ARA-S.N-arachidonoyl-serine

Pharmacologically, N-arachidonoyl serine is defined first by what it does not do: it barely displaces the radioligands of the CB1 and CB2 receptors, and it shows no measurable binding to the TRPV1 channel (Milman 2006). Its activity therefore runs through other targets. In the isolated rat mesenteric artery it produces an endothelium-dependent relaxation, and it activates large-conductance calcium-activated potassium channels without any involvement of cannabinoid receptors or G proteins; that activation nevertheless disappears after patch excision or membrane cholesterol depletion and is restored after cholesterol reconstitution, the authors concluding a direct activation conditioned by membrane cholesterol (Godlewski 2009). In endothelial cells it stimulates phosphorylation of the p44/42 kinases and of Akt and promotes proliferation, migration and angiogenesis, a response partly reduced by knockdown of the GPR55 receptor (Zhang 2010); in the mouse traumatic brain injury model, by contrast, a GPR55 antagonist did not suppress the effect, so this receptor's role remains debated (Cohen-Yeshurun 2011). At the GPR18 receptor it acts as a low-efficacy agonist and can oppose more efficacious agonists such as N-arachidonoyl glycine (McHugh 2010). In mice it reduces tissue loss after traumatic brain injury and changes the behaviour of neural progenitor cells, effects partly lifted by CB2 and TRPV1 antagonists despite negligible direct binding, which remains unexplained. All of these observations come from isolated preparations and animal models: human data are lacking, and no therapeutic indication is established.

Source

An endogenous constituent of the mammalian nervous system, unrelated to cannabis: the plant does not produce it and it has never been identified in a plant extract. It was first extracted from bovine brain (Milman 2006), and liquid chromatography–mass spectrometry methods measure it in mouse brain (Han 2013). The vascular endothelium is among its documented endogenous targets.

An amide formed between arachidonic acid and L-serine. The precise enzymatic pathway is not established; the authors of the first characterisation suggest a phosphatidylserine-type precursor, by analogy with the formation of anandamide from phosphatidylethanolamine. In mammals, the N-acyl amino acid family is jointly controlled by the secreted hydrolase PM20D1 and by FAAH, two enzymes capable of both forming and cleaving the amide bond, which makes production and degradation difficult to disentangle.

European Union

No international classification: the molecule appears neither in the schedules of the Single Convention of 1961, nor in the lists of the UNODC or the INCB, nor in the notifications of the EUDA early warning system on new psychoactive substances. Its European status is that of an endogenous compound and a research reagent. No authorisation has been granted under Regulation (EU) 2015/2283 on novel foods, and no EFSA assessment concerns it.

France

N-arachidonoyl-serine is an endogenous mammalian lipid, produced by the body itself. It is named in no annex of the decree of 22 February 1990 and does not fall under the generic clause of annex III, which covers tetrahydrocannabinols, their esters, ethers, salts and the salts of the aforementioned derivatives: the molecule is neither a tetrahydrocannabinol nor a tetrahydrocannabinol derivative, but an amide of a fatty acid and an amino acid. It is therefore not classified as a narcotic in France. Commercially, it exists only as a laboratory reagent: no food ingredient status, no novel food authorisation, no lawful presence in any consumer product.

Sources: EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA. Our method.

Family

Endocannabinoid or related mediator › Endocannabinoidome

Verification

Every fact on this entry was checked against its primary sources on 20 October 2026.

Wikipedia (English)

No dedicated article.

1. 1Milman G. et al., N-arachidonoyl L-serine, an endocannabinoid-like brain constituent with vasodilatory properties, PNAS 2006 (new tab)PMID 16467152
2. 2Godlewski G. et al., The endogenous brain constituent N-arachidonoyl L-serine is an activator of large conductance Ca2+-activated K+ channels, JPET 2009 (new tab)PMID 18923087
3. 3Zhang X. et al., Endocannabinoid-like N-arachidonoyl serine is a novel pro-angiogenic mediator, Br J Pharmacol 2010 (new tab)PMID 20649563
4. 4Cohen-Yeshurun A. et al., N-arachidonoyl-L-serine is neuroprotective after traumatic brain injury by reducing apoptosis, J Cereb Blood Flow Metab 2011 (new tab)PMID 21505478
5. 5Cohen-Yeshurun A. et al., N-arachidonoyl-L-serine (AraS) possesses proneurogenic properties in vitro and in vivo after traumatic brain injury, J Cereb Blood Flow Metab 2013 (new tab)PMID 23695434
6. 6Guo J., Williams D.J., Ikeda S.R., N-arachidonoyl L-serine, a putative endocannabinoid, alters the activation of N-type Ca2+ channels in sympathetic neurons, J Neurophysiol 2008 (new tab)PMID 18234973
7. 7Han B. et al., Quantitative LC-MS/MS analysis of arachidonoyl amino acids in mouse brain with treatment of FAAH inhibitor, Anal Biochem 2013 (new tab)PMID 23044255
8. 8McHugh D. et al., N-arachidonoyl glycine, an abundant endogenous lipid, potently drives directed cellular migration through GPR18, BMC Neurosci 2010 (new tab)PMID 20346144
9. 9PubChem, N-arachidonoyl L-serine, CID 10596625 (new tab)

SMILES

CCCCC/C=C\C/C=C\C/C=C\C/C=C\CCCC(=O)N[C@@H](CO)C(=O)O

Machine-readable entry (JSON)

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