Placebo Response and Media Attention in Randomized Clinical Trials Assessing Cannabis-Based Therapies for Pain: A Systematic Review and Meta-analysis

PainSci » bibliography » Gedin et al 2022
updated Sep 19, 2023

Two pages on PainSci cite Gedin 2022: 1. Marijuana for Pain 2. Cannabis hype control

PainSci commentary on Gedin 2022: ?This page is one of thousands in the PainScience.com bibliography. It is not a general article: it is focused on a single scientific paper, and it may provide only just enough context for the summary to make sense. Links to other papers and more general information are provided wherever possible.

This review of cannabis-for-pain studies found that “placebo contributes significantly to pain reduction” … with not so much contribution from the cannabis itself.

Translation: THC is not the active ingredient for what little pain relief there is to be had.

Interestingly, they also reported that study results hyped by the media are the most likely to be the most illusory — the most attributable to placebo — probably because of poor blinding.

Blinding or masking is all about keeping study subjects from knowing if they are getting a sham as members of the control group, or getting “the good stuff.” (If you hide their status from the researchers too, that’s double blinded.) Blinding is a key feature of a fair test, but full of gotchas, and “some placebo-controlled cannabis trials fail to ensure correct blinding which may have led to an overestimation of the effectiveness of medical cannabis.” There are many ways to botch blinding, but one of the main ones here is that — shocker! — it turns out people can tell the difference between real and fake marijuana! 🤣

The authors explain their work for a general audience quite nicely in this short article.

~ Paul Ingraham

original abstract †Abstracts here may not perfectly match originals, for a variety of technical and practical reasons. Some abstacts are truncated for my purposes here, if they are particularly long-winded and unhelpful. I occasionally add clarifying notes. And I make some minor corrections.

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.

DATA SOURCES: A systematic literature search was conducted within the MEDLINE and Embase databases. Studies published until September 2021 were considered.

STUDY SELECTION: Cannabinoid studies with a double-blind, placebo-controlled design with participants 18 years or older with clinical pain of any duration were included. Studies were excluded if they treated individuals with HIV/AIDS or severe skin disorders.

DATA EXTRACTION AND SYNTHESIS: The study followed the Preferred Reporting Items for Systematic Review and Meta-analyses reporting guideline. Data were extracted by independent reviewers. Quality assessment was performed using the Risk of Bias 2 tool. Attention and dissemination metrics for each trial were extracted from Altmetric and Crossref. Data were pooled and analyzed using a random-effects statistical model.

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.

original abstract †Abstracts here may not perfectly match originals, for a variety of technical and practical reasons. Some abstacts are truncated for my purposes here, if they are particularly long-winded and unhelpful. I occasionally add clarifying notes. And I make some minor corrections.

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