Delta-9-Tetrahydrocannabinol (Delta-9-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 Delta-9-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 Delta-9-THC versus diazepam, were more pathology on Delta-9-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 Delta-9-THC administration. One week after the study ended, each subject was given the highest dose level of Delta-9-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 post-dose for Delta-9-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 Delta-9-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.
