Ketamine's risks are under scrutiny as experts warn a crackdown could worsen access

Since 2020, ketamine therapy has been the only thing that effectively treats Mark's complex post-traumatic stress disorder (CPTSD), a mental condition akin to PTSD that, in Mark's case, stems from childhood developmental trauma. When Mark, a 73-year-old who worked in finance before retiring, learned that his provider was under investigation by the Drug Enforcement Agency (DEA) and would no longer be prescribing the anesthetic drug, he feared he wouldn't be able to get another prescription before his symptoms became debilitating. He was already out of the country in Mexico stretching his supply until he got back, and soon, his depression began to set in again.

"The only ketamine I could have gotten, had I pursued it at the time, would have been black market ketamine," Mark, who is using his first name only to protect his privacy, told Salon in a phone interview. "I didn't have a backup antidepressant, and I was terrified."

In Mexico, Mark could buy Prozac over-the-counter, and this antidepressant medication had helped him in the past to stabilize his depression. However, it could take a month or two to fully take effect, and ketamine plus intensive psychotherapy were really the only things that broke through to treating his CPTSD. Mark writes about his experience using ketamine online and is well-connected to existing resources, so he was able to rapidly find another provider. Within just a few weeks, he had another prescription of lozenges, or oral ketamine tablets, delivered to his home in Pennsylvania.

"It's not like finding another primary care provider or orthopedic surgeon, and this is an exceedingly difficult task for someone who is mentally ill to accomplish," Mark said. "I [was terrified] the DEA would suspend all other practitioners and maybe I wouldn't get my shipment."

Ketamine, an anesthetic administered through infusions that can have psychedelic properties, has been hailed as a life-saving treatment for some patients. Although it has not been approved to treat mental health conditions, it is increasingly being used off-label to treat depression, suicidality and PTSD, said Dr. Brent Turnipseed, the medical director of a ketamine clinic Roots Behavioral Health in Austin, Texas.

"We have many success stories where people have their function restored and can go back to school or get back to their job or their relationship improves — or they are not contemplating suicide anymore," Turnipseed told Salon in a phone interview. "We have many, many good experiences from using ketamine."

Like any drug, ketamine also carries risks, and some are concerned that the proliferation of clinics providing this treatment has outpaced what regulatory systems can support. Much of that concern stems from the relaxation of telehealth regulations that allowed doctors to prescribe oral ketamine tablets to patients at home, rather than having it be administered intravenously in a clinic.

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This summer, Martthew Perry's autopsy reported he died from the "acute effects of ketamine," putting into question how the drug is regulated. Perry also had multiple drugs in his system, including buprenorphine, a drug that treats opioid use disorder. He had been diagnosed with coronary artery disease and was found to have drowned in a hot tub.

Following the arrests made in connection to Perry's death, in an interview where CBS Face the Nation host Margaret Brennan likened ketamine abuse to the beginnings of the opioid epidemic, DEA administrator Anne Milgram said the agency would similarly target doctors and practitioners "who are violating this duty of trust to their patients by over-prescribing medicine, or prescribing medicine that isn't necessary."

However, some experts caution that overregulating ketamine carries its own risks and could decrease access for patients who depend on it to maintain their mental health. With a few high-profile cases like Perry's death recently circulating in the news, others are questioning whether it is time to develop a stronger regulatory network for ketamine prescribing to prevent misuse and diversion.

"There are some very good, high quality practices out there, and I think it's important that we set some of these guidelines," said Dr. Sandhya Prashad, president of the Association of Ketamine Physicians, Psychotherapists and Practitioners (ASKP3), the largest organization of ketamine providers in the country.

Ketamine is approved for anesthesia but the Food and Drug Administration (FDA) has not approved it for depression, except for a pricey version of the drug known as Spravato (esketamine.) Doctors can still prescribe ketamine for depression off-label, but insurance often won't cover drugs prescribed in ways the FDA hasn't approved.

All of this limits the data researchers have on how many people are prescribed the drug, in what doses, and the frequency of safety concerns, said Dr. Gerard Sanacora, a psychiatrist at Yale University who studies ketamine. The FDA has required Spravato be administered under a strict risk evaluation system to track this information.

"There is real concern that ketamine is a drug of potential abuse, and there is very little regulation about how it is being prescribed and used," Sanacora told Salon in a phone interview. "I've heard a lot of people say, 'Well, it's not as bad as oxycodone or it's not as bad as opioids.' Well, that's true, but it doesn't mean that we don't have to be concerned about it."

