One of the most interesting places to explore is our own mind, the well-spring of all dreams and nightmares. Ketamine is one of the safest anesthetics, both for its effects on the body and ease of handling. Lately, it has found an off-label use as a treatment for depression, with increasing numbers of clinics beginning to dispense the medication. But is this application helping patients or profits? Jeff Levine is an ex colleague of mine and former CNN medical correspondent investigating this question. His investigation is fascinating. After you read it, check out his conversation with Psychology Today. You can read that here.

“Neshama,” is the Hebrew word for soul.  It’s been updated by the founders of a spa-like clinic located in a prestigious Manhattan high-rise.  They call their recently opened “center,” “Nushama,” an iteration suggesting a modern-day shaman serving as a guide through the spiritual world. 

The clinic’s goal is to build wellness using the psychedelic drug ketamine to trigger a life-changing response.  Anxiety during Covid seems to rise with the sun and come out with the stars and that creates a demand for new mental health providers like Nushama.   They prescribe a mix of mysticism and medicine for a smorgasbord of disorders including depression, anxiety, PTSD and addiction in a distinctly non-medical setting.

A Kaiser Family Foundation poll taken before vaccines were available found that “[A]bout 4 in 10 adults in the U.S.  reported symptoms of anxiety or depressive disorder, up from one in ten adults from January to June 2019”—in other words, a four-fold increase as Covid cases surged.  Paula Echeverry, age 37, is one of many who fell into a mental health crisis during the pandemic. Then she received six doses of ketamine supplemented by boosters at Nushama.

“I survived cancer, but I was, like, dead inside.  I was, like, completely emotionless [now] I’m feeling great,” she says.

Echeverry, a career financial planner, describes her ketamine voyage in sublime terms. “It's just a warm feeling that enters your whole being… makes you take a step back and feel like, OK, things are going to be like, OK.”  Will the effect last?

There is still no big patient study that shows ketamine-treated depression is safe and effective for long-term use, but at Nushama they feel justified in prescribing it now.

Ketamine, Getting to the Root of Mental Illness?

“Why should we wait for people to be sick? Let's get to the essence…I want to go to the root,  the seed,” said Dr. Steven Radowitz, Nushama’s medical director.

Not everyone is convinced there’s value-added since it’s not clear who’s most likely to benefit from the treatment or if the results could be sustained.

“Certainly, there are ‘ketamine cowboys’ out there says Sandeep Nayak, a psychiatrist specializing in psychedelic medicine at Johns Hopkins.  “That is one thing I worry about in general, that if you have a hammer, everything is going to look like a nail…It's tricky; if you go to a ketamine clinic with a psychological problem, they're probably going to give you ketamine,” says Nayak, even if you don’t need it.

Nushama’s Atmosphere, More Seductive than Clinical

Rather than being a “hard sell,” if anything, the atmosphere at Nushama seems pleasantly seductive. Images of naked nymphs curl upward on branches of a dream-like nature mural in the pink and green waiting area.  Baskets of flowers hang from the ceiling.

Each of the 18 treatment rooms is named after a “luminary” in psychedelic medicine.  Room 12 commemorates Aldous Huxley whose iconic novel “Brave New World” warns about “Soma,” a hypothetical hypnotic that deprives people of the will to resist an authoritarian regime.  Huxley used himself as a research subject.

If there are traditional white coats here, they are kept discreetly out of sight in what is described as “another worldly universe” setting. The bookshelves are lined with titles like “Mindfulness,” “Letting Go,” “Becoming Supernatural” and “Stillness is the Key.”  “Moon pod” chairs are available for relaxation.

Potential Dangers of Ketamine

Luxury appointments notwithstanding, ketamine, the product marketed at Nushama has a potential for abuse and addiction.  While a recent study in the American Journal of Public Health found ketamine is used by less than one percent of Americans, rates are going up for medical purposes and as a “club drug” also known as “Special K.”

