Summary: Psilocybin, the psychoactive compound in magic mushrooms, is notably more effective at alleviating depression symptoms than conventional controls. Analyzing seven trials with 436 participants, researchers found a substantial improvement in depression scores following psilocybin treatment compared to placebos or other minor psychedelic doses, showcasing a large effect size.
Despite the promising results, the study highlights the need for further research to address variables such as type of depression, patient demographics, and treatment settings. The findings support psilocybin’s potential as a powerful antidepressant, yet call for a cautious approach in its clinical application due to current limitations in diverse participant representation and comprehensive impact assessment.
Key Facts:
- The study reviewed seven randomized controlled trials comparing psilocybin to standard controls, involving a total of 436 participants.
- Psilocybin showed a significantly greater improvement in depression scores, with a large effect size (Hedges’ g of 1.64).
- While promising, the study calls for more comprehensive research due to high heterogeneity among trials and limited generalizability given the predominantly white, 52% female participant base.
Source: BMJ
Psilocybin – the active ingredient in “magic” mushrooms – is a more effective treatment for symptoms of depression than controls, providing further support for its potential as an antidepressant, suggests a study published by The BMJ today.
The researchers say the findings are encouraging but “further research is needed to clarify the factors that maximise psilocybin’s treatment potential for symptoms of depression.”
Depression affects an estimated 300 million people worldwide and is a leading cause of disability.
Psilocybin has shown promise in reducing symptoms of depression after one or two doses with few side effects and no current evidence of causing addiction. However, studies published to date have not investigated factors that may moderate psilocybin’s effects, including type of depression, past use of psychedelics, dosage, and publication biases.
To address this, a team of UK researchers examined databases looking for randomised controlled trials that compared psilocybin as a treatment for symptoms of depression with controls, such as placebo, niacin (vitamin B), or micro doses of psychedelics.
They included studies where psychotherapy was present in both the experimental and the control conditions, so that the effects of psilocybin could be distinguished from those of psychotherapy.
They found seven relevant trials for analysis involving 436 participants with depression (52% female; 90% white). Changes in depression scores were measured using a statistical method called Hedges’ g. A Hedges’ g of 0.2 indicates a small effect, 0.5 a moderate effect, and 0.8 or more a large effect.
The change in depression scores was significantly greater after treatment with psilocybin than with a comparator treatment, with an overall Hedge’s g of 1.64 indicating a large effect size favouring psilocybin.
Further analyses to account for trial differences indicated that having secondary depression (related to an underlying disease) rather than primary depression, being assessed with a self-reported scale rather than a clinician assessed scale, older age, and previous use of psychedelics, were correlated with greater improvements.
The study authors acknowledge that high levels of variation (heterogeneity) between trials resulted in a low certainty of evidence to support a strong antidepressant effect of psilocybin, and generalisability of findings were limited by the lack of participant diversity.
Pre-treatment expectations and the extent to which participants knew they were being treated with psilocybin or placebo, were also not measured.
Furthermore, in clinical trials, patients receive psilocybin in a calm living room with soothing music, supervised by a psychotherapist, which is unlikely to be achievable in a healthcare system.
As such, the authors conclude that, although this review’s findings are encouraging for psilocybin’s potential as an effective antidepressant, issues such as cost, lack of regulatory guidelines and legal safeguards associated with psilocybin treatment need to be dealt with before it can be established in clinical practice.
This study is an important contribution to the evidence base for the use of psilocybin in depression, but it cannot answer several questions, say researchers unconnected to the study in a linked editorial.
For instance, they argue that it cannot provide evidence for psilocybin’s effectiveness (performance under ‘real-world’ conditions) in depression until more information about potential effect modifiers is gathered, and that pragmatic clinical trials and real world data could help to deliver that.
Furthermore, there is still ongoing debate on whether psychedelics can express antidepressant activity on their own rather than by assisting specific forms of psychotherapy.
Finally, and perhaps most importantly, the editorial authors say that, as per all analyses using aggregate data, we cannot differentiate between those individuals most likely to benefit from psilocybin and those who might instead experience adverse events.
As such, they conclude that these promising findings “support a prudent approach in both scholarly and public settings, because more and better evidence is needed before any clinical recommendation can be made about therapeutic use of psilocybin.”
About this psychopharmacology research news
Author: BMJ Media Relations
Source: BMJ
Contact: BMJ Media Relations – BMJ
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis” by Athina-Marina Metaxa et al. BMJ
Abstract
Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis
Objective
To determine the efficacy of psilocybin as an antidepressant compared with placebo or non-psychoactive drugs.
Design
Systematic review and meta-analysis.
Data sources
Five electronic databases of published literature (Cochrane Central Register of Controlled Trials, Medline, Embase, Science Citation Index and Conference Proceedings Citation Index, and PsycInfo) and four databases of unpublished and international literature (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, ProQuest Dissertations and Theses Global, and PsycEXTRA), and handsearching of reference lists, conference proceedings, and abstracts.
Data synthesis and study quality
Information on potential treatment effect moderators was extracted, including depression type (primary or secondary), previous use of psychedelics, psilocybin dosage, type of outcome measure (clinician rated or self-reported), and personal characteristics (eg, age, sex).
Data were synthesised using a random effects meta-analysis model, and observed heterogeneity and the effect of covariates were investigated with subgroup analyses and metaregression.
Hedges’ g was used as a measure of treatment effect size, to account for small sample effects and substantial differences between the included studies’ sample sizes. Study quality was appraised using Cochrane’s Risk of Bias 2 tool, and the quality of the aggregated evidence was evaluated using GRADE guidelines.
Eligibility criteria
Randomised trials in which psilocybin was administered as a standalone treatment for adults with clinically significant symptoms of depression and change in symptoms was measured using a validated clinician rated or self-report scale. Studies with directive psychotherapy were included if the psychotherapeutic component was present in both experimental and control conditions. Participants with depression regardless of comorbidities (eg, cancer) were eligible.
Results
Meta-analysis on 436 participants (228 female participants), average age 36-60 years, from seven of the nine included studies showed a significant benefit of psilocybin (Hedges’ g=1.64, 95% confidence interval (CI) 0.55 to 2.73, P<0.001) on change in depression scores compared with comparator treatment.
Subgroup analyses and metaregressions indicated that having secondary depression (Hedges’ g=3.25, 95% CI 0.97 to 5.53), being assessed with self-report depression scales such as the Beck depression inventory (3.25, 0.97 to 5.53), and older age and previous use of psychedelics (metaregression coefficient 0.16, 95% CI 0.08 to 0.24 and 4.2, 1.5 to 6.9, respectively) were correlated with greater improvements in symptoms.
All studies had a low risk of bias, but the change from baseline metric was associated with high heterogeneity and a statistically significant risk of small study bias, resulting in a low certainty of evidence rating.
Conclusion
Treatment effects of psilocybin were significantly larger among patients with secondary depression, when self-report scales were used to measure symptoms of depression, and when participants had previously used psychedelics. Further research is thus required to delineate the influence of expectancy effects, moderating factors, and treatment delivery on the efficacy of psilocybin as an antidepressant.
Systematic review registration
PROSPERO CRD42023388065.
