The anti-anxiety effects of ketamine are associated with specific brainwave changes, according to research published in the International Journal of Neuropsychopharmacology.

The study found the therapeutic effects of ketamine were linked to changes in theta brainwaves in the right frontal area of the brain.

“Ketamine appears effective in a wide range of ‘neurotic’ disorders: generalised anxiety disorder, depression, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, simple phobia, and social anxiety disorder — even when these are resistant to other treatments,” said study author Neil McNaughton of the University of Otago.

“But no one knows how it achieves these effects. So we measured brain activity in treatment-resistant anxiety patients before and during ketamine treatment.”

The researchers administered doses of ketamine to 12 patients with generalized anxiety disorder and/or social anxiety disorder, while monitoring their electrical brain activity.

“Ketamine did not systematically change the left-right balance or complexity of brain rhythms; but had a very wide range of effects on their power — increasing fast ones and decreasing slow ones,” McNaughton explained to PsyPost.

Ketamine was associated with reduced delta and theta brainwave oscillations, and increased gamma brainwave oscillations.

However, “only decreases in one medium-low frequency band (theta) at one right-frontal site related to therapeutic improvement. So ketamine has many effects on the brain but only a small subset produce therapeutic action,” McNaughton said.

Ketamine blocks the NMDA (N-methyl-d-aspartate) glutamate receptor. But there is still much to learn about how the drug impacts on the brain.

“This is a small, preliminary, study and — unlike a previous study from our laboratory — saw changes only in fear questionnaire scores but not Hamilton anxiety scale scores. It also only tested social and generalised anxiety patients,” McNaughton explained.

“EEG testing with ketamine treatment of depression, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, and simple phobia is needed to test how far the therapeutic link with theta rhythm is in general and how far it may be restricted to changes in anxiety. While we have demonstrated a specific brain change linked to therapeutic action, we still have no idea of the way that ketamine achieves this.”

McNaughton was involved with a previous study that found ketamine produced rapid anti-anxiety effects, which lasted for 3 to 7 days at higher doses.

“While it is effective, ketamine is not easy to administer and its actions appear to only last for about 1 week. Our results hint that its therapeutic action could be obtained with a more selective treatment, targeting right-frontal theta activity in particular, that may have fewer side effects, easier administration, and perhaps longer duration,” McNaughton said.

The study, “Ketamine Effects on EEG during Therapy of Treatment-Resistant Generalized Anxiety and Social Anxiety“, was authored by Shabah Mohammad Shadli, Tame Kawe, Daniel Martin, Neil McNaughton, Shona Neehoff, and Paul Glue.