Transcript:

Well, we haven't seen delirium yet, but delirium is usually not caused by procholinergic drugs. It's much more often caused by anticholinergic drugs, and so we can see they're being tested now actually in Alzheimer's psychosis, and those people might be more, you know, vulnerable to that.  

If they are tried, we may see that there, but hasn't been reported yet.  

Are there clinical trials that clients could be enrolled in? You know, there are. Talk to the Karuna people, they're doing an add-on study to schizophrenic patients on D2 antagonists. They're doing a psychosis in Alzheimer's study. check with the Karuna booth.

Will these new medications in development be LAI? I don't know, but perhaps not because there's 2 drugs in it. It's too early to tell, but maybe, it’d be a little complicated to do that.

Do you foresee any future applications of the muscarinic modulator for dementia? Absolutely. Should work at least in the psychosis of dementia and very well may work in the agitation of dementia. As you know, the Rexulti drug just got approved for agitation, depression, and dementia, and the Auvelity drug is about to be approved for that. So, agitation is amenable to pharmacological input in Alzheimer's disease. This could work as well, and it certainly should work for the psychosis.  

Will this work for bipolar patients? I don't know, but it could. I hope so. I think it's time to investigate. Totally plausible.

For the muscarinic modulation of dopamine, do we assume that that causes schizophrenia

due to malfunction of the GABA neurons in the frontal cortex? There are 2 major hypotheses, actually many. There's actually a third. There's one hypothesis that the brain doesn't make enough M1 receptors and they're deficient in certain subpopulations. And there's a group called the Dean group. Dr Dean has done scans showing that, and there are some autopsy studies showing deficient cholinergic receptors.  

However, more popular is the theory that there are sick GABA interneurons neurodevelopmentally. And finally, if you follow Danny Weinberger's work at Hopkins, he has reported, and it's been replicated, that there are both autopsy findings of deficient D2 receptors presynaptically in the VTA and also genetic studies that they're deficient. So, it's possible that the autoreceptor for the dopamine, in other words, the brake, as opposed to the accelerate, is gone. If the brake is gone, dopamine comes out. So, these are 3 of the major hypotheses of why this is wrong. But the fact that there is dopamine release is indisputable. The “why it is,” we're still working on.  

A teen bought a benzo and took Benadryl, and they hallucinated. Was this because the serum level of the benzo increased GABA? Glutamate stimulates NMDA, causing increase in dopamine. Well, Benadryl is really an anticholinergic, and so it probably did it through its anticholinergic effects, quite frankly. And a benzo is sedating, and the 2 together is again 1+1 equals 10, also on the side effect side. So, if you take that, he said thrown in a little alcohol, it would really made him fun.  

All right, ladies and gentlemen, we're done.