In a naturalistic observational study of 953 psilocybin microdosers and 180 non-microdosing controls followed for ≈30 days, microdosers showed small-to-medium improvements in mood and mental health across age, gender and mental-health status, with psychomotor gains evident specifically in older adults. Combining psilocybin with lion’s mane (Hericium erinaceus) and niacin (vitamin B3) did not alter mood outcomes but was associated with additional psychomotor improvements in older participants.
Psilocybin microdosing involves repeated self-administration of mushrooms containing psilocybin at doses small enough to not impact regular functioning. Microdose practices are diverse and include combining psilocybin with substances such as lion’s mane mushrooms (Hericium erinaceus; HE) and niacin (vitamin-B3). Public uptake of microdosing has outpaced evidence, mandating further prospective research. Using a naturalistic, observational design, we followed psilocybin microdosers (n = 953) and non-microdosing comparators (n = 180) for approximately 30 days and identified small- to medium-sized improvements in mood and mental health that were generally consistent across gender, age and presence of mental health concerns, as we all as improvements in psychomotor performance that were specific to older adults. Supplementary analyses indicated that combining psilocybin with HE and B3 did not impact changes in mood and mental health. However, among older microdosers combining psilocybin, HE and B3 was associated with psychomotor improvements relative to psilocybin alone and psilocybin and HE. Our findings of mood and mental health improvements associated with psilocybin microdosing add to previous studies of psychedelic microdosing by using a comparator group and by examining the consistency of effects across age, gender, and mental health. Findings regarding the combination of psilocybin, HE and B3 are novel and highlight the need for further research to confirm and elucidate these apparent effects.
The paper summarises renewed public and scientific interest in psilocybin, not only at full psychoactive doses but also at substantially lower ‘‘microdoses’’ that are intended not to disrupt normal functioning. Prior cross-sectional and a few prospective studies have reported that microdosing (commonly 0.1–0.3 g dried mushrooms, several times per week) is associated with self-reported improvements in mood, cognition and reductions in stress, depression and anxiety. However, existing longitudinal research is limited by small samples, inconsistent use of non-microdosing control groups, difficulties maintaining placebo/blind conditions, high rates of prior psychedelic experience among participants, and little investigation of combinations of microdosed psilocybin with other substances (so-called ‘‘stacking’’), such as lion's mane (Hericium erinaceus; HE) and niacin (vitamin B3; B3), which have been anecdotally combined with psilocybin in the community. K. and colleagues designed a large, naturalistic, prospective observational study to extend this literature. The study follows self-selected participants recruited via an iOS application, comparing individuals who microdose psilocybin-containing mushrooms against non-microdosing comparators over approximately 22–35 days. The authors aimed to examine changes in mood and mental health (including depression, anxiety and stress), and cognitive and psychomotor functioning, to investigate whether effects varied by age, gender or presence of mental health concerns, and to explore whether stacking psilocybin with HE and B3 was associated with different outcomes.
Papers cited by this study that are also in Blossom
Fadiman, J., Korb, S. · Journal of Psychoactive Drugs (2019)
Ona, G., Bouso, J. C. · Neuroscience and Biobehavioral Reviews (2020)
Kuypers, K. P. C., Erritzoe, D., Knudsen, G. M. et al. · Journal of Psychopharmacology (2019)
Polito, V., Stevenson, R. J. · PLOS ONE (2019)
The researchers conducted a naturalistic, observational prospective study integrated within an iOS application. Eligible participants were 18 years or older, English-literate and able to use an iOS device. Recruitment targeted both individuals who were microdosing and individuals not engaged in microdosing through media and presentations related to psychedelic use. Participants completed a baseline assessment and a follow-up assessment 22–35 days later; both assessments used equivalent schedules and took about 20–30 minutes. Informed consent was obtained and the study received institutional ethics approval. Hypotheses and outcomes were not pre-registered. Assessments included self-report measures of mood and mental health and brief cognitive and psychomotor tasks adapted from Apple ResearchKit. Mood was measured with the Positive and Negative Affect Schedule (PANAS); depressive, anxiety and stress symptoms were measured with the DASS-21 (scores converted to percentages for one PANAS negative item that was missing due to technical error). Psychomotor and cognitive performance were assessed using an adapted finger tap task (number of alternating taps in 10 s), an adapted Corsi Block-Tapping spatial span task (number correct), and an adapted Paced Auditory Serial Addition Test (PASAT; total correct). For statistical analysis the authors used mixed-effects linear models across eight outcomes (DASS depression, DASS anxiety, DASS stress, PANAS positive, PANAS negative, finger taps, spatial span, PASAT). Models included continuous Time (days since baseline) and a dichotomous Microdose group factor (non-microdosers = 0, microdosers = 1). To limit model complexity and preserve subgroup sizes, only one moderator was included per model: Age (dichotomised as 55 and over versus under 55) was used in models of cognitive and mood outcomes, while presence of Mental Health Concerns (self-reported current psychological, mental health or addiction concerns) was used in DASS models. Models retained variables that predicted outcomes or were part of higher-order significant interactions. Where a Microdose*Time interaction was found, full factorial models examined three-way interactions with Gender and either Age or Mental Health Concerns. Supplementary analyses included removal of outliers (>2 standard deviations), exclusion of participants who reported microdosing at baseline to examine incident microdosing effects, and a set of stacking analyses comparing Psilocybin-only microdosers to Psilocybin+HE and Psilocybin+HE+B3 subgroups. Chi-squared tests and random trimming were used to address subgroup imbalances in age, microdose frequency and dosage when comparing stacking groups.
