Cingulate biochemistry in heroin users on substitution pharmacotherapy.
OBJECTIVE
High doses of opiate substitution pharmacotherapy are associated with greater treatment retention and lower illicit drug consumption, although the neurobiological bases of these benefits are poorly understood. Dysfunction of the anterior cingulate cortex (ACC) is associated with greater addiction severity and mood dysregulation in opiate users, such that the beneficial effects of substitution pharmacotherapy may relate to normalisation of ACC function. This study aimed to investigate the differential impact of methadone compared with buprenorphine on dorsal ACC biochemistry. A secondary aim was to explore the differential effects of methadone and buprenorphine on dorsal ACC biochemistry in relation to depressive symptoms.


METHODS
Twenty-four heroin-dependent individuals stabilised on methadone (n=10) or buprenorphine (n=14) and 24 healthy controls were scanned using proton Magnetic Resonance Spectroscopy and compared for metabolite concentrations of N-acetylaspartate, glutamate/glutamine, and myo-inositol.


RESULTS
(1) Methadone was associated with normalisation of dorsal ACC biochemistry (increased N-acetylaspartate and glutamate/glutamine levels, and decreased myo-inositol levels) in a dose-dependent manner; (2) buprenorphine-treated individuals had higher myo-inositol and glutamate/glutamine levels than methadone-treated patients in the right dorsal ACC; and (3) myo-inositol levels were positively correlated with depressive symptoms in participants stabilised on buprenorphine.


CONCLUSIONS
These findings point to a beneficial role of high-dose methadone on dorsal ACC biochemistry, and suggest a link between elevated myo-inositol levels and depressive symptoms in the context of buprenorphine treatment.
1Melbourne Neuropsychiatry Centre, University of Melbourne, Melbourne, Australia.
Antonio
A
Verdejo-García
Dan I
DI
Lubman
Kim
K
Roffel
Raquel
R
Vilar-López
Emre
E
Bora
Trudi
T
MacKenzie
Murat
M
Yücel
D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D002047:Buprenorphine / Q000494:pharmacology / Q000627:therapeutic use*; D003863:Depression / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D059907:Functional Neuroimaging / Q000523:psychology; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism*; D006556:Heroin Dependence / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007294:Inositol / Q000378:metabolism; D008297:Male; D008691:Methadone / Q000494:pharmacology / Q000627:therapeutic use*; D058850:Opiate Substitution Treatment
D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; D002047:Buprenorphine; D007294:Inositol; C000179:N-acetylaspartate; D008691:Methadone