Depressive DisordersAnxiety DisordersChronic Pain

Discriminative Stimulus Effects of Substituted Tryptamines in Rats

This rat study (n=64) evaluated the hallucinogen-like effects of eight novel substituted tryptamines and characterized their potency and abuse liability according to their substituted side chains. All compounds fully substituted for the discriminative stimulus effects of 0.5 mg/kg DOM without any adverse effects, unlike other tryptamine analogs.

Authors

  • Theresa Carbonaro

Published

ACS Pharmacology and Translational Science
individual Study

Abstract

Introduction

Novel synthetic compounds have been available for decades as quasi-legal alternatives to controlled substances. The hallucinogen-like effects of eight novel substituted tryptamines were evaluated to determine their potential abuse liability.

Methods

Male Sprague-Dawley rats were trained to discriminate 2,5-dimethoxy-4-methylamphetamine (DOM, 0.5 mg/kg, i.p., 30 min) from saline. 4-Acetoxy-N,N-diethyltryptamine (4-AcO-DET), 4-hydroxy-N-methyl-N-ethyltryptamine (4-OH-MET), 4-hydroxy-N,N-diethyltryptamine (4-OH-DET), 4-acetoxy-N-methyl-N-isopropyltryptamine (4-AcO-MiPT), 4-acetoxy-N,N-dimethyltryptamine (4-AcO-DMT), 4-hydroxy-N,N-dimethyltryptamine (4-OH-DMT, psilocin), 5-methoxy-N-methyl-N-isopropyltryptamine (5-MeO-MiPT), 4-acetoxy-N,N-diisopropyltryptamine (4-AcO-DiPT), and 4-hydroxy-N,N-diisopropyltryptamine (4-OH-DiPT) were tested for their ability to substitute for the discriminative stimulus effects of DOM.

Results

All test compounds fully substituted for DOM with potencies less than or equal to that of DOM. 4-OH-MET, 4-OH-DET, 4-OH-DMT, and 4-AcO-DMT decreased response rate at doses that fully substituted.

Discussion

Because the test compounds produced DOM-like discriminative stimulus effects, they may have similar abuse liability as DOM. 4-Acetoxy substituted compounds were less potent than 4-hydroxy substituted compounds, and the N,N-diisopropyl compounds were less potent than the dimethyl, diethyl, N-methyl-N-ethyl, and N-methyl-N-isopropyl compounds.

Available with Blossom Pro

Research Summary of 'Discriminative Stimulus Effects of Substituted Tryptamines in Rats'

Introduction

Classic serotonin-mediated hallucinogens such as psilocybin have a long history of use and have recently been investigated in clinical trials for conditions including depression, anxiety related to cancer, persistent pain, and as adjuncts in substance-use cessation. At the same time, novel synthetic tryptamines continue to appear on recreational markets, many described in TiKHAL, and several have been identified as compounds of interest by the US Drug Enforcement Administration. These include a range of 4-acetoxy and 4-hydroxy substituted tryptamines and variants with different N-substituents; some have been detected in biological samples and others are readily available online. Gatch and colleagues set out to determine whether a set of eight substituted tryptamines produce hallucinogen-like discriminative stimulus effects in rats trained to discriminate the 5-HT2A-preferring hallucinogen DOM (0.5 mg/kg, i.p.) from saline. The rationale is that drug discrimination provides a useful preclinical model of subjective drug effects and can flag compounds with potential abuse liability when self-administration models are not informative for hallucinogens. The study therefore tested whether these DEA-noted tryptamines substitute for DOM and examined their relative potencies and effects on operant response rate.

Expert Research Summaries

Go Pro to access AI-powered section-by-section summaries, editorial takes, and the full research toolkit.

Study Details

References (13)

Papers cited by this study that are also in Blossom

Classic hallucinogens in the treatment of addictions

Bogenschutz, M. P., Johnson, M. W. · Progress in Neuro-Psychopharmacology and Biological Psychiatry (2016)

Heaven and Hell-A Phenomenological Study of Recreational Use of 4-HO-MET in Sweden

Kjellgren, A., Soussan, C. · Journal of Psychoactive Drugs (2011)

52 cited
A systematic study of microdosing psychedelics

Polito, V., Stevenson, R. J. · PLOS ONE (2019)

197 cited
Hallucinogens

Nichols, D. E. · Pharmacology and Therapeutics (2004)

The behavioral pharmacology of hallucinogens

Fantegrossi, W. E., Murnane, K. S., Reissig, C. J. · Biochemical Pharmacology (2007)

DARK Classics in Chemical Neuroscience: Psilocybin

Geiger, H. A., Wurst, M. G., Daniels, R. N. · ACS Chemical Neuroscience (2018)

Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens

Rickli, A., Moning, O. D., Hoener, M. C. et al. · European Neuropsychopharmacology (2016)

Show all 13 references
Psychedelics

Nichols, D. E. · Pharmacological Reviews (2016)

Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels

Madsen, M. K., Fisher, P. M., Burmester, D. et al. · Neuropsychopharmacology (2019)

Cited By (2)

Papers in Blossom that reference this study

The Promise of Psychedelic Science

Olson, D. E. · ACS Pharmacology and Translational Science (2021)

Your Personal Research Library

Go Pro to save papers, add notes, rate studies, and organize your research into custom shelves.

Discriminative Stimulus Effects of Substituted... — Research Summary & Context | Blossom