2-Arachidonoylglycerol

There's a feedback mechanism, and that's the endocannabinoid.

And the two major endocannabinoids, one is called anandamine and the other is 2-AG.

And the anandamine comes from the word ananda, which means pleasure and peace.

So I think what it does, it actually... modulates not just the nervous system, but the immune system as well.

rapidly changing legal and cultural status of cannabis globally, patients are constantly asking their doctors about using it for anxiety.

The textbook breaks down the endogenous ligands like anandamide and 2-AG and the primary receptors CB1 and CB2.

What is the fundamental neurobiological mechanism of this system?

The endocannabinoid system is unique.

So you go, wow, okay.

So based off endocannabinoid receptors, CB1, CB2, CB2, The individual cannabinoids that are made in the body, like 2-AG and anandamide, you go, okay, so we have adaptation to this, and the body seems to tolerate these chemicals well because there's some adaptation to it.

And when you realize what it does on a mechanistic level, and this is based off PET data in particular… Cannabis actually seems to have neuromodulatory properties.

So you go, this works like a homeostasis agent.

Then they discovered endocannabinoids, which I mean is the body produce its own cannabis.

It's on THC, what we call them endocannabinoids, anandamide and 2-AG.

And those are the endogenous ligand of this receptor.

And then this is a very complex system.

So is there a difference in the expression level of these receptors and the age? That is right.

Exactly.

After that, what I discovered that was the most important thing in, I think, the base of my story is What I discovered that, which is evolutionary concern, we don't know why, in particularly the hippocampus of the brain and 2-AG, which is main endogenous ligands of the cannabinoid 1 receptor, and it is biosynthesis enzyme, which we call DAGEL-alpha, significantly reduced during aging.

Significantly.

The evidence is overwhelming.

We didn't really get into it, but endocannabinoids, anandamide, and 2-AG also kill cancer cells.

So Phytocannabinoids and endocannabinoids kill cancer cells.

That's why cannabis is working so well in humans.

The study can't tell us that, but it can make us ask a much better question than, "Why do kinky people like being hurt?" Then I found another study by the same research group, this one called Between Pleasure and Pain, and here, things get even stranger.

They took blood samples from dominants and submissives before and after actual BDSM play and measured cortisol, which is involved in our stress response, as well as endocannabinoids, including anandamide and something called 2-AG.

Yes, I'm not pretending I know everything [laughs] and I also had no idea what the fuck an endocannabinoid was before I started researching this episode.

So basically, they are chemicals that our bodies naturally produce, and they're involved in things like pain, stress, mood, and reward.

Dominants involved in power play showed higher levels of the two endocannabinoids the researchers were studying.

For submissives, the pattern was different.

Pain play was associated with higher 2-AG.

Now, please don't leave this episode and tell somebody, "Oh, you know, science has proven dominants don't care about the pain.

There are two known endocannabinoids.

One is called anandamide, and the other one is called 2-AG.

And both of those re- both of those endocannabinoids tend to be, uh, lower in patients with chronic diseases.

And so one, and again, one other reason why cannabis can be utilized to compensate for the lack of natural occurring endocannabinoids, which is part and parcel of the problem of most chronic diseases.

Kanna like, uh, cannabis, and keys, uh, .com.

And so, um, there you'll find a lot of free information, while primarily it's directed at paid, at patients and clinicians on a subscription base.

But there's a lot of free information, a lot of introductory blog articles about the endocannabinoid system, about the, uh, uh, CB1 and CB2 receptor sites, about the e- endocannabinoids like anandamide or 2-AG.

We mentioned the ones that are associated with the runner's high.

very appropriate name.

And then there's a second one that I was involved in discovering, which is 2-AG.

And even, I think the field now has really recognized that these two signaling endocannabinoids, anandamide on one side and 2-AG on the other side, are actually doing very different things in the brain and have very different functions, even though they're both endocannabinoids and they act on cannabinoids we're going to be focusing on the cannabinoid CB1 receptors in the brain.

Got it.

So there's a bunch of different stuff in the brain and body, different types of signaling molecules, different classes, different structures, different functions.

So they are lipids.

And then we have enzymes that are going to cut those lipids, hydrolyze those lipids that are complex, and release smaller lipids that are going to be the endocannabinoids.

Those enzymes are going to be different if we're talking about the first endocannabinoid anandamide versus the second cannabinoid 2-AG.

So that's one of them.

And 2-AG is the other system.

We think it plays a role in various homeostasis.

So it seems to control appetite, sleep, but also cognition and immunity.