Death by tech has gone viral. At the Apple campus in Cupertino, Edward Thomas Mackowiak, an engineer described by a colleague as “driven to no end,” shot himself in a conference room. Uber coder Joseph Thomas left this world by “SIW” (self-inflicted wound). “I’m not dead but I wouldn’t describe myself as ok,” he wrote on Facebook a month before pulling the trigger in his San Francisco garage. Austen Heinz’s cause of death didn’t make the news feeds. One day the Cambrian Genomics founder showed up for work at his San Francisco start-up. The next day he didn’t. “He hung himself,” says his sister. This isn’t just a Silicon Valley phenomenon. Autumn Radtke, the CEO of a fledgling bitcoin exchange, jumped 16 stories from a high-rise in Singapore. Tech people are dying in India, too. Ask anyone who knew Lucky Gupta Agarwal. When Agarwal’s social network app failed, he filled his lungs with nitrogen: “painless” asphyxiation.
Frances Marks has thought about suicide, too. She was younger then, but thoughts linger. Live with depression long enough and that trapdoor never closes. Not that it shows. Tall, attractive, and fashionably dressed, with blond hair that falls to her shoulders in expensive layers, she projects the kind of confidence and success that people notice. As an executive at a start-up in Silicon Beach, she has the kind of job that people notice, too. Like all those other techies, though, cracks radiate beneath her sleek veneer like fault lines in the desert. So she’s made the trip from her Venice home to a medical clinic in Brentwood that specializes in treating depression.
Marks has thoroughly researched this new therapy, but her anxiety is palpable. In some medical circles the treatment is still considered experimental. Seated in a chunky padded chair, with electrodes attached to her torso, she feels more like a lab rat than a patient. To coax a delicate vein out of hiding, her right arm is tied off. After the surgical steel finds its mark, the chair reclines. She grips the armrests and stares at the IV needle stuck in the crook of her elbow like a tiny harpoon. Soon it will deliver ketamine, a drug that triggers hallucinations. Marks hopes it will also make her feel better.
According to the medical literature, the odds that this treatment will succeed are better than good. A friend of hers with chronic depression who sat in the same chair reported feeling “energized” afterward. Marks could use some of that. She has suffered from depression since her early teens. “I would always go to a sad place very quickly” is how she sums up her high school years. She underwent the usual barrage of talk therapy and prescription drugs, but, as she puts it, “nothing made me whole.” Since weaning herself off meds seven years ago, she wills herself through every day like an injured athlete grinding out a performance.
Outside of the office, the executive doesn’t have much of a social life. Evenings are spent plugged into a “recharging station” (the sofa), and weekends are wasted in bed, licking psychic wounds. Her optimism is tempered by modest expectations: “Nobody feels ten out of ten all the time, but when I wake up, I’m a five. It takes all I have to push that to a seven. Just a little boost would be a win.”
Dr. Steven Mandel is sitting in his office, observing Marks through a Nest Cam feed hooked up to a large flat screen. Short, bald, tan, and surprisingly muscular, the 75-year-old anesthesiologist projects the life force of a man half his age. He credits his vitality to a Spartan regimen that includes exercise, a vegan diet, no alcohol, and lots of fashion guts. His scrubs today are accessorized with a turquoise G-Shock and a raffish surgeon’s cap made from fabric printed with Van Gogh’s The Starry Night.
Mandel stares at the infusion room on the monitor. A parody of calming design elements, it looks like Martha Stewart’s idea of New Age chic: soft filtered light and a framed nature photo set against a canvas of cornflower blue paint. With a large eye shield hugging her face, the only thing Marks sees is darkness. On cue, a Spotify “Ambient” playlist starts streaming through her headphones. When a digital infusion pump releases the first dribble of liquid through a plastic tube and into her vein, Marks’s body goes limp.
About 350 million people suffer from depression, making it the leading cause of disability worldwide. Just in the U.S. that translates to a $210 billion hit to the economy every year. In L.A. County the rate of depression has only climbed—from an estimated 9 percent of adults in 1999 to 14 percent in 2011. It makes sense in an unforgiving metropolis where the pace of life is fast, the cost of living is high, and the competition for jobs—from aerospace to acting—is fierce.
