Cannabinoid receptor - wikipedia Cannabinoid receptor CB and CB structures. cannabinoid receptor 1 ( brain ) NMR solution structure of a peptide mimetic of the fourth cytoplasmic loop of the CB cannabinoid receptor based on the PDB : 2b0y ​ coordinates. Identifiers Symbol CNR1 Alt. symbols CNR Entrez 1268 HUGO 2159 OMIM 114610 Orthologs 7273 RefSeq NM_033181 UniProt P21554 Other data Locus Chr. 6 q14 - q15 cannabinoid receptor 2 ( macrophage ) Identifiers Symbol CNR2 Entrez 1269 HUGO 2160 OMIM 605051 Orthologs 1389 RefSeq NM_001841 UniProt P34972 Other data Locus Chr. 1 p Part of a series on Cannabis Chemistry Cannabinoid receptors Cannabinoid receptor type 1 Cannabinoid receptor type 2 Cannabinoids 2 - AG 2 - AGE, Noladin ether AEA CBC CBL CBD CBDV CBG CBN CBV NADA THC THCV Virodhamine Synthetic cannabinoids AM - 2201 CP - 55940 Dimethylheptylpyran HU - 210 HU - 331 JWH - 018 JWH - 073 JWH - 133 Levonantradol SR144528 WIN 55,212 - 2 Consumption Edibles Smoking Tea Economics Coffeeshop Cultivation Shop Social Club Grow house Grow shop Head shop Marijuana vending machine Effects Dependence Drug testing Effects of legalized cannabis Gateway drug theory Long term effects Medicine Memory Pregnancy Psychosis Time perception Forms Bhang Blunt Charas Flower essential oil Hash oil Hashish Hemp Hemp oil Joint Kief Roach Synthetic cannabis Thai stick Tincture Law Cannabis political parties Cannabis rights Legality of cannabis Timeline Cannabis Act of Canada Legal history in Canada Legality of cannabis in US Timeline US : ( Medical Non-medical Legal history Drug policy of California Drug policy of Colorado ) Drug policy of Portugal Drug policy of the Netherlands Regional Adult lifetime cannabis use by country Annual cannabis use by country Afghanistan Alabama American Samoa Arkansas Australia Canada California Chile Egypt Georgia ( USA ) Guam Idaho India Indiana Iowa Jamaica Kansas Kentucky Louisiana Maine Massachusetts Montana Morocco Nebraska New Zealand Nigeria North Dakota North Mariana Islands Oregon Palau Papua New Guinea Paraguay Portugal South Dakota Svalbard Switzerland Tennessee U.K. U.S. Uruguay Utah Vermont Virginia Virginia Wisconsin Wyoming American Indian reservations Marijuana tourism in the U.S. Variants Autoflowering cannabis Cannabis genus Cannabis indica Cannabis ruderalis Cannabis sativa Cannabis strains Acapulco Gold Blue Dream Charlotte 's web Kush Malawi Gold Sour Diesel Arts Culture 420 Names Religion Judaism Latter - day Saints Sikhism Stoner film Stoner rock Terms Related Drug culture Illegal drug trade Psychedelia Cannabis portal Medicine portal Agriculture portal Cannabinoid receptors, located throughout the body, are part of the endocannabinoid system, which is involved in a variety of physiological processes including appetite, pain - sensation, mood, and memory. Cannabinoid receptors are of a class of cell membrane receptors in the G protein - coupled receptor superfamily. As is typical of G protein - coupled receptors, the cannabinoid receptors contain seven transmembrane spanning domains. Cannabinoid receptors are activated by three major groups of ligands : endocannabinoids, produced by the mammillary body ; plant cannabinoids ( such as cannabidiol, produced by the cannabis plant ) ; and synthetic cannabinoids ( such as HU - 210 ). All of the endocannabinoids and phytocannabinoids ( plant based cannabinoids ) are lipophilic, such as fat soluble compounds. There are currently