The Brain on Ketamine: Potential Therapeutic Benefits Through Targeted Application

Monday - January 15 2024, 00:33 UTC - 10 months ago

Research by Columbia University reveals that repeated ketamine use causes significant structural changes in the brain's dopamine system and supports the development of more targeted therapies. These changes may explain ketamine's effects on mood and metabolism, and the importance of careful administration is highlighted. Further research may lead to ketamine becoming a valuable tool in treating a range of disorders and conditions.

Ketamine, once primarily known as an anesthetic and a recreational drug, has gained a new reputation due to its potential therapeutic benefits. This drug is now being utilized in various medical settings, notably as a substitute for opioids in pain management and in treating treatment-resistant depression. Recent research conducted by Columbia University’s biologists and biomedical engineers, published in the journal Cell Reports, reveals significant insights into ketamine’s impact on the brain.

Their study on mice indicates that prolonged and repeated ketamine use causes extensive structural alterations in the brain’s dopamine system. These findings support the development of more targeted ketamine therapies, which focus on specific brain regions instead of the current approach of general brain exposure to the drug.

“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 researchers’ highly detailed data also enabled them to track how ketamine affects dopamine networks across the brain. They found that ketamine reduced the density of dopamine axons, or nerve fibers, in the areas of the brain responsible for our hearing and vision, while increasing dopamine axons in the brain’s cognitive centers. These intriguing findings may help explain the dissociative behavioral effects observed in individuals exposed to ketamine.

“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.

Most studies of ketamine’s effects on the brain to date have looked at the effects of acute exposure – how one dose affects the brain in the immediate term. For this study, researchers examined repeated daily exposure over the course of up to ten days. Statistically significant alterations to the brain’s dopamine makeup were only measurably detectable after ten days of daily ketamine use. The researchers assessed the effects of repeated exposure to the drug at two doses, one dose analogous to the dose used to model depression treatment in mice, and another closer to the dose used recreationally. They found that both doses led to significant changes in the brain’s dopamine system, further emphasizing the importance of targeted, carefully administered ketamine therapies in clinical settings.

In conclusion, this study by Columbia University provides valuable insights into the effects of repeated ketamine use on the brain, shedding light on its potential as a therapeutic agent when used in targeted, controlled ways. With further research and development, ketamine may prove to be a valuable tool in treating a range of conditions and disorders, offering hope for those who have not responded to traditional treatments.