Background: Validation of animal models of hallucinogenic drugs' subjective effects requires human data. Previous human studies used varied groups of subjects and assessment methods. Rating scales for hallucinogen effects emphasized psychodynamic principles or the drugs' dysphoric properties. We describe the subjective effects of graded doses of N,N-dimethyltryptamine (DMT), an endogenous hallucinogen and drug of abuse, in a group of experienced hallucinogen users. We also present preliminary data from a new rating scale for these effects. Methods: Twelve highly motivated volunteers received two doses (0.04 and 0.4 mglkg) ofintravenous (IV) dimethyltryptamine fumarate "nonblind," before entering adoubleblind, saline placebo-controlled, randomized study using four doses of Iv DMT. Subj ects were carefully interviewed after resolution of drug effects, providing thorough and systematic descriptions ofDMT's effects. They also were administered anew instrument, the Hallucinogen Rating Scale (HRS). The HRSwas drafted from in~erviews obtained from an independent sample of 19 experienced DMT users, and modified during early stages of the study. Results: Psychological effects ofIVDMT began almost immediately after administration, peaked at 90 to 120 seconds, and were almost completely resolved by 30 minutes. This timecourseparalleledDMTbloodlevelspreviouslydescribed. Hallucinogenic effects were seen after 0.2 and 0.4 mglkg of dimethyltryptamine fumarate, and included arapidly moving, brightly colored visual display of images. Auditory effects were less common. "Loss of control," associated with a brief, but overwhelming "rush," led to a dissociated state, where euphoria alternated or coexisted with anxiety. These effects completly replaced subj ects' previously ongoing mental experience and were more vivid and compelling than dreams or waking awareness. Lower doses, 0.1 and 0.05 mgl kg,were primarily affectiveand soma esthetic, while 0.1 mglkg elicited the least desirable effects. Clustering ofHRS items, using either aclinical, mental status method or principal components factor analysis provided better resolution of dose effects than did the biological variables described previously. Conclusions: These clinical and preliminary quantitative data provide bases for further psychopharmacologic characterization of DMT's properties in humans. They also may be used to compare the effects of other agents affecting relevant brain receptors in volunteer and psychiatric populations.