Decoding Ketamine: Low-dose drug combos aim for rapid, safer antidepressant effects

Two studies reveal how ketamine triggers rapid antidepressant effects by briefly silencing interneuron brakes in the prefrontal cortex via mu-opioid receptors, and show that a low-dose three-drug combo can replicate this benefit with fewer side effects; longer-lasting relief depends on TrkB and mGluR5 receptor cross-talk driven by BDNF, which strengthens and stabilizes synapses. Researchers plan accelerated clinical trials using safe, existing drugs to translate these findings into patient treatments.