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Absence of behavioral sensitization in healthy human subjects following repeated exposure to ketamine

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Abstract

Rationale

Sensitization to the effects of N-methyl-d-aspartate (NMDA) glutamate receptor antagonists is robust in animals. However, the applicability of this model to humans is unclear because it currently rests on highly confounded retrospective studies of individuals who experienced protracted psychoses following repeated binges with NMDA receptor antagonists.

Objectives

The purpose of the current study was to determine whether there was evidence of sensitization to the behavioral effects of ketamine in healthy human subjects with repeated exposure to this drug.

Methods

Data were studied from 295 healthy human subjects who participated in one or more of 11 separate studies that involved ketamine administration over 14 years. Positive and negative symptoms (Brief Psychiatric Rating Scale: BPRS), perceptual alterations (Clinician-Administered Dissociative States Scale: CADSS), and “high” and “anxiety” states (Visual Analog Scale: VAS) that were measured in all studies were included as outcome measures.

Results

After including the number of previous exposures, number of previous studies, and time since first exposure as variables, repeated exposure to ketamine did not result in increased behavioral responses, suggestive of behavioral sensitization.

Conclusions

The current data do not provide evidence that repeated exposure to ketamine, albeit limited, is associated with sensitization to the behavioral effects of ketamine.

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Acknowledgements

NIAAA: KO5 AA 14906-01; I-P50 AA-12870-03 NIMH; 5P50 MH44866-12; VA Merit Review Grant (J.K.), VA Schizophrenia Biological Research Center, VA Alcohol Research Center, VA REAP, VA National Center for PTSD; NARSAD Independent Investigator Award (J.K.).

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Authors and Affiliations

  1. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA

    Hyun-Sang Cho, Deepak C. D’Souza, Edward B. Perry, Walid Abi-Saab, Deborah Lipschitz, John P. Seibyl & John H. Krystal

  2. Schizophrenia Biological Research Center, VA Connecticut Healthcare System, West Haven, CT, USA

    Hyun-Sang Cho, Deepak C. D’Souza, Edward B. Perry, John P. Seibyl & John H. Krystal

  3. Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT, USA

    Ralitza Gueorguieva, John P. Seibyl & John H. Krystal

  4. Division of Biostatistics, Department of Epidemiology and Public Health, Yale University, New Haven, CT, USA

    Ralitza Gueorguieva

  5. The Institute of Living, Hartford, CT, USA

    Steven Madonick

  6. Department of Psychiatry, LVH-M, Lehigh Valley Hospital and Health Network, Bethlehem, PV, USA

    Laurence P. Karper

  7. Department of Psychiatry, Columbia University, New York, NY, USA

    Anissa Abi-Dargham

  8. Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA

    Aysenil Belger

  9. Pfizer Global Research and Development, Groton, CT, USA

    Walid Abi-Saab

  10. Neuroscience Scientific Liaison, Ortho-McNeil Pharmaceutical, Pennington, NJ, USA

    Alexandre Bennet

  11. Department of Psychiatry, Yonsei University College of Medicine, Seoul, Republic of Korea

    Hyun-Sang Cho

  12. Psychiatry Service, 116A, VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT, 06516, USA

    John H. Krystal

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  1. Hyun-Sang Cho
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  2. Deepak C. D’Souza
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  10. Deborah Lipschitz
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  13. John H. Krystal
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Correspondence to John H. Krystal.

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Cho, HS., D’Souza, D.C., Gueorguieva, R. et al. Absence of behavioral sensitization in healthy human subjects following repeated exposure to ketamine. Psychopharmacology 179, 136–143 (2005). https://doi.org/10.1007/s00213-004-2066-5

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  • DOI: https://doi.org/10.1007/s00213-004-2066-5

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