How Ketamine May Help Pain
First it was a battlefield anesthetic, then a party drug with a hallucinogenic reputation. Now research is looking at ketamine as a way to treat pain. Here's what experts want you to know.
A new way to treat pain
For the 20 percent of Americans struggling with chronic pain, any new treatment is good news. And although the drug ketamine has been around for a long time for anesthesia, doctors are now starting to look at other uses for it.
“Ketamine is injectable anesthetic medication, which at low doses has been shown to be useful for acute and chronic pain,” says Asokumar Buvanendran, MD, interim chair of the Department of Anesthesiology at Rush University Medical Center in Chicago. “Also, there is evidence of low-dose ketamine being effective for depression.”
But its use beyond anesthesia is somewhat controversial because of some risks of addiction and side effects. Plus, the scientific evidence for its efficacy is still not complete or definitive.
Still, it may be a good option for some people who’ve been struggling to manage their pain. Here’s what you need to know about ketamine. (Find out more about how pain management specialists can help you treat chronic pain.)
What is ketamine?
First developed in the 1950s and ’60s, this chemical compound was used as an anesthetic during the Vietnam War.
“Ketamine is an anesthetic agent that has powerful pain-relieving properties and has been used for decades for pain relief and as an antidepressant, particularly in patients who have not responded to other treatments,” says Eric Schwenk, MD, a member of the American Society of Anesthesiologists’ Committee on Regional Anesthesia and Acute Pain, and associate professor of anesthesiology and orthopedic surgery in Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia.
Ketamine’s history took a darker turn a few decades later.
“While this is very uncommon now, ketamine was a popular party drug of abuse in the 1980s and 1990s because of its ability to alter perception,” says Dr. Schwenk.
In fact, your first thought when hearing the medication’s name may be of the hallucination-causing club drug, which went by names like “special K” and “vitamin K.”
Why is it being considered now for pain management?
In light of the ongoing opioid addiction crisis, doctors have been searching for new ways to treat pain, including with low-dose ketamine.
“It has received renewed interest in the research community in recent years as the United States continues to battle the opioid epidemic and tries to identify and study drugs that could be suitable alternative to opioids for pain management,” Dr. Schwenk says. “Ketamine is one such drug with a long-established record of safe use with generally mild and treatable side effects.”
He points to the different way ketamine works in the body: It primarily acts on different pain receptors than opioids. It also does not generally carry the same risks, such as impaired breathing, which can happen with opioid overdoses.
Results from studies on ketamine for pain have been encouraging.
“Researchers are looking into new uses because at low doses, ketamine has been found to help improve uncontrollable pain and improve patients’ response to pain medication,” says Olabisi Lane, MD, an assistant professor in the Department of Anesthesiology at Emory University School of Medicine and Emory Pain Center in Atlanta.
Plus, ketamine may also reduce opioid tolerance. And in some cases, it can prevent the need for higher doses of opioids, says Dr. Lane.
How ketamine works for pain
Ketamine works in several ways to help chronic pain. One way is by acting on a certain receptor called NMDA (N-methyl-D-aspartate) in cells in the body’s central nervous system.
“Studies have shown that the activation, or turning on, of the receptor can happen in chronic pain, making the patient more sensitive to pain,” Dr. Lane says. “The receptor can also be turned on with pain medication, which can lead to tolerance to the pain medication. Ketamine works by blocking, or turning off, the receptor, which can make pain medication work better or even help to reduce the amount of pain medication the patient is on and overall lessen pain.”
This is called a “dissociative state,” in which you feel less pain.
Researchers aren’t totally sure of all of ketamine’s mechanisms, though.
“It is not clearly known which other receptors this medication acts on to provide analgesia [pain relief],” Dr. Buvanendran says.
Researchers at Rush University are currently working on additional studies on the “receptor action” of ketamine.
In addition to reducing sensitivity to pain, ketamine also is broken down in the body into other molecules that have some pain-relieving properties themselves, Dr. Schwenk says.
What does the research show?
“Studies have shown that ketamine can improve pain in conditions that have historically been difficult to treat,” Dr. Schwenk says. “The relief is typically not permanent but can be dramatic in some patients.”
More research, though, is needed: In a 2019 meta-analysis published in the journal Anesthesia and Analgesia, only seven randomized controlled trials consisting of just 211 people in total met the criteria for inclusion. The review did find a benefit of ketamine for chronic pain over a placebo, but the authors noted that larger and longer-term studies are needed.
In 2018, given the growing popularity of ketamine for pain, several professional organizations—the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists—released ketamine guidelines for doctors.
