Phosphodiesterase-4 inhibitor

And then we actually put in kanna too, which if you're familiar with kanna, it has a couple alkaloids in there, which all the best drugs are alkaloids.

Like mesem- uh, mesembrine's one that actually inhibits PDE4 and your serotonin, um, tran- So it's called SERT, but it's the thing that metabolizes and breaks down serotonin.

And what's super cool about that is when you add even just a little bit of kanna into it, um, and have a little bit of extra serotonin and a little bit of that inhibition of, uh, PDE4, you actually have people, um, respond that they're in much less of a fear state, right? Much less anxious, much less, uh...

So what happens a lot of times is you create so much, you know, arousal that you end up just kinda clenching, right? Like how many times have you gotten tension headaches because you drank too much caffeine and all of a sudden you notice you're clenching your jaw, your neck hurts, or like everybody's got that weird knot in their shoulder blade.

It comes from like being overstimulated, right? And your, your breathing getting all weird.

And so there's possibly other effects on other monoamine signals.

And the other bit you mentioned, of course, was the phosphodiesterase inhibition, PDE4 in particular.

And that can influence a lot of downstream signaling pathways.

It's often a common second messenger within cells.

So the effects weren't a general improvement across all aspects of cognition, but appeared to be more specific to cognitive flexibility and executive function.

And these effects could potentially be relevant and beneficial in delaying or reversing age-related cognitive decline, and possibly have a role in Alzheimer's dementia.

One proposed mechanism for this is that mozembrane alkaloids inhibit phosphodiesterase 4, which we've talked about before, and inhibiting PDE4 increases intracellular cyclic AMP signaling, which can activate a transcription factor involved in synaptic plasticity and processes underlying learning and memory, but this mechanism hasn't been demonstrated directly.

Xenbrin also appears to have a positive effect on sleep onset as well.

Now, another one we talked about is Eucrisa or Crisabarol.

And this is a PDE4 inhibitor.

There's two PDE4 inhibitors.

There's this one as well as Zareve or Roflumilast.

And I feel like nobody likes you, Chrissa.

and very, very good safety overall.

The biggest issue with it is if you put enough on and in sensitive individuals, you can have a little bit of diarrhea and I've seen it.

And we think it's because in the distal colon, the PDE4 enzyme is actually used for water resorption.