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Cannabinoid
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=== Function === {{More citations needed|section|date=October 2018}} Endocannabinoids serve as [[Cellular communication (biology)#Intercellular communication|intercellular]] '[[lipid signaling|lipid messengers]]',<ref>{{cite web |title=What to know about endocannabinoids and the endocannabinoid system |url=https://www.medicalnewstoday.com/articles/endocannabinoid |website=Medical news Today |date=27 February 2021 |access-date=4 August 2021 |archive-date=4 August 2021 |archive-url=https://web.archive.org/web/20210804052706/https://www.medicalnewstoday.com/articles/endocannabinoid |url-status=live }}</ref> signaling molecules that are released from one cell and activating the cannabinoid receptors present on other nearby cells. Although in this intercellular signaling role they are similar to the well-known [[monoamine]] [[neurotransmitter]]s such as [[dopamine]], endocannabinoids differ in numerous ways from them. For instance, they are used in [[retrograde signaling]] between neurons.<ref>{{cite journal | vauthors = Kano M, Ohno-Shosaku T, Maejima T | title = Retrograde signaling at central synapses via endogenous cannabinoids | journal = Molecular Psychiatry | volume = 7 | issue = 3 | pages = 234β235 | year = 2002 | pmid = 11920149 | doi = 10.1038/sj.mp.4000999 | s2cid = 3200861 | doi-access = free }}</ref> Furthermore, endocannabinoids are [[lipophilic]] molecules that are not very soluble in water. They are not stored in vesicles and exist as integral constituents of the membrane bilayers that make up cells. They are believed to be synthesized 'on-demand' rather than made and stored for later use. As [[hydrophobic]] molecules, endocannabinoids cannot travel unaided for long distances in the aqueous medium surrounding the cells from which they are released and therefore act locally on nearby target cells. Hence, although emanating diffusely from their source cells, they have much more restricted spheres of influence than do [[hormone]]s, which can affect cells throughout the body. The mechanisms and enzymes underlying the biosynthesis of endocannabinoids remain elusive and continue to be an area of active research. The endocannabinoid [[2-AG]] has been found in [[bovine]] and human maternal milk.<ref>{{cite journal | vauthors = Fride E, Bregman T, Kirkham TC | title = Endocannabinoids and food intake: newborn suckling and appetite regulation in adulthood | journal = Experimental Biology and Medicine | volume = 230 | issue = 4 | pages = 225β234 | date = April 2005 | pmid = 15792943 | doi = 10.1177/153537020523000401 | s2cid = 25430588 }}</ref> A review by Matties et al. (1994) summed up the phenomenon of gustatory enhancement by certain cannabinoids.<ref>{{cite journal | vauthors = Mattes RD, Shaw LM, Engelman K | title = Effects of cannabinoids (marijuana) on taste intensity and hedonic ratings and salivary flow of adults | journal = Chemical Senses | volume = 19 | issue = 2 | pages = 125β140 | date = April 1994 | pmid = 8055263 | doi = 10.1093/chemse/19.2.125 }}</ref> The sweet receptor (Tlc1) is stimulated by indirectly increasing its expression and suppressing the activity of leptin, the Tlc1 antagonist. It is proposed that the competition of leptin and cannabinoids for Tlc1 is implicated in energy homeostasis.<ref>{{cite journal | vauthors = Yoshida R, Ohkuri T, Jyotaki M, Yasuo T, Horio N, Yasumatsu K, Sanematsu K, Shigemura N, Yamamoto T, Margolskee RF, Ninomiya Y | display-authors = 6 | title = Endocannabinoids selectively enhance sweet taste | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 2 | pages = 935β939 | date = January 2010 | pmid = 20080779 | pmc = 2818929 | doi = 10.1073/pnas.0912048107 | doi-access = free | bibcode = 2010PNAS..107..935Y }}</ref> ==== Retrograde signal ==== Conventional neurotransmitters are released from a 'presynaptic' cell and activate appropriate receptors on a 'postsynaptic' cell, where presynaptic and postsynaptic designate the sending and receiving sides of a synapse, respectively. Endocannabinoids, on the other hand, are described as [[Retrograde signaling|retrograde transmitters]] because they most commonly travel 'backward' against the usual synaptic transmitter flow. They are, in effect, released from the postsynaptic cell and act on the presynaptic cell, where the target receptors are densely concentrated on axonal terminals in the zones from which conventional neurotransmitters are released. Activation of cannabinoid receptors temporarily reduces the amount of conventional neurotransmitter released. This endocannabinoid-mediated system permits the postsynaptic cell to control its own incoming synaptic traffic. The ultimate effect on the endocannabinoid-releasing cell depends on the nature of the conventional transmitter being controlled. For instance, when the release of the inhibitory transmitter [[GABA]] is reduced, the net effect is an increase in the excitability of the endocannabinoid-releasing cell. On the converse, when release of the excitatory neurotransmitter [[Glutamate (neurotransmitter)|glutamate]] is reduced, the net effect is a decrease in the excitability of the endocannabinoid-releasing cell.<ref>{{cite book | vauthors = Vaughan CW, Christie MJ | title = Cannabinoids | chapter = Retrograde signalling by endocannabinoids | series = Handbook of Experimental Pharmacology | volume = 168 | issue = 168 | pages = 367β383 | date = 2005 | pmid = 16596781 | doi = 10.1007/3-540-26573-2_12 | isbn = 3-540-22565-X }}</ref> {{citation needed|date=December 2013}} ==== "Runner's high" ==== The [[Neurobiological effects of physical exercise|runner's high]], the feeling of euphoria that sometimes accompanies aerobic exercise, has often been attributed to the release of [[endorphins]], but newer research suggests that it might be due to endocannabinoids instead.<ref>{{Cite news |vauthors=Reynolds G |date=2021-03-10 |title=Getting to the Bottom of the Runner's High |language=en-US |work=The New York Times |url=https://www.nytimes.com/2021/03/10/well/move/running-exercise-mental-effects.html |access-date=2021-03-16 |issn=0362-4331 |archive-date=2021-03-15 |archive-url=https://web.archive.org/web/20210315225202/https://www.nytimes.com/2021/03/10/well/move/running-exercise-mental-effects.html |url-status=live }}</ref>
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