Differential effects of ketamine enantiomers on EEG parameters including the gamma-delta shift phenomenon.
British journal of pharmacology June 1, 2026 Szabolcs Koncz, Dóra Pothorszki, Noémi Papp et al. 2 citations
In rats, the (S)-enantiomer of ketamine (esketamine) produces a fourfold stronger wake-promoting effect and a twofold stronger increase in gamma brainwave power during wakefulness compared to the (R)-enantiomer (arketamine). Only esketamine enhances delta power during NREM sleep after gamma activity normalizes, a pattern called the gamma-delta shift. This shift, previously proposed as a marker of antidepressant activity for racemic ketamine, appears specific to esketamine. The findings help clarify which enantiomer drives the EEG changes and suggest that the gamma-delta shift may serve as a biomarker for antidepressant effects, relevant to treatment-resistant depression.