human
***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: Abstract Evidence for serotonin involvement in impulsivity has generated interest in the measurement of impulsivity in regular ecstasy users , who are thought to display serotonergic dysfunction . However , current findings are inconsistent . Here , we used a recently developed Information Sampling Test to measure ‘ reflection ’ impulsivity in 46 current ecstasy users , 14 subjects who used ecstasy in the past , 15 current cannabis users and 19 drug-naïve controls . Despite elevated scores on the Impulsivity subscale of the Eysenck Impulsiveness-Venturesomeness-Empathy question naire , the current and previous ecstasy users did not differ significantly from the drug-naive controls on the Information Sampling Test . In contrast , the cannabis users sample d significantly less information on the task , and tolerated a lower level of certainty in their decision-making , in comparison to the drug-naive controls . The effect in cannabis users extends our earlier observations in amphetamine- and opiate-dependent individuals ( Clark , et al. , 2006 , Biological Psychiatry 60 : 515–522 ) , and suggests that reduced reflection may be a common cognitive style across regular users of a variety of substances . However , the lack of effects in the two ecstasy groups suggests that the relationship between serotonin function , ecstasy use and impulsivity is more complex Abstract Exposure therapy is known to be an effective treatment for anxiety disorders . Nevertheless , exposure is not used as much as it should be , and instead patients are often given supportive medications such as serotonin reuptake inhibitors ( SSRIs ) and benzodiazepines , which may even interfere with the extinction learning that is the aim of treatment . Given that r and omized controlled trials are now investigating a few doses of ±3,4-methylenedioxymethamphetamine ( MDMA , ‘ ecstasy ’ ) in combination with psychotherapy for treatment-resistant anxiety disorders , we would like to suggest the following three mechanisms for this potentially important new approach : 1 ) MDMA  increases oxytocin levels , which may strengthen the therapeutic alliance ; 2 ) MDMA  increases ventromedial prefrontal activity and decreases amygdala activity , which may improve emotional regulation and decrease avoidance and 3 ) MDMA  increases norepinephrine release and circulating cortisol levels , which may facilitate emotional engagement and enhance extinction of learned fear associations . Thus , MDMA has a combination of pharmacological effects that , in a therapeutic setting , could provide a balance of activating emotions while feeling safe and in control , as described in case reports of MDMA-augmented psychotherapy . Further clinical and pre clinical studies of the therapeutic value of MDMA are indicated 3,4-Methylenedioxymethamphetamine ( MDMA , ' ecstasy ' ) releases serotonin and norepinephrine . MDMA is reported to produce empathogenic and prosocial feelings . It is unknown whether MDMA in fact alters empathic concern and prosocial behavior . We investigated the acute effects of MDMA using the Multifaceted Empathy Test ( MET ) , dynamic Face Emotion Recognition Task ( FERT ) and Social Value Orientation ( SVO ) test . We also assessed effects of MDMA on plasma levels of hormones involved in social behavior using a placebo-controlled , double-blind , r and om-order , cross-over design in 32 healthy volunteers ( 16 women ) .  MDMA enhanced explicit and implicit emotional empathy in the MET and increased prosocial behavior in the SVO test in men . MDMA did not alter cognitive empathy in the MET but impaired the identification of negative emotions , including fearful , angry and sad faces , in the FERT , particularly in women . MDMA increased plasma levels of cortisol and prolactin , which are markers of serotonergic and noradrenergic activity , and of oxytocin , which has been associated with prosocial behavior . In summary , MDMA sex-specifically altered the recognition of emotions , emotional empathy and prosociality . These effects likely enhance sociability when MDMA is used recreationally and may be useful when MDMA is administered in conjunction with psychotherapy in patients with social dysfunction or post-traumatic stress disorder While accumulating evidence suggests that effective real-life decision-making depends upon the functioning of the orbitofrontal cortex , much less is known about the involvement of the monoamine neurotransmitter systems and , in particular , serotonin . In the present study , we explored the impact of depleting the serotonin precursor , tryptophan , on human decision-making . Eighteen healthy volunteers consumed an amino-acid drink containing