The paper, of which Dr. Buvanendran and Dr. Schwenk were authors and which was published in the journal Regional Anesthesia and Pain Medicine, also noted the need for better research on ketamine’s effectiveness on different pain conditions, as well as the ideal dose range, long-term effects, and who best benefits.
How to take ketamine for pain
Although there are many ways for ketamine to be administered, it’s typically given at low doses through an IV in a monitored setting, says Dr. Lane. The patient can stay awake while they’re receiving the medication. It rarely impacts their breathing or heart function. They usually tolerate the drug and can be sent home the same day.
But, IV treatments aren’t exactly convenient.
“The current disadvantage of ketamine being used for chronic pain is that it needs to be administered intravenously; as such its use for chronic pain is challenging,” Dr. Buvanendran says. You’ll also need to make sure your insurance will cover the infusions.
Although Dr. Schwenk says the best evidence for ketamine for pain is through an infusion, other ways of giving ketamine may be in the works.
“While it is off label, ketamine can be prepared or ‘compounded’ in special pharmacies to be used as a nasal spray or oral medication in select cases when prescribed by a physician,” he says. “These are usually cases where most or all other pain medications have failed or a patient cannot tolerate alternatives. However, there is increasing interest in some of these other forms of ketamine in light of the opioid crisis.”
In some cases, Dr. Lane says that ketamine can also be applied on the skin as a cream or ointment.
Dangers of addiction or side effects
“Ketamine is a controlled substance and has the potential for abuse and addiction,” Dr. Schwenk says. “While ketamine does have its own set of side effects, such as hallucinations and nightmares [or vivid dreams], these are in a minority of patients. When given by a physician in intravenous form, steps are taken to minimize these side effects, including strictly controlling the dose, the duration, and sometimes giving other medications that can help decrease these side effects.”
Dr. Lane notes patients may also experience nausea, vomiting, or increased saliva production; when given in IV form it can cause an increase in heart rate and blood pressure.
However, “side effects of ketamine are minimal and depends on the route given and the dose,” she says. “All these are temporary and typically stop once the medication is discontinued.”
Still, Dr. Buvanendran says large, federally funded clinical trials are needed to study and fully understand the side effects.
Who might be a good candidate?
The best evidence for ketamine in chronic pain is in patients with complex regional pain syndrome (CRPS), fibromyalgia, and spinal cord injury, Dr. Schwenk says. There is some evidence that ketamine may also help with refractory headaches, which are persistent, debilitating headaches that don’t respond to traditional treatment.
Dr. Lane says people with nerve pain, cancer pain, and phantom limb pain may also benefit.
“Patients who are on increasing amounts of opioids but continue to have uncontrolled pain or are having increased sensitivity to [sensations] that are not normally considered painful, such as light touch, and those with chronic nerve pain of varying types should discuss a referral with their doctor,” she says.
In addition to pain relief, ketamine may also be helpful for improving mood, depression, or post-traumatic stress disorder (PTSD).
Who might not be a good candidate?
“Ketamine is not appropriate for everyone,” Dr. Lane says.
Because of the potential for abuse and addiction to ketamine, patients must be carefully assessed first by their doctor. The risk of abuse or addiction might be higher in people with a history of alcohol abuse or substance use disorder, she says.
You might not be a good candidate for ketamine if you have severe heart and liver disease, glaucoma, are pregnant, or have a history of a [liver] condition called porphyria. Dr. Schweck also says that ketamine abuse can lead to liver failure or bladder problems, so treatment should be carefully supervised by a doctor experienced in treating with ketamine.
Ultimately, “only a trained board-certified pain physician can evaluate the pro and con and make an appropriate recommendation,” Dr. Buvanendran says. If you have chronic pain and are interested in finding out more about ketamine for your individual case, talk to your doctor.
Next, check out these 16 quotes about pain to help you handle it.
- Centers for Disease Control and Prevention: "Prevalence of Chronic Pain and High-Impact Chronic Pain Among Adults: United States, 2016"
- Asokumar Buvanendran, MD, interim chair of the Department of Anesthesiology at Rush University Medical Center in Chicago
- Eric Schwenk, MD, member of the American Society of Anesthesiologists' Committee on Regional Anesthesia and Acute Pain, and associate professor of anesthesiology and orthopedic surgery in the Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia
- European Journal of Anaesthesiology: "History of anaesthesia"
- World Health Organization: "Opioid overdose"
- Olabisi Lane, MD, assistant professor in the Department of Anesthesiology at Emory University School of Medicine and Emory Pain Center in Atlanta
- Anesthesia and Analgesia: "Ketamine Infusions for Chronic Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials"
- Regional Anesthesia and Pain Medicine: "Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Chronic Pain From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists"