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Ketamine-Assisted Psychotherapy for Chronic Pain and Depression: A Promising New Pilot Study

Chronic pain is defined as pain that persists for longer than three to six months or, when associated with an injury, beyond the normal healing time. It is often multifactorial and dynamic, meaning chronic pain can wax and wane, frequently recurring and persisting despite treatment. Unsurprisingly, many individuals suffering from chronic pain also experience comorbid depression and high rates of alcohol and substance abuse, often as a means to cope and self-medicate. In addition to negatively affecting the quality of life for those afflicted, chronic pain and the frequently associated depression impose a significant financial burden on the nation, rendering many individuals unable to work. Chronic pain and depression are among the leading causes of long-term disability. Chronic pain accounts for more than 25% of all lost workdays and over 20% of all workers' compensation claims. Depression, on the other hand, costs the global economy an estimated $1 trillion per year in lost productivity, according to the World Health Organization (WHO).

While there is certainly a need for more effective treatments for chronic pain, ketamine presents a promising dual role in addressing both difficult-to-treat pain and mood disorders such as major depressive disorder and anxiety, which often coexist. A new pilot study investigated two different ketamine-assisted psychotherapy (KAP) approaches: one using a higher ketamine dose administered intramuscularly and the other using a lower dose taken orally. Researchers used ketamine to treat individuals who suffer from both chronic pain and major depressive disorder. Here is an in-depth look at the study and its findings.

Approaches to Ketamine-Assisted Psychotherapy (KAP)

While there are various ways to practice KAP, this study included two methods: the psychedelic approach and the psycholytic approach. Let’s take a closer look at each:

  • Psychedelic KAP: High-dose intravenous or intramuscular ketamine injections are followed by psychotherapy sessions 24-48 hours later. This method, which we utilize at Innerbloom, leads to alterations in consciousness where patients experience mystical or transcendental states. These experiences can lead to radical shifts in perspective, allowing patients to process trauma and confront deeply rooted psychological issues.
  • Psycholytic KAP: Low doses of ketamine are delivered via oral lozenges during therapy sessions. Patients experience mild alterations in consciousness, such as enhanced introspection, emotional release, and a slight loosening of psychological defenses. This approach facilitates emotional processing and insight while maintaining a relatively clear state of mind.

Chronic Pain Pilot Study Design

Ten adults with a prior diagnosis of major depressive disorder and a comorbid chronic pain condition were selected to participate in the study.

Participants were divided into two treatment groups: five in the psychedelic group and five in the psycholytic group.

Routes of ketamine administration were intramuscular (psychedelic group) and oral lozenges (psycholytic group). Those in the psychedelic group received two injections per session with escalating dosages in subsequent sessions, while those in the psycholytic group received oral lozenges with escalating dosages in subsequent sessions.

Participants underwent a total of six medicine sessions. Those treated with a psychedelic dose of ketamine completed psychotherapy sessions 24 hours after ketamine administration, while participants treated with a psycholytic dose of ketamine actively participated in a psychotherapy session immediately upon administration.

Participants completed various surveys throughout their treatment, including the Beck Depression Inventory (BDI), Brief Pain Inventory (BPI) Short Form, Generalized Anxiety Disorder (GAD-7) Scale, and Post-Traumatic Stress Disorder Checklist (PCL-5), to assess the impact on depressive, pain, anxiety, and PTSD symptoms.

Study Results

  • Safety: Both ketamine-assisted psychotherapy treatment approaches were well tolerated by all participants. There was no evidence of serious adverse events.
  • Pain Scores: The psychedelic group experienced a larger overall mean decrease in pain severity throughout treatment. The mean pain severity decreased by 21.88% in the psychedelic group, compared to a 3.39% decrease in the psycholytic group. The psycholytic group's progression was inconsistent, with a 32.81% decrease between session 1 and session 3, followed by a 24.56% increase between session 3 and session 6.
Average changes in pain severity measured at baseline and after sessions 1, 3, and 6 in both the psychedelic ketamine and the psycholytic ketamine treated groups
  • Pain Interference: The psychedelic group's pain interference, which refers to the extent to which pain hampers or disrupts various aspects of an individual's daily life, decreased by 36% throughout the sessions. In contrast, the psycholytic group's pain interference initially decreased but then increased, nearly returning to baseline.
  • Depression Scores: All participants, regardless of the treatment received, showed lower depression scores, with the psychedelic group exhibiting a more pronounced and persistent drop in depressive symptoms.
  • Anxiety and PTSD Symptoms: Secondary outcomes, including generalized anxiety and PTSD scores, also showed decreasing trends in both groups. However, the psychedelic group experienced more pronounced improvements, while the psycholytic group showed an initial decrease in PTSD scores, followed by a subsequent increase.

Final Thoughts

Although the results were not statistically significant due to the small sample size, the study suggests that both KAP approaches can decrease symptoms of pain, depression, anxiety, and PTSD. However, the psychedelic approach showed more consistent and marked overall improvement in symptoms. This indicates that higher doses of ketamine administered intramuscularly or intravenously, potentially due to more intense and transformative altered states of consciousness, could be more effective therapeutically through a fully psychedelic experience.

While further research with a larger sample size is needed, the results of this pilot study align with our clinical experience at the Innerbloom ketamine and psychedelic clinic in San Luis Obispo, CA. We have observed that pain patients typically require higher doses and experience improved outcomes when ketamine-assisted psychotherapy is incorporated into their treatment on days separate from medicine sessions. Future high-quality research could enhance our understanding of ketamine therapy for chronic pain and lead to improved treatment protocols. Additionally, increased implementation of ketamine-assisted psychotherapy may improve symptoms and pave the way for greater acceptance and use of other psychedelic-assisted therapies, that include substances such as psilocybin, LSD, and MDMA, which also have potential therapeutic effects for the treatment of mental health and pain.

About the Author

Dr. Ray Rivas, a former general and trauma surgeon with over a decade of experience utilizing ketamine, became a ketamine therapy specialist to treat mental health and pain after witnessing its profound impact on his hospital trauma patients and his own mental health. As the founder and medical director of Innerbloom Ketamine Therapy in San Luis Obispo, California, Dr. Rivas applies his extensive medical expertise to provide safe, evidence-based ketamine treatments for mood disorders, including depression, anxiety, PTSD, and chronic pain. His passion lies in helping patients find relief and rediscover hope through personalized, compassionate care.

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