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Abstract: 9-Tetrahyd rocannabinol (THC) decreases EEG activation and causes slow waves in the cat. The EEG slow-wave activity is accompanied by a concomitant decrease in acetylcholine release from the neocortex. The findings suggest that THC depresses the brain stem activating system. Large doses of and-THC increase brain acetylcholine levels in rodents such as the mouse and rat, but this effect is not seen with minimal doses of the cannabinoids which show behavioral effects. The most dramatic change produced by THC is that brain acetylcholine utilization is reduced primarily in the hippocampus. I T is still far from clear how cannabinoids produce their remarkable pharmacologic effects. The cannabinoids interact with many different neuronal and biochemical systems,”2 but which action is the most im-portant in relation to therapeutic effects is still unknown. Marihuana and z9-tetra-hydrocannabinol (THC) have remarkable effects on human memory and cogthfion.’ Recently, Ferraro6 has reviewed the exten-sive literature on this subject. Although marihuana’s acute effects on memory vary, he concluded that they are always detri-mental to the marihuana user. Our animal neurochemical research suggests that these undesirable side effects of cannabis and probably other synthetic cannabinoids are related to a decrease in the release of neuro-nal acetylcholine (ACh) and its turnover in certain regions of the brain. This report summarizes these results from our labora-tory. It should be pointed out that at least three other laboratories in the United States have been active in this field.7 The results from all four laboratories differ in details, but all agree that cannabis prepa-rations interact with the cholinergic sys-tem. Cannabinoids, especially the 7-OH de