I had an idea that I thought was pretty damn cool, but I'm not much of a designer, so, thought I'd cast it out there for anyone who wants it to take it on. This is for a custom story. The protagonist has ingested deadly nightshade (datura), a very powerful toxic deliriant. He doesn't recall his own name, he's hallucinating monsters that want to kill him, getting voices in his head, seeing nasty things that aren't there, and visual distortions especially when scared.
I picture a lot of this happening in the woods. There'd be a lot of opportunity to screw with the players' heads. For example, you might have them escape a particularly terrifying dungeon and find themselves in the broad eerie moonlight, only to suddenly get transported back there - ala Descent, they never left, they only imagined escaping. They'd find notes that don't actually convey any information, just ominous and otherworldly messages similar to schizophrenia. The objective would be to survive the trip.
I reckon it's a cool premise and there's a lot of room to be creative with it.
Here's a report from someone who took datura, to give you an idea of how very Dark Descent-esque it is. Please don't take it yourself. Hopefully someone likes my idea and runs with it for a custom story.