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

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

Biological Psychiatry May 1, 1996 DOI: 10.1016/0006-3223(95)00200-6 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Double-blind Peer reviewed
Sample size 13
Population Experienced hallucinogen users
Intervention DMT fumarate
Dose 0.3 mg/kg
Duration Four doses at 30 min intervals on 2 separate days
Topics 5-MeO-DMT DMT
Keywords Differential mechanical device Differential effects Pharmacology
Citations 129
Key findings Tolerance to the psychedelic effects of DMT did not occur with repeated dosing, but physiological responses such as ACTH, prolactin, cortisol, and heart rate decreased.

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.

Comparable studies

Other randomized controlled trials on 5-MeO-DMT, most cited first.

Study Year Design Participants
Dose-Response Study of N,N-Dimethyltryptamine in Humans Experienced hallucinogen users 1994 Double-blind, saline placebo-controlled, randomized study n = 12
Psychological Effects of (S)-Ketamine and N,N-Dimethyltryptamine (DMT): A Double-Blind, Cross-Over Study in Healthy Volunteers Healthy volunteers 2005 Double-blind crossover study n = 9
Pharmacokinetics of N,N-dimethyltryptamine in Humans. Healthy adults 2023 Phase I component of a phase I/IIa randomised, double-blind, placebo-controlled, parallel-group, dose-escalation trial n = 24
Prepulse inhibition of the startle reflex and its attentional modulation in the human S-ketamine and N,N-dimethyltryptamine (DMT) models of psychosis Healthy volunteers 2007 Double-blind crossover study n = 15
Phase 1, placebo-controlled, single ascending dose trial to evaluate the safety, pharmacokinetics and effect on altered states of consciousness of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine benzoate) in healthy participants. Healthy psychedelic-naïve participants 2024 Double-blind, placebo-controlled single ascending dose study n = 44

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5-MeO-DMT DMT