Marijuana as Medicine

Mary Albus
Overview
- Medical Marijuana in Pennsylvania
- Administration methods
- Research limitations
- Endocannabinoid System
- Risks to the general population
- Cannabis and appetite, weight gain, emesis
- Scientific Evidence
- Impact of cannabis on chronic medical conditions
- Role of the RD
Medical Marijuana in Pennsylvania
- In USA
- Legal in 29 US states + District of Columbia
- Open to people with qualifying conditions
- Dispensaries just opened in February 2018
- Enola, PA - Organic Remedies
- Others in Philadelphia and Pittsburgh
- State law allows oils, extracts, tinctures and concentrates.
- 30 day supply
- Not available in edible or smokable form
- Registration fee = $50
Common Conditions that qualify for Medical Marijuana:
Cancer MS Glaucoma PTSD HIV/AIDS Autism Pain

Epilepsy/Seizures Huntington’s Disease Terminal Illness Parkinson’s

Sickle Cell disease Neuropathy Nervous Tissue Damage ALS

Skeletal Muscular Spasticity IBD Muscle Spasms Arthritis Migraines

Alzheimer's Cirrhosis Mitochondrial disease Nausea Fibromyalgia

Hepatitis C Interstitial cystitis Lupus/Sjogren’s Myasthenia Gravis

Rheumatoid Arthritis Cachexia Anorexia

https://www.pa.gov/wp-content/uploads/2017/09/pennsylvania-medical-marijuana-postcard-1024x684.jpg
Administration Methods
- Vaporized/smoked
- Ingested orally
- Edibles
- Pill form
- Topical application
- Ointments
- Tinctures
Research Limitations
● Single molecule pharmaceuticals
○ Marinol (Schedule III)
○ Nabilone (Schedule II)
● Phytocannabinoid-dense botanicals
○ Cannabis – medicinal plant (Schedule I)
■ Not federally accepted for medical use
■ High potential for abuse
■ Lengthy application and approval time
■ Requires “research-grade” cannabis
■ Funding
■ Placebo Effect
What makes up Cannabis?
- Cannabinoids (100+) Main phytocannabinoids in
- Δ9 -tetrahydrocannabinol - THC cannabis that have a
- Cannabidiol – CBD medically beneficial effect on
- Cannabinol - CBN the body
- Terpenes/Terpenoids
- Flavonoids
- Sterols
- Thiols
- Phenols
- Lipids/waxes
- Fibrous material
Endocannabinoid System
- Main goal: Homeostasis
- Endocannabinoid receptors
- CB1: nervous system, connective tissues, gonads,
glands, organs
- CB2: immune system and associated structures
- Respond to:
- Endocannabinoids
● Anandamide
● 2-arachidonoylglycerol (2-AG)
- Phyotcannabinoids (THC/CBD)
- Synthetic cannabinoids
Anandamide and THC

Functions of Anandamide aka “the bliss molecule”:

- Spinal Cord: inhibits GLU & info transfer

between body and brain
- Results in decreased pain sensitivity
- Adipose tissue: Stimulates lipogenesis
- Results in increased adiposity
- Mood enhancer
- Joy, depression, anxiety, memory, appetite
Phytocannabinoids and the Endocannabinoid System
- THC - psychoactive
- Pain relief, appetite stimulation,
inflammation, relaxation,
spasticity, possible anti-tumor
effects
- CBD - not psychoactive
- Antioxidant, reduces anxiety,
relaxes mental state, sedative
- “The Entourage Effect”
Cannabis-like Pharmaceutical Drugs
- Synthetic cannabinoids
- FDA-approved ✅
- Most popular: Marinol (Dronabinol)
- AIDS and cancer-related anorexia
- Chemo-induced Nausea/vomiting
- Drawbacks
- Expensive
- Very high in “THC”, low in CBD
- Significant side effects
Risks to the General Population
Effects of short-term use
Impaired short-term memory
Impaired motor coordination
Confusion
Dry mouth
Altered judgment
Motor vehicle accidents (2x)
Paranoia and psychosis (high doses)
Effects of long-term use
Addiction (9% overall)
Altered brain development*
Cognitive impairment (with lower IQ)*
Diminished life satisfaction and
achievement*
Poor educational outcome
Symptoms of chronic bronchitis
Increased risk of chronic psychosis
disorders
*when used initially in early adolescence
Cannabis and Nausea/Vomiting

