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#200 Harms of Medical Cannabinoids: Up in Smoke!

What are the harms associated with medical cannabinoid therapy?

Compared to placebo, medical cannabinoids cause multiple different adverse events in patients, from visual disturbance or hypotension (1 in 3-10) to hallucination or paranoia (1 in 20). Stopping due to adverse effects occurs in 1 in every 8-20 patients. Regardless of the type of medical cannabinoid used, adverse events are common and likely underestimated. Given the extensive harms, potential benefits must be impressive to warrant a trial of therapy.    

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Eleven systematic reviews with meta-analyses of harm (in general or in treatment of pain/spasticity/nausea and vomiting)Statistically significant unless otherwise noted.     
  • Total adverse events: Four meta-analyses with 3-29 Randomized Controlled Trials (RCTs), 666-3,714 patients.1-5 
    • Range1-3 from relative risk 1.18 to odds ratio (OR) 3.03. 
    • Percent of patients: 4,5 79-92% cannabinoid versus 56-78% placebo. 
      • Number Needed to Harm (NNH)=5-8.   
  • Serious adverse eventsThree meta-analyses with 11-34 RCTs, 1,568-3,248 patients.1,2,6 
    • Two non-statistically significant.1,2 
    • Other OR 1.41 (1.04-1.92), absolute numbers not provided.6   
  • Stopped due to adverse eventsSeven meta-analyses (2-24 RCTs), 276-2,755 patients.2,5-10     
    • Range from2,7,8 OR 2.94 to Risk Ratio 6.85. 
    • Actual events:5-9 7-14% cannabinoid versus 1-5% placebo, NNH=8-22. 
    • One of the seven meta-analyses was not statistically significant.10     
  • Specific adverse events versus placebo 
    • Predictable effects: Sedation8 NNH=5, feeling high7,8 NNH=2-4, euphoria7,8 NNH=9. 
    • Common: Visual blurring/hallucination11 NNH=3, dizziness2,5,8,11 NNH=5, speech disorders11 NNH=5, ataxia/muscle twitching11 NNH=6, disconnected thought11 NNH=7dysphoria8 NNH=8, hypotension8 NNH=8impaired memory11 NNH=12disorientation11 NNH=15.  
      • Nausea (OR 2.1) and vomiting (OR 1.7) increasedNNH unavailable.2  
    • Other: Hallucination8 NNH=17, paranoia8 NNH=20. 
    • Versus other agents like prochlorperazine, cannabinoids also increased adverse events:7 Example sedation (NNH=7) and dizziness (NNH=3).
  • Adverse events rates varied little between different cannabinoid products (example nabiximol, nabilone, dronabinol, inhaled marijuana, etc.):2 NNH=4-7.  
  • See Tools for Practice #199 and #201 for potential benefits. 
  • Many studies enrolled patients with a history of medical or recreational cannabinoid use.11,12 Regular users will: 
    • Be more tolerant of cannabinoids and less likely to report adverse events.
    • Recognize if randomized to cannabinoids or placebo (up to 89% of the time).12   

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  • G. Michael Allan MD CCFP
  • Joey Ton PharmD

1. Wang T, Collet JP, Shapiro S, et al. CMAJ. 2008; 178(13):1669-78.

2. Whiting PF, Wolff RF, Deshpande S, et al. JAMA. 2015; 313(24):2456-73.

3. Meza R, Pena J, Garcia K, et al. Medwave. 2017; 17(Suppl1):e6865.

4. Lobos Urbina D, Peña Durán J. Medwave. 2016; 16 Suppl 3:e6539.

5. Wade DT, Collin C, Scott C, et al. Mult Scler. 2010; 16(6):707-14.

6. Petzke F, Enax-Krumova EK, Houses W. Schmerz. 2016; 30(1):62-88.

7. Smith LA, Azariah F, Lavender VTC, et al. Cochrane Database Syst Rev. 2016 Feb 2; 2:CD007786.

8. Tramer MR, Carroll D, Campbell FA, et al. BMJ. 2001; 323:16-21.

9. Koppel BS, Brust JCM, Fife T, et al. Neurology. 2014; 82:1556-63.

10. Iskedjian M, Bereza B, Gordon A, et al. Curr Med Res Opin. 2007; 23(1):17-24.

11. Martin-Sanchez E, Furukawa TA, Taylor J, et al. Pain Med. 2009;10(8):1353-68.

12. Wilsey B, Marcotte T, Deustch R, et al. J Pain. 2013; 14(2):136-48.

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.