Dark Classics in Chemical Neuroscience: Mescaline.

Archeological studies in the United States, Mexico, and Peru suggest that mescaline, as a cactus constituent, has been used for more than 6000 years. Although it is a widespread cactus alkaloid, it is present in high concentrations in few species, notably the North American peyote ( Lophophora williamsii) and the South American wachuma ( Trichocereus pachanoi, T. peruvianus, and T. bridgesii). Spanish 16th century chroniclers considered these cacti "diabolic", leading to their prohibition, but their use persisted to our days and has been spreading for the last 150 years. In the late 1800s, peyote attracted scientific attention; mescaline was isolated, and its role in the psychedelic effects of peyote tops or "mescal buttons" was demonstrated. Its structure was established by synthesis in 1929, and alternative routes were developed, providing larger amounts for pharmacological and biosynthetic research. Although its effects are attributed mainly to its action as a 5-HT2A serotonin receptor agonist, mescaline binds in a similar concentration range to 5-HT1A and α2A receptors. It is largely excreted unchanged in human urine, and its metabolic products are apparently unrelated to its psychedelic properties. Its low potency is probably responsible for its relative neglect by recreational substance users, as the successful search for structure-activity relationships in the hallucinogen field focused largely on finding more potent analogues. Renewed interest in the possible therapeutic applications of psychedelic drugs may hopefully lead to novel insights regarding the commonalities and differences between the actions of individual classic hallucinogens.

Charcot, Mitchell and Lees: neurology free thinkers and their experiences of psychoactive drugs.

Three world-famous neurologists, Charcot and Mitchell, in the 19th century, and Lees, in this century, all of whom had great scientific curiosity, experimented with the psychoactive drugs hashish, mescal and yagé, respectively, in an attempt to increase their knowledge of neurological diseases and how the brain works.

Charcot, Mitchell and Lees: neurology free thinkers and their experiences of psychoactive drugs / Charcot, Mitchell e Lees: livres-pensadores da neurologia e suas experiências com drogas psico-ativas

ABSTRACT Three world-famous neurologists, Charcot and Mitchell, in the 19th century, and Lees, in this century, all of whom had great scientific curiosity, experimented with the psychoactive drugs hashish, mescal and yagé, respectively, in an attempt to increase their knowledge of neurological diseases and how the brain works.

RESUMO Três mundialmente famosos neurologistas, Charcot e Mitchell, no século XIX, e Lees neste século, tiveram eles mesmos, experiências com drogas psico-ativas, com haxixe, mescalina e yagé, respectivamente, demonstrando a sua intensa curiosidade científica, na tentativa de aprimorar o seu conhecimento da função cerebral e das doenças neurológicas.

History, rationale and potential of human experimental hallucinogenic drug research in psychiatry.

Systematic scientific interest in psychedelic substances has a tradition of about 100 years. Numerous human experimental studies have confirmed the existence of a common nucleus of experiences in hallucinogen-induced states and the acute stages of schizophrenic psychoses. However, the degree of resemblance between endogenous and drug-induced psychotic states has been an issue of controversial debate. After the scheduling of psychedelics in the 1960s, human research became highly restricted worldwide and scientific interest in this field faded. The debate about the appropriateness of the psychedelic state as a model for endogenous psychosis therefore seemed to have little practical relevance. Currently there is a revival of scientific interest in human experimental psychedelic research. Consequently, the appropriateness of hallucinogen-induced states as models for psychosis needs to be reappraised. The arguments for and against are summarized in this paper. In conclusion, the drug-induced model psychosis is shown to be a useful model for acute psychotic stages, but not for the nosological entity schizophrenia.

Second thoughts on psychedelic drugs.

Psychedelic drugs are making a comeback. Proponents of psychedelics point to the widespread medical experimentation with mescaline and lysergic acid diethylamide-125 (LSD) in the 1950s as proof of their safety and efficacy. However, a review of the private and published writings of Sidney Cohen, MD, who conducted the first study of the safety of psychedelics, reveals that serious medical concerns about psychedelics arose before the public backlash against the drugs in the 1960s. The story of psychedelic research is a reminder of the inevitable complications involved in testing drugs on human subjects.