Psychopharm for Delusions

Hi all, I’m a 3rd year heavily interested in Psychiatry. This is a bit more theoretical of a question but just wanted to throw it out there and see if anyone had suggestions for addtl reading/literature. Sorry in advance for any misunderstandings that make you cringe.

I have always been interested in the cognitive side of things and the idea of delusions in psychosis have always fascinated me, how our normal DA antags treat positive symptoms but don’t always/usually resolve particular delusions. From my shadowing and discussion the psychiatrists ive talked to usually are handsoff on delusions, saying “theres plenty of delusional people in the world” and theres not much that can touch them if the antipsychotics don’t.

From what reading ive done (a bit over my head, but I try) it seems like DA works to signal significance to internal stimuli in psychosis and by antagonizing this we stop overweighting internal predictions/stimuli over external evidence so the delusion stops “growing”, but it remains aberrantly learned and doesn’t go away just because we stop feeding it with dopaminergic salience(?).

What ive been trying to look into is, are there proposed or trialled ways to instead *overweight* external stimuli over internal ones, almost like the opposite of what happens in psychosis cognitively? My thought would be that in this window psychotherapy to try and disassemble the delusions could be more effective? One thing i’d seen is 5HT2A psychedelics can seem to increase flexibility of mental models increasing permeability to new info but for many many reasons giving someone with psychosis an acid trip to try and reduce delusions sounds like… a very bad idea.

The other main candidate I saw was ACh agonism is said to increase weight of sensory info over internal models and that this may be a reason for schizophenia patients heavily indulging in nicotine because they find it helps them? And that there’s a non-dopaminergic antipsychotic KarXT that’s recently been making its way to market through agonizing muscarinic ACh?

Finally I read a bit about kappa opioid receptors proposed role in stress related cognitive distortions and how potentially antagonizing these could lead to less cognitive distortions.

Anyway the point of this post is to ask if anyone has experience eg with KarXT and if it had helped open the door to delusion reduction / lessen psychotic thinking in general compared to DA blockers, or if there’s other frontiers looking at ways to approach delusions from a psychopharm + therapy perspective, or if this concept I’ve been digging into is not realistic/dumb/misunderstanding/etc.

If anyone has suggestions for a med student interested in this kind of cognitive psych / psychopharm research as part of my career I’d be super interested to hear about that too! Sometimes I wonder if I should have just gone the PhD route in order to dig this deep buy hey, I’m here now, and I hope I can still be a part of it as an MD eventually too. Sorry again if any of this is cringe-inducing misunderstanding or not really the domain of clinical psychiatry practice.