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
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.
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.
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Study Details
- Study Typeindividual
- Journal
- Topics
- Author
- APA Citation
Gatch, M. B., Hoch, A., & Carbonaro, T. M. (2021). Discriminative Stimulus Effects of Substituted Tryptamines in Rats. ACS Pharmacology & Translational Science, 4(2), 467-471. https://doi.org/10.1021/acsptsci.0c00173
References (13)
Papers cited by this study that are also in Blossom
Griffiths, R. R., Johnson, M. W. · Journal of Psychopharmacology (2016)
Bogenschutz, M. P., Johnson, M. W. · Progress in Neuro-Psychopharmacology and Biological Psychiatry (2016)
Carbonaro, T. M., Johnson, M. W., Griffiths, R. R. · Psychopharmacology (2020)
Kjellgren, A., Soussan, C. · Journal of Psychoactive Drugs (2011)
Polito, V., Stevenson, R. J. · PLOS ONE (2019)
Nichols, D. E. · Pharmacology and Therapeutics (2004)
Fantegrossi, W. E., Murnane, K. S., Reissig, C. J. · Biochemical Pharmacology (2007)
Geiger, H. A., Wurst, M. G., Daniels, R. N. · ACS Chemical Neuroscience (2018)
Rickli, A., Moning, O. D., Hoener, M. C. et al. · European Neuropsychopharmacology (2016)
Carbonaro, T. M., Eshleman, A. J., Forster, M. J. et al. · Psychopharmacology (2014)
Show all 13 referencesShow fewer
Halberstadt, A. L., Chatha, M., Klein, A. K. et al. · Neuropharmacology (2020)
Nichols, D. E. · Pharmacological Reviews (2016)
Madsen, M. K., Fisher, P. M., Burmester, D. et al. · Neuropsychopharmacology (2019)
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Olson, D. E. · ACS Pharmacology and Translational Science (2021)
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