkin DP, Shapiro BJ, Lee YE,
common. Prevalence of ulcerative coli-
continued on next page
—12— O’Shaughnessy’s • Spring 2004

Which Conditions Are Treatable With Cannabis? from page 1

tis by age 30 for people born in 1970 is It is noteworthy that endocan-

30/10,000. The prevalence of Crohn’s nabinoid levels are elevated in the brains T, Peek L, Green ML, et al. Delta 9-Tetrahy-
disease by age 30 was 38/10,000. Both drocannabinol as an effective antidepressant
of schizophrenics (9), although the prac-
Crohn’s and ulcerative colitis are asso- and appetite- stimulating agent in advanced
tical significance of this finding is not cancer patients. In: In: Braude MC, Szara S,
ciated with considerable psychiatric co- yet clear. ed. Pharmacology of marihuana. Vol 2. New
morbidity including depression, anxiety,
York, Raven Press,; 1976. p. 763-776.
somatisation, and decreased quality of
life measures (3).
The cannabis component 13. Russo EB, Mathre ML, Byrne A,
Velin R, Bach PJ, Sanchez-Ramos J, et al.
The long historical usage of cannabis cannabidiol may possess anti- Chronic cannabis use in the Compassionate
for gastrointestinal complaints has been psychotic activity Investigational New Drug Program: An ex-
reviewed (4). Numerous studies in the amination of benefits and adverse effects of
1970s indicated that THC slowed intes- The cannabis component cannabidiol legal clinical cannabis. Journal of Cannabis
tinal passage of a charcoal meal in ro- Therapeutics 2002;2(1):3-57.
may possess anti-psychotic activity (10),
dents. Cannabidiol (CBD) had little ef- 14. Zuardi AW, Cosme RA, Graeff FG,
and a single case report was consistent Guimaraes FS. Effects of ipsapirone and can-
fect of its own, but synergized the ef- with this (11). nabidiol on human experimental anxiety.
fects of THC (5). The most topical re- 4. Russo EB. Role of cannabis and can- Benefits were noted in depression Journal of Psychopharmacology 1993;
view of cannabinoid effects on the gas- nabinoids in pain management. In: Weiner measures in cancer patients treated with 7(1):82-88.
trointestinal tract is that of Pertwee (6). RS, editor. Pain management: A practical THC (12), and this has been supported 15. Fabre LF, McLendon D (1981). The
To summarise the major points: guide for clinicians. 6th ed. Boca Raton, FL: by anecdotal reports (13). Both canna- efficacy and safety of nabilone (a synthetic
1) The enteric nervous systems of CRC Press; 2002. p. 357-375. http:// bidiol and nabilone (THC analogue) cannabinoid) in the treatment of anxiety. J
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have demonstrated apparent benefit in
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clinical and experimental anxiety (10,
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2) Observed effects include delayed mice. J Pharm Pharmacol 1974;26(2):136-7. nabis may alleviate symptoms of bipo- Grinspoon L, Bakalar JB. The use of can-
gastric emptying, some decrease in pep- 6. Pertwee RG. Cannabinoids and the lar disease (17). nabis as a mood stabilizer in bipolar disor-
tic acid production, and slowed enteric gastrointestinal tract. Gut 2001;48(6):859-67. der: anecdotal evidence and the need for clini-
motility, inhibition of stimulated acetyl- 7. Holdcroft A, Smith M, Jacklin A, cal research. J Psychoactive Drugs
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tractions of smooth muscle, whether cir- Mediterranean fever. Anaesthesia Bisogno T, Rammes G, Cascio MG, et al. The
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brain level as well as in the GI tract ganglion. Journal of Neurophysiology
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antagonists (e.g., SR141716A). 9. Wright K, Rooney N, Tate J, Feeney Degenerative Diseases
Holdcroft et al. were able to demon- M, Robertson D, Welham M, et al. Functional Neuroprotection represents a goal in
strate an analgesic (pain reducing) ben- cannabinoid receptor expression in human pharmacotherapy to reduce or eliminate
