Ketamine
Ketamine is a dissociative anesthetic that has been used in medicine since the 1960s and remains one of the most versatile and widely studied drugs in modern pharmacology. In 2026, ketamine is prescribed daily in hospitals and clinics across the United States, United Kingdom, Germany, Japan, China, Canada, France, Netherlands, Switzerland, Australia, Dubai, Finland, and Austria for anesthesia, acute pain management, procedural sedation, treatment-resistant depression, chronic neuropathic pain, and certain emergency psychiatric crises. What began as a battlefield anesthetic valued for its rapid onset, cardiovascular stability, and preservation of airway reflexes has evolved into one of the most promising tools for severe mood disorders and intractable pain conditions that do not respond to conventional therapies.
Ketamine acts primarily as an NMDA receptor antagonist, blocking glutamate transmission at these ionotropic channels. This disruption of glutamatergic signaling in key brain regions — particularly the prefrontal cortex, hippocampus, and limbic structures — produces rapid antidepressant effects through downstream increases in synaptic plasticity, BDNF release, mTOR pathway activation, and synaptogenesis. Unlike traditional antidepressants that target monoamine systems and require weeks to show benefit, ketamine can produce significant mood improvement within hours to days after a single sub-anesthetic dose. This fast onset is why ketamine infusion clinics, intranasal esketamine (Spravato), and off-label IV/IM protocols have proliferated globally for patients with treatment-resistant major depressive disorder, bipolar depression, postpartum depression, suicidal ideation, and severe anxiety states.
In anesthesia, ketamine remains a first-line agent in emergency, pediatric, and resource-limited settings. It induces a dissociative state characterized by profound analgesia, amnesia, and catalepsy while maintaining spontaneous breathing, airway reflexes, and hemodynamic stability — properties that make it uniquely safe compared to propofol, etomidate, or barbiturates in patients with shock, asthma, or hemodynamic instability. Low-dose ketamine infusions (0.1–0.5 mg/kg/h) are routinely used perioperatively to reduce postoperative opioid requirements, prevent chronic pain development after surgery, and manage acute pain in opioid-tolerant patients.
Chronic pain management represents another major clinical application. Low-dose ketamine infusions (typically 0.1–0.5 mg/kg/h over 4–7 days) or repeated outpatient boluses are frequently employed for complex regional pain syndrome (CRPS), fibromyalgia, neuropathic pain, phantom limb pain, central pain syndromes, migraine status, and severe cancer pain. The analgesic effects often outlast the pharmacokinetic duration of the drug, suggesting neuroplastic changes in central pain processing pathways. Many patients report 30–70% pain reduction lasting weeks to months after a single multi-day course, with reduced opioid requirements and improved function.
The most transformative use in recent years has been in psychiatry. Intravenous ketamine infusions (0.5 mg/kg over 40 minutes, typically 6 infusions over 2–3 weeks) produce robust antidepressant responses in 50–70% of patients with treatment-resistant depression, often within 4–24 hours. Esketamine nasal spray (Spravato), approved in 2019 and expanded since, is administered under supervision in certified clinics and has shown similar rapid efficacy for major depressive disorder with acute suicidal ideation or behavior. Maintenance regimens — weekly or biweekly boosters — help sustain response in many patients. These treatments are now covered by insurance in numerous countries when other therapies fail, reflecting the strength of the evidence base.
Despite its efficacy, ketamine is not without risks. Acute side effects during administration include dissociation, perceptual disturbances, elevated blood pressure, tachycardia, nausea, dizziness, and transient confusion — all usually short-lived. Psychiatric risks include emergence reactions (hallucinations, agitation) that are minimized with co-administration of benzodiazepines or proper set/setting. Long-term concerns center on bladder toxicity (ketamine cystitis/ulcerative cystitis) seen primarily in heavy recreational users, cognitive effects with very frequent high-dose exposure, and potential for misuse or dependence in vulnerable populations. Hepatotoxicity is rare but documented. Because of these risks, all approved protocols require medical supervision, baseline assessments, informed consent, and ongoing monitoring.
Ketamine is classified as a Schedule III controlled substance in the United States and similarly regulated in most other listed countries (Schedule 1 or equivalent in some jurisdictions with stricter controls). Medical use is tightly controlled through prescriptions, clinic certifications, and pharmacy dispensing. Recreational use remains illegal everywhere, with severe penalties in many regions.
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Ketamine remains a uniquely powerful tool in medicine — a dissociative anesthetic that doubles as a rapid-acting antidepressant, potent analgesic, and breakthrough therapy for some of the most treatment-resistant conditions. Its versatility, speed of action, and ability to produce lasting neuroplastic changes continue to make it one of the most important drugs in modern psychiatry and pain management — when used responsibly under medical supervision.
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