Cannabis sativa: effects on brain function and ultrastructure in rhesus monkeys.

Two studies, designed to control for as many variables as possible, were conducted in 21 rhesus monkeys, some with brain electrodes and some unoperated, to determine the effects of marijuana on brain function and ultrastructure. Some monkeys were exposed to smoke of active marijuana (using different dose schedules), some were administered delta-9-THC (0.69 mg/kg iv), and others were exposed to smoke of inactive marijuana (from which all cannabinols had been removed). To deliver smoke to the monkeys, two different apparatuses were used. Dose schedules comparable to those of human marijuana smokers were established, as determined by plasma levels of delta-9-THC. After 2- to 3-months' exposure, the monkeys that were heavy- and moderate-smokers of active marijuana, and those administered delta-9-THC iv, developed chronic recording changes at deep brain sites, most marked in the septal region, hippocampus, and amygdala. These changes persisted throughout the exposure period (6 or 8 months) and during the postexposure observation period (1 to 8 months). Brains of these electrode-implanted monkeys, as well as those without electrodes that were exposed to delta-9-THC, showed ultrastructural alterations characterized by changes at the synapse, destruction of rough endoplasmic reticulum, and development of nuclear inclusion bodies. In contrast, brains of monkeys exposed to smoke of inactive marijuana and of unexposed controls showed no ultrastructural changes. The findings indicate that exposure to delta-9-THC, the psychoactive ingredient of marijuana, at doses commensurate with those used by human marijuana smokers can produce permanent alterations in brain function and structure of monkeys.