For Greg Rice, ketamine was transformative. The drug, approved decades ago to sedate patients during surgery, was increasingly being used to treat mental health conditions like his depression.
Since his teenage years, Mr. Rice had cycled through a long list of medications. Searching for relief, he sometimes abused his prescriptions and experimented with LSD, psychedelic mushrooms and other illicit substances.
At a particularly low point following a breakup a few years ago, Mr. Rice, 38, bought ketamine through back channels and injected it nightly for two weeks. The psychedelic-like journeys seemed to loosen the grip of his negative thoughts. “That was probably not the best way of coping,” he acknowledged, “but it got me through a really rough experience.”
He continued using the drug periodically, he said, but was left hunting for a supply — until last year, when he discovered the freewheeling world of telemedicine.
Mr. Rice went online and made an appointment with a doctor more than 2,500 miles from his California home whom he had never met. After a 30-minute video call, he received a prescription for a month’s supply. “I finally had an avenue to get pure medical-grade ketamine for cheap, sent to me over the mail,” he said.
Not long ago, such an arrangement would have been illegal. Access to ketamine was tightly controlled by the Drug Enforcement Administration, which puts its risk of abuse one notch below that of opioids like oxycodone and fentanyl. While prescribing it for depression was allowed, patients needed to first meet in person with a doctor, and treatment was mostly limited to infusions in clinics.
But in 2020, at the height of the pandemic, the Trump administration made it easier to treat patients by telemedicine, including remotely prescribing controlled substances. These regulatory changes, which have continued under President Biden, have made all manner of medical care, from management of chronic diseases like diabetes to substance abuse treatment, more accessible and affordable.
While many patients have benefited, the rapid growth of remote prescribing and at-home use of various drugs has outpaced the evidence that doing so is safe and effective. As the gap between medical treatment and online shopping has narrowed, already-thorny debates over the proper balance between availability and safety have become increasingly urgent.
The ketamine boom is a particularly fraught case study of this new reality because of the drug’s powerful effects and the vulnerable patients drawn to it: typically those with severe depression or other mental health conditions who have not responded to traditional therapies. The shift away from clinics has led many patients to take the drug more frequently and for longer periods of time — multiple times a week, even daily in some cases, and for months or years — despite scant research on safety.
To better understand how this is playing out, The Times interviewed more than 40 patients who said their access to the drug was expanded through telehealth, spoke with two dozen doctors and other medical professionals, and reviewed scientific studies, case reports and data from researchers, government agencies and private analytics firms.
Many of the patients said ketamine was life-changing, the only drug that had ever relieved their crushing symptoms. But some described serious drawbacks — including addiction and bladder damage — that have been documented for years among recreational users but have been largely played down by the drug’s medical proponents.
On a Reddit forum devoted to ketamine therapy, an online community that has grown from fewer than 2,000 members in 2019 to more than 25,000 today, posts about misuse of the drug have appeared often enough that some members have pleaded for discretion, fearing a tightening of telehealth regulations.
“I feel like some authority at some point is going to want to crack down and be like, ‘No, we don’t think this is OK,’” said one ketamine patient, Samuel Brooks, in an interview.
Covid-19 exacerbated the nation’s mental health crisis and underscored the inadequacy of many existing treatments, accelerating a reconsideration of once-stigmatized psychedelics. Because the Food and Drug Administration approved ketamine as an anesthetic more than 50 years ago, federal rules allow doctors to prescribe it for other conditions as well, and its use for depression, anxiety and post-traumatic stress disorder was growing before the pandemic.
With the rule changes in 2020, the at-home ketamine industry appeared practically overnight.
Tech start-ups and individual doctors began offering medical services online, and so-called compounding pharmacies, which can make variations of approved drugs, found a market for tablet and lozenge versions of ketamine, normally manufactured as a liquid and distributed in vials.
Primed by glowing media coverage and aggressive advertising, many patients interviewed by The Times came to regard the drug — and its remote availability — as akin to a miracle cure with few risks.
They can now pursue a treatment course not approved by the F.D.A., taking forms of the drug that are also not approved, produced by companies operating largely outside the agency’s oversight — all without comprehensive monitoring.
Some found their way to online physicians like Scott Smith, a family medicine doctor who closed his practice in South Carolina in 2020 to focus full time on online ketamine treatment. In the past three years, Dr. Smith has remotely treated about 3,000 patients in 44 states, and has been featured in The Washington Post and on social media sites like YouTube and Reddit.
