Anandamide's effects can occur in either the central or peripheral nervous system. These distinct effects are mediated primarily by CB1cannabinoid receptors in the central nervous system, and CB2 cannabinoid receptors in the periphery. The latter are mainly involved in functions of the immune system. Cannabinoid receptors were originally discovered as being sensitive to Δ9-tetrahydrocannabinol (Δ9-THC, commonly called THC), which is the primary psychoactive cannabinoid found in cannabis. The discovery of anandamide came from research into CB1 and CB2, as it was inevitable that a naturally occurring (endogenous) chemical would be found to affect these receptors.
Anandamide has been shown to impair working memory in rats. Studies are under way to explore what role anandamide plays in human behavior, such as eating and sleep patterns, and pain relief.
Anandamide is also important for implantation of the early stage embryo in its blastocyst form into the uterus. Therefore, cannabinoids such as Δ9-THC might influence processes during the earliest stages of human pregnancy. 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 AEA (anandamide) levels. Subsequently, anandamide has been proposed as a biomarker of infertility, but so far lacks any predictive values in order to be used clinically.
Anandamide plays a role in the regulation of feeding behavior, and the neural generation of motivation and pleasure. In addition, anandamide injected directly into the forebrain reward-related brain structure nucleus accumbens enhances the pleasurable responses of rats to a rewarding sucrose taste, and enhances food intake as well. Moreover, the acute beneficial effects of exercise (termed as runner's high) seem to be mediated by anandamide in mice.
Anandamide is the precursor of a class of physiologically active substances, the prostamides.
Anandamide inhibits human breast cancer cell proliferation.
Anandamide is found in chocolate together with two substances that might mimic the effects of anandamide, N-oleoylethanolamine and N-linoleoylethanolamine.
Additionally, anandamide and other endocannabinoids are found in the model organism Drosophila melanogaster (fruit fly). Although no CB receptors have been found in any insects.
Paracetamol (or acetaminophen in the U.S.A. and Canada) is metabolically combined with arachidonic acid by FAAH to form AM404. This metabolite of paracetamol is a potent agonist at the TRPV1 vanilloid receptor, a weak agonist at both CB1 and CB2 receptors, and an inhibitor of anandamide reuptake. As a result, anandamide levels in the body and brain are elevated. In this fashion, paracetamol acts as a pro-drug for a cannabimimetic metabolite. This action may be partially or fully responsible for the analgesic effects of paracetamol.
It has been suggested that AM1172 could potentially be developed into a drug that would increase the brain's anandamide levels to help treat anxiety and depression. Black pepper contains an alkaloid, Guineensine, which appears to be a relatively potent Anandamide reuptake inhibitor, thus increasing its physiological effects.
Low dose intake has an anxiolytic effect. High dose intake in mice shows evident hippocampus death. It is not possible to train[clarification needed] tolerable maximum high dosage for mice. Expired patents from 2004 exist that describe anandamide as a vitalising additive for alcoholic and non-alcoholic beverages, including combining it with another additive, Oleoylethanolamide, recited as an invention from Nestle, to increase the "stimulus" effect, but since the patent expired anyone is free to synthetically produce it and add it to food. The amount of anandamide in cacao is 0.5 μg per gram. According to associate statistics world cacao production in 2013 had a value of around five million metric tons annually with a rising tendency.
^ abDevane, W.; Hanus, L; Breuer, A; Pertwee, R.; Stevenson, L.; Griffin, G; Gibson, D; Mandelbaum, A; Etinger, A; Mechoulam, R (18 December 1992). "Isolation and structure of a brain constituent that binds to the cannabinoid receptor". Science. 258 (5090): 1946–1949. Bibcode:1992Sci...258.1946D. doi:10.1126/science.1470919. PMID1470919.
^Mechoulam R, Fride E (1995). "The unpaved road to the endogenous brain cannabinoid ligands, the anandamides". In Pertwee RG. Cannabinoid receptors. Boston: Academic Press. pp. 233–258. ISBN0-12-551460-3.
^Gaetani, Silvana; Dipasquale, Pasqua; Romano, Adele; Righetti, Laura; Cassano, Tommaso; Piomelli, Daniele; Cuomo, Vincenzo (2009). "The endocannabinoid system as a target for novel anxiolytic and antidepressant drugs". International review of neurobiology. International Review of Neurobiology. 85: 57–72. doi:10.1016/S0074-7742(09)85005-8. ISBN9780123748935. PMID19607961.
^El-Talatini MR, Taylor AH, Konje JC (April 2010). "The relationship between plasma levels of the endocannabinoid, anandamide, sex steroids, and gonadotrophins during the menstrual cycle". Fertil. Steril. 93 (6): 1989–96. doi:10.1016/j.fertnstert.2008.12.033. PMID19200965.
^McPartland J, Di Marzo V, De Petrocellis L, Mercer A, Glass M. (Aug 2001). "Cannabinoid receptors are absent in insects". Journal of Comparative Neurology. 436 (4): 423–429. doi:10.1002/cne.1078. PMID11447587.CS1 maint: Uses authors parameter (link)
^Cadas H, di Tomaso E, Piomelli D (February 1997). "Occurrence and biosynthesis of endogenous cannabinoid precursor, N-arachidonoyl phosphatidylethanolamine, in rat brain". J. Neurosci. 17 (4): 1226–42. PMID9006968.
^Bertolini, Alfio; Ferrari, Anna; Ottani, Alessandra; Guerzoni, Simona; Tacchi, Raffaella; Leone, Sheila (September 2006). "Paracetamol: New Vistas of an Old Drug". CNS Drug Reviews. 12 (3–4): 250–275. doi:10.1111/j.1527-3458.2006.00250.x. PMID17227290.
^Sinning, Christian; Watzer, Bernhard; Coste, Ovidiu; Nüsing, Rolf M.; Ott, Ingo; Ligresti, Alessia; Marzo, Vincenzo Di; Imming, Peter (25 December 2008). "New Analgesics Synthetically Derived from the Paracetamol Metabolite-(4-Hydroxyphenyl)-(5,8,11,14)-icosatetra-5,8,11,14-enamide". Journal of Medicinal Chemistry. 51 (24): 7800–7805. doi:10.1021/jm800807k. PMID19053765.