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: Rationale Although 3,4-methylenedioxymethamphetamine ( MDMA ; Ecstasy ) has been reported to cause fatal hyperthermia , few studies of the effects of MDMA on core body temperature in humans have been conducted demonstrating increased body temperature . In rats , MDMA causes hyperthermia at warm ambient temperatures but hypothermia at cold ones . Objectives In this study , the physiological and subjective effects of MDMA in humans were determined at cold ( 18 ° C ) and warm ( 30 ° C ) ambient temperatures in a temperature and humidity-controlled laboratory . Methods Ten healthy volunteers who were recreational users of MDMA were recruited . Four laboratory sessions were conducted in a 2 × 2 design [ i.e. , two sessions at 30 ° C and two at 18 ° C , two during MDMA ( 2 mg/kg , p.o . ) and two during placebo , in double-blind fashion ] . Core body temperature ( ingested radiotelemetry pill ) , skin temperature ( four weighted sites ) , heart rate , blood pressure , metabolic rate ( indirect calorimetry ) , shivering ( electromyogram levels ) , and sweat rate ( capacitance hygrometry ) were measured as well as subjective effects for several time periods following capsule ingestion . Results MDMA produced significant elevations in core body temperature and metabolic rate in both warm and cold conditions . MDMA also produced significant elevations in blood pressure and heart rate and significantly increased several ratings of subjective effects similar to those previously reported . There were no differences related to ambient temperature for any of the subjective effects , except that ratings of cold and warm were appropriate to the ambient temperature and were not influenced by MDMA . Conclusions Unlike findings in rats , MDMA  increased core body temperature regardless of ambient temperature in humans . These increases appeared related to increases in metabolic rate , which were substantial . These findings warrant further investigations on the role of MDMA and other stimulants in altering metabolism and thermogenesis Rationale Recreational use of ecstasy ( 3,4-methylenedioxymethamphetamine [ MDMA ] ) has been associated with memory impairments . Functional neuroimaging studies with cross-sectional design s reported altered memory-related hippocampal functioning in ecstasy-polydrug users . However , differences might be pre-existing or related to the concomitant use of amphetamine . Objective To prospect ively investigate the specific effects of ecstasy on memory-related hippocampal functioning . Methods We used an associative memory task and functional magnetic resonance imaging ( fMRI ) in 40 ecstasy and /or amphetamine users at baseline ( t1 ) and after 12 months ( t2 ) . At t1 , all subjects had very limited amphetamine and /or ecstasy experience ( less than 5 units lifetime dose ) . Based on the reported drug use at t2 , subjects with continued ecstasy and /or amphetamine use ( n = 17 ) were compared to subjects who stopped use after t1 ( n = 12 ) . Results Analysis of repeated measures revealed that encoding-related activity in the left parahippocampal gyrus changed differentially between the groups . Activity in this region increased in abstinent subjects from t1 to t2 , however , decreased in subjects with continued use . Decreases within the left parahippocampal gyrus were associated with the use of ecstasy , but not amphetamine , during the follow-up period . However , there were no significant differences in memory performance . Conclusions The current findings suggest specific effects of ecstasy use on memory-related hippocampal functioning . However , alternative explanations such as (sub-)acute cannabis effects are conceivable Drug addiction is a chronic , relapsing brain disorder . The identification of biomarkers that render individuals vulnerable for the transition from occasional drug use to addiction is of key importance to develop early intervention strategies . The aim of the present study was to prospect ively assess brain structural markers for escalating drug use in two independent sample s of occasional amphetamine-type stimulant users . At baseline occasional users of amphetamine and 3,4-methylenedioxymethamphetamine ( cumulative lifetime use ≤10 units ) underwent structural brain imaging and were followed up at 12 months and 24 months ( Study 1 , n = 38 ; Study 2 , n = 28 ) . Structural vulnerability markers for escalating amphetamine-type drug use were examined by comparing baseline grey matter volumes of participants who increased use with those who maintained or reduced use during the follow-up period . Participants in both sample s who subsequently increased amphetamine-type drugs use displayed smaller medial prefrontal cortex volumes and , additionally , in the basolateral amygdala ( Study 1 ) and dorsal striatum ( Study 2 ) . In both sample s the baseline volumes were significantly negatively correlated with stimulant use during the subsequent 12 and 24 months . Additional multiple regression analyses on the pooled data sets revealed some evidence of a compound-specific association