Ketamine is primarily metabolized by CYP3A4 and CYP2B6, as well as CYP2C9, though to a lesser extent. “Moreover, due to its extensive metabolism, potentially dangerous interactions are expected when other drugs are taken together” 1.

Memantine is already known to reduce tolerance and potentiate some drugs due to its NMDA antagonism. However, could it also be potentiating drugs through enzyme inhibition, or both?

Besides being an NMDA antagonist, memantine is also one of the few known CYP2B6 inhibitors. "Memantine exerts selective inhibition of CYP2B6 activity at clinically relevant concentrations, suggesting the potential for clinically significant drug interactions" 2. While CYP3A4 inhibitors are commonly discussed in the context of potentiation, I've never heard of anyone experimenting with a CYP2B6 inhibitor.

I'm also currently researching Tagamet, which is a potent CYP3A4 inhibitor, similar to grapefruits. If anyone has any experience taking memantine or Tagamet with ketamine, let me know. :)

TL;DR: Memantine inhibits the enzyme CYP2B6, which is partially responsible for the breakdown of ketamine. This means it could potentially be a potentiator aside from it also being a NDMA antagonist.