Pharmacological and non-pharmacological predictors of the LSD experience in healthy participants.
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
Translational Psychiatry September 4, 2024 DOI: 10.1038/s41398-024-03074-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Analysis of nine double-blind, placebo-controlled, cross-over studies Peer reviewed |
|---|---|
| Sample size | 213 |
| Population | Healthy human subjects |
| Intervention | LSD |
| Dose | 25-200 µg |
| Topics | LSD |
| Keywords | Personality psychology Psychopharmacology Mental states Psychedelics |
| Citations | 15 |
| Key points | LSD dose, pre-drug mood states, openness to experiences, and prior hallucinogen use significantly predict subjective and autonomic responses to LSD, while sex and body weight do not. |
Abstract
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.
Comparable studies
Other randomized controlled trials on LSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases Patients with anxiety associated with life-threatening diseases | 2014 | Randomized controlled trial | n = 12 |
| Dose-Response Study of N,N-Dimethyltryptamine in Humans Experienced hallucinogen users | 1994 | Double-blind, saline placebo-controlled, randomized study | n = 12 |
| Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects Healthy subjects (8 women, 8 men) | 2014 | Double-blind, randomized, placebo-controlled, crossover study | n = 16 |
| Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor Healthy human participants | 2018 | Double-blind, randomized, counterbalanced, cross-over study | n = 24 |
| LSD-induced entropic brain activity predicts subsequent personality change. Healthy adults | 2016 | Balanced-order, placebo-controlled study | n = 19 |
Citations in the library
Cited by 19
- The intensity of the psychedelic experience is reliably associated with clinical improvements: A systematic review and meta-analysis. Neuroscience & Biobehavioral Reviews May 1, 2025
- Implementing psychedelic-assisted therapy: History and characteristics of the Swiss limited medical use program Neuroscience Applied 2025
- Acute Effects and Pharmacokinetics of LSD after Paroxetine or Placebo Pre‐Administration in a Randomized, Double‐Blind, Cross‐Over Phase I Trial Clinical Pharmacology & Therapeutics February 28, 2025
- Acute dose-dependent effects and self-guided titration of continuous N,N-dimethyltryptamine infusions in a double-blind placebo-controlled study in healthy participants Neuropsychopharmacology December 19, 2024
- Psychedelic-like effects induced by 2,5-dimethoxy-4-iodoamphetamine, lysergic acid diethylamide, and psilocybin in male and female C57BL/6J mice. Psychopharmacology May 17, 2025
and 14 more in the library
Cites 64
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
and 59 more in the library