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

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.

Predictors of Pharmacy Students' Attitudes About the Therapeutic Use of Psilocybin.

Background Psilocybin has been studied for its potential therapeutic benefits, particularly for the treatment of psychiatric disorders such as anxiety, depression, and obsessive-compulsive disorder. While more research is needed as psilocybin-assisted therapy becomes more prevalent, future pharmacists will probably be involved at some level. At present, pharmacists receive minimal training on psilocybin, and little is known about their attitudes toward its use for medical purposes. Findings from recent clinical studies have attempted to establish the safety and medical efficacy of psilocybin, leading to an increased interest in therapeutic psilocybin use in the United States. This study aimed to assess if self-assessed knowledge of psilocybin, concerns about adverse effects, and opinions about legalization will make statistically significant contributions to pharmacy students' attitudes about psilocybin use in practice. Methods Pharmacy students' self-assessed knowledge, concern for potential adverse effects, and perceptions of psilocybin were investigated using a cross-sectional survey study design. Data were collected from March 13 to April 7, 2023, from a convenience sample of 161 pharmacy students enrolled in an accredited pharmacy school in the southern region of the United States using a 41-item anonymous quantitative survey developed by the researchers that contained validated scales. The survey was delivered electronically. Multiple regression modeling was conducted to determine if self-assessed knowledge, concerns for adverse effects, and opinions about legalization would predict pharmacy students' attitudes about therapy-assisted psilocybin use. This study was approved by the Institutional Review Board of the authors' university. Results The mean age of the 161 participants was 24 years (SD = 2.981; range 20-40 years). Twenty (12.4%) participants reported previous use of psilocybin for recreational purposes and two (1.2%) reported having used it therapeutically. Many (n =121; 75.2%) of the participants believed that psilocybin should be decriminalized for therapeutic use, but only 54 (33.5%) thought it should be decriminalized for recreational use. A multiple linear regression model predicting "attitudes about psilocybin" (dependent variable) produced significant results: (F(4, 122) = 40.575, p < 0.001), with an R2 = 0.571 (adjusted R2 = 0.557). Greater "self-assessed knowledge about psilocybin," less "concern about possible negative effects," greater "belief in the decriminalization of psilocybin for recreational use," and greater "belief in the decriminalization of psilocybin for therapeutic use" (all independent variables) were associated with more positive perceptions about medical psilocybin. The percentage of variance in the scores accounted for by the model was 57%. Conclusions Pharmacy students may lack information and training regarding psilocybin and report a desire to learn more about it. Their attitudes about medical psilocybin may be driven by this desire to learn in addition to concerns about adverse effects and legalization issues. Due to the dearth of published information regarding the knowledge and acceptance of psilocybin as a viable treatment option for patients, further research in psychedelic-assisted treatments may be warranted.