Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing

Of 316 initial sign-ups, 63 were already microdosing and excluded; 253 participants completed the baseline survey and subsequent weekly completions fell to 162 (week 1), 115 (week 2), 102 (week 3) and 81 (week 4/key endpoint). The sample's mean age was 35.47 years (SD = 11.87) and 60.5% were male. A substantial proportion reported prior psychiatric diagnoses: 117 participants (46.2%) self-reported one or more of 15 specified disorders, most commonly major depressive disorder (N = 66, 26.1%) and anxiety disorder (N = 61, 24.1%). Lifetime use of classic psychedelics was common (215 participants, 84.9%) and 75 (29.6%) had prior microdosing experience. The baseline expectancy composite had a mean of 65.10 (SD = 19.95) on a 0–100 scale, indicating generally positive expectations. Among participants who completed all five timepoints and reported dosing details (n = 68), the mean number of dosing days during the study was 9.2 (SD = 2.31, range 4–18) and mean dosing days per week was 2.31 (SD = 0.58, range 1–5). Planned substances at baseline were predominantly psilocybin-containing mushrooms (N = 121, 47.82%) and LSD or analogues (N = 106, 41.9%); smaller fractions planned mixed use or other psychedelics. Primary and key secondary outcomes showed statistically significant changes over time. Psychological well-being (WEMWBS) increased across timepoints, with a main effect of time [F(2.9,191) = 14.441, p < 0.001, partial eta squared = 0.18]; the largest change occurred at week 1 and thereafter scores reached an asymptote. Depressive symptoms (QIDS-SR16) decreased over time [F(2.3,120.7) = 23.702, p < 0.001, partial eta squared = 0.31], most markedly at weeks 1 and 2 before plateauing. State anxiety (STAI-6) also declined [F(3.1,205.8) = 20.755, p < 0.001, partial eta squared = 0.24], again with the greatest change by week 1. Planned contrast analyses showed significant differences between baseline and each subsequent timepoint for these measures. Baseline positive expectancy predicted the magnitude of change by the four-week endpoint. One-tailed partial Pearson correlations controlling for baseline scores indicated that higher baseline expectancy was associated with greater increases in well-being (r = 0.275, p = 0.007), larger reductions in depressive symptoms (r = -0.263, p = 0.009) and larger reductions in state anxiety (r = -0.220, p = 0.025). Exploratory analyses in the total completer sample (N = 81) identified a significant increase in the personality facet emotional stability (p < 0.001, Cohen's d = 0.40). Additional exploratory changes were reported in agreeableness, social connectedness, nature relatedness, resilience, delusional ideation and psychological flexibility, but detailed statistics for these measures were presented as exploratory and without correction for multiple comparisons. The study experienced high attrition: the authors report a 68% dropout rate by the four-week endpoint; predictors of drop-out included lower baseline conscientiousness and younger age rather than early side-effects.

Kaertner and colleagues interpret their findings as showing apparent short-term improvements in multiple self-reported psychological domains following a naturalistic four-week microdosing period, but they emphasise that baseline positive expectations substantially predicted these improvements. The authors note that well-being increased and depressive symptoms, state anxiety and emotional stability improved—changes that emerged rapidly (by week 1) and then stabilised. Exploratory analyses suggested additional positive shifts in interpersonal and trait measures, but these were not the primary focus. The investigators position their results in the context of prior microdosing literature and placebo-controlled trials, arguing that the observed expectancy–outcome relationship aligns with concerns that non-pharmacological factors (including prior mindset and expectations) can drive perceived benefits. They stress that the finding does not uniquely implicate psychedelics—expectancy effects are a recognised phenomenon in clinical research—but it is particularly pertinent for microdosing research given null or mixed findings in some randomised placebo-controlled microdosing trials. The authors therefore advocate for careful measurement of expectations and the inclusion of appropriate placebo or active-placebo conditions in future trials to disentangle pharmacological from expectancy-related effects. Key limitations acknowledged by the study team include the observational, uncontrolled design, uncertain and heterogeneous dosing (including potential inaccuracies when converting diverse substances to 'LSD-equivalent' doses), inconsistent drug purity, high attrition, and a self-selected sample biased towards favourable attitudes to psychedelics. They also note the possibility of regression to the mean or spontaneous remission contributing to improvements and that many participants did not present with extreme baseline scores. The investigators recommend several methodological refinements for future work: randomised placebo-controlled trials with well-matched active placebos to preserve blinding, routine sampling of expectations and their dynamics over time, triangulation of subjective reports with objective physiological measures, and testing in clinical populations where baseline symptom severity may permit clearer detection of clinically meaningful effects. While the authors acknowledge a theoretical rationale for rapid antidepressant effects via 5-HT2A receptor-mediated mechanisms, they refrain from asserting causal therapeutic benefits for microdosing in the absence of controlled data. Their principal conclusion is that positive expectancy appears to play a substantial role in reported mental-health gains after microdosing, and this observation cautions against strong claims regarding the therapeutic value of microdosing until more rigorous evidence is available.