On ketamine's trip from anesthetic to anti-depressant and everything in between
It’s as if ketamine is inescapable today. It can be found in emergency rooms, psychiatrists’ offices and now, infusion clinics, for its ability to quickly numb even the sharpest of pangs.
And then there are the drug’s underground purposes: Last April, in the depths of the southern California desert, a string of baby-faced adults in short-shorts lined up outside of Indio’s Polo Fields, waiting for their turns to experience the first weekend of the Coachella Valley Music and Arts Festival. “I am in a K-hole,” one bleary-eyed attendee told another before taking a seat in the dirt. Inside of the venue, others reported to be swapping the classic club drug MDMA for ketamine’s promised disassociative and hallucinogenic properties.
Still, while the drug may be experiencing a resurgence in doctor’s offices, and while party-goers may be exploring it for the first time, ketamine is far from new. In fact, it’s been around for decades. Why is American society only now warming up to the anesthetic?
In 1961, Park-Davis—now a subsidiary of pharmacuetical company Pfizer— created ketamine as a more user-friendly version of the chemically similar anesthetic PCP. Almost immediately it gained popularity as a field anesthetic in Vietnam because of its easy administration and wide safety margin. At the same time, it did cause people to trip, known by clinicians as “ketamine-induced emergence syndrome.” But like so many pain killers, what was seen as a negative side effect by the scientific world reportedly turned out to be an opportunity for rogue chemists to sell the sort of “rock mescaline” as a synethic option for anyone seeking a mind-altering journey.
During the 1970s and through the 1980s, ketamine was used in emergency rooms and veterinarians’ offices. Counter-culture too was embracing the drug’s “emergence syndrome,” often injecting themselves with sub-anesthetic but quite psychedelic shots of it. It crept into the mainstream with the release of two books in 1978 that detailed personal accounts of self-exploration through ketamine, The Scientist by John Lilly and Journeys into the Bright World by Marcia Moore. Lilly, Moore and psychonauts of the time were using the drug to go into a full “K-hole” for about an hour, which is as long as the drug lasts before you come back to reality, making trips much shorter than psychedelics like LSD and magic mushrooms, which can last anywhere from five to 12 hours.
A full psychedelic experience on ketamine is somewhat dose-dependent, occurring at higher doses (generally above 100 milligrams). It’s distinct from a substance like LSD because you can’t move or talk for the 45-minute-or-so duration of the trip, which is unappealing to many seasoned psychonauts. The experience itself is often described as complete ego dissolution or even “near-death experience,” where you spend the next 30 minutes working your way back to yourself and out of “the hole.” It’s an all-encompassing feeling and can be quite confusing, especially because you can lose sense of who and what you are. But that’s not necessarily a bad thing.
I not only lost sense of who and what I was, but the idea that anyone could be anything at all.
For Dr. Eli Kolp, who has been studying and practicing Ketamine-assisted psychedelic therapy for more than 25 years, there are major benefits to the full ego dissolution of the ketamine experience, like long lasting anti-depressant effects, personality change or enlightenment. He explains Ketamine is stronger than other psychedelics, and there is less emphasis on the importance of patients “surrendering to the substance” because its effects are so overwhelming. For comparison, in psilocybin-assisted therapy, patients are taught to release their control to the substance for the best results, or “trust, let go, be open.” But with Ketamine, there’s no resisting the gravity of the experience. Still, what you do when you’re in “the hole”–like freak out and panic or embrace the chaos–is up to you, as well as your “set and setting”—an idea in the psychedelic community where your mindset and environment strongly influence the direction of a trip.
When I intentionally took a “K-hole” dose out of curiosity, I was unprepared for the full extent of the ego loss. In the past, I’d had somewhat transcendental experiences on mushrooms and LSD but ketamine was another level. I not only lost sense of who and what I was, but the idea that anyone could be anything at all. It was without a reality reference point, but I slowly realized I had taken ketamine and remembered somewhere that it would only last an hour; I wasn’t dead or insane or reincarnated in the body of another species with less mental faculties than I was used to.
No, I was in a K-hole, and I should just go along for the ride.
When I came back to, I felt reborn. I realized the only experience I’ve had that’s comparable to my ketamine near-death experience is the Salvia divinorum trip–a psychedelic flower native to Mexico you can buy at headshops in New York–which also tears down any sense of reality for only 10 to 15 minutes before dropping you back in yourself without many coherent words to explain the experience.
Kolp describes four distinct levels to the ketamine experience depending on the dose; the first two are only mildly dissociative and more similar to the effects of alcohol or MDMA. The higher two, the near-death experience and then the complete mystical experience (where you completely lose yourself and feel unity with God) have more potential for long-term healing and change. Because of these higher dose effects, psychedelic therapists of the 1970s also started using ketamine, first in Iran, Argentina and then Mexico, before it finally made its way to the US. The idea was very similar to the psychedelic-assisted therapy model of the time, which was still active with LSD until 1976. The point was to give psychiatric patients high doses of psychedelic substances to induce “mystical” or cathartic experiences which were seen as catalysts for change in conditions like alcoholism.
