Methadone maintenance dose modulates anterior cingulate glutamate levels in heroin-dependent individuals: A preliminary in vivo1H MRS study

Mu-opioid receptor agonists alter brain glutamate (GLU) levels in laboratory animals. This clinical study used proton magnetic resonance spectroscopy (1H 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 1H MRS data from midline pregenual anterior cingulate cortex (ACC) and thalamus (4.5 cm3 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.