Ketamine-Assisted Therapy: A New Paradigm for CRPS Treatment

Written for RSDSA by Benjamin Mati, MD – Owner & Medical Director of Horizon Healing

Complex Regional Pain Syndrome (CRPS) is a partially understood condition that can profoundly affect the physical, emotional, and spiritual quality of life of those who suffer from it. Anxiety and depression are often intertwined with myriad physical symptoms, creating a complex constellation of suffering.

While the standard of care involves a multimodal approach—ranging from neuropathic pain medications and nerve blocks to spinal cord stimulation—treatment failure remains very common. Ketamine has emerged as a medical whose unique properties show potential for treating both the physical and non-physical symptoms of CRPS.

What is Ketamine?

Ketamine is an FDA Schedule III medication, placing it in the same class as Tylenol with codeine. Known as a “dissociative anesthetic,” high doses temporarily reduce the brain’s awareness of the senses, creating a dissociation between mind and body.

Since the 1970s, it has been a staple in emergency medicine, anesthesia, and hospital medicine. It is considered so safe and effective that it is the World Health Organization’s (WHO) Essential Medicines List for all health care systems. Since the late 1990s, research has shown it to be a rapid, effective, and safe therapy for depression, PTSD, anxiety, and pain disorders. While these uses are “off-label” (not officially sanctioned by the FDA), they are allowed and supported by studies indicating safety and efficacy.

How Does Ketamine Work?

The human brain is complex, and we are only beginning to understand how substances interact with consciousness. However, we know that Ketamine acts on many receptors and areas of the body and brain. One important action is as an N-methyl-D-aspartate (NMDA) receptor antagonist which seems to do several things:

• Releasing the Brakes: Essentially, it “takes the foot off the brakes,” stopping brain cells that usually inhibit activity and allowing specific brain cells to become more active.
• New Connections: This increased activity can create new connections between brain areas. Ketamine stimulates the growth of brain cells and enhances neuroplasticity—the brain’s ability to change its structure and connections.
• Network Reset: It appears to turn down activity in the “default mode network” while promoting connectivity elsewhere

For CRPS specifically, ketamine decreases the activity of inflammatory cells and pain centers in the brain, interrupting the feedback loops associated with pain interpretation.

Methods of Delivery

Ketamine can be delivered in several ways, each with unique characteristics regarding onset and depth of experience.

Ketamine Therapy vs. Ketamine-Assisted Therapy (KAT)

It is important to distinguish between two different models of care.

• Ketamine Therapy (The Biomedical Model)
  • This model views ketamine primarily as a pharmacological intervention for “disorders”.
  • Focus: Treating symptoms and improving brain function
  • Limitations: It often assumes the mind and body are separate and may overlook social, emotional, and spiritual dimensions
  • Support: Often offered with minimal or no therapeutic support, and practitioners may lack specialized training in psychedelic-assisted therapy
• Ketamine-Assisted Therapy (KAT)
  • KAT draws from healing traditions that prioritize self-discovery and personal agency.
  • Focus: Ketamine is viewed not as a cure, but as a catalyst for accessing inner healing resources.
  • The Container: Providers are usually licensed professionals trained in creating a safe “container” for the experience.
  • The Process: Includes preparatory sessions to lay a foundation and integration sessions to help clients incorporate insights into daily life over weeks or months.

Ketamine for the CRPS

NMDA receptor overactivity is thought to play a key role in central sensitization, a process where the nervous system amplifies pain signals. By dampening this pathway, ketamine may help “reset” abnormal pain signaling. Current research suggests that ketamine therapy decreases pain symptoms in those suffering from severe CRPS. However, most studies focus on the biomedical IV model, using pain scores as the only endpoint.

Ketamine-Assisted Therapy seeks to meet patients where they are—addressing physical, emotional, psychological, and social symptoms simultaneously. While ketamine addresses physical symptoms, KAT does not hold that there is something to “fix”. Instead, it helps uncover new perspectives and reveal habitual ways of thinking. With the support of trained staff, KAT provides more than just medicine; it creates a holistic healing environment.