Effect of subanaesthetic ketamine on plasma and saliva cortisol secretion

The commonality between chronic conditions that are treated with low-dose ketamine, such as specific chronic pain conditions, depression, and post-traumatic stress disorder, can be found in relation to the stress system, particularly the hypothalamus-pituitary-adrenal axis. In this study we assess the effect of ketamine on the stress system by measuring plasma and saliva cortisol production during and following exposure to low-dose ketamine.

In a double-blind, randomized, placebo-controlled study, the influence of subanaesthetic ketamine (0.29 mg kg(-1) h(-1) for 1 h, followed by 0.57 mg kg(-1) h(-1) for another hour) was studied with repeated plasma and saliva cortisol samples in 12 healthy male volunteers. A pharmacokinetic-pharmacodynamic model was used to describe the circadian rhythm-dependent ketamine-induced production of cortisol.

The endogenous mean baseline cortisol production was 7.9 (SE 1.5) nM min(-1). Consistent with the circadian rhythm, cortisol production decayed by 1.25 nM min(-1) h(-1). Ketamine doubled the cortisol production at a concentration of 165 (SE 35) ng ml(-1). The salivary cortisol concentration closely mirrored the plasma concentration and was exponentially related to the plasma concentration with, at 100 ng ml(-1) ketamine, a saliva:plasma ratio of 0.036 (se 0.006).

Ketamine has an appreciable effect on cortisol production. This may impact on critical physiological and psychological functions.

This study was registered in the Dutch Trial Register under number NTR2717 at www.trialregister.nl.