In a double‑blind placebo‑controlled study of 34 people starting to microdose with 0.5 g dried Psilocybe cubensis, active doses produced noticeable subjective effects and reduced EEG theta power but did not improve creativity, cognition or well‑being, and showed small signs of cognitive impairment. Many reported effects were linked to participants correctly identifying their condition, indicating expectation/placebo contributes to anecdotal benefits.
The use of low sub-perceptual doses of psychedelics (“microdosing”) has gained popularity in recent years. Although anecdotal reports claim multiple benefits associated with this practice, the lack of placebo-controlled studies severely limits our knowledge of microdosing and its effects. Moreover, research conducted in standard laboratory settings could fail to capture the motivation of individuals engaged or planning to engage in microdosing protocols, thus underestimating the likelihood of positive effects on creativity and cognitive function. We recruited 34 individuals starting to microdose with psilocybin mushrooms (Psilocybe cubensis), one of the materials most frequently used for this purpose. Following a double-blind placebo-controlled experimental design, we investigated the acute and short-term effects of 0.5 g of dried mushrooms on subjective experience, behavior, creativity (divergent and convergent thinking), perception, cognition, and brain activity. The reported acute effects were significantly more intense for the active dose compared to the placebo, but only for participants who correctly identified their experimental condition. These changes were accompanied by reduced EEG power in the theta band, together with preserved levels of Lempel-Ziv broadband signal complexity. For all other measurements there was no effect of microdosing except for few small changes towards cognitive impairment. According to our findings, low doses of psilocybin mushrooms can result in noticeable subjective effects and altered EEG rhythms, but without evidence to support enhanced well-being, creativity and cognitive function. We conclude that expectation underlies at least some of the anecdotal benefits attributed to microdosing with psilocybin mushrooms.
Papers cited by this study that are also in Blossom
Ona, G., Bouso, J. C. · Neuroscience and Biobehavioral Reviews (2020)
Hutten, N. P. W., Mason, N. L., Dolder, P. C. et al. · International Journal of Neuropsychopharmacology (2019)
Polito, V., Stevenson, R. J. · PLOS ONE (2019)
Lea, T., Amada, N., Jungaberle, H. et al. · International Journal of Drug Policy (2020)
Interest in the practice of taking very low, sub-perceptual doses of psychedelics (“microdosing”) has expanded rapidly among the public and researchers. Anecdotal reports and observational studies claim improvements in mood, cognition, creativity and wellbeing, but these data are vulnerable to selection bias, expectancy effects and the lack of placebo controls. Neurobiological mechanisms remain underexplored for microdoses, although studies with full psychedelic doses show alterations in brain oscillations, connectivity and subjective experience that could in principle scale with dose. Cavanna and colleagues set out to evaluate the acute and short-term effects of a representative psilocybin mushroom microdose on subjective experience, behaviour, creativity (convergent and divergent thinking), perception, cognition and brain activity measured with EEG. To limit artificial motivation and to better reflect real-world practice, the investigators recruited people who were planning to start microdosing with their own Psilocybe cubensis material and implemented a randomized, double-blind, placebo-controlled within-subjects protocol using 0.5 g dried mushroom per dosing day versus an inert mushroom placebo.
