Anandamide

Source: Wikipedia, the free encyclopedia.
Anandamide
Names
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
)
ChEBI
ChEMBL
ChemSpider
IUPHAR/BPS
MeSH Anandamide
UNII
  • InChI=1S/C22H37NO2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-22(25)23-20-21-24/h6-7,9-10,12-13,15-16,24H,2-5,8,11,14,17-21H2,1H3,(H,23,25)/b7-6-,10-9-,13-12-,16-15- checkY
    Key: LGEQQWMQCRIYKG-DOFZRALJSA-N checkY
  • InChI=1/C22H37NO2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-22(25)23-20-21-24/h6-7,9-10,12-13,15-16,24H,2-5,8,11,14,17-21H2,1H3,(H,23,25)/b7-6-,10-9-,13-12-,16-15-
    Key: LGEQQWMQCRIYKG-DOFZRALJBA
  • O=C(NCCO)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC
  • CCCCC/C=C\C/C=C\C/C=C\C/C=C\CCCC(=O)NCCO
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).
☒N verify (what is checkY☒N ?)

Anandamide (ANA), also known as N-arachidonoylethanolamine (AEA), an

cannabinoid receptors, the same receptors that the psychoactive compound THC in cannabis acts on. Anandamide is found in nearly all tissues in a wide range of animals.[1][2] Anandamide has also been found in plants, including small amounts in chocolate.[3] The name 'anandamide' is taken from the Sanskrit word ananda, which means "joy, bliss, delight", plus amide.[1][4]

Anandamide is derived from the non-oxidative metabolism of

fatty acid amide hydrolase (FAAH) enzyme, which converts anandamide into ethanolamine and arachidonic acid. As such, inhibitors of FAAH lead to elevated anandamide levels and are being pursued for therapeutic use.[6][7]

Anandamide is also being explored for its role in

endovanilloid signalling modulates local pain,[10] as well as in reduction of inflammation associated with renal injury.[11]

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-tetrahydrocannabinol9-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

predictive values in order to be used clinically.[15]

The acute beneficial effects of exercise (termed as

runner's high) seem to be mediated by anandamide in mice.[16] Anandamide is the precursor of a class of physiologically active substances, the prostamides.[17] Anandamide was found in 2007 to inhibit the proliferation of certain human breast cancer cell lines in vitro.[18]

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

N-acyltransferase enzyme.[30][31] Anandamide synthesis from NAPE occurs via multiple pathways and includes enzymes such as phospholipase A2, phospholipase C and N-acetylphosphatidylethanolamine-hydrolysing phospholipase D (NAPE-PLD).[5]

The crystal structure of NAPE-PLD in complex with

intestine – modulate its biogenesis.[32]

Endogenous anandamide is present at very low levels and has a very short

essential fatty acids affect the levels of anandamide and other endocannabinoids in the brain.[33] High fat diet feeding in mice increases levels of anandamide in the liver and increases lipogenesis.[34]
Anandamide may be relevant to the development of obesity, at least in rodents.

pro-drug for a cannabimimetic metabolite. This action may be partially or fully responsible for the analgesic effects of paracetamol.[36][37]

It is found that anandamide prefers

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.[40]

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]

energy balance towards energy storage. A resultant decrease in energy expenditure is observed.[44]

Another study with rats found that reductions in AEA signaling through FAAH overexpression within the

psychological disorders. However, further work in this area of study is needed, as reduced anandamide signaling is believed at this moment to involve CB1 receptors as well as GABAergic and glutamatergic interactions.[45]

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

type 2 diabetes mellitus. Blockade of CB1 receptors was found significantly to improve lipid resistance and lipid profile in obese subjects, but also has potential to increase fat accumulation through increased food intake, favored lipogenesis and reduced energy expenditure. This may affect downstream systems like the pancreas, liver, adipose tissue, and skeletal muscle, with inflammation and apoptosis in the case of the pancreas. CB1R inhibition with peripherally restricted antagonists and inverse agonists may aid in the treatment of diabetic neuropathy and neuropathy. CB2R agonists may show promise for the treatment of inflammation, which contributes to renal injury.[48]

AEA was associated with

liver fibrosis. Data suggests AEA as a marker for cardiometabolic disease and NAFLD severity. NAFLD can progress to more severe diseases, like NASH, cirrhosis, and hepatocellular carcinoma.[49]

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

External links