Clinical Experience and Optimisation of the Cheung Glutamatergic Regimen for Refractory Psychiatric Diseases

An oral glutamatergic regimen combining dextromethorphan, a CYP2D6 inhibitor, piracetam, and l-glutamine shows promise for treating refractory mood and anxiety disorders, with case reports and small open series describing sudden, occasionally dramatic recoveries in depression, PTSD, chronic pain, and functional somatic syndromes. However, the pharmacokinetics require careful handling because the CYP2D6 blocker that maintains dextromethorphan levels can also push the drug or co-prescribed psychotropics into toxic territory, limiting the regimen's accessibility despite its potential to bring rapid-acting biology to outpatient clinics.

Study at a glance

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.