Review identifies factors associated with response to psilocybin

Several trials of psilocybin for symptoms of depression have shown encouraging findings, as have a number of systematic reviews and meta-­analyses. However, several of the reviews have included nonrandomized trials and studies in which psilocybin was used in conjunction with psychotherapeutic interventions, making it difficult to isolate psilocybin's effects. Investigators conducted a systematic review and meta-­analysis of psilocybin trials that focused on trials with an unconfounded evaluation of the psychedelic's effects. Eligible for inclusion were open-­label and double-blind adult trials that compared the efficacy of psilocybin with a non-­psychoactive drug or placebo. Studies involving healthy subjects and those using micro-­dosing of psilocybin were excluded. The investigators considered changes in symptoms as measured by validated clinician-­rated or self-­report scales, excluding any outcomes that were measured less than three hours after psilocybin administration. They conducted subgroup analyses based on demographic factors, comorbid illnesses, and psilocybin dosing variables. The review encompassed nine studies with a total of 436 participants. Seven of the nine studies showed a significant benefit of psilocybin over a comparator or placebo. Treatment response with psilocybin was around twice as likely as with placebo. Among the factors associated with greater likelihood of symptom improvement with psilocybin were having secondary depression, being assessed with a self-­report scale for depression such as the Beck Depression Inventory, and having previously used psychedelics. “More large-­scale randomized trials with long follow-­up are needed to fully understand psilocybin's treatment potential, and future studies should aim to recruit a more diverse population,” authors of the review and meta-­analysis wrote. [Metaxa, A., et al. (2024). BMJ. https://doi.org/10.1136/bmj-2023-078084]