Inter-individual variability in neural response to low doses of LSD
In a placebo-controlled trial of repeated low-dose LSD (N = 53), acute effects included reduced resting EEG delta/theta/alpha power and enhanced pre-attentive processing, plus blunted visual LTP after repeated dosing, and these effects depended on baseline cognitive state — stimulatory effects were largest in participants with low baseline arousal/attention while inhibitory effects were greatest in high memory performers. Decreases in delta power and enhanced pre-attentive processing persisted at 1-week follow-up, suggesting short-term neuroadaptations beyond treatment.
Authors
- Matthias Liechti
- Kim Kuypers
- Johannes Ramaekers
Published
Abstract
The repeated use of small doses of psychedelics (also referred to as “microdosing”) to facilitate benefits in mental health, cognition, and mood is a trending practice. Placebo-controlled studies however have largely failed to demonstrate strong benefits, possibly because of large inter-individual response variability. The current study tested the hypothesis that effects of low doses of LSD on arousal, attention and memory depend on an individual’s cognitive state at baseline. Healthy participants (N = 53) were randomly assigned to receive repeated doses of LSD (15 mcg) or placebo on 4 occasions divided over 2 weeks. Each treatment condition also consisted of a baseline and a 1-week follow-up visit. Neurophysiological measures of arousal (resting state EEG), pre-attentive processing (auditory oddball task), and perceptual learning and memory (visual long-term potentiation (LTP) paradigm) were assessed at baseline, dosing session 1 and 4, and follow-up. LSD produced stimulatory effects as reflected by a reduction in resting state EEG delta, theta, and alpha power, and enhanced pre-attentive processing during the acute dosing sessions. LSD also blunted the induction of LTP on dosing session 4. Stimulatory effects of LSD were strongest in individuals with low arousal and attention at baseline, while inhibitory effects were strongest in high memory performers at baseline. Decrements in delta EEG power and enhanced pre-attentive processing in the LSD treatment condition were still present during the 1-week follow-up. The current study demonstrates across three cognitive domains, that acute responses to low doses of LSD depend on the baseline state and provides some support for LSD induced neuroadaptations that sustain beyond treatment.
Research Summary of 'Inter-individual variability in neural response to low doses of LSD'
Introduction
Self-reported ‘‘microdosing’’ with psychedelics such as LSD and psilocybin to boost mood, cognition and mental health has become increasingly common, yet placebo-controlled studies have produced inconsistent results. The introduction frames several contributors to this inconsistency, including variability in dose, pharmacokinetics, genetic differences, personality and context, and highlights that baseline arousal may be an important moderator. Resting-state EEG power in low-frequency bands (delta, theta, alpha) and event-related potentials (ERPs) such as mismatch negativity (MMN) are presented as objective measures of arousal, attention and pre-attentive processing that can reveal subtle drug effects that behavioural measures might miss. Hutten and colleagues set out to test whether neurophysiological responses to repeated low doses of LSD (15 mcg) depend on individuals’ baseline cognitive state. The study targeted three domains assessed with EEG: resting-state oscillatory power (arousal), pre-attentive processing using a roving auditory oddball task (MMN, P3a), and perceptual learning/memory using a visual long-term potentiation (LTP) paradigm. Based on earlier low-dose work, the authors expected reductions in low-frequency EEG power reflecting increased arousal and hypothesised that stimulatory effects would be largest in participants with high baseline low-frequency power (interpreted as low arousal). No firm directional predictions were made for ERP measures, but baseline-dependent effects were anticipated.
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Study Details
- Study Typeindividual
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- APA Citation
Hutten, N. R. P. W., Quaedflieg, C. W. E. M., Mason, N. L., Theunissen, E. L., Liechti, M. E., Duthaler, U., Kuypers, K. P. C., Bonnelle, V., Feilding, A., & Ramaekers, J. G. (2024). Inter-individual variability in neural response to low doses of LSD. Translational Psychiatry, 14(1). https://doi.org/10.1038/s41398-024-03013-8
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