Ketamine
NMDA-antagonist dissociative anesthetic and rapid-acting antidepressant for treatment-resistant depression.
Pharmacology
Contents
WHAT IS KETAMINE?
Detailed overview
Ketamine is an arylcyclohexylamine dissociative anesthetic that acts as an uncompetitive, open-channel blocker of the NMDA-type glutamate receptor. Approved as an anesthetic and analgesic since the 1960s, over the past two decades it has become central to rapid-acting antidepressant research: at low, subanesthetic doses it often relieves treatment-resistant depression within hours, in contrast to the weeks required by conventional antidepressants. The S-enantiomer (esketamine, Spravato) received FDA and EMA approval as an intranasal treatment for treatment-resistant depression. The effect is linked to a glutamate surge, AMPA activation, and increased synaptic plasticity through the BDNF-TrkB-mTOR pathway. It is a prescription agent used only under medical supervision.
Mechanism
NMDA open-channel block + glutamate-AMPA surge
Evidence
Strong (multiple human randomized trials)
Legal status
Prescription (esketamine FDA/EMA-approved for TRD)
Receptor profile
- NMDA receptors (open-channel block)Strong
- Glutamate surge / AMPA activationStrong
- BDNF / TrkB-mTOR pathwayModerate
- μ/κ opioid receptors (modulatory)Weak
Safety
Side effects, stop signs, contraindications
Side effects · 6
- Dissociation, a sense of detachment from reality, and perceptual distortions during dosing
- Transient rise in blood pressure and heart rate
- Nausea, vomiting, dizziness, impaired coordination
- Emergence confusion, anxiety, or nightmarish experiences
- Bladder and urinary tract damage with repeated frequent use (ketamine cystitis)
- Risk of psychological dependence and abuse with recreational use
Contraindications · 5
- Uncontrolled hypertension, severe cardiovascular disease, aneurysm
- Psychosis, schizophrenia, or active mania: the experience may worsen them
- Pregnancy and breastfeeding: safety not established
- History of substance abuse or ketamine dependence
- Elevated intracranial or intraocular pressure
Related Nootropics
Same therapeutic category
Studies
Related research and clinical findings
Antidepressant effects of ketamine in depressed patients
Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH
A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression
Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK
Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial
Murrough JW, Iosifescu DV, Chang LC, et al.
The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis
Wilkinson ST, Ballard ED, Bloch MH, et al.
Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide
Canuso CM, Singh JB, Fedgchin M, et al.
FAQ
FAQ
NMDA-antagonist dissociative anesthetic and rapid-acting antidepressant for treatment-resistant depression.
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Structure & chemistry
The information here is strictly for educational and scientific purposes. It does not replace medical advice or clinical consultation, and it does not encourage illegal substance or pharmaceutical use. Data is sourced. When in doubt, consult your doctor.