Editing Cannabinoid receptor

{{short description|Group of receptors to cannabinoid compounds}}
{{human-centric|date=May 2024}}
{{Infobox protein
| Name       = [[cannabinoid receptor 1]]
| image      = Human cannabinoid receptor 1 (CB1) PDB 5XRA.png
| width      = 120
| caption    = Human cannabinoid receptor 1 (CB<sub>1</sub>) bound to tetrahydrocannabinol agonist AM11542 (black). {{PDB|5XRA}}
| Symbol     = CNR1
| AltSymbols = CNR
| IUPHAR_id  = 
| EntrezGene = 1268
| HGNCid     = 2159
| OMIM       = 114610
| HomoloGene = 7273
| RefSeq     = NM_033181
| UniProt    = P21554
| ECnumber   = 
| Chromosome = 6
| Arm        = q
| Band       = 14
| LocusSupplementaryData = -q15
}}
{{Infobox protein
| Name       = [[cannabinoid receptor 2]]
| image      = Human cannabinoid receptor 2 (CB2) PDB 5ZTY.png
| width      = 120
| caption    = Human cannabinoid receptor 2 (CB<sub>2</sub>) bound to agonist AM10257 (black). {{PDB|5ZTY}}
| Symbol     = CNR2
| AltSymbols = 
| IUPHAR_id  = 
| EntrezGene = 1269
| HGNCid     = 2160
| OMIM       = 605051
| HomoloGene = 1389
| PDB        = 
| RefSeq     = NM_001841
| UniProt    = P34972
| ECnumber   = 
| Chromosome = 1
| Arm        = p
| Band       = 
| LocusSupplementaryData = 
}}
{{Cannabis sidebar}}
[[File:Cb1 cb2 structure.png|class=skin-invert-image|thumb|237px|[[Cannabinoid receptor 1|CB<sub>1</sub>]] and [[Cannabinoid receptor 2|CB<sub>2</sub>]] structures]]

'''Cannabinoid receptors''', located throughout the body, are part of the [[endocannabinoid system]] of vertebrates{{ndash}} a class of [[cell membrane]] [[Receptor (biochemistry)|receptor]]s in the [[G protein-coupled receptor]] superfamily.<ref name="pmid12432948"/><ref name="pmid18426493"/><ref name="pmid19273110"/><ref>{{cite journal | vauthors = Aizpurua-Olaizola O, Elezgarai I, Rico-Barrio I, Zarandona I, Etxebarria N, Usobiaga A | title = Targeting the endocannabinoid system: future therapeutic strategies | journal = Drug Discovery Today | volume = 22 | issue = 1 | pages = 105–110 | date = January 2017 | pmid = 27554802 | doi = 10.1016/j.drudis.2016.08.005 | s2cid = 3460960 | url = https://figshare.com/articles/journal_contribution/5028362 | access-date = 2022-10-19 | archive-date = 2023-01-27 | archive-url = https://web.archive.org/web/20230127151549/https://figshare.com/articles/journal_contribution/Targeting_the_endocannabinoid_system_future_therapeutic_strategies/5028362 | url-status = live }}</ref> As is typical of G protein-coupled receptors, the cannabinoid receptors contain seven transmembrane spanning domains.<ref name="pmid7556170"/> Cannabinoid receptors are activated by three major groups of [[ligand (biochemistry)|ligands]]: 

* [[Endocannabinoids]]; 
* [[Phytocannabinoid]]s (plant-derived such as [[tetrahydrocannabinol]] (THC) produced by [[cannabis]]); 
* [[Chemical synthesis|Synthetic]] cannabinoids (such as [[HU-210]]). 

All endocannabinoids and phytocannabinoids are [[lipophilic]].