But not everyone is looking for a near-death or mystical experience when they take ketamine outside of a psychiatrist’s office. By the mid-1980s, users had discovered ketamine’s stimulating and “empathogenic” (or empathy and bliss inducing) low-dose effects. Instead of a high dose shot of ketamine to transport users to another reality, low dose pills and powder are popular at clubs and raves to loosen people up and help them dance. Low, “key bump” doses have a trippy edge and can mess with people’s vision slightly, but it’s more about feeling floaty, wavy, or “like you’re wearing moon boots at a Nascar race,” like one user tells PLAYBOY. It also has similar anti-anxiety or inhibition lowering effects to alcohol and even a euphoria similar to MDMA. “Psychologically, it makes the whole world and everything in it alright,” another user describes.
By the 1990s, low-dose, recreational ketamine had reached the mainstream, often called Special K, Ket, or just K, it was (and still is) popular in the club and electronic music scene for its stimulating effects and dance-enhancement, or sometimes sold as “fake E” (fake ecstasy). It’s also popular to mix with other substances, like cocaine and MDMA, but many prefer to use it on its own for its lack of a hangover compared to other drugs and alcohol.
Ketamine can still be called the “heroin of psychedelics” because it can be more addictive than entheogens like mushrooms. That’s partly because it has a much more pleasurable effect on the body at low doses than classic hallucinogens, and so can be used compulsively. But it doesn’t produce withdrawal symptoms like opioids, benzos or alcohol. Still, ketamine got a bad reputation around this time for its addiction potential, as well as media reports of violent veterinary burglaries and of its use as a date rape drug. It was finally classified by the Controlled Substances Act for the latter in 1999 as a Schedule III substance.
The universe is so large, and I am so small, but I am also so important, and it’s important that I am still here.
The “dark side” of ketamine and the “War on Drugs” seem to overshadow the more positive developments of the drug for mental health, which were also happening in the decade. In Russia in 1992, psychiatrist Evgeny Krupitsky successfully gave ketamine-assisted psychotherapy to alcoholics, and here in the U.S., Russian emigrated psychiatrist Eli Kolp got FDA approval to do the same thing in 1996 with veterans. However, the funding never came through. Kolp explains it was due to a change in leadership from an open-minded director to one more influenced by the War on Drugs propaganda machine. They said, “You cannot treat addiction with addictive drugs,” recalls Kolp. “If something bad happens, they thought we’d be on the front page of all the newspapers, that they allowed ‘mad scientist to shoot wounded American veterans with psychedelic drugs.’”
Instead, Kolp took ketamine into his private psychiatric practice, and around the same time, researchers at Yale University were also making significant strides in the development of ketamine for depression, even though that wasn’t originally their goal. The head of this research, Dr. John Krystal, who is now the chair of psychiatry at Yale, tells PLAYBOY they were initially giving people low doses of ketamine to try and understand the biology of schizophrenia. What they found instead was sub-anesthetic doses of ketamine had “rapid acting anti-depressant effects,” which they presented for the first time in 1997 at the Society for Biological Psychiatry.
“Our presentation stimulated excitement, but also skepticism from our colleagues,” says Krystal, and explains it wasn’t until 2006 when separate researchers published the first replication of their findings that the idea of Ketamine’s anti-depressant effects took off. In these early studies they used 40-minute-long ketamine infusions with doses around 0.5 mg per kilogram of body weight, essentially to minimize the “negative” psychedelic or “dissociative” effects. And people with treatment resistant depression were feeling better for the first time in years, but generally only for a week or two.
This essentially brings us to the present day, where ketamine infusion clinics for depression and mood disorders have been popping up in the United States since 2012, and provide a service based on those early studies. The psychedelic effect is still minimized and not considered the main “catalyst for change” like it would be in a higher dose psychedelic therapy session. “The dissociative symptoms are a marker of getting an effective dose into the patient rather than a producer of the antidepressant effect,” says Krystal. And the camp is still split on this issue, although with the current psychedelic renaissance, more and more clinicians are joining the higher dose, psychedelic side in private practice using intramuscular shots and sublingual lozenges as an adjunct to psychotherapy.
Some infusion clinics are also emphasizing the importance of the psychedelic effects, and provide on-staff therapeutic support for clients to adequately prepare for and integrate their psychedelic sessions, both staples of more traditional psychedelic therapy. For instance, at Innovative Ketamine, an infusion clinic in Chicago, Founder and CEO Dr. Rahul Khare, says he doesn’t see a difference between what he does and the traditional psychedelic therapy literature that he’s well versed in. He explains that ketamine, with the aid of a therapist, is helping his patients process trauma by moving it from the unconscious to the conscious mind. He also describes a common theme that he hears from almost every patient; “They tell me, the universe is so large, and I am so small, but I am also so important, and it’s important that I am still here.” This type of realization is quintessentially psychedelic, and could be a major step in recovering from mental health conditions, especially those that involve excessive rumination or obsessive thoughts and behaviors.
