Effects of delta 9-tetrahydrocannabinol and cannabidiol on phospholipase and other enzymes regulating arachidonate metabolism.

delta 9-Tetrahydrocannabinol (THC) and cannabidiol (CBD) caused a marked stimulation of phospholipase A2 when incubated with intact human platelets that were prelabeled with [14C] arachidonate. CBD was about 1.5 x as potent as THC in the same concentration range (10 leads to 80 microM) Most of the released arachidonate was converted to lipoxygenae products. When [14C] arachidonate was incubated with lysed platelet extracts, THC inhibited both thromboxane synthetase and prostaglandin cyclooxygenase, so that the net effect was a redistribution of products toward the lipoxygenase pathway at the same time that a decrease in total cyclooxygenase product formation occurred. THC did not directly affect arachidonate lipoxygenase. Both TCH and CBD also stimulated release from prelabeled neuroblastoma cells (NBA2), which do not contain an active lipoxygenase pathway. In this case, accumulation of free arachidonate was detected by autoradiography. The multiple effects of THC and CBD on phospholipase A2 and arachidonate metabolism may mediate some of the pharmacological actions of these compounds, such as their anticonvulsant, anti-inflammatory, and hypotensive properties.