Cannabinoid Receptor Phosphorylation Assays

Cannabinoid receptors are activated by endogenous ligands that include anandamide and 2-arachidonoyl-glycerol. Cannabinoid receptors were originally defined as those receptors that respond to cannabinoid drugs, such as Δ9-tetrahydrocannabinol (THC) derived from Cannabis sativa and its biologically active synthetic analogues. Two cannabinoid receptors, CB1 and CB2, have been described to date. CB1 cannabinoid receptors are coupled to pertussis toxin (PTX)-sensitive Gi/Go proteins. CB1 receptors are primarily located at central or peripheral nerve terminals where they mediate inhibition of on-going release of certain excitatory and inhibitory neurotransmitters. Most CB2 receptors are expressed by immune cells where they modulate immune cell migration and cytokine release. There are currently three licenced cannabinoid medicines each of which contains a compound that can activate CB1 and CB2 receptors. Two of these medicines were developed to suppress nausea and vomiting produced by chemotherapy. These are nabilone (Cesamet®) and synthetic Δ9-tetrahydrocannabinol (Marinol®), which can also be used as an appetite stimulant. The third medicine, Sativex®, contains mainly Δ9-tetrahydrocannabinol and cannabidiol, both extracted from cannabis, and is used to treat multiple sclerosis and cancer pain.