Dysregulated: The Patchwork Policies of Ketamine Therapy

After trying unsuccessfully to treat his depression with medication over several decades, Noel Farris, a 43-year-old web developer based in Philadelphia, found a ketamine clinic through a friend’s recommendation. He’d heard that the drug helped people mentally dissociate from the disease. So last year, he met with the clinic’s doctor, who recommended three intravenous infusions per week for a month, at $400 a session. He never saw or talked to the doctor again.

Instead, he said, a nurse took his blood pressure, placed the IV, then left the room each session. He was told to avoid driving for a few hours but was allowed to return to work. After several months and several thousand dollars, he stopped, saying he felt temporarily lighter, but didn’t see any long-term difference.

But Farris’ experience was specific to that one Philadelphia clinic. If he’d gone to a different site, even in the same city, he likely would have received a different treatment plan: a different dose, a different number of infusions, and different after-care instructions. And he might have experienced a different result.

In Jacksonville, Florida, Kevin Beaugrand, a 33-year-old restaurant server, received IV ketamine infusions while connected to a pulse oximeter, a blood pressure cuff, and an electrocardiogram. A medical professional stayed with him for most of the hour-long session, and his mother drove him home. After six treatments in two weeks — combined with outside counseling sessions — he started to feel better and purchased about 20 sessions over three years, at a total cost of about $10,000.

Across the country in Spokane, Washington, Jake Reinert, a 26-year-old insurance adjuster, said they started taking Spravato, a ketamine-derived nasal spray also known as esketamine, in April 2024. The first clinic Reinert tried required them to come in twice a week for a month and monitored their blood pressure from another room. Reinert then switched to a private psychiatrist and now pays $50 a month for a ketamine nasal spray made at a local pharmacy. At one point, Reinert was taking ketamine every day, and now uses the spray four times a week.

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For more than five decades, ketamine has been used as an inexpensive anesthetic in operating and emergency rooms. But in recent years, the drug has emerged as a last-chance treatment for depression. The market really took off after 2019, when the U.S. Food and Drug Administration approved Spravato, which is chemically related to ketamine, for treatment-resistant depression.

Ketamine itself, though, isn’t approved to treat any mental health condition, meaning it must be prescribed off-label. It’s now available across the U.S. through mail order and private IV infusion clinics, and in the form of nasal spray and medicated lozenges. And the drug has recently come into the national spotlight since billionaire tech mogul Elon Musk discussed his ketamine use in an interview, and suggested it could be an alternative to traditional antidepressants.

Evidence on the efficacy and safety of ketamine as a depression treatment is still evolving. But some patients who have tried other medications without success call the drug life changing. And it’s popular: More than 1,000 private IV ketamine clinics have reportedly cropped up in recent years. One 2023 market research report estimated the private ketamine market would double from $3.41 billion in 2023 to $6.9 billion in 2030.

Yet despite that popularity, there are few state regulations and little federal oversight about who can administer the drug, at what dose, and how many times. In fact, one state has pulled back on requirements to gather data about adverse events despite concerns of underreporting.

Experts say that lack of regulation and oversight is concerning and could be dangerous. While ketamine is unlikely to be fatal unless combined at high doses with other drugs, it’s regulated as a Schedule III controlled substance, meaning it has potential for addiction and abuse, like Tylenol with codeine. Repeated use has also been associated with damage to the bladder and kidneys, and studies on the effects of long-term use are limited. Safety concerns led the United Kingdom to consider putting ketamine in the same restricted class as cocaine and heroin after “Special K,” as ketamine is also known, became widely used as a party drug.

In the U.S, much of the challenge with using ketamine as a depression treatment is related to its off-label use. When a drug that can have serious side effects, like Spravato, is prescribed, doctors follow a safety program set by the FDA, called a Risk Evaluation and Mitigation Strategy. But such a program does not exist for ketamine.

In more than 30 interviews with private clinic owners, current and former federal sources and state government officials, researchers, and patients, Undark found that dosing, safety protocols, and administration methods varied significantly from provider to provider. One clinic director was unclear if they should be reporting serious adverse events like breathing problems and manic episodes to their state or to the FDA, which collects medical reactions in its national database. (An email to Undark that Emily Hilliard, deputy press secretary at the Department of Health and Human Services, requested be attributed to an FDA spokesperson, noted that distributors of the drug are required to submit reports of adverse events “that are both serious and unexpected.”)

Several experts Undark interviewed could not point to a state-by-state list of regulations, and independent searches revealed limited information.

