Mysteries of Ketamine: Unraveling its Mechanism in Alleviating Chronic Pain
Discover the life-altering effects of ketamine for chronic pain sufferers Explore the potential mechanisms behind its success Join CNN Health's newsletter for more
Emily Ryan's life underwent a dramatic transformation virtually overnight while she was in her first year of college.
She had been preparing for her final exams and came back from the library at around 10 p.m. Wanting to be considerate of her roommate who was already asleep, she tiptoed quietly to her bed.
Around 3 a.m., she woke up with intense pain radiating across her back.
"I could not feel my legs anymore," Ryan said. She also smelled urine. The sheets underneath her were soaked.
"At 19 years old, I didn't wet the bed, so it was quite unexpected."
That frightening incident marked the beginning of a 10-year search for relief from constant pain. Ryan eventually found it in an unexpected and controversial place - the psychedelic drug ketamine, which she now receives through intravenous infusions every 90 days, despite experts' differing opinions.
Since the 1970s, ketamine has been utilized as a surgical anesthetic. Its use became widespread in field hospitals during the Vietnam War due to its non-depressant effects on breathing and heart rate, unlike some other types of anesthesia. Additionally, it has the ability to elevate blood pressure and heart rate, which can be beneficial for patients who have experienced blood loss.
Matthew Perry at the premiere of "The Invention of Lying" in Los Angeles on Monday, Sept. 21, 2009.
Matt Sayles/AP
Autopsy shows Matthew Perry died of acute effects of ketamine
Like some other psychedelics, ketamine has also proven to be helpful for treating depression and trauma.
In 2019, a nasal spray version of the derivative ketamine, called esketamine, received approval from the US Food and Drug Administration for patients with treatment-resistant depression. Additionally, some hospitals and specialized pain clinics utilize off-label ketamine infusions to address severe and persistent pain, such as the type experienced by Ryan.
Dr. Pavan Tankha, a pain specialist at the Cleveland Clinic treating Ryan, expressed that many pain doctors view ketamine treatment as mysterious and questionable. Ketamine works rapidly in the body and is also eliminated quickly, typically within hours.
Despite skepticism from experts, Ryan and other chronic pain sufferers report experiencing months of relief following ketamine treatments. Tankha aims to raise funds for more comprehensive research on ketamine's effectiveness in treating chronic pain.
"The receptor binding typically lasts for 10 to 15 minutes, or possibly a few hours if you're fortunate. However, the extended duration of action raises the question - why does it continue to work for so long?" Tankha pondered.
"We are investigating the secondary effects resulting from the binding of ketamine. What other processes in the brain contribute to the prolonged therapeutic effects?" he explained.
29-year-old Emily Ryan, residing in Cincinnati, Ohio, is grateful for the relief she has found in ketamine treatment, despite not fully understanding how it works.
Getting to this point was a long journey. When her parents arrived at the hospital the night she woke up paralyzed in college, doctors initially suspected an infection or kidney stones due to blood in her urine. However, those possibilities were ruled out quickly.
At the local childrens hospital, they put the teen into an MRI machine and gave her a pair of special goggles so she could watch the movie "Frozen."
She watched it through once. And then again.
After the third time, I realized that something was seriously wrong if I was still stuck in this tube. It turned out to be a tumor pressing on my spine. Thankfully, it wasn't cancer, but the doctors explained that it was in a location that was compressing my nerves. They also admitted that they were uncertain how to treat it because the tumor was in a risky area, and surgery to remove it could potentially cause paralysis.
CNN
Study shows that ketamine infusions are effective in alleviating symptoms of depression, anxiety, and suicidal thoughts. Despite relying on a walker and experiencing bladder control loss, she tirelessly sought relief from her constant pain.
The doctors continued to prescribe narcotic painkillers, but both Ryan and her mom expressed fear of the drugs. "I don't want my insides to deteriorate and risk becoming dependent on medication," said Ryan. "It's a scary thought to think that this could be my reality for the rest of my life."
Her bladder incontinence improved after surgeons implanted a pacemaker device for her bladder. She also sought relief from her pain through the pain management program at the Cleveland Clinic.
Ryan underwent various procedures, including epidurals and long-term medications, in an attempt to alleviate her pain. Despite frequent visits to the pain clinic over four years, her condition did not improve. In addition, new tumors appeared along her spine during this time.
"When I tell you I have tried everything, we have tried everything," Ryan said.
The experience has been financially and emotionally draining.
Tankha, her pain specialist, was persistent and recommended that Ryan consider ketamine infusions for the treatment of her chronic pain. He explained that this treatment has been in use since the 1980s and was initially intended for the rare condition known as complex regional pain syndrome, or CRPS, but has shown potential for other chronic pain conditions as well.
While working at the VA hospital in New Haven, Connecticut, Tankha administered ketamine infusions to patients with CRPS. Another patient, who suffered from a different type of chronic pain, inquired about the possibility of using the same infusions for their discomfort. Tankha clarified that there were no studies on the use of ketamine for that particular type of pain, but the patient was willing to give it a try, so Tankha proceeded with the treatment.
