This essay maps out an unresolved, perhaps unresolvable, conceptual problem within psychedelic literature: authors have frequently noted the overlap between disease states and psychedelic states, complicating the case for their intellectual, spiritual, or therapeutic benefits. Firstly, Aldous Huxley (1894-1963) associated the psychedelic experience with the effects of extreme, disease-inducing ascetic practices. Secondly, psychedelic drugs have been viewed as psychotomimetic, inducing states thought to be phenomenologically or cognitively comparable to psychotic states. Thirdly, Huston Smith (1919-2016) and Raymond Harold Prince (1925-2012) have suggested that infectious diseases, like psychedelics, may induce religious experiences. Fourthly, psychedelic drugs arguably induce cognitive impairment and a delusional sense of insight (Roche 2010). Finally, it is widely believed that the parasitic fungus rye ergot (Claviceps purpurea) was deliberately ingested as a psychedelic drug by the ancient Greeks and others, despite ergotism being potentially lethal and having severe neuropsychiatric symptoms. I first clarify what it may mean to say that the psychedelic experience is a disease state, then assess the following counterarguments: (i) therapeutic use, (ii) traditional use, and (iii) cognitive enhancement (‘epistemic benefits’). The second part of the essay outlines the impact of ergotism on religious life in European history, and evidence for its ritual use.