Mescaline: The forgotten psychedelic
This review (2022) explores mescaline's pharmacological and behavioural effects using preclinical and clinical research. The pharmacological mechanisms of mescaline are similar to those of other classical psychedelics i.e. binding at the 5HT2A receptor. Mescaline can improve well-being and mental health conditions, particularly alcohol use disorder.
Abstract
Introduction: Mescaline (3,4,5-trimethoxyphenethylamine) is one of the oldest hallucinogens, with evidence of use dating back 5700 years. Mescaline is a naturally occurring alkaloid found in cacti, mainly in the peyote cactus (Lophophora williamsii) and in the cacti of the Echinopsis genus. Since the prohibition of psychoactive substances in the early 70s, research on mescaline and other classical psychedelics has been limited.
Objectives: This article aims to review the pharmacology and behavioural effects of mescaline, focusing on preclinical and clinical research.
Findings: Mescaline is a serotonin 5HT2A/2C receptor agonist, with its main hallucinogenic effects being mediated via its 5HT2A receptor agonist action. It also exerts effects via agonist binding at α1A/2A noradrenaline and D1/2/3 dopamine receptors. Overall, mescaline has anxiolytic-like effects in animals and increases prosocial behaviour, locomotion, and response reactivity. In humans, mescaline can induce euphoria, hallucinations, improvements in well-being and mental health conditions, and psychotomimetic effects in a naturalistic or religious setting.
Conclusion: The pharmacological mechanisms of mescaline are similar to those of other classical psychedelics, like psilocybin and lysergic acid diethylamide (LSD). Mescaline appears to be safe to consume, with most intoxications being mild and easily treatable. Improvement in mental well-being and its ability to overcome alcoholism render mescaline potentially beneficial in clinical settings.
Research Summary of 'Mescaline: The forgotten psychedelic'
Blossom's Take
This literature review provides a good grounding for our understanding of mesacline and how it's different from other psychedelics.
Introduction
Psychedelics have a long history of ritual and therapeutic use, and classical serotonergic psychedelics are now being reconsidered for psychiatric disorders. Vamvakopoulou and colleagues note that mescaline (a naturally occurring phenylalkylamine found mainly in peyote and several Echinopsis species) is one of the oldest known hallucinogens, with archaeological evidence of use dating back thousands of years. However, research on mescaline has been limited since the international prohibition of psychedelics in the early 1970s, and clinical data are sparse relative to substances such as psilocybin, LSD and DMT. Indigenous and ceremonial use of mescaline-containing cacti has continued and is cited as a source of observational evidence about possible therapeutic benefits. This review sets out to summarise the pharmacology and behavioural effects of mescaline, encompassing preclinical receptor and animal studies, pharmacokinetics and toxicology, human physiological and psychological effects, neuroimaging work, and historical and contemporary therapeutic observations. The authors aim to collate what is known about mescaline’s mechanisms and effects and to identify gaps where modern controlled research is needed to assess clinical utility.
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Vamvakopoulou, I. A., Narine, K. A., Campbell, I., Dyck, J. R., & Nutt, D. J. (2023). Mescaline: The forgotten psychedelic. Neuropharmacology, 222, 109294. https://doi.org/10.1016/j.neuropharm.2022.109294
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Cited By (3)
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Mueller, L., Klaiber, A., Ley, L. et al. · Clinical Pharmacokinetics (2025)
Mueller, J., Mueller, M. J., Aicher, H. D. et al. · International Journal of Neuropsychopharmacology (2025)
Zafar, R., Siegel, M., Harding, R. et al. · Frontiers in Psychiatry (2023)
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