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Psychopathological consequences of ketamine

Published online by Cambridge University Press:  02 January 2018

J. M. Stone
Affiliation:
Section of Neurochemical Imaging, King's College London, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK. Email: j.stone@iop.kcl.ac.uk
L. S. Pilowsky
Affiliation:
Section of Neurochemical Imaging, King's College London, Institute of Psychiatry, London, UK
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Abstract

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Copyright © Royal College of Psychiatrists, 2006 

Pomarol-Clotet et al (Reference Pomarol-Clotet, Honey and Murray2006) reported a range of perceptual distortions in healthy volunteers following ketamine administration but did not report hallucinations. They concluded that ketamine does not reproduce the full picture of schizophrenia, but there are similarities in terms of referential thinking and negative symptoms.

We also recently studied healthy volunteers following ketamine administration (Reference Stone, Erlandsson and ArstadStone et al, 2006) and, although previously unpublished, recorded phenomenological changes, including verbatim descriptions of their experiences. In keeping with Pomarol-Clotet et al, ketamine induced a wide range of abnormal perceptual experiences. However, no volunteers reported true hallucinations, although several reported eidetic imagery, and most reported visual illusions. Most experienced severe distortions of time, believing that a minute was several hours in duration. They also showed blunting of affect and loss of emotional reactivity. A few showed a marked disinhibition, with facetious replies to questions and apparent euphoria in the first 10–20 min after administration of ketamine. Several participants reported the belief that they were composed solely of thoughts, and that their bodies had either become nonexistent or were separate from them. One reported that he believed he could control people in the room by pointing with his hands, and another reported persecutory delusions.

Although we agree with Pomarol-Clotet et al that these drug-induced effects do not correspond directly to schizophrenic symptoms, we feel it would be remarkable if ketamine administration were to completely reproduce the idiopathic condition. Ketamine induces a syndrome which is much closer to schizophrenia than other classes of psychotogenic substance, and, along with other NMDA receptor antagonists, is unique in inducing negative symptoms (Reference Vollenweider and GeyerVollenweider & Geyer, 2001). As ketamine has direct effects at receptors other than the NMDA receptor (Reference Kapur and SeemanKapur & Seeman, 2002), we believe that the next step should be to elucidate which particular receptors are responsible for each of the symptoms observed following ketamine administration. This may be achieved using similar analyses of psychopathology to those employed by Pomarol-Clotet et al combined with in vivo neurochemical imaging.

References

Kapur, S. & Seeman, P. (2002) NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D(2) and serotonin 5-HT(2) receptors – implications for models of schizophrenia. Molecular Psychiatry, 7, 837844.CrossRefGoogle ScholarPubMed
Pomarol-Clotet, E., Honey, G. D., Murray, G. K., et al (2006) Psychological effects of ketamine in healthy volunteers: phenomenological study. British Journal of Psychiatry, 189, 173179.CrossRefGoogle ScholarPubMed
Stone, J. M., Erlandsson, K., Arstad, E., et al (2006) Ketamine displaces the novel NMDA receptor SPET probe [(123)1]CNS-1261 in humans in vivo. Nuclear Medicine and Biology, 33, 239243.CrossRefGoogle ScholarPubMed
Vollenweider, F. X. & Geyer, M. A. (2001) A systems model of altered consciousness: integrating natural and drug-induced psychoses. Brain Research Bulletin, 56, 494507.CrossRefGoogle ScholarPubMed
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