Food and Behaviour Research

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Emerging class of omega-3 fatty acid endocannabinoids & their derivatives

Watson JE, Kim JS, Das A (2019) Prostaglandins Other Lipid Mediat 2019 Aug 143:106337. doi: 10.1016/j.prostaglandins.2019.106337. Epub 2019 May 11. 

Web URL: Access the article via PMC here


Cannabinoid receptor activation is involved in homeostatic regulation of the body. These receptors are activated by cannabinoids, that include the active constituents of Cannabis sativa, as well as endocannabinoids (eCBs).

The eCBs are endogenously synthesized from the omega-6 and omega-3 polyunsaturated fatty acids (PUFAs). The consumption of omega-3 fatty acids shifts the balance towards a higher proportion of omega-3 eCBs, whose physiological functions warrants further investigation.

Herein, we review the discovery of omega-3 fatty acid derived eCBs that are generated from long chain omega-3 PUFAs - docosahexaenoyl ethanolamide (DHA-EA or synaptamide), docosahexanoyl-glycerol (DHG), eicosapentaenoyl ethanolamide (EPA-EA) and eicosapentanoylglycerol (EPG).

Furthermore, we outline the lesser known omega-3 eCB-like molecules that arise from the conjugation of omega-3 fatty acids with neurotransmitters serotonin and dopamine - DHA-serotonin (DHA-5HT), DHA-dopamine (DHA-DA), EPA-serotonin (EPA-5HT) and EPA-dopamine (EPA-DA).

Additionally, we describe the role of omega-3 eCBs and their derivatives in different disease states, such as pain, inflammation and cancer. Moreover, we detail the formation and potential physiological roles of the oxidative metabolites that arise from the metabolism of omega-3 eCBs by eicosanoid synthesizing enzymes - cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 epoxygenase (CYP450).

In summary, we outline the novel findings regarding a growing class of signaling molecules that can control the physiological and pathophysiological processes in the body.


Endo-cannabinoids are natural substances made within the body, which activate the same receptors and signalling systems as cannabinoid drugs, such as marijuana.

They were only first discovered in the mid-1990s, but are involved in almost all physiological and biochemical signalling systems in the body and brain, playing imporant roles in pain and inflammation control, appetite, sleep and temperature regulation as well as mood, perception, behaviour and cognition.

Importantly, the endocannabinoids are made from long-chain omega-3 and omega-6 polyunsaturated fatty acids (LC-PUFA) - which must be obtained from food and diet.

The dietary balance of omega-3 and omega-6 fats therefore has a key influence on the availability and activity of different endocannabinoids - with important implications for both physical and mental health and functioning.

This review provides an update on this rapidly developing area of research and its clinical implications.