- Serotonin + 5-HT3 receptors = N/V

- Stimulated CB1 interacts with 5-HT3
- Inhibits serotonin binding
- Zofran is a 5-HT3 receptor antagonist
- May be a beneficial combination with
cannabinoids
- Studies on this are limited to
chemotherapy-related nausea/vomiting

https://www.myvmc.com/treatments/5-ht3-receptor-antagonists-serotonin-blockers/
Cannabis and Appetite Stimulation
- Endocannabinoid system regulates
appetite
- THC binds to CB1 receptors
- Reward aspect of eating
- Signals food craving within the brain
- Traditional antiemetics prevent
nausea/vomiting
- Do not increase appetite
- Phytocannabinoids and cannabis
medicines do both
Cannabis and Weight Gain
- Cause is distinguishable from appetite stimulation
- CB1 receptors in adipocytes
- Increase of lipoprotein lipase activity
- Increases lipogenesis
- Decreases beta-oxidation
- Beneficial in reducing HIV-related anorexia
Scientific Evidence
- Conclusive
- Chronic Pain
- Patient-reported spasticity in MS patients
- Chemotherapy-induced nausea/vomiting
- Moderate
- Short-term sleep outcomes: obstructive sleep apnea, fibromyalgia, chronic pain, MS
- Limited
- Increasing appetite and decreasing weight loss with HIV/AIDS
- Tourettes
- Anxiety symptoms
- PTSD
- Better outcomes after TBI or intracranial hemorrhage
- Depression
- Intraocular pressure associated with glaucoma
 Cannabis and Chronic Non-Cancer Pain
- Double-blind, placebo-controlled, crossover study
- N = 39 individuals with neuropathic pain
- Three, 6-hour experimental sessions
- All participants received each treatment
- Placebo
- Low dose cannabis (1.29% THC)
- Medium dose cannabis (3.53% THC)
- Vaporized
Visual Analog Scale - Pain Distress
- 8-12 puffs each visit

Primary outcome variable

Wilsey, Barth, et al. 2013. “Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain.”
Cannabis and Chronic Non-Cancer Pain

Wilsey, Barth et al. 2013

Study Results
Reduction in pain Placebo reduction in pain P-value
intensity (VAS) intensity

Low-dose 57% 30% 0.0069

Medium-dose 61% 30% 0.0023

P-value 0.7

- Cannabis has analgesic efficacy

- Psychoactive effects were minimal and well tolerated
- Vaporized cannabis may be an effective option for patients with neuropathic
pain
Cannabis and Crohn’s Disease
- Prospective, randomized, double-blind place-controlled trial
- Objectives:
- Remission of Crohn’s as defined by Crohn’s Disease Activity Index (CDAI)
- Reduction in CRP by at least 0.5mg
- Improvement in quality of life by the SF-36
- N = 21 males
- Control group = 11
- Placebo group = 10
- 8 week long study
- Evaluated 0,2, 8, and 10 weeks

Naftali, T., et al (2013).Cannabis Induces a Clinical Response in Patients with Crohn's Disease: a Prospective Placebo-Controlled Study.
 Study Results
- Primary objective was not met
- 5/11 in control group achieved remission
- 1/10 in placebo group achieved remission
- P-value = 0.43
- CDAI score
- Significant at 8 weeks
- P-value = 0.028
- Not significant at 10 weeks
Naftali, T., et al (2013)
- Cannabis group
○ Significant increase in quality of life
○ Significantly less pain
○ Higher satisfaction from treatment
Cannabis and Cancer
- All new cancer patients using medical marijuana
- From 2015-2017 at a clinic in Israel
- N = 2970
- Medical marijuana: Vaporized or smoked
- Telephone interviews
- Initial
- One-month follow up
- Six-month follow up
- Primary Outcome: Treatment success
- Moderate or significant improvement in the patient's condition

Bar-Lev, L, et al. 2018. “Prospective Analysis of Safety and Efficacy of Medical Cannabis in Large Unselected Population of Patients with Cancer.”
Physiological Effects headaches, dizziness, nausea, vomiting, stomach ache, heart palpitation,
drop in blood pressure, drop in blood sugar, sleepiness, weakness, chills,
itching, red/irritated eyes, dry mouth, cough, increased appetite, blurred
vision, slurred speech

Cognitive Side Effects restlessness, fear, psychoactive effect, hallucinations, confusion and
disorientation, decreased concentration, decreased memory

General effect of significant improvement, moderate improvement, slight improvement, no

cannabis on change, slight deterioration, moderate deterioration, significant
participant’s condition deterioration

Pain Level 11-point scale (0=no pain, 10=worst pain of my life)

Quality of life Likert Scale: very poor, poor, neither poor nor good, good, very good
At 6 months: Pain and Quality of Life

Bar-Lev, L, et al. 2018.

