Tools for Practice


#200 Harms of Medical Cannabinoids: Up in Smoke!


CLINICAL QUESTION
What are the harms associated with medical cannabinoid therapy?

BOTTOM LINE
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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EVIDENCE
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 events: Three 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 events: Seven 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=7, dysphoria8 NNH=8, hypotension8 NNH=8, impaired memory11 NNH=12, disorientation11 NNH=15.  
      • Nausea (OR 2.1) and vomiting (OR 1.7) increased, NNH 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.  
Context:   
  • 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   
November 27, 2017

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Author(s):

  • 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.