The promises of the Prozac century have fallen short; the number of novel, therapeutically significant medications successfully completing development shrinks every year; and the demand for better treatments constantly grows. Answering these hardships is a renewed optimism concerning the efficacy of controlled psychedelic therapy, a renaissance that has seen the resurgence of a familiar concept: intoxication as model psychosis. And yet, little has been made of where this peculiar idea originates. Why did we come to liken psychosis to intoxication, and why is this an idea we find so hard to shake?