The hallucinogenic world of tryptamines: an updated review.

Tryptamines are a broad class of hallucinogens that act primarily as agonists of the 5-HT2A receptor, producing profound changes in sensory perception, mood, and thought. Historically, natural tryptamines like psilocybin and DMT have been used in ritual contexts, but synthetic tryptamines such as AMT, 5-MeO-DMT, and 5-MeO-DIPT have recently emerged as recreational drugs, often sold as 'research chemicals' online. Reports of intoxication and deaths have raised international concern, though the lack of pharmacological and toxicological data hampers assessment of their public health harm. This review covers historical background, prevalence, patterns of use, legal status, chemistry, toxicokinetics, toxicodynamics, and physiological and toxicological effects in animals and humans.

Study at a glance

Abstract

In the area of psychotropic drugs, tryptamines are known to be a broad class of classical or serotonergic hallucinogens. These drugs are capable of producing profound changes in sensory perception, mood and thought in humans and act primarily as agonists of the 5-HT2A receptor. Well-known tryptamines such as psilocybin contained in Aztec sacred mushrooms and N,N-dimethyltryptamine (DMT), present in South American psychoactive beverage ayahuasca, have been restrictedly used since ancient times in sociocultural and ritual contexts. However, with the discovery of hallucinogenic properties of lysergic acid diethylamide (LSD) in mid-1900s, tryptamines began to be used recreationally among young people. More recently, new synthetically produced tryptamine hallucinogens, such as alpha-methyltryptamine (AMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT), emerged in the recreational drug market, which have been claimed as the next-generation designer drugs to replace LSD ('legal' alternatives to LSD). Tryptamine derivatives are widely accessible over the Internet through companies selling them as 'research chemicals', but can also be sold in 'headshops' and street dealers. Reports of intoxication and deaths related to the use of new tryptamines have been described over the last years, raising international concern over tryptamines. However, the lack of literature pertaining to pharmacological and toxicological properties of new tryptamine hallucinogens hampers the assessment of their actual potential harm to general public health. This review provides a comprehensive update on tryptamine hallucinogens, concerning their historical background, prevalence, patterns of use and legal status, chemistry, toxicokinetics, toxicodynamics and their physiological and toxicological effects on animals and humans.