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

Kaertner and colleagues conducted a prospective, naturalistic web-based study that followed volunteers who planned to start a microdosing regimen. Participants registered on the study website, provided informed consent online, and completed survey batteries hosted on SurveyGizmo at a baseline timepoint (one week before or immediately after sign-up) and weekly for four weeks after their stated start date; two additional weekly surveys (weeks 5 and 6) and six- and twelve-month follow-ups were planned but not analysed due to insufficient completion. Individuals already microdosing at sign-up were excluded. Eligibility required being at least 18 years old, understanding English and intending to microdose with a listed psychedelic (psilocybin/magic mushrooms/truffles, LSD/1P-LSD, ayahuasca, DMT/5-MeO-DMT, salvia divinorum, mescaline, or iboga/ibogaine) for at least four weeks. Recruitment was online via social media and community forums, and participants were free to self-administer doses ad libitum rather than following a prescribed regimen, preserving ecological validity. The baseline survey collected demographics, psychiatric history, prior drug use and detailed planned microdosing parameters, plus a four-item expectancy measure (visual analogue scales adapted from the credibility/expectancy questionnaire) that produced a mean expectancy score (0–100). The primary outcome was the 14-item Warwick-Edinburgh Mental Well-being Scale (WEMWBS). Secondary and trait measures included the Quick Inventory of Depressive Symptomatology (QIDS-SR16), the short Spielberger State-Trait Anxiety Inventory (STAI-6), the Ten-Item Personality Inventory (TIPI), the modified Tellegen Absorption Scale (MODTAS), the Multidimensional Iowa Suggestibility Scale (short suggestibility scale), Social Connectedness Scale (SCS), Nature Relatedness Scale (NR-6), Brief Experiential Avoidance Questionnaire (BEAQ), Brief Resilience Scale (BRS) and the Peters Delusions Inventory (PDI). Weekly surveys re-assessed WEMWBS, QIDS-SR16 and STAI-6 and added acute-effect measures used in psychedelic research: eight subscales of the 11-Dimensional Altered States of Consciousness Rating Scale (11D-ASC) and the Ego Dissolution Inventory (EDI). Participants also reported weekly microdosing details (drug type, number of dosing days, dose categories referenced to LSD equivalents) and subjective intensity of effects. For analysis, the investigators used repeated-measures ANOVAs with Greenhouse-Geisser correction across five timepoints (baseline, weeks 1–4) and planned simple contrasts versus baseline. To probe expectancy effects, one-tailed partial Pearson correlations assessed associations between baseline expectancy and endpoint change scores while controlling for baseline values. Two-tailed dependent-samples t-tests evaluated other pre-post changes, and a supplementary mixed between-within ANOVA explored QIDS-SR16 changes in clinically relevant subgroups. The significance threshold was p < 0.05 and analyses were performed using IBM SPSS Statistics v25 and R 3.6.3.

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.