Editing Anandamide (section)

== Research ==
{{outdated|section|date=July 2024}}

According to in vitro research, anandamide effects are mediated primarily by CB<sub>1</sub> [[cannabinoid receptor]]s in the central nervous system, and CB<sub>2</sub> cannabinoid receptors in the periphery.<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> The latter appear to be involved in functions of the [[immune system]]. Cannabinoid receptors were originally discovered as sensitive to Δ<sup>9</sup>-[[tetrahydrocannabinol]] (Δ<sup>9</sup>-THC, commonly called THC), which is the primary psychoactive cannabinoid found in [[cannabis (drug)|cannabis]]. The discovery of anandamide came from research into CB<sub>1</sub> and CB<sub>2</sub>, as it was inevitable that a naturally occurring (endogenous) chemical would be found to affect these receptors.

Anandamide is under research for its potential involvement in the [[Implantation (embryology)|implantation]] of the early stage [[embryo]] in its [[blastocyst]] form into the [[uterus]]. Therefore, cannabinoids such as Δ<sup>9</sup>-THC might influence processes during the earliest stages of human pregnancy.<ref name="pmid14702623">{{cite journal | vauthors = Piomelli D | title = THC: moderation during implantation | journal = Nature Medicine | volume = 10 | issue = 1 | pages = 19–20 | date = January 2004 | pmid = 14702623 | doi = 10.1038/nm0104-19 | s2cid = 29207064 }}</ref> Peak plasma anandamide occurs at [[ovulation]] and positively correlates with peak [[estradiol]] and [[gonadotrophin]] levels, suggesting that these may be involved in the regulation of anandamide levels.<ref>{{cite journal | vauthors = El-Talatini MR, Taylor AH, Konje JC | title = The relationship between plasma levels of the endocannabinoid, anandamide, sex steroids, and gonadotrophins during the menstrual cycle | journal = Fertility and Sterility | volume = 93 | issue = 6 | pages = 1989–1996 | date = April 2010 | pmid = 19200965 | doi = 10.1016/j.fertnstert.2008.12.033 | doi-access = free }}</ref> Subsequently, anandamide has been proposed as a [[biomarker]] of [[infertility]], but so far lacks any [[predictive value]]s in order to be used clinically.<ref name="RapinoBattista2014">{{cite journal | vauthors = Rapino C, Battista N, Bari M, Maccarrone M | title = Endocannabinoids as biomarkers of human reproduction | journal = Human Reproduction Update | volume = 20 | issue = 4 | pages = 501–516 | year = 2014 | pmid = 24516083 | doi = 10.1093/humupd/dmu004 | doi-access = free }}</ref>

===Behavior===
Both the [[Cannabinoid receptor 1|CB1]] and [[Cannabinoid receptor 2|CB2]] receptors (the binding site of anandamide) are under research for a possible role in positive and negative interpretation of environment and setting.<ref>{{cite journal | vauthors = Crane NA, Schuster RM, Fusar-Poli P, Gonzalez R | title = Effects of cannabis on neurocognitive functioning: recent advances, neurodevelopmental influences, and sex differences | journal = Neuropsychology Review | volume = 23 | issue = 2 | pages = 117–137 | date = June 2013 | pmid = 23129391 | pmc = 3593817 | doi = 10.1007/s11065-012-9222-1 }}</ref> The binding relationship of anandamide and the CB1/CB2 may affect neurotransmission of dopamine, serotonin, GABA, and glutamate.<ref>{{cite journal | vauthors = Fantegrossi WE, Wilson CD, Berquist MD | title = Pro-psychotic effects of synthetic cannabinoids: interactions with central dopamine, serotonin, and glutamate systems | journal = Drug Metabolism Reviews | volume = 50 | issue = 1 | pages = 65–73 | date = February 2018 | pmid = 29385930 | pmc = 6419500 | doi = 10.1080/03602532.2018.1428343 }}</ref>

[[Endocannabinoid]]s may disturb [[homeostasis]] in several ways: by enhancing  [[appetite|hunger sensations]], encouraging increased [[food intake]], and shifting [[energy balance (biology)|energy balance]] towards [[lipogenesis|energy storage]]. A resultant decrease in energy expenditure is observed.<ref>{{cite journal | vauthors = Schulz P, Hryhorowicz S, Rychter AM, Zawada A, Słomski R, Dobrowolska A, Krela-Kaźmierczak I | title = What Role Does the Endocannabinoid System Play in the Pathogenesis of Obesity? | journal = Nutrients | volume = 13 | issue = 2 | pages = 373 | date = January 2021 | pmid = 33530406 | pmc = 7911032 | doi = 10.3390/nu13020373 | doi-access = free }}</ref>

Cortical glutamatergic transmission may be modulated by endocannabinoids during stress and fear [[habituation]].<ref>{{cite journal | vauthors = Kamprath K, Plendl W, Marsicano G, Deussing JM, Wurst W, Lutz B, Wotjak CT | title = Endocannabinoids mediate acute fear adaptation via glutamatergic neurons independently of corticotropin-releasing hormone signaling | journal = Genes, Brain and Behavior | volume = 8 | issue = 2 | pages = 203–211 | date = March 2009 | pmid = 19077175 | doi = 10.1111/j.1601-183X.2008.00463.x | s2cid = 21922344 | doi-access = free }}</ref>

===Obesity and liver disease===
Blockade of CB1 receptors was found to improve lipid resistance and lipid profile in obese subjects with [[type 2 diabetes]].<ref>{{cite journal | vauthors = Gruden G, Barutta F, Kunos G, Pacher P | title = Role of the endocannabinoid system in diabetes and diabetic complications | journal = British Journal of Pharmacology | volume = 173 | issue = 7 | pages = 1116–1127 | date = April 2016 | pmid = 26076890 | pmc = 4941127 | doi = 10.1111/bph.13226 }}</ref> Elevated anandamide levels are found in people with [[nonalcoholic fatty liver disease]], [[nonalcoholic steatohepatitis]], and [[liver fibrosis]].<ref>{{cite journal | vauthors = Kimberly WT, O'Sullivan JF, Nath AK, Keyes M, Shi X, Larson MG, Yang Q, Long MT, Vasan R, Peterson RT, Wang TJ, Corey KE, Gerszten RE | title = Metabolite profiling identifies anandamide as a biomarker of nonalcoholic steatohepatitis | journal = JCI Insight | volume = 2 | issue = 9 | pages = e92989 | date = May 2017 | pmid = 28469090 | pmc = 5414569 | doi = 10.1172/jci.insight.92989 }}</ref>

===Topical effects===

The [[American Academy of Dermatology]] has named topical anandamide a promising therapy for cutaneous [[lupus erythematosus]].<ref>{{cite journal |doi=10.1016/j.jaad.2023.07.014 |title=43357 Encapsulated anandamide: A promising therapy for cutaneous lupus erythematosus |date=2023 |journal=Journal of the American Academy of Dermatology |volume=89 |issue=3 |pages=AB1 | vauthors = McCormick E, Nussbaum D, Draganski A, Garcia S, Desai S, Friedman J, Friedman A }}</ref><ref>{{cite web | url=https://www.managedhealthcareexecutive.com/view/a-new-treatment-in-a-new-package-for-cutaneous-lupus-erythematosus | title=A New Treatment in a New Package for Cutaneous Lupus Erythematosus | date=19 March 2023 }}</ref>