Acute dose-dependent effects of mescaline in a double-blind placebo-controlled study in healthy subjects.
Aaron Klaiber, Yasmin Schmid, Anna M Becker, Isabelle Straumann, Livio Erne, Alen Jelusic, Jan Thomann, Dino Luethi, Matthias E. Liechti
Translational Psychiatry September 30, 2024 DOI: 10.1038/s41398-024-03116-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, double-blind, placebo-controlled, crossover design Peer reviewed |
|---|---|
| Sample size | 16 |
| Population | Healthy subjects (8 women) |
| Interventions | Mescaline Ketanserin |
| Dose | 100, 200, 400, and 800 mg mescaline; 40 mg ketanserin |
| Duration | Up to 30 h after drug administration |
| Topics | Mescaline |
| Keywords | Psychedelics Pharmacology Serotonin receptors Dose-response |
| Citations | 27 |
| Key points | Mescaline's acute subjective and autonomic effects are dose-dependent and primarily mediated by 5-HT2A receptors, with no ceiling effects in the subjective response up to 800 mg but lower tolerability at the highest doses. |
Abstract
Classic psychedelics have regained interest in research and therapy. Despite the long tradition of the human use of mescaline, modern data on its dose-dependent acute effects and pharmacokinetics are lacking. Additionally, its mechanism of action has not been investigated in humans. We used a randomized, double-blind, placebo-controlled, crossover design in 16 healthy subjects (8 women) who received placebo, mescaline (100, 200, 400, and 800 mg), and 800 mg mescaline together with the serotonin 5-hydroxytryptamine-2A (5-HT2A) receptor antagonist ketanserin (40 mg) to assess subjective effects, autonomic effects, adverse effects, and pharmacokinetics up to 30 h after drug administration. Mescaline at doses >100 mg induced dose-dependent acute subjective effects. Mescaline increased systolic and diastolic blood pressure at doses >100 mg, with no difference between doses of 200-800 mg. Heart rate increased dose-dependently. Pharmacokinetics of mescaline were dose-proportional. Maximal concentrations were reached after approximately 2 h, and the plasma elimination half-life was approximately 3.5 h. The average duration of subjective effects increased from 6.4 to 14 h with increasing doses of 100-800 mg mescaline. Nausea and emesis were frequent adverse effects at the 800 mg dose. Co-administration of ketanserin attenuated and shortened acute effects of 800 mg mescaline to become comparable to the 100 and 200 mg doses. There were no ceiling effects of the subjective response within the investigated dose range, but tolerability was lower at the highest doses. These results may assist with dose finding for future research and suggest that acute effects of mescaline are primarily mediated by 5-HT2A receptors.
Comparable studies
Other randomized controlled trials on mescaline, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Comparative acute effects of mescaline, lysergic acid diethylamide, and psilocybin in a randomized, double-blind, placebo-controlled cross-over study in healthy participants. Healthy participants | 2023 | Randomized, double-blind, placebo-controlled, cross-over | n = 32 |
| 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 |
Citations in the library
Cited by 25
- Classification schemes of altered states of consciousness. Neuroscience & Biobehavioral Reviews August 1, 2025
- Safety pharmacology of acute mescaline administration in healthy participants. British Journal of Clinical Pharmacology November 25, 2024
- Acute effects of MDMA, MDA, lysine-MDMA, and lysine-MDA in a randomized, double-blind, placebo-controlled, crossover trial in healthy participants. Neuropsychopharmacology 2026
- The 3D-ASCr scale: A revalidation of the core dimensions of the Altered States of Consciousness Rating Scale 5D(11)-ASC for psychedelic research. Journal of Psychopharmacology December 26, 2025
- Above the threshold, beyond the trip: the role of the 5-HT2A receptor in psychedelic-induced neuroplasticity and antidepressant effects Molecular Psychiatry August 23, 2025
and 20 more in the library
Cites 28
- 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
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
- Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin Journal of Psychopharmacology October 6, 2015
and 23 more in the library