Dolphin study identifies previously unknown endocannabinoid

The two best-known endocannabinoids are the’anandamide and 2-AG, which were discovered in the early 1990s. They are synthesized in the body from arachidonic acid, an essential fatty acid in the omega-6 family found in meat, eggs, milk, and fish, or converted from another omega-6 fatty acid called linoleic acid, which is present in nuts, seeds, and certain refined vegetable oils.

While anandamide and 2-AG have attracted attention, they are not the only ones that interact with the CB1 receptors and CB2. In an article published in 2019, researchers at the University of Illinois reported the recent discovery of four more endocannabinoids and their derivatives, all of which are synthesized in the body from two essential fatty acids in the omega-3 family that are found primarily in fish and supplements.

Which brings us to this recent discovery: a molecule called pentadecanoylcarnitine (PDC). According to the article published in Scientific Reports, PDC is synthesized in the body from another dietary fatty acid known as pentadecanoic acid or C15:0—which is found primarily in full-fat dairy products, but also in certain fish, plants, and other foods. It binds to CB1 and CB2 receptors, among others, and may play a role in various physiological processes related to inflammation regulation, pain, mood, and sleep.

The study summarizes its findings as follows: «Like humans, bottlenose dolphins are long-lived mammals with large brains. It has been shown that there are associations between higher circulating concentrations of C15:0 and C17:0 and lower risks of chronic metabolic conditions. When the dolphins were fed a modified diet of fish rich in C15:0, their serum metabolome changed, leading to lower insulin and cholesterol levels, as well as reduced anemia.»

To better understand these changes, the team this time sought to study the biological activities of the main C15:0 metabolites. First, they analyzed blood samples previously collected from dolphins on the modified diet to identify the compounds whose levels increased in tandem with fatty acid intake. After six months on the diet, pentadecanoylcarnitine emerged as the metabolite most strongly associated with—or predictive of—high C15:0 intake.

PDC was then tested in the laboratory on a dozen human cellular systems modeling various pathological conditions in order to elucidate its direct effects. It was found to exhibit dose-dependent anti-inflammatory activity in five of these systems, which are considered clinically relevant for treating cardiovascular, immune, neoplastic (tumor-related), pulmonary, and skin diseases.

Finally, to evaluate its molecular mechanisms of action, the researchers tested PDC’s activity on a series of targets, including receptors, transporters, ion channels, and enzymes. It was found to be a full agonist of the CB1 and CB2 receptors, a characteristic it shares with only one other known endocannabinoid, 2-AG.

The article concludes: «Due to the decline in whole milk consumption among the general population… further studies are needed to assess the possible links between the global increase in allergies, mental health disorders, and sleep disorders and nutritional deficiencies in C15:0.».

Further research on pentadecanoylcarnitine and its role as an endocannabinoid would also be welcome. While it appears to be one of at least seven endocannabinoids identified to date that serve as signaling molecules within the endocannabinoid system, the body’s primary regulatory system, has so far received very little attention in the scientific literature.