Thirty-four healthy adult volunteers (11 female; mean age 31.26 ± 4.41 years; mean weight 74 ± 17 kg) were recruited between December 2019 and August 2020. Participants reported prior psychedelic use (mean 11 ± 14.9 lifetime experiences) and only six had substantial prior microdosing experience. All provided written informed consent and completed the protocol. The study was registered (ClinicalTrials.gov NCT05160220) and approved by a local ethics committee. A within-subjects randomised double-blind design allocated each participant to two measurement weeks separated by one week without measurements: one week corresponding to an active condition (0.5 g ground dried Psilocybe cubensis in a gel capsule) and one to placebo (0.5 g edible mushroom prepared identically). Order was randomised by a third party so that both participants and experimenters were blind to condition during data collection. Participants completed two dosing days per measurement week (Wednesday and Friday) and underwent repeated assessments across those days. Primary and secondary measures spanned subjective and objective domains. Acute subjective effects were assessed with a 21-item visual analogue scale (VAS) adapted from prior psychedelic research. Trait and state questionnaires included the Big Five Inventory, State-Trait Anxiety Inventory, Short Suggestibility Scale, PANAS, Mind Wandering Scale, Perceived Stress Scale, Tellegen Absorption Scale, Psychological Well-being Scale, Flow State Scale, Creative Personality Scale, Cognitive-Affective Empathy Test and Cognitive Flexibility Scale. Creativity was probed with convergent and divergent tasks: the Remote Associates Test (RAT), the Alternative Uses Task (AUT) and the Wallach-Kogan (WK) test. Perceptual and cognitive tasks comprised backward masking, binocular rivalry, attentional blink, Go/No-Go, Stroop and the Trail Making Test (TMT). Daily physical activity was monitored with a Fitbit Charge 4 (steps and distance). Resting-state EEG (5 min eyes open, 5 min eyes closed) and an auditory Local-Global paradigm were recorded with a 24-channel mobile system. EEG preprocessing included bandpass filtering (1–90 Hz), notch filtering, channel rejection/interpolation, epoching, ICA-based artifact removal and power spectral density estimation in standard bands (delta, theta, alpha, beta, gamma). Broadband signal complexity was estimated using a Lempel–Ziv compression metric on binarised envelopes. Event-related potentials (ERPs) for local and global auditory deviants were analysed from −200 to +1300 ms relative to stimulus onset. Chemical analysis of mushroom samples (three independent sources) was performed by LC–MS on 150 mg aliquots, yielding concentrations of psilocybin (640.2 μg/g), psilocin (950.7 μg/g), baeocystin (50.4 μg/g) and norbaeocystin (12.5 μg/g). The authors report an estimated effective psilocybin-equivalent dose of ≈0.9 mg for the preparation used, but note possible variability across sources and potential degradation during storage. Statistical comparisons between active and placebo conditions used non-parametric paired Wilcoxon signed-rank tests (or Mann–Whitney U for unpaired data), with Bonferroni correction applied when indicated. Chi-squared tests evaluated breaking of the blind. Bayesian analyses computed BF10 values (Jeffrey–Zellner–Siow prior) to quantify evidence for alternative versus null hypotheses. Results are reported both uncorrected and with correction for multiple comparisons where applicable.
Blinding: Participants correctly identified the experimental condition in 49 of 64 measurement weeks (75%). For the active weeks, 25 of 34 (73.5%) were correctly unblinded; the placebo weeks showed a similar rate (70%). Chi-squared tests indicated that participants did not break blind in the first measurement week but did so in the second week. Acute subjective effects: Total VAS scores (sum of 21 items) were significantly higher for the active dose compared to placebo on dosing days. Crucially, this overall effect was driven by participants who correctly identified their condition: the “unblinded” subset showed significantly higher VAS totals for active versus placebo (Bayes factors BF10 > 30, very strong evidence), whereas the “blinded” subset did not show robust differences (BF10 values between 1/3 and 3, interpreted as inconclusive, with only a trend on the first dosing day). Individual VAS items showed differences on measures related to imagination, dreamlike quality, spatial distortions and mind-wandering, but these did not survive Bonferroni correction for multiple comparisons; most BF10 values for sub-items were inconclusive. Questionnaires and trait scales: No significant differences emerged between active and placebo conditions on the battery of self-report scales at p < 0.05 after correction. One uncorrected finding (conscientiousness, p = 0.01) did not remain significant after Bonferroni correction. Most BF10 values were <1/3, indicating moderate evidence favouring the null hypothesis. Analyses restricted to the blinded subset generally produced inconclusive Bayes factors (between 1/3 and 3), consistent with limited sample size. Creativity tests: Convergent (RAT) and divergent (WK, AUT) creativity measures showed no significant differences between active and placebo after correction. Two metrics (AUT fluency and WK elaboration) reached p < 0.05 uncorrected but did not survive Bonferroni correction; BF10 values predominantly supported the null hypothesis (most <1/3). Perception and cognition: Across the perceptual and cognitive battery, a few uncorrected differences were observed. Visibility of the second target in the attentional blink task was reduced at 300 ms lag under psilocybin relative to placebo (p < 0.05 uncorrected). Reaction times in the Stroop task were longer with psilocybin (p < 0.05 uncorrected). Part A completion time of the TMT was increased in the active condition. These effects did not consistently survive correction for multiple comparisons and are reported as trends toward impaired performance rather than robust enhancements. EEG and ERPs: Resting-state spectral analysis revealed decreased power in the theta band (4–8 Hz) during eyes-closed recordings under the active microdose compared with placebo; this reduction survived Bonferroni correction across frequency-band comparisons (n = 4). No reliable differences were found in alpha or beta bands. Global Lempel–Ziv complexity (a measure of signal diversity/entropy) did not differ between conditions for eyes-open or eyes-closed recordings. ERP analysis of the Local-Global auditory paradigm reproduced expected larger late amplitudes for global deviants versus local deviants at central-frontal sites (e.g. AFz) but revealed no significant differences between active and placebo conditions. Physical activity: Step counts, distance travelled and activity/resting times measured by Fitbit did not differ between active and placebo weeks (uncorrected comparisons). The authors note lower activity on Wednesdays, likely attributable to protocol-related seated measurements carried out that day. Chemical characterisation: LC–MS of sample aliquots gave psilocybin 640.2 μg/g and psilocin 950.7 μg/g. The authors estimated an effective psilocybin-equivalent per dose of ≈0.9 mg but emphasised inter-source variability and the potential for potency loss during storage.
