Psychiatry's next top model: cause for a re-think on drug models of psychosis and other psychiatric disorders.

Despite the widespread application of drug modelling in psychiatric research, the relative value of different models has never been formally compared in the same analysis. Here we compared the effects of five drugs (cannabis, psilocybin, amphetamine, ketamine and alcohol) in relation to psychiatric symptoms in a two-part subjective analysis. In the first part, mental health professionals associated statements referring to specific experiences, for example 'I don't bother to get out of bed', to one or more psychiatric symptom clusters, for example depression and negative psychotic symptoms. This measured the specificity of an experience for a particular disorder. In the second part, individuals with personal experience with each of the above-listed drugs were asked how reliably each drug produced the experiences listed in part 1, both acutely and sub-acutely. Part 1 failed to find any experiences that were specific for negative or cognitive psychotic symptoms over depression. The best model of positive symptoms was psilocybin and the best models overall were the acute alcohol and amphetamine models of mania. These results challenge current assumptions about drug models and motivate further research on this understudied area.