Psychiatric safety of ketamine in psychopharmacology research

Edward B. Perry, Joyce A. Cramer, Hyun Sang Cho, Ismene L. Petrakis, Laurence P. Karper, Angelina Genovese, Elizabeth O'Donnell, John H. Krystal, D. Cyril D'Souza, A. Abi-Dargham, D. Abi-Saab, W. Abi-Saab, Y. W. Ammerman, A. Anand, A. Belger, A. Bennett, R. M. Berman, N. Boutros, M. B. Bowers, A. BreierJ. D. Bremner, L. Brush, A. Cappiello, K. Cassello, D. S. Charney, H. Cho, N. L. Cooney, T. B. Cooper, J. Cramer, D. Damon, R. Delaney, D. C. D'Souza, G. K. Freeman, J. Gelernter, R. Gil, C. Grillon, R. Gueorguieva, G. R. Heninger, X. S. Hu, T. Hunsberger, P. Jatlow, L. P. Karper, J. H. Krystal, L. Levine, D. Limoncelli, D. S. Lipschitz, N. Liu, L. MacDougall, S. H. Madonick, K. Morrissey, S. Namenworth, D. A. Oren, E. B. Perry, I. L. Petrakis, J. P. Seibyl, P. Stetson, R. F. Suckow, L. A. Trevisan, S. Vegso, E. Webb, J. A. White, L. Zimmerman, E. Zuzarte

Research output: Contribution to journalArticle

83 Scopus citations


Rationale: A growing number of investigators are studying ketamine effects in healthy human subjects, but concerns remain about its safety as a research tool. Therefore, it is timely to revisit the safety of subanesthetic doses of ketamine in experimental psychopharmacology studies. Objective: To report on the safety of laboratory studies with subanesthetic doses of ketamine in healthy humans using an existing dataset. Materials and methods: Medically healthy subjects with no personal or familial Axis I psychotic spectrum disorders were administered subanesthetic doses of ketamine by intravenous infusion in a series of clinical investigations from 1989 to 2005. The safety of ketamine administration was monitored in these subjects. Results: Four hundred and fifty subjects received at least one dose of active ketamine. Eight hundred and thirty three active ketamine and 621 placebo infusions were administered. Ten adverse mental status events were documented in nine subjects/infusions that were deemed related to ketamine administration (2% of subjects, 1.45% of infusions). All but one adverse reaction resolved by the end of the test session. The side effects in the remaining individual were no longer clinically significant within 4 days of the test session. No residual sequelae were observed. Conclusion: Ketamine administration at subanesthetic doses appears to present an acceptable level of risk for carefully screened populations of healthy human subjects in the context of clinical research programs that intensively monitor subjects throughout their study participation.

Original languageEnglish (US)
Pages (from-to)253-260
Number of pages8
Issue number2
StatePublished - Jun 2007
Externally publishedYes


  • Antagonist
  • NMDA receptor

ASJC Scopus subject areas

  • Pharmacology

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    Perry, E. B., Cramer, J. A., Cho, H. S., Petrakis, I. L., Karper, L. P., Genovese, A., O'Donnell, E., Krystal, J. H., D'Souza, D. C., Abi-Dargham, A., Abi-Saab, D., Abi-Saab, W., Ammerman, Y. W., Anand, A., Belger, A., Bennett, A., Berman, R. M., Boutros, N., Bowers, M. B., ... Zuzarte, E. (2007). Psychiatric safety of ketamine in psychopharmacology research. Psychopharmacology, 192(2), 253-260.