title: Methadone maintenance dose modulates anterior cingulate glutamate levels in heroin-dependent individuals: A preliminary in vivo (1)H MRS study.
abstract: Mu-opioid receptor agonists alter brain glutamate (GLU) levels in laboratory animals. This clinical study used proton magnetic resonance spectroscopy ((1)H MRS) to examine regional brain GLU levels during experimental manipulation of methadone (MTD) maintenance dose under double-blind, within-subject conditions in seven heroin-dependent volunteers. Subjects were scanned first at a high MTD dose (100 mg/day), underwent a 3-week outpatient MTD dose taper, and then were scanned again at a low MTD dose (10-25 mg/day; modified for participant comfort). Five age- and cigarette smoking-matched controls were scanned once. In vivo short echo time (TE = 22 ms), single voxel (1)H MRS data from midline pregenual anterior cingulate cortex (ACC) and thalamus (4.5 cm(3) each) were collected using PRESS on a 4-Tesla MRI system. Absolute metabolite levels were quantified. GLU levels in the ACC, but not the thalamus, were higher at the low relative to the high MTD dose in heroin-dependent subjects. No other metabolites differed by MTD dose, or between control vs. heroin-dependent subjects (at either MTD dose). GLU levels in the ACC were inversely related to the duration of cigarette smoking (controls) and heroin use (experimental group). Future studies are warranted to investigate the relationship between GLU levels during treatment (and detoxification), and withdrawal symptoms or relapse.
authors.affiliation: Substance Abuse Research Division, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Tolan Park Medical Building, 3901 Chrysler Drive, Suite 2A, Detroit, MI 48201, USA; Department of Pharmacy Practice, Wayne State University, Detroit, MI, USA. Electronic address: mgreen@med.wayne.edu.
authors.forename: Mark K
authors.initials: MK
authors.lastname: Greenwald
authors.affiliation: Substance Abuse Research Division, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Tolan Park Medical Building, 3901 Chrysler Drive, Suite 2A, Detroit, MI 48201, USA; Brain Imaging Research Division, Wayne State University, Detroit, MI, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Woodcock
authors.affiliation: Brain Imaging Research Division, Wayne State University, Detroit, MI, USA.
authors.forename: Dalal
authors.initials: D
authors.lastname: Khatib
authors.affiliation: Brain Imaging Research Division, Wayne State University, Detroit, MI, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Stanley
mesh_terms: D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D018698:Glutamic Acid / Q000378:metabolism; D006179:Gyrus Cinguli / Q000187:drug effects* / Q000503:physiopathology; D006556:Heroin Dependence / Q000503:physiopathology* / Q000534:rehabilitation*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008691:Methadone / Q000008:administration & dosage*; D008875:Middle Aged; D058850:Opiate Substitution Treatment
chemical_list: D018698:Glutamic Acid; D008691:Methadone
keywords: Detoxification; Dose taper; Neurochemistry; Opioid use disorder; Pharmacotherapy; Proton magnetic resonance spectroscopy