IV Ketamine Shows Promise for Chronic Pain, But Doubts Remain

The Littleton, Colorado location of Ketamine Wellness Centers is in the basement level of an inconspicuous suburban office building. The largest of its four treatment rooms contains a wall-mounted TV, a couple of chairs piled with pillows, and a comfy black recliner next to an IV pole.

Infusions last about an hour. A registered nurse or paramedic is in the room at all times, monitoring heart rate and rhythm, blood pressure and oxygen saturation. Some patients play music or watch videos during their treatment. Some bring family members and talk, some bring eye masks and don’t.

Dissociative effects begin within minutestingling in their hands, maybe, or a sensation of floating, or brightly colored patterns or images from childhood when they close their eyes. Many feel a change immediately. “After that initial round of treatment,” said Michael Gustin, a 39-year-old Colorado resident with chronic nerve pain, “the world got better.”

IV ketamine infusion has caused a lot of buzz as a therapy for treatment-resistant mental illnesses like depression, but it has a second use that might be even more compelling: for treatment-resistant chronic pain. In the context of the opioid-involved overdose crisis, the fact that it’s helping people like Gustin switch from prescription painkillers has added significance.

Gustin suffers from chronic ulnar neuropathypainful, tingling nerve damage, like if you hit your funny bone and the sensation never went awayin his left arm, caused by a fall. By the time Gustin started ketamine, he’d been taking 10 mg of Oxycodone three times a day for a decade. He wanted an alternative.

“I lived from prescription to prescription,” Gustin told Filter. “I took my pills as prescribed, but my life was gonna be nothing but living from dose to dose.” He began IV ketamine in May 2018. He was off opioids by the Fourth of July.

Ketamine has shown intriguing promise with neuropathic pain (chronic pain resulting from nerve damage). That includes even trigeminal neuralgia, an incurable form of facial nerve pain resistant to most medications, including opioids, and so excruciating that it’s known colloquially as “the suicide disease.”

“Before ketamine, I wouldn’t even be out the door … now I carry with both arms equally.”

Ketamine Wellness Centers (KWC) considers treatment “successful” if it results in a 40 percent or more reduction in symptoms over time. The success rates it reports for fibromyalgia and chronic migraines is 80 percentabout the same rate that it reports for depression. For complex regional pain syndromea rare, incurable, often excruciating condition characterized by burning sensations and extreme sensitivityKWC reports a success rate of 90 percent. “We have a lot of people who get off their opioids, which is pretty awesome,” said KWC Clinical Administrator Shannon Keane.

For the first time since his fall, Gustin can carry things with his left arm. He described a post-ketamine visit to his disabled aunt to help her clear out around 40 boxes of medical supplies. “They’re not heavy, cuz they’re full of diapers, but still, 40 boxes,” Gustin said. “Before ketamine, I wouldn’t even be out the door to be able to help my aunt with that stuff. But to be able to lift boxes, to load and unloadI wouldn’t even hold a grocery bag in my left arm before I had the ketamine infusion, and now I carry with both arms equally.”

He can also run a snowblower again. He’s thinking about riding a roller coaster this summer for the first time in 10 years. He said most of the pain he feels in his arm these days seems to be from actually using it again.

“I’ve been so happy to be opioid-free, I cannot tell you,” Gustin said. “That’s what led me to the ketamine thing. I thought, y’know, the opioids I’ve been on, the pills my doctors have prescribed for insomnia⁠—they’re more dangerous than the ketamine, so why not try this?”

It should be noted that rates of problematic use or overdose for people who are prescribed opioids are very low (which hasn’t stopped onerous requirements being imposed on these patients in response to the perceived “opioid epidemic”). But all drugs come with potential risks and limitations, and it’s beneficial for patients to have choices.

An Unregulated Landscape

The FDA approved the first intravenous ketamine preparation for human use in 1970, and it’s been used to induce a state of temporary anesthesia, safely and with minimal side effects, ever since. It often causes feelings of dissociation, including hallucinations, but it doesn’t slow your breathing or lower your blood pressure the way other anesthetics do.

Ketamine’s history is why the FDA classifies it as a Schedule III drug, meaning it ostensibly has recognized medical value and a low-to-moderate potential for dependency and problematic use. The rising number of private ketamine clinics around the country can get the drug from the same big distributors that supply hospitals, like McKesson Medical-Surgical, or pretty much anywhere you can buy medical supplies. This makes ketamine very easy to prescribe. It also means the recent explosion in popularity is playing out in an unregulated market.

