Mescaline

Mescaline, also known as mescalin or mezcalin,^[13] and in chemical terms 3,4,5-trimethoxyphenethylamine, is a naturally occurring psychedelic protoalkaloid of the substituted phenethylamine class, found in cacti like peyote (Lophophora williamsii) and San Pedro (certain species of the genus Echinopsis) and known for its serotonergic hallucinogenic effects.^[6][1][8]

Mescaline is typically taken orally and used recreationally, spiritually, and medically, with psychedelic effects occurring at doses from 100 to 1,000 mg, including microdosing below 75 mg, and it can be consumed in pure form or via mescaline-containing cacti. Mescaline induces a psychedelic experience characterized by vivid visual patterns, altered perception of time and self, synesthesia, and spiritual effects, with an onset of 0.5 to 0.9 hours and a duration that increases with dose, ranging from about 6 to 14 hours. Mescaline has a high median lethal dose across species, with the human LD₅₀ estimated at approximately 880 mg/kg, making it very difficult to consume a fatal amount. Ketanserin blocks mescaline’s psychoactive effects, and while it's unclear if mescaline is metabolized by monoamine oxidase enzymes, but preliminary evidence suggests harmala alkaloids may potentiate its effects.

Mescaline primarily acts as a partial agonist at serotonin 5-HT_2A receptors, with varying affinity and efficacy across multiple serotonin, adrenergic, dopamine, histamine, muscarinic, and trace amine receptors, but shows low affinity for most non-serotonergic targets. It is a relatively hydrophilic psychedelic compound structurally related to catecholamines but acting on the serotonergic system, first synthesized in 1919, with numerous synthetic methods and potent analogues developed since. Mescaline occurs naturally in various cacti species, with concentrations varying widely, and is biosynthesized in plants from phenylalanine via catecholamine pathways likely linked to stress responses.

Mescaline-containing cacti use dates back over 6,000 years.^[6] Peyote was studied scientifically in the 19th and 20th centuries, culminating in the isolation of mescaline as its primary psychoactive compound, legal recognition of its religious use, and ongoing exploration of its therapeutic potential. Mescaline is largely illegal worldwide, though exceptions exist for religious, scientific, or ornamental use, and it has influenced many notable cultural figures through its psychoactive effects. Very few studies concerning mescaline's activity and potential therapeutic effects in people have been conducted since the early 1970s.