Efficacy and Safety of Psychedelic Microdosing on Psychological Outcomes in Healthy Adults: A Systematic Review and Meta-analysis

A systematic review and meta-analysis found that some observational microdosing studies reported improvements in mood and personality, but randomised controlled evidence did not demonstrate significant psychological benefits beyond placebo, leaving the evidence for clinical use inconclusive.

Meshkat et al. (2026) conducted a systematic review and meta-analysis of psychedelic microdosing in healthy/non-clinical adults. They searched Embase, MEDLINE and PsycINFO up to February 2026 and included 24 studies involving 3,681 participants. The review examined sub-hallucinogenic doses of psychedelics, primarily psilocybin and LSD, and assessed psychological outcomes including depression, anxiety and stress, as well as safety. Six studies contributed to quantitative meta-analyses

They found that psychedelic microdosing in healthy adults produced some subjective and neurophysiological effects but did not produce significant improvements in depression, anxiety or stress compared with control conditions in randomised trials, while observational benefits may be influenced by expectancy and other confounding factors.

Abstract

Background

Psychedelic microdosing has gained increasing popularity for enhancing mood and cognition, yet its effects on psychological outcomes in healthy adults remain unclear. We aim to evaluate the efficacy and safety of psychedelic microdosing on psychological outcomes in healthy/non-clinical adult population.

Methods

This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251035294). We searched Embase, MEDLINE, and PsycINFO from inception to February 2026 for original studies in healthy adults using sub-hallucinogenic psychedelic doses on separate days. We included randomized studies, nonrandomized prospective studies, cross-sectional studies, and observational longitudinal designs and stratified meta-analyses by design. Random-effects models were used; safety in randomized controlled trials (RCTs) was pooled as risk differences (RDs). Risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools appropriate for each study design.

Results

24 studies (3,681 participants) met inclusion criteria, 6 contributed to meta-analyses. RCTs of psilocybin and LSD microdosing showed subjective and neurophysiological effects but minimal impact on cognition, creativity, or sustained mood. Psilocybin altered EEG and speech with little behavioral change, while LSD caused transient mood and minor physiological effects without lasting cognitive or personality benefits. Observational studies indicated mood and personality improvements, likely influenced by expectancy or lifestyle factors. Meta-analyses included two parallel RCTs (3 comparisons; n = 117) and three non-RCT studies (n = 1,013). Adverse event analyses included two RCTs (4 comparisons; n = 109). RCTs showed no clear evidence of immediate symptom reduction: 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%),and stress (SMD = 0.02; 95% CI −0.39, 0.43; I2 = 0%). Non-RCT within-arm estimates were imprecise and heterogeneous for depressive symptoms (SMCC −0.33; 95% CI −0.75, 0.08) and anxiety (SMCC −0.29; 95% CI−0.84, 0.26). Exploratory pooling across all designs suggested decreases in depressive symptoms and stress, while anxiety remained uncertain. Adverse event risks were similar between treatment and control.

Conclusions

Microdosing does not show consistent immediate benefits for depressive, anxiety, or stress symptoms in healthy adults, and evidence from RCTs remains inconclusive. Although improvements were observed in some studies, these effects were not significantly different from placebo. Larger, well-designed RCTs are needed to clarify the efficacy and safety of psychedelic microdosing beyond placebo.

Meshkat, S., Leung, M., Meshkat, S. et al. Efficacy and Safety of Psychedelic Microdosing on Psychological Outcomes in Healthy Adults: A Systematic Review and Meta-analysis. CNS Drugs (2026). Read Paper

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