Comparative Acute Effects of LSD, Psilocybin and Mescaline

Summary

LSD, psilocybin and mescaline are widely used for recreational and ethnomedical purposes. All three substances are thought to induce prototypical psychedelic effects primarily via stimulation of the 5-HT2A receptor. However, there are differences in the substances' molecular structures and receptor activation profiles which may induce differential subjective effects. To date, there are no modern studies comparing LSD, psilocybin and mescaline directly within the same clinical study and research subjects using validated psychometric tools. Therefore, the LPM-Study compares the acute effects of LSD, psilocybin, mescaline and placebo in a double-blind, placebo-controlled, 4-period cross-over design with four treatment conditions: 1) 100 μg LSD, 2) 20 mg psilocybin, 3) 300 or 500 mg mescaline, and 4) placebo.

Timeline

Start

2020-05-19

Primary completion

2022-09-02

Completion

2022-09-02

Publications

• Mueller L, Klaiber A, Ley L, Becker AM, Thomann J, Luethi D, Schmid Y, Liechti ME. Pharmacokinetics, Pharmacodynamics, and Urinary Recovery of Oral Mescaline Hydrochloride in Healthy Participants. Clin Pharmacokinet. 2025 Oct;64(10):1495-1506. doi: 10.1007/s40262-025-01544-x. Epub 2025 Jul 14.
• Ley L, Holze F, Arikci D, Becker AM, Straumann I, Klaiber A, Coviello F, Dierbach S, Thomann J, Duthaler U, Luethi D, Varghese N, Eckert A, Liechti ME. Comparative acute effects of mescaline, lysergic acid diethylamide, and psilocybin in a randomized, double-blind, placebo-controlled cross-over study in healthy participants. Neuropsychopharmacology. 2023 Oct;48(11):1659-1667. doi: 10.1038/s41386-023-01607-2. Epub 2023 May 25.

Drugs

Indications

No indication recorded.