tryptophan and 18 healthy volunteers consumed an amino-acid drink without tryptophan , before choosing between simultaneously presented gambles , differing in the magnitude of expected gains ( ie reward ) , the magnitude of expected losses ( ie punishment ) , and the probabilities with which these outcomes were delivered . Volunteers also chose between gambles probing identified non-nomative biases in human decision-making , namely , risk-aversion when choosing between gains and risk-seeking when choosing between losses . Tryptophan-depleted volunteers showed reduced discrimination between magnitudes of expected gains associated with different choices . There was little evidence that tryptophan depletion was associated with altered discrimination between the magnitudes of expected losses , or altered discrimination between the relative probabilities with which these positive or negative outcomes were delivered . Risk-averse and risk-seeking biases were also unchanged . These results suggest that serotonin mediates decision-making in healthy volunteers by modulating the processing of reward cues , perhaps represented within the orbitofrontal cortex . It is possible that such a change in the cognition mediating human choice is one mechanism associated with the onset and maintenance of anhedonia and lowered mood in psychiatric illness Abstract . Rationale : ( ± ) 3,4-Methylenedioxymethamphetamine ( MDMA or " ecstasy " ) has been shown to cause long term damage to serotonergic cerebral neurons in animals . The neurotoxic effects in humans are less clear and little is known about the functional consequences , although some studies suggest memory impairment . Given the widespread use of MDMA , our lack of knowledge raises concerns . Objective : We investigated , in humans , the relation between past use of ecstasy and cognitive performance as well as serotonergic function . Methods : Two groups of 21 males with moderate and heavy recreational use of MDMA , respectively , and a control group of 20 males without use of MDMA were compared . All were from the same subculture . Reaction time , direct recall , and recognition were assessed . Serotonergic function was measured by the neuro-endocrine response to a placebo-controlled , crossover challenge with dexfenfluramine . Results : Ecstasy users showed a broad pattern of statistically significant , but clinical ly small , impairment of memory and prolonged reaction times . Heavy users were affected stronger than moderate users . Release of cortisol but not of prolactin  after dexfenfluramine administration was significantly reduced in both groups of ecstasy users compared with the controls . Analyses of covariance showed that likely confounding variables including recent exposure to ecstasy , psychosocial profiles and use of other drugs did not explain the differences found between the groups . Conclusions : These results provide further evidence that use of ecstasy may be associated with impairment of memory and of serotonergic function . These findings are compatible with neurotoxicity of ecstasy as shown in animals To examine the neurotoxic potential of continued  MDMA ( “ Ecstasy ” )  use in humans and its functional consequences over the course of 1 year , 15 MDMA users participated in a longitudinal study in which they completed a brief neuropsychological test battery composed mainly of retrospective and prospect i ve memory tasks . Subjects were abstinent for 2 weeks on initial and 1-year testing . Continued use of MDMA was associated with progressive decline in terms of immediate and delayed recall Ecstasy ( MDMA ; 3,4-methylenedioxymethamphetamine ) has a well-recognized neurotoxic effect on central serotonergic ( 5-HT ) systems in animals , and there is some evidence of persistent serotonergic dysregulation in human ecstasy users . Serotonin is believed to mediate impulsive behavior and effective decision-making . Thus , the aim of the present study was to investigate impulsive behavior and decision-making in abstinent regular ecstasy users . Three groups were compared : ‘ ecstasy users ’ ( recreational ecstasy users who reported modest use of illicit drugs other than cannabis ) , ‘ polydrug controls ’ ( ecstasy naïve illicit drug users ) , and ‘ drug-naïve controls ’ .  