There are two known subtypes of cannabinoid receptors, termed [[cannabinoid receptor type 1|CB<sub>1</sub>]] and [[cannabinoid receptor type 2|CB<sub>2</sub>]].<ref name="pmid2165569"/><ref name="pmid1718258"/> The CB<sub>1</sub> receptor is expressed mainly in the [[human brain|brain]] ([[central nervous system]] or "CNS"), but also in the [[lung]]s, [[liver]] and [[kidney]]s. The CB<sub>2</sub> receptor is expressed mainly in the [[immune system]], in [[Pluripotential hemopoietic stem cell|hematopoietic cells]],<ref name="pmid21295074">{{cite journal | vauthors = Pacher P, Mechoulam R | title = Is lipid signaling through cannabinoid 2 receptors part of a protective system? | journal = Progress in Lipid Research | volume = 50 | issue = 2 | pages = 193–211 | date = April 2011 | pmid = 21295074 | pmc = 3062638 | doi = 10.1016/j.plipres.2011.01.001 }}</ref> and in parts of the brain.<ref name="pmid30611802">{{cite journal | vauthors = Jordan CJ, Xi ZX | title = Progress in brain cannabinoid CB2 receptor research: From genes to behavior | journal = Neuroscience and Biobehavioral Reviews | volume = 98 | pages = 208–220 | date = March 2019 | pmid = 30611802 | doi = 10.1016/j.neubiorev.2018.12.026 | pmc = 6401261 }}</ref>

The protein sequences of CB<sub>1</sub> and CB<sub>2</sub> receptors are about 44% similar.<ref name=latek>{{cite journal | vauthors = Latek D, Kolinski M, Ghoshdastider U, Debinski A, Bombolewski R, Plazinska A, Jozwiak K, Filipek S | display-authors = 6 | title = Modeling of ligand binding to G protein coupled receptors: cannabinoid CB1, CB2 and adrenergic β 2 AR | journal = Journal of Molecular Modeling | volume = 17 | issue = 9 | pages = 2353–66 | date = September 2011 | pmid = 21365223 | doi = 10.1007/s00894-011-0986-7 | s2cid = 28365397 }}</ref><ref name="pmid7689702"/> When only the transmembrane regions of the receptors are considered, amino acid similarity between the two receptor subtypes is approximately 68%.<ref name="pmid7556170"/> In addition, minor variations in each receptor have been identified. Cannabinoids bind reversibly and [[stereochemistry|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.<ref name="pmid17148745">{{cite journal | vauthors = Kyrou I, Valsamakis G, Tsigos C | title = The endocannabinoid system as a target for the treatment of visceral obesity and metabolic syndrome | journal = Annals of the New York Academy of Sciences | volume = 1083 | issue =  1| pages = 270–305 | date = November 2006 | pmid = 17148745 | doi = 10.1196/annals.1367.024 | bibcode = 2006NYASA1083..270K | s2cid = 23486551 }}</ref>

Enzymes involved in biosynthesis/inactivation of [[endocannabinoid]]s and endocannabinoid signaling in general (involving targets other than CB1/2-type receptors) occur throughout the animal kingdom.<ref>{{cite journal | vauthors = Elphick MR | title = The evolution and comparative neurobiology of endocannabinoid signalling | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 367 | issue = 1607 | pages = 3201–15 | date = December 2012 | pmid = 23108540 | pmc = 3481536 | doi = 10.1098/rstb.2011.0394 }}</ref>

== Discovery ==

The existence of cannabinoid [[receptor (biochemistry)|receptors]] in the brain was discovered from [[in vitro]] studies in the 1980s, with the receptor designated as the [[cannabinoid receptor type 1]] or CB1.<ref name="elphick">{{cite journal | vauthors = Elphick MR, Egertová M | title = The neurobiology and evolution of cannabinoid signalling | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 356 | issue = 1407 | pages = 381–408 | date = March 2001 | pmid = 11316486 | pmc = 1088434 | doi = 10.1098/rstb.2000.0787 | type = Review }}</ref><ref name="Pertwee_2006">{{cite journal | vauthors = Pertwee RG | title = Cannabinoid pharmacology: the first 66 years | journal = British Journal of Pharmacology | volume = 147 | issue = Suppl 1 | pages = S163–71 | date = January 2006 | pmid = 16402100 | pmc = 1760722 | doi = 10.1038/sj.bjp.0706406 | type = Review }}</ref> The [[DNA sequencing|DNA sequence]] that encodes a [[G-protein]]-coupled cannabinoid receptor in the human brain was identified and [[cloning|cloned]] in 1990.<ref>{{cite journal | vauthors = Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI | title = Structure of a cannabinoid receptor and functional expression of the cloned cDNA | journal = Nature | volume = 346 | issue = 6284 | pages = 561–4 | date = August 1990 | pmid = 2165569 | doi = 10.1038/346561a0 | bibcode = 1990Natur.346..561M | s2cid = 4356509 }}</ref><ref name="Howlett_2002">{{cite journal | vauthors = Howlett AC, Barth F, Bonner TI, Cabral G, Casellas P, Devane WA, Felder CC, Herkenham M, Mackie K, Martin BR, Mechoulam R, Pertwee RG | display-authors = 6 | title = International Union of Pharmacology. XXVII. Classification of cannabinoid receptors | journal = Pharmacological Reviews | volume = 54 | issue = 2 | pages = 161–202 | date = June 2002 | pmid = 12037135 | doi =  10.1124/pr.54.2.161| s2cid = 8259002 | type = Review }}</ref> These discoveries led to determination in 1993 of a second brain cannabinoid receptor named [[cannabinoid receptor type 2]] or CB2.<ref name=Pertwee_2006/>