two known subtypes of cannabinoid receptors, termed CB and CB. The CB receptor is expressed mainly in the brain ( central nervous system or `` CNS '' ), but also in the lungs, liver and kidneys. The CB receptor is expressed mainly in the immune system and in hematopoietic cells. Mounting evidence suggests that there are novel cannabinoid receptors that is, non-CB and non-CB, which are expressed in endothelial cells and in the CNS. In 2007, the binding of several cannabinoids to the G protein - coupled receptor GPR55 in the brain was described. The protein sequences of CB and CB receptors are about 44 % similar. When only the transmembrane regions of the receptors are considered, amino acid similarity between the two receptor subtypes is approximately 68 %. In addition, minor variations in each receptor have been identified. Cannabinoids bind reversibly and stereo - selectively to the cannabinoid receptors. Subtype selective cannabinoids have been developed which theoretically may have advantages for treatment of certain diseases such as obesity. It appears that cannabinoid receptors are unique to the phylum Chordata and, as such, they have a rather restricted phylogenetic distribution in the animal kingdom. However, enzymes involved in biosynthesis / inactivation of endocannabinoids and endocannabinoid signalling in general ( involving targets other than CB1 / 2 - type receptors ) occur throughout the animal kingdom. Although the cannabinoid receptors are unique to Chordates, other organisms are still able to process the endocannabinoids through other techniques. Contents 1 CB 2 CB 3 Other cannabinoid receptors 4 Signaling 5 Physiology 5.1 Cardiovascular activity 6 Cannabinoid treatments 7 Ligands 7.1 Binding affinity and selectivity of cannabinoid ligands 8 See also 9 References 10 External links CB Main article : Cannabinoid receptor type 1 Cannabinoid receptor type 1 ( CB ) receptors are thought to be one of the most widely expressed G protein - coupled receptors in the brain. This is due to endocannabinoid - mediated depolarization - induced suppression of inhibition, a very common form of retrograde signaling, in which the depolarization of a single neuron induces a reduction in GABA - mediated neurotransmission. Endocannabinoids released from the depolarized post-synaptic neuron bind to CB receptors in the pre-synaptic neuron and cause a reduction in GABA release due to limited presynaptic calcium ions entry. They are also found in other parts of the body. For instance, in the liver, activation of the CB receptor is known to increase de novo lipogenesis. Prenatal cannabis exposure ( PCE ) perturbs the fetal endogenous cannabinoid signaling system ( ECSS ) which effects neurodevelopment and results in abnormalities in cognition and neuropsychiatric disorders. CB Main article : Cannabinoid receptor type 2 CB receptors are mainly expressed on T cells of the immune system, on macrophages and B cells, and in hematopoietic cells. They also have a function in keratinocytes. They are also expressed on peripheral nerve terminals. These receptors play a role in antinociception, or the relief of pain. In the brain, they are mainly expressed by microglial cells, where their role remains unclear. While the most likely cellular targets and executors of the CB receptor - mediated effects of endocannabinoids or synthetic agonists are the immune and immune - derived cells ( e.g. leukocytes, various populations of