Tolerance to the psychedelic effects of N,N-dimethyltryptamine (DMT) does not develop with repeated, closely spaced doses in humans. Thirteen experienced hallucinogen users received intravenous 0.3 mg/kg DMT fumarate or saline placebo four times at 30-minute intervals on two separate days in a randomized, double-blind design. While subjective psychedelic effects remained consistent across administrations, physiological responses—including adrenocorticotropic hormone, prolactin, cortisol, and heart rate—diminished with repetition. Blood pressure did not show this decrease. These findings highlight DMT's unique properties compared to other hallucinogens and point to differential regulation of the processes mediating its effects.
The Hallucinogen Rating Scale (HRS) is a widely used questionnaire for measuring subjective effects of psychedelics and other psychoactive drugs. By analyzing 991 questionnaires from 18 studies involving 13 substances, researchers identified 8 factors with good internal consistency that map onto psychedelic effects. The factor model fit the data better than previous models and showed dose responses for most drugs. Patterns on the 8 factors clearly distinguished classic psychedelics (psilocybin, DMT) from dissociatives (ketamine, salvinorin A), empathogens (MDMA), stimulants (methylphenidate, amphetamine), and THC. The meaningfulness factor uniquely differentiated psychedelics from all other substances, supporting the HRS as a psychometrically sound tool for measuring drug-induced altered states.