Depressive DisordersAnxiety DisordersObsessive-Compulsive Disorder (OCD)Eating DisordersNeuroimaging & Brain MeasuresHealthy VolunteersMicrodosingLSD

Low doses of LSD reduce broadband oscillatory power and modulate event-related potentials in healthy adults

This double-blind study (n=22) investigated the effects of microdosing LSD (13μg & 26μg) on resting-state electroencephalography (EEG) and event-related potential (ERP) in healthy adults. The study found that microdoses of LSD produced desynchronization patterns similar to those reported with higher doses of psychedelics, leading the authors to believe that microdoses of LSD may produce therapeutic effects in the absence of a full psychedelic experience.

Authors

  • Perry, C. M.
  • Malina, M.

Published

Psychopharmacology
individual Study

Abstract

Rationale

Classical psychedelics, including psilocybin and lysergic acid diethylamide (LSD), are under investigation as potential therapeutic agents in psychiatry. Whereas most studies utilize relatively high doses, there are also reports of beneficial effects of “microdosing,” or repeated use of very low doses of these drugs. The behavioural and neural effects of these low doses are not fully understood.

Objectives

To examine the effects of LSD (13 μg and 26 μg) versus placebo on resting-state electroencephalography (EEG) and event-related potential (ERP) responses in healthy adults.

Methods

Twenty-two healthy men and women, 18 to 35 years old, participated in 3 EEG sessions in which they received a placebo or LSD (13 μg and 26 μg) under double-blind conditions. During each session, participants completed drug effect and mood questionnaires at hourly intervals, and physiological measures were recorded. During the expected peak drug effect, EEG recordings were obtained, including resting-state neural oscillations in scalp electrodes over default mode network (DMN) regions and P300, N170, and P100 ERPs evoked during a visual oddball paradigm.

Results

LSD dose-dependently reduced oscillatory power across the delta, theta, alpha, beta, and gamma frequency bands during both eyes closed and eyes open resting conditions. During the oddball task, LSD dose-dependently reduced ERP amplitudes for P300 and N170 components and increased P100 latency. LSD also produced dose-related increases in a positive mood, elation, energy, and anxiety and increased heart rate and blood pressure. On a measure of altered states of consciousness, LSD dose-dependently increased Blissful State, but not other indices of perceptual or sensory effects typical of psychedelic drugs. The subjective effects of the drug were not correlated with the EEG measures.

Conclusions

Low doses of LSD produced broadband cortical desynchronization over the DMN during resting state and reduced P300 and N170 amplitudes, patterns similar to those reported with higher doses of psychedelics. Notably, these neurophysiological effects raise the possibility that very low doses of LSD may produce subtle behavioural and perhaps therapeutic effects that do not rely on the full psychedelic experience.

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Research Summary of 'Low doses of LSD reduce broadband oscillatory power and modulate event-related potentials in healthy adults'

Introduction

Research on classical psychedelics has expanded in the past decade, with clinical trials investigating relatively high doses of compounds such as psilocybin and LSD across disorders including depression, obsessive-compulsive disorder, addictions and anorexia. Parallel to these controlled trials, anecdotal and naturalistic reports of "microdosing"—regular ingestion of very low doses of LSD (around 10–15 μg)—have proliferated, with users reporting mood and cognitive benefits. Controlled laboratory work to date suggests single low doses can increase vigour, reduce attentional lapses and alter time perception, while producing few robust effects on mood or cognition; however, the neural effects of these very low doses remain poorly characterised. This study set out to characterise the acute neural signature of low doses of LSD in healthy adults, using electroencephalography (EEG). Specifically, Murray and colleagues tested whether single sublingual doses of 13 μg and 26 μg LSD, compared with placebo, would alter resting-state oscillatory power over scalp regions corresponding to default mode network (DMN) hubs and modulate event-related potentials (ERPs) evoked during a visual oddball task. The investigators also measured subjective drug effects, mood and cardiovascular responses, and explored relationships between EEG changes and subjective measures.

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Study Details

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