Comparative acute effects of mescaline, lysergic acid diethylamide, and psilocybin in a randomized, double-blind, placebo-controlled cross-over study in healthy participants.
Laura Ley, Friederike Holze, Denis Arikci, Anna M Becker, Isabelle Straumann, Aaron Klaiber, Fabio Coviello, Sophie Dierbach, Jan Thomann, Urs Duthaler, Dino Luethi, Nimmy Varghese, Anne Eckert, Matthias E. Liechti
Neuropsychopharmacology October 1, 2023 DOI: 10.1038/s41386-023-01607-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, double-blind, placebo-controlled, cross-over Qualitative Peer reviewed |
|---|---|
| Sample size | 32 |
| Population | Healthy participants |
| Interventions | Mescaline Lysergic acid diethylamide (LSD) Psilocybin |
| Dose | 300 mg or 500 mg mescaline, 100 µg LSD, 20 mg psilocybin |
| Topics | LSD Mescaline Psilocybin |
| Keywords | Psychedelics Hallucinogens Comparative drug research Pharmacology |
| Citations | 127 |
| Registration | NCT04227756 |
| Key points | At psychoactive-equivalent doses, mescaline, LSD, and psilocybin induce comparable subjective effects, with no qualitative differences in altered states of consciousness. |
Abstract
Mescaline, lysergic acid diethylamide (LSD), and psilocybin are classic serotonergic psychedelics. A valid, direct comparison of the effects of these substances is lacking. The main goal of the present study was to investigate potential pharmacological, physiological and phenomenological differences at psychoactive-equivalent doses of mescaline, LSD, and psilocybin. The present study used a randomized, double-blind, placebo-controlled, cross-over design to compare the acute subjective effects, autonomic effects, and pharmacokinetics of typically used, moderate to high doses of mescaline (300 and 500 mg), LSD (100 µg), and psilocybin (20 mg) in 32 healthy participants. A mescaline dose of 300 mg was used in the first 16 participants and 500 mg was used in the subsequent 16 participants. Acute subjective effects of 500 mg mescaline, LSD, and psilocybin were comparable across various psychometric scales. Autonomic effects of 500 mg mescaline, LSD, and psilocybin were moderate, with psilocybin causing a higher increase in diastolic blood pressure compared with LSD, and LSD showing a trend toward an increase in heart rate compared with psilocybin. The tolerability of mescaline, LSD, and psilocybin was comparable, with mescaline at both doses inducing slightly more subacute adverse effects (12-24 h) than LSD and psilocybin. Clear distinctions were seen in the duration of action between the three substances. Mescaline had the longest effect duration (mean: 11.1 h), followed by LSD (mean: 8.2 h), and psilocybin (mean: 4.9 h). Plasma elimination half-lives of mescaline and LSD were similar (approximately 3.5 h). The longer effect duration of mescaline compared with LSD was due to the longer time to reach maximal plasma concentrations and related peak effects. Mescaline and LSD, but not psilocybin, enhanced circulating oxytocin. None of the substances altered plasma brain-derived neurotrophic factor concentrations. In conclusion, the present study found no evidence of qualitative differences in altered states of consciousness that were induced by equally strong doses of mescaline, LSD, and psilocybin. The results indicate that any differences in the pharmacological profiles of mescaline, LSD, and psilocybin do not translate into relevant differences in the subjective experience. ClinicalTrials.gov identifier: NCT04227756.
Comparable studies
Other randomized controlled trials on mescaline, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| DOM (STP), a New Hallucinogenic Drug, and DOET: Effects in Normal Subjects Normal subjects | 1968 | Double-blind study | |
| Prepulse inhibition of the startle reflex and its attentional modulation in the human S-ketamine and N,N-dimethyltryptamine (DMT) models of psychosis Healthy volunteers | 2007 | Double-blind crossover study | n = 15 |
| Frenquel, a Blocking Agent Against Experimental LSD‐25 and Mescaline Psychosis Patients with ALS and pseudobulbar affect | 1955 | Randomized controlled trial | n = 140 |
| Assessment of the Acute Effects of 2C‐B vs. Psilocybin on Subjective Experience, Mood, and Cognition Healthy psychedelic-experienced participants | 2023 | Within-subjects, double-blind, placebo-controlled study | n = 22 |
| Acute dose-dependent effects of mescaline in a double-blind placebo-controlled study in healthy subjects. Healthy subjects (8 women) | 2024 | Randomized, double-blind, placebo-controlled, crossover design | n = 16 |
Citations in the library
Cited by 117
- Cardiovascular safety of psychedelic medicine: current status and future directions Pharmacological Reports October 24, 2023
- In vitro and in vivo metabolism of psilocybin’s active metabolite psilocin Frontiers in Pharmacology April 29, 2024
- Serotonergic Psychedelics: A Comparative Review of Efficacy, Safety, Pharmacokinetics, and Binding Profile Biological Psychiatry: Cognitive Neuroscience and Neuroimaging February 1, 2024
- Safety and risk assessment of psychedelic psychotherapy: A meta-analysis and systematic review. Psychiatry Research May 1, 2024
- The risk of chronic psychedelic and MDMA microdosing for valvular heart disease Journal of Psychopharmacology August 12, 2023
and 112 more in the library
Cites 39
- 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
- Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
- 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
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
and 34 more in the library