A [[neurotransmitter]] for a possible [[endocannabinoid]] system in the brain and [[peripheral nervous system]], [[anandamide]] (from 'ananda', [[Sanskrit]] for '[[pleasure|bliss]]'), was first characterized in 1992,<ref name="unpaved">{{cite book |vauthors=Mechoulam R, Fride E |editor=Pertwee RG |title=Cannabinoid receptors |publisher=Academic Press |location=Boston |year=1995 |pages=233–258 |chapter=The unpaved road to the endogenous brain cannabinoid ligands, the anandamides |isbn=978-0-12-551460-6 | type = Review}}</ref><ref>{{cite journal | vauthors = Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, Gibson D, Mandelbaum A, Etinger A, Mechoulam R | display-authors = 6 | title = Isolation and structure of a brain constituent that binds to the cannabinoid receptor | journal = Science | volume = 258 | issue = 5090 | pages = 1946–9 | date = December 1992 | pmid = 1470919 | doi = 10.1126/science.1470919 | bibcode = 1992Sci...258.1946D }}</ref><ref name="Hanus_2007">{{cite journal | vauthors = Hanus LO | title = Discovery and isolation of anandamide and other endocannabinoids | journal = Chemistry & Biodiversity | volume = 4 | issue = 8 | pages = 1828–41 | date = August 2007 | pmid = 17712821 | doi = 10.1002/cbdv.200790154 | s2cid = 745528 }}</ref> followed by discovery of other [[fatty acid]] neurotransmitters that behave as endogenous cannabinoids having a low-to-high range of efficacy for stimulating CB1 receptors in the brain and CB2 receptors in the periphery.<ref name=Pertwee_2006/><ref name=unpaved/>

== Types ==

=== CB<sub>1</sub> ===
{{Main|Cannabinoid receptor type 1}}

Cannabinoid receptor type 1 (CB<sub>1</sub>) receptors are thought to be one of the most widely [[Gene expression|expressed]] G<sub>αi</sub> protein-coupled receptors in the brain. One mechanism through which they function is 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<sub>1</sub> receptors in the pre-synaptic neuron and cause a reduction in GABA release due to limited presynaptic calcium ions entry.{{medcn|date=December 2017}}

They are also found in other parts of the body. For instance, in the liver, activation of the CB<sub>1</sub> receptor is known to increase de novo [[lipogenesis]].<ref name="pmid15864349"/>