“Even though ketamine has been shown to help with various mental health conditions, it’s still an important point to keep in mind that there is plenty that can go wrong with its administration and addiction is a very real possibility,” wrote Lawrence Weinstein, MD in response to a query. 

He’s the chief medical officer of the American Addiction Centers which bills itself as the largest drug treatment network in the country.  Still, the number of ketamine patients treated for addiction at these clinics is “extremely small.”

Nushama’s patients enjoy their ketamine “journeys” in zero-gravity chairs, blindfolded while listening to a curated playlist as the drug drips through an I-V bag drop by drop.  Should something go wrong, a panic button can summon someone who ends the trip. 

Ketamine Has Become Big Business

“What ketamine does is turn off what’s not us and you’re left with this essence, this inner essence.  Some people say it’s spiritual,” said Radowitz.

Spiritual or not the rewards from giving patients ketamine are distinctly material. It’s an anesthetic that’s been around for decades, but the old wine has been repurposed and repackaged as a new therapy over the last two decades which the FDA has yet to approve for treating mental problems. 

Even though it’s an inexpensive generic, ketamine therapy at Nushama costs $4,500 for six sessions and a booster.  Individual infusions at other clinics typically cost several hundred dollars and may not be covered by insurance.  A course of treatment generally runs a few weeks.

Ketamine is big news.  The “New York Times” has published half-a-dozen stories on the pluses and minuses of the drug in the past year.  Last October “Forbes” ran a story headlined, “Why Ketamine-Assisted Therapy Has Gone Mainstream.”  Ketamine clinics have grown to a $1 billion business in the past two decades.

Margaret Chisolm, also a psychiatrist at Johns Hopkins, says drugs are important but there are other pathways to mental health using personal commitment and community resources.  She’s skeptical about “flashy clinics.”

“That’s getting a lot of press. It has a lot of allure.  You know when there’s money to be made off the backs of patients… This happened with pain clinics, with opioid medications being prescribed in ‘pain mills’ that were set up to make money off of people desperate for relief,” says Chisolm, author of “From Survive to Thrive” about ways of turning mental illness into a tool for better living.

Nushama’s tony facility seems a far remove from the downtrodden “dope sick” towns of Appalachia or patients addicted to opioids by drug company dissembling, but ketamine clinics are threading a regulatory needle.  

Is Off-Label Ketamine a Problem?

While doctors have the option to prescribe drugs “off-label” as they deem necessary, for ketamine clinics this exception is frequently touted online to anyone who needs emotional help.  How does that work?  Radowitz describes ketamine’s effect as short-circuiting the “default mode”—our normal resting state of mind.

“You're going to put the brain in freefall and almost reset it…You want to reprogram it with something new, right? Otherwise, you're just going to default to where you were before,” he says.

The idea of a chemically induced epiphany was popularized by Timothy Leary, a psychedelic apostle of the ’60s, who coined the phrase, “Turn on, tune in, drop out.”  That idea was largely discredited at the time. However, the notion that the personality, or ego, could be physically identified and mapped as a default mode network has since been suggested by several MRI brain studies. Perhaps, then, could the mind could be reshaped, maybe by ketamine or some other substance?

Nayak at Johns Hopkins says there’s a lot of “hype” surrounding the default mode network, “So, it sounds nice but it’s not clear that it explains much at all,” Further, he maintains, it’s not “a biomarker for the ego.”

As Pandemic Rages, Ketamine Clinics Thrive

Whatever the mechanism a growing number of entrepreneurs in the U.S. and abroad see subjective ketamine “trips” and other psychedelic experiences as a significant financial opportunity. A ketamine provider group boasts 400 members in the United States and 50 countries.  

“The American Society of Ketamine Physicians, Psychotherapists & Practitioners has been at the forefront of advocating for patients who have benefited from this forward-leaning therapy. Ketamine therapy continues to be an essential service during [the Covid-19] crisis,” states the organization's website.

