Cannabis no more effective than placebo

According to a study published in The Journal of the American Medical Association (JAMA) Network Open, the majority of clinical trials evaluating the effect of cannabis on pain indicate that placebos have an equally strong analgesic effect. However, the abundant media coverage of these clinical studies often ignores that the virtues of cannabis are equivalent to those of the placebo.

Given the growing interest in cannabis for treating persistent and recalcitrant pain, a team of researchers from the department of clinical neurosciences at the Karolinska Institute, Sweden, wanted to assess the magnitude of the placebo effect measured in clinical trials. double-blind randomized (i.e., on the one hand, the patients who receive the placebo are chosen at random and, on the other hand, the patients and the experimenters do not know what each patient receives) comparing an active compound from cannabis (a cannabinoid) to a placebo that looks, smells or tastes the same.

They therefore analyzed the results of 20 studies published since September 2021 which included a total of 1,459 people aged 33 to 62, of whom just over half were women. Pain intensity was assessed (via self-report) before and after treatment (cannabinoid or placebo).

This meta-analysis did not show a significant difference between the effect of the placebo and that of the real cannabinoid in relieving the pain experienced by the participants, like another meta-analysis published in 2021 in the journal Bread. “The placebo provided moderate to high, clinically relevant relief,” suggesting that “the placebo effect contributes significantly to the pain reduction observed in these randomized clinical trials,” the researchers write in The JAMA Network Open.

Additionally, the duration of the clinical trial, whether 45 minutes or several months, had no significant effect on the placebo response.

These scientists also observed an association between the risk of bias in a study and the strength of the placebo effect measured in it. Several clinical trials comparing a cannabinoid to a placebo indeed fail to adequately conceal what the patient is receiving, as many participants are able to distinguish the placebo from the active cannabinoid, despite having the same smells, tastes and appearances. However, these studies generally lead to an overestimation of the effectiveness of cannabis, the researchers point out.

Studies have shown that reports in the mass media and the popular press as well as information obtained on the Internet raise expectations for treatment

Among the studies analyzed by the Karolinska Institutet researchers, those that presented a low risk of bias (that is to say that best concealed what was administered to the participants) were also those where the response to the placebo was the higher. “Probably, in these studies, the participants were able to maintain their positive expectations of the treatment throughout the trial and thus benefited more from the placebo effect”, advance the authors of the study.

The latter also underline the fact that “contextual factors play an important role in placebo responses”. “Communication about treatments, their effectiveness and their adverse effects shape patients’ expectations as well as their response to the placebo”, they report in an article published in Nature Reviews Neuroscience.

For this reason, they analyzed the media coverage (by mass media and scientific journals) that each of the clinical studies in their meta-analysis had received.

They observed that these studies aimed at evaluating the effect of cannabinoids on pain had received very high media attention and strong engagement on social networks. These were most often positive, regardless of the clinical results, which were not very clear in favor of cannabis, as described by the researchers in the first part of their article.

In particular, they found that news articles and blogs, in particular, had a strong positive bias towards the effectiveness of cannabinoids in the treatment of pain. The Karolinska Institutet scientists believe that this favorable media coverage may even partly explain the strong placebo responses they observed in their meta-analysis, as “studies have shown that reports in mass media and the press popular as well as information obtained from the Internet stimulated expectations for treatment.

“This extraordinary media attention composed of positive reports towards cannabinoids ignoring the scientific results [soit de l’ampleur de l’effet examiné ainsi que de la qualité des études] could help maintain high expectations among people who will participate in future clinical trials, and even influence their placebo response. And as such, it could have an impact on the results of these future studies, as well as on regulatory decisions, clinical practice as well as patient access to cannabinoids for pain relief,” they conclude.

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