Cannabinoids exert their effects by interacting with cannabinoid receptors present on the surface of cells in different parts of the central nervous system.
To date, only two types of cannabinoid receptor have been identified, the CB1 receptor which was cloned in 1990 and the CB2 receptor which was cloned in 1993. These two receptors only share 48% amino acid sequence identity, are distributed in different tissues and also have different signalling mechanisms. They also differ in their sensitivity to agonists and antagonists. Studies show that activation of the cannabinoid receptors leads to inhibition of adenylate cyclase, which stops the conversion of ATP to cyclic AMP (cAMP).
A naturally occurring substance within the brain called anandamide that binds to CB1 was detected in 1992. This cannabinoid-like chemical and others that were later discovered, are referred to as endocannabinoids.
Location of the receptors
The CB1 receptors are primarily located on nerve cells in the brain, spinal cord, but they are also found in some peripheral organs and tissues such as the spleen, white blood cells, endocrine gland and parts of the reproductive, gastrointestinal and urinary tracts.
In the brain, the CB1 receptors are abundant in the cerebellum, basal ganglia, hippocampus and dorsal primary afferent spinal cord regions, which is why cannabinoids influence functions such as memory processing, pain regulation and motor control. In the brain stem, the concentration of cannabinoids is low, which may be related to why cannabis use is not associated with sudden death due to depressed respiration, for example.
The CB2 receptors are mainly found on white blood cells, in the tonsils and in the spleen. The immune cells also express CB1, although there are fewer of them than CB2. In the immune system, one important function of the cannabinoid receptors is the regulation of cytokine release. Stimulation of the CB1 receptor produces marijuana-like effects on the psyche and circulation, while no such effect is seen when the CB2 receptor is activated. Therefore, selective CB2 receptor agonists have become increasingly popular subjects of research for their potential anti-inflammatory and anti-cancer effects.