Even worse, many of these strivers are single transplants from distant cities, with no family members nearby to offer emotional support.
To combat this pandemic, psychiatrists have relied on the familiar alphabet soup of pills: SSRIs, SNRIs, MAOIs, TCAs. Sometimes they work. When they don’t, these patients are said to have treatment-resistant depression, or TRD. They’re also at greater risk of suicide.
That’s partly what makes ketamine therapy so radical: The hallucinogen has been in use for decades as an anesthetic—and, of course, as the club drug Special K. Only recently did practitioners and researchers begin to look into its potential as a treatment for depression that typically defies treatment.
Advocates are hailing ketamine therapy and its attendant hallucinations as the ultimate brain hack. Prominent doctors and even the stodgy National Institute of Mental Health have championed the treatment as a powerful weapon in the battle against depression, one that could potentially prevent people from taking their own lives.
Blue-chip establishments like Massachusetts General Hospital and the Yale University School of Medicine—never quick to support controversial drug therapies—have been conducting ketamine trials on TRD patients. Kaiser Permanente, one of the more conservative medical institutions in the country, is on board, too. It recently opened four ketamine clinics in Northern California and is rolling out four more in the months ahead. Closer to home, the Semel Institute for Neuroscience and Human Behavior at UCLA is conducting a ketamine clinical trial to treat depression.
But Mandel is well past the trial stage in his own practice. He’s been operating the Ketamine Clinics of Los Angeles in a glass tower planted on a dreary stretch of Wilshire Boulevard, just off South Barrington, for the past four years. Hard-luck TRD cases seeking psychic redemption have come here from as far away as New Zealand and Saudi Arabia, but most of his business is local. The patient roster is a perfect microcosm of L.A.’s privileged class: art dealers and Rodeo Drive merchants, clothing designers and Boeing middle managers, studio execs and the trophy wives who will eventually divorce them.
His biggest constituency of all, though, is from Silicon Beach—the coders, engineers, and execs like Frances Marks who make the shiny toys we clamor for. At 1,100 start-ups and counting, this rapidly expanding tech zone is filled with enough depressed employees to keep a dozen psychiatric clinics busy. The most compelling data on techie depression is a 2015 study that assessed the health of Indian software developers and IT workers. The researchers concluded that of about 1,000 test subjects who filled out a detailed questionnaire, 54 percent reported having depression, anxiety, and insomnia. “Employees working in [the] IT industry are prone to develop a lot of health problems due to continuous physical and mental stress of their work,” reads the paper. “Diseases are either induced, sustained or exacerbated by stress.”
On shows like HBO’s Silicon Valley, nobody mentions diseases. Stress is played for laughs. That’s not dramatic license—it’s reality. The people who work at start-ups play it for laughs, too. Sleep deprivation is hilarious. They may play Ping-Pong , wear flip-flops, and insist that they’re “crushing it,” but it’s all an act.
The resurgence in ketamine experiments has been a long time coming. After the Nixon administration declared its “War on Drugs” policy in 1971, research into the therapeutic potential of psychedelics was abandoned. Now exploring ketamine to treat depression and suicide ideation is at the forefront of the modern day “psychedelic science” movement. That explains why clinicaltrials.gov, a searchable registry database of federally and privately supported trials in the U.S. and other countries, currently lists 163 studies under the search term “ketamine depression.”
Adrienne Heinz, a San Francisco-based clinical psychologist and the sister of the late Cambrian Genomics founder Austen Heinz, is intimately familiar with the perils of the tech world. “The circumstances of Austen’s depression were really exacerbated by founding a start-up ,” she says bluntly. “I see these people in my practice. They have strained relationships, insomnia, panic attacks, virtually no self-care—it’s an unsustainable way of living.” She hesitates. Revisiting the past dredges up painful memories. “At the end Austen had psychomotor retardation and could barely move. He pulled it together for work, but the rest of the time he stared at walls, almost catatonic.”
