Longevity & AgingAdenosine Unlocks How Ketamine and ECT Fight Treatment-Resistant Depression
Researchers at Chinese brain research institutes used genetically encoded adenosine sensors to show that both ketamine and electroconvulsive therapy (ECT) rapidly elevate extracellular adenosine in the medial prefrontal cortex and hippocampus of mice. Blocking A1 and A2A adenosine receptors abolished antidepressant effects, while activating them mimicked therapy. Ketamine boosts adenosine through cellular metabolic shifts, not neuronal hyperactivity. Based on this, novel ketamine derivatives were developed with stronger adenosine-boosting properties, better antidepressant efficacy, and fewer side effects. Strikingly, acute intermittent hypoxia—a non-drug approach—replicated these effects by also raising brain adenosine, suggesting scalable non-pharmacological treatment paths.
