Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans
This randomised, double-blind study (n=13) investigated tolerance of repeated doses of 21mg/70kg DMT fumarate in hallucinogen-experienced users. Tolerance to “psychedelic” subjective effects did not occur according to either clinical interview or Hallucinogen Rating Scale scores.
Abstract
Tolerance to 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.
Research Summary of 'Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans'
Introduction
Hallucinogens evoke profound alterations of perception, cognition, and affect while often leaving a relatively clear sensorium. Previous research indicates that longer-acting classic hallucinogens (for example LSD, psilocybin, mescaline) readily produce tolerance after repeated daily exposure, but DMT (N,N-dimethyltryptamine), a short-acting endogenous compound, has shown inconsistent tolerance in animals and has not reliably produced tolerance in humans. The absence of cross-tolerance between LSD and DMT in prior work also challenges the assumption that all classic hallucinogens act by identical mechanisms, highlighting the need to characterise DMT’s time course and regulatory mechanisms more precisely. Strassman and colleagues designed the present study to determine whether tolerance to both subjective (psychedelic) and biological (neuroendocrine, cardiovascular, thermoregulatory) effects could be produced within a single day by closely spaced repeated intravenous doses of DMT. The aim was to compare responses across four 30-minute-spaced injections and to determine whether subjective reports and physiological biomarkers showed parallel patterns of attenuation (tolerance) or differential regulation, thereby clarifying DMT’s pharmacological uniqueness among classic hallucinogens.
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Study Details
- Study Typeindividual
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- APA Citation
Strassman, R. J., Qualls, C. R., & Berg, L. M. (1996). Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans. Biological Psychiatry, 39(9), 784-795. https://doi.org/10.1016/0006-3223(95)00200-6
References (1)
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