Efficacy and Safety of Psychedelic Microdosing on Psychological Outcomes in Healthy Adults: A Systematic Review and Meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized and non-randomized studies
PubMed 42593636 · doi:10.1007/s40263-026-01325-5
What was done
A systematic review (PROSPERO CRD420251035294) searched Embase, MEDLINE, and PsycINFO through February 2026 for studies on sub-hallucinogenic psychedelic microdoses on separate days in healthy/non-clinical adults. Study designs included randomized trials, nonrandomized prospective studies, cross-sectional studies, and observational longitudinal studies. Risk of bias was evaluated using Joanna Briggs Institute tools, and random-effects meta-analyses were stratified by design.
What was found
Of 24 included studies (3,681 participants), 6 contributed to meta-analyses. In parallel RCTs (2 studies, 3 comparisons, n = 117), microdosing showed no significant differences versus placebo for depressive symptoms (SMD = -0.19; 95% CI -0.56, 0.19; I² = 0%), anxiety (SMD = -0.20; 95% CI -1.11, 0.71; I² = 82.3%), or stress (SMD = 0.02; 95% CI -0.39, 0.43; I² = 0%). Non-RCT within-arm estimates were also imprecise and non-significant for depressive symptoms (SMCC = -0.33; 95% CI -0.75, 0.08) and anxiety (SMCC = -0.29; 95% CI -0.84, 0.26). Adverse event risks were similar between treatment and control in RCTs (2 RCTs, 4 comparisons, n = 109).
Why it matters
Self-reported benefits of psychedelic microdosing on mood, stress, and cognition are largely unsupported in placebo-controlled trials, indicating that observed real-world improvements are likely driven by expectancy and placebo effects.
Limits
The randomized evidence base is very small (only 2 parallel RCTs with 117 participants), leading to substantial imprecision. Most data rely on observational designs vulnerable to self-selection and expectancy bias. Heterogeneity was high for anxiety outcomes in RCTs.