依存症研究と治療ジャーナル

抽象的な

Withdrawal from Buprenorphine/Naloxone and Maintenance with a Natural Dopaminergic Agonist: A Cautionary Note

Kenneth Blum, Marlene Oscar-Berman, John Femino, Roger L Waite, Lisa Benya, John Giordano, Joan Borsten, William B Downs, Eric R Braverman, Raquel Loehmann, Kristina Dushaj, David Han, Thomas Simpatico, Mary Hauser, Debmalya Barh and Thomas McLaughlin

Background: While numerous studies support the efficacy of methadone and buprenorphine for the stabilization and maintenance of opioid dependence, clinically significant opioid withdrawal symptoms occur upon tapering and cessation of dosage.

Methods: We present a case study of a 35 year old Caucasian female (Krissie) who was prescribed increasing dosages of prescription opioids after carpel tunnel surgery secondary to chronic pain from reflex sympathetic dystrophy and fibromyalgia. Over the next 5 years, daily dosage requirements increased to over 80 mg of Methadone and 300 ug/hr Fentanyl transdermal patches, along with combinations of 12-14 1600 mcg Actig lollipop and oral 100 mg Morphine and 30 mg oxycodone 1-2 tabs q4-6hr PRN for breakthrough pain. Total monthly prescription costs including supplemental benzodiazepines, hypnotics and stimulants exceeded $50,000. The patient was subsequently transferred to Suboxone® in 2008, and the dosage was gradually tapered until her admission for inpatient detoxification with KB220Z a natural dopaminergic agonist. We carefully documented her withdrawal symptoms when she precipitously stopped taking buprenorphine/naloxone and during follow-up while taking KB220Z daily. We also genotyped the patient using a reward gene panel including (9 genes 18 alleles): DRD 2,3,4; MOA-A; COMT; DAT1; 5HTTLLR; OPRM1; and GABRA3.

Findings: At 432 days post Suboxone® withdrawal the patient is being maintained on KB220Z, has been urine tested and is opioid free. Genotyping data revealed a moderate genetic risk for addiction showing a hypodopaminergic trait. This preliminary case data suggest that the daily use of KB220Z could provide a cost effective alternative substitution adjunctive modality for Suboxone®. We encourage double-blind randomized –placebo controlled studies to test the proposition that KB220Z may act as a putative natural opioid substitution maintenance adjunct.