Depression doesn’t carry the same stigma that it did during the postwar tech boom. Legislation like the Americans with Disabilities Act (which covers depression) increased social awareness, and the mainstreaming of therapists and antidepressants has served to normalize depression. Still, it’s nothing you want to advertise, especially in the high-pressure world of VC checks and IPOs, where the 100-hour workweek is a badge of honor and just the hint of human frailty can thwart a vital cash infusion.
Marks is no exception. She frowns when asked if her boss knows about this interview. “People in tech are afraid to talk about depression,” she says. “The emphasis is always on being positive and ‘crushing it.’ ” When we first meet, she agrees to appear in the story without an alias, saying, “If I can help somebody who’s struggling—just one person, a version of myself 15 years ago—I’m all for it.” But then fears about damaging her career kick in. Frances Marks is not her real name.
Satisfied the drug is being well tolerated by his patient, Mandel bumps up the infusion rate, delivering the payload that will spike the ketamine in her bloodstream. This critical mass is called the “bolus.” It’s a sub-anesthetic dose, a tiny fraction of the average recreational “K-hole” hit, but still enough to induce mild hallucinations. Marks exhales slowly and says, “I feel sleepy.”
An hour later she removes the eye shield. She’s never had a hallucination before, and if her face is any indication, she isn’t looking forward to the next one. “I was definitely flying,” she says between sips on a juice box. “I saw lots of strange shapes and textures.” But the darkness hasn’t lifted. “Everything is still the same,” she tells me. Mandel says it may take a day before the drug gains traction. She nods. Her friend will drive her home. As Marks walks toward the door, her legs wobble slightly, as if she had been at sea for a week.
Unlike Marks, Sean Spencer relishes the fantastic imagery that these infusions spark. At 40, he is the cofounder of MirMir, an L.A.-based media service better known as “the Kardashians’ favorite photo booth.” He’s spent a career worrying about what “naive investors” might do if they learned of his depression, but now that the business is “hitting critical mass and really exploding,” he wants to talk.
Spencer describes his life before depression as “chill and nonstressed.” With his model good looks, a body sculpted from surfing waves in Ventura, and a 30-foot sailboat docked at Marina del Rey, that’s not difficult to imagine. But one year into the start-up frenzy, he was leveled by a severe panic attack. “I was wearing way too many hats and working too much, combined with some personal drama” is the way he explains it. “Many more attacks followed. That led me down a rabbit hole.” He was so overcome by anxiety that he couldn’t leave his Studio City apartment without a Xanax bar in his wallet.
To regain control of an increasingly erratic mind, he tried SSRIs (“After three weeks, I wanted to kill myself”) as well as alternatives like neurofeedback and supplement therapy (“They didn’t work”). The only thing that provided some relief was meditation. “That was the highlight of my day,” he says. “But it only lasted ten minutes, and depression is a constant tidal movement.”
Then his brother, a local stand-up comic who is a patient at Mandel’s clinic, suggested ketamine. Spencer says the infusions are like meditation, only better. “With meditation I can only stay in that deep, peaceful state for ten minutes. That’s if I can get there. Ketamine forces me straight to that place of perfect stillness and zero brain noise, and it lasts for an hour.”
Even though Mandel’s therapeutic dose is minuscule compared with a recreational hit (as much as 40 times less) and slowly infused over the course of an hour instead of snorted up in a couple of minutes, there’s always a slight head trip. Spencer admits that getting high is part of the allure for him: “Pulling away from body and mind provides a whole new perspective. It’s like peeking over the wall. You’re not going to get that by taking a pill.”
More on Spencer’s story from Wired:
Long before Ketamine became a buzzword in Los Angeles, it was CI-581. First synthesized in 1962 by Parke-Davis, ketamine was created to replace PCP, a powerful anesthetic that had one slight drawback: severe hallucinations that could trigger post-op psychosis. The idea was to preserve PCP’s knockout punch while dulling its potentially dangerous “angel dust” high. It worked. Ketamine was a safe, effective general anesthetic.
