Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans.

Strassman, Rick J.; Qualls, Clifford R.; Berg, Laura M.

doi:10.1016/0006-3223(95)00200-6

Cited by 130Psychedelics and Drug StudiesNeurotransmitter Receptor Influence on BehaviorHallucinations in medical conditions

Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans.

Strassman, Rick J., Qualls, Clifford R., Berg, Laura M.·1996·Biological Psychiatry

DOI 10.1016/0006-3223(95)00200-6

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Abstract

Tolerance of the behavioral effects of the short-acting, endogenous hallucinogen, N,N-dimethyltryptamine (DMT) is seen inconsistently in animals, and has not been produced in humans. The nature and time course of responses to repetitive, closely spaced administrations of an hallucinogenic dose of DMT were characterized. Thirteen experienced hallucinogen users received intravenous 0.3 mg/kg DMT fumarate, or saline placebo, four times, at 30 min intervals, on 2 separate days, in a randomized, double-blind, design. Tolerance to "psychedelic" subjective effects did not occur according to either clinical interview or Hallucinogen Rating Scale scores. Adrenocorticotropic hormone (ACTH), prolactin, cortisol, and heart rate responses decreased with repeated DMT administration, although blood pressure did not. These data demonstrate the unique properties of DMT relative to other hallucinogens and underscore the differential regulation of the multiple processes mediating the effects of DMT.

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DMT does not precipitate tolerance upon repeated use, unlike the related tryptamine derivative psilocybin.
“Unlike the related tryptamine derivative psilocybin, DMT does not precipitate tolerance upon repeated use (Strassman et al., 1996); this produces further complications for simple receptor-based interpretations.”
From The therapeutic potentials of Ayahuasca: possible effects against various diseases of civilization (2016) · cites this paper as Strassman et al., 1996

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Authors: Strassman, R. J., Qualls, C. R., & Berg, L. M.
Affiliations: University of New Mexico (US)
Corresponding author: Strassman, Rick J.
ORCID: Qualls, Clifford R.
Venue: Biological Psychiatry
Publisher: Elsevier BV
Published: 1996-05
Volume: 39
Issue: 9
Pages: 784-795
ISSN: 0006-3223 (ISSN-L)
DOI: 10.1016/0006-3223(95)00200-6
OpenAlex: W2115359142
Cited by: 130
References: 50
Citations by year: 2026: 7 · 2025: 7 · 2024: 10 · 2023: 14 · 2022: 8 · 2021: 4 · 2020: 5 · 2019: 3 · 2018: 6 · 2017: 5 · 2016: 8 · 2015: 6 · 2014: 4 · 2013: 3 · 2012: 8
FWCI: 3.68
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biological Psychiatry (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (1r01da008096-01)
National Institute on Drug Abuse (R01-DA08096)
National Center for Research Resources (RR00997-15, M01RR000997)
Topics: Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cognitive Neuroscience › Hallucinations in medical conditions
Keywords: N,N-dimethyltryptamine, repeated dosing, ACTH, prolactin, cortisol, heart rate, blood pressure
MeSH terms: Adrenocorticotropic Hormone, Adult, Arousal, N,N-Dimethyltryptamine, Double-Blind Method, Drug Tolerance, Female, Hallucinations, Hallucinogens, Humans, Hydrocortisone, Male, Middle Aged, Perception, Prolactin

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Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans.

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