delta 9-Tetrahydrocannabinol: EEG changes, bradycardia and hypothermia in the rhesus monkey

Administration of delta 9-tetrahydrocannabinol (THC; 0.75-4.0 mg/kg IP) to rhesus monkeys produced a biphasic pattern of high-voltage slow waves (HVSW) and fast waves (HVFW) EEG, along with behavioral depression and alertness, respectively. The HVSW phase appeared 20 to 30 min after drug injection and was uniquely characterized by spike-bursts in frontal and temporal lobes and hypothalamus, theta-waves in parietal and occipital lobes, and generalized HVSW in subcortical regions. During the HVSW phase, bradycardia and hypothermia occurred, and animals exhibited depression or sedation. After the HVSW phase lasting for 3-4 hr, HVFW predominated in overall EEGs with marked decrease in neocortical spike-bursts. Bradycardia and hypothermia occurred simultaneously 20 to 30 min after drug injection and reached maximal levels (30-40 percent decrease in heart rate, 1.5-2.0 degrees C decrease in body temperature) 2 to 3 hr after injection. The dose- and time-response relationships for bradycardia and hypothermia paralleled the HVSW phase with behavioral depression. Animals were alert and calm during recovery from bradycardia and hypothermia. THC levels and disposition in blood correlated with bradycardia, hypothermia and EEGs and behavioral changes following THC administration.