Cannabinoid Receptor 1 (Brain), CNR1, Cannabinoid Receptor 1, CANN6, CB-R, CNR, CB1, Central Cannabinoid Receptor, CB1K5, CB1A, CB1R, Receptor, Cannabinoid, CB1


G-protein coupled receptor for endogenous cannabinoids (eCBs), including N-arachidonoylethanolamide (also called anandamide or AEA) and 2-arachidonoylglycerol (2-AG), as well as phytocannabinoids, such as delta-tetrahydrocannabinol (THC) . Mediates many cannabinoid-induced effects, acting, among others, on food intake, memory loss, gastrointestinal motility, catalepsy, ambulatory activity, anxiety, chronic pain. Signaling typically involves reduction in cyclic AMP . In the hypothalamus, may have a dual effect on mitochondrial respiration depending upon the agonist dose and possibly upon the cell type. Increases respiration at low doses, while decreases respiration at high doses. At high doses, CNR1 signal transduction involves G-protein alpha-i protein activation and subsequent inhibition of mitochondrial soluble adenylate cyclase, decrease in cyclic AMP concentration, inhibition of protein kinase A (PKA)-dependent phosphorylation of specific subunits of the mitochondrial electron transport system, including NDUFS2. In the hypothalamus, inhibits leptin-induced reactive oxygen species (ROS) formation and mediates cannabinoid-induced increase in SREBF1 and FASN gene expression. In response to cannabinoids, drives the release of orexigenic beta-endorphin, but not that of melanocyte-stimulating hormone alpha/alpha-MSH, from hypothalamic POMC neurons, hence promoting food intake. In the hippocampus, regulates cellular respiration and energy production in response to cannabinoids. Involved in cannabinoid-dependent depolarization-induced suppression of inhibition (DSI), a process in which depolarization of CA1 postsynaptic pyramidal neurons mobilizes eCBs, which retrogradely activate presynaptic CB1 receptors, transiently decreasing GABAergic inhibitory neurotransmission. Also reduces excitatory synaptic transmission. In superior cervical ganglions and cerebral vascular smooth muscle cells, inhibits voltage-gated Ca channels in a constitutive, as well as agonist-dependent manner . In cerebral vascular smooth muscle cells, cannabinoid-induced inhibition of voltage-gated Ca channels leads to vasodilation and decreased vascular tone. Induces leptin production in adipocytes and reduces LRP2-mediated leptin clearance in the kidney, hence participating in hyperleptinemia. In adipose tissue, CNR1 signaling leads to increased expression of SREBF1, ACACA and FASN genes. In the liver, activation by endocannabinoids leads to increased de novo lipogenesis and reduced fatty acid catabolism, associated with increased expression of SREBF1/SREBP-1, GCK, ACACA, ACACB and FASN genes. May also affect de novo cholesterol synthesis and HDL-cholesteryl ether uptake. Peripherally modulates energy metabolism. In high carbohydrate diet-induced obesity, may decrease the expression of mitochondrial dihydrolipoyl dehydrogenase/DLD in striated muscles, as well as that of selected glucose/ pyruvate metabolic enzymes, hence affecting energy expenditure through mitochondrial metabolism. In response to cannabinoid anandamide, elicits a proinflammatory response in macrophages, which involves NLRP3 inflammasome activation and IL1B and IL18 secretion. In macrophages infiltrating pancreatic islets, this process may participate in the progression of type-2 diabetes and associated loss of pancreatic beta-cells .Binds both 2-AG and anandamide.Only binds 2-AG with high affinity. Contrary to its effect on isoform 1, 2-AG behaves as an inverse agonist on isoform 2 in assays measuring GTP binding to membranes.Only binds 2-AG with high affinity. Contrary to its effect on isoform 1, 2-AG behaves as an inverse agonist on isoform 3 in assays measuring GTP binding to membranes.

KO Status

RenMab: Antibody Discovery

Drug Information

Launched drugs: 2
Drugs in clinical trials: 15
Latest Research Phase: Approved

Drug Name





Clinical Trials


BTX-1503, BTX-1801, GWP-42003-P, BOL-DP-o-05, GW-42003, BTX-1204, ZYN-002, PTL-101, CHI-902, APH-1501, AVCN-583601, GLA-015, BTX-1702, PBX-1308, ART-12.11, ART-1211