T and B lymphocytes, monocytes / macrophages, dendritic cells, mast cells, microglia in the brain, Kupffer cells in the liver, astrocytes, etc. ), the number of other potential cellular targets is expanding, now including endothelial and smooth muscle cells, fibroblasts of various origins, cardiomyocytes, and certain neuronal elements of the peripheral or central nervous systems. Other cannabinoid receptors The existence of additional cannabinoid receptors has long been suspected, due to the actions of compounds such as abnormal cannabidiol that produce cannabinoid - like effects on blood pressure and inflammation, yet do not activate either CB or CB. Recent research strongly supports the hypothesis that the N - arachidonoyl glycine ( NAGly ) receptor GPR18 is the molecular identity of the abnormal cannabidiol receptor and additionally suggests that NAGly, the endogenous lipid metabolite of anandamide ( also known as arachidonoylethanolamide or AEA ), initiates directed microglial migration in the CNS through activation of GPR18. Other molecular biology studies have suggested that the orphan receptor GPR55 should in fact be characterised as a cannabinoid receptor, on the basis of sequence homology at the binding site. Subsequent studies showed that GPR55 does indeed respond to cannabinoid ligands. This profile as a distinct non-CB / CB receptor that responds to a variety of both endogenous and exogenous cannabinoid ligands, has led some groups to suggest GPR55 should be categorized as the CB receptor, and this re-classification may follow in time. However this is complicated by the fact that another possible cannabinoid receptor has been discovered in the hippocampus, although its gene has not yet been cloned, suggesting that there may be at least two more cannabinoid receptors to be discovered, in addition to the two that are already known. GPR119 has been suggested as a fifth possible cannabinoid receptor. Signaling Cannabinoid receptors are activated by cannabinoids, generated naturally inside the body ( endocannabinoids ) or introduced into the body as cannabis or a related synthetic compound. Similar responses are produced when introduced in alternative methods, only in a more concentrated form than what is naturally occurring. After the receptor is engaged, multiple intracellular signal transduction pathways are activated. At first, it was thought that cannabinoid receptors mainly inhibited the enzyme adenylate cyclase ( and thereby the production of the second messenger molecule cyclic AMP ), and positively influenced inwardly rectifying potassium channels ( = Kir or IRK ). However, a much more complex picture has appeared in different cell types, implicating other potassium ion channels, calcium channels, protein kinase A and C, Raf - 1, ERK, JNK, p38, c - fos, c - jun and many more. Separation between the therapeutically undesirable psychotropic effects, and the clinically desirable ones, however, has not been reported with agonists that bind to cannabinoid receptors. THC, as well as the two major endogenous compounds identified so far that bind to the cannabinoid receptors -- anandamide and 2 - arachidonylglycerol ( 2 - AG ) -- produce most of their effects by binding to both the CB and CB cannabinoid receptors. While the effects mediated by CB, mostly in the central nervous system, have been thoroughly investigated, those mediated by CB are not equally well defined. Physiology Cardiovascular