All participants completed personal details and general drug history question naires , the National Adult Reading Test , Matching Familiar Figures Test ( MFF20 ) , a risky decision-making task ( RDMT ) , and the Card Arranging Reward Responsivity Objective Test ( CARROT ) . The groups did not differ on the CARROT measure of responsiveness to financial incentive ; however , the ecstasy group displayed significantly elevated MFF20 impulsivity , and showed reduced discrimination between magnitudes of prospect i ve gains and losses when making risky decisions , compared to the ‘ polydrug ’ and ‘ drug-naïve ’ control groups . These findings may reflect a vulnerability of 5-HT systems in the orbital prefrontal cortex and interconnected corticolimbic circuitry to the cumulative neurotoxic effects of ecstasy and have clinical significance for regular ecstasy users . The combination of elevated impulsivity and impaired use of reinforcement cues in uncertain decision-making may comprise risk factors for continued drug abuse and everyday functioning (±)3,4-Methylenedioxymethamphetamine ( MDMA ; “ Ecstasy ” ) , an increasingly popular recreational drug , is known to damage brain serotonin 5-hydroxytryptamine ( 5-HT ) neurons in experimental animals . Whether MDMA is neurotoxic in humans has not been established . Thirty MDMA users and 28 controls were admitted to a controlled inpatient setting for measurement of biologic and behavioral indexes of central 5-HT function . Outcome measures obtained after at least 2 weeks of drug abstinence included concentrations of monoamine metabolites in cerebrospinal fluid ( CSF ) , prolactin responses to L-tryptophan , nociceptive responses to ischemic pain , and personality characteristics in which 5-HT has been implicated ( i.e. , impulsivity and aggression ) . Subjects with a history of MDMA exposure had lower levels of CSF 5-hydroxyindoleacetic acid ( the major metabolite of 5-HT ) than controls ( p = .002 ) . Although they resembled controls in their prolactin response to L-tryptophan and their response to ischemic pain ,  MDMA  users had lower scores on personality measures of impulsivity ( p = . 004 ) and indirect hostility ( p = .009 ) . The CSF findings suggest that 5-HT neurotoxicity may be a potential complication of MDMA use . Further , differences in personality support the view that 5-HT systems are involved in modulating impulsive and aggressive personality traits . Additional studies of  MDMA-exposed individuals are needed to confirm and extend the present findings . Such studies could help eluci date the role of 5-HT in normal brain function as well as in neuropsychiatric disease states Case reports indicate that psychiatrists administered ±3,4-methylenedioxymethamphetamine ( MDMA ) as a catalyst to psychotherapy before recreational use of MDMA as ‘ Ecstasy ’ result ed in its criminalization in 1985 . Over two decades later , this study is the first completed clinical trial evaluating MDMA as a therapeutic adjunct . Twenty patients with chronic posttraumatic stress disorder , refractory to both psychotherapy and psychopharmacology , were r and omly assigned to psychotherapy with concomitant active drug ( n = 12 ) or inactive placebo ( n = 8) administered during two 8-h experimental psychotherapy sessions . Both groups received preparatory and follow-up non-drug psychotherapy . The primary outcome measure was the Clinician-Administered PTSD Scale , administered at baseline , 4 days after each experimental session , and 2 months after the second session . Neurocognitive testing , blood pressure , and temperature monitoring were performed . After 2-month follow-up , placebo subjects were offered the option to re-enroll in the experimental procedure with open-label MDMA .  Decrease in Clinician-Administered PTSD Scale scores from baseline was significantly greater for the group that received MDMA than for the placebo group at all three time points after baseline . The rate of clinical response was 10/12 ( 83 % ) in the active treatment group versus 2/8 ( 25 % ) in the placebo group . There were no drug-related serious adverse events , adverse neurocognitive effects or clinical ly significant blood pressure increases . MDMA-assisted psychotherapy can be administered to posttraumatic stress disorder patients without evidence of harm , and it may be useful in patients refractory to other treatments Recent pre clinical evidence suggests that repeated exposure to 3 , 4-methylenedioxy-methamphetamine ( MDMA ; “ ecstasy ” ) produces long-term reductions in serotonin ( 5-HT ) levels . 5-HT has been implicated in the regulation of mood , anxiety , aggression , impulsivity , and cognition . Accordingly , in the first of two separate studies , these variables were investigated in three groups : ( 1 ) MDMA group — recreational ecstasy users ( who also used other illicit substances ) ; ( 2 ) polydrug controls — who had never taken ecstasy , but otherwise had drug histories and personal characteristics similar to the ecstasy users ; and ( 3 ) n 
    Output:
    
agent
Thus , the current state of research does not allow for the conclusion that long-term use of MDMA affects decision-making behavior in general .
