Here is an explanation of the interaction between rapamycin and therapeutic ketamine:

Rapamycin is an immunosuppressant medication that inhibits the mTOR (mammalian target of rapamycin) pathway. Ketamine is used therapeutically as an anesthetic and for the treatment of depression. When used together, rapamycin and ketamine can potentially interact through several mechanisms:

  1. Rapamycin inhibits the CYP3A4 enzyme system, which is important for metabolizing ketamine.1 Inhibition of CYP3A4 by rapamycin can decrease ketamine clearance, leading to increased ketamine levels and enhanced or prolonged effects.2
  2. The mTOR pathway plays a role in synaptogenesis and regulation of glutamate signaling. Ketamine exerts some of its antidepressant effects through mTOR activation.3 Rapamycin blocks mTOR, which could theoretically inhibit or reduce ketamine’s antidepressant actions.4
  3. Both rapamycin and ketamine can affect immune function through mTOR inhibition and NMDA receptor antagonism, respectively. Combined use may lead to excessive immunosuppression, increasing risks of infection.5
  4. High ketamine doses can cause psychotomimetic effects. These effects might be enhanced by co-administration with rapamycin through the mechanisms outlined above. Lower ketamine dosing may be warranted with concurrent rapamycin use.
  5. Rapamycin and ketamine are individually cleared primarily by hepatic metabolism. Competition for metabolic pathways could lead to increased levels of both drugs. Dose adjustments may be needed to avoid toxicity.

Overall, concurrent use of rapamycin and ketamine warrants close monitoring due to potentially interacting mechanisms involving CYP3A4, mTOR signaling, and drug clearance. Dose reductions may be necessary to mitigate risks of side effects.

In general, the interaction between rapamycin and ketamine has only recently been identified, so studies are actively taking place as this page is being written. Please research this on the broader internet and discuss it with your provider, as it can potentially make your ketamine therapy more effective.


  1. https://www.ncbi.nlm.nih.gov/pubmed/15920153
  2. https://www.ncbi.nlm.nih.gov/pubmed/25973616
  3. https://www.ncbi.nlm.nih.gov/pubmed/23129553
  4. https://www.ncbi.nlm.nih.gov/pubmed/28834488
  5. https://www.ncbi.nlm.nih.gov/pubmed/29481485

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