=== CB<sub>2</sub> ===
{{Main|Cannabinoid receptor type 2}}

[[Cannabinoid receptor 2 (macrophage)|CB<sub>2</sub>]] receptors are expressed on [[T cell]]s of the [[immune system]], on [[macrophage]]s and [[B cell]]s, in [[Pluripotential hemopoietic stem cell|hematopoietic cells]], and in the brain and CNS (2019).<ref>{{cite book |vauthors=Onaivi J |chapter=Endocannabinoid System Components: Overview and Tissue Distribution |chapter-url=https://doi.org/10.1007/978-3-030-21737-2_1 |title=Recent Advances in Cannabinoid Physiology and Pathology |veditors=Bukiya A |publisher=Springer |location=Cham. |series=Advances in Experimental Medicine and Biology |year=2019 |volume=1162 |pages=1–12 |doi=10.1007/978-3-030-21737-2_1 |pmid=31332731 |isbn=978-3-030-21736-5 |s2cid=198172390 |access-date=19 October 2021 |archive-date=20 April 2023 |archive-url=https://web.archive.org/web/20230420210524/https://link.springer.com/chapter/10.1007/978-3-030-21737-2_1 |url-status=live }}</ref> They also have a function in [[keratinocyte]]s. 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 [[Microglia|microglial cells]], where their role remains unclear. While the most likely cellular targets and executors of the CB<sub>2</sub> 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, [[Monocyte|monocytes]]/[[Macrophage|macrophages]], [[Dendritic cell|dendritic cells]], [[Mast cell|mast cells]], microglia in the brain, [[Kupffer cell|Kupffer cells]] in the liver, [[Astrocyte|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 (2011).<ref name="pmid21295074"/>

=== Other ===
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<sub>1</sub> or CB<sub>2</sub>.<ref name="pmid10570211"/><ref name="pmid17965195"/> 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 [[Microglia#Chemokines|microglial migration]] in the CNS through activation of [[GPR18]].<ref name="pmid20346144"/> 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.<ref name="pmid17876302"/><ref name="pmid17704827"/> This profile as a distinct non-CB<sub>1</sub>/CB<sub>2</sub> 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<sub>3</sub> receptor, and this re-classification may follow in time.<ref name="pmid16517404"/> 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,<ref name="pmid18482429"/> 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,<ref name="pmid17906678"/> while the [[PPAR]] family of nuclear hormone receptors can also respond to certain types of cannabinoid.<ref>{{cite journal | vauthors = O'Sullivan SE | title = An update on PPAR activation by cannabinoids | journal = British Journal of Pharmacology | volume = 173 | issue = 12 | pages = 1899–910 | date = June 2016 | pmid = 27077495 | pmc = 4882496 | doi = 10.1111/bph.13497 }}</ref>

== Signaling ==
Cannabinoid receptors are activated by cannabinoids, generated naturally inside the body ([[Cannabinoid#Endocannabinoids|endocannabinoids]]) or introduced into the body as [[cannabis (drug)|cannabis]] or a related [[Chemical synthesis|synthetic]] compound.<ref name=latek /> 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 [[Inward-rectifier potassium ion channel|inwardly rectifying potassium channels]] (=Kir or IRK).<ref name="pmid16109430"/> However, a much more complex picture has appeared in different cell types, implicating other [[potassium ion channels]], [[calcium channel]]s, [[protein kinase A]] and [[protein kinase C|C]], [[C-Raf|Raf-1]], [[Extracellular signal-regulated kinases|ERK]], [[JNK]], [[p38 mitogen-activated protein kinases|p38]], [[c-fos]], [[c-jun]] and many more.<ref name="pmid16109430"/> For example, in human primary leukocytes CB<sub>2</sub> displays a complex signalling profile, activating [[adenylate cyclase]] via stimulatory [[Gs alpha subunit|G<sub>αs</sub>]] alongside the classical [[Gi alpha subunit|G<sub>αi</sub>]] signalling, and induces [[Extracellular signal-regulated kinases|ERK]], [[p38 mitogen-activated protein kinases|p38]] and [[CREB|pCREB]] pathways.<ref name="Saroz _2019">{{cite journal| vauthors = Saroz Y, Kho DT, Glass M, Graham ES, Grimsey NL | date = October 2019 |title = Cannabinoid Receptor 2 (CB2) Signals via G-alpha-s and Induces IL-6 and IL-10 Cytokine Secretion in Human Primary Leukocytes |journal=ACS Pharmacology & Translational Science | pages = 414–428 | doi = 10.1021/acsptsci.9b00049 | doi-access = free | pmid = 32259074 | pmc = 7088898 | volume = 2 | issue = 6 }}</ref>

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<sub>1</sub> and CB<sub>2</sub> cannabinoid receptors. While the effects mediated by CB<sub>1</sub>, mostly in the central nervous system, have been thoroughly investigated, those mediated by CB<sub>2</sub> are not equally well defined.

