Ketamine: Compound Guide

If someone is in danger right now

Slow or shallow breathing, being unable to wake someone, chest pain, severe confusion or thoughts of suicide need emergency help: call 911 in the United States, or call or text 988 for a mental health crisis. US Poison Help is 1-800-222-1222. NIDA found that using opioids or GHB with ketamine led to the most health problems, some life-threatening. [1]

What ketamine is

Ketamine is a dissociative medicine. NIDA groups ketamine with PCP as drugs that block the brain's NMDA (glutamate) receptors and can make people feel detached from their body and surroundings. Classic psychedelics such as psilocybin and LSD mainly act on serotonin receptors instead. [2] Ketamine is not a natural product or a classic psychedelic; it was developed decades ago as an anesthetic. [1] See Dissociatives: How They Differ From Classic Psychedelics and Ketamine vs Classic Psychedelics.

Ordinary ketamine is a mixture of two mirror-image molecules, R-ketamine (arketamine) and S-ketamine (esketamine). The FDA states this and notes that the nasal spray Spravato contains only the esketamine molecule. [3] Ketamine and esketamine are different medicines with different approvals. See Esketamine (Spravato): Compound Guide and Ketamine vs Esketamine.

Regulatory category

Evidence labels used on this page: approved medicine, promising but limited, mixed, insufficient evidence, evidence of harm.

• Approved medicine (anesthesia). The FDA-approved Ketalar label lists three uses: as the sole anesthetic for procedures that do not need muscle relaxation, to start anesthesia before other anesthetics, and as a supplement to other anesthetics. [4]
• Mental health: not FDA approved. NIDA says ketamine itself is not approved for any mental health disorder, although many US clinics offer it off-label for depression, anxiety and other conditions. [1] The FDA says it has not determined that ketamine is safe and effective for psychiatric uses. [3]
• United States (federal). Ketamine is a Schedule III controlled substance in the Drug Enforcement Administration's regulations (21 CFR 1308.13). [5] Read 2026-10-22. Laws change and this is not legal advice. Other countries: not verified here.

What research shows

Treatment-resistant depression: promising but limited, and mixed on how it compares. A two-site trial gave 73 people with treatment-resistant depression a single intravenous infusion of ketamine or the anesthetic midazolam as an "active placebo". Twenty-four hours later, depression scores were about 8 points lower with ketamine, and 64% responded against 28%. The authors said more was needed on durability and safety. [6]

A larger open-label trial (ELEKT-D, 403 people) compared ketamine with electroconvulsive therapy (ECT). Response was 55.4% with ketamine and 41.2% with ECT, and ketamine was judged noninferior; ECT affected memory recall more, while ketamine caused dissociation. [7] A later meta-analysis of six randomized trials (655 patients) did not find ketamine noninferior overall, and ketamine was inferior to ECT in inpatients. [8] These findings are mixed. A network meta-analysis found intravenous ketamine ranked above intranasal esketamine in indirect comparisons, but the number of patients given intravenous ketamine was small. [9] For the esketamine label evidence, see the esketamine guide.

Suicidal thoughts: mixed. A 2025 meta-analysis of 13 trials found racemic ketamine raised the rate of remission of suicidal thoughts in the short term, but whether this lasts is unclear. [10]

Chronic pain: no clear evidence of benefit. A 2025 Cochrane review found no clear evidence that intravenous, oral or topical ketamine reduced chronic pain intensity compared with placebo (mostly low or very low certainty), and intravenous ketamine may increase adverse events. [11]

Addiction treatment: insufficient evidence. NIDA says ketamine is being investigated for alcohol, opioid and cocaine use disorders and is not approved for any substance use disorder. [1]

Risks and adverse effects

• Short term. Headache, dizziness, sleepiness, feeling strange, trouble speaking, numbness, blurred vision, nausea, and changes in blood pressure and heart rate. [1]
• Trial side effects. A systematic review of 60 articles found psychiatric, psychotomimetic, cardiovascular and other side effects more often after ketamine than placebo in depression, and noted limited long-term reporting. [12]
• Unsupervised use. Respiratory depression (dangerously slow, shallow breathing) is a risk; poison-control reports about ketamine rose 81% from 2019 to 2021. [1]
• Long-term heavy use. Memory problems, depression, anxiety, stomach pain ("k-cramps"), and ketamine-induced bladder damage (uropathy). [1] The Ketalar label warns of liver injury with recurrent use and of urological complications. [4]
• Mental illness. NIDA reports ketamine can worsen symptoms in people with schizophrenia and can cause short-term psychosis. [2]
• Long-term monitored treatment. A 2026 systematic review of 32 studies (follow-up 3 months to 9 years) found no evidence of cumulative organ toxicity during maintenance treatment, but reported inconsistent safety monitoring across studies. [13]
• Addiction. Regular use is linked to signs of addiction, though how addictive ketamine is needs more research. [1]

Special groups and interactions

The label says ketamine should not be used where a large rise in blood pressure would be a serious hazard. It warns that benzodiazepines, opioids and other CNS depressants can cause profound sedation, respiratory depression, coma or death, and that theophylline or aminophylline can lower the seizure threshold. [4] In children 3 and under, use longer than 3 hours may cause long-term cognitive deficits. [4] Do not change any medicine because of this page; talk with the prescriber. See Combining Psychoactive Substances, Alcohol and Other Sedatives.

Quality and labeling

Compounded ketamine products are not FDA approved, so the FDA has not evaluated their safety, effectiveness or quality, and the FDA has not established safe or effective dosing of ketamine for any psychiatric use. [3] Products sold illicitly as ecstasy may also contain ketamine. [14] See Clinical Formulations vs Nonmedical Products.