Ketamine

An anesthetic with a second life

Ketamine was approved in 1970 as a surgical anesthetic, and that is still its only FDA-approved use. Hospitals have relied on it for more than fifty years because, unlike most anesthetics, it tends to keep people breathing and keeps blood pressure up. Over the past two decades it has found a second life in much smaller amounts: first for hard-to-treat depression, then for chronic pain, and lately as a product sold through telehealth clinics and mailed to patients’ homes. The DEA lists ketamine in Schedule III – a controlled substance with accepted medical uses and a real potential for misuse.

If you have been living with pain that nothing seems to touch, it is natural to wonder about it. This page explains what ketamine does in the nervous system, what the evidence for chronic pain honestly shows, and why the setting it is given in matters so much. It describes; it does not prescribe.

How it works: turning down the volume knob

Ketamine is not an opioid. Its main target is the NMDA receptor, a docking site on nerve cells that helps pain signals get louder as they pass through the spinal cord. When pain goes on for months, these receptors can become over-responsive – part of what scientists call central sensitization, where the nervous system amplifies signals that would once have been faint. Ketamine blocks the NMDA receptor, which is a bit like turning a volume knob down at the spinal cord rather than at the source of the pain.

That is the theory behind using it for nerve pain and for complex regional pain syndrome (CRPS), conditions where the amplifier seems stuck on. It is also why the effects feel strange: NMDA receptors are everywhere in the brain, so blocking them produces dissociation – a dreamlike sense of being detached from your body or surroundings – along with drowsiness, blurred vision, nausea, and a rise in blood pressure and heart rate. These are not rare side effects. They are the drug working, in places other than the pain pathway.

What the evidence shows – and doesn’t

The strongest claim the evidence supports is a modest one. In 2018, three professional societies – the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists – published consensus guidelines on IV ketamine infusions for chronic pain. Their reading of the literature: evidence supports its use, but it “varies by condition and dose range,” and most studies were small, uncontrolled, and poorly blinded. The clearest signal was for CRPS and for some neuropathic pain; the data for fibromyalgia, headache, and spinal pain were weaker.

A 2019 meta-analysis in Anesthesia & Analgesia pooled seven randomized trials – 211 patients in all – and found a small benefit lasting up to about two weeks after an infusion: roughly 1.8 points on a 0-to-10 pain scale, with about half of ketamine patients counted as responders versus a fifth on placebo. Six of the seven trials were at high risk of bias. The 2025 Cochrane review, the most rigorous look so far, went further in its caution: in 39 ketamine trials it found “no clear evidence” that IV, oral, or topical ketamine reduces chronic pain intensity, rated the evidence low to very low certainty, and found that IV ketamine may raise the risk of adverse events.

So the honest summary is this: for some people with stubborn neuropathic or CRPS pain, a monitored infusion can bring real relief for days to a few weeks. Whether that relief lasts, whether repeated infusions are safe over years, and whether lozenges or nasal sprays do anything comparable – none of that has been settled. Ketamine is not FDA-approved for any pain condition; every use for pain is off-label, which is legal and common in medicine but means the usual proof of benefit and safety has not been gathered.

Why a monitored infusion is a different thing

An infusion for pain is given in a clinic, through an IV, over hours, often on several days in a row. The 2018 guidelines describe what that setting is supposed to include: a clinician trained in airway management and resuscitation, continuous monitoring of oxygen, heart rate, and blood pressure, and medications on hand to blunt nausea or a sharp rise in blood pressure. The reason is simple. Ketamine’s effects – sedation, dissociation, blood-pressure swings, and in rare cases slowed breathing – arrive quickly, and someone has to be watching for them.

At-home ketamine is usually a compounded lozenge, tablet, or nasal spray, prescribed after a video visit and shipped to the door. The molecule is the same. What is missing is everyone and everything in the left half of the figure above. In October 2023 the FDA warned that taking compounded ketamine at home carries added risk precisely because no provider is present to monitor for sedation and dissociation, that the amount of drug in these products can vary, and that it has never found ketamine safe or effective for any psychiatric use. Compounded products are not FDA-approved, and the agency does not check their quality before they are sold.

What the anesthesiologists are asking for

The American Society of Anesthesiologists – the specialty that has used ketamine longest – has spent 2026 pressing lawmakers and state medical boards on this point. In a June 2026 statement, ASA President Patrick Giam put it plainly: “We have grave concerns about the home delivery and use of ketamine. You can move very quickly from feeling relaxed to becoming deeply sedated, and without proper monitoring and supervision, this can become dangerous.” The society’s updated guidance says ketamine used outside the operating room should meet the same safety standards as any anesthetic: in-person evaluation, a physician immediately available, a monitored setting with rescue equipment – and it states that a telehealth visit does not satisfy that requirement.

Concretely, the ASA is asking states to require direct physician supervision for ketamine given by injection or infusion, to limit prescribing for unsupervised home use, and to back the bills now moving in Texas, Georgia, Missouri, and Utah. The stance is not that ketamine is bad; it is that a powerful anesthetic should not be handed out faster than the safety rules around it.

Risks with repeated use

One infusion in a monitored setting is, for most people, uneventful beyond the strange hours it produces. The concerns grow with repetition. Regular use can injure the bladder – inflammation, urgency, pain, and blood in the urine, a pattern seen most in people who use ketamine often and sometimes slow to reverse. Liver and memory effects have been reported with heavy use. And ketamine can produce dependence: tolerance builds, the dissociative effects can become something people seek, and stopping after sustained use can be hard. None of this means a supervised course for pain will lead there; it means that frequency and oversight matter, and that a plan should have an endpoint.

Ketamine is also riskier combined with other sedating drugs. Taking it alongside opioids, benzodiazepines, or alcohol stacks the effects on breathing and alertness – one more reason monitored settings screen for these first. If ketamine, opioids, or any substance use has become hard to control, the SAMHSA helpline, 1-800-662-4357, is free, confidential, and answers around the clock.

Seek urgent care if someone who has used ketamine cannot be roused, is breathing slowly or irregularly, has chest pain, a seizure, or severe agitation – call 911. Blood in the urine or new, persistent bladder pain should be reported to your physician promptly.

How it fits with other options

In pain medicine, ketamine infusion is a late rung on the ladder: a specialist option for pain that has not responded to the nerve-pain medications, physical and psychological therapies, and interventional procedures with better long-term track records. It is usually offered as a short course with a clear goal – a window of lower pain in which rehabilitation can gain ground – rather than as a maintenance drug. Insurance often does not cover it for pain, and cash prices vary widely, which is part of why the at-home market grew.

If you are considering it, the questions worth bringing to a pain physician are the ones the evidence leaves open: what condition is being treated, what response would count as success, how many sessions, who will be monitoring, and what the plan is if it does not help. A fellowship-trained pain specialist can answer those honestly. Your pain is real; the goal is a treatment whose benefits and risks are just as real to the people giving it.