Ketamine went on to become the world’s top-selling anesthetic. Pediatricians use it to operate on infants. Dentists and veterinarians use it for surgery, too. Because it’s so safe and cheap ($1 a dose), it’s still the most common operating room drug in developing nations. The World Health Organization has dubbed it the “No. 1 injectable anesthetic.”
In little more than a decade the drug found its way onto the dance floor of the 1970s disco scene and has hung on ever since. Even the Amish have heard of Special K. Recreational users claim that a snort of the stuff (some prefer injection) can make a Daft Punk concert transcendent, while hard core users know that too much can result in “K-bladder,” an unenviable condition that shrinks and petrifies the bladder; tabloid reporters have documented cases of addicts reduced to urinating in colostomy bags.
Ketamine emerged as a therapeutic drug in the mid-1990s, when researchers started testing it on psychiatric patients. Not only did the subjects improve dramatically, the anti-depressive effect took hold in minutes and lasted for several days. “Patients described their depression getting lighter—some even said they were ‘all better,’ ” recalls John Krystal, the Yale neuroscientist who coauthored the first paper to document the powerful antidepressant effect of ketamine IVs. “It was a real aha moment. We were thrilled.”
Asked to explain how this drug works, Krystal uses a computer analogy. Everyone, actually, seems to use a computer analogy. Patients invariably talk about how their depression can cause a “hard drive crash” and that they use ketamine to “reboot the brain.” As Krystal puts it, “With severe chronic stress, connecting circuits are retracted. Imagine short wires not making contact in your brain. Ketamine lengthens those wires. It’s like rebuilding circuits in a computer.”
What he means is this: In depressed persons the dendrites—the spindly receptors on neurons that facilitate signal transmission actually recede. The amygdala and hippocampus, two clumps of gray matter that help govern our moods and emotions, shrink as well. It’s long been known that things like exercise, meditation, and memorization—which increase circulation, relieve stress, and focus the mind—can spur the growth of new brain tissue. This cellular regeneration is known as neuroplasticity.
Traditional selective serotonin reuptake inhibitors like Prozac can do the same thing, but that process could take months. Ketamine promotes neural growth within days, sometimes hours. At least it does in rats, with treated animals exhibiting dendrites that lengthened and grew more tendrils, like a tree sprouting new branches. NIMH scientists suspect that the same thing is happening in humans who have received ketamine infusions—a hypothesis based on changes they’ve observed in brain wave activity, suggesting the drug had bolstered connections between neurons in the specific areas of the brain associated with depression.
Glen Brooks, the founder of Manhattan’s NY Ketamine Infusions clinic and the only doctor in the country who has administered more ketamine infusions than Mandel, has a computer analogy of his own: “For the past 50 years the drug companies have told us that depression is caused by a ‘chemical imbalance.’ You need more dopamine, or more serotonin. They approached depression as a software problem when it’s really a hardware malfunction—the neurons in the prefrontal cortex aren’t firing correctly.”
However it works, ketamine isn’t FDA approved to treat depression, so most insurance carriers won’t cover this off-label use. That means patients often pay for their treatment out of pocket and through the nose. Some clinics charge as much as $1,200 per infusion, which makes Mandel’s fees sound almost reasonable: $750 for the first two IVs and $600 for each subsequent one (he chalks up the cost to overhead—rent, staff, equipment, et cetera).
Kaiser Permanente, on the other hand, is now covering every infusion that its expanding network of Northern California clinics doles out through the company’s pre-paid health plan. It’s easy to imagine that the accountants at the country’s largest managed-care organization crunched the numbers and concluded that treating certain patients with ketamine will cost far less than footing the bill for monthly SSRI scripts and expensive emergency room visits.
Advocates believe this move will further legitimize ketamine and pave the way for other insurance carriers to cover the treatment. Dr. Mason Turner, the assistant director of Regional Mental Health Services for Kaiser in Northern California, says that ketamine is more than just a great antidepressant—it’s a smart drug: “Depressed people have trouble learning new material. Ketamine clears out the cobwebs and increases substances in the brain that improve learning. Right now ketamine is a fourth- or fifth-line agent. Maybe we can start to use it earlier in depression treatment, before drugs like Prozac.”
