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.

Effect of craving induction on inhibitory control in opiate dependence.

RATIONALE: Current neurobiological models of addiction posit that drug seeking is much more likely to occur during emotionally charged states (such as craving), as deficits in inhibitory control become more pronounced during heightened motivational states. OBJECTIVE: The purpose of this study was to examine the effect of cue-induced craving states on attention and inhibitory control within addicted individuals. METHODS: We tested the performance of 39 opiate-dependent individuals on cognitive measures of attention (Digit Span, Digit Symbol, and Telephone Search) and inhibitory control (Counting Stroop and Go-No-Go) both before and after exposure to an autobiographical craving script. A non-drug using healthy control group (n = 19) performed the same tasks before and after listening to a relaxation tape. RESULTS: Following craving induction, opiate-dependent individuals demonstrated improved performance on tests of processing speed and attentional span (consistent with the practice effect observed in controls) and increased their response errors on the Stroop task (in contrast to controls), while selective attention was unaffected. Individual differences in compulsivity mediated the association between craving and Stroop performance, such that low-compulsive (but not high-compulsive) individuals committed more response errors after craving induction. CONCLUSIONS: These findings challenge the notion of cue-induced craving as a primary trigger of disrupted cognition and drug-seeking behavior in addicted individuals, and raise the need to explore individual differences in compulsivity when addressing the links between craving and loss of control within research and clinical settings.

Responsiveness to drug cues and natural rewards in opiate addiction: associations with later heroin use.

CONTEXT: Although drug cues reliably activate the brain's reward system, studies rarely examine how the processing of drug stimuli compares with natural reinforcers or relates to clinical outcomes. OBJECTIVES: To determine hedonic responses to natural and drug reinforcers in long-term heroin users and to examine the utility of these responses in predicting future heroin use. DESIGN: Prospective design examining experiential, expressive, reflex modulation, and cortical/attentional responses to opiate-related and affective stimuli. The opiate-dependent group was reassessed a median of 6 months after testing to determine their level of heroin use during the intervening period. SETTING: Community drug and alcohol services and a clinical research facility. PARTICIPANTS: Thirty-three opiate-dependent individuals (mean age, 31.6 years) with stabilized opiate-substitution pharmacotherapy and 19 sex- and age-matched healthy non-drug users (mean age, 30 years). MAIN OUTCOME MEASURES: Self-ratings, facial electromyography, startle-elicited postauricular reflex, and event-related potentials combined with measures of heroin use at baseline and follow-up. RESULTS: Relative to the control group, the opiate-dependent group rated pleasant pictures as less arousing and showed increased corrugator activity, less postauricular potentiation, and decreased startle-elicited P300 attenuation while viewing pleasant pictures. The opiate-dependent group rated the drug-related pictures as more pleasant and arousing, and demonstrated greater startle-elicited P300 attenuation while viewing them. Although a startle-elicited P300 amplitude response to pleasant (relative to drug-related) pictures significantly predicted regular (at least weekly) heroin use at follow-up, subjective valence ratings of pleasant pictures remained the superior predictor of use after controlling for baseline craving and heroin use. CONCLUSIONS: Heroin users demonstrated reduced responsiveness to natural reinforcers across a range of psychophysiological measures. Subjective rating of pleasant pictures robustly predicted future heroin use. Our findings highlight the importance of targeting anhedonic symptoms within clinical treatment settings.