(GluEsk) Glutamate and Esketamine
Sponsored by University of Oxford
About This Study
Esketamine is the S-enantiomer of racemic ketamine, a N-methyl-D-aspartate (NMDA) receptor antagonist. Esketamine and other antidepressant NMDA receptor antagonists are hypothesised to act by producing a rapid increase in brain glutamate release, which then stimulates α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. This activity in turn is thought to restore synaptic functioning, neuroplasticity, and connectivity in brain regions involved in mood regulation, which would be ultimately responsible for the antidepressant effect of esketamine. However, the effect of esketamine on glutamate release in humans has not previously been studied. In this study we therefore aim to ascertain the effect of esketamine on dynamic brain glutamate release, resting state connectivity, and neuroplasticity as measured via fMRS, BOLD-rs-fMRI, and a behavioural computerised visual task respectively.
Conditions Studied
Interventions
- •Esketamine nasal spray
- •Placebo
Eligibility
View full eligibility criteria
Inclusion Criteria: * Aged 18 to 50 years * Body Mass Index in the range of 18-30 * Sufficiently fluent in English to understand the study instructions * Willing and able to give informed consent for participation in the research Exclusion Criteria: * Currently on any regular prescribed medications (except the contraceptive pill), unless unlikely to compromise safety or affect data quality in the opinion of the Investigator * Known hypersensitivity to the study drug (i.e., esketamine) * History of, or current significant alcohol or substance misuse disorder * Any use of recreational drugs over the last 3 months * Any lifetime use of ketamine or phencyclidine (PCP) * Currently smoking \>/=20 cigarettes/day * History of, or current significant cardiovascular disorder (e.g., hypertension, myocardial infarction) * History of, or current significant neurological disorder (e.g., epilepsy, migraine) or cerebrovascular disorder (e.g., haemorrhagic or ischemic stroke, aneurysmal vascular disease, raised intracranial pressure) * History of, or current significant respiratory, hepatic, urinary tract, or thyroid disorders * History of, or current acute porphyria * History of, or current significant psychiatric disorder (e.g., psychosis, mania, depression) * History of, or current eye disorder, not including refractive error that can be corrected with glasses or contact lenses) * Pregnant, breast feeding, women of child-bearing potential not using appropriate contraceptive measures * Any contraindication to 7T MRI