Others sought out fledgling tech companies like Joyous, which offers rock-bottom pricing and daily dosing adjusted by text message, or a host of more established firms.
Studies of recreational users have documented that ketamine — popularly known as K or Special K, with a reputation as a club drug — can be addictive and, when taken chronically in high doses, can cause severe bladder damage that in the worst cases requires surgical reconstruction of the organ. There are indications that abuse may also lead to cognitive impairment.
Advocates of increased therapeutic use say those issues are exceedingly rare or nonexistent at the doses and frequencies commonly prescribed. But because treatment is remote and there is little mandatory reporting of side effects, it is nearly impossible to accurately gauge their prevalence.
Patients who told The Times they began experiencing problems after starting ketamine included a 50-year-old man who must use a catheter to empty his bladder and a 37-year-old woman who wears adult diapers.
More on the Coronavirus Pandemic
Some said they concealed problems from their telehealth providers for fear of losing access to the only treatment that had ever helped, while others acknowledged abusing their prescriptions, taking too much and in some cases dissolving and injecting the drug.
On private online forums for medical professionals, accounts of bladder issues are common enough that some providers are becoming more restrained in their prescriptions, according to multiple people with access to the websites. Some psychiatrists at prominent institutions have published cautionary reports.
The approaches of patients like Mr. Rice highlight the underlying tension. He acknowledged his “addictive tendencies” with ketamine, but his top priority in choosing online treatment was clear: “I wanted something hands-off.”
A Trip With Risks
Many ketamine patients described the drug as a reset button for the brain. During treatment sessions, they experienced pleasant visualizations, sometimes accompanied by a sense of existing outside themselves and melding with the universe. Afterward, their daily problems seemed less weighty.
The considerable hype surrounding ketamine stems in part from the drug’s ability to affect brain receptors that traditional antidepressants do not target. The psychedelic-like trip, many believe, is integral to the drug’s therapeutic effect.
But for some patients who spoke to The Times, including a Tennessee cybersecurity manager and a former Pennsylvania factory worker, the profound experiences of their early sessions faded. Chasing the lost high, they sought increased doses, took multiple days’ worth at once or altered the medicine to release more of its payload.
For others — a Utah data analyst, a California bartender and a Pennsylvania internet entrepreneur — ketamine treatment eventually meant dealing with a constant urge to urinate, often painfully, as well as other bladder ailments.
The experiences of the dozens of patients who shared their stories with The Times encapsulate both the well-publicized promise of ketamine and the lesser-discussed risks.
Driving the interest are early-stage studies showing that the drug can rapidly and dramatically relieve symptoms of depression. But there has been little research on how to maintain the improvements and even less on whether prolonged treatment is safe.
When discussing the risks, prescribers often insist there is a sharp line between chronic abuse and medical use.
“That happens in people that abuse ketamine and use more than a thousand milligrams on a daily basis,” Dr. Smith, the online physician from South Carolina, said of bladder damage. “We’re treating most people with 200 milligrams every three days. We haven’t seen anybody that’s had that problem.”
Still, two of Dr. Smith’s former patients said in interviews that they experienced serious issues that required care from a urologist. Both said they did not tell Dr. Smith because they felt addicted to the drug and wanted to continue their prescriptions, which they were misusing.
Among the 12 patients who described bladder problems, most saw their symptoms resolve after they stopped taking ketamine. Most said their doctors couldn’t conclusively peg the cause of their problems but identified ketamine as the likely culprit.
Three patients said their troubles persisted. One of them, a man living in Utah, recounted the painful daily ritual of using a catheter to empty his bladder but expressed no regrets. Without ketamine, he said, he might have killed himself.
For other patients, a similar calculus led them to stay on ketamine despite the harm. All of them spoke on the condition that their full names not be published, for fear of losing access to the drug or affecting their job prospects.
Sarah, a 30-year-old Californian, said she had tried more than a dozen psychotropic medications and undergone more than 30 electroconvulsive therapy treatments before finding ketamine. Now, between periodic infusions at a local clinic, she takes tablets at home that she gets through an online service.
But she has not told either provider about her worsening bladder issues. Her urologist may soon need to inject Botox into her bladder, a treatment for certain urinary problems.
