Inter-individual variability in neural response to low doses of LSD.
Nadia R. P. W. Hutten, Conny W E M Quaedflieg, Natasha L. Mason, Eef L. Theunissen, Matthias E. Liechti, Urs Duthaler, Kim P. C. Kuypers, Valerie Bonnelle, Amanda Feilding, Johannes G. Ramaekers
Translational Psychiatry July 15, 2024 DOI: 10.1038/s41398-024-03013-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Peer reviewed |
|---|---|
| Sample size | 53 |
| Population | Healthy participants |
| Intervention | LSD |
| Dose | 15 mcg |
| Duration | 2-week treatment period with 4 dosing sessions, plus baseline and 1-week follow-up visits |
| Topics | Microdosing LSD |
| Keywords | Cognitive enhancement Psychedelics Mental health |
| Citations | 16 |
| Key findings | Acute responses to low doses of LSD depend on an individual's baseline cognitive state, with stimulatory effects strongest in those with low arousal and attention and inhibitory effects strongest in high memory performers. |
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.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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Acute responses to low doses of LSD (15 mcg) depended on baseline cognitive state, with stimulatory effects strongest in those with low arousal and attention and inhibitory effects strongest in high memory performers.
Synthesized
Comparable studies
Other randomized controlled trials on LSD and microdosing, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Preliminary Report on the Effects of a Low Dose of LSD on Resting-State Amygdala Functional Connectivity. Healthy young adults, 18 to 35 years old | 2019 | Randomized controlled trial | n = 20 |
| Acute Mood-Elevating Properties of Microdosed Lysergic Acid Diethylamide in Healthy Volunteers: A Home-Administered Randomized Controlled Trial. Healthy male volunteers | 2023 | Randomized controlled trial | n = 80 |
| Low doses of lysergic acid diethylamide (LSD) increase reward-related brain activity. Healthy adults | 2023 | Within-subject, double-blind, placebo-controlled experiment | n = 18 |
| Greater subjective effects of a low dose of LSD in participants with depressed mood. Adults with mild depressed mood (scoring high or low on the Beck Depression-II inventory) | 2024 | Randomized controlled trial | n = 39 |
| LSD increases sleep duration the night after microdosing. Healthy adult male volunteers | 2024 | Randomized controlled trial | n = 80 |