Across the principal mental health outcomes, the authors report small-to-medium improvements among microdosers relative to non-microdosers over the ~30-day interval. Mixed-effects models identified significant Microdose*Time effects for depressive, anxiety and stress symptoms (DASS domains) and for positive and negative affect (PANAS), and these effects were generally robust to removal of outliers and to analyses restricted to participants who were not microdosing at baseline. The Microdose*Time reduction in depressive symptoms was moderated by gender, with stronger reductions among females than males (Microdose*Gender*Time: F(1,1016)=6.61, b=0.17). Interactions between Microdose and Mental Health Concerns were non-significant, indicating that improvements associated with microdosing were observed both in participants who did and did not report current mental health concerns. For illustrative numerical changes, among microdosers reporting mental health concerns at baseline mean (SD) DASS depression changed from 18.85 (12.03) at baseline to 11.73 (9.85) at Month 1; anxiety from 11.04 (8.48) to 7.46 (6.68); and stress from 19.93 (9.71) to 13.91 (9.02). Among respondents without mental health concerns, depression changed from 10.40 (9.78) to 6.65 (7.60); anxiety from 6.53 (6.50) to 4.81 (5.57); and stress from 13.96 (9.12) to 9.78 (7.50). On mood measures (PANAS), Microdose*Time effects were observed and were equivalent across age groups (Age*Microdose*Time not significant for either positive or negative affect). Stacking (addition of HE or HE+B3) did not influence PANAS outcomes. Cognitive and psychomotor results were mixed. The finger tap task showed a main microdosing effect: microdosers demonstrated greater improvement in tapping performance than non-microdosers (F(1,886)=9.09, b=-0.24, p=0.03). This effect remained when excluding participants who were microdosing at baseline and after outlier removal. No main effects were observed for the spatial span task (F(1,944)=0.24, p=0.63) or PASAT (F(1,775)=0.21, p=0.65). Supplementary stacking analyses found no differences between Psilocybin-only and Psilocybin+HE microdosers on the DASS domains or finger tap. In contrast, comparison of Psilocybin-only versus Psilocybin+HE+B3 showed relatively greater improvement in finger tap scores with the addition of both HE and B3 (F(1,732)=3.93, b=-0.51, p<0.05). A three-way interaction with Age indicated that this stacking-related psychomotor improvement was driven by older respondents (Psilocybin only vs Psilocybin+HE+B3 * Time * Age: F(1,732)=8.4, b=0.6, p=0.004), with follow-up tests suggesting effects concentrated in participants aged 55 and over. These stacking findings were robust to controlling for subgroup differences in age, microdose frequency and dosage. The authors note that subgroup sample sizes for stacking comparisons—especially involving B3—were relatively small.
