Add time:08/17/2019         Source:sciencedirect.com

A long-retained cannabinoid metabolite has been detected in rat tissue after intravenous administration of Δ9-tetrahydrocannabinol (THC) and has been identified as a fatty acid conjugate of psychoactive 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-Δ9-THC) and palmitic acid. The objective of these studies was to determine if this compound, 11-palmitoyloxy-Δ9-tetrahydrocannabinol (11-palm-Δ9-THC) is pharmacologically active. Intravenously injected 11-palm-Δ9-THC decreased thermal sensitivity and induced catalepsy in rats, responses similar to those produced by 11-OH-Δ9-THC, but less pronounced and more delayed. To further characterize the response, animals were intracisternally injected with 11-OH-Δ9-THC or 11-palm-Δ9-THC. Catalepsy and decreased thermal sensitivity were seen in the 11-OH-Δ9-THC and 11-palm-Δ9-THC groups, and again, 11-OH-Δ9-THC appeared to be the more potent of the two cannabinoids. In contrast to the intravenous study, 11-palm-Δ9-THC-induced effects were seen soon after treatment and appeared to be fully developed by the first test time (15 min). The intracisternal results suggest that 11-palm-Δ9-THC itself is active; however, since it is known that the fatty acid conjugate is hydrolyzed in vivo to 11-OH-Δ9-THC in the rat, the possibility remains that the effects of 11-palm-Δ9-THC are due to metabolic conversion to 11-OH-Δ9-THC.

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