Anandamide
Names | |
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Preferred IUPAC name
(5Z,8Z,11Z,14Z)-N-(2-hydroxyethyl)icosa-5,8,11,14-tetraenamide | |
Other names
N-arachidonoylethanolamine
arachidonoylethanolamide | |
Identifiers | |
3D model (
JSmol ) |
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ChEBI | |
ChEMBL | |
ChemSpider | |
IUPHAR/BPS |
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MeSH | Anandamide |
PubChem CID
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UNII | |
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Properties | |
C22H37NO2 | |
Molar mass | 347.53 g/mol |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Anandamide (ANA), also known as N-arachidonoylethanolamine (AEA), an
Anandamide is derived from the non-oxidative metabolism of
Anandamide is also being explored for its role in
Physiological functions
Anandamide's effects can occur in either the central or peripheral nervous system. These distinct effects are mediated primarily by CB1 cannabinoid receptors in the central nervous system, and CB2 cannabinoid receptors in the periphery.[12] 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 is also important for the
The acute beneficial effects of exercise (termed as
Anandamide is found in chocolate together with two substances that might mimic the effects of anandamide, N-oleoylethanolamine and N-linoleoylethanolamine.[19]
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.[20][21]
Effects on behavior
Both the CB1 and CB2 receptors (the bonding site of anandamide) seem to play a role in the identification of positive and negative interpretation of environment and setting.[22] In animal models, anandamide mediates the interpretation of stimulus; specifically, optimism and pessimism in the presence of an ambiguous cue.[23] Anandamide has been shown to impair working memory in rats,[24] while THC (the compound in cannabis that binds to the CB1 and CB2 receptors) also shows a deficit in working memory.[25]
This binding relationship of anandamide and the CB1/CB2 may affect neurotransmission of dopamine, serotonin, GABA, and glutamate.[26] There is currently encouraging, albeit embryonic, evidence for medicinal cannabis in the treatment of a range of psychiatric disorders. Supportive findings are emerging for some key isolates, however, clinicians need to be mindful of a range of prescriptive and occupational safety considerations, especially if initiating higher dose THC formulas.[27]
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.[28] Increasing anandamide seems to increase the intrinsic value of food, not necessarily by stimulation of appetite or hunger.[29]
Anandamide may affect hunger, sleep, pain modulation, working memory, identification of novelty, and interpretation of environment.[citation needed]
Synthesis and degradation
In humans, anandamide is biosynthesized from N-arachidonoyl phosphatidylethanolamine (NAPE). In turn, NAPE arises by transfer of
The crystal structure of NAPE-PLD in complex with
Endogenous anandamide is present at very low levels and has a very short
It is found that anandamide prefers
Research and production
Black pepper contains the alkaloid guineesine, which is an anandamide reuptake inhibitor. It may therefore increase anandamide's physiological effects.[41]
Low-dose anandamide has an anxiolytic effect, while in one study, high doses injected directly into the cerebral fluid of the brain of mice shows evident cell apoptosis (programmed cell death) in vitro as opposed to necrosis.[42] That being said, another study conducted under similar conditions demonstrated neuronal growth both in vitro and in vivo.[43]
Another study with rats found that reductions in AEA signaling through FAAH overexpression within the
Cortical glutamatergic transmission may be modulated by endocannabinoids during stress and fear habituation.[46] Glutamatergic interaction in the BLA believed to be responsible for changes in anxiety, appears to normalize stress-induced anxiety-like behavior. A study indicated that infusion of the GluK1 receptor agonist ATPA into the BLA enhanced GABAergic neurotransmission, which is currently believed to have a large role in the reduction of anxiety symptoms.[47]
Additionally, the ECs, along with AEA, have been highlighted for their potential involvement in obesity development and harmful effects on lipid and glucose metabolism, which may contribute to insulin resistance and deficiency, both of which are major risk factors for developing
AEA was associated with
A Scottish woman with a rare mutation in her FAAH gene that resulted in 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 more rapidly than was expected.[50][51][52]
Topical Anandamide was found to reduce peripheral neuropathic pain by interaction with peripheral cannabinoid receptors.[53]
The American Academy of Dermatology has named topical Anandamide a promising therapy for cutaneous lupus erythematosus. [54][55]
See also
References
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- ^ Murphy H (28 March 2019). "At 71, She's Never Felt Pain or Anxiety. Now Scientists Know Why". The New York Times. Retrieved 29 March 2019.
- ^ Sample I (28 March 2019). "Scientists find genetic mutation that makes woman feel no pain". The Guardian. Retrieved 29 March 2019.
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- ^ "AAD ePosters".
- ^ "A New Treatment in a New Package for Cutaneous Lupus Erythematosus". 19 March 2023.
External links
- Could anandamide be the missing link to "runner's high"? Accessed 2015-10-31
- Sparling PB, Giuffrida A, Piomelli D, Rosskopf L, Dietrich A (December 2003). "Exercise activates the endocannabinoid system". NeuroReport. 14 (17): 2209–2211. S2CID 1971671.