An overview of cannabinoids as medicine

1. Marijuana as Medicine
Arlen Meyers, MD, MBA

3. Topics
1. Basic pharmacology
2. Routes of administration
3. Clinical evidence
4. Adverse events
5. Practice prescribing issues
6. Use and abuse
http://jaoa.org/article.aspx?articleid=2671435

4. Endocannabinoid receptors
CB1 and CB 2

5. ECS ligands
Ligands are substances that attach to receptors
Substances that attach to or activate the ECS receptors are all cannabinoids
There are 3 sources of cannabinoids: 1) endocannabinoids made in the body, 2)144
different phytocannabinoids that come from marijuana plant, and 3) synthetic
cannabinoids

6. 3 species of Cannabis
Cannabis sativa, cannabis indica, cannabis ruderalis

7. Terpenes
Gives cannabis its aroma and part of its medicinal properties
Each cannabis variety has a unique mix of terpenes: the terpene profile that can vary
from plant to plant

8. Flavinoids
Nutrient rich pigments (flavus=yellow) found in plants, fruits and teas
Broad range of biological and pharmacological activities e.g. anti-inflammatory, anti-
allergy and anti-tumor
Cannabis contains 29 different flavinoids

9. FDA approved synthetic cannabinoids
Dronabinol
Nabiximols
Nabilone
Approved to treat anorexia or wasting caused by HIV and AIDS and nausea and
vomiting caused by chemotherapy for cancer treatment

10. Colorado’s Medical MJ Laws
https://www.safeaccessnow.org/colorados_medical_marijuana_laws
To recommend medical marijuana, a physician must: 1. Have an active MD or DO
license in good standing with the state of Colorado. 2. Submit a copy of your current
DEA Certificate to the Registry. If a copy of the DEA certificate is not already on file,
please email it to: medical.marijuana@state.co.us 3. Have a bona fide physician-
patient relationship with the patient. 4. Conduct a physical examination each year and
review patient’s medical history to certify the patient has a qualifying debilitating or
disabling medical condition. 5. Complete a physician certification for the patient. A
new physician certification is required each year as part of the patient’s renewal
process. 6. Provide a copy of the physician certification to the patient for their
application packet. 7. Keep a copy of the completed physician certification in the
patient’s medical record.
https://www.colorado.gov/pacific/sites/default/files/CHED_MMR_Physician-
Certification_6_28_17.pdf

11. Hemp v CBD v MJ
https://www.thegrowthop.com/cannabis-health/cannabis-medical/whats-the-
difference-between-marijuana-cbd-and-hemp-cbd
Hemp, or industrial hemp, typically found in the northern hemisphere, is a variety of
the Cannabis sativa plant species that is grown specifically for the industrial uses of its
derived products. It is one of the fastest growing plants and was one of the first plants
to be spun into usable fiber 10,000 years ago.
There is significant over and under labeling of hemp derived CBD products
https://jamanetwork.com/journals/jama/fullarticle/2661569

14. CO qualifying conditions
Cancer
Glaucoma
HIV or AIDS
Cachexia
Persistent muscle spasms
Seizures
Severe nausea
Severe pain
Post Traumatic Stress Disorder (PTSD)
https://www.colorado.gov/pacific/cdphe/qualifying-medical-conditions-medical-
marijuana-registry

15. JAMA review article
Conclusions and Relevance There was moderate-quality evidence to support the use
of cannabinoids for the treatment of chronic pain and spasticity. There was low-
quality evidence suggesting that cannabinoids were associated with improvements in
nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep
disorders, and Tourette syndrome. Cannabinoids were associated with an increased
risk of short-term AEs.
Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria,
vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination.
https://jamanetwork.com/journals/jama/fullarticle/2338251

16. Pain control and opioid addition
https://www.linkedin.com/pulse/amid-opioid-crisis-researchers-aim-put-medical-
marijuana-arney-benson/

17. Behavioral health and QOL
May be significant QOL benefits, including decreased anxiety, pain and depression
and increased appetite and general feelings of well being associated with marijuana
us amonth patients with newly diagnosed head and neck cancer
https://www.medpagetoday.com/hematologyoncology/othercancers/74387

18. What determines your response?
Your pharmacogenetics
Your disease
The components and their concentrations in different products
Contaminants, like fungi, bacteria and chemicals

19. The entourage effect
Although the precise mechanisms of the entourage effect in epilepsy and other
disorders isn’t fully established, there are a number of potential explanations for the
greater effectiveness of whole-plant CBD-rich oil extracts compared to CBD isolates.
Cannabis contains THC and many minor compounds with potential anti-epileptic
activity, including THCV (tetrahydrocannabivarin (THCV) , CBDV (CANNABIDIVARIN)
, and the terpene linalool, among others. These chemicals interact synergistically with
cannabidiol to confer a holistic “entourage” or “ensemble” effect so that the
therapeutic impact of the whole plant is greater than the sum of its parts.
https://www.projectcbd.org/cannabidiol-and-epilepsy-meta-analysis