activity Studies have suggested that activation of CB receptors in human and rodent cardiomyocytes, coronary artery endothelial and inflammatory cells promotes activation of mitogen - activated protein ( MAP ) kinases p38 and JNK, reactive oxygen species generation, cell death, and cardiovascular inflammatory response both in vitro, as well as in models of heart failure, atherosclerosis and vascular inflammation. Cannabinoid treatments Main article : Medical cannabis Synthetic tetrahydrocannabinol ( THC ) is prescribed under the INN dronabinol or the brand name Marinol, to treat vomiting and for enhancement of appetite, mainly in people with AIDS as well as for refractory nausea and vomiting in people undergoing chemotherapy. Use of synthetic THC is becoming more common as the known benefits become more prominent within the medical industry. THC is also an active ingredient in nabiximols, a specific extract of Cannabis that was approved as a botanical drug in the United Kingdom in 2010 as a mouth spray for people with multiple sclerosis to alleviate neuropathic pain, spasticity, overactive bladder, and other symptoms. Ligands See also : cannabinoid receptor type 1 ligands, cannabinoid receptor type 2 ligands Binding affinity and selectivity of cannabinoid ligands CB affinity ( K ) Efficacy towards CB CB affinity ( K ) Efficacy towards CB Type References Anandamide 78nM Full agonist 370nM ? Endogenous N - Arachidonoyl dopamine ? Agonist ? ? Endogenous 2 - Arachidonoylglycerol ? Full agonist ? ? Endogenous 2 - Arachidonyl glyceryl ether 21 nM Full agonist 480nM Full agonist Endogenous Δ - 9 - Tetrahydrocannabinol 10nM Partial agonist 24nM Partial agonist Phytogenic EGCG 33.6 μM Agonist > 50μM ? Phytogenic Yangonin 0.72 μM ? > 10 μM ? Phytogenic AM - 1221 52.3 nM Agonist 0.28 nM Agonist Synthetic AM - 1235 1.5 nM Agonist 20.4 nM Agonist Synthetic AM - 2232 0.28 nM Agonist 1.48 nM Agonist Synthetic UR - 144 150nM Full agonist 1.8 nM Full agonist Synthetic JWH - 007 9.0 nM Agonist 2.94 nM Agonist Synthetic JWH - 015 383nM Agonist 13.8 nM Agonist Synthetic JWH - 018 9.00 ± 5.00 nM Full agonist 2.94 ± 2.65 nM Full agonist Synthetic See also Cannabinoid receptor antagonist Endocannabinoid enhancer Endocannabinoid reuptake inhibitor Cannabidiol Effects of cannabis References Jump up ^ Aizpurua - Olaizola O, Elezgarai I, Rico - Barrio I, Zarandona I, Etxebarria N, Usobiaga A ( January 2017 ). `` Targeting the endocannabinoid system : future therapeutic strategies ''. Drug Discovery Today. 22 ( 1 ) : 105 -- 110. doi : 10.1016 / j. drudis. 2016.08. 005. PMID 27554802. Jump up ^ Howlett AC ( August 2002 ). `` The cannabinoid receptors ''. 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External links Cannabinoid + Receptors at the US National Library of Medicine Medical Subject Headings ( MeSH ) The Endocannabinoid System Network ( ECSN ) - CB receptor `` Cannabinoid Receptors ''. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Cell surface receptor : G protein - coupled receptors Class A : Rhodopsin - like Neurotransmitter Adrenergic α1 ( A D ) α2 ( A C ) β1 β2 β3 Purinergic Adenosine ( A1 A2A A2B A3 ) P2Y ( 1 5 6 8 9 10 11 12 13 14 ) Serotonin ( all but 5 - HT3 ) 5 - HT1 ( A F ) 5 - HT2 ( A C ) 5 - HT ( 4 5A 6 7 ) Other Acetylcholine ( M1 M2 M3 M4 M5 ) Dopamine D1 D2 D3 D4 D5 GHB receptor Histamine H1 H2 H3 H4 Melatonin ( 1A 1B 1C ) TAAR ( 1 5 6 8 9 ) Metabolites and signaling molecules Eicosanoid