between the baseline volume of the left basolateral amygdala and the subsequent use of amphetamine . These findings indicate that smaller brain volumes in fronto-striato-limbic regions implicated in impulsivity and decision-making might render an individual vulnerable for the transition from occasional to escalating amphetamine-type stimulant use Previous studies have suggested toxic effects of recreational ecstasy use on the serotonin system of the brain . However , it can not be excluded that observed differences between users and non-users are the cause rather than the consequence of ecstasy use . As part of the Netherl and s XTC Toxicity ( NeXT ) study , we prospect ively assessed sustained effects of ecstasy use on the brain in novel ecstasy users using repeated measurements with a combination of different neuroimaging parameters of neurotoxicity . At baseline , 188 ecstasy-naive volunteers with high probability of first ecstasy use were examined . After a mean period of 17 months follow-up , neuroimaging was repeated in 59 incident ecstasy users and 56 matched persistent ecstasy-naives and their outcomes were compared . Neuroimaging included [(123)I]beta-carbomethoxy-3beta-(4-iodophenyl)tropane ( CIT ) SPECT to measure serotonin transporter densities as indicators of serotonergic function ; (1)H-MR spectroscopy ( (1)H-MRS ) to measure brain metabolites as indicators of neuronal damage ; diffusion tensor imaging ( DTI ) to measure the apparent diffusion coefficient and fractional anisotropy ( FA ) of the diffusional motion of water molecules in the brain as indicators of axonal integrity ; and perfusion weighted imaging ( PWI ) to measure regional relative cerebral blood volume ( rrCBV ) which indicates brain perfusion . With this approach , both structural ( (1)H-MRS and DTI ) and functional ( [(123)I]beta-CIT SPECT and PWI ) aspects of neurotoxicity were combined . Compared to persistent ecstasy-naives , novel low-dose ecstasy users ( mean 6.0 , median 2.0 tablets ) showed decreased rrCBV in the globus pallidus and putamen ; decreased FA in thalamus and frontoparietal white matter ; increased FA in globus pallidus ; and increased apparent diffusion coefficient in the thalamus . No changes in serotonin transporter densities and brain metabolites were observed . These findings suggest sustained effects of ecstasy on brain microvasculature , white matter maturation and possibly axonal damage due to low dosages of ecstasy . Although we do not know yet whether these effects are reversible or not , we can not exclude that ecstasy even in low doses is neurotoxic to the brain Rationale Neurotoxic effects of 3,4-methylenedioxymethamphetamine ( MDMA , “ ecstasy ” ) on the serotonin ( 5-HT ) system have been described in animals and humans , but little is known about long-term effects of ecstasy use on mood . Objectives To investigate short-term and long-term effects of ecstasy use on mood and its association with 5-HT neurotoxicity , dose , and gender in humans . Methods Fifteen moderate ecstasy users , 23 heavy ecstasy users , 16 former heavy ecstasy users and 15 drug-using , but ecstasy-naive controls were included .  Mood was assessed using the Composite International Diagnostic Interview ( CIDI ) and the Beck Depression Inventory ( BDI ) . Outcomes were correlated with 5-HT transporter ( SERT ) density , assessed with [123I]β-CIT single photon emission computed tomography ( SPECT ) . Results The prevalence of mood disorders assessed by CIDI did not differ between all groups . The overall test for differences in BDI scores between groups was near significance ( P=0.056 ) , with BDI scores higher in former heavy ecstasy users than in ecstasy-naive controls ( P=0.045 ) . BDI scores were correlated with the total number of ecstasy tablets used ( r=0.310 ; P=0.021 ) . No associations between CIDI or BDI outcomes and SERT density or gender were observed . Conclusions These results suggest that ecstasy use is not associated with clinical depression ( CIDI ) . However , the number of ecstasy tablets taken lifetime was associated with higher BDI scores for depressive mood , and this relationship seemed to persist after ecstasy use had stopped . We did not find that depressed mood in ecstasy users was associated with decrease in SERT density . Prospect i ve studies are needed to establish the causal relationship between ecstasy use and depressed mood OBJECTIVE To determine incidence and patterns of natural course of ecstasy/stimulant/hallucinogen ( ESH ) use and disorders as well as cohort effects in a community sample of adolescents and young adults . METHOD Cumulative incidence and patterns of ecstasy use and disorders were examined in a prospect i ve longitudinal design ( mean follow-up period=42 months ) in a representative sample ( N=2446 ) aged 14 - 24 years at the outset of the study . Patterns of DSM-IV defined ESH use , abuse and dependence were assessed with the Munich Composite International Diagnostic Interview ( M-CIDI ) . RESULTS ( 1 ) Cumulative lifetime incidence for use of ESH at second follow-up : 9.1 % , 1.0 % for abuse , 0.6 % for dependence ; ( 2 ) men