efit (p<0.001) of THC 50 mg per day in colonic epithelium. In: 2003 Symposium on cell death after traumatic or hypoxic in-
5 split doses in a patient with relapsing the Cannabinoids; 2003; Cornwall, ON, The recent discovery that endocan- sults to the brain such as cerebrovascu-
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blind placebo-controlled trial (7). Nor- or as a result of degenerative diseases,
10. Malfait AM, Gallily R, Sumariwalla the use of phytocannabinoids in treat-
mally, this form of pain is extremely dif- PF, Malik AS, Andreakos E, Mechoulam R, such as Alzheimer’s, Huntington’s,
ficult to control with narcotics or other ment of post-traumatic stress disorder Parkinson’s, amyotrophic lateral sclero-
et al. The nonpsychoactive cannabis constitu-
analgesics. Additionally, anandamide ent cannabidiol is an oral anti-arthritic thera- (PTSD). sis, multiple sclerosis, severe seizure dis-
and other cannabinoid agonists inhibit peutic in murine collagen-induced arthritis. orders (epilepsy), or other conditions
rat serotonin type 3 (5-HT3) receptors Proc Natl Acad Sci U S A 2000;97(17):9561-6. including glaucoma and diabetes melli-
1. Russo EB. Handbook of psychotropic
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sponses. investigations support the prospect of
Depression/Mental Illness for psychiatric conditions. Binghamton, NY:
The most compelling new data re- Haworth Press; 2001. cannabis-based medicines having impor-
The use of cannabis by people with
cently has been that of Karen Wright (9). 2. Grinspoon L, Bakalar JB. Marihuana, tant applications in such areas.
mental illness has historically been as-
Her group compared immunohistologi- the forbidden medicine. Rev. and exp. ed. The first reference describing
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harms (1, 2). In its recent review, the 3. Joy JE, Watson SJ, Benson JA, Jr.
mal colonic tissue samples to those from be the Shen Nong Ben Cao Jing, a tradi-
Institute of Medicine (3) observed (p. Marijuana and medicine: Assessing the sci-
inflammatory bowel disease patients. In tional herbal written down in the 1st or
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normals, CB1 was expressed in the co- 2nd centuries, but based on the oral tra-
a family history of schizophrenia are Medicine; 1999.
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ages of the lamina propria. Striking im- scripts. Lancet, ii, 1483 -86 one fat, strong, and never senile.’
that marijuana alone produces a psycho-
munofluorescence was demonstrable in 5. Johns A. Psychiatric effects of can-
sis that persists after the period of intoxi- nabis. Br J Psychiatry 2001;178:116-22.
the disease state.
cation.’ Queen Victoria’s personal
Cannabis extracts may be well suited 6. Buhler B, Hambrecht M, Loffler W,
to treatment of inflammatory diseases
In modern times, the suggestion that an der Heiden W, Hafner H. Precipitation and physician wrote of his
recreational cannabis use may be a risk determination of the onset and course of experience with Cannabis
due to their multiple mechanisms of ac-
factor for schizophrenia was first raised schizophrenia by substance abuse—a retro-
tion. THC seemingly alleviates pain,
by Andreasson and collegeagues (4). spective and prospective study of 232 popu- indica in dementia
spasm and diarrhoea, while the CBD lation-based first illness episodes. Schizophr
Many of the other studies exploring this
component presents the likelihood of Res 2002;54(3):243-51. Similar claims were advanced by Sir
apparent association consist of retrospec-
immunomodulatory benefits. One re- 7. Degenhardt L, Hall W. Cannabis and John Russell Reynolds, Queen Victoria’s
tive analyses often relying on unreliable
cently demonstrated CBD effect is its psychosis. Curr Psychiatry Rep 2002; personal physician, who wrote of his ex-
measures such as self-report, and are 4(3):191-6.
