Ketamine

Also known as: ketamine HCl, esketamine (Spravato) is the related approved form

Wellness

In plain English

Ketamine is an FDA-approved anesthetic that, at lower doses, can rapidly improve severe depression and is used off-label for mood disorders and chronic pain (as troches, nasal spray, or injections). A closely related nasal form (esketamine/Spravato) is FDA-approved for treatment-resistant depression. It can cause dissociation (feeling detached), raised blood pressure, and has misuse potential, so it should be used under medical supervision.

The science

Ketamine is a non-competitive NMDA-receptor antagonist; its rapid antidepressant effect is linked to a glutamate surge, AMPA-receptor activation, and downstream synaptogenesis (including BDNF/mTOR signaling). The intranasal S-enantiomer esketamine has randomized evidence: in a phase 2 dose-ranging trial adjunctive to oral antidepressants in treatment-resistant depression (Daly et al., JAMA Psychiatry 2018), esketamine produced dose-dependent, rapid MADRS improvement versus placebo, supporting its later FDA approval (Spravato). Off-label compounded ketamine (troche/nasal/IM) for depression and pain is common but less rigorously standardized. Acute dissociation, hypertension, and abuse liability require monitoring; it is a controlled substance.

References

• Daly EJ et al., JAMA Psychiatry 2018 (intranasal esketamine)