Oxford study gives new insights into impact of ketamine on brain activity
Findings could lead to development of better antidepressant treatments
A study led by researchers at the University of Oxford has revealed new evidence on how ketamine affects the brain, providing insights that could ultimately help in the development of treatments for depression.
The research focused on the habenula, a small brain region that plays an important role in processing negative experiences and guiding how we learn from them.
Using functional magnetic resonance imaging (fMRI), researchers studied healthy volunteers, some of whom had received ketamine the previous day, administered by a healthcare professional.
The study found that those who had received ketamine showed reduced activity in the habenula in response to unpleasant stimulation.
The findings align with previous research in animals which suggested that excessive activity in the habenula may be associated with depression and that ketamine can act on this region.
Erdem Pulcu, Senior Researcher at the Department of Psychiatry, University of Oxford, and lead author of the study, said: “Ketamine is particularly interesting because its antidepressant effects can emerge much faster than those of conventional antidepressants, but we still have a great deal to learn about how those effects arise in the human brain.
“Our findings point to the habenula as one part of that mechanism. This small brain region plays an important role in how we respond to and learn from negative experiences, and we found that ketamine reduced its response to unpleasant events.
“What is particularly encouraging is that our findings align with earlier research in animal models. Establishing this kind of correspondence between animal and human studies is important if we want to use discoveries about ketamine to develop new treatments that retain its potential benefits while reducing unwanted effects and risks.”
The study also found preliminary evidence that this change could influence how unpleasant experiences are remembered, with those experiences potentially recalled as less negative.
Researchers emphasised that the study was conducted in healthy volunteers rather than people with depression.
It therefore does not establish that changes in habenula activity are responsible for ketamine’s antidepressant effects in patients.
Further research will investigate whether ketamine produces similar changes in the habenula in people with depression who have not responded to conventional antidepressant treatments.
Catherine Harmer, Professor of Cognitive Neuroscience at the Department of Psychiatry, University of Oxford, and one of the senior authors of the study, said: “The important next question is whether we see the same mechanism in people living with difficult-to-treat depression.
“If we do, it could help us understand why ketamine works for some patients and ultimately guide the development of safer and more effective antidepressant treatments.”