Key Points
Question What is the size of the placebo response in cannabinoid trials for clinical pain, and is the magnitude of placebo response associated with media attention on the trials?
Findings: This meta-analysis of 20 studies of 1459 individuals found a significant pain reduction in response to placebo in cannabinoid randomized clinical trials. Media attention was proportionally high, with a strong positive bias, yet not associated with the clinical outcomes.
Meaning: These findings suggest that placebo has a significant association with pain reduction as seen in cannabinoid clinical trials, and the positive media attention may shape placebo responses in future trials.
Abstract
Importance: Persistent pain is a common and disabling health problem that is often difficult to treat. There is an increasing interest in medicinal cannabis for treatment of persistent pain; however, the limited superiority of cannabinoids over placebo in clinical trials suggests that positive expectations may contribute to the improvements.
Objective: To evaluate the size of placebo responses in randomized clinical trials in which cannabinoids were compared with placebo in the treatment of pain and to correlate these responses to objective estimates of media attention.
Main Outcomes and Measures: Change in pain intensity from before to after treatment, measured as bias-corrected standardized mean difference (Hedges g).
Results: Twenty studies, including 1459 individuals (mean [SD] age, 51 [7] years; age range, 33-62 years; 815 female [56%]), were included. Pain intensity was associated with a significant reduction in response to placebo, with a moderate to large effect size (mean [SE] Hedges g, 0.64 [0.13]; P < .001). Trials with low risk of bias had greater placebo responses (q1 = 5.47; I2 = 87.08; P = .02). The amount of media attention and dissemination linked to each trial was proportionally high, with a strong positive bias, but was not associated with the clinical outcomes.
Conclusions and Relevance: Placebo contributes significantly to pain reduction seen in cannabinoid clinical trials. The positive media attention and wide dissemination may uphold high expectations and shape placebo responses in future trials, which has the potential to affect the outcome of clinical trials, regulatory decisions, clinical practice, and ultimately patient access to cannabinoids for pain relief. (Source: JAMA Open Network)
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