Pharmacokinetics, Pharmacodynamics, and Urinary Recovery of Oral Mescaline Hydrochloride in Healthy Participants.
Clinical pharmacokinetics – July 14, 2025
Source: PubMed
Summary
Did you know mescaline's psychedelic effects can last up to 15 hours? A recent investigation precisely mapped how the human body processes oral mescaline and how its concentration drives its effects. Scientists analyzed 105 doses given to 49 healthy individuals. Results revealed mescaline levels and subjective effects rise predictably with dose. Peak effects typically emerge around two hours. Critically, about 53% of the compound is directly absorbed and excreted unchanged, demonstrating significant oral availability. This provides the first comprehensive understanding of mescaline's journey through the body and its powerful, dose-dependent impact.
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.