Psychiatry’s next top model: cause for a re-think on drug models of psychosis and other psychiatric disorders
Using a two-part subjective analysis that combined clinicians mapping experiences to symptom clusters and drug-experienced individuals rating reliability, the authors formally compared five drug models (cannabis, psilocybin, amphetamine, ketamine and alcohol). They found no experiences selectively modelling negative or cognitive psychotic symptoms over depression, identified psilocybin as the best model of positive symptoms, and acute alcohol and amphetamine as the most faithful models of mania, challenging prevailing assumptions about drug models in psychiatry.
Authors
- Robin Carhart-Harris
- David Nutt
- James Stone
Published
Abstract
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.
Research Summary of 'Psychiatry’s next top model: cause for a re-think on drug models of psychosis and other psychiatric disorders'
Introduction
Drug models have been widely used in psychiatry to generate hypotheses about the biology of mental disorders and to provide experimental platforms for testing treatments. Carhart-Harris and colleagues note that psychosis in particular has attracted attention because several psychoactive substances (cannabis/THC, serotonergic psychedelics such as psilocybin and LSD, amphetamines, and dissociatives like PCP and ketamine) can produce symptoms resembling psychosis. Despite this, few studies have compared different drug models directly, and uncertainty remains about which substances most closely and reliably mirror particular psychiatric symptom clusters. To address that gap, the investigators designed a two-part pilot, subjective study to compare five drugs (high-potency cannabis, psilocybin-containing mushrooms, amphetamine, ketamine and alcohol) on two dimensions: how specifically first‑person experiential statements map onto psychiatric symptom clusters, and how reliably each drug produces those experiences acutely and in the sub-acute period. The stated aim was to identify which drugs serve as the best models for particular psychiatric states and to use the findings to motivate more rigorous controlled work.
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Study Details
- Study Typeindividual
- Journal
- Compounds
- Topics
- Authors
- APA Citation
Carhart-Harris, R., Brugger, S., Nutt, D., & Stone, J. (2013). Psychiatry’s next top model: cause for a re-think on drug models of psychosis and other psychiatric disorders. Journal of Psychopharmacology, 27(9), 771-778. https://doi.org/10.1177/0269881113494107
References (7)
Papers cited by this study that are also in Blossom
Carhart-Harris, R. L., Nutt, D. J. · Journal of Substance Use (2010)
Gouzoulis-Mayfrank, E., Heekeren, K., Neukirch, A. et al. · Pharmacopsychiatry (2005)
Griffiths, R. R. · Journal of Psychopharmacology (2008)
Griffiths, R. R., Richards, W. A., Mccann, U. et al. · Journal of Psychopharmacology (2006)
Grob, C. S., Danforth, A. L., Chopra, G. S. et al. · JAMA Psychiatry (2011)
Hoch, P. H., Cattell, J. P., Pennes, H. H. · American Journal of Psychiatry (1952)
Vollenweider, F. X., Kometer, M. · Nature Reviews Neuroscience (2010)
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Dourron, H. M., Bradley, M. K., Copes, H. et al. · International Journal of Mental Health and Addiction (2026)
Rajpal, H., Mediano, P. A. M., Rosas, F. E. et al. · NeuroImage (2022)
Kuc, J., Kettner, H., Rosas, F. E. et al. · Psychopharmacology (2021)
Sanz, C., Pallavicini, C., Carrillo, F. et al. · Consciousness and Cognition (2021)
Brouwer, A., Carhart-Harris, R. L. · Journal of Psychopharmacology (2020)
Vollenweider, F. X., Preller, K. H. · Nature Reviews Neuroscience (2020)
Timmermann, C., Spriggs, M. J., Kaelen, M. et al. · Neuropharmacology (2018)
Carhart-Harris, R. L., Nutt, D. J. · Journal of Psychopharmacology (2017)
Carhart-Harris, R. L., Kaelen, M., Bolstridge, M. et al. · Psychological Medicine (2016)
Marta, C. J., Ryan, W. C., Kopelowicz, A. et al. · The American Journal on Addictions (2015)
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Steeds, H., Carhart-Harris, R. L., Stone, J. M. · Therapeutic Advances in Psychopharmacology (2014)
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