Ketamine may soon join marijuana as a demonized recreational drug rehabilitated for medical use. Unlike cannabis, ketamine has continued to have accepted medical applications throughout the time of its criminalization for recreational use, but these applications may soon be expanded from anesthetics to treatment for depression.

Discovered in 1962, ketamine started being used for anesthesia and the treatment of chronic pain soon afterward. In the early 1970s, it started being used as a recreational drug. By the 1990s, under the name Special-K, it was popular in the dance club scene for its hallucinatory and dissociative effects.

Although ketamine is short-lasting, it has been associated with drownings and deaths through traffic accidents. It can also dangerously raise blood pressure levels, particularly in combination with other drugs.

Predictably, the tragic deaths associated with ketamine use have led to scare campaigns and widespread heavy policing. This has stymied research into medical uses, but slowly the evidence that ketamine can be an effective antidepressant is starting to come out.

A recent review led by Matthew Cooper of Dalhousie University, Canada, in The World Journal of Biological Psychiatry examined all peer-reviewed reports on the use of ketamine to treat depression. The evidence is a mix of small trials and individual case reports, but collectively they build a powerful picture.

Reported benefits are often dramatic. In an interview with The Washington Post, Dennis Hartman, a man whose depression was so long-lasting and severe that a ketamine trial was his last effort before intended suicide, said: “My life will always be divided into the time before that first infusion and the time after. That sense of suffering and pain draining away. I was bewildered by the absence of pain.”

The administration of ketamine in these trials is very different both from its use in anesthetics and the way it is taken by partygoers. Cooper's paper reports that “Currently, intranasal administration presents as the most promising strategy to mitigate dissociative and psychotomimetic effects.” Other trials have used intravenous drips. The dosage is also far lower than in preparing for surgery.

Anecdotal accounts and case reports indicate ketamine administered in this way has an almost immediate effect, unlike the commonly used class of antidepressants called selective serotonin re-uptake inhibitors (SSRIs), which usually take weeks or months to improve mood, if at all. In addition, effects seem to last long after the drug has been removed from the body. 

Unlike some reported antidepressant treatments, we have at least a starting idea of how ketamine works. Its capacity to block the N-methyl-D-aspartate (NMDA) glutamate receptor, which is implicated in depression, is well-established, preventing the overstimulation of brain cells that glutamate can induce.

The evidence has prompted the American Psychiatric Association (APA) to establish a task force and consider endorsing its use as a treatment for depression and PTSD. Even at low doses, ketamine can sometimes induce hallucinations and dissociative states, but so far there is no evidence for serious damage or addiction when treatment is applied under controlled conditions.

Despite its potential, the combination of legal issues and the drug's image have made accessing therapeutic ketamine challenging, but the Ketamine Advocacy Network, which Hartman helped found, hopes APA support (even if highly conditional) will be the spark for change.