Nobody in the psychiatric community disputes that ketamine infusions are a highly effective treatment for depression. In fact, the American Psychiatric Association published an official “advisory” in the March 1, 2017, issue of JAMA Psychiatry. The article outlines a standard dose protocol and emphasizes that to discourage patient abuse, only qualified doctors should administer the drug. It’s a mixed bag. The authors concede that ketamine offers a “robust” antidepressant effect but add that there are “major gaps” in the medical literature regarding long-term efficacy and safety. Despite the cautionary tone, it’s a big concession from an organization known for being exceedingly cautious.
Dr. Alan F. Schatzberg isn’t convinced. The director of Stanford’s Mood Disorders Center, he published an anti-ketamine editorial three years ago in The American Journal of Psychiatry. Too little is known about how the drug works, he argued in his piece. Today he still worries about ketamine’s dissociation effect and that people might abuse it. “The issue is repeated use,” he says. “There are a lot of drugs out there that people thought were safe—ketamine is neurotoxic.” He won’t be changing his mind anytime soon. “This cavalier attitude about safety is concerning. Suddenly we’re going to abandon the standard way we evaluate drugs—it’s unbelievable.”
Schatzberg is referring to the concern that while it might be a perfectly safe occasional anesthetic, ketamine might not be safe to take over a period of years. “There is no miracle here without knowing potentially what the mechanism is and what the down side is,” he says. “You can give people heroin. A lot of them will feel better, too.”
Dr. Charles Nemeroff, chair of psychiatry at the University of Miami and the person pegged by the APA to lead the group that wrote the JAMA Psychiatry advisory, is also a skeptic. “Ketamine is not ready for prime time,” he says. “We don’t even know which brain receptors are involved.” Then he lowers the boom: “Some people think ketamine may be opiate-like.” He’s referring to research that indicates ketamine targets the same receptors in the brain that opiates act on. “I just want to make sure when we open Pandora’s box, hell doesn’t come out. We don’t need another opioid epidemic.”
Mandel scoffs at this, insisting there’s no danger of tolerance or addiction. “Ketamine is the most widely used anesthetic on earth,” he says. “It’s been given hundreds of millions of times. So you can’t argue it’s not safe. There’s also lots of evidence that it has a ‘robust’ antidepressive effect.” He finishes with the line any juror would remember: “You can’t put the genie back in the bottle.”
Before opening his private practice, Mandel was drawing a cushy salary as an anesthesiologist at a successful plastic surgery center in Santa Monica. He says that making the switch to all-ketamine-all-the-time wasn’t about the money—it was about an accident involving a favorite niece. The police report tells the story: A car traveling during daylight hours on a clear, dry, level road hits a tree at 90 mph. Victim’s age: 23. “Her death didn’t end up as a suicide statistic, but Julie killed herself,” he says.
The family tragedy gave him renewed purpose. He devoured all the medical literature on ketamine and depression. Then he borrowed a surgeon’s recovery room and started sticking veins. “After treating the first few patients, I knew this stuff worked,” he says.
Mandel insists he can save other Julies. He says that one treatment can buy ten days of relief. Two is usually good for a couple of weeks. A full cycle of six treatments may keep the “black dog” at bay for several months. Permanent remission cases are as rare as planetary alignment. A quarterly “booster” IV, for maintenance, is typically required. Some single-infusion patients, though, have gone longer than a year between clinic visits.
He says he gets longer-lasting results than others do and for a simple reason: Where Yale and NIMH scientists have established a standard dosage of 0.5 milligrams per kilogram of body weight administered over a 40-minute period, Mandel’s ketamine protocol is supersize: 0.7 “migs per kig” for up to 55 minutes. “Most doctors are too timid with ketamine,” he says irritably. “There’s a lot of brain tissue—you have to crank it up.” (There are no published head-to-head trials that compare various ketamine dosages and infusion times, but a dose-finding study involving the NIMH and multiple universities is under way.)
