The phospholipases controlling the release of arachidonic acid in mouse peritoneal macrophages have been shown to be stimulated by the natural psychoactive cannabinoids. A close correlation was observed between the potencies of these substances in elevating arachidonate levels in vitro and the reported activities in a behavioral assay in monkeys and in producing a "high" in humans. The order of activity with the macrophages was delta 1-tetrahydrocannabinol (delta 1-THC) greater than 7-OH-delta 1-THC greater than 6 alpha-OH-delta 1-THC greater than 6 beta-delta 1-THC much greater than delta 6-THC-7-oic acid. It is suggested that this effect, which has now been shown in several diverse cell types, may serve as a model for studying the mechanism of action of THC.
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