The chemistry of the brain

The active compound in herbal cannabis, D9-tetrahydro-cannabinol, exerts all of its known central effects through the CB1 cannabinoid receptor. Research on cannabinoid mechanisms has been facilitated by the availability of selective antagonists acting at CB1 recep-tors and the generation of CB1 receptor knockout mice. Particularly important classes of neurons that express high levels of CB1 receptors are GABAergic interneur-ons in hippocampus, amygdala and cerebral cortex, which also contain the neuropeptides cholecystokinin. Activation of CB1 receptors leads to inhibition of the release of amino acid and monoamine neurotransmit-ters. The lipid derivatives anandamide and 2-arachido-nylglycerol act as endogenous ligands for CB1 receptors (endocannabinoids). They may act as retrograde synap