Cannabinoid receptors

Two cannabinoid receptors are known, CB1 and CB2.  CB1 receptors have been cloned from rat, mouse and human tissues, and are primarily located at central and peripheral nerve terminals.  The CB2 cannabinoid receptor was discovered as a cDNA fragment that exhibited 68% homology with CB1.  CB2 receptors are predominantly expressed in non-neuronal tissues, particularly immune cells, where they modulate cytokine release and cell migration.  Both CB1 and CB2 receptors are activated by endogenous ligands including anandamide, N-homo-γ-linolenoylethanolamine, N-docosatetra-7,10,13,16-enoylethanolamine and 2-arachidonoylglycerol.  Responses to cannabinoid receptor agonists include analgesia, attenuation of nausea, appetite stimulation, and decreased intestinal motility.  Other effects include alterations in cognition and memory, dysphoria-euphoria and sedation.  Cannabinoid based medicines are used clinically to suppress nausea and vomiting produced by chemotherapy, as appetite stimulants and to treat multiple sclerosis and cancer pain.

Further reading

Felder et al (1995) Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors. Mol Pharmacol. 48(3) 443 PMID: 7565624

Mackie (2008) Cannabinoid receptors: where they are and what they do. J Neuroendocrinol. 20 Suppl 1:10 PMID: 18426493

Shahbazi et al (2020) Cannabinoids and Cannabinoid Receptors: The Story so Far. iScience 23(7) 101301 PMID: 32629422

Haspula and Clark (2020)  Cannabinoid Receptors: An Update on Cell Signaling, Pathophysiological Roles and Therapeutic Opportunities in Neurological, Cardiovascular, and Inflammatory Diseases. Int J Mol Sci. 21(20) 7693 PMID: 33080916

Abood et al (2023) Cannabinoid receptors. IUPHAR/BPS Guide to Pharmacology.  https://doi.org/10.2218/gtopdb/F13/2023.1.

Valentino and Volkow (2024) Cannabis and Cannabinoid Signaling: Research Gaps and Opportunities. J Pharmacol Exp Ther. 2024 391(2) 154 PMID: 39060161

Tseng and Molla (2005) Cannabinoid CB1 receptor-sensitive neurodevelopmental processes and trajectories. Mol Psychiatry https://doi.org/10.1038/s41380-025-03057-2