New study maps ketamine's effects on brain

Ketamine-an anesthetic also known for its illicit use as a recreational drug-has undergone a thorough reputational rehabilitation in recent years as the medical establishment has begun to recognize its wide-ranging therapeutic effects. The drug is increasingly used for a range of medical purposes, including as a painkiller alternative to opioids, and as a therapy for treatment-resistant depression.

In a new study published in the journal Cell Reports, Columbia biologists and biomedical engineers mapped ketamine’s effects on the brains of mice, and found that repeated use over extended periods of time leads to widespread structural changes in the brain’s dopamine system. The findings bolster the case for developing ketamine therapies that target specific areas of the brain, rather than administering doses that wash the entire brain in ketamine.

“Instead of bathing the entire brain in ketamine, as most therapies now do, our whole-brain mapping data indicates that a safer approach would be to target specific parts of the brain with it, so as to minimize unintended effects on other dopamine regions of the brain,” Raju Tomer, the senior author of the paper said.

The study found that repeated ketamine exposure leads to a decrease in dopamine neurons in regions of the midbrain that are linked to regulating mood, as well as an increase in dopamine neurons in the hypothalamus, which regulates the body’s basic functions like metabolism and homeostasis. The former finding, that ketamine decreases dopamine in the midbrain, may indicate why long-term abuse of ketamine could cause users to exhibit similar symptoms to people with schizophrenia, a mood disorder. The latter finding, that ketamine increases dopamine in the parts of the brain that regulate metabolism, on the other hand, may help explain why it shows promise in treating eating disorders.

“The restructuring of the brain’s dopamine system that we see after repeated ketamine use may be linked to cognitive behavioral changes over time,” Malika Datta, a co-author of the paper said.

Reference: New study maps ketamine's effects on brain; Cell Reports, DOI: 10.1016/j.celrep.2023.113491