Positive Media Coverage of Cannabis Trials Could Be Influencing Placebo Effect, Study Claims

Individuals who take a placebo in cannabis-pain trials tend to report roughly the same levels of pain relief as those who receive the active cannabinoid, a new meta-analysis has found.

Published in JAMA Network Open, the meta-analysis reviewed 20 unique cannabis trials focusing on pain-related conditions. While the authors found no statistically significant differences in outcomes between those receiving cannabis preparations compared to those receiving placebos in these studies, they did note that the mass media attention given to this research was very high, often with strong positive biases. This attention could be adding to the size of the placebo effect, they suggest.

Little difference seen between cannabis and placebo medications

Chronic pain is one of the most commonly reported reasons for medical cannabis use. However, the actual effectiveness of different cannabis formulations in tackling pain is still unclear.

A review from the International Association for the Study of Pain (IASP) recently concluded that while pre-clinical studies “support the concept of cannabinoid-mediated analgesia”, current clinical studies tend to be at a high risk of bias and have not provided sufficient high-quality evidence. As a result, the IASP announced that it “cannot endorse the general use of cannabinoids for treatment of pain at this time”, but would welcome further research.

“Although cannabis (and cannabis-derived products, such as CBD) may be widely used for reducing pain, how effective it really is in doing this is still unclear,” first author Filip Gedin, a postdoc researcher at the Karolinska Institute’s Department of Clinical Neuroscience, wrote in a recent guest article for The Conversation.

“This is what our recent systematic review and meta-analysis sought to uncover. Our study, published in the Journal of the American Medical Association, suggests cannabis is no better at relieving pain than a placebo.”

In this latest meta-analysis, Gedin and colleagues identified 20 relevant studies on cannabis and pain, involving a total of nearly 1,500 individuals. The studies focused on a variety of pain conditions, including neuropathic pain and multiple sclerosis. They also used a variety of different cannabis-based medicines, including THC and/or CBD, nabilone, dronabinol, and nabiximols, which were administered either as a pill, spray, oil, or smoke/vapor. Most of the studies were based in the US, the UK, or Canada, though some studies from Brazil, Belgium, Germany, France, the Netherlands, Israel, the Czech Republic, and Spain were also included.

The meta-analysis revealed that, while cannabis treatments did provide a large reduction in subjective pain ratings, the placebo treatments also reduced pain by moderate-to-large amounts. However, no statistically significant between-group differences were observed between the active drug and placebo groups, overall.

The researchers also examined the risk of bias for each study and noted an interesting association; studies with a lower risk of bias tended to have higher placebo responses. The meta-analysis also revealed that many participants were able to distinguish between the cannabis and the placebo treatment, suggesting that some of the current placebo-controlled trials are failing to properly blind participants. This could lead to an overestimation of the effect of medical cannabis on pain, the authors warn.

Media coverage is generally positive, regardless of drug effects

In addition to evaluating the current body of research on cannabis and pain, the researchers were also interested in investigating the wider impacts of these studies.

Using Altmetric, an online tracker of research papers and their impact, the researchers identified a total of 136 news items published about these studies, which were individually reviewed by the researchers and categorized as either being positive, neutral, or negative about the outcomes of the cannabis trials.

Overwhelmingly, the news items had a strong positive bias towards the efficacy of cannabinoid treatments for pain, despite the significant relief also reported by placebo groups. The researchers also found that the overall media attention given to each study did not have any significant associations with how biased the study was, how high the placebo response was, or how low the treatment effect was.

“We see that cannabis studies are often described in positive terms in the media regardless of their results,” Gedin said in a statement.

“This is problematic and can influence expectations when it comes to the effects of cannabis therapy on pain. The greater the benefit a treatment is assumed to have, the more potential harms can be tolerated.”

Media attention may be affecting the placebo response

This relationship between media reporting and the placebo effect is a difficult, but important, thread to unravel.

Previous studies have shown that reporting in the mass media and information available online can foster the development of expectancy effects. The concern is that this becomes a feedback loop, wherein media reports positively speak about the effects of a treatment (regardless of its actual results compared to a placebo), the general public begins to expect positive outcomes from this treatment, and trial participants subsequently experience even more powerful placebo effects.

“The findings of this systematic review and meta-analysis suggest that placebo responses contribute significantly to pain reduction in cannabinoid clinical trials,” wrote the authors of this most recent study.

“The unusually high media attention surrounding cannabinoid trials, with positive reports irrespective of scientific results, may uphold high expectations and shape placebo responses in future trials. This influence may impact the outcome of clinical trials, regulatory decisions, clinical practice, and ultimately patient access to cannabinoids for pain relief.”

The authors are not suggesting that media coverage is completely responsible for the high placebo response seen in these cannabis trials, but they do believe that this study highlights the importance of thinking about the placebo effect and how it can be influenced by external factors, such as media coverage, outside of a clinical trial.

In an interesting parallel, the power of the placebo effect is also gaining attention in psychedelic science circles. Recently, researchers have suggested that the positive outcomes associated with microdosing psychedelics are likely the result of the placebo effect. Similarly, participants in European ayahuasca retreats tend to report similar improvements in stress, anxiety, and depression whether they actually take the hallucinogenic brew or not.