title: Buprenorphine-induced changes in mu-opioid receptor availability in male heroin-dependent volunteers: a preliminary study.
abstract: A principle of opioid pharmacotherapy is that high medication doses should occupy fractionally more opioid receptors that mediate heroin effects. In this preliminary study we examined in vivo mu opioid receptor (muOR) binding in three healthy opioid-dependent volunteers during maintenance on 2 and 16 mg sublingual buprenorphine (BUP) liquid, and after detoxification (0 mg) under double-blind, placebo-controlled conditions, and once in matched controls. Binding measures were obtained with the muOR-selective radioligand [11C]carfentanil (CFN) and PET 4 hrs after BUP administration. BUP induced dose-dependent reductions in muOR availability, 36-50% at 2 mg and 79-95% at 16 mg relative to placebo. Heroin abusers also had greater muOR binding potential in the inferofrontal cortex and anterior cingulate regions during placebo, compared to matched controls. Further studies are warranted to examine the relationship of muOR availability with BUP therapeutic actions, and the clinical implications of increased muOR binding during withdrawal.
authors.affiliation: Neurosciences, University of Michigan, Ann Arbor 48104-1687, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zubieta
authors.forename: M K
authors.initials: MK
authors.lastname: Greenwald
authors.forename: U
authors.initials: U
authors.lastname: Lombardi
authors.forename: J H
authors.initials: JH
authors.lastname: Woods
authors.forename: M R
authors.initials: MR
authors.lastname: Kilbourn
authors.forename: D M
authors.initials: DM
authors.lastname: Jewett
authors.forename: R A
authors.initials: RA
authors.lastname: Koeppe
authors.forename: C R
authors.initials: CR
authors.lastname: Schuster
authors.forename: C E
authors.initials: CE
authors.lastname: Johanson
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid; D001921:Brain / Q000000981:diagnostic imaging; D001923:Brain Chemistry; D002047:Buprenorphine / Q000494:pharmacology*; D004311:Double-Blind Method; D005283:Fentanyl / Q000031:analogs & derivatives; D006556:Heroin Dependence / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009294:Narcotics / Q000494:pharmacology*; D017450:Receptors, Opioid, mu / Q000187:drug effects*; D014055:Tomography, Emission-Computed
chemical_list: D000701:Analgesics, Opioid; D009294:Narcotics; D017450:Receptors, Opioid, mu; D002047:Buprenorphine; C017114:carfentanil; D005283:Fentanyl