DOSE-RESPONSE STUDY OF N,N-DIMETHYLTRYPTAMINE IN HUMANS .2. SUBJECTIVE EFFECTS AND PRELIMINARY-RESULTS OF A NEW RATING-SCALE

Background: Validation of animal models of hallucinogenic drugs' subje ctive effects requires human data. Previous human studies used varied groups of subjects and assessment methods. Rating scales for hallucino gen effects emphasized psychodynamic principles or the drugs' dysphori c properties. We describe the subjective effects of graded doses of N, N-dimethyltryptamine (DMT), an endogenous hallucinogen and drug of abu se, in a group of experienced hallucinogen users. We also present prel iminary data from a new rating scale for these effects. Methods: Twelv e highly motivated volunteers received two doses (0.04 and 0.4 mg/kg) of intravenous (IV) dimethyltryptamine fumarate ''nonblind,'' before e ntering a double-blind, saline placebo-controlled, randomized study us ing four doses of IV DMT. Subjects were carefully interviewed after re solution of drug effects, providing thorough and systematic descriptio ns of DMT's effects. They also were administered a new instrument, the Hallucinogen Rating Scale (HRS). The HRS was drafted from interviews obtained from an independent sample of 19 experienced DMT users, and m odified during early stages of the study. R Results: Psychological eff ects of IV DMT began almost immediately after administration, peaked a t 90 to 120 seconds, and were almost completely resolved by 30 minutes . This time course paralleled DMT blood levels previously described. H allucinogenic effects were seen after 0.2 and 0.4 mg/kg of dimethyltry ptamine fumarate, and included a rapidly moving, brightly colored visu al display of images. Auditory effects were less common. ''Loss of con trol,'' associated with a brief, but overwhelming ''rush,'' led to a d issociated state, where euphoria alternated or coexisted with anxiety. These effects completly replaced subjects' previously ongoing mental experience and were more vivid and compelling than dreams or waking aw areness. Lower doses, 0.1 and 0.05 mg/kg, were primarily affective and somaesthetic, while 0.1 mg/kg elicited the least desirable effects. C lustering of HRS items, using either a clinical, mental status method or principal components factor analysis provided better resolution of dose effects than did the biological variables described previously. C onclusions: These clinical and preliminary quantitative data provide b ases for further psychopharmacologic characterization of DMT's propert ies in humans. They also may be used to compare the effects of other a gents affecting relevant brain receptors in volunteer and psychiatric populations.