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 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. 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.
Endogenous anandamide is present at very low levels and has a very short half-life due to the action of the enzyme fatty acid amide hydrolase (FAAH), which breaks it down into free arachidonic acid and ethanolamine. Studies of piglets show that dietary levels of arachidonic acid and other essential fatty acids affect the levels of anandamide and other endocannabinoids in the brain. High fat diet feeding in mice increases levels of anandamide in the liver and increases lipogenesis. This suggests that anandamide may play a role in the development of obesity, at least in rodents.
Paracetamol (called acetaminophen in the US 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 is found that anandamide prefer cholesterol and ceramide more than other membrane lipids, and cholesterol can behave as a binding partner for it, and following an initial interaction mediated by the establishment of a hydrogen bond, the endocannabinoid is attracted towards the membrane interior, where it forms a molecular complex with cholesterol after a functional conformation adaptation to the apolar membrane milieu, and from there, the complex is further directed to the cannabinoid receptor (CB1) and out.
Low dose intake of anandamide has an anxiolytic effect, but high dose intake in mice shows evident hippocampus death.
A Scottish woman with a rare genetic mutation in her FAAH gene with resultant elevated anandamide levels was reported to be immune to anxiety, unable to experience fear and insensitive to pain. The frequent burns and cuts she suffered due to her hypoalgesia healed quicker than average.
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