Mescaline: The forgotten psychedelic

A recent 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 abuse 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.”

Highlights

Mescaline is a naturally occurring alkaloid found in cacti, including the peyote cactus (Lophophora williamsii) and San Pedro cactus (Echinopsis pachanoi).•

Mescaline is a serotonin 5HT2A/2C receptor agonist that also exerts its effects via agonist binding on dopaminergic D1/2/3 and adrenergic α1A/2A receptors.•

Mescaline may be useful to treat alcoholism and improve mental well-being in a naturalistic or religious setting.

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