Editing Cannabinoid (section)

== Cannabinoid receptors ==
Before the 1980s, cannabinoids were speculated to produce their [[physiological]] and behavioral effects via nonspecific interaction with [[cell membranes]], instead of interacting with specific [[membrane-bound]] [[Receptor (biochemistry)|receptors]]. The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate.<ref name="PMID 2848184">{{cite journal | vauthors = Devane WA, Dysarz FA, Johnson MR, Melvin LS, Howlett AC | title = Determination and characterization of a cannabinoid receptor in rat brain | journal = Molecular Pharmacology | volume = 34 | issue = 5 | pages = 605–613 | date = November 1988 | pmid = 2848184 | url = http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=2848184 | ref = 56 | access-date = 2015-12-24 | archive-date = 2023-04-20 | archive-url = https://web.archive.org/web/20230420163537/https://molpharm.aspetjournals.org/content/34/5/605.long | url-status = live }}</ref> These receptors are common in animals. Two known cannabinoid receptors are termed [[CB1 receptor|CB<sub>1</sub>]] and [[CB2 receptor|CB<sub>2</sub>]],<ref name="pmid16968947">{{cite journal | vauthors = Pacher P, Bátkai S, Kunos G | title = The endocannabinoid system as an emerging target of pharmacotherapy | journal = Pharmacological Reviews | volume = 58 | issue = 3 | pages = 389–462 | date = September 2006 | pmid = 16968947 | pmc = 2241751 | doi = 10.1124/pr.58.3.2 }}</ref> with mounting evidence of more.<ref name="pmid15866316">{{cite journal | vauthors = Begg M, Pacher P, Bátkai S, Osei-Hyiaman D, Offertáler L, Mo FM, Liu J, Kunos G | display-authors = 6 | title = Evidence for novel cannabinoid receptors | journal = Pharmacology & Therapeutics | volume = 106 | issue = 2 | pages = 133–145 | date = May 2005 | pmid = 15866316 | doi = 10.1016/j.pharmthera.2004.11.005 }}</ref> The human brain has more cannabinoid receptors than any other [[G protein-coupled receptor]] (GPCR) type.<ref name="Medical Physiology">{{cite book| veditors = Boron WG, Boulpaep EL |title=Medical Physiology: A Cellular and Molecular Approach |year=2009 |publisher=Saunders |isbn=978-1-4160-3115-4 |page=331}}</ref>

The [[endocannabinoid system]] (ECS) regulates many functions of the human body. The ECS plays an important role in multiple aspects of [[Neuron|neural]] functions, including the control of movement and motor coordination, learning and memory, emotion and motivation, addictive-like behavior and pain modulation, among others.<ref>{{cite book | vauthors = Kalant H | chapter = Effects of cannabis and cannabinoids in the human nervous system. | title = The effects of drug abuse on the human nervous system | date = January 2014 | pages = 387–422 | publisher = Academic Press | doi = 10.1016/B978-0-12-418679-8.00013-7 | isbn = 978-0-12-418679-8 }}</ref>

=== Cannabinoid receptor type 1 ===
{{Main|Cannabinoid receptor 1}}
CB<sub>1</sub> receptors are found primarily in the [[brain]], more specifically in the [[basal ganglia]] and in the [[limbic system]], including the [[hippocampus]]<ref name="pmid16968947" /> and the [[striatum]]. They are also found in the [[cerebellum]] and in both male and female [[reproductive system]]s. CB<sub>1</sub> receptors are absent in the [[medulla oblongata]], the part of the [[brain stem]] responsible for respiratory and cardiovascular functions. CB1 is also found in the human anterior eye and retina.<ref>{{cite journal | vauthors = Straiker AJ, Maguire G, Mackie K, Lindsey J | title = Localization of cannabinoid CB1 receptors in the human anterior eye and retina | journal = Investigative Ophthalmology & Visual Science | volume = 40 | issue = 10 | pages = 2442–2448 | date = September 1999 | pmid = 10476817 }}</ref>

=== Cannabinoid receptor type 2 ===
{{Main|Cannabinoid receptor 2}}

CB<sub>2</sub> receptors are predominantly found in the [[immune system]], or immune-derived cells<ref>{{cite journal | vauthors = Marchand J, Bord A, Pénarier G, Lauré F, Carayon P, Casellas P | title = Quantitative method to determine mRNA levels by reverse transcriptase-polymerase chain reaction from leukocyte subsets purified by fluorescence-activated cell sorting: application to peripheral cannabinoid receptors | journal = Cytometry | volume = 35 | issue = 3 | pages = 227–234 | date = March 1999 | pmid = 10082303 | doi = 10.1002/(SICI)1097-0320(19990301)35:3<227::AID-CYTO5>3.0.CO;2-4 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Galiègue S, Mary S, Marchand J, Dussossoy D, Carrière D, Carayon P, Bouaboula M, Shire D, Le Fur G, Casellas P | display-authors = 6 | title = Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations | journal = European Journal of Biochemistry | volume = 232 | issue = 1 | pages = 54–61 | date = August 1995 | pmid = 7556170 | doi = 10.1111/j.1432-1033.1995.tb20780.x | doi-access = free }}</ref><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><ref name="Saroz acsptsci.9b00049">{{cite journal | vauthors = Saroz Y, Kho DT, Glass M, Graham ES, Grimsey NL | title = Cannabinoid Receptor 2 (CB<sub>2</sub>) Signals via G-alpha-s and Induces IL-6 and IL-10 Cytokine Secretion in Human Primary Leukocytes | journal = ACS Pharmacology & Translational Science | volume = 2 | issue = 6 | pages = 414–428 | date = December 2019 | pmid = 32259074 | pmc = 7088898 | doi = 10.1021/acsptsci.9b00049 }}</ref> with varying expression patterns. While found only in the peripheral nervous system, a report does indicate that CB<sub>2</sub> is expressed by a subpopulation of [[microglia]] in the human [[cerebellum]].<ref name="pmid15266552">{{cite journal | vauthors = Núñez E, Benito C, Pazos MR, Barbachano A, Fajardo O, González S, Tolón RM, Romero J | display-authors = 6 | title = Cannabinoid CB2 receptors are expressed by perivascular microglial cells in the human brain: an immunohistochemical study | journal = Synapse | volume = 53 | issue = 4 | pages = 208–213 | date = September 2004 | pmid = 15266552 | doi = 10.1002/syn.20050 | s2cid = 40738073 }}</ref> CB<sub>2</sub> receptors appear to be responsible for immunomodulatory<ref name="Saroz acsptsci.9b00049" /> and possibly other therapeutic effects of cannabinoid as seen in vitro and in animal models.<ref name="pmid21295074" />