Although medical providers at clinics must register with the Drug Enforcement Administration for approval to administer a controlled substance, that’s about the limit as far as regulations. Seth Mehr, who started his own ketamine clinic, Cascade Psychedelic Medicine, in Portland, Oregon in 2021, said he is frustrated by the lack of state and federal guidelines about how a ketamine clinic should operate, calling the system “a sea of non-answers.”

“You don’t have to register with anybody to open a ketamine clinic,” said Mehr, a former emergency room physician. “There’s not a gold standard set of rules as far as who needs to be there, how many people need to be there, what kind of safety equipment you can use, what dosing ranges you’re allowed to use. Really, none of that exists.”

For-profit clinics do have to adhere to general safety regulations and may face varying restrictions on how they can operate, depending on the state. But because treatments at such clinics are usually not covered by insurance, clinic directors can set their own prices and the number of sessions recommended — with little science to guide any standard.

Some in the field have tried to collect data on ketamine use for years, as the number of private clinics and telehealth businesses continued to grow.

Gerard Sanacora, a professor of psychiatry and director of the Yale Depression Research Program, who has long studied the impact of ketamine on depression, is among those who have called for a “ketamine registry,” to track dosage, treatment frequency, and adverse events.

But that, too, has its challenges, he said. “While it seems like such a simple thing — that we should be having some way of tracking this and registering it and everything else,” Sanacora said, adding that “it’s really hard to set up a regulatory control over it without dramatically limiting access to people that will need it to have their wisdom teeth extracted,” among other applications. He said that he has spoken to many regulatory agencies, including the FDA and National Institute of Mental Health, as well as professional societies, about increasing ketamine oversight and data collection.

“It really is one of these unique things that just seems to fall through the cracks,” Sanacora said.

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Ketamine was first developed in 1962, and soon began to be used as a battlefield anesthetic in the Vietnam War. Army doctors had previously relied on a related compound, phencyclidine, otherwise known as PCP, but some patients experienced hallucinations and convulsions after use. Ketamine seemed to induce similar dissociative effects but was shorter-acting and safer.

It wasn’t until the 1990s that researchers became increasingly interested in its potential as an antidepressant. Studies began to find that subanesthetic doses of ketamine — meaning below the threshold dose for anesthesia — relieved symptoms of major depression and reduced suicidal thoughts.

Researchers and psychiatrists were excited about ketamine because it acts quickly and dissipates from the body within a few hours, compared to SSRIs — selective serotonin reuptake inhibitors — which can take weeks or months to have an impact and often have side effects like changes in appetite.

Although there are few studies addressing the long-term impact of ketamine efficacy, some small trials have shown that ketamine could have an impact in just a few hours where others failed, particularly for suicidal patients. One 2024 study of 75 people who received three ketamine IV infusion treatments over 11 days found that two-thirds of the participants experienced at least a 50 percent reduction in suicidality as measured by a self-reported questionnaire. And meta-analyses have found the drug to be a promising antidepressant.

Patients characterized the impact of ketamine treatments in different ways. Just one patient interviewed for this story described the ketamine experience as a high. Some said that ketamine allowed them to separate their thoughts from their emotions, or that they felt the weight of their depression lift.

Although everyone’s experience with IV infusion was slightly different, most people interviewed said their sessions lasted about 45 minutes to an hour. Some wore eye masks, some did not. And some listened to music. And while ketamine isn’t generally considered to be a classic psychedelic like LSD or psilocybin, it can induce a psychedelic effect at high doses.

“It sort of takes you out of your body into what feels like another realm or bubble or plane of existence,” said Beaugrand, the Florida restaurant server. He said he frequently listened to a reggae-version of Pink Floyd’s “The Dark Side of the Moon,” and would, at times, experience “visual hallucinations that make you leave your body when your eyes closed, are very vivid in real life, and it can be kind of disconcerting.”

Despite its promise as an antidepressant, doctors warn that ketamine is not a good choice for everyone. It raises blood pressure and heart rate, so isn’t recommended for people with uncontrolled heart disease. Several guidelines advise those with a history of mania or psychosis to avoid the drug. And there is concern about long-term use causing cognitive impairment and what’s known as “ketamine bladder,” which can cause the bladder to shrink and become irreversibly damaged.

Kimberly Juroviesky is a nurse practitioner and a captain in the Air Force who was disabled during active duty and started receiving ketamine treatments for chronic pain. She also is president of The Ketamine Taskforce, a volunteer organization aimed at improving education, access, and insurance coverage for ketamine.

“You watch any drug commercial on television and what are they going to say, ‘may cause kidney issues, may cause this, may cause that, may cause death,’” she said, noting that she now limits her ketamine treatments to once every four to six weeks. “That’s why you have to have guidelines, that’s why you have to use it appropriately.”