In response to the demand for ketamine treatment, the American Psychiatric Association issued a detailed consensus statement in 2017 about administering the drug safely. However, there’s no guarantee individual clinicians follow this best practice advice.

 Radowitz says at Nushama everyone gets a thorough mental evaluation before undergoing treatment and the company has just hired a psychiatric nurse practitioner qualified in psychotherapy.   Jay Godfrey co-founded Nushama after careers in high fashion and finance.  At age 42, he was motivated by the failure of traditional psychotherapy to solve his problems as well as the potential of psychedelic research.

“It's a gray area for big pharma, but it's a huge opportunity for patients and for people who suffer,” said Godfrey.  Nushama now refers to its patients as “members” to avoid stigmatizing people getting ketamine. 

“This is not an appropriate treatment for everybody.  It's only as good as the right preparation,” said Godfrey.   He says the break-even point for the clinic is 1,000 patients, a metric he hopes to meet in a year.

Ketamine Can Help When Other Treatments Don’t

Why are more people going to ketamine clinics for help?  Maybe, like Godfrey, they aren’t getting relief even after years of conventional treatment.  Or perhaps they’re not aware of other options that might be as good or better.  Or that ketamine, because it’s a psychedelic, is just something they haven’t already tried.

Another issue is that, again, according to the Kaiser Family Foundation’s 2021 analysis, there is an acute shortage of mental health providers leaving more than 120 million Americans without adequate access to treatment. This restlessness has created a space for the “ketamine cowboys” to capture a share of the estimated $225-billion market for treating mental health. 

Johns Hopkins, like Harvard and Yale, has a psychedelic research program as well as a clinic where patients can get the nasal spray, Spravato, made from a ketamine derivative called esketamine.  It’s the only form of ketamine that’s FDA approved to treat extreme depression and prevent suicide.  However, patients must wait two hours in a certified doctor’s office after inhaling the drug in case of side effects like anxiety or dizziness.  Still, Chisolm says Spravato has had limited success. 

Other Options for Depression

“It always kind of shocks me when people call me and say, you know, I have depression, I want to use esketamine. I'm like, well, what about all the other cheaper, easier medications to use?” asks Chisolm. 

“But people like things that are new,” she says.

However, conventional drugs like SSRIs don’t work for about one-third of patients and there hasn’t been a new drug class for depression since Prozac was introduced in the 70s. It boosts serotonin, a mood-regulating messenger chemical in the brain but side effects like dizziness and sexual dysfunction can be hard to tolerate.  Another disadvantage—the drugs may take weeks to work.

In contrast, Ketamine’s effect is almost immediately, though it tends to wear off quickly—hence the need for repeated doses.  This rapid response is particularly important for treating patients who are on the brink of suicide.

“So that’s where it’s really useful,” says Ladan Eshkevari, Ph.D.

In addition to operating the Avesta ketamine clinics in the Washington, DC area, she’s also on the medical faculty at Georgetown University as a nurse anesthetist with expertise in human physiology. For her, the anatomic logic behind ketamine is that rats and humans share roughly similar brains.

“That’s where a lot of the basic science research has really shown some really cool impact on what happens in the brain subsequent to receiving sequential ketamine treatments, “says Eshkevari.  “It almost gives [patients] a rest from their own thinking which tends to be part of the problem and people who are depressed and anxious [about] ruminating on negative thoughts.”    

If this sounds like something dusted off from the drug haze of the 60s there’s scientific excitement about ketamine.

 “Ketamine is quite effective for anxiety related to depression. And there are studies going on not only within our lab but throughout the country looking at the use of ketamine for various anxiety disorders,” says researcher Lawrence Park, a psychiatrist, and researcher at the National Institute of Mental Health at the National Institutes of Health. 

The drug appears to target glutamate, another neurotransmitter or messenger linked to learning and memory as well as the ability of neurons to communicate and possibly make new connections.  Exactly how ketamine works is a question to be answered but it may raise glutamate levels by blocking a receptor that locks in the chemical.

“Our hope is that we're getting to the point where we're going to be able to refine this treatment and really come up with an easier to take and safer treatment for everyone,” says Park.  Since ketamine is off-patent it wouldn’t be profitable for a drug company to make the substantial development investment necessary to bring it to market for depression or other emotional disorders.

Hazards from a Popular Calming Drug

Meanwhile, many suffering from severe anxiety or panic are defaulting to benzodiazepines that are increasingly prescribed by primary care providers. Under heavy stress during the  pandemic, they may not have time to offer psychological counseling.  Jonathan Avery, a psychiatrist at Weill Cornell Medicine in New York, says one out of four visits for primary care results in a prescription for Xanax.  Like other benzos, this addictive drug is particularly dangerous in combination with opioids.

“We’re in a little bit of a benzodiazepine epidemic because these pills are flooding the market,” says Avery.  “The withdrawal states from Xanax can be very dramatic, especially if on a higher dose, can involve seizures or more serious consequences,” he says.   However, whatever the merits, many psychiatrists are still reluctant to prescribe ketamine until it’s formally approved for depression.  

Ketamine is frequently dispensed by anesthesiologists, who are familiar with it as a tool of their trade.  Nushama ‘s Co-founder and Chief Medical Officer Elena Ocher, MD, compares the situation to the Wild West.  She’s an anesthesiologist trained as a neurosurgeon in Russia and says ketamine clinics need to follow Nushama’s standards. 

“It’s not up to me to say if they’re doing the right thing,” she said. “So, if they’re not getting training in it, they’re not qualified. Period,” she said.

At a low dose, ketamine has what is known as dissociative properties:  Your mind seems to separate from your body.  This can open the door to new, even transformative experiences.  One patient who asked not to be identified described the sensation this way:

“I feel like I went to the place that you would go when you die or where you go before, you're born. Like where your soul lives, before you choose to come into this earth, right? I feel like I went all the way back to that place.”

Ketamine Clinics Continue to Open

Ketamine clinics say they are providing relief for many with as much as a 90 percent success rate, but is it just a short-term lift or a response that abides?  While a number of small research studies show a statistical benefit with ketamine, they have yet to be confirmed by a major study comparing the drug to a placebo.

Regardless, in the last fifteen years, ketamine clinics have proliferated not just on the coasts and in big cities but in places like Boise, Idaho and Tulsa, Oklahoma.

Tulsa television station KJRH recently reported that Jackson Mitchell, an 18-year-old suffering from depression since early childhood, tried ketamine at the Oklahoma Interventional Infusion Center after many conventional treatments failed.

“This has, like, really helped my depression,” he says. "Yeah, since I was about 7 or 8. I tried all sorts of medicines, and I did therapy. The medicines were like Prozac, Zoloft, and Effexor," he said.

Admittedly, he had some anxiety about trying another drug.

“Going into it I was pretty scared, but once I got on it, like, all that went away,” says Mitchell.

With greater demand, the price of ketamine treatments might be coming down.  Nushama is launching more “cost-effective” group sessions where the drug is injected instead of infused.

Ketamine Wellness Centers, an operator of 10 clinics that has provided some 50,000 treatments, is offering Spravato at certified locations; and since that drug is approved insurers may be more willing to cover the expense.  The greater availability of an officially sanctioned drug may also encourage otherwise reluctant patients hoping for relief.

Prior to her Nushama treatments, Echeverry tried psychotherapy and drugs to overcome what she describes as PTSD, not only from cancer but Covid and family loss.  Nothing worked until she tried ketamine.

“If anything, it made me realize and appreciate my life even more.  It made me want to come back,” says Echeverry.

In the end, ketamine clinics may be filling a gap that public health has yet to fully address.

“The impact of these illnesses is huge. But when you look at the support for research and the support for health care, you know, mental health issues are so far down the line compared to other specialties that it just makes the job very difficult,” says Park.