Similarly, Sophie Saint Thomas, a ketamine infusion patient in New York and author of Finding Your Higher Self: Your Guide to Cannabis for Self-Care, confirms she’s never gone into a full “K-hole” during her infusion sessions, but that doesn’t mean they’re not psychedelic. “I close my eyes and there are some hallucinations, everything from mermaids to a mountain of skulls (I liked it, it wasn’t scary) and I often feel like I’m flying or swimming,” she explains. “The visuals often contain people or situations close to me and act as sort of a reshuffling. What’s important becomes apparent and worries that may have been all-consuming before the infusion fade away. This insight gleaned does stay with me afterward.”
Khare notes that not all clinics are like his in this belief that the psychedelic aspects of the experience have benefits, and many give intentionally low doses and combine ketamine with benzodiazepines to minimize the psychedelic effects even further. Kolp thinks that’s partly in an attempt to keep people coming back for more, in what he calls “capitalist medicine,” rather than treat people once and for all with ketamine-assisted psychedelic therapy. After all, the beneficial effects of infusions don’t seem to last more than a week or two, maybe up to a month, while psychedelic therapy is meant to heal people for good. “It’s my own cynical point of view,” Kolp admits. “When ketamine became popular in mainstream medicine as an anti-depressant in 2006, it was a great disappointment to me because. I thought, ‘Dang, now here we have a powerful tool, like a microscope, and all those fools out there are using it as a nutcracker.’”
I close my eyes and there are some hallucinations, everything from mermaids to a mountain of skulls (I liked it, it wasn’t scary) and I often feel like I’m flying or swimming.
The psychedelic side of ketamine research may be onto something considering recent studies on psilocybin-assisted therapy (the main psychoactive ingredient in magic mushrooms). Researchers at esteemed institutions such as John Hopkins University and New York University are finding participants in their trials who have the most “mystical” or “spiritual” experiences while on moderately high doses of psilocybin seem to benefit the most from the therapy, whether it’s for treatment-resistant depression, addiction, or end-of-life anxiety. And a similar correlation is emerging in the ketamine world, although its highly contested among clinicians. But in 2013 researchers in the Czech Republic found a connection between ketamine’s psychedelic (or “dissociative”) effects and patients’ depression improvement, as did scientists in the United States a year later.
The debate continues, with more “psychologically”-minded practitioners emphasizing the psychedelic effects and more “biological” clinicians minimizing them. Regardless, ketamine infusions seem to be helping people with treatment resistant depression, suicidal thoughts and other mental health conditions like bipolar disorder, obsessive compulsive disorder, post-traumatic stress disorder, eating disorders, addiction and even chronic pain and fibromyalgia. However, there are currently no studies comparing the efficacy of high-dose ketamine shots with lower dose ketamine infusions.
What they both have in common is being pricier than conventional depression treatment. And because they’re both prescribed “off-label” by physicians (meaning the FDA has not yet approved ketamine shots, lozenges or infusions for depression), insurance typically doesn’t cover their cost. Khare says the average price for an infusion runs around $550 per session but can be as high as $1,200, and people need them somewhat frequently to keep their depression at bay. The typical course of treatment looks like six infusions in the first two weeks then one “booster” session every four to six weeks for a year to keep depression in remission. And this doesn’t include the price of talk therapy that should accompany the process for the best results. The psychedelic-assisted therapy model, on the other hand, would look like one drug administration session, which is likely to cost about $300, and that’s it, besides weeks (or likely more) of talk therapy before and after the “trip treatment.”
The third and most recent player that’s changing the accessibility of ketamine is the Spravato nasal spray which was just approved by the FDA for treatment resistant depression in March. Developed by a Johnson & Johnson subsidiary, Spravato actually contains esketamine, which is technically only half of what makes up the Ketamine hydrochloride used by doctors, veterinarians, and psychiatrists. According to researchers, esketamine has a stronger biological anti-depressant effect, with less negative side effects, including the psychedelic or “dissociative” ones. Khare explains Spravato cuts costs for people because its FDA-approval makes it deductible by insurance and so folks don’t have to pay for it out-of-pocket. He says he still prefers the infusions because of their accurate dosing and the high rate of success he’s seen, but that he offers Spravato, especially for booster doses, to clients who can’t afford more infusions.
Considering Spravato was the first new class of anti-depressants to be approved by the FDA in nearly 30 years, everyone seems to agree it’s an exciting time, whether they oppose minimizing ketamine’s psychedelic effects or not. And while there’s still a lot to learn about ketamine’s anti-depressant effects, because it’s a Schedule III substance rather than Schedule I like other psychedelics, it’s easier to research, and so progress is happening fast.
“I’ve never seen a medication that will, I feel, change the landscape of mental health in my career,” says Khare. “To me, Ketamine is the first target that’s going to change the landscape of not only mental health, but healthcare in general.”