When the FDA approved the nasal spray Spravato — otherwise known as esketamine — it came with strict treatment guidelines: Clients had to have tried and failed at least two oral antidepressants first. Treatment also required a two-hour monitoring period in which a health care provider watched for serious side effects such as vomiting or dizziness.

Psychiatrists started using ketamine off-label in the late 2000s, after a study found that 71 percent of participants who received intravenous ketamine reported feeling better. But the number of clinics expanded significantly after Spravato was approved. And those clinics didn’t have to follow the strict guidelines required for Spravato.

When the Covid-19 pandemic hit a year later, the FDA allowed providers to prescribe controlled substances virtually. That’s when telehealth companies like Mindbloom became popular; they created online consults and sent medicated ketamine lozenges, called troches, through the mail. The lozenges release the drug more slowly than through an IV. Trapped in their homes, people reached out, looking for relief from their depression and fear.

While state boards of medicine oversee the medical practitioners administering the ketamine, and the Drug Enforcement Administration issues licenses to those prescribing controlled substances, it’s up to states to decide who can administer the treatments, what data to collect, if any, and what safety standards to impose, said Seth Mailhot, a former FDA investigator and compliance officer who specializes in FDA regulations for Husch Blackwell legal firm in Washington D.C.

This January, Mindbloom announced an injectable program, allowing patients to draw a dose from a vial of ketamine at home. Concerns about safety abounded, but Mailhot said it’s unclear if, in general, telehealth companies legally fall under the state where they send the product, or where the company is based.

Meanwhile, the landscape could change dramatically in the next couple years. During Covid-19, regulations passed to allow practitioners to prescribe controlled substances to patients after telehealth appointments. But those regulations are set to expire on Dec. 31, 2025.

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In untangling the patchwork policies, Undark examined three states with contrasting ketamine approaches: Pennsylvania, Utah, and Oregon. Pennsylvania, recognizing the growth of private ketamine clinics, created a task force to develop general guidelines in 2020, early in the ketamine boom. Utah, at one point, appeared to have very strict rules for ketamine clinics. And Oregon’s guidelines for its ketamine clinics differ from its psilocybin centers, which were legalized in 2020.

Most states have guidelines — voluntary rules for ketamine clinics, not regulations. Regulations would take a legal process, and states would need the money and manpower to enforce those laws, whether it be through regular inspections or data collection, said Mailhot.

In Pennsylvania, the challenge was that when those guidelines were developed, it was unclear what potential issues might arise.

“We were aware that there were a lot of clinics opening up, but probably not with the appropriate providers or equipment, and we realized that this was a space that really wasn’t governed or regulated in Pennsylvania,” said Jessica Poole, a nurse anesthetist who served on the state’s task force and helped develop state guidelines for best dosing practices.

The current guidelines recommend strict monitoring, including blood pressure, cardiac, and neurological checks, and the availability of emergency equipment. But Poole said there are a lot of gray areas for clinics operating outside of hospitals and ambulatory surgical facilities (ASFs), which specialize in outpatient procedures. The guidelines do not require clinic directors to report adverse events to state or federal agencies.

“There are not any strict black and whites on it when we’re talking about clinics outside of a hospital or an ASF unfortunately,” she said.

Although private ketamine clinics in Pennsylvania do not have to register with the state department of health, practitioners do need to have a DEA license and to follow the same license rules as any other business, according to Barry Ciccocioppo, communications director for the Pennsylvania Department of Health.

The current guidelines also recommend that a physician or a certified registered nurse anesthetist who has adequate training and experience supervise any ketamine administration. But again, Poole said, those are only guidelines, not requirements.

In 2023, Evan Husted, an emergency room physician, opened Mindstream Medicine, a private ketamine clinic in Philadelphia, after, he said, he had a positive experience with ketamine himself. But he said the state guidelines were often unclear about safety protocol. For example, he was unsure if he was supposed to be reporting adverse events and to whom. (Pennsylvania guidelines call for monitoring for adverse events, but do not require adverse event reporting.)

As an emergency physician, Husted said he’s comfortable handling physical issues that may come up — for example, increased blood pressure and heart rate. But because he doesn’t have a psychiatric background, he chose not to accept bipolar patients or those with a history of psychosis, as some evidence suggests ketamine treatments can trigger rare manic episodes. The Pennsylvania guidelines, however, don’t stipulate which medical or psychiatric conditions should exclude patients from treatment. They simply caution that patients with high-risk coronary artery disease and poorly controlled psychosis are at increased risk for adverse events following ketamine infusion.

