Anxiety DisordersDepressive DisordersMicrodosingPsilocybin

Psilocybin microdosing does not affect emotion-related symptoms and processing: A preregistered field and lab-based study

In a preregistered double-blind, placebo-controlled within-subject crossover study, psilocybin microdosing over three weeks did not alter emotion processing, self-reported interoceptive awareness or symptoms of anxiety and depression compared with placebo. Exploratory analyses showed reductions in depression and stress in the first block and participant unblinding in the second, indicating possible expectancy or sample effects and the need for further trials in substance-naïve clinical populations.

Authors

  • Michal Kuchar
  • Michiel Van Elk

Published

Journal of Psychopharmacology
individual Study

Abstract

Background

Microdoses of psychedelics (i.e. a sub-hallucinogenic dose taken every third day) can reduce symptoms of depression, anxiety and stress according to anecdotal reports and observational studies. Research with medium to high doses of psilocybin points towards potential underlying mechanisms, including the modulation of emotion and interoceptive processing.

Aims

In this preregistered study, we investigated whether psilocybin microdoses alter self-reported interoceptive awareness and whether repeated microdosing over 3 weeks modulates emotion processing and reduces symptoms of anxiety and depression.

Methods

We used a double-blind, placebo-controlled, within-subject crossover design. Participants completed the Multidimensional Assessment of Interoceptive Awareness Questionnaire 1½ h after self-administering their second dose (or placebo), and the emotional go/no-go task and the shortened Depression Anxiety Stress Scale 1½ h after self-administering their seventh dose.

Results

Our confirmatory analyses revealed that psilocybin microdosing did not affect emotion processing or symptoms of anxiety and depression compared with placebo. Our exploratory analyses revealed that psilocybin microdosing did not affect self-reported interoceptive awareness, that symptoms of depression and stress were significantly reduced in the first block compared with baseline, that participants broke blind in the second block and that there was no effect of expectations. Further research in a substance-naïve population with clinical range anxiety and depressive symptoms is needed to substantiate the potential beneficial effects of microdosing.

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Research Summary of 'Psilocybin microdosing does not affect emotion-related symptoms and processing: A preregistered field and lab-based study'

Introduction

Microdosing — the regular ingestion of sub-hallucinogenic doses of psychedelics, typically around 5–10% of a standard dose — has been promoted anecdotally and in observational studies as improving mood and reducing anxiety. Earlier experimental work on microdosing is inconsistent: most controlled human trials found no reliable antidepressant or anxiolytic effects, some observational longitudinal studies have reported improvements without placebo controls, and animal studies have produced mixed findings. Research with standard (full) doses of psilocybin suggests possible mechanisms relevant to mood change, including altered emotion processing and changes in interoceptive awareness, but it is unclear whether these mechanisms operate at microdose levels or after repeated low-dose administration. Marschall and colleagues designed a preregistered, double-blind, placebo-controlled, within-subject crossover study to test whether repeated psilocybin microdosing over two 3-week blocks would: (1) reduce symptoms of depression and anxiety as measured by the DASS-21, (2) alter emotion processing (slower reaction times for negative facial expressions) on an emotional go/no-go task, and (3) increase interoceptive awareness on selected MAIA subscales. The study combined field-based dosing (participants prepared capsules at a microdosing workshop) with lab-based behavioural testing timed 1.5 h after dosing to capture acute effects; confirmatory hypotheses and analysis plans for the DASS-21 and emotional go/no-go task were preregistered, while MAIA and other analyses were exploratory.

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Study Details

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