BTS #35 Excerpt: What is the Endocannabinoidome? w/ Vincenzo Di Marzo, PhD


Absolutely. And for those listening that maybe don't have such a technical technical background on cannabinoids science. How would you describe the concept of the Endo cannabinoid Dome to somebody? Okay. So basically, you know with the word. Oh now we make new words containing the the the prefix the suffix off to identify very large system. So we have the Janome with the metabolism. We have the proteome and so on and so forth. So the Endo the endocannabinoid Ang Ang came in a way from you mentioned before the the study that roughly mechoulam in which we collaborating collaborated on the Entourage effect. So basically what we perceived is that in what we were measuring. In fact when we were measuring endocannabinoids is that this these two molecules and under minded to a g were accompanied by dog Plethora of other compounds and this compounds this metabolites were chemically and biochemically similar meaning that you know, an undermined into a Jeep belongs to you know, mm different families of metabolites. And these are the Ennis. I'll at the moment and the and the monocyte whistles some of which were already known. In fact, even one of two thousand kids, but even longer than that before the end of cannabinoids were discovered. So the nobody knew really how these molecules were acting so Rafi in a vegetative way that this is really is his main feature is creativity and Imagination thought about this. These are accompanying molecules that are there too practical to make make the two big actors look even more important than they are so it's an Entourage or you know, when politicians go around and they take with them a lot of birth. Of the accompanying people and that that's certainly part of the of the picture but that then we started realizing that these compounds in fact do have a molecules do have targets of their own. So the endocannabinoid if you wish is is a kind of evolution of the of the Entourage effect. Molecules like the NSA little minds or the Mona Lisa started being investigated receptors were being found and and this created of course exciting but also complications because you know, the pharmacologists ended the drug developers were the therapeutic drug developers were we're thinking okay, we can we can manipulate wage levels of the end of since they are so strongly involved in pathology. We can manipulate the levels of the endocannabinoids of an undermined and 2G in order to make more of these compounds where they're needed or to reduce the amount their amount where they're produced in an excessive that manner so you can do that by manipulating the the degradation of the biosynthesis of endocannabinoids, but then when it was found that and we found we and many others that and under might has the same biochemical Pathways as other in a salad all mines which have different receptors from the cannabinoid. Just this created a strong complication. We cannot really manipulate the levels of an endermite in this way without manipulating the levels of the other previously known as entering compounds but having an identity and and in the mechanism of action of independent from the endocannabinoids of their own so they can have been a dome is basically the the the bigger System including Napoleon undermine and 2G and their main receptors which are simply one CB2 but also bought some of the other receptors foreign under my tend to agree because these are two very promiscuous molecules unlike THC. This is one major difference from between between the endocannabinoids and the plants and and happy now it's dead or at least between between the endocannabinoid and THC and then it was found that in fact, even the biosynthesis and degradation of of these 2 khong Will not be only mediated by one or two enzymes there was a redundancy of biosynthetic and degrading enzymes and and sometimes it ingredient X will not degrade enzymes because they were simply converting an undermined and 2 g into molecules which had different receptors. And this is you know, this is this may seem strange but not two people like like me off at the bioactive lipids all their life, you know, all bye-bye activities are transformed into something different and come from something different with the different biological a month or so, and then there is the containers of an under my dental legited what we call the previously the Entourage compound which have their own receptors, even though they share with the endocannabinoid the same battle synthetical Pathways. And then finally there were other molecules which have different biochemical dead. Pathways as the end of cannabinoids better nevertheless, they're not congeneres. They're not like cousins not they're not like brothers and sisters but their cousins so you have a tennis I'll amide. And in fact when we collaborated with the and with with the with the other groups, we we found that in fact particularly with the group of my coworker the late my coworker. We we found that many many compound many amino acids could make a might with fatty acids and this could create an almost incredible number of new combinations between the 10 or 15 fatty acids and 20 amino acids. So just just imagine all the permutations and and so this compounds actually exist as as the group of other brands show as also recently investigated and and so it's really we're talking now about a huge number of chemical mediators. So the endocannabinoid open their containers their analogues, which may or may have not different similar biochemical Pathways normally have different receptors dead. We we talking about the several other targets that undermined into the G have Beyond City 162. We're talking about other enzymes. So we're talking about something something about more than a 250 chemical mediators more than fifty enzymes and and receptors and some of these receptors were actually known previously like the wage channels or the or the P bars and and and the interesting thing is that you know, of course we when the end of conversation became so big Then the next question was okay. THC is the only out of 100 and more a plan cannot be known that interact with the endocannabinoid system. What about maybe maybe if you don't look only at the end of can access them, but we look at the expanded n. Can have this Summit this and maybe the other cannabinoids with interact with the endocannabinoid home, even though they don't in fact with the entertainment system. This is true to a large

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