Bengaluru: Previous studies have shown that ketamine is a rapid antidepressant, acting in just hours to produce a substantial alteration in a patient’s state of mind, unlike traditional antidepressants which can take several weeks to show results.
Now, to understand the molecular mechanism of how the drug works so quickly, a team of researchers from Chicago, USA observed neural activity in the brains of mice exposed to ketamine.
The results of the study, which were peer-reviewed, have been published in the scientific journal Nature Communication last month.
Ketamine is an anesthetic, primarily used to induce strong pain relief and sedation. It is commonly used as a surgical anesthetic for animals. It has also been used recreationally since its inception in various forms and can be addictive when used frequently.
A single dose of ketamine can decrease depressive symptoms within hours and its effects on the brain can persist for up to three weeks. Previous studies show that even patients resistant to antidepressants respond to even a single dose of ketamine.
Traditional antidepressants work through neurogenesis, or the creation of new neurons, while ketamine, according to the Chicago scientists, appears to work like other psychedelics – illuminating existing pathways in the brain that were previously turned off, indicating depression. This effect was observed within hours by researchers when cells were activated by ketamine in mouse models.
The authors of the Nature study noted that ketamine treatment activated neurons in the hippocampus – the region of the brain associated primarily with memory and learning — stressed and unstressed mice.
However, since ketamine can have significant and serious side effects – blurred vision, nausea, insomnia, drowsiness and addiction – it can only be used for a limited time.
For the study, the scientists genetically modified the test mice so that they could switch on and off the activity of newly born neurons in adult mice, also called adult-born immature granule neurons (ABIN).
Ketamine treatment activated ABINs in stressed and unstressed mice. And, they found that blocking ABIN activity also blocked the antidepressant effects of ketamine.
Thus, the researchers were able to reduce the change in neuronal activity without any change in the number of neurons, stating that “the increased activity of ABINs is sufficient for rapid antidepressant effects”.
Although the beneficial effects of ketamine do not appear to last as long as those of some psychedelics, the latest findings have offered a deeper window into how these drugs work, as the study identified a specific cell population that can potentially be targeted to limit the negative effects. of ketamine while preserving therapeutics and benefits.
Ketamine to treat addiction
Increasingly, research has shown that certain substances, classified as “gateway drugs,” such as psychedelics (psilocybin in mushrooms, ayahuasca, LSD), help reverse depression. They, too, work by activating previously existing neural connections that had been turned off in brain regions associated with depressive disorder.
Ketamine has also shown promise in the treatment of addiction. When combined with therapy, the drug has been shown to help rewire the brains of alcohol addicts and reverse their addiction.
Neurons are normally produced continuously in the brain and the process of neurogenesis takes weeks to complete. As a result, standard depression treatments also take weeks to see small results.
But studies have indicated that substances that haven’t been well studied and have been classified as illegal drugs can actually act instantly like antidepressants, often retaining rewired neural connections for weeks or even months.
(Editing by Zinnia Ray Chaudhuri)
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