Mini - Review 11 - Nor - 9 - carboxy - ∆ 9 - tetrahydrocannabinol – a ubiquitous yet underresearched cannabinoid . A re - view of the literature

Synthetic ∆ 9 -tetrahydrocannabinol (THC), pharmaceutical grade herbal cannabis as well as formulations of well-defined cannabis extracts are available as registered medicines in several countries. It is generally accepted that the main central and peripheral pharmacological effects of THC are mediated by CB1 and CB2 cannabinoid receptors. Cytochrome P450-mediated oxidations of THC afford the non-psychoactive 11-nor-9-carboxy-THC (THC-COOH) as main metabolite. The pharmacokinetics of THC-COOH has been studied thoroughly and this abundant acid metabolite has become an established urinary marker of cannabis consumption in forensic, clinical and environmental analyses. Surprisingly, however, data on the biological activity of this ubiquitous metabolite are scarce. A few studies have examined the effect of THC-COOH on the biosynthesis of prostaglandins and other eicosanoids, on capsaicin-sensitive sensory nerves, on the multidrug transporter P-glycoprotein, on the cannabinoid and estrogen receptors in vitro, as well as its anticataleptic, analgesic, platelet-activating factor inhibitory and anti-inflammatory activities in vivo; THC-COOH has also been reported to block certain behavioural effects of THC in rodents. Hereby we provide a literature review on the reported pharmacological effects of THC-COOH and advocate further studies to reveal any potential involvement of this abundant metabolite in the complex pharmacology and in the proven therapeutic effects of THC-containing preparations.