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

Background: 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. Methods: 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. Results: 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. Discussion: 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.