Role of the Serotonin 5-HT2A Receptor in Mescaline-induced Altered States of Consciousness

The present MDR-study will characterize the subjective effects of different doses of mescaline using modern psychometric instruments and examine the contribution of the 5-HT2A receptor in the mescaline-induced alterations of consciousness.

Topic Healthy Subjects
Compound Placebo Mescaline
Country Switzerland
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Trial Details



Trial Number

Sponsors & Collaborators

University of Basel
The University of Basel Department of Biomedicine hosts the Liechti Lab research group, headed by Matthias Liechti.

MindMed
MindMed is one of the largest companies in the psychedelics space and is developing various psychedelics for mental health disorders.

Heffter Research Institute
The Heffter Research Institute has been advancing psychedelics (psilocybin) as medicines since 1993.

Papers

Acute dose-dependent effects of mescaline in a double-blind placebo-controlled study in healthy subjects
This randomized, double-blind, placebo-controlled, crossover study (n=16) investigates the dose-dependent acute effects, pharmacokinetics, and mechanism of action of mescaline (100-800mg; 5x) in healthy subjects. It finds that mescaline induces dose-dependent subjective effects, increases blood pressure and heart rate, and has dose-proportional pharmacokinetics, with effects primarily mediated by 5-HT2A receptors as demonstrated by ketanserin co-administration.

Pharmacokinetics, Pharmacodynamics, and Urinary Recovery of Oral Mescaline Hydrochloride in Healthy Participants
This pharmacokinetic-pharmacodynamic analysis (n=46) of two Phase I trials of oral mescaline (100-800 mg) showed dose-proportional exposure with peak concentrations at 2 hours, a half-life of 3.5 hours, onset of effects around 1 hour post-dose, maximum effect intensity and duration ranging from 13% and 2.8 hours (100 mg) to 89% and 15 hours (800 mg), with 53% urinary excretion unchanged and 31% as the main metabolite, indicating at least 53% oral bioavailability.

Safety pharmacology of acute mescaline administration in healthy participants
This pooled analysis of two RCTs (n=48) investigates the safety of mescaline in single oral doses of 100–800 mg (96 administrations). Positive subjective effects increased dose-dependently, while autonomic effects were moderate. Adverse effects, including nausea (dose-limiting), were recorded, but no significant issues with liver/kidney function or blood cell counts occurred. "Flashbacks" were reported in 2% of administrations. Mescaline doses up to 800 mg were deemed safe in a controlled clinical setting for healthy participants.

Data attribution

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