Cannabinoid receptors

The cannabinoid receptors are a class of receptors which belong to the G-protein coupled receptor superfamily. Their ligands are known as cannabinoids.

Cannabinoids, a group of C21 compounds present in Cannabis sativa L., their carboxylic acids, analogs, and transformation products, are the active ingredients found in hashish and marijuana. Cannabis affect cognition and memory, euphoria and sedation, and antinociception (analgesia) without the respiratory depression problems associated with opioid analgesics.

CB1 and CB2 cannabinoid receptors are the primary targets of endogenous cannabinoids (endocannabinoids). These G protein-coupled receptors play an important role in many processes, including metabolic regulation, craving, pain, anxiety, bone growth, and immune function. Cannabinoid receptors can be engaged directly by agonists or antagonists, or indirectly by manipulating endocannabinoid metabolism.

There are currently two known subtypes of cannabinoid receptors - CB1, which is expressed mainly in the basal ganglia and the limbic system of the brain and also in the lungs, liver and kidneys and CB2 which is expressed on T cells of the immune system.

Cannabinoid receptors work by inhibiting adenylate cyclase and thereby inhibit production of the second messenger molecule cyclic AMP. They are activated by cannabinoids, found naturally inside the body or introduced as a drug (which may be a synthetic compound or a herbal extract.)

The protein sequences of CB1 and CB2 receptors are about 45% similar. Cannabinoids bind reversibly and stereo-selectively to the cannabinoid receptors. The affinity of an individual cannabinoid to each receptor determines the effect of that cannabinoid. Cannabinoids that bind more selectively to certain receptors are more desirable for medical usage.

Cannabinoids are well known for their cardiovascular activity. Activation of peripheral CB1 receptors contributes to hemorrhagic and endotoxin-induced hypotension. Anandamide and 2-AG, produced by macrophages and platelets, respectively, may mediate this effect. It has been observed that several synthetic cannabinoids have been shown to bind to the CB2 receptor with a higher affinity than to the CB1 receptor.