LEA.Linoleoylethanolamide

A C18:2-chain congener of anandamide, linoleoylethanolamide illustrates the boundary between true endocannabinoids and merely related mediators: no primary source attributes any activity at the CB1 and CB2 receptors to it. Its activity runs through other targets: agonism at the GPR119 receptor of enteroendocrine cells, where it ranks among the most potent endogenous lipids alongside oleoylethanolamide, and where, in mice, its intestinal level rises sharply after refeeding (Syed 2012); activation of the nuclear receptor PPAR-alpha, shared by the N-acylethanolamines tested by Artmann et al. (2008). An activation then desensitisation of the TRPV1 channel is reported by review literature, without primary demonstration (Sihag 2022). In humans, plasma concentrations are higher in overweight people, body mass index above 25, and correlate with cholesterol and triglycerides, which for now makes it a marker rather than a treatment. The only repeated-administration study, in rats made obese by a cafeteria diet and treated with 10 mg/kg intraperitoneally for 14 days, reports weight loss and a fall in triglycerides, cholesterol, interleukin 6 and TNF alpha, without correction of liver steatosis (Tovar 2023). Human efficacy and safety data are entirely lacking.

Source

An endogenous mammalian molecule, produced in most tissues and among the most abundant N-acylethanolamines of plasma and gut (Tovar 2023). In rats, a diet enriched in linoleic acid increases linoleoylethanolamide and linoleic acid in brain, jejunum and liver (Artmann 2008). It is also supplied by the diet, where it is found notably in cereals (Tovar 2023); dietary levels of N-acylethanolamines and of their NAPE precursors have been compiled in a dedicated database (De Luca 2019). It does not belong to the phytocannabinoid family and does not come from the biosynthetic pathway specific to cannabis.

On-demand membrane synthesis: an N-acyltransferase transfers a linoleoyl residue onto phosphatidylethanolamine to form N-linoleoyl-phosphatidylethanolamine, which NAPE-PLD then hydrolyses into linoleoylethanolamide. Precursor availability depends directly on dietary linoleic acid intake, so that tissue levels follow the fatty acid composition of the diet. Degradation is mainly the work of FAAH, more marginally of NAAA.

European Union

No European instrument classifies this molecule. It appears neither in the schedules of the 1961 and 1971 United Nations conventions nor among the new psychoactive substances monitored by the EUDA, which is consistent with its endogenous character and its natural presence in food. An isolated ingredient intended for human consumption would fall under Regulation (EU) 2015/2283 on novel foods and would have to obtain authorisation following assessment by EFSA.

France

Linoleoylethanolamide is an endogenous mammalian molecule and a natural constituent of many everyday foods. It is named in no annex of the decree of 22 February 1990 setting the list of substances classified as narcotics, nor is it captured by the generic clause of annex III covering tetrahydrocannabinols, their esters, ethers, salts and the salts of the aforementioned derivatives, since it does not derive from THC. It is therefore neither a narcotic classified by name nor a derivative caught by a generic clause. Placing an isolated form on the market as a food supplement would, by contrast, fall under the novel foods regime, for want of a documented history of consumption of the purified molecule, and no health claim is authorised in its regard.

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. 1Syed S.K. et al., Regulation of GPR119 receptor activity with endocannabinoid-like lipids, Am J Physiol Endocrinol Metab 2012 (new tab)PMID 23074242
2. 2Artmann A. et al., Influence of dietary fatty acids on endocannabinoid and N-acylethanolamine levels in rat brain, liver and small intestine, Biochim Biophys Acta 2008 (new tab)PMID 18316044
3. 3Tovar R., de Ceglia M. et al., Administration of linoleoylethanolamide reduced weight gain, dyslipidemia and inflammation associated with high-fat-diet-induced obesity, Nutrients 2023 (new tab)PMID 37892524
4. 4Sihag J., Di Marzo V., (Wh)olistic endocannabinoidome-microbiome-axis modulation through nutrition, Nutr Metab (Lond) 2022 (review: LEA targets mentioned, degradation by FAAH and NAAA) (new tab)PMID 35027074
5. 5De Luca L. et al., Food database of N-acyl-phosphatidylethanolamines, N-acylethanolamines and endocannabinoids, Food Chem 2019 (new tab)PMID 31351254
6. 6Bachur N.R., Masek K., Melmon K.L., Udenfriend S., Fatty acid amides of ethanolamine in mammalian tissues, J Biol Chem 1965 (new tab)PMID 14284696
7. 7Order of 22 February 1990 setting the list of substances classified as narcotics (consolidated text, Légifrance) (new tab)

SMILES

CCCCC/C=C\C/C=C\CCCCCCCC(=O)NCCO

Machine-readable entry (JSON)

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