MicrodosingPsilocybinLSDPlacebo

Is microdosing a placebo? A rapid review of low-dose LSD and psilocybin research

This review (2024) critically assesses the available evidence from dose-controlled studies investigating low doses of LSD and psilocybin. It proposes eight potential issues, such as small sample sizes, a limited number of controlled studies, and the possibility of selection bias, that challenge the claims that microdosing is predominantly a placebo effect. It suggests that it is currently inconclusive whether microdosing is merely a placebo.

Authors

  • Paul Liknaitzky
  • Vince Polito

Published

Journal of Psychopharmacology
meta Study

Abstract

Some recent research and commentary have suggested that most or all the effects reported by people who microdose psychedelics may be explained by expectations or placebo effects. In this rapid review, we aimed to evaluate the strength of evidence for a placebo explanation of the reported effects of microdosing. We conducted a PubMed search for all studies investigating psychedelic microdosing with controlled doses and a placebo comparator. We identified 19 placebo-controlled microdosing studies and summarised all positive and null findings across this literature. Risk of bias was assessed using the Cochrane risk-of-bias tool for randomised trials. The reviewed papers indicated that microdosing with LSD and psilocybin leads to changes in neurobiology, physiology, subjective experience, affect, and cognition relative to placebo. We evaluate methodological gaps and challenges in microdosing research and suggest eight reasons why current claims that microdosing is predominately a placebo are premature and possibly wrong: (1) there have been only a small number of controlled studies; (2) studies have had small sample sizes; (3) there is evidence of dose-dependent effects; (4) studies have only investigated the effects of a small number of doses; (5) the doses investigated may have been too small; (6) studies have looked only at non-clinical populations; (7) studies so far have been susceptible to selection bias; and (8) the measured impact of expectancy is small. Considering the available evidence, we conclude that it is not yet possible to determine whether microdosing is a placebo.

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Research Summary of 'Is microdosing a placebo? A rapid review of low-dose LSD and psilocybin research'

Introduction

Microdosing—the regular ingestion of sub-hallucinogenic amounts of classic serotonergic psychedelics such as LSD or psilocybin—became widely discussed from about 2015, fuelled by anecdote and media reports claiming benefits for mood, cognition and wellbeing. Early academic work was dominated by surveys, qualitative interviews and observational prospective studies; more rigorous controlled research only began to appear from 2018. Importantly, some early controlled designs that attempted to blind participants, including a notable self-blinding prospective study, found little difference between placebo and active microdoses and suggested that participants' beliefs about what they had taken strongly influenced outcomes. In response to this mixed picture, Polito and colleagues carried out a rapid review that focused specifically on microdosing studies in which the quantity of psychedelic administered was known and a placebo comparison was included. The stated aim was to synthesise the controlled-dose literature in order to evaluate the extent to which observed effects might reflect pharmacology versus placebo or expectancy effects, and to identify methodological gaps that limit causal inference in this field.

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References (33)

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