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I was first introduced to ketamine’s exploding popularity at the incomparable Glastonbury Music Festival in June 2003. This was my first summer in the U.K. (I grew up in Toronto—painfully wholesome by comparison.) On the hectic festival party scene, K was the new kid on the block — exotic, potent, and more than a little odd. Ecstasy had been the drug of choice in the ’90s, LSD felt like a relic from the ’60s, and mushrooms were as old as the hills. But in K, drug enthusiasts in search of something wonkyand intense felt they had found the ideal high.
By 2007, K was widespread, in part because it was so cheap. One gram of K could cost as little as $6, compared to $25 to $50 for a gram of MDMA or $60 to $125 for cocaine. I frequently went to student house parties where liters of liquid K were cooking away on the kitchen stove.
Most people know that ketamine is a medical anesthetic, but you might not know it is considered so important that the World Health Organization includes ketamine on its List of Essential Medicines. It doesn’t require the oxygen or electricity supply that other anesthetics need, and it doesn’t pose the risk of respiratory suppression, making ketamine an ideal painkiller to be carried in ambulances. It is the only anesthetic available in many developing countries.
Yet ketamine’s importance in the history of medicine has been overshadowed by its reputation as the club drug K, ket, Special K, horse tranquilizer, the “Marmite of drugs” (meaning you love it or you hate it), and my personal favorite, “regretamine.”
The high is neither up nor down, but sideways. Take enough of it and you’ll descend into a “K hole” — a 15-minute dive into another dimension where you are completely divorced from yourself in space and time. That physical and psychological dissociation is exactly what people either love or hate about it.
Ketamine is considered to be the only addictive psychedelic, which means people who get into snorting it in a serious way can escalate their usage to three, five, even 10 grams a day. Ketamine has a high tolerance profile, which means users must take larger and larger volumes to feel the effects. More significantly, it is an extremely strong painkiller — psychologically as well as physically. Its chemical makeup includes chlorine, a component that can wither teeth, mangle kidneys, dissolve bladder linings, and cause a profoundly painful condition known as ulcerative cystitis.
“We saw a woman who had used 20 grams of ketamine daily for eight years,” says Owen Bowden Jones, a consultant psychiatrist in the faculty of medicine and an honorary senior lecturer at Imperial College in the Division of Brain Science. “There is an overrepresentation of ketamine abuse by traumatized women using it as an emotional anesthetic.”
Women who use ketamine can develop cysts of fluid in the space between their vaginas and urethras, requiring painful surgical removal and months of pain and celibacy. In other severe cases, addicts have required bladder transplants — even teenagers.
As far back as 2000, users have been experiencing abdominal “K cramps” and rotting teeth and feeling unable to stop themselves from devouring ever larger quantities of the stuff. Yet medical and scientific authorities refused to believe ketamine was addictive; “K heads” were told their addiction was all “in their heads.” Doctors flatly refused to believe that ketamine could cause chemical dependency in the same manner as heroin or nicotine.
Celia Morgan, a professor of psychopharmacology at the University of Exeter, has been researching ketamine since 2009 and trying to bridge the divide between medical professionals and K users. Her latest work explores how K could help treat depression, heroin addiction, and alcohol dependence, which involves treating 96 alcoholics with a once-a-week low-dose injection of ketamine in a study funded by the U.K.’s prestigious Medical Research Council.
Previously, a small pilot study found that ketamine injections compared to placebo injections reduced rates of relapse in alcoholics by 76 percent compared to 34 percent. That’s significant, Morgan says, as alcoholics are notoriously prone to falling off the wagon. With conventional therapies, typically 50 percent of alcoholics relapse at three months and 70 percent at six months.
“It has been interesting to see ketamine, an addictive drug of abuse, become repurposed as an actual treatment for addiction,” Morgan says. Thankfully, we have a heads up on how addictive ketamine can be, she says, so physicians can monitor patients from the get-go for problematic usage.
The use of ketamine as a treatment for addiction has been tested before. In the USSR in the 1980s, Evgeny Krupitsky at the Leningrad Regional Center for Alcoholism and Drug Addiction Therapy was inspired to try ketamine injections on a number of hardcore alcoholics, based on what he already knew about the drug’s psychedelic effects. His results were startling: 66 percent of them abstained for a year, compared to 24 percent in the control group.