ability to inhibit TNF-a (tissue necrosis perience with Cannabis indica in demen-
unable to distinguish association from 8. Bersani G, Orlandi V, Kotzalidis GD,
factor-alpha)(10), a proven mechanism tia in 1890 (2). It not only calmed his
causation. (5)(6)(7)(8). Pancheri P. Cannabis and schizophrenia: im-
of other agents employed to treat inflam- patient of his nocturnal agitation, but
A recent retrospective and prospec- pact on onset, course, psychopathology and
matory bowel seemingly arrested progression of the
tive examination of 232 newly diagnosed outcomes. Eur Arch Psychiatry Clin Neurosci
schizophrenic patients demonstrated no 2002;252(2):86-92. disease for years without increase in
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1. Knutson D, Greenberg G, Cronau H. temporal correlation between substance
Emrich HM, Piomelli D. Elevated endog-
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disorder and severity of inflammatory bowel
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O’Shaughnessy’s • Spring 2004 —13—

Conditions Treatable by Cannabis from previous page

degenerative disorders, presenting the potential of cannabinoids in neurological dis- 2. O’Shaughnessy WB. On the prepara- be therapeutically useful.” Similarly, the
potential for therapeutic intervention (re- orders. In: Mechoulam R, editor. Cannab- tions of the Indian hemp, or gunjah (Cannabis American Institute of Medicine stated
viewed in (4)). inoids as therapeutic agents. Boca Raton, FL: indica) ; Their effects on the animal system (12), “Given the present state of knowl-
CRC Press; 1986. p. 21-49. in health, and their utility in the treatment of
edge, clinical studies of cannabinods in
10. Carter GT, Rosen BS. Marijuana in tetanus and other convulsive diseases. Trans-
In Hunting-ton’s disease, a the management of amyotrophic lateral scle- actions of the Medical and Physical Society epilepsy are not indicated.”
striking loss of cannabinoid rosis. Am J Hosp Palliat Care of Bengal 1838-1840:71-102, 421-461. Seizure threshold appears to
2001;18(4):264-70. 3. Dixon WE. The pharmacology of Can- be mediated by cannabinoid
receptor expression occurring nabis indica. British Medical Journal
in step with degenerative sta- 1899;2:1354-1357. mechanisms
Eating Disorders 4. Foltin RW, Fischman MW, Byrne MF.
tus has been observed The appetite stimulating power of Effects of smoked marijuana on food intake Some subsequent laboratory work
cannabis and THC are among its most and body weight of humans living in a resi- has changed the landscape. Seizure
THC as Marinol(r) has been shown well known effects. This phenomenon dential laboratory. Appetite 1988;11(1):1-14. threshold appears to be mediated by can-
to reduce disturbed behaviour in was first documented in Western litera- 5. Volicer L, Stelly M, Morris J,
nabinoid mechanisms (13). In rats (14),
Alzheimer’s disease (5), but a possible ture by the physician and explorer, McLaughlin J, Volicer BJ. Effects of
dronabinol on anorexia and disturbed behav- THC produced a 100% reduction in sei-
impact upon disease Garcia da Orta, in ior in patients with Alzheimer’s disease. Int zures, whereas phenobarbital and diphe-
progression has not India in the 16th J Geriatr Psychiatry 1997;12(9):913-9. nylhydantoin did not. The animals dem-
yet been evaluated. century (1), as he 6. Carter GT, Rosen BS. Marijuana in the onstrated both acute increases in
In Huntington’s dis- observed (p. 56), management of amyotrophic lateral sclerosis. endocannabinoid production and a long-
ease, a striking loss “Those of my ser- Am J Hosp Palliat Care 2001;18(4):264-70. term up-regulation of CB1 production as
of cannabinoid re- vants who took it, 7. Williams CM, Kirkham TC. Ananda- apparent compensatory effects counter-
ceptor expression mide induces overeating: mediation by cen-
unknown to me, acting glutamate excitotoxicity. The an-
occurring in step tral cannabinoid (CB1) receptors. Psychop-
said that it made harmacology (Berl) 1999;143(3):315-7.
ticonvulsant effect was present at sub-
with degenerative them so as not to sedating levels.
