Comparison between Single-Dose and Two-Dose Psilocybin Administration in the Treatment of Major Depression: A Systematic Review and Meta-Analysis of Current Clinical Trials.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of clinical trials
PubMed 39199520 · doi:10.3390/brainsci14080829
What was done
A systematic review and meta-analysis was conducted following PRISMA guidelines to evaluate the therapeutic efficacy of single-dose versus two-dose psilocybin administration on depressive symptom severity. Searches across EBSCOhost and PubMed identified 425 records (287 unique), yielding 12 clinical trials meeting inclusion criteria for quantitative analysis in patients with primary major depressive disorder (MDD) or treatment-resistant depression (TRD).
What was found
The abstract reports no numerical effect sizes, confidence intervals, or p-values. Quantitative analysis reportedly showed that both single-dose and two-dose psilocybin significantly reduced depressive symptom severity in MDD and TRD. Two-dose regimens sometimes demonstrated more pronounced and durable improvements compared to single-dose protocols, though the authors note it remains unclear whether this difference was attributable solely to dose frequency or confounding trial variables.
Why it matters
Identifying optimal dosing regimens is critical for clinical translation and resource allocation in psychedelic-assisted psychotherapy for major depression.
Limits
The abstract provides no specific pooled effect sizes, participant totals, doses, or follow-up durations. It remains unclear whether differences between single- and two-dose regimens reflect true pharmacological superiority or cross-study heterogeneity in psychotherapeutic support, baseline severity, and study designs.
Cited by
- context In clinical trials for major depression that has not responded to other treatments, high-dose psilocybin-assisted psychotherapy yields significant relief or remission in 60% to 70% of patients.