Depressive DisordersAnxiety DisordersSubstance Use Disorders (SUD)Healthy VolunteersMicrodosingCreativitySafety & Risk ManagementInterpersonal Functioning & Social Connectedness

The therapeutic potential of microdosing psychedelics in depression

This review of the effect of microdosing on depression found that there still isn't much evidence available, but points towards increased cognitive flexibility and decreased rumination of possible mechanism.

Authors

  • Kim Kuypers

Published

Therapeutic Advances in Psychopharmacology
meta Study

Abstract

Microdosing psychedelics is the repeated use of small doses of, for example, lysergic acid diethylamide (LSD) and psilocybin, typically for a few weeks. Despite the popular and scientific attention in recent years, and claims by users that it has therapeutic value in affective disorders like depression, little scientific knowledge is available to back this. The purpose of this review was to investigate whether there are scientific grounds to state that this practice could be helpful in the treatment of affective disorders, and safe to use repeatedly. To that end, the literature (PubMed, MedLine) was searched, looking for (controlled) experimental studies with low doses of LSD and/or psilocybin, in healthy volunteers and patient samples. After a selection process and the addition of relevant articles, 14 experimental studies entered this review. Findings show that both LSD (10-20mcg) and psilocybin (<1-3mg) have subtle (positive) effects on cognitive processes (time perception, convergent and divergent thinking) and brain regions involved in affective processes. Besides the pleasant experience, increased anxiety and a cycling pattern of depressive and euphoric mood were also found. With regard to safety, it was demonstrated that low doses are well tolerated (in healthy volunteers) and have no-to-minimal effects on physiological measures. While it is yet unclear whether psychedelic microdosing is of therapeutic value for depression, the aforementioned effects on selective processes suggest that low doses of psychedelics could play a role in depression by inducing some kind of cognitive flexibility, which might lead to decreased rumination. While previous studies were conducted mostly in small samples of healthy volunteers, future placebo-controlled clinical trials in depressed patients are required to understand the therapeutic value of microdosing psychedelics, how this differs from therapy using full psychedelic doses, and whether different psychedelics have different effect patterns. The proposed research will give new insights into the potential of future alternative psychiatric treatment forms that are fiercely needed.

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Research Summary of 'The therapeutic potential of microdosing psychedelics in depression'

Introduction

Classical psychedelics such as lysergic acid diethylamide (LSD) and psilocybin produce perceptual and subjective effects primarily via agonism at the serotonin 5-HT2A receptor. Kuypers summarises earlier controlled research showing that full psychedelic doses (for example, 100–200 mcg LSD or about 15 mg psilocybin) can increase positive mood, social behaviour and emotional empathy, and reduce recognition of negative emotional states. Alongside supervised clinical work suggesting a favourable safety profile and emerging therapeutic promise in affective and substance use disorders, anecdotal reports have popularised the repeated use of subperceptual doses — microdosing — as self-treatment for depression and related conditions. This review set out to examine whether experimental evidence supports the therapeutic potential and safety of microdosing for affective disorders. Kuypers therefore searched for controlled experimental human studies administering low doses of LSD or psilocybin and synthesised findings on psychological, cognitive and physiological effects to assess whether these effects plausibly relate to antidepressant mechanisms and whether repeated low-dose use appears safe.

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