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Δ9-Tetrahydrocannabinol (Δ9-THC), the most prominent psychoactive cannabinoid in Cannabis sativa L. (marijuana), has been reported to have properties of appetite stimulation, promotion of weight gain, and antiemetic efficacy in selected patient populations. In this 4-week, double-blind, crossover study, 11 female patients with primary anorexia nervosa (PAN) were evaluated on Δ9-THC and on an active placebo, diazepam. All patients participated in a standardized behavior modification treatment program. The following data were obtained: (1) daily weight, (2) daily caloric intake, and (3) weekly psychiatric assessments. The two groups were comparable on all measures at baseline except for two items on the behavioral rating scales. The only significant differences found between the changes over time on Δ9-THC versus diazepam were more pathology on Δ9-THC for somatization, interpersonal sensitivity, and sleep disturbance. Three patients experienced severe dysphoric reactions consisting of paranoid ideation and feelings of loss of control during Δ9-THC administration. One week after the study ended, each subject was given the highest dose level of Δ8-THC achieved in the study, and periodic blood samples were obtained coincident with self-rated “subjective high” assessments and pulse measurements. Quantitative analyses of these samples indicated peak times of 1 to 5 hours postdose for Δ9- THC and for its primary active metabolite, 11-hydroxy-THC, which generally coincided with peak times for “subjective high” and pulse rate. The results of this clinical investigation suggest that Δ9-THC is not efficacious, in short-term administration, in the treatment of primary anorexia nervosa and is associated with significant psychic disturbance in some PAN patients.