Pharmacological and therapeutic targets for Delta(9)-tetrahydrocannabinol and cannabidiol

Cannabis is the unique source of a set of at least 66 compounds known collectively as cannabinoids. Of these, most is known about the pharmacology of Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the main psychoactive constituent of cannabis, and about cannabidiol (CBD), which lacks psychoactivity. Accordingly, this paper focuses on the pharmacological and therapeutic targets of these two cannabinoids. Many of the effects of Delta(9)-THC are mediated by cannabinoid receptors of which at least two types, CB1 and CB2, are present in mammalian tissues. Endogenous agonists for cannabinoid receptors have also been discovered. CB1 receptors are present at the terminals of central and peripheral neurones, where they modulate transmitter release. They also exist in some non-neuronal cells. CB2 receptors are expressed mainly by immune cells, one of their roles being to alter cytokine release. Delta(9)-THC also appears to have non-CB1, non-CB2 pharmacological targets. It is already licensed for clinical use in the U.S.A. as an anti-emetic and appetite stimulant and both Delta(9)-THC and Delta(9)-THC-rich cannabis extracts show therapeutic potential as neuroprotective and anticancer agents and for the management of glaucoma, pain and various kinds of motor dysfunction associated, for example, with multiple sclerosis and spinal cord injury. CBD has much less affinity for CB1 and CB2 receptors than Delta(9)-THC and its pharmacological actions have been less well characterized. Potential clinical applications of CBD and CBD-rich cannabis extracts include the production of anti-inflammatory and neuroprotective effects, the management of epilepsy, anxiety disorders, glaucoma and nausea, and the modulation of some effects of Delta(9)-THC.