#63: Medical Marijuana: Is it really dope?

October 23, 2017 | By Molly Heublein

Expand your consciousness around medical cannabis (aka marijuana) with expert Dr Donald Abrams, Chief of the Hematology-Oncology Division at San Francisco General Hospital and a Professor of Clinical Medicine at the University of California San Francisco. We explain the cannabinoid system, THC, CBD aka cannabidiol, limitations surrounding cannabis research, current and future medical uses for medical cannabis (marijuana), and potential conditions it may benefit. We take a deep dive on the potential harms of medical cannabis and how to counsel patients on safe use. Plus, the return past guest and new correspondent, Dr Molly Heublein, Assistant Professor of Medicine from UCSF. Thanks to Dr Heublein for writing and producing this episode and it’s show notes!

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Clinical case from Kashlak Memorial:  MM is a 62 yo woman with a history of osteoarthritis and breast cancer, now on an aromatase inhibitor. She struggles with aching and stiffness in her hands, shoulders, knees, and hips. A friend suggested she try medical marijuana. She wants her provider’s opinion on if this is safe and effective.

Background:
Cannabis and Marijuana are both terms for the whole plant/flower. Dr Abrams prefers the term cannabis due to stigma around marijuana, but we will use the terms interchangeably here. Tetrahydrocannabinol (THC) and Cannabidiol (CBD)  are the best studied cannabinoids (active components of cannabis), but there are an estimated 140 biologically active components in the marijuana plant. CBD is less psychoactive than THC since this compound does not bind to cannabinoid receptors in the brain. Cannabis is available as herbal cannabis products (e.g. “weed”, oils, edibles), or as synthetic cannabinoids like dronabinol (synthetic delta-9 THC).

The pharmacodynamics of cannabis differ by route of ingestion. Orally, cannabis has low and variable bioavailability with a peak plasma concentration in ~2.5 hours, and a half-life of 20-30 hours. Delta-9 THC undergoes 1st pass metabolism through the liver and is converted to an even more psychoactive 11-hydroxy metabolite. When inhaled cannabis achieves peak plasma concentration within 2.5 minutes, dissipates rapidly over 30 minutes, and has less psychoactive effects since it largely avoids 1st pass metabolism by the liver. The body has it’s own endocannabinoid system with many of the effects from THC and CBD occurring via agonism or antagonism at cannabinoid receptors, CB1 and CB2. Fun fact: CB1 is the most densely populated receptor in the brain and responsible for many of the mood, motor, and cognitive effects of cannabis!

Cannabis cannot be prescribed without a schedule one license, but in California, cannabis can be “recommended” for specific indications by physicians. A letter of support is written and the patient brings this to the dispensary. At the dispensary, the “budtender” can recommend specific strains or preparations based on patient’s situation. Patients discover the most effective product by trial and error. In California, marijuana dispensaries offer a wide range of products: under the tongue sprays, tinctures, topical salves, suppositories, and snacks…even potato chips! There is no data about the bioavailability/metabolism of these products. The reported THC/CBD ratio reported by dispensary products is often incorrect.

Please note that in some states, only CBD is legal. Check your local laws here for specifics of how it works in your area.

Marijuana’s classification as a schedule one drug limits its ability to be studied as it is listed as a drug of abuse with no medical benefit.  NIDA (National Institute on Drug Abuse) primarily funds research into the harms of cannabis, rather than benefits, so the literature around its uses is limited.

Clinical Pearls

1. THC: more medically active component of cannabis. Dr. Abrams, recommends using it as a whole plant since other terpenoids, flavonoids, and cannabinoids may support the beneficial aspects of THC and downplay some of the adverse effects.
2. Cannabis is a “folk medicine” and a botanical in Dr Abrams’ opinion.  Given the variety of strains (indica, sativa, high THC vs CBD, and many possibly active compounds) it will likely never be studied like other medications. Dr Abrams’ views cannabis as a “modality” rather than a “medicine”
3. Slow onset of oral cannabis (e.g. edibles) may prompt patient to take too much, then 1st pass metabolism in liver boosts psychoactive effects of THC and causes patient distress +/- ED visits! Dr Abrams recommends inhaled cannabis which allows more flexibility/control over dosage.
4. Dronabinol is approved for chemotherapy induced n/v and anorexia associated w/AIDS wasting.
5. Dr Abrams frequently recommends cannabis for anorexia, nausea, vomiting, weight loss, pain, sleep, depression, and anxiety in his cancer patients. He has extensive personal experience with patients getting benefit for these symptoms, although there is little hard data from RCTs.
6. Cannabis does not seem to affect pharmacokinetics of opiates, but seems to be synergistic for pain relief!
7. Cannabis is better for chronic pain than acute pain. Some evidence supports use for pain and spasticity patients with multiple sclerosis.  
8. Early research in animals has suggested anti-cancer effects of cannabis leading some patients to dangerously forgo proven curative therapy for their illness.
9. Future areas of interest: PTSD, autism, Crohn’s, and ADHD may be potentially responsive to cannabinoids, but research is still very limited.
10. Safety concerns w/cannabis: Probably safer than tobacco, alcohol, and even sugar.  Known harms include reduced cognitive functions, increased HR, and increase or decrease in BP. Early observational data suggest possible risk for ischemic CVA, and MI. Postural hypotension with increased falls risk is a concern in the elderly. The risk of MVA is doubled under the influence of cannabis. THC overdoses are not seen since CB1 receptors are nearly absent in the brainstem. Cannabis may increase risk for chronic bronchitis. Studies are mixed on whether cannabis increases risk for COPD in smokers. Studies have not seen increased rates of lung or head and neck cancers, possibly due to its anti-inflammatory effects. Observational data suggests an increased incidence of testicular cancer– possibly due to demographics of who smokes (young men).
11. Cannabis induced hyperemesis syndrome: Idiosyncratic response to heavy marijuana use is rare, but tends to cause recurrent vomiting which improves with a warm shower. Tx = stop or reduce cannabis use.
12. Dr Abrams says we have all been trained “in an era of marijuana prohibition” and lack knowledge of cannabinoids. Time to educate yourself about cannabis!

