Just telling yourself you were given ketamine could be enough to treat depression

For those suffering from stubbornly resistant forms of severe depression, ketamine is increasingly emerging as a solution. Years of research have hinted at the therapeutic potential of the dissociative anesthetic where other drugs have failed, promising the benefits of electroconvulsive therapy with far fewer risks.

Despite all the enthusiasm, separating hope from hype has been challenged by the drug’s powerful psychoactive effects. How can we blindly test a drug that so blatantly detaches the mind from the body?

Taking advantage of the unconscious state of patients under general anesthesia, researchers at Stanford University School of Medicine in the United States put ketamine to the ultimate gold standard test.

Their randomized, triple-blind study found that a single dose of ketamine is as likely as a saline infusion to improve the mood of patients diagnosed with moderate to severe depression in the following days.

“I was very surprised to see this result, especially after talking to some of these patients who said, ‘My life has changed, I’ve never felt this way before,’ but they were in the placebo group.” said the lead author of the study. Boris Heifets, an anesthesiologist at Stanford University School of Medicine.

Developed in the 1960s as part of the search for new anesthetics and painkillers, ketamine has quite a history in medicine. Still used today in emergency care as a quick and reliable way to treat patients suffering from extreme pain and distress, its illicit use for recreational purposes thanks to its dreamlike and dissociative effects has also slowly faded. developed over the years.

Over the past decade, its potential as an antidepressant has attracted renewed interest in the pharmaceutical sector. Clinically speaking, relatively small amounts of the psychedelic improved rats’ moods, even after a single dose.

Potential explanations were quickly identified in various studies in anatomical and animal models, linking the compound’s effects to changes in functional connectivity and activity in regions associated with depression.

Studies of patients diagnosed with severe depression subsequently found a significant reduction in suicidal thoughts and improved mood, leading to FDA approval of ketamine as a nasal spray for depression. resistant to treatment.

Behind the hopeful headlines remains the possibility that the experience of taking a powerful psychoactive substance may itself be essential to its therapeutic benefits.

To “mask” the drug’s psychotropic effects from other possible mechanisms, Heifets and his team assigned 40 surgical patients to one of two groups; one to receive ketamine under general anesthesia, the other a saline solution.

Neither the patient, nor the investigators, nor the nursing staff knew what they were receiving. Two weeks after their surgery, by the end of the trial, just over a third of the total number of recruits had correctly guessed which group they belonged to.

Yet, in the days following their infusion, a number of patients in both groups showed improvement in their mood based on the Montgomerysberg Depression Rating Scale, suggesting that the benefits of the infusion ketamine might largely depend on the psychology of medical treatment in general.

This does not necessarily mean that ketamine is a complete failure in treating depression, although it does imply that any influence it might have might be more a consequence of general experience than a biochemical adjustment.

“We also considered the possibility that surgery and general anesthesia without ketamine have an antidepressant effect,” the researchers write. “However, our review of previous studies measuring depression symptoms during the perioperative period strongly suggests otherwise.”

Brains are complex engines, with depression itself proving to be a complicated phenomenon that defies simple explanations of “chemical imbalances” or maladaptive circuitry.

Just as we find that MDMA mixed with therapy can provide healing experiences for PTSD patients, controlled doses of ketamine in an appropriate environment may well help those suffering from severe depression find a way forward.

“There is definitely a physiological mechanism, something that happens between your ears, when you instill hope,” Heifets says.

This research was published in Natural mental health.

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