***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: Abstract Evidence for serotonin involvement in impulsivity has generated interest in the measurement of impulsivity in regular ecstasy users , who are thought to display serotonergic dysfunction . However , current findings are inconsistent . Here , we used a recently developed Information Sampling Test to measure ‘ reflection ’ impulsivity in 46 current ecstasy users , 14 subjects who used ecstasy in the past , 15 current cannabis users and 19 drug-naïve controls . Despite elevated scores on the Impulsivity subscale of the Eysenck Impulsiveness-Venturesomeness-Empathy question naire , the current and previous ecstasy users did not differ significantly from the drug-naive controls on the Information Sampling Test . In contrast , the cannabis users sample d significantly less information on the task , and tolerated a lower level of certainty in their decision-making , in comparison to the drug-naive controls . The effect in cannabis users extends our earlier observations in amphetamine- and opiate-dependent individuals ( Clark , et al. , 2006 , Biological Psychiatry 60 : 515–522 ) , and suggests that reduced reflection may be a common cognitive style across regular users of a variety of substances . However , the lack of effects in the two ecstasy groups suggests that the relationship between serotonin function , ecstasy use and impulsivity is more complex Abstract Exposure therapy is known to be an effective treatment for anxiety disorders . Nevertheless , exposure is not used as much as it should be , and instead patients are often given supportive medications such as serotonin reuptake inhibitors ( SSRIs ) and benzodiazepines , which may even interfere with the extinction learning that is the aim of treatment . Given that r and omized controlled trials are now investigating a few doses of ±3,4-methylenedioxymethamphetamine ( MDMA , ‘ ecstasy ’ ) in combination with psychotherapy for treatment-resistant anxiety disorders , we would like to suggest the following three mechanisms for this potentially important new approach : 1 ) MDMA  increases oxytocin levels , which may strengthen the therapeutic alliance ; 2 ) MDMA  increases ventromedial prefrontal activity and decreases amygdala activity , which may improve emotional regulation and decrease avoidance and 3 ) MDMA  increases norepinephrine release and circulating cortisol levels , which may facilitate emotional engagement and enhance extinction of learned fear associations . Thus , MDMA has a combination of pharmacological effects that , in a therapeutic setting , could provide a balance of activating emotions while feeling safe and in control , as described in case reports of MDMA-augmented psychotherapy . Further clinical and pre clinical studies of the therapeutic value of MDMA are indicated 3,4-Methylenedioxymethamphetamine ( MDMA , ' ecstasy ' ) releases serotonin and norepinephrine . MDMA is reported to produce empathogenic and prosocial feelings . It is unknown whether MDMA in fact alters empathic concern and prosocial behavior . We investigated the acute effects of MDMA using the Multifaceted Empathy Test ( MET ) , dynamic Face Emotion Recognition Task ( FERT ) and Social Value Orientation ( SVO ) test . We also assessed effects of MDMA on plasma levels of hormones involved in social behavior using a placebo-controlled , double-blind , r and om-order , cross-over design in 32 healthy volunteers ( 16 women ) .  MDMA enhanced explicit and implicit emotional empathy in the MET and increased prosocial behavior in the SVO test in men . MDMA did not alter cognitive empathy in the MET but impaired the identification of negative emotions , including fearful , angry and sad faces , in the FERT , particularly in women . MDMA increased plasma levels of cortisol and prolactin , which are markers of serotonergic and noradrenergic activity , and of oxytocin , which has been associated with prosocial behavior . In summary , MDMA sex-specifically altered the recognition of emotions , emotional empathy and prosociality . These effects likely enhance sociability when MDMA is used recreationally and may be useful when MDMA is administered in conjunction with psychotherapy in patients with social dysfunction or post-traumatic stress disorder While accumulating evidence suggests that effective real-life decision-making depends upon the functioning of the orbitofrontal cortex , much less is known about the involvement of the monoamine neurotransmitter systems and , in particular , serotonin . In the present study , we explored the impact of depleting the serotonin precursor , tryptophan , on human decision-making . Eighteen healthy