K. and colleagues interpret their findings as broadly consistent with earlier longitudinal studies of psychedelic microdosing: microdosers experienced improvements in mood and reductions in symptoms of depression, anxiety and stress over about one month, with effect sizes described as small to medium. The study is presented as the largest prospective investigation of psilocybin microdosing to date and one of the few to include a non-microdosing comparison group, lending weight to the observed associations. The authors highlight that participants who reported mental health concerns at baseline showed an average reduction in depressive symptoms that shifted from the moderate range to the mild range over the study period, a result the authors consider noteworthy given the public health burden of depression. The authors emphasise limits to causal inference in a non-randomised, unblinded observational design. They acknowledge that both microdosers and non-microdosers knew their group assignment, so expectancy or placebo effects could contribute to differences; they also note broader practical difficulties in achieving effective blinding with psychoactive compounds. The authors argue that naturalistic large-cohort designs remain valuable for examining consistency of effects across demographic and clinical subgroups, even if they do not fully isolate direct pharmacological effects. Regarding cognitive and psychomotor outcomes, the authors report mixed evidence: no effects on spatial memory or processing speed, but improved finger tap performance among microdosers, particularly in older participants combining psilocybin with HE and B3. They caution that these stacking-related psychomotor findings are novel, based on relatively small subgroups, and may be anomalous; the study lacked sufficient numbers to disentangle the effects of B3 alone versus the full combination, and the age cut-off at 55 was chosen for pragmatic power reasons. Consequently, the authors call for replication before drawing clinical implications. The authors list additional limitations: observational and exploratory design, potential response bias from self-selection and recruitment through pro-psychedelic venues, restriction to Apple iOS users, lack of assessment of dose and dosing practices, and no systematic measurement of adverse effects or interactions with common antidepressants or anxiolytics. They recommend future research with more systematic recruitment, randomised and placebo-controlled designs where feasible, and studies that assess dosing, potency, adverse effects and interactions to better define safety, efficacy and optimal practices for microdosing.
Mixed linear effects models were generated across 8 outcomes: DASS depression, DASS anxiety, DASS stress, PANAS positive, PANAS negative, finger tap test number of taps, spatial span score, and PASAT score. Multilevel modelling was selected for analysis for its ability to simultaneously test betweenand within-group differences, incorporate unequally spaced observations among participants, as was common in the present study, and for its robustness to Type I error inflation resulting from multiple testing. All models included the continuous effect of Time (days since baseline response) and the dichotomous microdose group factor (non-microdosers coded as 0, microdosers coded as 1). To build parsimonious models and maintain adequately sized sub-groups, only one additional moderator was included in the models. Age was examined as the moderator for tests of cognitive functioning and mood, whereas given its relevance to the DASS domains of depression, anxiety and stress, the presence of mental health concerns was examined instead of age as the moderator in the three models that examined DASS scores. Specifically, Age was entered as a dichotomous betweenperson variable in models with PANAS; finger tap, PASAT and spatial span tests, and Mental Health Concerns was included in models with DASS domains. Models were built such that variables were retained if they predicted model outcome or were a constituent of a higher level significant interaction. For outcomes where a Microdose*Time interaction was identified, full factorial models were built including the three-way interaction of Microdose*Time*Gender, and either Microdose*Time*Age or Microdose*Time*Mental Health Concerns and all lower level main and two-way interaction effects. Supplementary analyses removed outlier responses that exceeded two standard deviations from the mean of its respective group. A second set of supplementary analyses excluded participants who reported microdosing prior to study initiation to control for potential carry over effects associated with microdosing history. Specifically, participants who reported an active microdosing practice at the baseline assessment were removed; thus we compared microdosers who initiated their practice subsequent to baseline and follow-up assessment to those who did not microdose during this period. To assess stacking, we followed up these analyses with up to three sets of supplementary analyses in the microdoser group. These supplementary analyses were limited to outcomes that evinced a Microdose*Time effect in order to prevent inflation of Type I error due to multiple testing. In the first of these analyses, Psilocybin + HE microdosers were compared to Psilocybin only microdosers. A second set of analyses compared Psilocybin + HE + B3 microdosers to Psilocybin only microdosers. As in the primary analyses, we also examined moderating effects of either Age or Mental Health Concerns. In cases where either of these two supplemental analyses noted significant two-or three-way interaction effects, they were followed with a final supplemental analysis that compared Psilocybin + HE to Psilocybin + HE + B3 