Decrease in prostaglandin level is a prerequisite for the expression of cannabinoid withdrawal: a quasi abstinence approach.

Cannabinoid withdrawal has been indicated in both human and animal subjects. One of pathways proposed to facilitate cannabinoid action is the arachidonic acid cascade. Previously, we have shown that prostaglandin attenuated the expression of withdrawal signs in tetrahydrocannabinol-dependent mice. It follows that the cascade might participate in the expression of cannabinoid withdrawal. We utilized a quasi abstinence approach (the induction of a state of cannabinoid withdrawal without giving any cannabinoid substances in a naïve animal) to describe the relationship between the change in prostaglandin level, an end product of the arachidonic acid cascade, and the expression of cannabinoid withdrawal. Administration of 10 mg/kg diclofenac, a prostaglandin synthesis inhibitor, i.p. 30 min before SR 141716A induced cannabinoid withdrawal signs in naïve mice, which were comparable to the true abstinence in cannabinoid-tolerant mice. In turn, 10 mg/kg Delta(8)-THC i.p., given 15 min prior to SR 141716A, blocked the expression of these signs. These results suggested that the decrease in prostaglandin level is a prerequisite for the expression of cannabinoid withdrawal.