8. Ravinet Trillou C, Arnone M, Delgorge
status has been ob- feel work, to be C, Gonalons N, Keane P, Maffrand JP, et al. While available clinical evidence
served (6), and may very happy, and to Anti-obesity effect of SR141716, a CB1 re- provides no compelling support for THC
represent a target in have a craving for ceptor antagonist, in diet-induced obese mice. having proconvulsant properties in hu-
therapy. In Parkin- food.” Am J Physiol Regul Integr Comp Physiol mans, clinical researchers must remain
son’s disease, the Similar ben- 2003;284(2):R345-53. cautious, as animal data do raise that
synthetic cannab- efits of Indian 9. Le Fur G, Arnone M, Rinaldi-Carmona possibility. Further testing with CBD-
inoid nabilone re- M, Barth F, Heshmati H. SR141716, a selec-
hemp were noted rich extracts seem warranted.
tive antagonist of CB1 receptors and obesity.
duced dyskinetic movements from L- by O’Shaughnessy in India, as extracts In: Symposium on the Cannabinoids; 2001
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fatal, and existing agents offer little con- ing sections), leading to the approval in lation and 200,000 patients take anticon- tions of the Indian hemp, or gunjah (Cannabis
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1913. continued on next page
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Conditions Treatable by Cannabis from previous page

Glaucoma 5. McPartland J, Russo E (2001). Can- historical and scientific review. Pain
Glaucoma is a common condition in nabis and cannabis extracts: greater than the 1998;76(1-2):3-8.
which there is a build-up of intraocular sum of their parts? Journal of Cannabis 5. Russo EB. Hemp for headache: An in-
pressure (IOP) in the eye. This may cause Therapeutics 1, 103-32 depth historical and scientific review of can-
eye and head pain, haloes in the vision, Migraine nabis in migraine treatment. Journal of Can-
constriction of the visual field, or merely nabis Therapeutics 2001;1(2):21-92. http://
Migraine is a severe headache disor-
a progressive loss of vision without other
der producing pain, hypersensitivity to 6. Snyder SH. Uses of marijuana. New
symptoms. It is the major cause of irre-
light and noise (photophobia and phono- York: Oxford University Press; 1971.
versible blindness in Western societies.
phobia), and occasional visual loss or 7. Russo EB. Clinical endocannabinoid
A variety of oral medicines or eye drops deficiency (CECD): Can this concept explain
distortion. While it most commonly oc-
are customarily employed, but are not therapeutic benefits of cannabis in migraine,
curs in discrete attacks, frequently
uniformly effective (1). fibromyalgia, irritable bowel syndrome and
perimenstrual in young women, it does
The ability of cannabis and THC to other treatment-resistant conditions?
affect both sexes at any age, and may
lower intra-ocular pressure in glaucoma Neuroendocrinol Lett 2004;(in press).
develop into chronic or daily forms (1). 8. Bisogno T, Hanus L, De Petrocellis L,
was serendipitously discovered in the
Some 8-14% of teens and young adults Tchilibon S, Ponde DE, Brandi I, et al. Mo-
late 1970’s by a variety of patients and
may be affected (2) and the economic lecular targets for cannabidiol and its syn-
researchers (2, 3). Several patients in the clinical cannabis. Journal of Cannabis Thera- losses attributable to migraine in the thetic analogues: effect on vanilloid VR1 re-
U.S. Compassionate Use Investigational peutics 2002;2(1):3-57. USA in 1992 were as much as $17 bil- ceptors and on the cellular uptake and enzy-
New Drug Program maintained their vi- 5. Joy JE, Watson SJ, Benson JA, Jr. matic hydrolysis of anandamide. Br J
lion (3).
sion while employing large amounts of Marijuana and medicine: Assessing the sci- Pharmacol 2001;134(4):845-52.
daily cannabis in situations where stan- ence base. Washington, DC: Institute of
dard drug therapy failed (4). Medicine; 1999. Cannabis was a mainstream
6. Pate DW. Anandamide structure-activ- medication for migraine Multiple Sclerosis
ity relationships and mechanisms of action Multiple sclerosis (MS) is a disease
on intraocular pressure in the normotensive between 1842 and 1942 in affecting the Central Nervous System
rabbit model. Kuopio, Finland: University of Europe and America (CNS). MS exacerbations appear to be
Kuopio; 1999.
caused by abnormal immune activity that
7. Hampson AJ, Grimaldi M, Axelrod J,
Wink D. Cannabidiol and (-)Delta9-tetrahy-
Drug therapy consists of treatment causes inflammation and the destruction
drocannabinol are neuroprotective antioxi- for individual attacks, and a preventive of myelin (the protective covering of
dants. Proc Natl Acad Sci U S A approach for frequent or daily afflictions. nerve fibres) in the brain or spinal cord.