[[Cannabis in pregnancy|Prenatal cannabis exposure]] (PCE) has been shown to perturb the fetal endogenous cannabinoid signaling system. This perturbation has not been shown to directly affect [[neurodevelopment]] nor cause lifelong cognitive, behavioral, or functional abnormalities, but it may predispose offspring to abnormalities in [[cognition]] and altered emotionality from post-natal factors.<ref name="pmid27567698">{{cite journal | vauthors = Richardson KA, Hester AK, McLemore GL | title = Prenatal cannabis exposure - The "first hit" to the endocannabinoid system | journal = Neurotoxicology and Teratology | volume = 58 | pages = 5–14 | date = 2016 | pmid = 27567698 | doi = 10.1016/j.ntt.2016.08.003 | s2cid = 5656802 | department = review }}</ref> Additionally, PCE may alter the wiring of brain circuitry in foetal development and cause significant molecular modifications to neurodevelopmental programs that may lead to neurophysiological disorders and behavioural abnormalities.<ref name="Calvigioni_2014">{{cite journal | vauthors = Calvigioni D, Hurd YL, Harkany T, Keimpema E | title = Neuronal substrates and functional consequences of prenatal cannabis exposure | journal = European Child & Adolescent Psychiatry | volume = 23 | issue = 10 | pages = 931–41 | date = October 2014 | pmid = 24793873 | pmc = 4459494 | doi = 10.1007/s00787-014-0550-y | department = review }}</ref>

== Cannabinoid treatments ==
{{main|Medical cannabis}}
Synthetic [[tetrahydrocannabinol]] (THC) is prescribed under the [[International Nonproprietary Name|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]].<ref>{{cite journal | vauthors = Badowski ME | title = A review of oral cannabinoids and medical marijuana for the treatment of chemotherapy-induced nausea and vomiting: a focus on pharmacokinetic variability and pharmacodynamics | journal = Cancer Chemotherapy and Pharmacology | volume = 80 | issue = 3 | pages = 441–449 | date = September 2017 | pmid = 28780725 | pmc = 5573753 | doi = 10.1007/s00280-017-3387-5 }}</ref> Use of synthetic THC is becoming more common as the known benefits become more prominent within the medical industry. THC is also an [[active pharmaceutical ingredient|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.<ref>{{cite web|title=Sativex Oromucosal Spray - Summary of Product Characteristics|url=http://www.medicines.org.uk/emc/medicine/23262|publisher=UK Electronic Medicines Compendium|language=en|date=March 2015|access-date=2017-10-09|archive-url=https://web.archive.org/web/20160822231728/http://www.medicines.org.uk/emc/medicine/23262|archive-date=2016-08-22|url-status=dead}}</ref>

== Ligands ==
{{further|Cannabinoid receptor type 1#Ligands|Cannabinoid receptor type 2#Ligands}}

Binding affinity and selectivity of cannabinoid ligands:
{| class="wikitable sortable" style="font-size: smaller; text-align: center; width: auto;"
|-
! style="width: 12em"|
! CB<sub>1</sub> affinity (K<sub>i</sub>)
! Efficacy towards CB<sub>1</sub>
! CB<sub>2</sub> affinity (K<sub>i</sub>)
! Efficacy towards CB<sub>2</sub>
! Type
! References

