This pooled analysis of nine double-blind, placebo-controlled, cross-over studies (n=213) investigates predictors of LSD effects in healthy subjects. It finds that LSD dose is the most influential predictor, with pre-drug mental states, personality traits, and previous hallucinogen experiences also significantly affecting the subjective experience.
Abstract of Pharmacological and non-pharmacological predictors of the LSD experience in healthy participants
“The pharmacodynamic effects of lysergic acid diethylamide (LSD) are diverse and different in different individuals. Effects of other psychoactive substances have been shown to be critically influenced by non-pharmacological factors such as personality traits and mood states. The aim of this study was to determine pharmacological and psychological predictors of the LSD effects in healthy human subjects. This analysis is based on nine double-blind, placebo-controlled, cross-over studies with a total of 213 healthy subjects receiving between 25–200 µg LSD. The influence of sex, age, dose, body weight, pharmacogenetic, drug experience, personality, setting, and mood before drug intake on the peak autonomic and total subjective responses to LSD was investigated using multiple linear mixed effects models and Least Absolute Shrinkage and Selection Operator regression. Results were adjusted for LSD dose and corrected for multiple testing. LSD dose emerged as the most influential predictor, exhibiting a positive correlation with most response variables. Pre-drug mental states such as “Well-Being”, “Emotional Excitability”, and “Anxiety” were also important predictor for a range of subjective effects but also heart rate and body temperature. The trait “Openness to Experiences” was positively correlated with elevated ratings in “Oceanic Boundlessness” and mystical-type effects. Previous experiences with hallucinogens have been negatively associated with the overall altered state of consciousness and particularly with “Anxious Ego Dissolution”. Acute anxiety negatively correlated with the genetically determined functionality of the Cytochrome 2D6 enzyme. In summary, besides the amount of drug consumed, non-pharmacological factors such as personal traits and current mood also significantly predicted the subjective drug experience. Sex and body weight were not significant factors in influencing the drug experience.”
Authors: Patrick Vizeli, Erich Studerus, Friederike Holze, Yasmin Schmid, Patrick C. Dolder, Laura Ley, Isabelle Straumann, Anna M. Becker, Felix Müller, Denis Arikci & Matthias E. Liechti
Summary of Pharmacological and non-pharmacological predictors of the LSD experience in healthy participants
The introduction begins by highlighting the renewed interest in the potential therapeutic applications of psychedelics, particularly for mental health conditions like depression, anxiety, and substance use disorders. The authors specifically focus on lysergic acid diethylamide (LSD), a potent psychedelic known for its profound and diverse effects on consciousness. While acknowledging the dose-dependent nature of LSD’s effects, the authors emphasise the significant role played by non-pharmacological factors, often referred to as “set” and “setting”, in shaping individual experiences.
The introduction then delves into the importance of understanding these modulating factors, especially given the increasing exploration of LSD as a potential therapeutic agent. The quality of the acute psychedelic experience, including the occurrence of mystical-type experiences, has been linked to therapeutic outcomes. Therefore, identifying the factors that contribute to a positive and insightful experience is crucial for optimising therapeutic applications.
It concludes by stating the study’s objective: to examine the influence of various predictors, both pharmacological and psychological, on the acute physiological and psychological responses to LSD in healthy individuals.
Methods and Materials
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Pharmacological and non-pharmacological predictors of the LSD experience in healthy participants
https://doi.org/10.1038/s41398-024-03074-9
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Cite this paper (APA)
Vizeli, P., Studerus, E., Holze, F., Schmid, Y., Dolder, P. C., Ley, L., ... & Liechti, M. E. (2024). Pharmacological and non-pharmacological predictors of the LSD experience in healthy participants. Translational Psychiatry, 14(1), 357.
Study details
Compounds studied
LSD
Topics studied
Healthy Subjects
Study characteristics
Meta-Analysis
Participants
213
Humans
Compound Details
The psychedelics given at which dose and how many times
LSD 25 - 200μg | 1x