2-EPG.2-eicosapentaenoylglycerol

2-eicosapentaenoylglycerol is the omega-3 congener of 2-arachidonoylglycerol: the same glycerol head, the same twenty-carbon chain length, but five n-3 double bonds inherited from EPA. It is formed by the phospholipase C then diacylglycerol lipase sequence, like 2-AG, and degraded by the same serine hydrolases, which gives it a short tissue lifetime; human eosinophils produce its congeners from EPA and DHA, a pathway up to about 100-fold more prominent than in mice (Archambault 2022). On the receptor side, caution is required: reviews place it in the omega-3 endocannabinoidome (Watson 2019) and it is measured as such, but no binding study has published a CB1 or CB2 affinity for it. The available work concerns a different molecule, the EPA monoglyceride given orally: in a model of chemically induced colitis in rats it reduced histological lesions and tissue cytokines (Morin 2016), and in human mononuclear cells stimulated ex vivo, cytokine production (Morin 2017). No human data document the effect of 2-EPG itself.

Source

An endogenous lipid, not reported in cannabis. 2-EPG derives from eicosapentaenoic acid (EPA, 20:5 n-3), a dietary omega-3 esterified in membrane phospholipids. It has been quantified in human lipidomic panels, notably breast milk (Gaitán 2019) and a clinical cohort where its level fell after oral cannabinoid administration (Giorgini 2026). Human eosinophils produce 2-arachidonoylglycerol and its congeners derived from EPA and DHA, a pathway up to about 100-fold more prominent than in mice (Archambault 2022).

2-EPG follows the 2-monoacylglycerol route: the fatty acid esterified at the sn-2 position of membrane phosphoinositides is released as a diacylglycerol by a phospholipase C, then a diacylglycerol lipase removes the sn-1 chain and leaves the monoacylglycerol. Archambault et al. (2022) showed that human eosinophils biosynthesise 2-AG and its congeners from EPA and DHA. Degradation follows the same logic as for 2-AG: hydrolysis by monoacylglycerol serine hydrolases, releasing free EPA and glycerol.

European Union

2-eicosapentaenoylglycerol is listed in no schedule of the 1961 and 1971 United Nations conventions and is subject to no European Union control measure. Marine oils rich in EPA fall under European food law.

France

An endogenous lipid, 2-eicosapentaenoylglycerol appears on no French list of narcotics or psychotropic substances (orders of 22 February 1990), and no ANSM decision covers it. Its dietary precursor, EPA, falls under food law.

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. 1Watson J.E., Kim J.S., Das A., Emerging class of omega-3 fatty acid endocannabinoids and their derivatives, Prostaglandins Other Lipid Mediat 2019 (new tab)PMID 31085370
2. 2Archambault A.S. et al., Human and Mouse Eosinophils Differ in Their Ability to Biosynthesize Eicosanoids, Docosanoids, the Endocannabinoid 2-Arachidonoyl-glycerol and Its Congeners, Cells 2022 (new tab)PMID 35011703
3. 3Schaaf O., Dettner K., Polyunsaturated monoglycerides and a pregnadiene in defensive glands of the water beetle Agabus affinis, Lipids 2000 (new tab)PMID 10907789
4. 4Sugiura T. et al., Evidence that the cannabinoid CB1 receptor is a 2-arachidonoylglycerol receptor. Structure-activity relationship of 2-arachidonoylglycerol, ether-linked analogues, and related compounds, J Biol Chem 1999 (new tab)PMID 9915812
5. 5Gaitán A.V. et al., Endocannabinoid Metabolome Characterization of Milk from Guatemalan Women Living in the Western Highlands, Curr Dev Nutr 2019 (new tab)PMID 31111118
6. 6Giorgini G. et al., Impact of Oral Cannabinoids on the Endocannabinoidome and Gut Microbiome in People with HIV, Cannabis and Cannabinoid Research 2026 (new tab)PMID 40879543
7. 7Morin C., Blier P.U., Fortin S., MAG-EPA reduces severity of DSS-induced colitis in rats, Am J Physiol Gastrointest Liver Physiol 2016 (new tab)PMID 27012773
8. 8Morin C. et al., Eicosapentaenoic acid monoglyceride resolves inflammation in an ex vivo model of human peripheral blood mononuclear cell, Eur J Pharmacol 2017 (new tab)PMID 28501579
9. 9Cuenoud B. et al., Monoacylglycerol Form of Omega-3s Improves Its Bioavailability in Humans Compared to Other Forms, Nutrients 2020 (new tab)PMID 32272659
10. 10Rouzer C.A., Ghebreselasie K., Marnett L.J., Chemical stability of 2-arachidonylglycerol under biological conditions, Chem Phys Lipids 2002 (new tab)PMID 12270674
11. 11PubChem CID 11660820, 2-eicosapentaenoyl-glycerol (new tab)

SMILES

CC/C=C\C/C=C\C/C=C\C/C=C\C/C=C\CCCC(=O)OC(CO)CO

Machine-readable entry (JSON)

LLM ingestion format: a structured superset of the entry (identifiers, binding, versioned legal status). Full corpus.