Ketamine is not FDA approved for the treatment of pain. The only FDA-approved indication for ketamine is as an anesthetic, specifically for induction and maintenance of general anesthesia. Despite this, ketamine is widely used off-label for chronic pain conditions, and a growing number of clinics offer ketamine infusions for pain management. Understanding the gap between its official approval status and its real-world use is important if you’re considering this treatment.
What Ketamine Is Actually Approved For
Ketamine is a Schedule III controlled substance that received FDA approval solely as an anesthetic agent. It has been used in surgical settings since the 1960s, primarily for short-term sedation and anesthesia. That remains its only approved use in its original form.
A related drug, esketamine (sold as Spravato), is a nasal spray approved in 2019 for treatment-resistant depression and for depressive symptoms in adults with major depressive disorder who have suicidal thoughts. The Spravato label explicitly states it is “not for use as a medicine to prevent or relieve pain” and that its safety and effectiveness as a pain medication have not been established. So neither ketamine nor esketamine carries FDA approval for any pain condition.
Why Doctors Still Use It for Pain
Off-label prescribing is legal and common in medicine. Doctors can prescribe an FDA-approved drug for conditions beyond its official label when they believe the evidence supports it. Ketamine falls into this category for chronic pain, particularly for conditions like complex regional pain syndrome (CRPS), nerve pain, fibromyalgia, and cancer-related pain.
The biological rationale is straightforward. Chronic pain involves changes in how the nervous system processes signals. Neurons involved in pain pathways become increasingly excitable over time, a process driven in part by a specific type of receptor in the brain and spinal cord. Ketamine blocks this receptor, which may slow or reduce the amplification of pain signals. It may also work by changing how the brain processes the emotional experience of pain, not just the physical sensation.
What the Evidence Actually Shows
The evidence for ketamine’s effectiveness varies significantly depending on the pain condition. Consensus guidelines from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists break it down this way:
- Complex regional pain syndrome (CRPS): Moderate evidence supports improvement lasting up to 12 weeks.
- Spinal cord injury pain: Weak evidence supports short-term improvement only.
- Other conditions (fibromyalgia, cancer pain, headache, spinal pain, mixed nerve pain): Weak or no evidence for immediate improvement.
CRPS is the condition with the strongest support, though even that evidence is considered low to moderate certainty. For most other chronic pain conditions, the data is thin. A review from Neuroscience Research Australia noted there is no clear overall benefit for chronic pain from ketamine, underscoring how far the clinical enthusiasm has outpaced the evidence base.
Oral ketamine has also been studied. A five-year retrospective study of 51 patients found pain was reduced or eliminated in about two-thirds of cases, with patients on opioid therapy responding better (only 7% failure rate compared to 36% for those not on opioids). The average effective oral dose was about 2 mg/kg. However, half of patients experienced side effects, and roughly 15% had to stop treatment because of them.
What a Typical Treatment Looks Like
Ketamine for pain is most commonly given as an intravenous infusion at doses far below what’s used for anesthesia. Guidelines suggest starting with a single outpatient infusion of at least 80 mg over more than two hours, then reassessing before committing to further sessions. Higher doses and longer infusion periods tend to produce better results, with evidence supporting a dose-response relationship.
After a single outpatient infusion, pain relief lasting more than three weeks is considered a reasonable benchmark for success. After a series of infusions, the goal is relief lasting at least six weeks. Guidelines recommend limiting treatments to 6 to 12 sessions per year, though exceptions are made in severe cases. The treatments are done in a clinical setting with monitoring, not at home.
Risks and Side Effects
During an infusion, common short-term effects include feeling disconnected from your body, distortions in how you perceive time and space, and changes in vision and hearing. At higher doses, these dissociative effects become more intense and can include hallucinations, confusion, and delirium. These effects are temporary and resolve after the infusion ends.
The more serious concerns relate to repeated use over time. Regular ketamine use increases the risk of bladder inflammation (called ketamine-induced cystitis) by three to four times. Symptoms include urinary urgency, painful urination, blood in urine, and increased frequency. In severe cases, prolonged use can lead to bladder wall scarring, damage to the tubes connecting the kidneys to the bladder, and even chronic kidney failure. Stopping ketamine usually improves these symptoms, but not always completely.
Ketamine also carries a risk of psychological dependence. The dissociative experience itself can become habit-forming. Guidelines recommend against using serial ketamine infusions in patients with active substance abuse problems, and clinicians are advised to monitor for signs of misuse.
Who Should Not Receive Ketamine for Pain
Professional guidelines identify several groups who should avoid ketamine infusions. People with poorly controlled heart disease or certain psychotic disorders should not receive it. Those with severe liver disease are also excluded, since the liver processes ketamine. Patients with elevated pressure in the brain or eyes should either avoid ketamine entirely or use only very low doses under close supervision. Anyone with an active substance abuse problem is not a good candidate.
Because ketamine for pain is entirely off-label, insurance coverage is inconsistent. Many patients pay out of pocket, and costs for a series of infusions can run into thousands of dollars. The lack of FDA approval means there are no standardized treatment protocols enforced across clinics, so the quality of care and monitoring can vary widely from one provider to another.