Influenced by a school shooting, a neuroscientist is on a mission to change how both the brain and immune system handle stress.
“…By the time Brachman’s results were published, in January 2015, she’d long since moved on to and completed a doctoral program at Columbia University, where she had begun collaborating with the neurobiologist Christine Denny.* In the course of her career, Denny had seen thousands of mice anesthetized with ketamine, the drug also known as special-K, for various studies, and recognized that there were lasting effects. Ketamine was by then also being used to treat depression in adults. Brachman and Denny decided to test whether ketamine had any effect on how mice react to stress. They gave the drug to lab mice, waited one week, then put those mice, as well as untreated mice, through stressful situations. The study results showed that for up to four weeks after the injection, the mice that were given ketamine were more social and less afraid than the control animals. They also exhibited fewer depressive-like symptoms after facing stressful situations.
Brachman’s results consistently showed that there are ways to build resilience to stress, by both injecting immune cells from another animal and giving a dose of ketamine prior to stress. This runs counter to the long-accepted notion that stress leads to illness because of risk factors such as genetic mutations, compromised immune systems, and prior exposures. Perhaps the relationship between stress and illness has more to do with a person’s level of resilience—and perhaps specific interventions could boost this.
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Brachman is not the first scientist to suggest vaccinating against stress. For decades, the Stanford University neuroscientist Robert Sapolsky has focused on muting the brain’s chemical response to stressful situations. In the most basic terms, Sapolosky’s approach cuts off the release of stress hormones when they’re starting to overwhelm the body. “We’ve proved that it’s possible,” he told Wiredin 2010. He has since tested a version of the “vaccine” in rodents, and his research is ongoing.
The results of Brachman and Denny’s research on ketamine were repeated shortly after their study came out, when a study published in the Journal of Neuroscience showed the same protective potential of ketamine in rats, and added that the drug produces the same effects whether it is administered two hours, one week, or two weeks prior to a stressful event.
As Brachman finalized her NIH results paper, Georgia Hodes, of the Icahn School of Medicine at Mount Sinai, led a study investigating the link between increased immune system inflammation and depression in mice. The researchers determined that inflammation is not caused by stress; rather, stress comes first, and leaves people more susceptible to stress-related illness. They subsequently found that anti-inflammatories prevent stress-related depression in mice. In the same vein, researchers at the University of Colorado, Boulder, showed that anti-inflammatories help reduce fear in lab mice. But just like Brachman’s immune and ketamine results, these are far from being replicated—or even tested—in humans.
Patients who received ketamine “had a lower prevalence of PTSD … despite having larger burns, higher injury severity score, undergoing more operations, and spending more time in the ICU,” the authors wrote. Yet in a later military study ketamine had no impact on the likelihood of developing PTSD. This could have been due to the severity of the burns, to the timing of the dosage, or other factors, according to Denny. But whatever the cause for the different results, it was discouraging.
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Denny and Brachman are currently studying the long-term effects of ketamine, the ideal timeframe to administer it, and whether similar compounds (and non-psychedelics) can produce the same effect. They have so far seen that the benefits of ketamine last at least a month, and that it’s significantly more effective when administered prior to stress than when used as a treatment for stress-related conditions. Giving the drug to a control animal, even if it’s never exposed to stress, doesn’t produce any cognitive changes, which indicates that ketamine would not be dangerous to administer as a precaution when people know that they are heading into potentially stressful events, such as a soldiers heading to a war zone. (The follow-up military study supports this, as it concluded that administering ketamine does not increase the likelihood of developing PTSD or other conditions.) ”