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Substance Profile
Ketamine is a dissociative anesthetic and non-competitive NMDA receptor antagonist with unique rapid-onset antidepressant properties. Licensed as an anesthetic since the 1960s, it has experienced a renaissance as an antidepressant over the past two decades. Sub-anesthetic doses produce a dissociative experience and stimulate synaptic plasticity through AMPA receptor potentiation and mTOR signaling pathways. Esketamine (Spravato) has been approved since 2019 for treatment-resistant depression, representing the first fundamentally new mechanism of action in depression treatment in decades.
Non-competitive blockade producing dissociation
Glutamate burst β AMPA β BDNF/mTOR cascade within hours
Disrupts depressive rumination patterns
Reported subjective effects based on clinical and community data
Detecting neuroplastic effects induced by ketamine in healthy human subjects: A multimodal approach.
Ketamine Use for ED Sedation: Pharmacologic Basis, Clinical Applications, and Safety Considerations.