Dose-response relationships of LSD-induced subjective experiences in humans
This meta-analysis of studies using 5D‑ASC, 11‑ASC and MEQ30 establishes dose–response curves for LSD up to 200 μg, finding sigmoid‑like increases in subjective effects that plateau at around 100 μg. The strongest dose‑dependent effects were perceptual changes and illusory imagination, followed by positive ego‑dissolution, while anxiety and dread remained minimal, and substantial variability points to important non‑pharmacological influences.
Abstract
Lysergic acid diethylamide (LSD) is a potent classic serotonergic psychedelic, which facilitates a variety of altered states of consciousness. Here we present the first meta-analysis establishing dose-response relationship estimates of the altered states of consciousness induced by LSD. Data extracted from articles identified by a systematic literature review following PRISMA guidelines were obtained from the Altered States Database. The psychometric data comprised ratings of subjective effects from standardized and validated questionnaires: the Altered States of Consciousness Rating Scale (5D-ASC, 11-ASC) and the Mystical Experience Questionnaire (MEQ30). We performed meta-regression analyses using restricted cubic splines for data from studies with LSD doses of up to 200 μg base. Most scales revealed a sigmoid-like increase of effects, with a plateauing at around 100 μg. The most strongly modulated factors referred to changes in perception and illusory imagination, followed by positively experienced ego-dissolution, while only small effects were found for Anxiety and Dread of Ego Dissolution. The considerable variability observed in most factors and scales points to the role of non-pharmacological factors in shaping subjective experiences. The established dose-response relationships may be used as general references for future experimental and clinical research on LSD to compare observed with expected subjective effects and to elucidate phenomenological differences between psychedelics.
Research Summary of 'Dose-response relationships of LSD-induced subjective experiences in humans'
Introduction
Prugger and colleagues situate LSD within the class of classic serotonergic psychedelics, noting that these substances principally act at the 5-HT2A receptor but differ in molecular structure and broader pharmacology. Earlier research has produced extensive descriptive and clinical literature on LSD from the 1950s–1970s, followed by a research hiatus and a more recent focus on other psychedelics such as psilocybin and N,N-DMT. The authors highlight that acute psychedelic effects are temporally dynamic and that the intensity and quality of the acute experience may predict therapeutic outcomes, so characterising dose-dependent subjective effects is clinically and experimentally important. They also note that contemporary experimental doses are generally lower than many historical studies and that no prior meta-analysis has quantified dose-response relationships for LSD-induced subjective experiences using modern psychometric instruments. The present study therefore aims to estimate dose-response relationships between LSD dose (within a range of 25 µg to 200 µg) and the intensity and quality of acute subjective experiences in healthy, highly selected participants. Using psychometric data from validated questionnaires aggregated in the Altered States Database (ASDB), the investigators seek to provide reference dose-response estimates for commonly used scales measuring altered states of consciousness, to support future experimental and clinical research on low to moderate LSD dosages.
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Hirschfeld, T., Prugger, J., Majić, T., & Schmidt, T. T. (2023). Dose-response relationships of LSD-induced subjective experiences in humans. Neuropsychopharmacology, 48(11), 1602-1611. https://doi.org/10.1038/s41386-023-01588-2
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