PSYCHEDELIC GUIDES · GUIDE 05
Ketamine & esketamine
Ketamine is a dissociative anesthetic in medical use since the 1970s; at lower doses it alters perception and can lift severe depression with unusual speed. Esketamine — one half of the ketamine molecule — is its regulated nasal-spray form: an approved medicine, given only under supervision in certified clinics.
This project examines psychedelic research; it does not recommend psychedelic use. Outside approved medical care and registered clinical trials, these substances are illegal in most places, uncontrolled in content and dose, and genuinely dangerous for some people. Nothing in these guides is a how-to. If you are struggling, established treatments exist — and the medication and treatment sections of this site cover many of them.
EVIDENCE REVIEW
OCTOBER 18, 2026
What the research shows
Esketamine (Spravato) is FDA-approved for treatment-resistant depression (2019), for depressive symptoms in major depression with acute suicidal ideation (2020), and, since January 2025, as a stand-alone treatment. It is administered in a certified healthcare setting with observation afterward, because of sedation and dissociation. IV ketamine for depression is off-label: genuinely promising in trials and widely offered, but without FDA approval for that use, and with thinner long-term data. The effects of both can be rapid — and are often temporary without a maintenance plan.
Risks — and who should not take them
Both can cause dissociation, sedation, nausea, and blood-pressure elevation during treatment. Ketamine carries misuse and dependence potential, and heavy long-term use can damage the bladder and cognition; it must be used cautiously in people with psychosis, uncontrolled blood pressure, or substance-use disorders. Driving after treatment is unsafe — clinics require observation and a ride home. Ketamine obtained outside medical care, of uncertain dose and purity, has caused real harm, including deaths.
Legal status
Ketamine is a US federal Schedule III controlled substance: legal as a medicine, illegal to possess without a prescription. Esketamine is available only through a restricted program (REMS) at certified sites. Compounded and gray-market ketamine products occupy a legal gray zone that regulators have repeatedly warned about.
