CB1

CB1 receptor, or cannabinoid receptor type 1, is a G protein-coupled receptor in the endocannabinoid system. It is encoded by the CNR1 gene and binds endogenous ligands such as anandamide and 2-arachidonoylglycerol (2-AG), as well as exogenous cannabinoids including delta-9-tetrahydrocannabinol (THC). CB1 signaling modulates neuronal activity throughout the brain and, to a lesser extent, in peripheral tissues.

CB1 receptors are highly expressed in the central nervous system, particularly in the cerebral cortex, hippocampus, basal ganglia, and cerebellum, with lower levels in adipose tissue, liver, and immune cells. They are predominantly located on presynaptic terminals where they regulate neurotransmitter release via retrograde signaling.

Most CB1 receptors couple to Gi/o proteins, inhibiting adenylyl cyclase, decreasing cAMP, and modulating calcium and potassium ion channels. This typically reduces neurotransmitter release and alters synaptic plasticity. Activation of CB1 receptors influences diverse physiological processes, including pain modulation, appetite and energy balance, mood, memory, coordination, and reward.

Pharmacology and clinical relevance: Endocannabinoids are produced on demand and terminated by reuptake and degradation. Pharmacological manipulation includes CB1 agonists used in antiemetic and analgesic contexts (for example, dronabinol, nabilone). CB1 antagonists have been explored for obesity treatment but were associated with psychiatric side effects, limiting their development (notably rimonabant). Genetic or pharmacological disruption of CB1 signaling in animal models alters pain, energy balance, and mood regulation.

CB1 was identified in the 1990s as part of uncovering the molecular basis of cannabis action. It is one of two main cannabinoid receptors, the other being CB2, which is primarily expressed in the immune system.