microdosers. Chi-squared analyses assessed subgroups for equivalency across age, past-month microdose days, and microdose dosage; differences in these factors were controlled for by randomly trimming participants from the subgroup that was disproportionately). These effects remained consistent following the removal of 124, 82, and 75 outliers within Depression, Anxiety, and Stress domains respectively for scores exceeding 2 standard deviations from the mean (all Microdose*time F > 7.99 p < 0.01), and in parallel analyses restricted to the 594 participants who did not report microdosing prior to baseline (all Microdose*time F > 4.17, p < 0.05). We identified a Microdose*Gender*Time interaction such that the effect of microdosing over time was found to be moderated by gender in DASS depression. Specifically, microdose-related reductions in depression were stronger among females than among males (F (1, 1016) = 6.61, b = 0.17 The interactions between Mental Health Concerns and Microdose groups were not significant for any of the domains (all Microdose*Mental Health Concerns*Time Fs < 1.16; p > 0.10), indicating that the main effects of microdosing were consistent across respondents with and without mental health conditions. Among microdosers with Mental Health Concerns, scores on depression changed from 18.85 (12.03) at baseline to 11.73 (9.85) at Month-1; for anxiety, 11.04 (8.48) at baseline to 7.46 (6.68) at Month-1; and for stress, 19.93 (9.71) at baseline to 13.91 (9.02) at Month-1. Among respondents without a history of Mental Health Concerns, scores on depression changed from 10.40 (9.78) at baseline to 6.65 (7.60) at Month-1; for anxiety, 6.53 (6.50) at baseline to 4.81 (5.57) at Month-1; and for stress, 13.96 (9.12) at baseline to 9.78 (7.50) at Month-1. Supplementary analyses compared stacking conditions on changes in DASS depression, anxiety and stress scores from baseline to month-1. No differences between Psilocybin Only Microdosers and Psilocybin + HE Microdosers (all F < 0.70; p > 0.10) were noted. Likewise, no differences between Psilocybin Only Microdosers and Psilocybin + HE + B3 Microdosers were identified (all F < 0.77; p > 0.10). positive and negative mood respectively for scores that exceeded two standard deviations above or below the mean (all Microdose*time F > 26.32; p < 0.01), and among the 479 participants who were microdosing at the time of study initiation (all Microdose*time F > 22.05; p < 0.01). Additionally, moderator analyses indicated that these effects remained stable across gender (all Microdose*Gender*Time F < 1.94; p > 0.05).
The interaction between age, microdose status and time was not significant for either positive mood (F (1, 1058) = 0.21, b = -0.05, p = 0.65) or negative mood (F (1, 1059) = 1.38, b = 0.13 p = 0.24), indicating equivalence of mood effects across age. Follow-up analyses did not identify significant differences in changes in either positive or negative mood over time between Psilocybin Only Microdosers and either the Psilocybin + HE microdosers (all F < 0.52, p > 0.47) or the Psilocybin + HE + B3 microdosers (all F < 2.44, p > 0.12). Psychomotor performance and cognition. Analyses of the finger tap test identified a main effect for microdosing, such that microdosers demonstrated a more positive change in performance than non-microdosers (F (1, 886) = 9.09, b = -0.24, p = 0.03; Table). Supplementary analyses did not reveal a significant 3-way interaction across Microdose, Gender and Time, indicating that microdosing effects were consistent across Gender (F = 0.26, b = 0.94, p = 0.61). The effect of microdosing on tap score over time was robust to the removal of 16 outlier responses with scores 2 standard deviations from the mean (Microdose*Time F = 7.23, b = -0.21, p = 0.07), and treatment effects remained consistent when the study sample was limited to the 515 participants that were not microdosing at baseline (Microdose*Time F = 5.07, b = 0.22, p = 0.03). Finally, the interaction between Microdose* Time*Age was not significant (F = 3.41, b = 0.43, p = 0.06), indicating that the effect of microdosing was consistent across age. Analyses of stacking among microdosers (Fig.) found no interaction of Psilocybin only versus psilocybin + HE*Time, suggesting that the addition of HE did not impact the effect of psilocybin on finger tap (F (1, 524) = 0.284, b = 0.12, p = 0.67). In contrast, the Psilocybin only vs psilocybin + HE + B3*Time interaction indicated relatively greater improvement in tap scores with the addition of both HE and B3 to psilocybin (F (1, 732) = 3.93, b = -0.51, p < 0.05). This finding was followed by examination of the moderating effect of age, which identified a Psilocybin only vs psilocybin + HE + B3 * Time *Age interaction (F (1, 732) = 8.4, b = 0.6, p = 0.004), which reflected that the addition of HE and B3 was impactful among older respondents but not among younger respondents. Supplementary analyses of Psilocybin + HE vs psilocybin + HE + B3 * Time revealed a trend toward significance (F (1, 427) = 3.26, b = -0.56, p = 0.07), and the three-way Psilocybin + HE vs psilocybin + HE + B3 * Time*Age interaction was identified (F (1, 427) = 6.71, b = 0.66, p = 0.01), indicating that effects were more pronounced among older respondents. Follow-up supplemental analyses indicated that these findings were robust after controlling for subgroup differences in age, microdose frequency and microdose dosage (all 3-way interaction Fs > 6.20, p < 0.05). Comparisons of microdosers to non-microdosers in change from baseline to month 1 indicated no differences for either the spatial span task (F (1, 944) = 0.24, b = -0.07, p = 0.63) or the PASAT (F (1, 775) = 0.21, b = 0.02, p = 0.65). In light of this absence of main effects, no follow-up analyses were conducted.