In Mandel’s perfect world, ketamine would be FDA approved to treat depression and suicide ideation. He thinks it’s absurd that his magic bullet IVs are only medically sanctioned for “off-label” use. It’s this sketchy limbo status—FDA approved for anesthesia but not for depression—that prevents most health insurance carriers from covering this simple outpatient treatment. He says that without such insurance, many patients are needlessly suffering—and dying.
Providing the road map to navigate the complex terrain of distressed brain tissue is quite a legacy for any drug, much less a humble anesthetic. Scientists hope that by studying the neurobiological cascade of events that ketamine sets in motion, they’ll learn how to engineer a better class of antidepressants.
For now the holy grail seems to be tweaking ketamine’s molecular structure to capture the drug’s unrivaled therapeutic effect while eliminating those pesky hallucinations. Drug companies have spent hundreds of millions of dollars to do just that—and, not incidentally, to come up with a patent that would generate far more revenue than ketamine, whose patent expired years ago. The rapidly growing antidepressant market is too big to pass up: $14.5 billion globally, projected to hit $17 billion by 2020.
So far “ketamine mimics” have flopped in FDA trials. But one drug company is convinced it has finally made a breakthrough: Janssen Research & Development, a Belgium-based drug lab that’s part of the health care behemoth Johnson & Johnson. Janssen is currently in late-stage Phase III trials of a ketamine clone that is widely expected to gain FDA approval sometime next year. What’s interesting is that despite the company’s considerable R&D investment, this isn’t a new drug. Ketamine is actually a combination of two molecules that are mirror images of each other. Janssen is using only one of these “optical isomers”—esketamine, which is an anesthetic that’s been used in Europe for the past 15 years. But by securing the rights for a use patent on the intranasal de livery of esketamine (think of squeezing an Afrin bottle), insiders believe Janssen might be sitting on the Prozac of the 21st century.
Dr. David Hough, the team leader on Janssen’s esketamine project, certainly thinks so. He touts esketamine’s “high bioavailability”— meaning that more of the drug makes its way to the brain—and some stellar numbers: a 60 to 70 percent response rate and six to eight weeks of relief. “Esketamine is an exciting drug that can make a difference,” he says. “It will give people their lives back.” Perhaps. But as those aerosolized molecules travel through the brain, they will also give people a serious buzz. The fact that Big Pharma’s first ketamine copycat will be bundled with hallucinations is no small irony. It’s as if Janssen is hedging its bet to minimize risk of failure in case those drug-induced hallucinations are more than just a screwy slide show. A Janssen rep downplayed the drug’s dissociation effect, insisting that it lasted no more than two hours and that, with repeated dosing, the “symptoms reduced significantly.” To discourage abuse, esketamine will be supervised by doctors only during office hours.
But what if chemists stopped trying to eliminate the dissociation effect and embraced their inner shaman? What if those hallucinations are an integral component of the healing process? There’s a wealth of anecdotal evidence from patients like Sean Spencer and doctors who insist this is the case. However, only a single published scientific paper has delved into this contentious subject, and the results were inconclusive. A larger follow-up trial has been completed, but the results have not been released. Dawn Ionescu, a psychiatrist at Massachusetts General Hospital and one of the first study’s authors, suggests a theory that should make Big Pharma nervous: “If dissociation is indeed found to be important for ketamine’s effects, then it may explain why many of the new ketamine-like compounds have failed to have the same robust antidepressant effects as ketamine.”
Angel Piper got her start in tech testing video games. At 38, she still looks like a gamer. The short dark hair and big brown eyes pop against her pale skin. Although her depression has improved greatly, she rarely strays far from her home in Irvine. Being unemployed, she doesn’t have to. Hospitalized numerous times for suicide ideation, she received two infusions from Mandel about eight months ago. They worked. Parked on a couch in the clinic’s waiting room, she describes a “180-degree difference” in her mental health. As with many patients, her behavior, not how she felt, was the bellwether: “I noticed the trash had to be taken out. So I did it. Next I saw dog poop on the lawn and thought, ‘I better pick that up.’ Then I looked down, saw some weeds, and pulled them.” She stops abruptly, still inspired by these seemingly insignificant domestic victories. “I suddenly realized I was doing all the things that were so impossible to do for so long.”
