Acute Adverse Effects of Therapeutic Doses of Psilocybin

Summary & key facts

Researchers combined results from six carefully controlled clinical trials that gave a single therapeutic dose of psilocybin to people being treated for depression or anxiety. The pooled data covered about 530 people with a median age near 40 and showed several short-term side effects were more common after psilocybin than after placebo or low doses. Headache, nausea, feeling anxious, dizziness, and higher blood pressure were seen more often, but these effects were usually short-lived and went away within about two days. The researchers say the immediate safety profile looks tolerable, but more studies are needed to learn how best to manage these side effects.

Key facts:

• The analysis pooled six randomized, double-blind trials that included about 530 people being treated for depression or anxiety.
• About half the participants were female and the typical (median) age was around 40 years.
• Compared with placebo or low-dose psilocybin, people who got a therapeutic single dose had about twice the risk of headache.
• Nausea was much more common after psilocybin — roughly nine times more likely in the combined data.
• Feelings of anxiety were also increased, at about double the risk compared with controls.
• Dizziness occurred more often after psilocybin, roughly six times more likely in the pooled results.
• Elevated blood pressure was about twice as likely after psilocybin than in comparison groups.
• The increased risks above were reported as unlikely to be due to random chance when the studies were combined.
• Most of these adverse effects were temporary and resolved within about 48 hours.
• The review included only six studies, so the authors say more research is needed on how to prevent and manage these side effects.

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.

Topics

Forensic Toxicology and Drug Analysis Pain Management and Placebo Effect Psychedelics and Drug Studies

Categories

Clinical Psychology Psychology Social Sciences

Tags

Adverse effect Alternative medicine Anxiety Clinical trial Hallucinogen Internal medicine Medicine Pathology Placebo Psilocybin Psychiatry Randomized controlled trial

Substances

Psilocybin

Conditions & symptoms

Anxiety Depression Anxiety or worry