Gw Pharmaceuticals, Insys Therapeutics, Isa Pharmaceuticals

Acne Vulgaris, Migraine Disorders, Schizophrenia, Seizures, Anxiety, Fatty Liver, Autism Spectrum Disorder, Tuberous Sclerosis, Diabetes Mellitus, Type 2, Rett Syndrome, Inflammatory Bowel Diseases, Graft vs Host Disease, Musculoskeletal Pain, Diabetic Neuropathies, Chronic Urticaria, Opioid-Related Disorders, Neoplasms, Lennox Gastaut Syndrome, Phobia, Social, Multiple Sclerosis, Azotemia, Stroke, Fragile X Syndrome, Epilepsy, Absence, Spasms, Infantile, Dyslipidemias, Epilepsy, Prader-Willi Syndrome, Colitis, Ulcerative, Fear, Hepatitis, Autoimmune, Stress Disorders, Post-Traumatic, Substance Withdrawal Syndrome, Panic, Drug Resistant Epilepsy, Epilepsies, Myoclonic, Crohn Disease, Dermatitis, Atopic


BOL-DP-o-04, GW-1000-02, PPP-001, MGC-ODT, GW-1000


Gw Pharmaceuticals

Peripheral Nervous System Diseases, Pain, Chronic Pain, Squamous Cell Carcinoma of Head and Neck, Renal Insufficiency, Spasm, Cancer Pain, Marijuana Use, Neoplasms, Neck Pain, Diabetic Neuropathies, Kidney Diseases, Multiple Sclerosis, Neuralgia, Postherpetic, Muscle Spasticity, Sciatica, Acute Pain, Back Pain, Hepatic Insufficiency, Neuralgia, Osteoarthritis, Knee, Stress Disorders, Post-Traumatic, Hidradenitis Suppurativa, Cerebral Palsy, Low Back Pain



Phase 3 Clinical

Low Back Pain


RYI-018, RYI-028, JNJ-2463

Phase 2 Clinical

Bird Rock Bio, Janssen Global Services Llc

Non-alcoholic Fatty Liver Disease, Diabetic Nephropathies, Obesity, Diabetic Gastroparesis


THCV, O-4394, GW-42004, GWP-42004, DELTA9-THCV

Phase 2 Clinical

Gw Pharmaceuticals Plc

Diabetes Mellitus, Type 2, Dyslipidemias



Phase 2 Clinical

National Institute On Drug Abuse, Aelis Farma

Substance-Related Disorders, Marijuana Abuse



Phase 2 Clinical

Eli Lilly And Company

Substance-Related Disorders, Obesity



Phase 2 Clinical

Axim Biotech

Psoriasis, Dermatitis, Atopic, Vitiligo


V-24343, ANEB-001

Phase 2 Clinical


Poisoning, Obesity

Cannabidiol/Tetrahydrocannabivarin (40:1)

Phase 2 Clinical

Gw Pharmaceuticals Plc






The DNA sequence and analysis of human chromosome 6

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Nature 425:805-811(2003)

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)

The MGC Project Team,

Genome Res. 14:2121-2127(2004)

CB1 cannabinoid receptor activity is modulated by the cannabinoid receptor interacting protein CRIP 1a

Niehaus J.L., Liu Y., Wallis K.T., Egertova M., Bhartur S.G., Mukhopadhyay S., Shi S., He H., Selley D.E., Howlett A.C., Elphick M.R., Lewis D.L.,

Mol. Pharmacol. 72:1557-1566(2007)

Effects of palmitoylation of Cys(415) in helix 8 of the CB(1) cannabinoid receptor on membrane localization and signalling

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Br. J. Pharmacol. 165:2635-2651(2012)

The acyclic CB1R inverse agonist taranabant mediates weight loss by increasing energy expenditure and decreasing caloric intake

Addy C., Wright H., Van Laere K., Gantz I., Erondu N., Musser B.J., Lu K., Yuan J., Sanabria-Bohorquez S.M., Stoch A., Stevens C., Fong T.M., De Lepeleire I., Cilissen C., Cote J., Rosko K., Gendrano I.N. III, Nguyen A.M., Heymsfield S.B.,

Cell Metab. 7:68-78(2008)

Activation of the Nlrp3 inflammasome in infiltrating macrophages by endocannabinoids mediates beta cell loss in type 2 diabetes

Jourdan T., Godlewski G., Cinar R., Bertola A., Szanda G., Liu J., Tam J., Han T., Mukhopadhyay B., Skarulis M.C., Ju C., Aouadi M., Czech M.P., Kunos G.,

Nat. Med. 19:1132-1140(2013)

Cannabinoid receptor-G protein interactions: G(alphai1)-bound structures of IC3 and a mutant with altered G protein specificity

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Protein Sci. 11:2526-2531(2002)

Crystal structure of the human cannabinoid receptor CB1

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Cell 167:750-762(2016)

High-resolution crystal structure of the human CB1 cannabinoid receptor

Shao Z., Yin J., Chapman K., Grzemska M., Clark L., Wang J., Rosenbaum D.M.,

Nature 540:602-606(2016)

An amino-terminal variant of the central cannabinoid receptor resulting from alternative splicing

Shire D., Carillon C., Kaghad M., Calandra B., Rinaldi-Carmona M., Le Fur G., Caput D., Ferrara P.,

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