Recreational Use, Analysis and Toxicity of Tryptamines

Abstract

The definition New psychoactive substances (NPS) refers to emerging drugs whose chemical structures are similar to other psychoactive compounds but not identical, representing a “legal” alternative to internationally controlled drugs. There are many categories of NPS, such as synthetic cannabinoids, synthetic cathinones, phenylethylamines, piperazines, ketamine derivatives and tryptamines. Tryptamines are naturally occurring compounds, which can derive from the amino acid tryptophan by several biosynthetic pathways: their structure is a combination of a benzene ring and a pyrrole ring, with the addition of a 2-carbon side chain. Tryptamines include serotonin and melatonin as well as other compounds known for their hallucinogenic properties, such as psilocybin in ‘Magic mushrooms’ and dimethyltryptamine (DMT) in Ayahuasca brews.Aim: To review the scientific literature regarding tryptamines and their derivatives, providing a summary of all the available information about the structure of these compounds, their effects in relationship with the routes of administration, their pharmacology and toxicity, including articles reporting cases of death related to intake of these substances.Methods: A comprehensive review of the published scientific literature was performed, using also non peer-reviewed information sources, such as books, government publications and drug user web fora.Conclusions: Information from Internet and from published scientific literature, organized in the way we proposed in this review, provides an effective tool for specialists facing the emerging NPS threat to public health and public security, including the personnel working in Emergency Department.

Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens

“…However, many synthetic tryptamine derivatives have been synthesized and are recreationally used as novel psychoactive substances (Araujo et al, 2015;EMCDDA, 2014;Helander et al, 2014;Kamour et al, 2014;Shulgin and Shulgin, 1997;Tittarelli et al, 2015;Winstock et al, 2014). Tryptamines share their core structure with the neurotransmitter serotonin (5-hydroxytryptamine ).…”

“…The psychoactive effects of hallucinogens, including those of tryptamines, are thought to be mediated mainly by the 5-HT 2A receptor (Glennon et al, 1984;Nichols, 2004;Titeler et al, 1988;Vollenweider et al, 1998) but may also be modulated by interactions with other targets, including other 5-HT receptors, monoamine transporters, and trace amineassociated receptors (Baumeister et al, 2014;Bunzow et al, 2001;Cozzi et al, 2009;Fantegrossi et al, 2006;McKenna et al, 1990;Nagai et al, 2007;Nichols, 2004;Ray, 2010). Structural alterations of tryptamines have been shown to result in different pharmacological and psychoactive profiles (Araujo et al, 2015;McKenna et al, 1990;Repke et al, 1985;Shulgin and Shulgin, 1997;Tittarelli et al, 2015;Trachsel et al, 2013). For example, compounds that have no substitutions or a 4-hydroxyl group (e.g., DMT or psilocin, respectively; Fig.…”

“…1) produce hallucinogenic effects with relative low potency in man (Repke et al, 1985). Psilocin is orally psychoactive above 5-10 mg, and DMT is active at parenteral doses of 20-100 mg (Araujo et al, 2015;Shulgin and Shulgin, 1997;Studerus et al, 2011;Tittarelli et al, 2015). In contrast, a 5-methoxy group, such as in 5-MeO-AMT ( Fig.…”

“…Different N-substitutions also influenced in vivo potency (Nichols et al, 2015;Repke et al, 1985). The pharmacological profiles of many tryptamines have been studied previously at selected targets (Blough et al, 2014;Gatch et al, 2011;McKenna et al, 1990;Nichols et al, 2015;Repke et al, 1985;Shulgin and Carter, 1980), and new and pharmacologically unknown tryptamine derivatives are constantly emerging on the illicit drug market (Araujo et al, 2015;Corkery et al, 2012;EMCDDA, 2014;Greene, 2013;Helander et al, 2014;Tittarelli et al, 2015).…”

“…The present study included recreationally used tryptamines (Araujo et al, 2015;EMCDDA, 2014;Greene, 2013;Schmidt et al, 2011;Tittarelli et al, 2015), including…”