Husted said more guidelines are needed, both for patients and for the medical practitioners trying to provide a uniform treatment.

“You can go to 10 different clinics — not even in other parts of the state, but just other parts of the city of Philadelphia and the suburbs — and find people using ketamine in 10 different ways,” he said.

Among those major differences is dosing, which is largely left up to providers.

Some experts, like Sandhya Prashad, a practicing psychiatrist near Houston and president of the American Society of Ketamine Physicians, Psychotherapists, and Practitioners (ASKP3), caution against using high doses due to safety concerns.

But Husted, for one, said he believes patients get more out of a level of what he called “therapeutic intoxication,” though he said that dose differs dramatically from person to person.

“There’s no telling how much ketamine someone’s going to need to get to the level you’re trying to get them to,” Husted said, “and so I would be wary of regulations that tell me I can only give so many milligrams per kilogram [of body weight] and still be operating in good practice as a ketamine clinic.”

In contrast to Pennsylvania’s minimal oversight, Utah started out as a strict outlier. In 2017, the state passed a law requiring clinics to track adverse events related to outpatient anesthesia. However, the monitoring ended in 2023 despite a Utah Department of Health and Human Services task force recommendation that it continue until 2025, amid concerns of underreporting. Of the 14 adverse events reported during that time, eight of them involved dental procedures. It was unclear if any involved ketamine infusion clinics.

It was also unclear why the monitoring ended. Melanie Hall, communications director for the state Department of Commerce, which oversees the Division of Professional Licensing, said there was a “sunset” date of 2023 on the monitoring law: “We do not monitor the use of ketamine or any adverse events associated with it,” she wrote in an email.

Some clinic directors said the Utah oversight was helpful, particularly when Covid shut many of the clinics down and providers switched to providing ketamine via mail. When the pandemic shut down services, William Beesley, founder of Restorative Health — a clinic that offers ketamine treatments as well as weight management and hair loss therapies in Sandy, Utah — said he was able to call the state and see what they could provide, and under what circumstances.

Beesley also noted that the state keeps a controlled substances database so providers can confirm that patients are not getting ketamine from other clinics. According to Patrick Fitzgibbon, a spokesman from Utah’s Division of Professional Licensing, telemedicine prescriptions would be in the database if reported by the pharmacy.

“Utah’s systems seem to work better to me,” he said. “It’s a very, very, very complicated situation but the state is handling it better than the national government.”

Meanwhile, in Oregon, clinics face an additional challenge, as many of them provide both ketamine and psilocybin treatments. But the state takes a much stricter approach with the latter: Oregon requires providers at its psilocybin centers to take a verified training course, register with the state, and collect data on any events requiring emergency medical attention. Tim Heider, a spokesperson with the state’s health authority, noted in an email that the agency does not regulate ketamine.

It’s confusing for the clinic directors and the patients, said Mehr, the emergency room doctor who founded Cascade Psychedelic Medicine. The private clinic offers both ketamine and psilocybin treatments. Mehr said he remains with patients throughout the experience and asks them to seek additional mental health support as part of the treatment process.

Like Husted in Philadelphia, Mehr uses doses of ketamine high enough to induce a psychedelic state. He said he turns down about 10 to 15 percent of patients who apply for treatment due to mental health concerns or physical health issues. Patients typically start with sessions twice a week for a few weeks, and then taper from there. They generally move to sessions every other week for a few months, Mehr said, and then once a month after that. An individual session is $685, although a sliding scale is available. About 50 percent of the treatments are now partially covered by insurance, he said.

He said part of the problem is that there are so many organizations developing their own versions of guidelines. All of them are voluntary. The reality, he said, is that ketamine practitioners are held accountable by two entities: the legal system and the state medical boards, the latter of which will investigate if there is a complaint.

“Being accountable to a lawsuit and being able to demonstrate that you are practicing within community standards, that’s how a malpractice suit is defined,” he said. “Then there’s the boards themselves that regulate their providers the same way they do everything else.”

Eric Hermes, the national director of psychopharmacology and somatic treatments at the Veterans Health Administration Office of Mental Health and Suicide Prevention, said the VA has two national programs to train personnel about ketamine, from clinical needs to developing ketamine programs at facilities. He said because IV ketamine is unregulated, providers tend to use higher doses because some feel that the length of dissociation is linked to overall effectiveness in treating depression long term, but that has not been proven in the research or in his experience.

Another challenge with ketamine, he added, is ending treatment: “What we’ve found in clinical treatment is that some patients, sometimes a large proportion of patients, don’t do well when you try to taper off ketamine.”

