How Ketamine Impairs Brain Circuitry

Researchers at the University of California, San Diego (UCSD) School of Medicine... have found that ketamine leads to the impairments in brain circuitry observed in both drug abusers and schizophrenic patients by causing increased production of a toxic free radical called “superoxide.”

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It was known that ketamine initially impairs the inhibitory circuitry in the brain’s cortex and hippocampus by blocking the NMDA receptor, a molecule on the cell surface that controls the activity of neurons. But the UCSD researchers discovered that, as a result of blocking the receptor, ketamine also substantially increased the activity of NADPH oxidase, causing further disruption of neuronal signaling.

“Ketamine causes a ‘disinhibition’ of brain circuitry, taking the brakes off the system and causing overexcitation of the brain in response to a stimulus,” said Behrens. “This overexcitation activates NADPH oxidase, which then produces superoxide – resulting in detrimental changes in key synaptic proteins and profoundly affecting nervous system function.”

The result is impairment of the brain circuitry involved in memory, attention and other key functions related to learning. Loss of such functions sets up individuals for psychosis and deficits in information processing, resulting in symptoms such as hallucinations and delusions, as well as social withdrawal and cognitive problems, according to Behrens.

Speaking from some experience I can say that there is definitely some adverse affect in cognitive rationality associated with chronic Ketamine use, but it also appears to be reversible. Given that Ketamine is hot in the research community right now, I'm sure this is not the last we're gong to hear on this subject.