volunteers consumed an amino-acid drink containing tryptophan and 18 healthy volunteers consumed an amino-acid drink without tryptophan , before choosing between simultaneously presented gambles , differing in the magnitude of expected gains ( ie reward ) , the magnitude of expected losses ( ie punishment ) , and the probabilities with which these outcomes were delivered . Volunteers also chose between gambles probing identified non-nomative biases in human decision-making , namely , risk-aversion when choosing between gains and risk-seeking when choosing between losses . Tryptophan-depleted volunteers showed reduced discrimination between magnitudes of expected gains associated with different choices . There was little evidence that tryptophan depletion was associated with altered discrimination between the magnitudes of expected losses , or altered discrimination between the relative probabilities with which these positive or negative outcomes were delivered . Risk-averse and risk-seeking biases were also unchanged . These results suggest that serotonin mediates decision-making in healthy volunteers by modulating the processing of reward cues , perhaps represented within the orbitofrontal cortex . It is possible that such a change in the cognition mediating human choice is one mechanism associated with the onset and maintenance of anhedonia and lowered mood in psychiatric illness Abstract . Rationale : ( ± ) 3,4-Methylenedioxymethamphetamine ( MDMA or " ecstasy " ) has been shown to cause long term damage to serotonergic cerebral neurons in animals . The neurotoxic effects in humans are less clear and little is known about the functional consequences , although some studies suggest memory impairment . Given the widespread use of MDMA , our lack of knowledge raises concerns . Objective : We investigated , in humans , the relation between past use of ecstasy and cognitive performance as well as serotonergic function . Methods : Two groups of 21 males with moderate and heavy recreational use of MDMA , respectively , and a control group of 20 males without use of MDMA were compared . All were from the same subculture . Reaction time , direct recall , and recognition were assessed . Serotonergic function was measured by the neuro-endocrine response to a placebo-controlled , crossover challenge with dexfenfluramine . Results : Ecstasy users showed a broad pattern of statistically significant , but clinical ly small , impairment of memory and prolonged reaction times . Heavy users were affected stronger than moderate users . Release of cortisol but not of prolactin  after dexfenfluramine administration was significantly reduced in both groups of ecstasy users compared with the controls . Analyses of covariance showed that likely confounding variables including recent exposure to ecstasy , psychosocial profiles and use of other drugs did not explain the differences found between the groups . Conclusions : These results provide further evidence that use of ecstasy may be associated with impairment of memory and of serotonergic function . These findings are compatible with neurotoxicity of ecstasy as shown in animals To examine the neurotoxic potential of continued  MDMA ( “ Ecstasy ” )  use in humans and its functional consequences over the course of 1 year , 15 MDMA users participated in a longitudinal study in which they completed a brief neuropsychological test battery composed mainly of retrospective and prospect i ve memory tasks . Subjects were abstinent for 2 weeks on initial and 1-year testing . Continued use of MDMA was associated with progressive decline in terms of immediate and delayed recall Ecstasy ( MDMA ; 3,4-methylenedioxymethamphetamine ) has a well-recognized neurotoxic effect on central serotonergic ( 5-HT ) systems in animals , and there is some evidence of persistent serotonergic dysregulation in human ecstasy users . Serotonin is believed to mediate impulsive behavior and effective decision-making . Thus , the aim of the present study was to investigate impulsive behavior and decision-making in abstinent regular ecstasy users . Three groups were compared : ‘ ecstasy users ’ ( recreational ecstasy users who reported modest use of illicit drugs other than cannabis ) , ‘ polydrug controls ’ ( ecstasy naïve illicit drug users ) , and ‘ drug-naïve controls ’ .  