“It’s kind of a lot to admit that you have bladder issues as a 30-year-old, mostly because you’re causing it,” she said.
Many ketamine proponents minimize the potential for addiction and abuse. Dr. Smith said that of the thousands of patients he had treated, only two or three had misused the drug, and that he got them help. He said he had reported one patient to the D.E.A. tip line and also stopped treating a handful of patients after learning they were taking more than prescribed.
“I have to go through hoops to be licensed to treat people with controlled substances,” he said. “So I comply with all federal and state laws regarding that. And part of my daily job is to look for people that are abusing the medicine or diverting the medicine.”
Three of Dr. Smith’s patients told The Times they abused their prescriptions and concealed it from him. Two others described dissolving the tablet or lozenge and administering it rectally, a practice known as boofing that some believe produces a faster and more intense high.
Abuse is “absolutely unacceptable,” Dr. Smith said, but “just because there’s a handful of people that don’t follow directions, that does not mean that this medicine is not safe for the rest of the population of competent adults.”
Six patients of various medical providers said they came to crave the ketamine trip so much they began to use the drug compulsively. The more they took, some found, the more they needed.
“It’s pretty powerful,” said a 59-year-old woman from Philadelphia who sometimes takes more than prescribed, runs out early and tries to buy the drug on the dark web.
A 41-year-old man from Nashville who has battled depression since childhood described the drug as his “superpower.” People liked him more, he had more energy and “I got more stuff done.”
After undergoing infusions at a clinic, he said, he transitioned during the pandemic to taking small lozenges called troches at home. He started at 100 milligrams a day, then took 200, then 400. His provider would not increase the dose any further, so he now exhausts his monthly prescription early — taking 800 milligrams a day.
Speaking on a Tuesday afternoon in December, he said he had just received a performance review at the company where he works in cybersecurity.
“My boss was like, ‘You’re not meeting expectations,’” he said.
“I’m using it right now,” he continued. “Since the start of this call, I’ve taken 400 milligrams.”
In the Absence of Science
While proponents of at-home ketamine stress the lack of scientific studies showing that long-term medical use might be harmful, the converse is also true: There are few studies showing that it isn’t. Some urge caution.
“We know at a certain point you will get both the neurotoxic and the bladder-toxic effects — we just don’t know at what level,” said Dr. Gerard Sanacora, a psychiatrist and leading ketamine researcher at Yale University.
In the absence of data, some medical professionals said they were becoming more conservative in their prescribing because of anecdotes in published case reports or online forums.
Professional groups have developed informal guidelines that emphasize catching symptoms early, reducing the dose and spacing out treatments. But some at-home providers are pushing in the opposite direction, viewing ketamine as just another medicine to be taken regularly.
“I would be worried about chronic usage” said Dr. Adam Howe, a urologist at Albany Medical Center who advises a group developing treatment guidance. Damage is avoidable with proper safeguards, he said, but “common sense would tell you, if you’re to use this every day for years on end, then at a certain point, you’re going to be damaging your bladder probably.”
The literature on addiction and abuse among medical users is also thin and inconclusive. Supporters point to studies indicating that patients on ketamine rarely, if ever, have those issues. Others note a pattern common in drug development: an initial overestimation of benefit, followed by more tempered results and recognition of previously undetected harm.
“We really don’t know what sort of addiction we might be causing,” said Dr. Noah Capurso, a Yale psychiatrist who co-wrote a case study of a patient whose at-home, prescribed use rapidly escalated until he was involuntarily admitted to a psychiatric unit.
Doctors at the Baylor College of Medicine and the Mayo Clinic have published similar accounts. In one case, after a 52-year-old man who regularly took more than prescribed had to be hospitalized, his family said the drug was “ripping his life apart” and he had “no control over it.”
Production Is Booming
For years, mental health clinics have administered the F.D.A.-approved liquid form of ketamine that doctors also use to sedate patients in surgery. But at-home treatment created demand for a version that was less potent and easier to take — something not available from drugmakers.
Enter a uniquely positioned industry: compounding pharmacies.
These specialized companies operate in a murky regulatory space somewhere between a corner drugstore and a pharmaceutical manufacturer. They can produce variations of approved drugs but do not have to follow the same quality-control rules as drugmakers.
