Ketamine is a powerful anesthetic that, at lower doses, produces rapid antidepressant effects, pain relief, and a dissociative state where you feel detached from your body and surroundings. Originally developed for surgical anesthesia in the 1960s, it has become one of the most significant breakthroughs in mental health treatment in decades, particularly for people whose depression hasn’t responded to other medications.
How Ketamine Works in the Brain
Ketamine’s primary target is a receptor involved in how brain cells communicate using glutamate, the brain’s main excitatory chemical messenger. By blocking this receptor on specific inhibitory brain cells, ketamine triggers a surge of glutamate release in the prefrontal cortex, the region responsible for mood, decision-making, and complex thought. That burst of activity sets off a chain reaction that ultimately increases production of a key growth factor called BDNF, which helps neurons repair and strengthen their connections.
This is what makes ketamine fundamentally different from traditional antidepressants. SSRIs and similar drugs slowly adjust serotonin levels over weeks. Ketamine rapidly stimulates the brain’s ability to form new neural connections, a process called synaptogenesis. In animal studies, a single dose of ketamine increased the density of dendritic spines (the tiny structures neurons use to communicate with each other) in the prefrontal cortex for up to two weeks. Some of those newly formed connections became permanent, functional synapses. This structural rewiring is thought to explain why ketamine’s antidepressant effects can last well beyond the time the drug is active in your system.
Effects on Depression
Ketamine’s most remarkable property is how fast it works for severe depression. Many people experience noticeable improvement within hours of a single infusion, compared to the four to six weeks typical antidepressants require. In a major trial comparing ketamine to electroconvulsive therapy (ECT), 55% of patients receiving ketamine saw at least a 50% improvement in their depressive symptoms, along with better quality of life that persisted through six months of follow-up. For context, 41% of those receiving ECT, long considered the gold standard for treatment-resistant depression, achieved the same benchmark.
The FDA has approved a nasal spray form called esketamine (brand name Spravato) for two specific situations: treatment-resistant depression in adults, and depressive symptoms in adults with major depression who are experiencing acute suicidal thoughts or behavior. In both cases, it can be used alongside a standard oral antidepressant. Because of risks including sedation, dissociation, and breathing problems, the nasal spray is only available through a restricted program. You cannot take it home. It must be administered in a certified healthcare setting, where a provider watches you take it and monitors you for at least two hours afterward.
For psychiatric use, ketamine is given at doses far below what’s used for surgery. A typical infusion protocol uses 0.5 mg/kg delivered intravenously, compared to 1 to 4.5 mg/kg for surgical anesthesia. That’s roughly one-quarter to one-eighth of an anesthetic dose.
Pain Relief
Ketamine is increasingly used for chronic pain conditions that haven’t responded to conventional treatments. It works through a different pathway than opioids, which makes it a useful option when standard painkillers fall short. One common protocol involves 0.5 mg/kg infused over 40 minutes daily for five consecutive days. Anti-nausea medication is typically given beforehand to prevent one of the most common side effects.
Conditions where ketamine infusions are most often considered include complex regional pain syndrome (CRPS), neuropathic pain, and certain types of widespread chronic pain. The relief doesn’t always last permanently, and repeat courses may be needed, but for some people it provides meaningful improvement where nothing else has worked.
What It Feels Like During Treatment
At subanesthetic doses, ketamine produces a dissociative state. You may feel disconnected from your body, experience distorted perception of time and space, or have visual changes. Some people describe it as dreamlike or floating. These effects typically begin within minutes of administration and fade relatively quickly. The experience can feel disorienting, which is one reason clinical settings require monitoring.
Blood pressure and heart rate both rise during ketamine administration, usually peaking within a few minutes. Systolic and diastolic blood pressure typically increase 10% to 50% above baseline, then return to normal within about 15 minutes. These cardiovascular effects are dose-dependent, meaning higher doses produce larger increases. This is why ketamine is contraindicated for people with certain vascular conditions, including aneurysms or a history of bleeding in the brain.
Short-Term Side Effects
The most common side effects during or shortly after a session include nausea, dizziness, increased blood pressure, and dissociation. Some people experience anxiety or confusion during the dissociative state. These effects are generally short-lived and resolve within a couple of hours, which is the reason for the mandatory observation period with the FDA-approved nasal spray.
Risks of Long-Term or Recreational Use
The safety profile looks quite different for people who use ketamine frequently or recreationally compared to those receiving supervised medical treatment. The most serious long-term risk involves the urinary system. A UK-wide prevalence study found that 26.6% of regular ketamine users experience at least one urinary symptom. These symptoms include needing to urinate constantly, waking up at night to urinate, painful urination, incontinence, blood in the urine, and severe bladder pain.
About half of ketamine users who develop urinary problems don’t seek medical help right away, with symptoms often becoming more noticeable after two years of use. Snorting ketamine causes more urinary damage than taking it orally. The good news is that roughly 51% of people see improvement in their symptoms after they stop using ketamine, though some sustain lasting bladder damage.
Ketamine also carries a risk of psychological dependence. The dissociative and euphoric effects can be reinforcing, which is why medical use is carefully controlled. The FDA’s restricted distribution program for esketamine exists specifically because of concerns about abuse, misuse, and the potential for diversion.
Anesthetic Use
Ketamine remains widely used as an anesthetic, particularly in emergency medicine, pediatric procedures, and settings where other anesthetics may be too risky. It has a unique advantage: unlike most anesthetics, it doesn’t suppress breathing or lower blood pressure at standard doses. For surgical anesthesia, doses range from 1 to 4.5 mg/kg intravenously, or 6.5 to 13 mg/kg when given as an intramuscular injection. At these higher doses, it produces complete loss of consciousness and profound pain relief.