1998;95(14):8268-73. Treatment failure rates with the many MS usually commences in early adult
available agents still approach 30%, and life, most frequently presenting at onset
Intractable Breathlessness there are no specific cures, although vari- as a relapsing and remitting disorder,
There are a number of lung diseases ous 19th century authorities claimed suc- where symptoms come and go, and is
that are capable of producing shortness cess with Indian hemp (cannabis) prepa- more common in females. Current treat-
GLAUCOMA PATIENT Elvy Musika rations (4, 5). Cannabis was a main- ment of MS is primarily symptomatic,
with cannister of 300 machine-rolled of breath that is often extremely distress-
ing to the patient. Many of these condi- stream medication for migraine between focussing on such problems as spastic-
marijuana cigarets that the U.S.
government provides monthly. tions are irreversible, so it becomes nec- 1842 and 1942 in Europe and America ity, pain, fatigue, bladder problems and
essary to target the symptom itself. (4, 5). Its use for this purpose was en- depression.
The 1999 US Institute of Medicine dorsed even in 1971 by the neuroscien- In the last 15 years, immunotherapy
The sensation of breathlessness is a
report noted the ability of cannabis to tist, Solomon Snyder (6). approaches have become available, but
complicated phenomenon that seems to
lower IOP, but did not endorse its usage their efficacy in producing long-term
depend upon central processing through
due to its relatively short effects and con- benefits has been questioned (1). MS is
respiratory and non-respiratory mecha-
cerns about the need to smoke the drug nisms. Ideally, a treatment would relieve one of the most frequent reasons that
on a chronic basis (5). patients employ cannabis. Excellent re-
the unpleasant sensation without further
compromising respiratory function. views of THC, cannabis and MS are
Glaucoma may represent a Opioids and benzodiazepines produce available (2, 3).
Interim results of a small study (11
progressive vascular retin- some relief but may have the dangerous
side effect of depressing respiration. patients) of cannabis based medicine
opathy that requires a neuro- extracts (CBMEs) in bladder dysfunc-
Patients have reported anecdotally
protectant to preserve vision that cannabis can relieve breathlessness tion were presented at a meeting of the
by relieving anxiety and promoting re- International Association for Cannabis
A very interesting development was laxation. CB1 receptors are virtually as Medicine (IACM)(4). Improvements
the discovery that the endocannabinoid absent from the part of the brain-stem were shown, compared to placebo, in
anandamide acts as a regulator of in- which drives respiration (1), so it is to Cannabis and its components inter- nocturia, daytime frequency and incon-
traocular pressure (6). However, it is be hoped that symptom relief may be act in a potentially beneficial way with tinence episodes.
apparent that there is more to glaucoma achieved without negative effects upon a number of systems of relevance to this
treatment than merely controlling IOP, breathing. THC has been shown to have disease: effects on serotonergic, dopam- Data supporting the benefit
as even effective management may fail anxiety-reducing and sedating effects (2, inergic, opioid, substance P, calcitonin of cannabinoid treatment of
to avert visual loss over time. An emerg- 3), as has CBD (4). Additionally, CBD gene-related peptide and NMDA recep-
ing concept is that glaucoma represents tors by cannabis components have been
spasticity in MS is now as
is thought to have useful modulating ef-
a progressive vascular retinopathy that fects on some of the undesirable effects extensively supported (5). Although no strong as for any available
requires a neuroprotectant to preserve of THC (5). clinical trials of cannabis treatment in pharmaceutical agent
vision (1). Some of the resulting optic Exploratory research of THC/CBD migraine have been performed, it has
nerve damage accrues due to NMDA combinations in refractory breathless- recently been suggested that migraine
hyperexcitability, an effect that THC and A recent study in the UK of more than
ness is indicated, incorporating careful may represent a clinical endocan-
CBD may counter as neuroprotective an- 600 MS patients has demonstrated im-
monitoring of respiratory function. nabinoid deficiency (CECD) disorder
tioxidants (7). Thus, glaucoma is an area provement with twice-daily oral THC
(7), and that the ability of cannabidiol
where cannabis and cannabinoids may and a THC/CBD cannabis extract on
References (CBD) to regulate anandamide levels (8)
offer particular advantages over avail- walking times, and subjective measures
1. Herkenham M, Lynn AB, Little MD, may contribute a key to its long-term
able single ingredient ocular anti-hyper- Johnson MR, Melvin LS, de Costa BR, Rice of pain and spasticity, although an ob-
control. It is hoped that clinical trials may
tensive agents. Delivery methods remain KC. Cannabinoid receptor localization in jective measure of spasticity (Ashworth
be undertaken in the future.
