Mescaline

Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens

This study (2016) investigated the biochemical properties of a number of novel psychoactive drugs and found that their receptor interaction profiles predict effects similar to those of classic psychedelics and MDMA.

Authors

  • Matthias Liechti

Published

European Neuropsychopharmacology
individual Study

Abstract

The present study investigated interactions between the novel psychoactive tryptamines DiPT, 4-OH-DiPT, 4-OH-MET, 5-MeO-AMT, and 5-MeO-MiPT at monoamine receptors and transporters compared with the classic hallucinogens lysergic acid diethylamide (LSD), psilocin, N,N-dimethyltryptamine (DMT), and mescaline. We investigated binding affinities at human monoamine receptors and determined functional serotonin (5-hydroxytryptamine [5-HT]) 5-HT2A and 5-HT2B receptor activation. Binding at and the inhibition of human monoamine uptake transporters and transporter-mediated monoamine release were also determined. All of the novel tryptamines interacted with 5-HT2A receptors and were partial or full 5-HT2A agonists. Binding affinity to the 5-HT2A receptor was lower for all of the tryptamines, including psilocin and DMT, compared with LSD and correlated with the reported psychoactive doses in humans. Several tryptamines, including psilocin, DMT, DiPT, 4-OH-DiPT, and 4-OH-MET, interacted with the serotonin transporter and partially the norepinephrine transporter, similar to 3,4-methylenedioxymethamphetamine but in contrast to LSD and mescaline. LSD but not the tryptamines interacted with adrenergic and dopaminergic receptors. In conclusion, the receptor interaction profiles of the tryptamines predict hallucinogenic effects that are similar to classic serotonergic hallucinogens but also MDMA-like psychoactive properties.

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Research Summary of 'Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens'

Introduction

Classic serotonergic hallucinogens comprise several chemical families, including tryptamines (e.g. psilocin, DMT), ergolines (LSD), and phenethylamines (mescaline). Rickli and colleagues note that many synthetic tryptamine derivatives have emerged as novel psychoactive substances and that small structural changes alter pharmacology and subjective effects. Prior work implicates the serotonin 5-HT2A receptor as the principal mediator of hallucinogenic effects, but modulation by other targets such as additional 5-HT receptors, monoamine transporters and trace amine-associated receptors (TAARs) is also possible. The authors highlight gaps in knowledge about the receptor and transporter interaction profiles of several recreational tryptamines, including DiPT, 4-OH-DiPT, 4-OH-MET, 5-MeO-AMT and 5-MeO-MiPT. This study aimed to characterise in vitro interactions of these novel tryptamines across human monoamine receptors and transporters and to compare them with classic hallucinogens (LSD, psilocin, DMT, mescaline). Outcomes included binding affinities (Ki), functional activation at 5-HT2A and 5-HT2B receptors (EC50 and efficacy), inhibition of the norepinephrine (NET), dopamine (DAT) and serotonin (SERT) transporters (IC50), and transporter-mediated monoamine release. MDMA was included as a comparator in transporter assays. By generating systematic, comparable data across the same assays and cell batches, the authors sought to better predict psychotropic effects and potential acute toxicities of these substances.

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Study Details

  • Study Type
    individual
  • Journal
    European Neuropsychopharmacology
  • Compound
    Mescaline
  • Author
    Matthias Liechti
  • APA Citation

    Rickli, A., Moning, O. D., Hoener, M. C., & Liechti, M. E. (2016). Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. European Neuropsychopharmacology, 26(8), 1327-1337. https://doi.org/10.1016/j.euroneuro.2016.05.001

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