Glutamate and Opioid Mechanisms of Antidepressant Response to Ketamine
Research type
Research Study
Full title
Investigating Glutamate and Opioid Mechanisms of Antidepressant Response to Ketamine (GO-MARK)
IRAS ID
291439
Contact name
Allan Young
Contact email
Sponsor organisation
King’s College London
Duration of Study in the UK
2 years, 1 months, 31 days
Research summary
Ketamine, a widely used anaesthetic, has emerged as an effective, rapid-acting antidepressant with promising effects in treatment-resistant depression (TRD). However, it is not fully understood how ketamine works in the brain to cause these effects.
Ketamine acts at receptors in the brain (NMDA receptors), leading to changes in levels of glutamate, the brain’s main excitatory chemical transmitter. Ketamine also interacts with brain receptors called opioid receptors. It has been suggested that both the glutamate and opioid systems may be involved in ketamine’s antidepressant effects. This study aims to understand the changes that occur in the brain immediately after receiving ketamine in individuals with TRD, how the glutamate and opioid systems are involved, and how this relates to changes in depressive symptoms.
Participants with TRD will receive ketamine infusions during two separate visits. Before one of the ketamine infusions they will receive a naltrexone tablet (a drug that blocks opioid receptors) and on the other an inactive placebo. We will test the theory that ketamine causes an acute increase in glutamate levels using an imaging method (functional 1H-MRS) which allows measurement of glutamate using a magnetic resonance imaging scanner and explore whether naltrexone blocks this effect. We will also use other scanning techniques to measure brain blood flow and connectivity changes (ASL and resting state fMRI) following ketamine administration and investigate whether naltrexone blocks any of these effects.
This study will help us to understand the contribution of the glutamate and opioid systems to the acute effects of ketamine on the brain in individuals with TRD. It will also help us to understand how these effects on the brain relate to changes in depressive symptoms. This may eventually help us identify depressed patients who are most likely to respond to ketamine and also help in the development of new antidepressants.
REC name
London - City & East Research Ethics Committee
REC reference
21/LO/0334
Date of REC Opinion
13 May 2021
REC opinion
Favourable Opinion