We investigated the effects of acute i.v. administration of 2 mg of delta 9-tetrahydrocannabinol (THC) on regional brain glucose metabolism using 18F-2-fluoro-2-deoxyglucose and positron emission tomography (PET) in eight normal subjects. Subjects were tested twice: during baseline conditions and 30-40 min after THC administration. Changes in global cerebral glucose metabolism in response to THC were variable: three subjects showed an increase, three showed a decrease, and two showed no change. In contrast, all subjects showed an increase in normalized metabolism in the cerebellum following THC administration. Cerebellar changes were the only significant regional metabolic changes due to THC administration. The increase in metabolic activity in the cerebellum was correlated with the subjective sense of THC intoxication and with plasma THC concentration. Cerebellar localization of metabolic effects due to THC administration corresponds well with the high density of cannabinoid receptors known to be in this area.