After successfully undergoing the infusion, this individual experienced four months of relief. This got me thinking - if it works for him, who else could benefit from it?
Medical experts believe that chronic pain, such as Ryan's, has the potential to rewire the nervous system, resulting in increased sensitivity and susceptibility to pain triggers. This phenomenon, known as centralized pain or central sensitization, can manifest in various conditions, including arthritis and fibromyalgia. In such cases, the body begins to generate its own form of pain, known as neuropathic pain.
According to Dr. Steven P. Cohen, a professor at Johns Hopkins School of Medicine, approximately 15% to 35% of individuals with conditions like arthritis, neck pain, or back pain experience a significant presence of central sensitization. This means that their pain levels are much more intense than would be indicated by X-rays, even if they have an underlying condition like arthritis.
Cohen helped develop the American Academy of Pain Medicines 2018 guidelines for the use of ketamine in treating chronic pain.
US Customs and Border Protection officers in Atlanta intercepted nearly 100 pounds of Ketamine Hydrochloride on May 16.
Mani Albrecht/US Customs and Border Protection Office
Illicit ketamine on the rise in the US, research suggests
He says ketamine binds toand blocksa receptor in the brain thats responsible for the central sensitization of pain in the body.
According to Cohen, some people describe it as a way of resetting the nervous system. However, this explanation may not fully clarify the mechanisms of its effectiveness. In the approximately seven placebo-controlled trials involving ketamine for chronic pain, most have been small in scale and patients often accurately determine when they receive it. This raises the possibility that the reported benefits may be influenced by bias in the study.
He expressed skepticism about the strength of the evidence, and questioned the unclear biological mechanism behind the continued effectiveness of ketamine long after it has left the body. If ketamine blocks pain receptors, why does it still work after it is no longer present in the body?
Cohen suggests that ketamine has been demonstrated to have long-term effects on emotion, which plays a significant role in the sensation of pain; perhaps the drug is not only affecting pain signals in the body but also the distress it induces.
"It could involve varying mechanisms for different individuals, and there may be some overlap," he remarked.
Throughout the years, Tankha has perfected the treatment by administering a lower dosage of ketamine over a longer duration to minimize adverse effects. Patients receive infusions lasting 1 to 3 hours each day in a specialized clinic, where they are closely monitored and assisted during their hallucinogenic experiences. Potential negative side effects of the treatment can include nausea, vomiting, disorientation, confusion, and a loss of coordination. Ketamine may also elevate blood pressure and heart rate, as well as increase breathing and heart rate.
Ryan mentions that she takes an anti-nausea medication before her treatments and feels exhausted afterward. She typically returns to her hotel room and rests.
Ketamine infusions, as Tankha mentioned, are utilized in other specialized pain clinics, often based on the experience of a specific provider. However, it is not widely accessible, and clinics that do offer it typically have lengthy waiting lists for patients seeking treatment.
{{img_placeholder_3}}
Emily Ryan gets ketamine infusions at the Cleveland Clinic for chronic pain.
Emily Ryan
Ryan mentioned that she brings headphones to listen to music during the 1 to 3-hour session. She expressed gratitude for being a happy tripper and shared that she has visions of her childhood dogs. "I went in with no expectations because I've tried so many things," Ryan said.
Upon returning to her hotel room after the initial treatment over a year ago, she recalls sleeping for approximately five hours. The following day, she woke up feeling as if she had never fallen ill.
"Since my treatments, I have been completely pain free," said Ryan, who has undergone five or six courses of infusions over five days each. The cost of ketamine infusions is high, but Ryan feels lucky that her state Medicaid plan covers her treatments, which have greatly improved her quality of life. Although she still has to cover the expenses of a five-day hotel stay and the co-pays, she believes it is a worthwhile investment.
Ryan mentioned that she used to consume 40 to 50 pills daily, but now she only takes 8. She added that she still relies on gabapentin for better sleep. Despite this, she has been able to work out at the gym and spend extended periods arranging flowers at her florist business, activities that she found difficult before. Emily, who used to struggle to walk her dog for more than a mile without experiencing pain, can now walk him for three to four miles without any issues, thanks to ketamine.
Outside experts caution that every patient may not experience the same good results.
Get CNN Health's weekly newsletter
Join us to receive The Results Are In with Dr. Sanjay Gupta every Tuesday, brought to you by the CNN Health team.
"Several individuals have experienced significant success with it," stated Dr. Charles Argoff, director of the comprehensive pain center at Albany Medical College.
"We still don't have a clear understanding of why ketamine is successful for some people in the long-term but not for others. It's unclear who is likely to benefit from it," Argoff stated.
Argoff emphasized the importance of using ketamine under the supervision of a qualified medical professional. He warned against the rise of ketamine clinics with questionable credentials and highlighted the recent death of actor Matthew Perry as a reminder of the potential dangers of using ketamine without proper oversight.
Ketamine infusion insurance coverage is inconsistent, according to Argoff. "This means that people may be spending significant amounts of money without any guarantee that it will be effective," he explained.
In the case of Emily Ryan, she has returned to her favorite activities such as playing tennis, pickleball, and participating in fitness bootcamps.
"Now I go to them with no issues," she said.
