Pharmacokinetics, Pharmacodynamics, and Urinary Recovery of Oral Mescaline Hydrochloride in Healthy Participants.
Lorenz Mueller, Aaron Klaiber, Laura Ley, Anna M Becker, Jan Thomann, Dino Luethi, Yasmin Schmid, Matthias E. Liechti
Clinical Pharmacokinetics July 14, 2025 DOI: 10.1007/s40262-025-01544-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Clinical trial (phase I) Peer reviewed |
|---|---|
| Sample size | 49 |
| Population | Healthy human participants |
| Intervention | Mescaline hydrochloride |
| Dose | 100-800 mg |
| Duration | 24-30 h urine collection |
| Topics | Mescaline |
| Keywords | Compound Substance Pharmacokinetics Drug processing Absorption Excretion Oral availability Bioavailability Drug journey Drug levels Concentration Pharmacodynamics Drug effects Psychedelic effects Subjective effects Dose-response Dose-dependent impact Peak effects Drug impact Clinical study Human study Drug research Scientific investigation Drug analysis Human trials |
| Citations | 4 |
| Registration | NCT04227756 NCT04849013 |
| Key findings | Mescaline exhibits dose-proportional pharmacokinetics with an oral bioavailability of at least 53%, and its subjective effects increase in intensity and duration with dose. |
Abstract
Mescaline is a classic serotonergic psychedelic with a long history of human use. The present study analyzed the pharmacokinetics, pharmacokinetic-pharmacodynamic relationship, and urinary recovery of oral mescaline hydrochloride. Data from 105 single-dose administrations (100-800 mg) in 49 participants from two phase I trials were analyzed with compartmental pharmacokinetics and pharmacokinetic-pharmacodynamic modeling. A one-compartment model with first-order absorption, elimination, and a lag time was used to describe mescaline plasma concentrations. Acute subjective effects, assessed by visual analog scales (range 0-100%), were modeled using a sigmoid Emax model linked to plasma concentrations via a first-order rate constant (ke0). Mescaline showed dose-proportional increases in total exposure and maximal concentrations, with a peak concentration reached within 2.0 h (geometric mean) and a half-life of 3.5 h across all doses. Mean model-predicted onset of "any drug effect" occurred around 1 hour post-dose. Maximum predicted effect intensity and duration increased with dose, from 13% and 2.8 h at 100 mg to 89% and 15 h at 800 mg. Over all conditions, 53% of the dose was excreted into urine unchanged, and 31% was excreted as the main metabolite 3,4,5-trimethoxyphenylacetic acid over 24-30 h. These findings provide the first detailed pharmacokinetic-pharmacodynamic characterization of mescaline in humans and indicate an oral bioavailability of at least 53%, limited by first-pass metabolism to 3,4,5-trimethoxyphenylacetic acid, followed by predominant renal elimination of both analytes. ClinicalTrials.gov identifier: NCT04227756 and NCT04849013.