CB1
Synonyms
CNR1, Cannabinoid Receptor 1, CANN6, CB-R, CNR, CB1, Central Cannabinoid Receptor, CB1K5, CB1A, CB1R, Receptor, Cannabinoid, CB1, Cannabinoid Receptor 1 (Brain)
Description
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
In Vitro
Drug Information
Launched drugs: 2
Drugs in clinical trials: 11
Latest Research Phase: Approved
Drug Name
Code
Phase
Company
Indications
Clinical Trials
Cannabidiol/Dronabinol
GW-1000, MGC-ODT, PPP-001, GW-1000-02, BOL-DP-o-04
Approved
Gw Pharmaceuticals
Peripheral Nervous System Diseases, Cancer Pain, Chronic Pain, Spasm, Pain, Squamous Cell Carcinoma of Head and Neck, Renal Insufficiency, Diabetic Neuropathies, Neoplasms, Kidney Diseases, Multiple Sclerosis, Neuralgia, Postherpetic, Muscle Spasticity, Acute Pain, Sciatica, Neuralgia, Stress Disorders, Post-Traumatic, Osteoarthritis, Knee, Hepatic Insufficiency, Hidradenitis Suppurativa, Low Back Pain, Cerebral Palsy
Cannabidiol
GWP-42003-P, BOL-DP-o-05, GW-42003, BTX-1204, ZYN-002, PTL-101, CHI-902, APH-1501, AVCN-583601, GLA-015, BTX-1503, BTX-1801, BTX-1702, PBX-1308
Approved
Gw Pharmaceuticals, Insys Therapeutics, Isa Pharmaceuticals
Migraine Disorders, Seizures, Tuberous Sclerosis, Rett Syndrome, Anxiety, Schizophrenia, Diabetes Mellitus, Type 2, Fatty Liver, Autism Spectrum Disorder, Graft vs Host Disease, Musculoskeletal Pain, Diabetic Neuropathies, Chronic Urticaria, Opioid-Related Disorders, Lennox Gastaut Syndrome, Azotemia, Multiple Sclerosis, Phobia, Social, Fragile X Syndrome, Spasms, Infantile, Epilepsy, Absence, Dyslipidemias, Epilepsy, Prader-Willi Syndrome, Fear, Hepatitis, Autoimmune, Substance Withdrawal Syndrome, Colitis, Ulcerative, Drug Resistant Epilepsy, Panic, Epilepsies, Myoclonic, Crohn Disease, Dermatitis, Atopic
AEF-0117
AEF-0117
Phase 2 Clinical
National Institute On Drug Abuse, Aelis Farma
Substance-Related Disorders, Marijuana Abuse
AX-1602
AX-1602
Phase 2 Clinical
Axim Biotech
Psoriasis, Dermatitis, Atopic, Vitiligo
11C-MePPEP
11C-MePPEP
Phase 2 Clinical
Eli Lilly And Company
Substance-Related Disorders, Obesity
Nimacimab
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
Tetrahydrocannabivarin
THCV, O-4394, GW-42004, GWP-42004, DELTA9-THCV
Phase 2 Clinical
Gw Pharmaceuticals Plc
Diabetes Mellitus, Type 2, Dyslipidemias
Cannabidiol/Tetrahydrocannabivarin (40:1)
Phase 2 Clinical
Gw Pharmaceuticals Plc
Schizophrenia
ART-2713
ART-2713
Phase 1 Clinical
Astra Zeneca Gmbh, Neomed Inc, Pfizer Pharmaceuticals Ltd (China)
Anorexia
ZYN-001
ZYN-001
Phase 1 Clinical
Zynerba Pharmaceuticals
Neuralgia, Fibromyalgia
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