What number of endocannabinoids are there? You’d be forgiven for considering simply two, however a number of others have been recognized – and researchers in San Diego, California, say they simply discovered one other one.
Earlier than we get into that information, let’s again up. Endocannabinoids are generally known as the physique’s personal hashish: molecules that activate and modulate the endocannabinoid system (ECS), each to make you are feeling good and to assist preserve you properly, through a pair of mobile receptors generally known as cannabinoid receptor sorts 1 and a couple of, or CB1 and CB2.
The 2 most well-known endocannabinoids are anandamide and 2-AG, found within the early Nineties. They’re synthesized within the physique from arachidonic acid, an omega-6 important fatty acid obtained by way of meat, eggs, milk, and fish, or transformed from one other omega-6 known as linoleic acid, present in nuts, seeds, and a few refined vegetable oils.
Important Fatty Acids
Whereas anandamide and 2-AG get many of the consideration and are definitely crucial, they aren’t alone in interacting with CB1 and CB2. In a 2019 paper, researchers on the College of Illinois reported on latest discoveries of one other 4 endocannabinoids and their derivatives, all synthesized within the physique from two omega-3 important fatty acids discovered primarily in fish and dietary supplements.1
On the danger of getting misplaced in alphabet soup: from docosahexaenoic acid (DHA) come each DHA–EA (additionally known as synaptamide) and DHG. And from eicosapentaenoic acid (EPA) come EPA–EA and EPG. They’re not but family names (and should by no means be), however nonetheless seem like critically necessary to the ECS’s mission of sustaining homeostasis and general well being, partly as a counterbalance to the omega-6-derived endocannabinoids.2
Which brings us to the most recent discovery, a mouthful of a molecule known as pentadecanoylcarnitine (PDC). In line with the latest paper in Scientific Stories3 describing its discovery and preliminary testing, PDC is synthesized within the physique from one other dietary fatty acid generally known as pentadecanoic acid or C15:0 (discovered largely in full-fat dairy but additionally some fish, vegetation, and different meals). It binds with each CB1 and CB2, amongst different receptors, and should play a job in a wide range of physiological processes associated to the regulation of irritation, ache, temper, and sleep.
Dolphins, Dietary supplements, and the ECS
The story of PDC’s discovery is a wierd one. It includes the US Navy Marine Mammal Program, a drug-discovery firm known as Epitracker, and an Epitracker spinoff known as Seraphina Therapeutics that’s at the moment advertising and marketing and promoting C15:0 as a dietary complement known as Fatty 15.
Each corporations are run by the husband-and-wife workforce of Stephanie and Eric Venn-Watson. Each additionally maintain unique licensing rights from the US Navy to commercialize odd-chain saturated fatty acids as human and animal well being merchandise. On high of that, Eric is a longtime Navy doctor. Suffice to say there are conflicts of curiosity upon conflicts of curiosity.
With that in thoughts, let’s have a look at what they did – beginning with the dolphins. Stephanie Venn-Watson has been learning bottlenose dolphins as an animal mannequin for understanding the metabolism and well being results of fatty acid consumption in people for years; she served as lead writer of a pair of associated papers revealed in 20154; and 2020.5
The most recent paper summarizes her earlier work thusly: “Just like people, bottlenose dolphins are long-lived, large-brained mammals with demonstrated associations between larger circulating C15:0 and C17:0 concentrations and decrease dangers of continual metabolic circumstances. When dolphins have been fed a modified, high-C15:0 fish food plan, their serum metabolome shifted, leading to decrease insulin and ldl cholesterol, in addition to attenuated anemia.”
To higher perceive these adjustments, this time across the workforce sought to review the organic actions of key C15:0 metabolites. First, they analyzed beforehand collected blood checks from dolphins fed the modified food plan to establish compounds whose ranges rose in tandem with elevated fatty acid consumption. After six months of feeding, pentadecanoylcarnitine emerged because the number-one metabolite most related to, or predictive of, elevated C15:0 consumption.
PDC was then examined within the lab on a dozen human cell methods modeling varied illness states to elucidate its direct results. It was discovered to have dose-dependent anti-inflammatory actions in 5 of those methods which can be thought of clinically related to treating cardiovascular, immune, neoplastic (tumor-related), pulmonary, and pores and skin ailments.
Lastly, to evaluate its molecular mechanisms of motion, the researchers examined PDC’s exercise at a spread of targets together with receptors, transporters, ion channels, and enzymes. It was discovered to be a full agonist of each CB1 and CB2, a trait it shares with just one different recognized endocannabinoid, 2-AG.6 Moreover, PDC had dose-response antagonist actions for each histamine H1 and H2 receptors, making it an antihistamine, and agonist actions for each serotonin 1A and 1B receptors, that means it could assist psychological well being by way of serotonin launch, the authors report.
Given all this and the conflicts of curiosity beforehand disclosed, the large promote within the paper’s closing sentence ought to come as no shock: “As a consequence of population-wide decreases in entire fats milk consumption … additional research are wanted to judge attainable hyperlinks between the worldwide rise in allergic reactions, psychological well being circumstances, and sleep problems and C15:0 dietary deficiencies.”
Extra analysis into pentadecanoylcarnitine and its position as an endocannabinoid would even be welcome. It’s at the moment talked about solely a pair different occasions within the scientific literature, in each circumstances acknowledged as one in all many fatty acid metabolites, however not way more. The truth is it appears to be one in all a minimum of seven endocannabinoids recognized to date that function signaling brokers throughout the ECS, the physique’s grasp regulatory system.
Nate Seltenrich, an unbiased science journalist primarily based within the San Francisco Bay Space, covers a variety of topics together with environmental well being, neuroscience, and pharmacology.
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