All participants completed personal details and general drug history question naires , the National Adult Reading Test , Matching Familiar Figures Test ( MFF20 ) , a risky decision-making task ( RDMT ) , and the Card Arranging Reward Responsivity Objective Test ( CARROT ) . The groups did not differ on the CARROT measure of responsiveness to financial incentive ; however , the ecstasy group displayed significantly elevated MFF20 impulsivity , and showed reduced discrimination between magnitudes of prospect i ve gains and losses when making risky decisions , compared to the ‘ polydrug ’ and ‘ drug-naïve ’ control groups . These findings may reflect a vulnerability of 5-HT systems in the orbital prefrontal cortex and interconnected corticolimbic circuitry to the cumulative neurotoxic effects of ecstasy and have clinical significance for regular ecstasy users . The combination of elevated impulsivity and impaired use of reinforcement cues in uncertain decision-making may comprise risk factors for continued drug abuse and everyday functioning (±)3,4-Methylenedioxymethamphetamine ( MDMA ; “ Ecstasy ” ) , an increasingly popular recreational drug , is known to damage brain serotonin 5-hydroxytryptamine ( 5-HT ) neurons in experimental animals . Whether MDMA is neurotoxic in humans has not been established . Thirty MDMA users and 28 controls were admitted to a controlled inpatient setting for measurement of biologic and behavioral indexes of central 5-HT function . Outcome measures obtained after at least 2 weeks of drug abstinence included concentrations of monoamine metabolites in cerebrospinal fluid ( CSF ) , prolactin responses to L-tryptophan , nociceptive responses to ischemic pain , and personality characteristics in which 5-HT has been implicated ( i.e. , impulsivity and aggression ) . Subjects with a history of MDMA exposure had lower levels of CSF 5-hydroxyindoleacetic acid ( the major metabolite of 5-HT ) than controls ( p = .002 ) . Although they resembled controls in their prolactin response to L-tryptophan and their response to ischemic pain ,  MDMA  users had lower scores on personality measures of impulsivity ( p = . 004 ) and indirect hostility ( p = .009 ) . The CSF findings suggest that 5-HT neurotoxicity may be a potential complication of MDMA use . Further , differences in personality support the view that 5-HT systems are involved in modulating impulsive and aggressive personality traits . Additional studies of  MDMA-exposed individuals are needed to confirm and extend the present findings . Such studies could help eluci date the role of 5-HT in normal brain function as well as in neuropsychiatric disease states Case reports indicate that psychiatrists administered ±3,4-methylenedioxymethamphetamine ( MDMA ) as a catalyst to psychotherapy before recreational use of MDMA as ‘ Ecstasy ’ result ed in its criminalization in 1985 . Over two decades later , this study is the first completed clinical trial evaluating MDMA as a therapeutic adjunct . Twenty patients with chronic posttraumatic stress disorder , refractory to both psychotherapy and psychopharmacology , were r and omly assigned to psychotherapy with concomitant active drug ( n = 12 ) or inactive placebo ( n = 8) administered during two 8-h experimental psychotherapy sessions . Both groups received preparatory and follow-up non-drug psychotherapy . The primary outcome measure was the Clinician-Administered PTSD Scale , administered at baseline , 4 days after each experimental session , and 2 months after the second session . Neurocognitive testing , blood pressure , and temperature monitoring were performed . After 2-month follow-up , placebo subjects were offered the option to re-enroll in the experimental procedure with open-label MDMA .  Decrease in Clinician-Administered PTSD Scale scores from baseline was significantly greater for the group that received MDMA than for the placebo group at all three time points after baseline . The rate of clinical response was 10/12 ( 83 % ) in the active treatment group versus 2/8 ( 25 % ) in the placebo group . There were no drug-related serious adverse events , adverse neurocognitive effects or clinical ly significant blood pressure increases . MDMA-assisted psychotherapy can be administered to posttraumatic stress disorder patients without evidence of harm , and it may be useful in patients refractory to other treatments Recent pre clinical evidence suggests that repeated exposure to 3 , 4-methylenedioxy-methamphetamine ( MDMA ; “ ecstasy ” ) produces long-term reductions in serotonin ( 5-HT ) levels . 5-HT has been implicated in the regulation of mood , anxiety , aggression , impulsivity , and cognition . Accordingly , in the first of two separate studies , these variables were investigated in three groups : ( 1 ) MDMA group — recreational ecstasy users ( who also used other illicit substances ) ; ( 2 ) polydrug controls — who had never taken ecstasy , but otherwise had drug histories and personal characteristics similar to the ecstasy users ; and ( 3 ) n 
    Output:
    