Goal:  Listeners will have a greater knowledge of medical marijuana and the evidence behind its use for various medical conditions.

Learning objectives:
After listening to this episode listeners will…

1. Recall the limited evidence base for the use of medical marijuana
2. Review the various biologically active compounds in the marijuana plant
3. Counsel patients on the benefits and harms of medical cannabis
4. Consider clinical scenarios where a provider may recommend medical marijuana and how to counsel patients regarding its use
5. Choose the appropriate agent based on a patient’s condition and its pharmacologic properties

Disclosures: Dr Abrams reports acting as a Scientific Advisor to ABcann, AXIM Biotechnologies, Inc, Maui Wellness Group, Scriptyx, and Tikun Olam.

Time Stamps
00:00 Intro
01:30 Picks of the week
03:40 Guest bio
05:11 Getting to know our guest
11:03 Clinical case
11:40 Limitations for cannabis research
12:59 Discussion of THC and cannabidiol
14:50 Smoking versus ingesting cannabis products
16:40 Recap of cannabinoid mechanism of action
18:30 Cannabis and cannabinoid products available
20:20 Synthetic THC (dronabinol)
21:46 How “recommending” cannabis and dispensaries work
25:46 Conditions that respond to medical cannabis
29:15 Potential harms of medical cannabis
34:51 Future directions of cannabinoid medicine research
37:24 Cannabis induced hyperemesis syndrome
39:00 Possible lung cancer risk
40:12 Take home points
42:54 The Curbsiders recap and share their views on the medical cannabis controversy
49:40 Outro

Links from the show:

1. Molly’s pick of the week: Red Cross https://www.redcross.org/donate/1017c
2. Paul’s pick of the week: Baby Driver (film) by Edgar Wright
3. Stuart’s pick of the week: Name of the Wind (book) by Patrick Rothfuss
4. Donald’s book suggestions: A Constellation of Vital Phenomena: A Novel by Anthony Marra. The Story of a Brief Marriage, a Novel by Anuk Arudpragasam.  When Breath Becomes Air by Paul Kalanithi and Abraham Verghese
5. National Comprehensive Cancer Network Guidelines.  https://www.nccn.org/professionals/physician_gls/f_guidelines.asp
6. University of Arizona Center for Integrative Medicine- online and continuing learning  https://integrativemedicine.arizona.edu/education/index.html
7. Oxford University Press, Weil Integrative Medicine Library.  Series on integrative medicine topics: https://global.oup.com/academic/content/series/w/weil-integrative-medicine-library-iml/?cc=us&lang=en&
8. CNN’s documentary Weed Parts 1-3 with Dr Sanjay Gupta https://www.youtube.com/watch?v=PRLYV0_6zY8
9. The Health Effects of Cannabis and Cannabanoids. The Current State of Evidence and Recommendations for Research by NASEM 2017.    
10. Nugent, SM. The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms: A Systematic Review. Ann Int Med 2017 (Subscription required)
11. Hill, KP. Medical Marijuana for Treatment of Chronic Pain and Other Medical and Psychiatric Problems: A Clinical Review. JAMA 2015 (Subscription required)
12. Pletcher MJ et al. Association Between Marijuana Exposure and Pulmonary Function Over 20 Years. JAMA. 2012
13. Tashkin DP.  Effects of marijuana smoking on the lung.  Ann Am Thorac Soc. 2013 Jun;10(3):239-47. doi: 10.1513/AnnalsATS.201212-127FR. Review.
14. Marijuana use and cancer incidence (California, United States).
15. Jouanjus, E. What is the Current Knowledge About the Cardiovascular Risk for Users of Cannabis-Based Products? A Systematic Review. Curr Atheroscler Rep. 2017 (Abstract only)
16. Callaghan RC, Allebeck P, Sidorchuk A. Marijuana use and risk of lung cancer: a 40-year cohort study.  Cancer Causes Control. 2013 Oct;24(10):1811-20. doi: 10.1007/s10552-013-0259-0. Epub 2013 Jul 12.
17. Information by state on marijuana laws:  http://norml.org/legal/medical-marijuana-2