A person that knows they're under the influence of something has an explanation for why everything is all wierd...
But somebody that's never been under the influence of anything... and somebody slips them a little, say, acid without telling them... very, very bad.
Little guy has no idea why things are just all freaky all of a sudden.
Yup. That's what I figure.
He knows ~something~ is wrong and is trying to fight it off. And Tweek is missing - no doubt adding to his mental hysteria.