The Evidence Alex Crawley, BSP, ACPR RxFiles Academic Detailing Program
Disclosure I have no relationships with commercial entities I have no real or perceived conflicts of interest I am employed by the RxFiles academic detailing program
Disclosure Unfortunately, I haven t had the chance to try out any of the products I ll be talking about today
JAMA Pediatr. 2016 Jul 25:e160971. doi: 10.1001/jamapediatrics.2016.0971. Unintentional Pediatric Exposures to Marijuana in Colorado, 2009-2015. Wang GS1, Le Lait MC2, Deakyne SJ3, Bronstein AC2, Bajaj L4, Roosevelt G5.
Clinical question of the day: Should I be recommending and/or prescribing marijuana to my patients?
Initial orientation When people talk about marijuana, distinguish between cannabis and cannabinoids cannabis aka marijuana contains hundreds of cannabinoids cannabinoids isolated compound e.g. THC far, far more studies
Trials Cannabinoid trials over 70 RCTs often associated with improvements evidence is of low quality & high bias risk 3 products with indications in Canada Cannabis trials < 10 RCTs more detail to follow Whiting PF et al. JAMA. 2015 Jun 23-30;313(24):2456-73. Deshpande A et al.. 2015 Aug;61(8):e372-81. Review.
Cannabinoid Options Product Indications Cost per 30 days Comments Dronabinol (= THC) MARINOL, SYNDROS nausea/vomiting in chemotherapy AIDS-related anorexia $200-500 Usually 1 cap four times per day. Currently unavailable in Canada. Nabilone CESAMET nausea/vomiting in chemotherapy AIDS-related anorexia $100-300 Usually 1 cap daily to BID. Generic available. Some drug coverage. Tetranabinex/nabidiolex SATIVEX cancer-related pain MS-related pain/spasticity $520 per 200 doses Labeled: 12 sprays per day; up to 48 sprays studied
A note on dosing Let s try to standardize in terms of THC content 1. ~400mg THC/day amount of THC the average smoker might get. One cigarette is about 1 gram of marijuana & contains 10-20% THC. 2. 20-40mg THC/day approximate THC dose if using cannabinoids. 3. <34mg THC/day approximate THC dose studied in most RCTS examining cannabis efficacy in pain.
So does marijuana work? Very difficult to say with our meager RCTs No landmark trials Existing studies are usually low quality, have evidence of bias, or have lots of withdrawals. Trials are often very short (5 days of treatment or less!) Difficult to even pick a dose based on trial evidence.
Marijuana claims "It's great for [put your indication here]" Anecdotal evidence is available for nearly any indication of marijuana you can think of In general, we don't have RCT support The trials we do have often look at soft outcomes e.g. in glaucoma e.g. in chronic pain
Marijuana claims "Your pain patients will be able to reduce their opioid doses, as the combination is synergistic" this has been reported in a few case studies however, the few RCTs we have do not show statistically significant opioid dose reductions.
Marijuana claims This is a safe product humans have used for a thousand years Best safety data comes from COMPASS, a 1 year study on 215 chronic pain pts already using cannabis, vs 216 pts not on cannabis (no placebo) Patients smoked on average 2.5 grams cannabis per day (~300mg THC) Adverse effects: psychiatric disturbance (27% vs 11%, e.g. depression, anxiety, euphoria, panic, paranoia, apathy, etc. ), headache (18% vs 11%), nausea (17% vs 10%), somnolence (13% vs 5%), cough (7% vs 1%). 77 cannabis users dropped out, vs 34 non-cannabis users. Ware MA, Wang T, Shapiro S, Collet JP; COMPASS study team. Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS). J Pain. 2015 Dec;16(12):1233-42.
So does marijuana work? Quote from the RxFiles 10 th Edition: "Limited RCTs makes evaluating marijuana efficacy almost impossible.
Who should definitely NOT use marijuana? Pregnancy / breast-feeding Kids 18 years Patients with psychiatric history Drivers / heavy equipment operators
If you are thinking about recommending it Usually consider other agents first 1 st line for none, 4 th line for all Watch for drug seeking behaviour (e.g. Nothing else works! ) consider: does patient want marijuana to replace coping skills? May steer people away from smoking it (consider edibles,?vaporizers) Start at a low dose and titrate slowly Monitor carefully for adverse effects Watch for patients with contraindications
References Ware MA, Wang T, Shapiro S, Collet JP; COMPASS study team. Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS). J Pain. 2015 Dec;16(12):1233-42. Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, Keurentjes JC, Lang S, Misso K, Ryder S, Schmidlkofer S, Westwood M, Kleijnen J. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA. 2015 Jun 23-30;313(24):2456-73. Deshpande A, Mailis-Gagnon A, Zoheiry N, Lakha SF. Efficacy and adverse effects of medical marijuana for chronic noncancer pain: Systematic review of randomized controlled trials. Can Fam Physician. 2015 Aug;61(8):e372-81. Review. Murnion B. Medicinal cannabis. Australian Prescriber. 2015;38(6):212-215. Wang GS1, Le Lait MC2, Deakyne SJ3, Bronstein AC2, Bajaj L4, Roosevelt G5. Unintentional Pediatric Exposures to Marijuana in Colorado, 2009-2015. JAMA Pediatr. 2016 Jul 25:e160971 Wilsey, B., Marcotte, T., Tsodikov, A., Millman, J., Bentley, H., Gouaux, B., et al. (2008). A Randomized, Placebo- Controlled, Crossover Trial of Cannabis Cigarettes in Neuropathic Pain. J Pain. Abrams, D. I., Jay, C. A., Shade, S. B., Vizoso, H., Reda, H., Press, S., et al. (2007). Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology, 68(7), 515-521. Ellis, R. J., Toperoff, W., Vaida, F., van den Brande, G., Gonzales, J., Gouaux, B., et al. (2008). Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology, 34(3), 672-680.