an exacting challenge. brain. PNAS 1990;87:1932-1936. score) did not show a significant effect
2. Fabre LF, McLendon D (1981). The References (5). The authors concluded that their
References efficacy and safety of nabilone ( a synthetic 1. Russo EB. Migraine: Indications for findings provide evidence that cannab-
1. Jarvinen T, Pate D, Laine K. Cannab- cannabinoid) in the treatment of anxiety. cannabis and THC. In: Grotenhermen F, inoids could be clinically useful in the
inoids in the treatment of glaucoma. Journal of Clinical Pharmacology, 21, 377- Russo EB, editors. Cannabis and cannab- treatment of symptoms related to MS.
Pharmacol Ther 2002;95(2):203. 82S inoids. Binghampton, NY: Haworth Press; Although, the effects were modest, an
2. Merritt JC, Crawford WJ, Alexander 3. Nicholson AN, Robson PJ, Stone BM, 2001.
Turner C (2003). Effect of delta-9- tetrahy-
accompanying editorial pointed out that
PC, Anduze AL, Gelbart SS. Effect of mari- 2. Linet MS, Stewart WF. Migraine head- current data supporting the benefit of
huana on intraocular and blood pressure in drocannabinol and cannabidiol on nocturnal ache: epidemiologic perspectives. Epidemiol
sleep and early morning behaviour in youn cannabinoid treatment of spasticity in
glaucoma. Ophthalmology 1980;87(3):222-8. Rev 1984;6:107-39.
3. Randall RC, O’Leary AM. Marijuana adults. Journal of Sleep Research In Press. 3. Stewart WF, Lipton RB, Celentano MS is now as strong as for any available
Rx: The patients’ fight for medicinal pot. New 4. Zuardi AW, Guimaraes FS. Canna- DD, Reed ML. Prevalence of migraine head- pharmaceutical agent (6).
York: Thunder’s Mouth Press; 1998. bidiol as an anxiolytic and antipsychotic. In: ache in the United States. Relation to age, The results of a Phase II study of
4. Russo EB, Mathre ML, Byrne A, Velin Mathre ML, editor. Cannabis in medical prac- income, race, and other sociodemographic CBME have also been published (7),
R, Bach PJ, Sanchez-Ramos J, et al. Chronic tice: a legal, historical and pharmacological factors. Journal of the American Medical performed in 24 subjects (18 with treat-
cannabis use in the Compassionate Investi- overview of the therapeutic use of marijuana. Association 1992;267(1):64-9. ment-resistant MS) and employing a
gational New Drug Program: An examina- Jefferson, NC: McFarland; 1997. p. 133-141. 4. Russo E. Cannabis for migraine treat-
tion of benefits and adverse effects of legal ment: The once and future prescription? An continued on next page
O’Shaughnessy’s • Spring 2004 —15—

Conditions Treatable By Cannabis from previous page

consecutive series management have been thoroughly re-

allaying vomiting in 480 dose applica- to modern folk use in Jamaica (11, 12).
