Ketamine for depression may contribute to opioid dependence

Earlier this year, Medical News Today reported on research that found that ketamine can quickly relieve symptoms of severe depression, such as suicidal thoughts.

That being said, researchers are still working to understand what makes ketamine so effective, and even more importantly, whether the temporary relief it provides is worth it compared with side effects such as dissociation and risks such as addiction.

Some studies have suggested that ketamine’s effect on symptoms of depression is due to its NMDA receptor antagonist properties, which also allow it to work as an anesthetic.

Now, a study published in the American Journal of Psychiatry says that ketamine’s antidepressant properties are due to the fact that it activates the opioid system.

The opioid system is made of opioid receptors found in the brain, and these receptors react to opioid drugs, such as morphine, which are highly addictive.

In the new study, Drs. Nolan Williams, Boris Heifets, and team from Stanford University in California explored how ketamine’s interaction with the opioid system affects its antidepressant properties and dissociative effects in people with depression who are resistant to traditional treatments.

Testing whether ketamine acts like an opioid

The researchers based the study — a randomized double-blind crossover trial — on the hypothesis that ketamine interacts with opioid receptors. To test this idea, they wanted to see how an opioid blocker called naltrexone would interfere with ketamine’s effects on depression.

Dr. Williams and team recruited 30 participants with treatment-resistant depression. All were enrolled to receive ketamine for their symptoms; however, some also received naltrexone beforehand, while others took a placebo.

Of all of the participants, 12 took both naltroxene plus ketamine, and a placebo plus ketamine, in random order.

The researchers found that taking naltroxene before ingesting ketamine lessened or blocked the drug’s antidepressant effects, but not the sensation of dissociation that it induced.

Due to these outcomes, the researchers had to put a stop to the trial early to safeguard the participants’ well-being.

‘We should be cautious’ about ketamine

The editorial that accompanies the study paper warns that ketamine comes with unknown risks for health and urges researchers to delve deeper into the mechanisms that this drug sets in motion.

“We would hate to treat the depression and suicide epidemics by overusing ketamine, which might perhaps unintentionally grow the third head of opioid dependence,” writes the editorial’s author Dr. Mark George, from the Medical University of South Carolina in Charleston.

[W]ith these new findings, we should be cautious about widespread and repeated use of ketamine before further mechanistic testing has been performed to determine whether ketamine is merely another opioid in a novel form.”

Dr. Mark George

In the future, Dr. George also suggests, researchers may want to also invest more time in studying some other underused treatments for depression, such as electroconvulsive therapy, transcranial magnetic stimulation, and vagus nerve stimulation.

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