***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: AIMS To evaluate the efficacy and safety of orally administered naltrexone , alone or in combination with nicotine patches , as a treatment for cigarette smoking .  DESIGN R and omized , partially-blinded , 2 x 2 factorial trial using naltrexone ( active vs. placebo ) and nicotine patches ( active vs. none ) . PARTICIPANTS One hundred cigarette smokers . INTERVENTION Twelve weeks of either placebo-only , naltrexone-only , placebo with nicotine patches or naltrexone with nicotine patches . The naltrexone dose was 50 mg taken once daily , and the nicotine patch dose was 21 mg/24-hour for the first 8 weeks and 14 mg/24-hour for the remaining 4 weeks . Brief behavioral intervention was provided at each visit . MEASUREMENTS One-week point-prevalence smoking abstinence rates confirmed by an expired air carbon monoxide level of 8 parts per million ( ppm ) or less , daily cigarette smoking and cigarette craving . FINDINGS At the end of treatment , there was no effect of naltrexone on smoking abstinence . The smoking abstinence rates were 19 % and 22 % for the placebo only and naltrexone only treatment groups , respectively , and 48 % and 46 % for the placebo with nicotine patch and naltrexone with nicotine patch groups , respectively . However , the effect of the nicotine patch at this time was significant ( p = 0.006 ) , but not at the 6-month follow-up . No significant effect of naltrexone was observed on daily cigarette smoking on cigarette craving during the study . CONCLUSIONS The opioid antagonist naltrexone was not found to be effective for smoking cessation and had no significant effect on daily cigarette consumption or craving . The results of the present study provide no support for the use of naltrexone , alone or in combination with nicotine patches , as a therapeutic treatment for smoking cessation A promising option in substance abuse treatment is the Community Reinforcement Approach ( CRA ) . The opioid antagonist naltrexone ( NTX ) may work in combination with nicotine replacement therapy ( NRT ) to block the effects of smoking stimuli in abstinent smokers . Effects of lower doses than 50 mg/dd . have not been reported . A study was conducted in Amsterdam in 2000/2001 with the objective to explore the effects of the combination NTX ( 25/50-mg dd . ) , NRT , and CRA in terms of craving and abstinence . In a r and omized open label , 2 × 2 between subjects design , 25 recovered spontaneous pneumothorax ( SP ) participants received 8 weeks of treatment . Due to side effects , only 3 participants were compliant in the 50-mg NTX condition . Craving significantly declined between each measurement and there was a significant interaction between decline in craving and craving measured at baseline . The abstinence rate in the CRA group was nearly double that in the non-psychosocial therapy group ( 46 % vs. 25 % ; NS ) at 3 months follow-up after treatment Rationale Human behavioral pharmacology studies can examine how medications that target different neurotransmitter systems influence different aspects of smoking . Naltrexone and bupropion have been shown to alter ad lib smoking behavior ; however , medication effects on nicotine reward in a cigarette choice paradigm have yet to be investigated . Objective This study explored the effects of an acute dose of naltrexone , bupropion , or placebo on the relative reinforcing value of nicotine from cigarette smoking using new nicotine and de-nicotinized ( Quest , 0.6 and 0.05 mg = “ denicotinized ” ) cigarettes . Methods In a double-blind , within-subjects design , 26 dependent smokers participated in three experimental cigarette smoking sessions following pretreatment with either naltrexone ( 50 mg ) , bupropion ( 300 mg ) , or placebo . After medication administration and 2 h of monitored deprivation from cigarettes and food , participants rated their responses to the initial exposure to the cigarettes and then participated in four choice sessions over a 2-h period during which they could take four puffs from either cigarette . Results The relative reinforcing value of nicotine , as measured by the number of nicotine puffs chosen out of 16 , was significantly