Background: Mescaline (3,4,5-trimethoxyphenethylamine), mainly found in the Peyote cactus
(Lophophora williamsii), is one of the oldest known hallucinogenic agents that influence human and
animal behavior, but its psychoactive mechanisms remain poorly understood.
Objectives: This article aims to fully review pharmacokinetics and pharmacodynamics of mescaline,
focusing on the in vivo and in vitro metabolic profile of the drug and its implications for the variability
Methods: Mescaline pharmacokinetic and pharmacodynamic aspects were searched in books and in
PubMed (U.S. National Library of Medicine) without a limiting period. Biological effects of other
compounds found in peyote were also reviewed.
Results: Although its illicit administration is less common, in comparison with cocaine and Cannabis, it
has been extensively described in adolescents and young adults, and licit consumption often occurs in
religious and therapeutic rituals practiced by the Native American Church. Its pharmacodynamic
mechanisms of action are primarily attributed to the interaction with the serotonergic 5-HT2A-C receptors,
and therefore clinical effects are similar to those elicited by other psychoactive substances, such as
lysergic acid diethylamide (LSD) and psilocybin, which include euphoria, hallucinations, depersonalization
and psychoses. Moreover, as a phenethylamine derivative, signs and symptoms are consistent
with a sympathomimetic effect. Mescaline is mainly metabolized into trimethoxyphenylacetic acid by
oxidative deamination but several minor metabolites with possible clinical and forensic repercussions
have also been reported.
Conclusion: Most reports concerning mescaline were presented in a complete absence of exposure
confirmation, since toxicological analysis is not widely available. Addiction and dependence are practically
absent and it is clear that most intoxications appear to be mild and are unlikely to produce lifethreatening
symptoms, which favors the contemporary interest in the therapeutic potential of the drugs
of the class.