|-
! '''[[Anandamide]]'''
| 78nM
| Partial 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
| <ref name="whoa">{{cite web|title=PDSP Database - UNC|url=http://pdsp.med.unc.edu/pdsp.php?|access-date=11 June 2013|url-status=dead|archive-url=https://web.archive.org/web/20131108013656/http://pdsp.med.unc.edu/pdsp.php|archive-date=8 November 2013}}</ref>
|-
! [[EGCG]]
| 33,600 nM
| Agonist
| >50,000 nM
| ?
| Phytogenic
|<ref name="ecgc">{{cite journal | vauthors = Korte G, Dreiseitel A, Schreier P, Oehme A, Locher S, Geiger S, Heilmann J, Sand PG | display-authors = 6 | title = Tea catechins' affinity for human cannabinoid receptors | journal = Phytomedicine | volume = 17 | issue = 1 | pages = 19–22 | date = January 2010 | pmid = 19897346 | doi = 10.1016/j.phymed.2009.10.001 }}</ref>
|-
! [[Yangonin]]
| 720 nM
| ?
|  >10,000 nM
| ?
| Phytogenic
| <ref>{{cite journal | vauthors = Ligresti A, Villano R, Allarà M, Ujváry I, Di Marzo V | title = Kavalactones and the endocannabinoid system: the plant-derived yangonin is a novel CB₁ receptor ligand | journal = Pharmacological Research | volume = 66 | issue = 2 | pages = 163–9 | date = August 2012 | pmid = 22525682 | doi = 10.1016/j.phrs.2012.04.003 }}</ref>
|- 
! [[AM-1221]]
|  52.3nM
|  Agonist
|  0.28nM
|  Agonist
|  Synthetic
| <ref name="dude">{{Ref patent2 |country= WO |number= 200128557 |status= granted |title= Cannabimimetic indole derivatives |pubdate= 2001-04-26 |gdate= 2001-06-07 |pridate= 1999-10-18 |inventor= [[Makriyannis A]], Deng H }}</ref>
|-
! [[AM-1235]]
|  1.5nM
|  Agonist
|  20.4nM
|  Agonist
|  Synthetic
| <ref name="like">{{Ref patent2 | country = US | number = 7241799 | status = granted | title = Cannabimimetic indole derivatives | pubdate = 2004-11-05 | gdate = 2007-07-10 | pridate= 2004-11-05 | inventor = Makriyannis A, Deng H | assign1= }}</ref>
|-
! [[AM-2232]]
|  0.28nM
|  Agonist
|  1.48nM
|  Agonist
|  Synthetic
|  <ref name="like"/>
|-
! [[UR-144]]
|  150nM
|  Full agonist
|  1.8nM
|  Full agonist
|  Synthetic
| <ref name="myhandsareamazing">{{cite journal | vauthors = Frost JM, Dart MJ, Tietje KR, Garrison TR, Grayson GK, Daza AV, El-Kouhen OF, Yao BB, Hsieh GC, Pai M, Zhu CZ, Chandran P, Meyer MD | display-authors = 6 | title = Indol-3-ylcycloalkyl ketones: effects of N1 substituted indole side chain variations on CB(2) cannabinoid receptor activity | journal = Journal of Medicinal Chemistry | volume = 53 | issue = 1 | pages = 295–315 | date = January 2010 | pmid = 19921781 | doi = 10.1021/jm901214q }}</ref>
|-
! [[JWH-007]]
|  9.0nM
|  Agonist
|  2.94nM
|  Agonist
|  Synthetic
|  <ref name="Aung_2000">{{cite journal | vauthors = Aung MM, Griffin G, Huffman JW, Wu M, Keel C, Yang B, Showalter VM, Abood ME, Martin BR | display-authors = 6 | title = Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB(1) and CB(2) receptor binding | journal = Drug and Alcohol Dependence | volume = 60 | issue = 2 | pages = 133–40 | date = August 2000 | pmid = 10940540 | doi = 10.1016/S0376-8716(99)00152-0 }}</ref>
|-
! [[JWH-015]]
|  383nM
|  Agonist
|  13.8nM
|  Agonist
|  Synthetic
| <ref name="Aung_2000"/>
|-
! [[JWH-018]]
|  9.00 ± 5.00 nM
|  Full agonist
|  2.94 ± 2.65 nM
|  Full agonist
|  Synthetic
| <ref name="Aung_2000"/>
|-
|}

== See also ==
* [[Cannabinoid receptor antagonist]]
* [[Endocannabinoid enhancer]]
* [[Endocannabinoid reuptake inhibitor]]
* [[Cannabidiol]]
* [[Effects of cannabis]]

== References ==
{{reflist|refs=
<ref name="pmid12432948">{{cite journal | vauthors = Howlett AC | title = The cannabinoid receptors | journal = Prostaglandins & Other Lipid Mediators | volume = 68–69 | pages = 619–31 | date = August 2002 | pmid = 12432948 | doi = 10.1016/S0090-6980(02)00060-6 }}</ref>

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}}

== External links ==
* {{MeshName|Cannabinoid+Receptors}}

{{G protein-coupled receptors}}
{{Cannabinoidergics}}

{{DEFAULTSORT:Cannabinoid Receptor}}
[[Category:G protein-coupled receptors]]