CysLT ( 1 2 ) LTB4 FPRL1 OXE Prostaglandin DP ( 1 2 ), EP ( 1 4 ), FP Prostacyclin Thromboxane Other Bile acid Cannabinoid ( CB1 CB2, GPR ( 18 55 119 ) ) EBI2 Estrogen Free fatty acid ( 1 4 ) Hydroxycarboxylic acids Lysophosphatidic acid ( 1 5 6 ) Lysophospholipid ( 1 5 6 7 8 ) Oxoglutarate PAF Sphingosine - 1 - phosphate ( 1 5 ) Succinate Peptide Neuropeptide B / W ( 1 2 ) FF ( 1 2 ) Y ( 1 5 ) Neuromedin ( B U ( 1 2 ) ) Neurotensin ( 1 2 ) Other Anaphylatoxin ( C3a C5a ) Angiotensin ( 1 2 ) Apelin Bombesin BRS3 GRPR NMBR ) Bradykinin ( B1 B2 ) Chemokine Cholecystokinin ( A B) Endothelin Formyl peptide ( 1 3 ) FSH Galanin ( 1 3 ) Gonadotropin - releasing hormone ( 1 2 ) Ghrelin Kisspeptin Luteinizing hormone / choriogonadotropin MAS ( 1 1L X1 X2 X3 X4 ) Melanocortin ( 1 5 ) MCHR ( 1 2 ) Motilin Opioid ( Delta Kappa Mu Nociceptin & Zeta, but not Sigma ) Orexin ( 1 2 ) Oxytocin Prokineticin ( 1 2 ) Prolactin - releasing peptide Relaxin ( 1 4 ) Somatostatin ( 1 5 ) Tachykinin ( 1 3 ) Thyrotropin Thyrotropin - releasing hormone Urotensin - II Vasopressin ( 1A 1B 2 ) Miscellaneous Orphan GPR ( 1 6 12 15 17 18 19 20 21 22 23 25 26 27 31 32 33 34 35 37 39 42 44 45 50 52 55 61 62 63 65 68 75 77 78 81 82 83 84 85 87 88 92 101 103 109A 109B 119 120 132 135 137B 139 141 142 146 148 149 150 151 152 153 160 161 162 171 173 174 176 177 182 183 ) Other Adrenomedullin Olfactory Opsin ( 3 5 1LW 1MW 1SW RGR RRH ) Protease - activated ( 1 4 ) SREB ( 1 3 ) Class B : Secretin - like Adhesion ADGRG ( 1 5 6 7 ) Orphan GPR ( 56 64 97 98 110 111 112 113 114 115 116 123 124 125 126 128 133 143 144 155 157 ) Other Brain - specific angiogenesis inhibitor ( 1 3 ) Cadherin ( 1 3 ) Calcitonin CALCRL CD97 Corticotropin - releasing hormone ( 1 2 ) EMR ( 1 3 ) Glucagon ( GR GIPR GLP1R GLP2R ) Growth - hormone - releasing hormone PACAPR1 GPR Latrophilin ( 1 ELTD1 ) Methuselah - like proteins Parathyroid hormone ( 1 2 ) Secretin Vasoactive intestinal peptide ( 1 2 ) Class C : Metabotropic glutamate / pheromone Taste TAS1R ( 1 3 ) TAS2R ( 1 5 7 8 9 10 13 14 16 19 20 30 31 38 39 40 41 42 43 45 46 50 60 Vomeronasal receptor ) Other Calcium - sensing receptor GABA ( 1 2 ) Glutamate receptor ( Metabotropic glutamate ( 1 5 6 7 8 ) ) GPRC6A GPR ( 156 158 179 ) RAIG ( 1 4 ) Class F : Frizzled & Smoothened Frizzled Frizzled ( 1 5 6 7 8 9 10 ) Smoothened Smoothened Cannabinoid receptor modulators Receptor ( ligands ) CB Agonists ( abridged ; see here for more ) : 2 - AG 2 - AGE ( noladin ether ) 11 - Hydroxy - THC α - Amyrin β - Amyrin AB - CHMINACA AM - 1172 AM - 1220 AM - 1221 AM - 1235 AM - 2201 AM - 2232 Anandamide Arvanil AZ - 11713908 Cannabinol CB - 13 CP 47,497 CP 55,940 Dimethylheptylpyran DEA ECG EGCG Epicatechin Gallocatechol ( gallocatechin ) Honokiol HU - 210 JWH - 007 JWH - 015 JWH - 018 JWH - 073 Kavain L - 759,633 Levonantradol Menabitan Nabilone Nabitan NADA O - 1812 Oleamide Pravadoline Serinolamide A THC ( dronabinol ) UR - 144 WIN 55,212 - 2 Yangonin Antagonists : AM - 251 AM - 6545 Cannabidiol Cannabigerol Drinabant Falcarinol ( carotatoxin ) Hemopressin Ibipinabant LY - 320,135 MK - 9470 NESS - 0327 O - 2050 Otenabant PF - 514273 PipISB Rimonabant Rosonabant Surinabant Taranabant THCV TM - 38837 VCHSR Virodhamine Antibodies : Brizantin ( Бризантин ) Dietressa ( Диетресса ) Unknown / unsorted : MAFP CB Agonists : 2 - AG 2 - AGE ( noladin ether ) 3, 3 ' - Diindolylmethane 4 - O - Methylhonokiol α - Amyrin β - Amyrin A-796,260 