Microevidence for microdosing with psilocybin mushrooms: a double-blind placebo-controlled study of subjective effects, behavior, creativity, perception, cognition, and brain activity

This double-blind placebo-controlled preprint study (n=34) assessed the effects of microdosing psilocybin (0.5g dried mushrooms, about 0.9mg psilocybin) on subjective experience, behaviour, creativity, perception, cognition, and brain activity. Participants received two doses (psilocybin/placebo) which were administered separately, one week apart. Subjective effects were more intense for the active dose, while null effects or a trend towards cognitive impairment was observed. Expectation effects may be, in part, responsible for the anecdotal benefits of microdosing.

Abstract

“The use of low sub-hallucinogenic 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 limits our knowledge of microdosing and its effects. Moreover, research conducted in laboratory settings might fail to capture the motivation of individuals engaged in microdosing protocols. We recruited 34 individuals planning to microdose with psilocybin mushrooms (Psilocybe cubensis), one of the materials most frequently used for this purpose. Following a double-blind placebo-controlled design, we investigated the effects of 0.5 g dried mushrooms on subjective experience, behavior, creativity, perception, cognition, and brain activity. The reported acute effects were significantly more intense for the active dose compared to the placebo, which could be explained by unblinding. For the other measurements, we observed either null effects or a trend towards cognitive impairment and, in the case of EEG, towards reduced theta band spectral power. Our findings support the possibility that expectation effects underlie at least some of the anecdotal benefits attributed to microdosing with psilocybin mushrooms.”

Authors: Federico Cavanna, Stephanie Muller, Laura A. de la Fuente, Federico Zamberlan, Matias Palmucci, Lucie Janeckova, Martin Kuchar, Carla Pallavicini & Enzo R. Tagliazucchi

Notes

The practice of microdosing, the use of sub-hallucinogenic doses of psychedelics, is currently garnering significant attention in the psychedelic community in wake of some recent publications. While we have become all too familiar with overwhelmingly positive anecdotal reports from self-reported microdosers in the media, survey studies and beyond, the exact science leading to these perceived benefits remains open to debate. Much of this debate stems from the lack of appropriately designed clinical trials as well as some important parameters being overlooked in the reporting of results.

The present study sought to explore the effects of microdosing 0.5g of dried Psilocybe cubensis mushrooms (roughly 0.9mg of psilocin, or 1/25th of a high dose) in 34 volunteers who were already planning to start their own microdosing protocol. The trial assessed these effects across a number of different aspects of human behaviour, cognition, perception, and convergent/divergent thinking. Importantly, the trial was designed in a double-blind placebo-controlled fashion, the gold standard in modern clinical research. Moreover, the effects of microdosing on measures of personality, anxiety, mood, cognitive flexibility, amongst a host of other measures were assessed.

In the trial, participants received two doses, one of the dried psychoactive mushrooms and the other dose being the placebo, which in this case was 0.5g of dried non-psychoactive edible mushrooms. On the first dosing day (Wednesday week 1), participants were instructed to randomly select one of two envelopes containing either the active or placebo dose. The unselected envelope was left for the following session one week later (Friday week 2). A number of different measurements were taken on different days of the two-week-long trial period. Participants completed self-report scales prior to each session in order to assess psychological traits and expectations as well as completing tasks and activities following dosing days. Electroencephalography (EEG) recordings were used to investigate brain function.

The main findings:

  • The overall acute effects induced by the microdose (measured using the Visual Analog Scale) reached significance, however, these findings were not consistent across participants i.e results were subjective in nature
  • Reported acute effects were significantly higher for the active dose which the researchers attributed to unblinding
  • A trend toward cognitive impairment was observed in some cognitive tasks but overall, microdosing did not significantly impact any of the measured domains
  • EEG results showed that the active dose decreased the theta band spectra power, which is consistent with the findings in studies using higher doses of psilocybin

The present paper adds to the somewhat scarce literature on rigorously designed microdosing trials. Although significant subjective effects were observed in some participants, most were effects were negligible and across some of the measured domains, even indicative of impaired performance.

Furthermore, the findings of this study support the idea that expectancy plays a role in the anecdotal benefits of microdosing. Given that people tend to microdose for periods much longer than two weeks, future research should explore the effects of microdosing over a longer time period using a study design similar to the research at hand.

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