Ru-Band Lu, Sheng-Yu Lee, Shiou-Lan Chen and Yun-Hsuan Chang
Accepted Abstracts: J Neurol Neurophysiol
Neurodegeneration may be involved in pathogenesis and treatment response for major mental illnesses. Over-inflammatory inducing cytokines has been reported to be related to neurodegeneration and progression of heroin dependence. Methadone maintenance therapy is effective for opioid dependence, but methadone is an artificial opioid compound. Chronic methadone use lowered the striatal dopamine transporter function, impaired cognitive function, sustained attention and increased neurodegeneration. Both memantine and dextromethorphan (DM) belong to noncompetitive NMDA receptor antagonist, but low dose memantine/DM might possess anti-inflammatory effect that is mechanistically remote from an NMDA receptor. A randomized, double-blind, placebo-controlled 12-week study was conducted. Patients with heroin dependence undergoing regular methadone maintenance therapy were randomly assigned to one of the groups: Memantine (5 mg/day), DM (60~120 mg/day) or Placebo. Inflammatory factors including plasma TNF- α , IL-8, and TGF-β1 levels were examined during weeks 0, 1, 4, 8, and 12. After treatment, inhibition of tolerance to methadone and decreased methadone dosage would be found in both patient groups who received memantine/DM compared to the placebo group. In addition, reduced plasma, TNF- α was found in both patient groups received memantine/DM while increased TGF-β1was found only in the memantine group and IL-8 in DM group compared to the placebo group. We would suggest that low-dose memantine/DM might be a feasible adjuvant therapy for attenuating inflammation, providing neuroprotection, and inhibiting methadone tolerance in heroin dependent. From our results, that regulating over-inflammation or autoimmune system may be effective for heroin dependence or other mental disorders.
Ru-Band Lu graduated from National Defense Medical center Taipei, Taiwan. Since 1992 to 1993, he was a visiting research scientist in Human Genetics at Yale University, New Haven, CT, USA. In the past years, he studied molecular genetics and psycho-neuroimmune Pharmacology in mood disorders and substance use disorders. In this decade, he works in mood and substance use disorders as well as the developmental navel treatment model in major mental illness. He has published more than hundred and fifty research articles in the recent ten years.