“The problem with IV ketamine is that it’s a generic drug,” said Dr. Steven Cohen, a professor of anesthesiology and critical care medicine at the Johns Hopkins University School of Medicine and a lead author of the national consensus guidelines issued in 2018 in response to the IV ketamine boom. This means there’s no financial incentive to conduct research. “No [company] stands to make huge amounts of money, such that they’re gonna perform trials that … would be millions and millions and millions of dollars.”

“The people who operate ketamine clinics … have a vested interest in these [treatments] working and reporting high success rates.”

Most of the promising statistics about IV ketamine infusions, then, are coming from the clinics that sell them. This doesn’t necessarily mean they’re not true, or that experiences like Gustin’s are aberrations. But it does mean that, for the time being at least, the evidence and people’s interpretations of it are mixed.

“This is the problem with pain,” Cohen said. “People have conflicts of interest. The people who operate ketamine clinics, obviously they don’t have equipoise, they have a vested interest in these [treatments] working and reporting high success rates. But there’s nothing that really reliably shows … the ability to reduce opioids in people with chronic pain.”

Clinics like KWC have screening processes for prospective patients, but the surge of interest in ketamineafter eight years as a one-clinic operation in Phoenix, Arizona, KWC has opened six more locations across five states in the last two-and-a-half years; nationwide, the total number of clinics is unknownhas brought concern about laxer standards. In this landscape, treatment may be administered not necessarily to the patients best suited for it, but simply to the patients who can afford it.

Infusions can cost upwards of $500 each, which puts long-term treatment in the neighborhood of $4,000 a year at the low end. Most insurance doesn’t cover it. As more and more infusions are sold across the country, experts are concerned that not all of them will ultimately be in patients’ best interests.

Evidence Still Lacking

“Having worked with chronic pain patients for 25 years, it is my opinion that it is simply naive to think that such a complex problem will be resolved by a drug, whether it be an opioid or ketamine,” Dr. Rae Frances Bell, an anesthesiology specialist at the Haukeland University Hospital in Norway, told Filter over email. “Analgesics generally have poor effect in chronic pain and may even compound the problem by causing dependency and adverse effects (and financial problems!).”

In the short term, ketamine seems safe and generally well tolerated. As Cohen noted, “people aren’t dropping dead from ketamine from respiratory depression.” In the long term, though, patient outcomes are a bit murkier.

“We do not know what are the long-term effects of repeated IV ketamine infusions for chronic pain,” Bell continued. “This particular treatment is not evidence-based, so it is extremely important that clinicians adhere to national guidelines and carefully document all treatment. What we do know is that ketamine has a range of dose-dependent adverse effects.”

Both Bell and Cohen referenced increasing reports of long-term complications like liver toxicity, ulcerative cystitis, potential for addiction, and cognitive impairment including memory loss and a decrease in the brain’s grey matter. The crucial variable herethe dosingis also an area where the limited peer-reviewed data is at odds with what you might hear from clinics and patients.

“Ketamine is not a panacea and if it is not used judiciously, I fear that some patients could be harmed and that ketamine may come into disrepute.”

An unregulated market allows for widely varying practices. Cohen said he’s been contacted by “many, many, many attorneys” and patients describing increased tolerance and a need for higher and higher doses, administered more frequently. Clinics like KWC, however, describe an experience of back-to-back infusions in the early days of treatment that gradually space out into a maintenance routine.

Over the past year, Gustin has been able to stretch his time between infusions from four weeks to eight. “Part of what I really like about this treatment is their goal is to see you less and less,” he said. “Not a lot of that going on in the medical world.”

Gustin now has a one-inch by two-inch tattoo of a ketamine moleculeon his bad arm. It was no more or less painful than any of his other five tattoos. “I’m the best version of myself that I’ve ever been because of it,” he said.

“Ketamine is a fascinating drug which can be very useful in specific medical settings,” Bell wrote. “It may also be useful for opioid-resistant pain in patients with terminal illness, although the evidence for this is limited. That said, ketamine is not a panacea and if it is not used judiciously, I fear that some patients could be harmed and that ketamine may ultimately come into disrepute.”


Photo via Pickpik/Public Domain

Kastalia Medrano

Kastalia is a journalist interested in stories about drugs, mental illness and public health. Her work has appeared in publications including Newsweek, Vice, Gizmodo, Vox and Teen Vogue. She is a volunteer at the Lower East Side Harm Reduction Center and lives in Manhattan.

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