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A cannabinoid is a chemical compound that acts on cannabinoid receptors in cells that alter the release of neurotransmitters in the brain. Ligands for these receptor proteins include the endocannabinoids (which are naturally produced in the body by animals and humans), the phytocannabinoids (found in cannabis and some other plants) and synthetic cannabinoids (artificially manufactured). The most striking cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC), the primary psychoactive substance in cannabis. Cannabidiol (CBD) is another important component of the plant. There are at least 113 different cannabinoids isolated from cannabis, with varied effects.
Before the 1980s, it was often speculated that cannabinoids produced their physiological and behavioral effects through non-specific interaction with cell membranes, rather than interacting with specific membrane-bound receptors. The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate. These receptors are common in animals and are found in mammals, birds, fish and reptiles. Presently, two types of cannabinoid receptors are known, CB1 and CB2, with increasing evidence of more. The human brain has more cannabinoid receptors than any other type of G protein-coupled receptor (GPCR).
CB1 receptors are found mainly in the brain, more specifically in the basal ganglia and in the limbic system, including the hippocampus and the striatum. They are also found in the cerebellum and in both male and female reproductive systems.
CB1 receptors are absent in the medulla oblongata, the part of the brainstem that is responsible for respiratory and cardiovascular functions. CB1 also occurs in the human front eye and retina.
CB2 receptors are found predominantly in the immune system or in cells that are immune with greatest density in the spleen. Although only found in the peripheral nervous system, a report indicates that CB2 is expressed by a subpopulation of microglia in the human cerebellum. CB2 receptors appear to be responsible for the anti-inflammatory and possibly other therapeutic effects of cannabis in animal models.