From Scientific American By Heidi Ledford: The popular club drug ketamine—or 'Special K'—is also a fast-acting antidepressant, but how it works has eluded scientists. Now a team reports in Nature that the mood-lifting effect may not be caused by the drug itself, but by one of the products formed when the body breaks the drug down into smaller molecules.
If the findings, from a study in mice, hold true in humans, they could suggest a way to provide quick relief for people with depression—without patients having to experience ketamine’s ‘high’. Such a drug would be welcome news to the many people with major depressive disorder who do not find relief in currently available antidepressants. Ketamine also eases depression in a matter of hours, whereas other drugs take weeks to reach their full effect.
“The whole field has become interested in ketamine,” says Todd Gould, a neuroscientist at the University of Maryland School of Medicine in Baltimore who led the study. “It does something different in patients than any other drug we have available.”
But ketamine has its drawbacks: some people are turned off by the high—a feeling of dissociation and sensory distortion that lasts for about an hour. For others, the effect is an incentive to misuse the drug. Ketamine is not yet approved to treat depression in the United States, but ketamine clinics have sprung up around the country to administer it off-label.
Researchers have been racing to find other drugs that produce ketamine’s antidepressant effects without the high, but have been struggling to do so without a clear idea of how ketamine fights depression. Many of those efforts have focused on drugs that target cellular receptors in the brain called NMDA receptors. These were thought to be ketamine’s target, but clinical trials of other drugs that target them have largely yielded disappointing effects on depression, says Gould.