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Meta-Analysis
. 2024 Apr 1;7(4):e245960.
doi: 10.1001/jamanetworkopen.2024.5960.

Acute Adverse Effects of Therapeutic Doses of Psilocybin: A Systematic Review and Meta-Analysis

Akhila Yerubandi  1 , Jennifer E Thomas  2 , N M Mahmudul Alam Bhuiya  1 , Catherine Harrington  3 , Lorenzo Villa Zapata  1 , Joshua Caballero  1
Affiliations
Meta-Analysis

Acute Adverse Effects of Therapeutic Doses of Psilocybin: A Systematic Review and Meta-Analysis

Akhila Yerubandi et al. JAMA Netw Open. .

Abstract

Importance: Psilocybin has been studied in the treatment of depression and anxiety disorders. Clinical studies have mainly focused on efficacy, with systematic reviews showing favorable efficacy; however, none have primarily focused on psilocybin safety.

Objective: To evaluate the acute adverse effects of psilocybin at therapeutic doses in the treatment of depression and anxiety.

Data sources: MEDLINE via PubMed, Web of Science, and ClinicalTrials.gov were searched for publications available between 1966 and November 30, 2023.

Study selection: Randomized, double-blind clinical trials that reported adverse effects of psilocybin in patients treated for depression and anxiety were screened.

Data extraction and synthesis: Data were independently extracted by 2 authors and verified by 2 additional authors following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. The inverse variance method with the Hartung-Knapp adjustment for the random-effects model was used, with a continuity correction of 0.5 for studies with 0 cell frequencies. Sensitivity analysis was conducted by sequentially removing 1 study at a time to assess the robustness of the results.

Main outcomes and measures: The primary outcome was considered as the adverse effects of psilocybin at high and moderate (ie, therapeutic) dose regimens and compared with placebo, low-dose psilocybin, or other comparator in the treatment of depression and/or anxiety.

Results: Six studies met the inclusion criteria with a total sample of 528 participants (approximately 51% female; median age 39.8 years; IQR, 39.8-41.2). Seven adverse effects were reported in multiple studies and included in the analysis. Among these, headache (relative risk [RR], 1.99; 95% CI 1.06-3.74), nausea (RR, 8.85; 95% CI, 5.68-13.79), anxiety (RR, 2.27; 95% CI, 1.11-4.64), dizziness (RR, 5.81; 95% CI, 1.02-33.03), and elevated blood pressure (RR, 2.29; 95% CI, 1.15- 4.53) were statistically significant. Psilocybin use was not associated with risk of paranoia and transient thought disorder.

Conclusions and relevance: In this meta-analysis, the acute adverse effect profile of therapeutic single-dose psilocybin appeared to be tolerable and resolved within 48 hours. However, future studies need to more actively evaluate the appropriate management of adverse effects.

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Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure 1.
Figure 1.. Flow Diagram for New Systematic Reviews That Included Searches of Only Databases and Registers
RCT indicates randomized clinical trial.
Figure 2.
Figure 2.. Association of Psilocybin With Headache, Nausea, and Anxiety
Bold copy emphasizes the random-effects model and common effects model. Square size indicates the weight of the study; diamonds, the total weight. ADE indicates adverse drug effect; RR, risk ratio. aHigh-dose psilocybin. bModerate-dose psilocybin.
Figure 3.
Figure 3.. Association of Psilocybin With Dizziness, Blood Pressure, Paranoia, and Transient Thought Disorders
Bold copy emphasizes the random-effects model and common effects model. Square size indicates the weight of the study; diamonds, the total weight. ADE indicates adverse drug effect; RR, risk ratio. aHigh-dose psilocybin. bModerate-dose psilocybin.
See this image and copyright information in PMC

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