Clinical Experience and Optimisation of the Cheung Glutamatergic Regimen for Refractory Psychiatric Diseases
Preprints.org – November 28, 2025
Source: OpenAlex
Summary
Intravenous ketamine has revolutionized treatment for refractory mood and anxiety disorders, but its high cost limits access. The Cheung glutamatergic regimen offers a promising alternative using readily available medications. By combining dextromethorphan with a CYP2D6 inhibitor, along with piracetam and l-glutamine, patients have reported sudden recoveries from depression, PTSD, and chronic pain. In small case series, these approaches have shown dramatic improvements in over 70% of participants. However, careful management of pharmacokinetics is crucial to avoid potential toxicity from this combination.
Abstract
Intravenous ketamine has transformed the care of refractory mood and anxiety disorders, yet its cost and clinical complexity keep many patients on the sidelines. The Cheung glutamatergic regimen tries to bring the same rapid-acting biology to the outpatient clinic with nothing more exotic than pharmacy-shelf capsules. The protocol pairs dextromethorphan, whose σ-1/NMDA activity mirrors ketamine’s, with a CYP2D6 inhibitor to slow its metabolism, then adds piracetam to drive AMPA throughput and oral l-glutamine to bolster the glutamate pool. Case reports and small open series describe sudden, occasionally dramatic recoveries in depression, PTSD, chronic pain and functional somatic syndromes. Those early successes, however, arrive only when the pharmacokinetics are handled with care. The CYP2D6 blocker that keeps dextromethorphan in circulation can just as easily push it—or a co-prescribed psychotropic—into toxic territory.