20. Why use and abuse?
https://www.nytimes.com/2018/10/27/style/cbd-
benefits.html?action=click&module=Well&pgtype=Homepage&section=Style
Off label use

21. Is MJ addictive?
Marijuana use can lead to the development of problem use, known as a marijuana
use disorder, which takes the form of addiction in severe cases. Recent data suggest
that 30 percent of those who use marijuana may have some degree of marijuana use
disorder.18 People who begin using marijuana before the age of 18 are four to seven
times more likely to develop a marijuana use disorder than adults.19
Marijuana use disorders are often associated with dependence—in which a person
feels withdrawal symptoms when not taking the drug.
https://www.drugabuse.gov/publications/research-reports/marijuana/marijuana-addictive

22. MJ deaths?
The authors report an 11-month-old male who, followingcannabis exposure,
presented with central nervous system depression after seizure, and progressed
tocardiac arrest and died. Myocarditis was diagnosed post-mortem and cannabis
exposure was confirmed.
https://escholarship.org/uc/item/1n10w5pc#main

23. Epidiolex
The twice-daily oral solution is approved for use in patients 2 and older to treat two
types of epileptic syndromes: Dravet syndrome, a rare genetic dysfunction of the
brain that begins in the first year of life, and Lennox-Gastaut syndrome, a form of
epilepsy with multiple types of seizures that begin in early childhood, usually between
3 and 5.
https://www.cnn.com/2018/06/25/health/fda-approves-first-cannabis-drug-
bn/index.html

24. Adverse effects
Death
Intoxication
Impaired performance/driving
Psychosis
Anxiety and paranoia
Nausea and vomiting
Sedation
Change in appetite
Change in heart rate or BP
Drug interactions
Effects of passive smoke on children

25. Bronchiolitis and THC levels
One in six children hospitalized for bronchiolitis in Colorado had been exposed to
marijuana, according to data presented at the Pediatric Academic Societies Meeting.
https://www.healio.com/family-medicine/pediatrics/news/online/%7B7ca05a32-
6331-4a36-92e8-bb5f3ffc2911%7D/one-in-six-children-hospitalized-for-bronchiolitis-
tested-positive-for-marijuana-exposure

26. Cannabis hyperemesis syndrome
This is a very rare syndrome that occurs in long-term heavy users of THC-rich
cannabis. CHS was first reported in the medical literature in 2004. Symptoms include
nausea, vomiting and abdominal pain. More than 90% of cannabis users who
experience these symptoms also have a compulsion to bathe in hot water during the
episode, reporting that it alleviates the discomfort.

27. Marijuana allergy
Can cause symptoms similar to hay fever, or
Contact dermatitis, or
Anaphylactic shock (if left untreated could be fatal)
Hazard for those working in the cannabis industry
https://www.healthline.com/health/allergic-to-marijuana#symptoms

28. Is Smoking Cannabis Before or After Surgery
Safe?
Best not to smoke anything before surgery
May contribute to postop bleeding
May affect appetite following bariatric surgery
https://www.leafly.com/news/health/smoking-marijuana-before-or-after-surgery

29. Does smoking MJ cause cancer?
34 epidemiologic studies on upper aerodigestive tract cancers (n=11), lung cancer
(n=6), testicular cancer (n=3), childhood cancers (n=6), all cancers (n=1), anal cancer
(n=1), penile cancer (n=1), non-Hodgkin's lymphoma (n=2), malignant primary
gliomas(n=1), bladder cancer (n=1), and Kaposi's sarcoma (n=1).
Evidence insufficient, but may change as more patients smoke more pot.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302404/

30. Use and abuse
5% of pregnant women smoke marijuana
What Happens to Child Custody If One Spouse is Using Marijuana During a Divorce?
Is the Use of Marijuana Considered Child Endangerment?
https://www.legalmatch.com/law-library/article/marijuana-and-child-custody-
lawyers.html

31. The placebo and nocebo effect
a beneficial effect, produced by a placebo drug or treatment, that cannot be
attributed to the properties of the placebo itself, and must therefore be due to the
patient's belief in that treatment.
There is also the nocebo effect: the phenomenon in which inert substances or mere
suggestions of substances actually bring about negative effects in a patient or
research participant.
There may be a biochemical and genetic basis for both
https://www.nytimes.com/2018/11/07/magazine/placebo-effect-
medicine.html?action=click&module=Well&pgtype=Homepage&section=The%20Ne
w%20York%20Times%20Magazine