After the fall of the iron curtain, U.S. scientists started exploring the same area. Krupitsky came to Yale in 1996, expanding his research to explore how ketamine could be used to treat heroin addiction. In one study of 70 addicts who had already detoxified, half were given a high dose of ketamine and the other half an extremely low dose. Seventeen percent of those given the high dose were still abstaining from heroin two years later, while just 2 percent of those given the vanishingly small dose were still clean. Other studies with heroin have found the same: The stronger the dose or the more doses given, the greater the chance of long-term sobriety. Researchers have also started to look at using ketamine to help people hooked on cocaine and nicotine.
Other researchers have focused on ketamine’s potential to treat an even bigger problem: the 300 million people worldwide who suffer from depression. In trials, patients have experienced relief in just hours, rather than weeks or months as with conventional drugs. In 2000, researchers at Yale published the first report of ketamine’s so-called rapid antidepressanteffect. In the two decades since, dozens of studies have been published supporting the idea that ketamine could be given either once or as a monthly or weekly shot in a doctor’s office.
Compared to conventional antidepressants, ketamine holds enormous appeal because the effects are rapid, it doesn’t require daily doses, and it appears not to carry the unsavory side effects of weight gain, emotional numbness, and flattened libido.
Moreover, ketamine is already legal and regulated. Unlike new pharmaceutical drugs that require years of clinical trials before getting the green light — or banned psychedelics, like LSD and psilocybin, which might not be legally available for a decade or more — ketamine can already be given as an off-label treatment. There is also hope that ketamine could help treatment-resistant depression, giving relief to the third to half of all patients who do not respond to conventional antidepressants.
“Ketamine works in people for whom nothing else has worked,” says Rupert McShane, associate professor in the Department of Psychiatry at the University of Oxford. Since 2014, he has treated more than 100 patients with ketamine, usually injected once or twice weekly for three weeks. “The effects can be really marked and quite quick,” McShane says. “This has got the research community excited, and this is why drug companies are gettinginvolved.”
In September 2018, pharmaceutical company Janssen applied to the FDA for a patent on an intranasal spray of a related compound, esketamine, for adults with treatment-resistant depression, which they could self-administer rather than having to undergo intramuscular injections. That’s right: a snortable form of medical-grade ketamine.
Most conventional antidepressants, such as Prozac, are selective serotonin reuptake inhibitors (SSRIs), which modulate levels of the chemical serotonin. Ketamine instead modulates glutamate, a different neurotransmitter, resulting in surges of the chemical BDNF, which stands for brain-derived neurotrophic factor. You can think of BDNF as a “fertilizer” for the brain, McShane says. The end result: neurogenesis, the growth of new brain cells, and synaptogenesis, the formation of new connections between brain cells.
“Ketamine is a bit like a repair kit — and you need to do physical repairs before you can do the work involved in psychotherapy needed for real improvement,” McShane says. Despite the apparent benefits, he’s in no rush to see the widespread introduction of ketamine to treat depression.
“It is wonderful to see people get better so quickly, but that can make you feel like this is a drug you should try with everybody — and that is a problem,” he says. “Every single potent psychiatric physical intervention that has ever been invented — ECT, antidepressants, opiates, benzos — has been overused, invariably resulting in backlash and then stigma. It would be nice to think there could be nice, clean drugs that can be taken once or twice without risk, but I don’t think that’s likely.”
Back in 1895, Bayer attempted to advertise diacetylmorphine as “heroin” — a “nonaddictive” alternative to morphine. Later, Valium became “mother’s little helper” and was proffered as a cure-all until we realized how addictive benzodiazepines really are. And more recently, OxyContin was marketed as a nonaddictive opiate and sparked the opiate crisis.
Despite reservations, Will Lawn, a postdoctoral researcher at University College London, still thinks ketamine is the psychedelic most likely to reach legal status first, ahead of experimental uses of DMT and LSD. “I genuinely think we will see ketamine legally prescribed in the U.K. as an antidepressant for patients who haven’t responded to other medications within five years,” he says. “It holds more promise to make a real difference to people’s lives in the near future, while other psychedelics don’t. Ketamine represents the most feasible way of moving psychedelic research and treatment into the mainstream.”