You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Impulsive and self-control choices in opioid-dependent patients and non-drug-using control participants: drug and monetary rewards.
Abstract 1:
Delay discounting was investigated in opioid-dependent and non-drug-using control participants . The latter participants were matched to the former on age , gender , education , and IQ . Participants in both groups chose between hypothetical monetary rewards available either immediately or after a delay . Delayed rewards were $ 1,000 , and the immediate-reward amount was adjusted until choices reflected indifference . This procedure was repeated at each of 7 delays ( 1 week to 25 years ) . Opioid-dependent participants were given a second series of choices between immediate and delayed heroin , using the same procedures ( i.e. , the amount of delayed heroin was that which could be purchased with $ 1,000 ) . Opioid-dependent participants  discounted delayed monetary rewards significantly more than did non-drug-using participants . Furthermore opioid-dependent participants discounted delayed heroin significantly more than delayed money


Title 2:
Improvement of saccadic functions after dosing with methadone in opioid addicted individuals
Abstract 2:
ABSTRACT In the current experiment , we used the saccadometric test to study the effect of a single therapeutic dose of methadone on the integrity of cortico-subcortical brain functioning . In this prospect i ve study , we used the Saccadometer System ( Advanced Clinical Instrumentation , Cambridge , UK ) . The saccadometric test was performed before and 1.5 hours after methadone dosing . We analyzed the following saccadic parameters : latency , duration , amplitude , average and peak velocity , and processing performance ( promptness ) as well as a number of different types of saccades ( like correct/incorrect , under/overshoot , and left-sided/right-sided ) . The sample consists of 40 subjects with an average 18 years of opioid addiction . The mean age is 35.3 ± 7 ( 80 % males and 20 % females ) . The mean period of heroin dependence is 15.3 ± 6.3 years . The mean daily dose of methadone in substitution therapy is 90 ± 26.5 mg . After administration of a single therapeutic dose of methadone , there were statistically significant differences in the values of saccade duration and latency when compared to the values before the drug administration . Average duration of saccade was significantly longer [ 51.40 ± 8.75 ms versus 48.93 ± 6.91 ms , z = 2.53 , p = .01 ] and average latency was significantly longer [ 198.85 ± 52.57 ms versus 183.05 ± 30.95 ms , z = 2.09 p < .03 ] . This is the first study to test the therapeutic effect of daily methadone dosing on the integrity of the cortico-subcortical brain functions as measured by the saccadometry . More research is needed to explore the effect of illicit opioid use on the integrity of brain structures and functions , and the protective effect of opioid agonist therapy on reversing the damaging effects of illicit opioid use


Title 3:
Delay discounting of money and alcohol in actively using alcoholics, currently abstinent alcoholics, and controls
Abstract 3:
Abstract . Rationale : Impulsivity is implicated in alcohol dependence , and discounting of delayed rewards may be an objective indicator of impulsiveness . Objectives : This study evaluated  delay discounting functions  in alcoholics and controls . It compared discounting rates between different magnitudes ( $ 1000 and $ 100 ) and different types ( money and alcohol ) of rewards . Methods : Active alcoholics ( n=19 ) , currently abstinent alcoholics ( n=12 ) and controls ( n=15 ) indicated preferences for immediate versus delayed rewards using a titration procedure that determined indifference points at various delays . Four conditions were presented , and the delayed rewards in the four conditions were $ 1000 , $ 100 , 150 bottles of an alcoholic beverage , and 15 bottles of an alcoholic beverage . Results : In all three groups across all four conditions , hyperbolic discounting functions provided a good fit of the data . Linear contrasts , predicting the most rapid discounting rates in active alcoholics , intermediary rates in currently abstinent alcoholics , and the least rapid rates in controls , were significant for three of the four conditions . Alcohol was discounted more rapidly than money . Conclusions : These data provide further evidence of more rapid discounting of delayed rewards in alcohol abusers compared to controls , and especially steep discounting among current users . Rapid discounting of delayed rewards may be a feature related to addictive disorders . A better underst and ing of how delaying rewards in time impacts their value may have implication s for treatment


Title 4:
Heroin addicts have higher discount rates for delayed rewards than non-drug-using controls.
Abstract 4:
Fifty-six heroin addicts and 60 age-matched controls were offered choices between monetary rewards ( $ 11-$80 ) available immediately and larger rewards ( $ 25-$85 ) available after delays ranging from 1 week to 6 months . Participants had a 1-in-6 chance of winning a reward that they chose on one r and omly selected trial .  Delay-discounting rates were estimated from the pattern of participants ' choices . The discounting model of impulsiveness ( Ainslie , 1975 ) implies that delay-discounting rates are positively correlated with impulsiveness . On average , heroin addicts ' discount rates were twice those of controls ( p = .004 ) , and discount rates were positively correlated with impulsivity as measured by self-report question naires ( p < .05 ) . The results lend external validity to the  delay-discounting rate  as a measure of impulsiveness , a characteristic associated with substance abuse