There has been an increase in adverse events related to ketamine reported in national data systems. Still, those events remain relatively low, said Joseph Palamar, PhD, a drug use epidemiologist at NYU Langone. The DEA has also reported increased seizures of illicit ketamine in recent years at rates far lower than seizures of fentanyl or other far more deadly and prevalent illegal drugs. The DEA did not respond to Salon's request for comment.

" Reports to poison control , for example, have increased over the years, but it's nothing compared to opioids or cocaine or anything like that," Palamar told Salon in a phone interview.

At this point, the scale of ketamine misuse hardly compares to the opioid overdose crisis, which kills tens of thousands of Americans every year. In a national survey of U.S. adults conducted between 2015 and 2019, 0.13% of the population reported using ketamine in the past year. Meanwhile, 3.1% of the population reported misusing prescription pain relievers like opioids or fentanyl in the past year in the 2021 National Survey on Drug Use and Health.

Since 2021, more than 100,000 people in the U.S. have died each year from the overdose crisis, whereas ketamine was detected in 0.5% of overdose deaths in 2023, which corresponds to 107 deaths. Moreover, 82% of those deaths in which ketamine was detected involved other substances like fentanyl or methamphetamine, according to data from the Centers for Disease Control and Prevention .

People can develop a dependency for ketamine and have misused it with side effects to the bladder and other organs. Still, its potential for addiction is far lower than opioids, which can cause deadly physical withdrawals .

"From a toxicology perspective, [ketamine] is objectively safer than many other drugs, especially when compared to opioids," said Dr. Ryan Marino, the medical director of toxicology and addiction medicine at University Hospitals in Cleveland. "Matthew Perry's tragic death by drowning while intoxicated illustrates that the greatest risks from ketamine are not direct effects of the drug but from using outside of medical settings or without proper monitoring."

Recent media attention stemming from high-profile cases of ketamine use have shone a light on misuse. In addition to Perry's death, ketamine was also involved in Sean "Diddy" Comb's high profile charges . In a different but also highly publicized case from 2019, first responders injected Elijah McClain , a 23-year-old Black man, with ketamine against his will. He later died after being restrained by police , the cause determined as ketamine overdose. The paramedics responsible were sentenced earlier this year with 14 months in jail .

Providers told Salon they haven't seen a widescale crackdown on ketamine clinics yet. In January, the DEA charged two doctors in St. Louis, Missouri for distributing ketamine without authorization, and the agency also charged two doctors in connection to Perry's death this summer.

The DEA also suspended the controlled substances license of Dr. Scott William Smith, Mark's doctor, who became licensed to prescribe ketamine in 48 states under the relaxation of the telehealth regulations during the pandemic. In a Reddit thread addressing the situation, Dr. Smith said he was put under scrutiny because he did not obtain state controlled substance certificates in Connecticut and Oklahoma and failed to sign up for state Prescription Drug Monitoring Programs in several states. He did not respond to a request to comment before this story was published.

"Ultimately it is my responsibility to meet these requirements. I failed due to my lack of fully understanding how the PDMP system does and does not function across all 50 states," Smith wrote. "I would like to openly apologize to this entire community for failing you in this manner."

Dozens of patients on Smith's Reddit thread wrote to share their gratitude for how his services had changed their lives. Online services, including numerous telehealth companies , also send ketamine to patients' homes virtually. These companies have the potential to increase access to the medication and reduce cost, yet online and take-home services also increase the chances of misuse or diversion, Turnipseed said.

Introducing new regulations for ketamine prescribing could help organize the $3 billion ketamine industry that has developed in recent years. The ASKP3 regulates some 600 clinics that administer in-office intravenous ketamine, but thousands of other providers are estimated to operate in other clinics and online.

"I'm sure there are many that are practicing at a very high level of integrity and medical sophistication, but I'm sure there are also some that are not," Sanacora said.

Still, others are cautious of the harm that could be done with overregulating ketamine.

"One thing we actually know very well is that criminalization and prohibition of drugs drives people to use drugs in less safe ways and can actually increase risks of harms like overdose and death," Marino told Salon in an email. Indeed some critics have pointed to the DEA's crackdown on opioid "pill mills" with pushing more people to use street heroin and eventually fentanyl, which resulted in overdoses soaring as prescriptions fell . As with any health policy, it's likely the most effective means of regulating the industry lies somewhere in the middle.

"It's that balance between having access to the people that really could benefit from this ... and making sure that we're not causing more harm overall than we're benefiting," Sanacora said.