Cnr1

CNR1, also known as the cannabinoid receptor 1 gene, encodes the cannabinoid receptor type 1 (CB1), a G protein-coupled receptor that mediates endocannabinoid signaling. The CB1 receptor is widely expressed in the central nervous system and plays a key role in modulating neuronal communication and synaptic plasticity. In humans, the CNR1 gene is located on chromosome 6 (6q15).

CB1 is a seven-transmembrane-domain receptor that primarily couples to Gi/o proteins. Activation inhibits adenylyl cyclase, reduces cAMP formation, and modulates ion channels, including voltage-gated calcium channels and inward-rectifier potassium channels. This leads to decreased neurotransmitter release and involvement in retrograde signaling at synapses, contributing to processes such as learning, memory, pain modulation, appetite, and mood regulation. The receptor is highly expressed in brain regions such as the cortex, hippocampus, basal ganglia, and cerebellum, with additional expression in peripheral tissues.

Endocannabinoids, including anandamide (AEA) and 2-arachidonoylglycerol (2-AG), are endogenous ligands that activate CB1. Exogenous ligands include Δ9-tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis, as well as synthetic cannabinoids. Antagonists and inverse agonists, such as rimonabant, have been used in research and were pursued clinically for obesity but were withdrawn due to adverse effects.

Physiological roles of CB1 signaling encompass appetite regulation, analgesia, mood, memory, motor control, and reward pathways, with implications for addiction and neuropsychiatric disorders. Genetic variation in CNR1 can influence receptor expression and individual responses to cannabinoids, contributing to variability in behavioral and clinical outcomes.