The findings of this study contribute to the growing literature on microdosing in several ways. First, although our study design differs substantially from the designs of the relatively few prior longitudinal studies of microdosing psychedelics-particularly with regard to attempts to account for the potential influence of expectancies-our findings of improved mood and reduced symptoms of depression, anxiety and stress are nonetheless generally similar in direction and size to the unadjusted small to medium positive effects reported in those investigations. To our knowledge, this is the largest longitudinal study to date of microdosing psilocybin and one of the few studies to engage a control group. In light of these methodological strengths, the comparability of our findings with those of prior research from diverse locations and with different methodologies suggests a relatively consistent association between microdosing and improved mental health. Notably, the subgroup of respondents who reported mental health concerns at the time of baseline assessment exhibited an average reduction in depressive symptoms that resulted in a change from moderate to mild depression following approximately 30 days of microdosing psychedelics. Considering the tremendous health costs and ubiquity of depression, as well as the sizable proportion of patients who do not respond to extant treatments, the potential for another approach to addressing this deadly disorder warrants substantial consideration. The potential that psilocybin microdosing may provide a means to improve depression and anxiety clearly points to the need for further research to more firmly establish the nature of the relationship between microdosing, mood and mental health, and the extent to which these effects are directly attributable to psilocybin. A potential contribution of future research with placebo-controlled designs would be the capacity to disaggregate the contributions of positive expectancies and placebo effects. Although our use of a non-microdosing group that was equivalent to microdosers with regard to demographics and engagement with study procedures is a clear strength, both microdosers and non-microdosers in our study were aware of their status from the onset of the study, making it impossible to rule out the contributions of greater expectancies among the microdosing versus non-microdosing group. However, in consideration of the challenges associated with conducting RCTs in the current restrictive regulatory environment and recognizing the broader challenges to effective blinding of a research drug with well-known and distinctive psychoactive effects, we encourage research to take an expansive perspective on putative placebo effects. Specifically, the clinical reconsideration and study of psychedelics presents an opportunity to reevaluate the extent to which expectancies and frank psychoactive effects might combine to influence subjective well-being in potentially meaningful ways. The impact of microdosing on tests of cognitive and psychomotor functioning was mixed and limited to psychomotor performance, with no apparent impact on spatial memory or processing speed. Moreover, the magnitude of these effects appeared to be contingent on age and on combining psilocybin with both HE and B3. This specificity for psychomotor performance and reliance on the combination of constituents warrant cautious interpretation, as the literature on microdosing and cognitive performance is scantand no prior studies have focused on the combination of psilocybin with other putatively active substances. Indeed, although our large sample allowed for a novel level of granularity in our examination of distinct practices among age-related subgroups of microdosers, these groups were nonetheless relatively small, which increases the possibility that our findings of tap test facilitation among individuals over 55 who microdose the combination of psilocybin, HE and B3 may be anomalous. In addition, due to the small number of participants taking B3 without psilocybin or HE, we lacked power to investigate the extent to which these findings were driven by the combination of psilocybin, B3 and HE, as opposed to B3 alone. Moreover, age was collected categorically and the cut-off age of 55 was selected as a convenience based on power; leaving us unable to determine the extent to which the observed effects would be maintained if other cut scores for age were used. As such, replication is required prior to an estimation of potential clinical implications. Nonetheless, should these findings prove robust across diverse samples and investigators, the present results may represent an important first step in the development of novel treatments for prevalent and refractory neurological disorders. Finally, although these findings might be best described as suggestive they nonetheless add preliminary credence to anecdotal reports of benefit from the specific combination of psilocybin, HE and B3. In addition to small samples in subgroups, observational design, and a generally exploratory approach, interpretation is further limited by potential response bias related to participant self-selection and recruitment through venues that are favorable toward psychedelic use, which may have resulted in overrepresentation in our sample by individuals who respond favorably to microdosing. Further, unavailability of an Android OS version of the application at the time of study limited participation to those with access to Apple devices. This study also did not investigate the influence of dose and dosing practices on outcomes. Future studies with designs that allow for the careful evaluation of the potency, composition and quantity of microdosed materials will be required to refine our understanding of the influence of these key factors. Likewise, adverse effects and interactions with typical antidepressants and anxiolytics were not assessed; such data will be necessary to inform our understanding of microdosing safety and acceptability. In light of these limitations, we encourage future research that employs a more systematic recruitment approach, and designs that assess optimal dosage, best practices and adverse effects associated with psychedelic microdosing.
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