lower following naltrexone compared to placebo . There were no effects of an acute dose of bupropion on nicotine choices . Conclusions These results suggest that naltrexone may reduce the relative reinforcing effects of nicotine via cigarette smoking and support ongoing investigation of opioid antagonists as potential smoking cessation pharmacotherapies E FOR AN association between nicotine and the endogenous opioid system comes from several lines of research . Studies have shown that administration of nicotine and /or stimulation of nicotinic receptors activates -endorphin and enkephalin release and bio synthesis ( Eiden et al. , 1984 ; Gilbert et al. , 1992 ; Houdi et al. , 1991 ; Pomerleau et al. , 1983 ) . In addition to having higher rates of smoking than in the general population , heroin addicts have been shown to smoke more during heroin selfinjection ( Mello et al. , 1980 ) and smoke less during methadone dose tapering ( Bigelow et al. , 1981 ) . Furthermore , opioid antagonists block certain effects of nicotine , including antinociception , operant responding , and prolactin release ( Aceto et al. , 1993 ; Corrigall et al. , 1988 ; Flores et al. , 1989 ) . The opioid antagonist naloxone has also been shown to induce withdrawal-like states in nicotine-dependent rats and humans ( Krishnan-Sarin et al. , 1999 ; Malin et al. , 1993 , 1996 ) . Conversely , nicotine has also been shown to suppress opioid antagonist effects such as decreasing naloxone-induced jumping in morphine-dependent mice ( Brase et al. , 1974 ; Zarrindast and Farzin , 1996 ) . Although there seems to be evidence of an opioid – nicotine interaction from in vivo and in vitro studies , human pre clinical studies have largely shown mixed results . Specifically , there are varied results from laboratory studies on the effects of the opioid antagonists naltrexone ( or intravenous naloxone ) on aspects of smoking response . Some studies have shown that naltrexone or naloxone significantly reduce subjects ’ self-reported pleasure or satisfaction from smoking ; perceived difficulty in abstaining , craving , and urge to smoke ; and the number of cigarettes smoked or puffs taken ( Gorelick et al. , 1989 ; Houtsmuller et al. , 1997 ; Karras and Kane , 1980 ; King and Meyer , 2000 ; Palmer and Berens , 1983 ; Sutherl and et al. , 1995 ; Wewers et al. , 1998 ) . In conjunction with the nicotine patch , naltrexone has also been shown to significantly decrease negative affect and craving after presentation of a smoking cue ( Hutchison et al. , 1999 ) . However , these findings are not ubiquitous , as other studies have failed to show significant effects of opioid antagonists on altering ad libitum smoking , number of cigarettes or puffs taken , or desire to smoke ( Gorelick et al. , 1989 ; Houtsmuller et al. , 1997 ; NemethCoslett and Griffiths , 1986 ; Sutherl and et al. , 1995 ) . Also , naltrexone or naloxone has been shown to increase smokers ’ negative mood and withdrawal-like symptoms ( Brauer et al. , 1999 ; Krishnan-Sarin et al. , 1999 ) . Collectively , there seems to be a lack of consistency in findings from pre clinical human laboratory studies on opioid antagonist effects on smoking behaviors . Although there are no simple explanations , several method ological issues may be contributing to this disparity , such as the use of small sample sizes , lack of statistical power , a range of naltrexone or naloxone doses or routes of administration , and fundamental differences in paradigms ( timing issues , degree of naturalism , baseline abstinence , etc . ) . A few studies have examined naltrexone in smoking cessation , and no studies have examined concurrent smoking and alcohol behaviors in study patients . As in laboratory studies , the results from clinical trials using adjunct treatment with naltrexone for nicotine dependence have shown mixed results , with negative findings in one study ( Wong et al. , 1999 ) and positive or mixed findings in two other studies ( Covey et al. , 1999 ; O’Malley et al. , 1997 ) . Although it is well established that alcohol may increase the risk for smoking relapse ( Baer and Lichtenstein , 1988 ; Br and on et al. , 1990 ; Shiffman 1982 , 1986 ) , smoking cessation