Cavanna and colleagues interpret their findings as showing that a single microdose regimen of 0.5 g dried Psilocybe cubensis (per dosing day) produced noticeable subjective effects for participants who correctly identified receiving the active material, but did not yield reliable improvements in creativity, cognition, physical activity or self-reported wellbeing. Rather than consistent benefit, some cognitive tasks showed trends toward impaired performance under the active condition. The EEG finding of reduced theta power during eyes-closed resting state aligns with previous reports of broadband power reductions at higher psychedelic doses, while the absence of increased Lempel–Ziv complexity suggests that signal entropy elevation may be a feature of full psychedelic states rather than low-dose exposure. The investigators emphasise the role of expectation and unblinding: subjective acute effects were largely limited to participants who correctly guessed the condition, and unblinding rates were high (≈75% of measurement weeks). They note that prior open-label and survey-based reports of microdosing are vulnerable to confirmation and placebo biases, and that several other double-blind studies have yielded minimal or mixed effects. Bayesian analyses suggested insufficient evidence to resolve effects in the blinded subgroup, highlighting sample size constraints for that comparison. Key limitations acknowledged by the authors include variability in alkaloid content across mushroom sources and potential loss of potency during storage, absence of dose adjustment by participant body weight, and the short-term, two-dose-per-week design that precludes assessment of cumulative or schedule-dependent effects. The sample comprised healthy volunteers, so ceiling effects could have masked benefits that might appear in clinical populations. The study also prioritised acute laboratory assessments (e.g. computer tasks, EEG) that were impractical to repeat over extended dosing periods. For future research, the authors recommend studies that test a variety of dosing schedules and durations, include patient populations with baseline impairments, measure longer-term outcomes and safety-relevant physiological endpoints (for example, effects of chronic 5-HT2B receptor stimulation on cardiovascular health). They conclude that, based on their controlled data, small amounts of dried Psilocybe cubensis can induce subjective effects and alter EEG rhythms, but do not provide conclusive evidence of enhanced wellbeing, creativity or cognitive function; expectation effects likely account for at least some of the anecdotal benefits attributed to microdosing.
The supplementary methods contain further details on recruitment, inclusion and exclusion criteria, blinding procedure, experimental setting, chemical analysis of the samples, questionnaires and tasks, as well as the motivation for their inclusion in this study.
Results from both conditions (active dose and placebo) were compared using non-parametric paired Wilcoxon signed-rank tests or Whitney-Manney U tests in the case of unpaired data. Results without correction for multiple comparisons are reported when p < 0.05, and it is also indicated whether they remain statistically significant when adopting the Bonferroni correction for multiple comparisons, explicitly stating the number of comparisons. We did not estimate statistical power since we did not know a priori what effect size could be expected for the tasks and conditions of the experiment. Chi 2 squared tests were applied to the contingency tables to determine whether participants were breaking the blind, both after the first and second measurement week. These tests were applied as implemented in Python's scipy library (). Frequentist methods were complemented using Bayesian statistics to compare the evidence in favor of the null hypothesis with that in favor of the alternative hypothesis. We computed the Bayesian statistic BF10 (Bayes factor in favor of the alternative hypothesis over the null hypothesis) using the Jeffrey-Zellner-Siow (JZS) prior as implemented in Python's pingouin library (). In the figures, all boxplots extend from the lower to upper quartile values with a line at the median; the whiskers extend from the upper/lower quartiles up to 1.5 times the interquartile range. Individual subjects are represented with single points scattered on top of the boxplots.
