The benefits associated with medical cannabis therapy may be overestimated because of inadequate blinding in clinical trials, according to an article published in JAMA Internal Medicine.

David Casarett, MD, MA, of Duke University School of Medicine, Durham, North Carolina, notes that many trials are flawed by inadequate blinding because subjects can distinguish between active cannabis and placebo. In one placebo-controlled crossover trial, 93% of those assigned to the active treatment group first guessed their treatment assignment correctly, whereas only 38% of those assigned to placebo guessed correctly, but almost all (92%) of the participants in the second group guessed correctly when they crossed over to active cannabis.

Inadequate blinding can lead subjects to overestimate the beneficial effects of an intervention. However, Dr Casarett notes that designing a well-blinded study for cannabis therapy is difficult, as most participants can detect the psychoactive properties of active cannabis treatment.

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Dr Casarett suggests that randomized clinical trials of medical cannabis should include a psychoactive control, but it is not clear what might best serve as a psychoactive control to cannabis. The control would have to mimic the most prominent effects, such as dry mouth, increased heart rate, and euphoria, while at the same time having no effect on the primary end point. He also suggests recruiting only participants who are naive to cannabis, but this may increase the risk for new adverse effects or addiction in these subjects. Researchers could also assess the adequacy of blinding by questioning participants’ beliefs regarding which treatment group they are in. These assessments could then serve to guide the interpretation of the trial results.

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The author’s final suggestion is to explore the use of cannabis strains that are enriched for cannabidiol, which does not have the psychoactive effects of tetrahydrocannabinol. However, obtaining such tailored strains of cannabis from a reputable source poses a problem. 

Dr Casarett suggests that in the meantime, patients and physicians use caution when interpreting the findings of cannabis trials.


Casarett D. The Achilles heel of medical cannabis research—inadequate blinding of placebo-controlled trials [published online November 20, 2017]. JAMA Intern Med. doi:10.1001/jamainternmed.2017.5308