Researchers have found that ketamine can act quickly to relieve symptoms of severe depression, but it remains unclear how. A new study asks whether this drug is just "another opioid" in disguise and advises specialists to exercise caution.
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.
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.