According to our results, 0.5 g of dried mushroom material did not present significantly positive impact on creativity (divergent and convergent thinking), cognition, physical activity levels, and selfreported measures of mental health and well-being. However, we observed a trend towards impaired performance in some cognitive tasks (i.e., attentional blink and Stroop). In contrast, the overall acute effects induced by the microdose (VAS total score) were significant, although they lacked consistency across participants. We also found decreased EEG power in the theta band under psilocybin, which is consistent with the broadband spectral power reductions reported for higher doses. Ample anecdotal evidence suggests that microdosing can improve mood, well-being, creativity, and cognition, and recent uncontrolled, open-label observational studies have provided some empirical support for these claims [. While encouraging, these studies are vulnerable to experimental biases, including confirmation bias and placebo effects. This is especially problematic in the case of microdosing, since users make up a self-selected sample with optimistic expectations about the outcome of the practice. This positivity bias, combined with the low doses and selfassessment of the drug effects via scales and questionnaires, paves the way for a strong placebo response. To date, we could identify relatively few human studies of microdosing with psychedelics following a rigorous experimental design. The first was conducted by Yanakieva and colleagues, who investigated three comparatively low doses of LSD (5, 10, and 20 µg), concluding that LSD affected the estimation of time intervals, without other significant changes in perception, mental processes and concentration. However, the researchers did not assess the preexisting motivations and expectations of the participants, and the laboratory setting of the experiment might have contributed to their suboptimal performance. Bershad and colleagues investigated an inactive placebo and three different doses of LSD (6.3, 13, and 26 µg) separated by 1-week intervals. At the highest dose, the drug increased ratings of vigor and slightly decreased positivity ratings of images with positive emotional content. Measurements of mood, cognition, and physiological responses did not show differences between conditions. Another study by the same groupshowed that a low dose of LSD (13 µg) increased amygdala seed-based connectivity with the right angular gyrus, right middle frontal gyrus, and the cerebellum, and decreased amygdala connectivity with the left and right postcentral gyrus and the superior temporal gyrus. Although this dose of LSD had weak effects on mood, they were positively correlated with the increase in amygdala-middle frontal gyrus connectivity strength. Family et al. established the safety of LSD microdosing in older volunteers, but did not report substantial positive effects. Hutten and colleagues reported dose-dependent positive effects on mood, but also anxiety and cognitive impairment; also, the same group showed that low doses of LSD can increase brain-derived neurotrophic factor blood plasma levels in healthy volunteers. Finally, both Szigeti et al.. and Van Elk et al.. combined double-blind placebocontrolled design with field measurements under natural conditions. Both found positive effects of microdosing on the primary outcome of their respective studies; however, these results could be explained by breaking of the placebo condition. In particular, Van Elk et al. found that more than 60% of the participants were breaking blind to the experimental condition, consistent with the unblinding rate found in our study (75%). Our results add to this series of double-blind placebo-controlled studies questioning the validity of anecdotal evidence for microdosing. In comparison to previous studies, most results remained negative even when the statistical analyses were restricted to measurements obtained from unblinded subjects (with the exception of the VAS total scores of acute effects, see Fig.). We note, however, that Bayesian statistics suggested insufficient sample size for the blinded group, a limitation to be overcome by future studies. Overall, few uncorrected differences were found. In the case of tasks to assess cognitive function, these differences were indicative of impaired performance, which is consistent with previous experimentsand with the observation that higher doses of serotonergic psychedelics negatively affect cognitive functions such as attention and decision making. It has also been suggested that psychedelics might facilitate visual perception by increasing the broadband of consciously perceived information. This was supported by studies of binocular rivalry, showing that two doses of psilocybin (115 μg/kg and 250 μg/kg) slowed down the rate of binocular rivalry switching and increased the proportion of reports of mixed percepts. Our study failed to replicate these findings, possibly due to the lower effective dose of psilocybin contained in the mushroom preparations. Also, we directly investigated the potential influence of microdosing on conscious perception using a backward masking paradigm (for visual perception)and the Global-Local paradigm combined with EEG for ERP analysis of global and local deviants (for auditory perception). Neither of these tasks revealed a significant effect of Psilocybe cubensis microdosing on conscious information processing. We found reduced power of EEG theta oscillations during the effects of the psilocybin microdose, heralding the larger broadband reductions observed for higher doses. However, the analysis of Lempel-Ziv complexity failed to reveal differences between conditions, suggesting that increased signal entropy could constitute a specific signature of the altered consciousness elicited by psychedelics or other non-pharmacological mechanisms. Reduced vigilance