Good quality of life: Intake: 18.7% 6 months: 69.5% P-value <0.001

Study Results: Symptom Relief & Treatment Success

Total (2970) Symptom Gone Improvement No change

Sleep disorders 2329 (78.4%) 155 (16.7%) 655 (70.8%) 114 (12.3%)

Nausea/vomiting 1662 (56%) 251 (36.3%) 378 (54.7%) 62 (9%)

Restlessness 602 (20.3%) 36 (15.6%) 166 (71.9%) 29 (12.6%)

Anxiety and depression 1694 (57%) 62 (10.1%) 455 (74.1%) 97 (15.8%)

Headaches 686 (23.1%) 78 (30.2%) 132 (51.2%) 48 (18.6%)

Treatment Success:
50.8% significant improvement, 45.1% moderate improvement, 4% no improvement
Cannabis and Multiple Sclerosis
- Randomized, placebo controlled trial
- N = 30 people with MS spasticity
- 8 visits over a period of 2 weeks
- Measurements:
- Ashworth Scale for spasticity (primary outcome)
- Visual Analog Scale for pain Before and 45
- Paced Auditory Serial Addition Test - cognitive test minutes after
- Timed walk each treatment

3 days of cannabis 11 day “wash-out” 3 days of placebo

Study Results
Mean Spasticity Pain (points) Timed Walk Cognitive Function
Measures (points) (seconds) (points)

Placebo -0.21 -2.99 +0.03 +0.35

Cannabis -2.95 -8.27 +1.23 -8.32

p-value < 0.001 0.008 0.2 0.003

- Not so “blind”
- Cannabis effective in reducing patient-reported spasticity and pain
- Limited clinically-measured evidence, long term studies are needed
Role of the Dietitian
- Be familiar with evolving laws
- Review recent scientific literature
- Consider the type of patient
- Child?
- At high risk for substance abuse?
- Understand the nutritional implications of marijuana use
- Weight gain, appetite stimulation
- Overcome personal bias
- Consult and collaborate with medical team
- Cannabis is a therapeutic treatment option
Ethics Case Study
Patient: 34 year old male in need of a liver transplant due to primary sclerosing
cholangitis. Patient has 3 daughters. He and his wife own a small business in town.

Hx: No history of drug or alcohol use, 10% weight loss over past 2 months due to
lack of appetite and nausea, transplant is last option for treatment

Current status of transplant: Patient is ineligible for a transplant due to nutritional

status not meeting the requirements for a transplant. The transplant team told the
patient that when he gains the weight back, he will be able to receive the transplant.
Patient is desperately searching for a way to do this so he tells you he is going to
start using marijuana. After 1 month, his appetite is back and he has gained enough
weight to meet the nutritional status for a transplant. You know that he will not be
able to get a transplant if the transplant team finds out that he has used marijuana.
What would you do?
Conclusions
- Phytocannabinoids can be medically beneficial
- Synthetic cannabinoids have pros and cons
- Cannabis has risks
- Beneficial for appetite, weight gain, and nausea/vomiting
- Significant scientific evidence for some conditions
- More research is needed
- Medical Marijuana: therapeutic option for patients
References:
- Atakan, Zerrin. “Cannabis, a Complex Plant: Different Compounds and Different Effects on Individuals.” Therapeutic Advances in Psychopharmacology, SAGE
Publications, Dec. 2012, www.ncbi.nlm.nih.gov/pmc/articles/PMC3736954/.

- Bar-Lev, L, et al. “Prospective Analysis of Safety and Efficacy of Medical Cannabis in Large Unselected Population of Patients with Cancer.” European Journal of
Internal Medicine., U.S. National Library of Medicine, Mar. 2018, www.ncbi.nlm.nih.gov/pubmed/29482741.

- Borgelt, Laura, and Zachari Breeding. “Going Green: Use of Medical Cannabis in Medical Nutrition Therapy.” FNCE 2017. FNCE 2017, Oct. 2017,
Chicago, IL.

- Corey-Bloom J, Wolfson T, Gamst A, et al. Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo controlled trial. CMAJ 2012;184(10):1143–50

- Naftali, T., Schleider, L., Dotan I., Lansky P., Dotan I., Lanskey E., Benjaminov F., Konikoff F., (2013). Cannabis Induces a Clinical Response in Patients with Crohns
Disease: a Prospective Placebo-Controlled Study. PubMed. doi:10.3410/f.718008150.793485982

- National Institute on Drug Abuse. “NIDA's Role in Providing Marijuana for Research.” NIDA,
www.drugabuse.gov/drugs-abuse/marijuana/nidas-role-in-providing-marijuana-research.

- PACHER, PÁL, SÁNDOR BÁTKAI, and GEORGE KUNOS. “The Endocannabinoid System as an Emerging Target of Pharmacotherapy.” Pharmacological reviews
58.3 (2006): 389–462. PMC. Web.

- ProCon.org. (2018, March 16). Medical Marijuana ProCon.org. Retrieved from http://medicalmarijuana.procon.org

- Smith, Gregory L. Medical Cannabis: Basic Science & Clinical Applications: What Clinicians Need to Know and Why. OEM Press, 2016.

- US Department of Justice. DEA / Drug Scheduling, www.dea.gov/druginfo/ds.shtml.

- Wilsey, Barth, et al. “Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain.” Official Journal of the American Pain Society, U.S. National Library of
Medicine, Feb. 2013, www.ncbi.nlm.nih.gov/pmc/articles/PMC3566631/.
 Thank you!
Questions/Discussion