Conventional antidepressants can take weeks to work and fail many patients altogether, which is why ketamine's capacity to lift mood within hours has attracted intense research interest. Yet how the drug achieves this in the human brain has remained unclear. A study published in Current Biology, led from Oxford's Department of Psychiatry and funded by the Medical Research Council, now points to the habenula, a small region that processes unpleasant experiences and shapes how we learn from them.
Animal work had suggested that an overactive habenula is associated with depression and that ketamine acts on the region. The Oxford team tested the idea in people, scanning healthy volunteers with functional MRI at the Oxford Centre for Integrative Neuroimaging while they received mild, individually calibrated electrical stimulation to the hand. Participants who had been given ketamine the previous day showed measurably reduced habenula responses to the unpleasant stimulus.
The study also found preliminary evidence that this dampening alters memory, with unpleasant experiences subsequently recalled as less negative. The correspondence between human and animal findings matters: it gives drug developers a concrete circuit to target in the search for treatments that retain ketamine's rapid benefits while reducing its side effects and risks, a long-standing goal in a field where therapeutic innovation has been slow.