is a potential nonpharmacological mechanism underlying the observed changes in theta power. Given that theta power is increased as vigilance is reduced, the result would be consistent with participants becoming drowsy under the placebo, while maintaining alertness under the active dose. This explanation is consistent with a slightly stimulant effect of the psilocybin microdose; however, changes in vigilance would be expected to affect other frequency bands as well, and this was not observed in the data. Daily levels of physical activity constitute a proxy of the potential effects of microdosing on mood and well-being. The relationship between physical activity and mental health is wellestablishedand has been adopted as a marker of treatment efficacy for depression. Currently, the potential association between changes in physical activity levels and psychedelic use remains unexplored. While our results did not reveal an effect of microdosing on this domain, future studies could further this investigation using higher doses of serotonergic psychedelics, both in healthy and clinical populations, and conducting measurements over longer time periods. While the study of microdosing with Psilocybe cubensis mushrooms presents advantages in terms of ecological validity, it also raises problems associated with unknown or inconsistent chemical composition. We analyzed the contents of three samples pooled together, estimating an effective dose of ≈0.9 mg of psilocybin; however, this dose could have been higher or lower depending on the source of the mushrooms consumed by each participant. Also, we did not correct the effective psilocybin dose using the weight of the participants. While this adjustment might not be necessary for larger doses, its importance for microdosing remains unexplored. The amount of psilocybin/psilocin found in our samples is within the expected values for the mushrooms or truffles that are consumed in the context of microdosing; in particular, it is almost identical to the values reported by Prochazkova et al.. Nevertheless, other recent studies used truffles with higher concentrations of psilocin and psilocybin; for instance, Van Elk and colleagues investigated the effects of 0.7 g of psilocybincontaining truffles, with an estimated amount of 1.5 mg of psilocybin per dose. As acknowledged by the authors of this study, 0.7 g exceeds what is frequently considered the upper limit when microdosing with psilocybin mushrooms (note, however, that what constitutes "microdosing" is not precisely defined). It is also important to consider the possibility that our samples lost potency between the experiment and their chemical analysis. As shown by Gotvaldová and colleagues, the concentration of psilocybin can drop up to 50% during the first months of storage, which in our case would imply original concentrations similar to those reported by Van Elk and colleagues. Finally, our samples contained small amounts baeocystin and norbaeocystin; whether these compounds are psychoactive in humans is still under discussion. It is possible that the experimental design of this study was not optimal to detect some of the claimed positive effects of microdosing. We investigated the effects of two doses per week, yet microdosing is generally conducted over extended periods of time according to an ample variety of dosing schedules. By design, our study could not assess the cumulative effects of microdoses consumed over periods of several days. Instead, we decided to include time-consuming assessments which required active participation of the research team (e.g., computer-based cognitive tasks, EEG), which were too disruptive to be repeated routinely for an extended period of time, but at the same time addressed comparatively understudied potential effects of microdosing. Due to the build-up of tolerance after repeated administration of serotonergic psychedelics, we speculated that the intensity of these effects could only decrease in time; further motivating our focus on the acute effects of microdosing instead of its potential cumulative effects. This decision was also based on the variability of microdosing schedules adopted by users and represented in the current literature, which raises the concern of schedule-specific results as an obstacle to address the consistency of findings between studies. Future research should explore whether the positive effects of microdosing can be selectively enabled or facilitated by certain long-term dosing schedules. Also, this study was conducted in healthy participants, and thus the lack of significant findings could stem from ceiling effects. It remains possible that microdoses of psilocybin mushrooms exert positive effects on cognition and mental health, but only in populations of patients already suffering from impairments in these domains. In conclusion, we conducted a controlled study of microdosing in individuals who were already planning to start their own microdosing protocol. While small amounts of dried Psilocybe cubensis mushrooms reliably induced significant subjective effects, their impact in other domains was negligible or even indicative of impaired performance. Clearly, more research is needed to decide whether microdosing with psychedelics can deliver at least some of its promised positive effects. This future research should also explore the potential impact of microdosing on aspects of human physiology that could compromise its long-term safety; for instance, by addressing the potential consequences of chronic 5-HT 2B receptor stimulation on the health of the circulatory system, among other important points. Until this research is conducted, it remains impossible to ascertain that long-term microdosing is a safe practice with desirable effects, and to rule out that these effects arise as a consequence of expectation or confirmation biases.
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