Ketamine is a dissociative anesthetic drug found to have rapid antidepressant effects in people with major depression. Research suggests that one of the key mechanisms behind ketamine’s antidepressant actions involves enhancing neurogenesis in the hippocampus.

Specifically, ketamine increases the proliferation and development of new neurons from neural stem cells. It does this primarily by activating the mTOR (mechanistic target of rapamycin) pathway, which stimulates synaptogenesis and growth of new dendrites on developing neurons1. Ketamine also seems to increase levels of BDNF (brain-derived neurotrophic factor), an important neural growth factor2.

Through these effects, a single low dose of ketamine can rapidly increase the birth of new neurons and the integration of those neurons into functional circuits in the hippocampus3. This enhances neural plasticity, allowing depressed patients to process emotions better and be more resilient to stress. The new hippocampal neurons and connections may essentially “rewire” circuits negatively affected by depression.

Sustained enhancement of neurogenesis induced by ketamine and its metabolites likely contributes to the rapid and sustained antidepressant effects seen with ketamine treatment in many patients, even after the drug is no longer detectable in the body. The mood-lifting effects of ketamine may depend on its unique ability to stimulate neurogenesis.

  1. Li N, Lee B, Liu RJ, et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science. 2010;329(5994):959-964.
  2. Garcia LS, Comim CM, Valvassori SS, et al. Ketamine treatment reverses behavioral and physiological alterations induced by chronic mild stress in rats. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2009;33(3):450-455.
  3. Moda-Sava RN, Murata Y, Bourg J, et al. Sustained rescue of prefrontal circuit dysfunction by antidepressant-induced spine formation. Science. 2019;364(6436):eaat8078.

Notify of

Inline Feedbacks
View all comments