Psilocybin for depression, anxiety holds manageable safety profile

In the treatment of individuals with depression and anxiety, therapeutic single-dose psilocybin appears to be tolerable, with acute adverse effects that are resolved within 48 hours, according to the results of a meta-analyses.

Researchers searched multiple online databases for randomized, double-blind clinical trials wherein the adverse effects of psilocybin in patients treated for depression and anxiety were reported. Data were evaluated and extracted 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 sensitivity analysis conducted by sequentially removing one study at a time to assess the robustness of the results.

Six studies met the eligibility criteria and were included in the analysis. The total study population comprised 528 participants (median age 39.8 years, 51 percent female, >90 percent White). The overall risk of bias was low for all included studies.

Several adverse effects were identified across the studies. Comparators used included placebo, niacin, escitalopram, and low-dose psilocybin (1–3 mg). In general, adverse events occurred immediately or within 24 hours after administration of various doses of psilocybin.

Pooled data showed that therapeutic psilocybin dosing was associated with significantly increased frequency of headache (relative risk [RR], 1.99, 95 percent confidence interval [CI], 1.06–3.74), nausea (RR, 8.85, 95 percent CI, 5.68–13.79), anxiety (RR, 2.27, 95 percent CI, 1.11–4.64), dizziness (RR, 5.81, 95 percent CI, 1.02–33.03), and elevated blood pressure (RR, 2.29, 95 percent CI, 1.15–4.53).

There was no association observed for the risk of paranoia and transient thought disorder.

Of note, the adverse effects were tolerable and typically resolved within 24 to 48 hours.