A-834,735 A-836,339 AM - 1172 AM - 1221 AM - 1235 AM - 1241 AM - 2232 Anandamide AZ - 11713908 Cannabinol Caryophyllene CB - 13 CBS - 0550 CP - 55,940 GW - 405,833 ( L - 768,242 ) GW - 842,166 X HU - 308 JTE 7 - 31 JWH - 007 JWH - 015 JWH - 018 JWH - 73 JWH - 133 L - 759,633 L - 759,656 Lenabasum ( anabasum ) Magnolol MDA - 19 Nabitan NADA Olorinab ( APD - 371 ) PF - 03550096 S - 444,823 SER - 601 Serinolamide A UR - 144 Tedalinab THC ( dronabinol ) THCV Tetrahydromagnolol Virodhamine Antagonists : 4 - O - Methylhonokiol AM - 630 BML - 190 Cannabidiol Honokiol JTE - 907 SR - 144,528 WIN 54,461 WIN 56,098 NAGly ( GPR18 ) Agonists : Abnormal cannabidiol ACPA AM251 Anandamide Cannabidiol NADGly THC ( dronabinol ) O - 1602 Antagonists : CID - 85469571 O - 1918 GPR55 Agonists : 2 - AGE ( noladin ether ) 2 - ALPI Abnormal cannabidiol AM - 251 CID1011163 CID1252842 CID1792579 CP 55,940 GSK - 494581A Lysophosphatidylinositol ML - 184 ML - 185 ML - 186 O - 1602 Oleoylethanolamide Palmitoylethanolamide THC ( dronabinol ) Antagonists : Cannabidiol CID - 16020046 ML - 191 ML - 192 ML - 193 O - 1918 PSB - SB - 487 PSB - SB - 1202 PSB - SB - 1203 Tetrahydromagnolol GPR119 Agonists : 2 - Oleoylglycerol Anandamide APD668 AR - 231,453 AS - 1269574 MBX - 2982 N - Oleoyldopamine Oleoylethanolamide Olvanil PSN - 375,963 PSN - 632,408 Unsorted Agonists : Revosimeline Transporter ( modulators ) eCBTs Inhibitors : 5 ' - DMH - CBD AM - 404 AM - 1172 Arachidonoyl serotonin Arvanil Cannabidiol Guineensine LY - 2183240 O - 2093 OMDM - 2 Paracetamol ( acetaminophen ) SB - FI - 26 UCM - 707 URB - 597 VDM - 11 WOBE490 WOBE491 WOBE492 Enzyme ( modulators ) FAAH Inhibitors : 4 - Nonylphenylboronic acid AACOCF AM - 404 Arachidonoyl serotonin BIA 10 - 2474 Biochanin A Genistein IDFP JNJ - 1661010 JNJ - 42165279 JZL - 195 Kaempferol LY - 2183240 MAFP Palmitoylisopropylamide Paracetamol ( acetaminophen ) PF - 3845 PF - 04457845 PF - 750 SA - 47 SA - 57 TAK 21d TC - F 2 UCM710 URB - 597 Activators : PDP - EA MAGL Inhibitors : ABX - 1431 IDFP JJKK 048 JW 642 JZL - 184 JZL - 195 JZP - 361 KML 29 MAFP MJN110 NAM Pristimerin URB - 602 ABHD6 Inhibitors : JZP - 169 JZP - 430 KT182 KT185 KT195 KT203 LEI - 106 ML294 ML295 ML296 UCM710 WWL - 70 ABHD12 Inhibitors : Betulinic acid Maslinic acid MAFP Oleanolic acid Orlistat ( tetrahydrolipstatin ) Ursolic acid Others Precursors : Phosphatidylethanolamine NAPE Diacylglycerol Others : 2 - PG ( directly potentiates activity of 2 - AG at CB receptor ) ARN - 272 ( FAAH - like anandamide transporter inhibitor ) See also Receptor / signaling modulators Cannabinoids ( cannabinoids by structure ) Retrieved from `` https://en.wikipedia.org/w/index.php?title=Cannabinoid_receptor&oldid=864540634 '' Categories : Genes on human chromosome 6 Genes on human chromosome 1 G protein - coupled receptors Hidden categories : Protein pages needing a picture All articles with unsourced statements Articles with unsourced statements from October 2018 Articles with unsourced statements from December 2017 Talk Variants Contents About Wikipedia Català Čeština Deutsch Español فارسی Italiano Nederlands Polski Português Română Русский Српски / srpski Srpskohrvatski / српскохрватски Suomi Svenska Українська 8 more Edit links This page was last edited on 17 October 2018, at 21 : 49 ( UTC ). 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Question: where are cannabinoid receptors located in the brain
Answer: central nervous system