, Volume 235, Issue 4, pp 1273–1282 | Cite as

Neurocognitive and behavioural performance of healthy volunteers receiving an increasing analgesic-range infusion of ketamine

  • Amie Hayley
  • Maja Green
  • Luke Downey
  • Michael Keane
  • Panagiota Kostakis
  • Yahya Shehabi
Original Investigation



The acute and delayed effect of analgesic-range doses of ketamine on neurocognitive and behavioural outcomes is understudied. Using a non-controlled open-labelled design, three (1-h duration) increasing intravenous (IV) ketamine infusions comprising (i) 30 mg bolus of ketamine + 8 mg/h IV infusion, (ii) 12 mg/h IV infusion and (iii) 20 mg/h infusion were administered to 20 participants (15 male, 5 female, mean age = 30.8 years). Whole-blood ketamine and norketamine concentrations were determined at each treatment step and post-infusion.


The Cambridge Neuropsychological Test Automated Battery (CANTAB) was used to assess reaction/movement time (RTI, Simple and 5-Choice), visuospatial working memory (SWM), spatial planning (SOC) and subjective effects (visual analogue scale; VAS) during treatment and at post-treatment.


Significant main effects were reported for time (dose) on CANTAB RTI 5-Choice reaction (F(4,18) = 3.41, p = 0.029) and movement time (F(4,18) = 4.42, p = 0.011), SWM (F(4,18) = 4.19, p = 0.014) and SOC (F(4,18) = 4.13, p = 0.015), but not RTI Simple reaction or movement time. Post hoc analyses revealed dose-dependent effects for both RTI 5-Choice reaction and movement time (all p < 0.05). Post-treatment performance on all neurocognitive and behavioural tasks returned to baseline levels. Regression analyses revealed a weak positive linear association between SWM ‘strategy’ score (R2 = 0.103, p < 0.001), all performance-based CANTAB VAS items (R2 range 0.005–0.137, all p < 0.05) and ketamine blood concentrations.


The open-label, non-controlled trial design somewhat precludes the ability to adequately account for random treatment effects. Notwithstanding, these results suggest that analgesic doses of ketamine produce acute, selective, dose-dependent deficits in higher-order neurocognitive and behavioural domains.


Ketamine Neurocognitive Behavioural Intravenous Therapeutic 


Compliance with ethical standards

The research was approved by Monash Health Human Research Ethics committee (approval number: HREC/16/MonH/240). All participants provided written informed consent prior to commencing any study procedures. This study was registered on the Australia and New Zealand Clinical Trials registry (; trial number ACTRN12616001485426.

Conflict of interest

Dr. Amie Hayley is supported by a National Health and Medical Council (NHMRC) Peter Doherty Biomedical Early Career Research Fellowship (APP1119960). A/Prof Downey is supported by an NHMRC R.D. Wright Biomedical Career Development Fellowship (CDF: 2017-2020). Dr. Green, Dr. Keane, Ms. Kostakis and Prof Shehabi declare no potential conflicts of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Centre for Human Psychopharmacology, Faculty of Health, Arts and DesignSwinburne University of TechnologyHawthornAustralia
  2. 2.Program of Critical Care and Perioperative Medicine, School of Clinical SciencesMonash UniversityMelbourneAustralia
  3. 3.Department of Oncology, Monash Health Translation PrecinctMonash UniversityClaytonAustralia
  4. 4.Institute for Breathing and SleepAustin HospitalMelbourneAustralia
  5. 5.Forensic Science South Australia (FSSA)AdelaideAustralia

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