The Effect Of Methadone Maintenance Treatment Duration And Dosage On Brain Response To Drug Cues In Former Heroin-dependent Individuals: An Event-related FMRI Study

ObjectiveHeroin addiction has become a severe medical and social problem over the world,especially in our country. Currently methadone maintenance treatment (MMT) is one ofthe safe and effective treatment for heroin addiction. The long-term MMT will help reducethe relapse rate of heroin addicts, the high-dose MMT will help the opioid withdrawal andthe high retention rate, it is may related to the environment-induced drug craving, but nofunctional imaging evidence to support these inferences. At the same time, the effect ofMMT duration and dosage is still no uniform conclusion. In the present study, we usedfunctional magnetic resonance imaging (fMRI) to investigate the effect of MMT duration on brain response to heroin-related cues in former heroin-dependent individuals and theacute effect of MMT doses on brain response to drug cues in former heroin-dependentindividuals. Hopely, it is useful to help define the effects of MMT duration and dosage onbehavior of the patients, and benefit the MMT paradigm.Methods1Fifteen patients (duration of MMT≤1year,≤1year group) and eleven patients(duration of MMT2-3year,2-3year group) were included in the study. Their age,gender, education level, cigarette use history, heroin use history and the daily dose ofmethadone were well matched. An event-related cue-reactivity paradigm wasemployed, while changes in blood oxygen level-dependent (BOLD) signals wereacquired by fMRI. For each participant, the subjective craving for heroin wasassessed before and shortly after the MRI scan. Corrlelation analyses were performedbetween cue-induced BOLD signal intensity and heroin use history and methadoneuse history among all of the patients.2Fifteen heroin addicts (daily dose of methadone≤40mg,≤40mg/d group) andfourteen heroin addicts (daily dose of methadone>40mg,>40mg/d group)participated in this study. Their age, gender, education level, cigarette use history,heroin use history and the MMT duration were well matched. An event-relatedcue-reactivity paradigm was employed. Subjective craving for heroin was assessedbefore and shortly after the MRI scan. Corrlelation analyses were performed betweencue-induced BOLD signal intensity and heroin use history and methadone use historyamong all of the patients.Results1The self-reported heroin craving score demonstrated no significant difference betweentwo groups (t=2.9, P>0.05). Compared to the2-3year group, the≤1year groupdemonstrated greater activation in the bilateral caudate. Meanwhile, controllingeducation, age, daily cigarette consumption and heroin use history, the cue inducedBOLD signal intensity in the right caudate was significantly negatively associatedwith the total dose of methadone and the duration of MMT respectively (r=-0.539, P=0.008; r=-0.511, P=0.013). The signal intensity of left caudate was significantlynegatively associated with the total dose of methadone (r=-0.597, P=0.003). Wheneducation, age, MMT history and daily cigarette consumption were controlled, thedrug-related activity intensity in right caudate had a positive correlation with dailyheroin dosage (r=0.47, P=0.036).2There was no difference in craving changes between the two groups (t=-0.69,P>0.05). Compared to the>40mg/d group, the≤40mg/d group demonstratedgreater activation in the left caudate. Meanwhile, controlling age, daily cigarettes,education and heroin use history, the activation of left caudate was significantlynegatively associated with the daily dose of methadone (r=-0.465, P=0.025).Conclusion1The present study indicates that the duration of MMT can result in different nervousresponse when exposed to heroin cue. Before subjective craving have reduced inheroin addicts undering MMT for2-3years, may improve the brain craving responseby regulate the impaired function of caudate nucle. Therefore, we considered thatMMT for2-3years can reduce craving and improve the retention.2When exposed to heroin cue, distinctive acute nervous response can be found inheroin addicts with different MMT dosage, daily dose of methadone>40mg canreduce the response of caudate nucle to drug-cue. We considered that, daily dose ofmethadone>40mg can reduce the salience value of heroin-related cues by regulatethe function of caudate nucle, accordingly reduce the susceptibility of relapse in formerheroin addicts.