Most compounding pharmacies do not have to notify federal regulators when they learn of a patient experiencing a problem, and they are rarely, if ever, inspected by the F.D.A. In many cases, the agency may not even know they exist.
The companies were originally granted legal leeway to produce small amounts of drugs for patients with particular needs, such as an allergy to an ingredient in a commercial product or an inability to swallow a pill. But some have dramatically grown their production capacity and reach.
Companies that once served primarily local customers now ship their products across the country as the ketamine boom has presented an alluring opportunity.
“It’s become the new buzz in this space,” said Jeanine Sinanan-Singh, chief executive of Vitae Industries, which sells a machine that compounding pharmacies can use to produce doses at a faster clip than with other methods.
The size of this new market is difficult to gauge. The number of mental health patients prescribed ketamine more than doubled from just under 15,000 in 2016 to nearly 30,000 in 2021, according to data from the analytics company Komodo Health. But the actual numbers are likely to be far higher because the data is drawn from insurance claims, and plans tend not to cover the drug’s off-label uses.
Most compounders do not report the amount of ketamine they produce to the F.D.A., and the agency refuses to disclose data from those that do, asserting that it is confidential commercial information. In a statement, the F.D.A. noted its limited authority over most compounding pharmacies and said it “continues to monitor reports of adverse events or other complaints involving compounded ketamine.”
Some compounding pharmacies have gone public with stepped-up efforts to attract customers. In social media posts and mailers to doctors, they extol the benefits of ketamine, and some offer to connect patients with prescribers. They promise fast shipping and low prices. Compounders can formulate troches from inexpensive generic ketamine and charge between $50 and $100 for a month’s supply, a fraction of the cost of receiving treatment at a clinic.
After a deadly meningitis outbreak was linked to one compounding pharmacy in 2012, the F.D.A. sought to impose greater oversight on companies that mailed drugs to other states in large volumes, but the industry has successfully stalled the restrictions. As a result, most of the largest ketamine compounders can ship across the country with little federal scrutiny.
Scott Brunner, chief executive of the Alliance for Pharmacy Compounding, a trade group, said that the F.D.A.’s proposals constituted overreach but that the industry was open to some reporting of interstate shipments and adverse events. “Compounding pharmacists’ concern is always the health and safety of their patients,” he said.
Just one of the major at-home ketamine compounders appears to have registered with the F.D.A., and the resulting inspections have turned up serious quality problems, according to agency records.
That company, Empower Pharmacy, ships to all 50 states. Three times over the past five years, F.D.A. inspectors have visited its Houston production site and cited violations, including inadequate monitoring for contamination, insufficient investigations of batches that failed quality tests and a failure to properly report adverse events.
During a visit last summer, inspectors found that the company had been producing ketamine nasal spray for more than two years without ever conducting potency tests to ensure the product had the correct strength.
Empower did not respond to questions from The Times. In a letter to the F.D.A. after last year’s inspection, the company said it had been “steadily improving its management and corporate governance” and “restructuring its manufacturing, quality and compliance departments for greater oversight.”
Daily Doses at Bargain Rates
Cost concerns led Chad Curl to the telehealth start-up Joyous. After trying seemingly everything — prescription pills, electroconvulsive therapy, an implanted nerve stimulator — he found relief from depression at a clinic administering a closely related drug, esketamine, which is a nasal spray approved by the F.D.A. as a mental health treatment. But it cannot be taken at home, and he could afford only a few sessions.
Searching online for alternatives last fall, he found an apparent bargain: $129 a month, ketamine included. He filled out Joyous’s intake questionnaire, had a 20-minute virtual appointment and received a prescription, all in the same night.
“I was like, ‘Wow, I didn’t even plan on this today, and here we go,’” he said.
Joyous is the new kid on the at-home ketamine block, a reflection of where market forces and scant regulation have taken the fledgling industry. The company has sought to distinguish itself by promoting its tech-driven, customizable treatment plans, but the real draw for many patients is its pricing.
“I signed up for Joyous, if we’re being honest, just because of the price,” said Francisco Llauger, who, like Mr. Curl, found in-clinic treatments effective but too expensive.
Joyous illustrates a reality of how at-home ketamine has evolved: Patients with some of the most serious and complicated mental health challenges are turning to some of the most hands-off treatment, according to The Times’s interviews.
The company has carved out its place with a novel approach: Instead of prescribing higher doses to be taken once or twice a week, Joyous offers lower doses to be taken daily.
