Does Ketamine Actually Help Chronic Pain?
No one can say for certain. A 2025 Cochrane review of 67 trials and more than 2,300 adults found no clear evidence of benefit for ketamine in chronic pain, with low to very low certainty, though its authors say the question remains open. Avesta uses ketamine off-label for chronic pain, after screening each patient.
How Does Ketamine Act on the Glutamate System?
At Avesta, we place our trust in science and therefore, base our clinical approach on research-backed theses. After years of teaching about ketamine to graduate students at Georgetown University, our lead clinician, Dr. Ladan Eshkevari, opened Avesta because recent scientific research has shown that ketamine can help decrease symptoms for many individuals with mood disorders, PTSD and chronic pain.
How Does Ketamine Work?
Ketamine acts on the glutamate system. Glutamate is a neurotransmitter that is present throughout the brain, and regulates brain functionality. It connects with many other neurotransmitter pathways to ensure normal physiological function.
When glutamate is not connecting the right neurons to the right receptors, physical and mental health problems can arise. Ketamine blocks neurons from connecting to certain glutamine receptors and sends them to different receptors where they can be more functional. This can lead to a decrease in mental health and pain symptoms. Ketamine works with a variety of receptors to exert its effects, some of which we are just starting to discover.
How Does Ketamine Work for Pain Management?
Scientifically, ketamine for pain management makes sense. Individuals with chronic pain commonly have an overactive N-methyl-D-aspartate (NMDA) receptor. The NMDA receptor is a glutamate receptor and ion channel found in neurons, but when it is not functioning at the level it should be, it can cause chronic pain. As published in USPharmacists.com, a resource for practicing pharmacists, “the activation of NMDA receptors has been associated with hyperalgesia, neuropathic pain, and reduced functionality of opioid receptors.” Ketamine blocks this receptor, which is how it can be helpful in regulating pain. Ketamine can also change the route of the neurons so they are no longer activating the NMDA receptor at the same levels.
What Does the Research Say?
According to an NIH meta-analysis, Ketamine for chronic pain: risks and benefits, “current data on short term infusions indicate that ketamine produces potent analgesia during administration only, while three studies on the effect of prolonged infusion (4-14 days) show long-term analgesic effects up to 3 months following infusion.”(1,2) There have been limited studies on ketamine’s effects on long term pain; however, there is some data to support that it has helped some chronic pain patients.
The same NIH review sets limits. Its authors found only three long-term placebo-controlled trials, reported that short infusions relieve pain mainly during the infusion, and advised restricting ketamine to patients with therapy-resistant severe neuropathic pain until benefits are shown to outweigh risks.
| Source | What it covered | Finding |
|---|---|---|
| Cochrane review (2025) | 67 trials, 2,300+ adults, five NMDA receptor antagonists including ketamine | No clear evidence of benefit for chronic pain; certainty low to very low; more psychotomimetic effects and nausea; authors say this does not show ketamine is ineffective |
| Niesters et al. (2014) | Review of ketamine for chronic pain | Strong analgesia in neuropathic pain (for example CRPS-1) mainly during infusion; 4 to 14 day infusions gave effects up to about 3 months; only three long-term placebo-controlled trials |
What Are the Risks Compared With the Possible Benefit?
The Cochrane review linked ketamine to more psychotomimetic effects, including delusions, delirium and paranoia, and to more nausea and vomiting. At Avesta, most people describe a floaty, dreamlike state that settles within about 20 minutes of the infusion ending, and dizziness, blurred vision or mild nausea are treatable on the spot.
A clinician is present and vitals are monitored for every dose, and emergency protocols and medications are on site at every clinic.
Who Is Most Likely to Be a Good Candidate?
A person with a diagnosed chronic pain condition lasting months or longer, whose standard treatments have not given enough relief, is the likely candidate. Screening happens before anything is booked, and being told no is a legitimate outcome of the consult.
| Likely a good fit | Avesta pauses or refers out |
|---|---|
| A diagnosed chronic pain condition lasting months or longer | Uncontrolled high blood pressure, or a recent heart attack or stroke |
| Medication, physical therapy or nerve blocks have not given enough relief | Active, untreated psychosis or mania |
| Stable or well-managed blood pressure and cardiac history | Pregnancy or breastfeeding |
| A ride home after each session and 3 to 5 consecutive treatment days | Active, unmanaged substance use; a history that points to a different treatment |
A clinician reviews your pain history, prior treatments and current medications in a free 30-minute consult and tells you candidly whether ketamine is a reasonable next step.
What to Expect During a Pain Management Ketamine Treatment at Avesta?
Prior to coming in, we will schedule a free phone consultation with you and Dr. Eshkevari, who has years of experience in anesthesia and pain management, to develop a treatment plan for your pain. At Avesta, the chronic pain protocol follows the Johns Hopkins protocol: 3 to 5 infusions on consecutive days, each about four hours long. During your first session, we will go over anything else you would like to discuss, take your vitals, and set up the infusion. Our treatment rooms are cozy, aesthetically pleasing and private. We provide blankets, and we have a comfortable waiting room if you bring a loved one with you. We recommend bringing headphones and a gentle playlist to listen to during your infusion. We will come in to take vitals and check on you a few times throughout the session, and when you are done, we will take final vitals and provide snacks and water.
Chronic Pain: Will Ketamine Work for My Pain?
First, we understand that chronic pain is difficult to live with, both for the patient, and their loved ones. As providers, we try to understand what is causing it. The overactivation of certain receptors is certainly part of the cause. Is ketamine going to work for your pain? The short answer is: maybe. We genuinely hope it does, but we cannot tell you with certainty that it will. We have patients in whom it has been immensely helpful; however, as with all treatment resistant health problems, no drug works the same for everyone. While our brains are all made up of the same components, the varying levels of neurotransmitters, hormones, and pathways make each one unique.
Ketamine is promising and growing as a treatment option for a variety of health issues. It is also being studied more and more, and with more research comes more answers. Contact us today for a free consultation to see if it is right for you.
About the co-author: Stephanie Gordon, BA
Stephanie graduated from the University of Miami with a BA in public health and psychology in 2018. She has a passion for helping people and families through difficult times. As part of Avesta’s team, she strives to influence the healthcare system, facilitating access to treatments, like Ketamine therapy to become affordable, better understood, and incorporated as a holistic approach to mood and pain disorders. She fully believes in the combination of Ketamine infusions and cognitive therapy, and fits well with Avesta’s mission in helping people with mood disorders optimize their health, and wellbeing, and live their best lives!
