Combining ketamine and psychotherapy is a safe and feasible treatment with promising benefits for people experiencing chronic neuropathic pain, according to a new study by researchers at St. Michael's Hospital, the University of Toronto and York University.
Neuropathic pain occurs when nerves are damaged or compressed, leading to chronic pain. Symptoms may vary from a dull ache to burning or stabbing sensations that can affect different areas of the body.
The condition has a profound impact on a person's physical and emotional well-being.
"This is a novel treatment paradigm for a patient population that is suffering greatly," says Akash Goel, the study's lead author, a clinician-investigator at St. Michael's Hospital, Unity Health Toronto, and an assistant professor of anesthesiology and pain medicine at U of T's Temerty Faculty of Medicine.
The trial took place at St. Michael's Hospital between 2023 and 2025 and included 30 participants who were randomly assigned to receive one of three treatments: ketamine infusions, weekly psychotherapy sessions or both. Each treatment program lasted 16 weeks. In their paper published in the journal Med , the researchers report high levels of participant retention and treatment adherence, demonstrating the feasibility of this approach. Importantly, they did not observe any serious adverse effects related to the study's three treatment arms.
Twenty weeks after completing treatment, participants in all three groups reported less pain intensity, depression and anxiety. But those who received both ketamine and psychotherapy saw the greatest benefit. Nearly 80 per cent of participants in the combined treatment arm reported a clinically meaningful reduction in their pain interference score, which measures how much pain interferes with a person's daily life. That's compared to 50 to 60 per cent among those who received either ketamine or psychotherapy alone.
For study participant Carmelina Crudo, the trial brought long-lasting improvements in her health and overall quality of life.
"The pain was incessant, it was unbelievable," says Crudo, who has lived with chronic neuropathic pain for more than 20 years.
A surgery to address the initial cause of Crudo's pain provided temporary relief, but the physical demands of being a caregiver to her son and her mother caused an old injury - and pain - to flare back up. Crudo says the pain was so debilitating that she spent several years completely bedridden and unable to do basic tasks like dressing herself.
"I felt like I was living inside a torture chamber. It was very hard on my mental health because I was barely surviving and it became very isolating," she says.
As part of the trial, she received weekly psychotherapy sessions and three ketamine infusions over 16 weeks. Crudo says that while she had tried psychotherapy before and found it helpful, her experience in the study was unlike her previous psychotherapy sessions. She believes the ketamine treatments enhanced the effectiveness of psychotherapy by helping her mind and body feel more at ease and open to new things.
"When I started the ketamine and psychotherapy at St. Michael's, I could feel subtle changes happening," she says.
Her experience echoes the study's qualitative findings where participants in the combined treatment group described ketamine as creating "a temporary window of relief." Psychotherapy helped to harness these openings and turn them into sustained improvements.
"There is increasing data that ketamine might increase neuroplasticity, or the brain's ability to acquire and learn new concepts," says Goel.
He notes that people living with chronic pain often develop maladaptive thoughts, such as catastrophizing and rumination, that can prolong or worsen pain. Goel likens the brain of these individuals to a garden taken over by weeds.
"Ketamine allows us to basically remove those weeds and plant new seeds for new flowers to grow. It creates the conditions for us to administer the psychotherapy and for the patient to benefit long term," he says.
Participants who received both treatments also attributed their improvement to the combined intervention's ability to simultaneously address the biological and psychosocial aspects of pain.
Goel cautions that because the trial was designed as a pilot feasibility study and had a small sample size, the findings do not conclusively show that ketamine and psychotherapy together are more effective than either treatment alone.
"The signals were really promising and strong enough that it's encouraging us to proceed to do a multi-centre trial across Canada," he says.
The researchers hope to secure funding to conduct a larger, placebo-controlled trial that can generate stronger evidence about the effectiveness of a ketamine and psychotherapy combination approach to treat chronic neuropathic pain. Goel says he has already heard from six institutions in Ontario, Saskatchewan and British Columbia who are interested in participating in a study.
Crudo credits the ketamine and psychotherapy she received with improving her mental health and helping get her life back.
"It was instrumental in getting me to a place where I could start thinking more clearly, get more information and get more therapies," she says. "The mind shift really helped me get out of that dark place. I don't feel doom and gloom anymore. I wake up positive now and I love life."
Crudo has continued ketamine infusions and psychotherapy and incorporated other approaches to manage her pain. Today, she is grateful to be able to do the little things that she enjoys like going for a walk or swim, cooking a meal and spending time with her grandson.
"It's important to me that other people don't suffer the way that I did," she says.
"If my experience can help one person, then I'm all in."
The research was funded by the Canadian Pain Society, St. Michael's Hospital Innovation Fund and the Physician Services Incorporation.
