What Does Ketamine Actually Do?

There’s a lot of talk about it, but what actually is it and how does it work?

Sometimes Too-Special K

Ketamine was developed more than 60 years ago as an anesthetic and is also used for pain relief, dissociation, and depression treatment; it exists as two mirror-image forms, esketamine and arketamine, with much of the current research focused on esketamine.

How it works: ketamine blocks NMDA receptors, reducing the activity of cells that normally respond to glutamate and altering patterns of communication throughout the brain; it also interacts with opioid, nicotine, dopamine, and other receptors, while its antidepressant effects can additionally involve changes in gene expression, immune activity, inflammation, and neuron growth.

The main uses:

• Post-operative recovery: ketamine and esketamine have been associated with reduced postoperative and postpartum depression symptoms, and a 2024 meta-analysis found benefits for depression, pain, and overall recovery during the first day after surgery; esketamine is also FDA-approved for treatment-resistant depression.
• Suicidal ideation: a small emergency-department trial found that 12 of 15 people given ketamine no longer had suicidal thoughts within hours, with improvements reportedly persisting during follow-up over the following month, although the sample was very small.

The main risks:

• Dissociation: at subanesthetic doses, ketamine can produce hallucinations and a sense of disconnection by changing which brain cells are active and disrupting communication involved in processing sensory information and its context.
• Blood pressure and heart rate: ketamine can temporarily increase both, with a meta-analysis of 15 studies finding an average increase of about four heartbeats per minute; blood pressure increases could reach hypertensive levels but generally declined quickly after treatment, while some individuals experienced substantially larger increases.
• Overdoses (fatal and otherwise): incorrect dosing can be toxic, and among FDA reports of negative ketamine outcomes, about 20% resulted in hospitalization and about 5% in death, although these reports represent adverse-event reports rather than the risk experienced by typical patients receiving supervised treatment.

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Take care!