trials have not systematic ally targeted pharmacological treatment strategies that may affect both behaviors . It is possible that naltrexone , a medication used for alcohol dependence ( O’Malley et al. , 1992 ; Volpicelli et al. , 1992 ) and posited to block alcohol ’s pleasurable effects ( King et al. , 1997 ; O’Malley et al. , 1996 ; Swift et al. , 1994 ; Volpicelli et al. , 1995 ) , might theoretically be an effective smoking cessation treatment agent , especially in smokers who drink . This may be due in part to direct nicotine – opioid system interactions ( as stated earlier ) , as well as blockade of alcohol reward and concomitant drinking episodes , which bode poorly for smoking outcome . Finally , the timing of naltrexone may be an important variable . Data from our previous laboratory study ( King and Meyer , 2000 ) indicate that naltrexone attenuated smoking urge and pleasure during and after cigarette exposure ; therefore , medication r and omization From the Department of Psychiatry , University of Chicago Pritzker School of Medicine , Chicago , Illinois . Received for publication August 2 , 2002 ; accepted September 5 , 2002 . Supported by NIH K08-AA00276 , P30 CA14599 - 28 , and M01-RR00055 . Reprint requests : Reprint requests : And rea King , PhD , University of Chicago , Department of Psychiatry , 5841 S. Maryl and Avenue , Chicago , IL 60637 ; Fax : 773 - 702 - 6454 ; E-mail : aking@yoda.bsd.uchicago.edu Copyright © 2002 by the Research Society on Alcoholism Rationale : The role of endogenous opiate systems in cigarette smoking remains unclear . In laboratory animals , opiate antagonists block many of the effects of nicotine , but in humans they do not consistently alter smoking behavior . Objective : This study explored the effects of naltrexone , alone and in combination with nicotine , on smoking behavior . Methods : In a double-blind , double-dummy , within-subjects design , 19 regular smokers received four treatments of 1 week duration : naltrexone tablet ( 50 mg ) plus placebo skin patch , placebo tablet plus nicotine skin patch ( 21 mg/24 h ) , naltrexone tablet plus nicotine skin patch , and placebo tablet plus placebo skin patch . During each treatment , subjects rated their responses to nicotine-containing and denicotinized cigarettes in the laboratory , and to their own br and of cigarette smoked ad libitum outside the laboratory . Results : Pretreatment with the nicotine patch attenuated smoking-induced decreases in craving , negative affect , and rates of ad lib smoking , and potentiated the aversiveness of a cigarette .  Naltrexone reversed these effects of the nicotine patch , and produced negative effects on mood . Conclusions : The blockade of nicotine ’s effects by naltrexone supports a role for opioid mechanisms in cigarette smoking This within-subjects , placebo-controlled laboratory study was design ed to examine the effects of naltrexone on cigarette response in 44 chronic smokers ( 23 male , 21 female ) . Each participant received either 50-mg oral naltrexone or identical placebo during the morning of the session after maintaining overnight abstinence . Subsequently , the participant was administered a smoking cue ( holding lit cigarette ) to examine craving and associated features of smoking , and instructed to smoke a cigarette 1 h later . This was followed by a smoking interval in which participants could choose to smoke up to four more cigarettes over a 2-h period . Subjective measures ( withdrawal , craving , affect , and side effects ) and smoking behavior were assessed throughout the session . Naltrexone significantly reduced the total number of choice cigarettes smoked and expired carbon monoxide levels ( Ps<.05 ) . Naltrexone significantly increased total side effects , especially for sedation ( P<.01 ) . Further , naltrexone significantly increased overall negative 
    Output:
    
AUTHORS ' CONCLUSIONS Based on data from eight trials and over 1200 individuals , there was no evidence of an effect of naltrexone alone or as an adjunct to NRT on long-term smoking abstinence , with a point estimate strongly suggesting no effect and confidence intervals that make a clinical ly important effect of treatment unlikely .