That results in some VA patients receiving what he called “long term serial treatments,” even though there is not a lot of data about the benefits and risks of long-term use.

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In a 2023 article looking at legislative reform for psychedelic drugs including MDMA and psilocybin, Joshua Siegel, a psychiatrist then at Washington University, wrote that “legislative reform for psychedelic drugs has been proceeding in a rapid, patchwork fashion in the U.S.” For ketamine, he said, the legal situation is even more challenging, since it’s already an approved drug but is being prescribed off-label.

The lack of regulations could have serious consequences, said Siegel, now an assistant professor at New York University’s Center for Psychedelic Medicine, because while overdoses with ketamine are uncommon, they do happen, particularly when combined with other drugs.

“You can overdose on ketamine and stop breathing,” he said. “But that’s not the case with LSD and psilocybin, where you don’t really see overdoses like you do with ketamine.”

Siegel pointed out that at least in a clinic, there is some medical oversight and someone is physically in the clinic in case something goes wrong. That’s not the case with mail-order services, leading to a higher-risk situation, he said.

Prashad, president of ASKP3, echoed safety concerns, particularly regarding dosing.

Patients have come to see her, “and they’ve seen someone else in the past that administered IV ketamine, and they gave them such high doses they were practically anesthetized,” she said. “There’s no data that suggests that that’s what you should be doing. In fact, there’s data that shows that that’s neurotoxic.”

ASKP3 is working to develop updated guidelines for drug type, dose, and frequency, though it would be voluntary for practitioners to follow them.

L. Alison McInnes, a psychiatrist and former medical director for Kaiser Permanente Northern California’s ketamine infusion therapy program, agreed with Mehr that enforcing those guidelines will likely only happen through patient lawsuits.

“If you have standard of care out there,” she said, “then malpractice courts have something to deal with.”

But Mailhot said it’s up to the states to create legislation — like Utah did requiring adverse event reporting. But most states haven’t issued more regulations because state legislators aren’t comfortable weighing in on the practice of medicine for fear of unintended consequences, he said.

He pointed to the effort it took to shut down opioid “pill mills,” noting that the government was able to track the biggest offenders through the number of prescriptions, but that’s harder to do with ketamine because it is not being tracked, and it is not being used in the same volume.

“When there’s enough of an outcry to the safety issues, they’ll crack down,” he said, noting that the country is currently in a “deregulation environment.” “But for now, you can’t stop everything from happening.”

While states and professional organizations are struggling to address the increasing number of private ketamine avenues, experts like McInnes are trying to work with clinics through an entirely different path: She’s the vice president of scientific affairs for Osmind, an electronic health record system specifically for clinicians administering psychiatric medications and treatments like ketamine.

As of late May, she said at least 200 clinics had signed up, including more than 250,000 patients. The record template includes vital signs, doses, any medication the patient is on, and any side effects. And there’s a new record for each infusion, she said.

The clinics and patients consent to use the data — without identifying factors — for research. Right now, McInnes is working on a paper in consultation with a researcher at Yale University comparing esketamine results with those from ketamine infusion therapy.

She said it would be helpful if there was a nationally recognized ketamine certification program for providers and those working in the field. Instead, she said, there are some “charismatic figures” offering training courses for thousands of dollars, but there’s no standardization.

McInnes said that, from her data, most people don’t need more than six ketamine infusions to treat their depression. But for many clinics, there is no end point for its use.

“It’s just really quite egregious,” she said.

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For patients who work with ketamine, part of the challenge is figuring out how to use the drug as a tool and not a crutch.

Reinert, the insurance adjuster from Spokane, has been regularly taking ketamine since October 2024, increasing the dose to where they are now taking 140 mg several times a week. The treatment has been life changing, Reinert said. At one point, Reinert had taken a medical leave to deal with their depression but is now working full time and taking a full load of college courses, aiming for a degree in sociology.

“I’ve tried other antidepressants but this is the first that has launched me towards life goals,” they wrote in an email.

The challenge is that Reinert plans to move to Australia in a year, where ketamine treatments are much, much harder to find. They are working with their psychiatrist to come up with a plan to drastically reduce their use of the medication.

The longest Reinert has been off the drug was three weeks, and they said their mood plummeted. They were a little worried about life without ketamine.

“They say it’ll be six sessions, but from my experience it does seem to be a long-term thing,” Reinert said. “And once you stop, the benefits also stop.”

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Dawn Fallik is a medical and science reporter specializing in data analysis. She worked as a staff writer for The Associated Press, St. Louis Post-Dispatch, and The Philadelphia Inquirer, and has won awards for investigative reporting, feature writing, and column writing. She is now a professor at the University of Delaware.