Title 5:
Regional homogeneity changes in heroin-dependent individuals: resting-state functional MR imaging study.
Abstract 5:
PURPOSE To identify heroin-related modulations of neural activity in the resting state in heroin-dependent individuals ( HDIs ) by using resting-state functional magnetic resonance ( MR ) imaging and a regional homogeneity method and to investigate whether these changes of neural activity can be related to duration of heroin use and to decision-making deficits in HDIs . MATERIAL S AND METHODS This prospect i ve study was approved by the appropriate ethics committee , and written informed consent was obtained from each participant . Thirty-one HDIs receiving methadone-maintained treatment and 24 control subjects participated .  Resting-state functional MR imaging was performed by using a gradient-echo echo-planar imaging sequence . Regional homogeneity was calculated by using software . Voxel-based analysis of the regional homogeneity maps between control and HDI groups was performed with two- sample t tests by using software . Statistical maps were set at P less than .05 and were corrected for multiple comparisons . The  Iowa gambling task ( IGT ) was used to assess participant decision making during uncertainty . Abnormal clusters revealed by group comparison were extracted and correlated with behavioral performance at the IGT and with duration of heroin use . RESULTS Regional homogeneity was diminished in the bilateral medial orbitofrontal cortex ( OFC ) , bilateral dorsal medial thalamus , bilateral cuneus , and lingual gyrus in HDIs compared with control subjects . There were negative correlations between mean regional homogeneity in the medial OFC , bilateral cuneus , and lingual gyrus and duration of heroin use . There was a positive correlation between mean regional homogeneity in the medial OFC and performance level at the IGT . CONCLUSION The present study reveals resting-state abnormalities in HDIs that may lead to further improvement of the underst and ing of the neural substrates of cognitive impairment in HDIs


Title 6:
Decision making in pathological gambling: a comparison between pathological gamblers, alcohol dependents, persons with Tourette syndrome, and normal controls.
Abstract 6:
Decision making deficits play an important role in the definition of pathological gambling ( PG ) . However , only few empirical studies are available regarding decision making processes in PG . This study therefore compares decision making processes in PG and normal controls in detail using three decision making tasks examining general performance levels on these tasks as well as feedback processing using reaction time analyses . To investigate the specificity of decision making deficits in PG , a substance dependence group ( alcohol dependence ; AD ) and an impulse control disordered group ( Tourette syndrome ; TS ) were included . The PG group ( n = 48 ) , AD group ( n = 46 ) , TS group ( n = 47 ) , and a normal control ( NC ) group ( n = 49 ) were administered ( 1 ) the Iowa Gambling Task ( IGT ) , an ecologically valid gambling task ; ( 2 ) the Card Playing Task , a task measuring perseveration for reward ; and ( 3 ) a Go/No-Go discrimination task , a task measuring reward and response cost sensitivity . The PG group showed a diminished performance on all tasks and deficient feedback processing as compared to the NC group on the IGT and the Card Playing Task . In general , performance measures were not associated with levels of comorbidity or with self-reported motivational measures . For the larger part , deficiencies in decision making processes in the PG group were also present in the AD group , but not in the TS group . Subgroup analyses revealed larger decision making deficits in pathological slot machine gamblers than in pathological casino gamblers . Deficits in decision making and feedback processing in PG should be addressed in treatment and incorporated more explicitly in theoretical models of PG


Title 7:
Heroin and cocaine abusers have higher discount rates for delayed rewards than alcoholics or non-drug-using controls.
Abstract 7:
AIMS To test a prediction of the discounting model of impulsiveness that discount rates would be positively associated with addiction .  The delay-discount rate refers to the rate of reduction in the present value of a future reward as the delay to that reward increases . DESIGN AND MEASUREMENTS We estimated participants ' discount rates on the basis of their pattern of choices between smaller immediate rewards ( $ 11 - 80 ) and larger , delayed rewards ( $ 25 - 85 ; at delays from 1 week to 6 months ) in a question naire format . Participants had a one-in-six chance of winning a reward that they chose on one r and omly selected trial . PARTICIPANTS AND SETTING Heroin ( n = 27 ) , cocaine ( n = 41 ) and alcohol ( n = 33 ) abusers and non-drug-using controls ( n = 44 ) were recruited from advertisements . They were tested in a drug abuse research clinic at a medical school . FINDINGS On average , the cocaine and heroin groups had higher rates than controls ( both P < 0.001 ) , but alcoholics did not ( P = 0.44 ) . Abstinence was associated with lower rates for heroin abusers ( P = 0.03 ) , but not for cocaine or alcohol abusers ( both P > 0.50 ) . CONCLUSIONS These data suggest that discount rates vary with the preferred drug of abuse , and that high discount rates should be considered in the development of substance abuse prevention and treatment efforts
Based on the 21 studies included in the current review , there is evidence that heroin use may have a direct and damaging effect on certain brain functions and that these changes may be associated with impulsive and unhealthy decision making .
From the review of these studies , the authors underst and that a longer duration of heroin use may be associated with more damaging effects on brain functions .
The authors also underst and that these brain changes could last long after abstinence , which may increase the risk of relapse to heroin use .