New Study Reveals Omega-3 Fatty Acids Can Produce Some Of The Same Medicinal Effects As Cannabinoids
Most people have probably heard of the two major classes of polyunsaturated fatty acids (PUFAs) – the omega-3 and omega-6 fatty acids.
They are called “essential” fatty acids because the human body is not capable of producing them on its own but requires a steady dose of them to maintain good health. It has long been known that PUFAs play fundamental roles in many cellular and multicellular processes, including inflammation, immunity, and neurotransmission – although the biochemical mechanisms facilitating these beneficial effects are yet to be fully understood.
Because we don’t produce these fatty acids, humans must rely on foods in our diet to supply these beneficial compounds. The typical western diet often contains high levels of omega-6s but very low levels of omega-3s – which results in deficiencies of these important PUFAs.
Omega-3 fatty acids – also written as ω-3 fatty acids – are present in certain foods such as flaxseed and fish, as well as dietary supplements such as fish oil. Eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are two of the most important omega-3s, and consuming EPA and DHA directly from foods and/or dietary supplements is the only practical way to increase levels of these fatty acids in the body. Many people supplement their diets with products like fish oils and krill oils to ensure they’re getting their recommended daily intake of omega-3s.
Interestingly, the endocannabinoid system (ECS) found in the human body is directly related to PUFAs.
The ECS includes G-protein coupled receptors, namely CB1 and CB2, their endogenous lipid ligands (endocannabinoids), and enzymes that regulate their biosynthesis and degradation. However, the endocannabinoids – the body’s own natural versions of the chemical compounds found in the cannabis sativa plant – are actually derived from PUFAs.
Converting PUFAs to endocannabinoids
Both omega-6 and omega-3 dietary fatty acids are stored in the plasma membrane and can be converted to different endocannabinoids.
For example, the endocannabinoid anandamide (AEA) – also known as the “bliss molecule” – is a fatty acid neurotransmitter that signals through both cannabinoid receptors and regulates physiological processes in both the central nervous system and peripheral tissues. It is derived from the non-oxidative metabolism of arachidonic acid (AA), which is an essential omega-6 polyunsaturated fatty acid.
The endocannabinoid 2-arachidonoylglycerol (2-AG) is an ester formed from AA and glycerol. 2-AG may play an important role in the regulation of appetite, mood, metabolism, immune system functions, pain management, reproduction, memory, sleep, and more.
Both DHEA and EPEA are known as ω-3 endocannabinoids. And similar to the conversion of AA into AEA, omega-3 fatty acids DHA and EPA are also converted into docosahexaenoyl ethanolamide (DHEA) and eicosapentaenoyl ethanolamide (EPEA) through the N-acyl ethanolamine synthesis pathway.
DHEA exhibits anticancer, anti-inflammatory, and synaptogenic (involved in the formation of synapses between neurons and the nervous system) properties and has been detected in both the brain and retina at concentrations comparable to those of AEA. EPEA also has been shown to activate anti-inflammatory pathways.
However, a new study in animal tissue has recently revealed the cascade of chemical reactions that converts omega-3 fatty acids into a previously unknown class of omega-3 PUFA–derived lipid metabolites. Called omega-3 endocannabinoid epoxides, they have been shown to have potent anti-inflammatory effects – but without the psychotropic high.
Researchers discover naturally occurring omega-3–derived endocannabinoid epoxides with some of the same medicinal effects as cannabinoids found in cannabis
In a recent 2017 study published in the Proceedings of the National Academy of Sciences and led by Aditi Das, a University of Illinois professor of comparative biosciences and biochemistry, researchers discovered an enzymatic pathway that converts omega-3-derived endocannabinoids into more potent anti-inflammatory molecules that predominantly bind to the receptors found in the immune system.
Their findings demonstrate how omega-3 fatty acids can produce some of the same medicinal qualities as cannabis, but without the psychotropic effect.
They discovered that once DHA and EPA are converted into DHEA and EPEA, respectively, these endocannabinoids can be broken down further to generate complex lipid metabolites with distinct biological functions.
For example, the metabolism of AEA by Cytochrome P450 (CYP) enzymes (involved in the breakdown of substances in the body) produces epoxyeicosatrienoic-ethanolamide (EET-EA) metabolites. These metabolites have been shown to be potent cannabinoid receptor type 2 (CB2) agonists that have anti-inflammatory effects.
Similarly, the metabolism of EPEA and DHEA by CYP enzymes leads to the formation of the omega-3 endocannabinoid epoxides epoxyeicosatetraenoic acid-ethanolamide (EEQ-EA) and epoxydocosapentaenoic acid-ethanolamide (EDP-EA), respectively.
The researchers found that these newly discovered epoxides (chemical compounds known as ethers that are comprised of 3-membered rings) display potent anti-inflammatory effects. These were achieved through CB2 activation by inhibiting the production of proinflammatory biomarkers, while simultaneously increasing production of an anti-inflammatory cell signaling molecule (or cytokine). They also found that these actions were produced without a psychotropic effect.
Some cannabinoids, such as the psychoactive component of cannabis known as delta-9-tetrahydrocannabinol (THC), can bind to CB receptors and elicit anti-inflammatory and anti-pain actions. The non-psychoactive cannabidiol (CBD) is also known to exert potent anti-inflammatory actions through various mechanisms of action on the vanilloid receptor TRPV1 and also as a reuptake inhibitor of adenosine.
In addition to the anti-inflammatory effects, the epoxides were also found to exert antiangiogenic effects by inhibiting the growth of new blood vessels. Antiangiogenic agents are interesting because they may help prevent or slow the growth of cancer.
Finally, the endocannabinoid epoxides were also found to the dilate blood vessels in the coronary arteries of cows (decreasing blood pressure) and regulate platelet aggregation in washed human platelets. Platelet aggregation is the clumping together of platelets in the blood and is an important part of the sequence of events leading to the formation of a thrombus (or clot).
Because these newly discovered omega-3 endocannabinoid epoxides are found at concentrations comparable to those of other endocannabinoids, the researchers concluded that they are expected to play critical roles during inflammation in the body. This breakthrough may be critical in the development of therapeutics for neuroinflammatory and cerebrovascular diseases in the future.
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