Ketamine prescriptions for chronic pain have skyrocketed more than 500 percent in just five years, but a major new scientific review finds no solid evidence the drug actually works for long-term pain relief—and warns it may cause serious side effects, including delusions and paranoia.
“We would encourage clinicians to have frank discussions with their patients about the uncertain benefits and potential for distressing side effects,” Michael Ferraro, the review’s first author and doctoral candidate at the University of New South Wales (UNSW) and Neuroscience Research Australia (NeuRA), told The Epoch Times.
The growth in ketamine use comes as doctors search for alternatives to opioids in treating chronic pain. Originally developed as an anesthetic for medical procedures and short-term pain relief, ketamine is increasingly being prescribed “off-label”—meaning for conditions beyond its approved uses—to treat both chronic pain and depression.
Significant Side Effects Raise Concerns
The review, recently published in Cochrane Library, not only warns that using ketamine off-label to treat chronic pain lacks solid scientific support, but also that the drug may pose health risks.
Conducted by researchers from UNSW Sydney, NeuRA, and Brunel University of London, the review analyzed 67 randomized controlled trials involving more than 2,300 adults.
The findings show that when compared against placebos, there is no clear proof that ketamine helps with chronic pain, and it carries the risk of side effects, including delusions, delirium, paranoia, nausea, and vomiting.
The evidence for ketamine in chronic pain was rated as low to very low certainty because many of the studies examined were of poor quality and had small sample sizes.
Ketamine works to block nerve-related pain by binding to N-methyl-D-aspartate receptors on the nerves. At high doses, ketamine causes complete loss of sensation and consciousness, while at low doses, it provides general pain relief and sedation. Ketamine is currently approved by the Food and Drug Administration for general anesthesia.
Ferraro emphasized that he and his team are not saying ketamine is ineffective, but rather that there is significant uncertainty: The data could indicate a benefit or no effect at all. However, given what the review found, they cannot say for certain.
The challenge lies in dosing. Doctors struggle to find the right amount that might provide pain relief without triggering psychological symptoms. This is not always achieved, Ferraro noted.
“Our findings indicate that guideline recommendations to use ketamine may be premature,” he added in a statement. “Given the widespread use and uncertainty around benefits, policymakers should urgently consider funding definitive trials of ketamine for chronic pain.”
The review authors hope their research will help guide patients and clinicians in assessing risks and benefits while emphasizing the need for more rigorous research.
Growing Demand Amid Opioid Crisis
The surge in ketamine use highlights the medical community’s search for alternative pain management options amid the opioid crisis, which has led to stricter regulations on narcotic painkillers. However, researchers caution against rushing into widespread adoption without sufficient evidence of safety and efficacy.
“We’ve seen the harm that can come from taking medicines developed for acute pain and applying them to chronic pain—opioids are a prime example,” James McAuley, a professor at UNSW and senior researcher at NeuRA, said in a statement. He noted that currently, a similar pattern may be developing with ketamine.
The review found no evidence that ketamine effectively treats depression in chronic pain patients or helps those who have developed tolerance to opioids—two benefits often cited by proponents.
“This group of drugs, and ketamine in particular, are in relatively common use for chronic pain around the world. Yet we have no convincing evidence that they are delivering meaningful benefits for people with pain, even in the short term,” co-senior author of the review Neil O’Connell, a professor at Brunel University, said in a statement.
Clinicians Defend Ketamine’s Role
Not all pain specialists agree with dismissing ketamine entirely. Dr. Evan Peskin, a dual-board certified anesthesiologist and pain medicine physician who co-founded Sanctuary Healthcare, a ketamine treatment center, argues there is a “long history” of research showing the drug’s value for nerve-related pain conditions.
“It’s inconsistent to dismiss ketamine as having ‘no evidence’ while also acknowledging the data may point to a benefit,” Peskin said.
He noted that for patients with severe, treatment-resistant conditions such as nerve damage or complex regional pain syndrome—a form of chronic pain that usually affects the limbs—ketamine can be an “important option” when other therapies fail.
Peskin said that ketamine is not experimental, calling it “a well-established anesthetic with decades of safe use when administered under proper protocol.” He compared temporary side effects such as nausea and dissociation to chemotherapy’s side effects, arguing that “short-lived discomfort” should not overshadow potential long-term relief.