of double-blind, viewed (5, 6). Key areas of cannabis
tions without significant adverse effects. Modern pharmacological studies
randomised, pla- therapeutics revolve around its roles in
A large body of knowledge has now have demonstrated the basis for these
cebo-controlled neuropathic pain (7, 8), as an anti-inflam-
been amassed in this context as a result claims (2, 13, 14). Drugs are rightly es-
single patient cross- matory agent, and usage in musculosk-
of state-sponsored studies in the USA in chewed when possible in pregnancy, but
over trials. Twenty eletal pain.
cancer chemotherapy (6). Pooling avail- cases arise frequently wherein such treat-
of the subjects com- able data in some 768 patients, oral THC ment is necessary, even to save the life
pleted the trial. Pain provided 76-88% relief of nausea and THC is the main contributor
relief was signifi- vomiting, while smoked cannabis figures of cannabis to control of pain,
cantly superior to supported 70-100% relief in the various
placebo and there via its actions on the central
surveys. However, there are no compara-
were subjective improvements in spasm tive trials with newer agents, such as the nervous system cannabinoid
frequency, bladder control, spasticity and selective 5HT3 antagonists (e.g. receptors
sleep. Of particular note was the finding ondansetron, granisetron).
that non-psychoactive cannabidiol The biochemical basis of this anti- One of the primary functions of the
(CBD) appears to have significant anal- emetic effect is still being explored, but endogenous cannabinoid system is
gesic and anti-spasticity effects. Adverse it is known that cannabinoids experimen- modulation of pain control, in parallel
effects in the trial were predictable and tally inhibit the activity of 5-HT3 recep- of mother and child. Close scrutiny of with the endogenous opioid and
well tolerated. tors (7), the primary mode of action for the literature supports the relative safety vanilloid systems. THC is the main con-
Subsequent Phase III GW Pharma- the standard drugs ondansetron and of cannabis in such applications, though tributor of cannabis to control of pain,
ceuticals trials have shown positive re- granistetron. the ethical and methodological chal- via its actions on CB1, the central ner-
sults including statistically significant Recent data also supports the anti- lenges to conducting modern clinic tri- vous system cannabinoid receptors that
reductions in neuropathic pain, spastic- emetic properties of cannabidiol in ex- als seem formidable indeed. occur in key pain-modulating areas of
ity and sleep disturbance. These results, perimental animals (8-10). The combi- the spinal cord, and brainstem.
summarized in a Nov. 22 GW press re- nation of CBD and THC in cannabis References Although a review of the analgesic
lease, are currently awaiting publication. extracts may well have additive or syn- 1. Thompson RC. A dictionary of effects of cannabinoids concluded that
ergistic effects that deserve investigation Assyrian botany. London: British Academy; they have little demonstrated benefit to
References in clinical trials. 1949. date (9), the controlled clinical studies
1. Filippini G, Munari L, Incorvaia B, 2. Russo E. Cannabis treatments in ob-
available for analysis were few and most
Ebers GC, Polman C, D’Amico R, et al. stetrics and gynecology: A historical review.
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1. British Medical Association. Therapeu- the subject of a critical response (10, 11).
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Academic Publishers; 1997.
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2. Joy JE, Watson SJ, Benson JA, Jr.
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ficient new cannabinoid antiemetic in pedi-
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man fertility. Journal of Cannabis Thera-
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Cannabis has been employed quite Pain tee for Treatment and Research in Mul-
the American Institute of Medicine (2).
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This indication for cannabis has be- The analgesic or pain reducing prop-
ric and gynaecological indications, dat- ductions favouring CBME were found
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tients, was the subject of a popular book at least 4000 years, from the time of the
topic has been extensively reviewed re- sleep disturbance, and patients treated
(3), and has received endorsement from Ancient Assyrians (1). The modern era
cently (2), and has included use as an with CBME were more likely to feel
some American oncologists in a survey of scientific study of cannabinoids and
aid to childbirth from Ancient Egypt (3) “much” or “very much improved” than
study (4). It was also the original indi- pain began in 1974 with the studies of
to 19th century England (4) and 20th those receiving placebo.
cation for Marinol(r) (synthetic THC) Noyes et al. (2-4), in which it was noted
century America (5). Additionally, can-
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of cannabis and cannabinoids in pain
continued on next page
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