Piper isn’t here for an infusion. She’s seeking advice. A cousin’s wedding on the East Coast is coming up, and she plans to attend. But the thought of being 3,000 miles away from home is distressing. What if she needs a booster? Mandel points to a box containing samples of small white lozenges. Made to order at a compounding pharmacy, the meds dissolve under the tongue. Because of their poor bioavailability, the quick-hit lozenges are K-lite, no substitute for an IV. But they’re cheap ($75 for a 30- day supply) and can buy precious time. “It’s like taking an umbrella when you leave the house on a sunny day,” says Mandel. “You probably won’t need it, but you’ll feel better that you have the insurance.”
These particular lozenges contain no active ingredient. Mandel uses them to gauge flavor preference among his patients. Piper pops a mint sample and finds it bitter. “Try the strawberry-marshmallow,” suggests Mandel, flashing his best Willy Wonka grin. “It’s the least offensive.” Piper agrees and places an order. Knowing she can hop a plane with a candy-coated security blanket in her purse is a great relief.
The Jerry Springer take would be to dismiss Mandel as nothing more than a high-class drug dealer, a new Dr. Feelgood for L.A.’s well-heeled melancholics. Mandel chuckles at the thought of his clinic being a front for a K-hole shooting gallery. “Nobody comes to me because they want to get high,” he says incredulously. “Most of my patients don’t start feeling better until after the treatment.”
These words aren’t reassuring to Frances Marks, though. Five days into her treatment cycle, she says she is still depressed. The second and third infusions, administered 24 hours apart, didn’t move the needle. There’s no good news the next day either, or the day after that. “Disappointing,” says Mandel.
Then on Saturday morning, exactly one week after her first infusion, Marks sends me a text “Have good news to report.” When she phones in later, her voice sounds a full octave higher, and she’s speaking at a faster clip, the words tumbling out like water from a faucet. “I woke up today, and the mental hurdles weren’t there anymore,” she says excitedly. “I’m happier in every area of my life because everything’s easier.” She rattles off a recent list of accomplishments: attending a meditation class, ordering a baby shower gift, making a Craigslist sale. “I even went to the grocery store to pick up salsa,” she says proudly. “Normally I’d be like, ‘That’s 50 energy points—no way! I’ll call my roommate.’ But it was no big deal.”
The clincher is that she no longer feels the need to “recharge” at the end of the day. “Instead of lying on the couch, I went to a work event and had dinner with a friend,” she says triumphantly. And instead of wasting another weekend in bed, she went on a bicycle ride, something she hadn’t been able to do for the last 18 months. “I thought that ketamine would give me all this energy, like I’d want to run ten miles in the morning. That didn’t happen. But now anytime I need to do something, it’s just that much easier. It’s not rocket boosters. It’s more like power steering, but that feels really, really nice.”
Stephen Hawking knows just how Marks feels. The famous scientist, whose own mental anguish dates back to Cambridge in the 1960s, once compared depression to a black hole: “No matter how dark they seem, neither is impossible to escape.” For many patients, though, escape is impossible. Now an old drug is offering patients new hope. Go to Mandel’s clinic and you’ll see these people. They know about the black hole of depression and the wormhole that transports them to a better place.
Janssen’s new drug might offer an even better wormhole, or at least one that’s more commercially viable—faster, cheaper, and stripped of the unsavory junkie fix ritual. Mandel is pessimistic. “I’m not a fan of intranasal delivery,” he grumbles. “You can’t control the dosage precisely. It’s short, quick bursts instead of a long, continuous flow—I think that’s important.” Maybe. We’ll know soon enough. In the meantime, the receptionist books more patients into the clinic’s infusion rooms. Needles are prepped, pumps are programmed, and the ketamine keeps flowing.
Rene Chun has written for a variety of publications, including The New York Times, The Atlantic, and Wired, where he is a contributing editor.
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