Melding the argots of Silicon Valley and self-care, Joyous delivers treatment primarily by text message, replete with exclamation points and emojis. Each morning, patients receive a questionnaire on their phones asking about symptoms and side effects, and each evening, they get a text with the next day’s recommended dose.
“Our algorithms use all of this information to tailor the protocol exactly to your brain and body’s needs,” Sharon Niv, co-founder and chief of customer experience, says in a video.In written responses to questions from The Times, the company said its general treatment approach “has been adapted and used by providers nationally and internationally” for more than five years and its internal data indicated that “this medicine is highly effective for both anxiety and depression.” It declined to provide details about how its technology works.
The company says lower doses translate to lower risk. Yet most of the eight Joyous patients who spoke with The Times said their doses reached the maximum the company would prescribe within weeks. Some providers who generally support at-home treatment expressed concern that taking ketamine every day, even at lower doses, could heighten the risk of tolerance, addiction and bladder problems.
“Patient outcomes are our highest priority,” the company said in its written responses. “Joyous takes patient safety and risk mitigation very seriously.”
Joyous said it had procedures to detect and address abuse and addiction, including using screening tools, state prescription databases and regular patient monitoring. While bladder damage has been documented among those abusing ketamine, the company said, “it is not a known risk of low doses.” The company, nonetheless, said it informed patients of all risks before providing treatment, including bladder risk.
“We believe that the patients who choose Joyous understand the risks and feel that the benefits outweigh the potential risks,” the company said, adding that nine out of every 10 patients “report feeling better overall.”
“We want to emphasize that Joyous is a public benefits corporation,” the company said, “meaning that we prioritize public goods over profits.”
Joyous describes itself as a collaboration between “medical experts, psychology specialists and Silicon Valley technologists.” The company’s co-founder and chief medical officer, Dr. Bobbi Leben, has a physical rehabilitation and pain management practice in the Florida Keys, and Joyous is not her first foray into telehealth entrepreneurship.
Archived versions of the website for a company called Everyone’s M.D. identify Dr. Leben as a co-founder and offer treatments including ketamine, generic Viagra, wrinkle-reduction cream and hemp cream for pain. Joyous said she “was involved in the initial discussion” about the company but “was not involved in the launch” and now had no affiliation with the firm.
Joyous patients typically receive ketamine from SmartScript, a compounding pharmacy in Wisconsin, records show, that is managed by Dr. Leben’s husband, Daniel. In its written responses, Joyous said that patients were free to choose where their prescription was filled.
As Joyous’s customer base has grown, so have complaints. Messages to the company’s support line go unreturned for days, multiple patients said. Mr. Curl, who initially praised Joyous in an interview in November, expressed exasperation last month: “They don’t respond to your comments anymore, and I figure, what’s the point?”
For patients dealing with debilitating depression or thoughts of self-harm, delayed or cookie-cutter responses in the weeks or months between video appointments can amplify stress.
A 27-year-old California woman said her depression symptoms worsened and she began cutting herself while receiving treatment from Joyous. For 10 straight weeks, she reported having suicidal thoughts in her responses to a company questionnaire. Each time, she received the same text message in reply.
It contained the number of the national suicide and crisis lifeline and concluded, “We hope you start feeling better very soon!”
“Not once,” the woman said, “did a human being ever check on me.”
Joyous said it could not discuss specific patients because of privacy laws but said the company followed federal guidance in such situations, adding, “Patients always have the option to schedule live telemedicine visits with their providers at any time for no additional cost.”
The future of the ketamine boom depends largely on the actions of the federal government in the coming months. While states have some authority, the most important policy decision rests with the D.E.A. If the agency doesn’t take action before the Covid-19 public health emergency is scheduled to end in May, patients may be required to have at least one in-person visit before they can be prescribed ketamine. The D.E.A. declined to comment on its plans.
Many patients who spoke with The Times expressed hope for a middle ground: something more stringent than the current laissez-faire approach but not so restrictive that a potentially lifesaving treatment became inaccessible.
Mr. Curl said he hoped that his and other patients’ negative experiences would not ruin the at-home ketamine experiment more broadly.
“I’m not on a mission to get them shut down or anything,” he said, “because that’s not going to solve any problems for people like me.”
Produced by Carrie Mifsud and Rumsey Taylor.