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 typically referred to 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 maintain you effectively, by way of a pair of mobile receptors referred to as cannabinoid receptor varieties 1 and a couple of, or CB1 and CB2.
The 2 most well-known endocannabinoids are anandamide and 2-AG, found within the early Nineteen Nineties. They’re synthesized within the physique from arachidonic acid, an omega-6 important fatty acid obtained via meat, eggs, milk, and fish, or transformed from one other omega-6 referred to as linoleic acid, present in nuts, seeds, and a few refined vegetable oils.
Important Fatty Acids
Whereas anandamide and 2-AG get a lot of the consideration and are actually essential, they don’t seem to be alone in interacting with CB1 and CB2. In a 2019 paper, researchers on the College of Illinois reported on current 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 threat of getting misplaced in alphabet soup: from docosahexaenoic acid (DHA) come each DHA–EA (additionally referred to 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 look like critically essential 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 referred to as pentadecanoylcarnitine (PDC). In response to the current paper in Scientific Reports3 describing its discovery and preliminary testing, PDC is synthesized within the physique from one other dietary fatty acid referred to as pentadecanoic acid or C15:0 (discovered largely in full-fat dairy but additionally some fish, crops, and different meals). It binds with each CB1 and CB2, amongst different receptors, and should play a task 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 entails the US Navy Marine Mammal Program, a drug-discovery firm referred to as Epitracker, and an Epitracker spinoff referred to as Seraphina Therapeutics that’s at the moment advertising and marketing and promoting C15:0 as a dietary complement referred to as Fatty 15.
Each corporations are run by the husband-and-wife group 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 prime 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 take 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 creator of a pair of associated papers printed in 20154; and 2020.5
The newest paper summarizes her earlier work thusly: “Just like people, bottlenose dolphins are long-lived, large-brained mammals with demonstrated associations between increased circulating C15:0 and C17:0 concentrations and decrease dangers of continual metabolic situations. When dolphins have been fed a modified, high-C15:0 fish weight loss plan, their serum metabolome shifted, leading to decrease insulin and ldl cholesterol, in addition to attenuated anemia.”
Pentadecanoylcarnitine
To raised perceive these modifications, this time across the group sought to review the organic actions of key C15:0 metabolites. First, they analyzed beforehand collected blood assessments from dolphins fed the modified weight loss plan to determine 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 are thought-about 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 variety 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 via serotonin launch, the authors report.
Given all this and the conflicts of curiosity beforehand disclosed, the massive promote within the paper’s closing sentence ought to come as no shock: “Attributable to population-wide decreases in entire fats milk consumption … additional research are wanted to judge potential hyperlinks between the worldwide rise in allergy symptoms, psychological well being situations, and sleep problems and C15:0 dietary deficiencies.”
Extra analysis into pentadecanoylcarnitine and its function as an endocannabinoid would even be welcome. It’s at the moment talked about solely a pair different instances within the scientific literature, in each circumstances acknowledged as one in every of many fatty acid metabolites, however not far more. In truth it appears to be one in every of no less than seven endocannabinoids recognized thus far 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.
Copyright, Mission CBD. Is probably not reprinted with out permission.
Footnotes