used and abused ESH more often than women ; ( 3 ) the younger birth cohort ( 1977 - 81 ) tended to start earlier with substance (ab)use compared to the older birth cohort ( 1970 - 77 ) ; ( 4 ) use of ESH was associated with increasing rates of concomitant use of other licit and illicit drugs ; ( 5 ) the majority of the lifetime ESH users without disorder had stopped to use these substances and not consumed them during the 12 months preceding the second follow-up ; ( 6 ) those who had stopped to take ecstasy and related drugs at follow-up also took other illicit drugs  less often than those who continued to consume ESH . CONCLUSIONS Use of design er drugs is widespread in our sample , but the probability of developing use disorders is fairly low ( 1.6 % ) . The majority of the ESH users stopped their use spontaneously in their twenties ( 80 % of the prior users without disorder , 67 % of the prior abusers ) , but 50 % of those that once had fulfilled DSM-IV criteria of dependence continued to use these substances 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 It is debated whether ecstasy use has neurotoxic effects on the human brain and what the effects are of a low dose of ecstasy use . We prospect ively studied sustained effects ( > 2 weeks abstinence ) of a low dose of ecstasy on the brain in ecstasy-naive volunteers using a combination of advanced MR techniques and self-report question naires on psychopathology as part of the NeXT ( Netherl and s XTC Toxicity ) study . Outcomes of  proton magnetic resonance spectroscopy ( 1H-MRS ) , diffusion tensor imaging ( DTI ) , perfusion-weighted imaging ( PWI 
    Output:
    
agent
There is no convincing evidence that moderate MDMA use is associated with structural or functional brain alterations in neuroimaging measures .
***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: Rationale Although 3,4-methylenedioxymethamphetamine ( MDMA ; Ecstasy ) has been reported to cause fatal hyperthermia , few studies of the effects of MDMA on core body temperature in humans have been conducted demonstrating increased body temperature . In rats , MDMA causes hyperthermia at warm ambient temperatures but hypothermia at cold ones . Objectives In this study , the physiological and subjective effects of MDMA in humans were determined at cold ( 18 ° C ) and warm ( 30 ° C ) ambient temperatures in a temperature and humidity-controlled laboratory . Methods Ten healthy volunteers who were recreational users of MDMA were recruited . Four laboratory sessions were conducted in a 2 × 2 design [ i.e. , two sessions at 30 ° C and two at 18 ° C , two during MDMA ( 2 mg/kg , p.o . ) and two during placebo , in double-blind fashion ] . Core body temperature ( ingested radiotelemetry pill ) , skin temperature ( four weighted sites ) , heart rate , blood pressure , metabolic rate ( indirect calorimetry ) , shivering ( electromyogram levels ) , and sweat rate ( capacitance hygrometry ) were measured as well as subjective effects for several time periods following capsule ingestion . Results MDMA produced significant elevations in core body temperature and metabolic rate in both warm and cold conditions . MDMA also produced significant elevations in blood pressure and heart rate and significantly increased several ratings of subjective effects similar to those previously reported . There were no differences related to ambient temperature for any of the subjective effects , except that ratings of cold and warm were appropriate to the ambient temperature and were not influenced by MDMA . Conclusions Unlike findings in rats , MDMA  increased core body temperature regardless of ambient temperature in humans . These increases appeared related to increases in metabolic rate , which were substantial . These findings warrant further investigations on the role of MDMA and other stimulants in altering metabolism and thermogenesis Rationale Recreational use of ecstasy ( 3,4-methylenedioxymethamphetamine [ MDMA ] ) has been associated with memory impairments . Functional neuroimaging studies with cross-sectional design s reported altered memory-related hippocampal functioning in ecstasy-polydrug users . However , differences might be pre-existing or related to the concomitant use of amphetamine . Objective To prospect ively investigate the specific effects of ecstasy on memory-related hippocampal functioning . Methods We used an associative memory task and functional magnetic resonance imaging ( fMRI ) in 40 ecstasy and /or amphetamine users at baseline ( t1 ) and after 12 months ( t2 ) . At t1 , all subjects had very limited amphetamine and /or ecstasy experience ( less than 5 units lifetime dose ) . Based on the reported drug use at t2 , subjects with continued ecstasy and /or amphetamine use ( n = 17 ) were compared to subjects who stopped use after t1 ( n = 12 ) . Results Analysis of repeated measures revealed that encoding-related activity in the left parahippocampal gyrus changed differentially between the groups . Activity in this region increased in abstinent subjects from t1 to t2 , however , decreased in subjects with continued use . Decreases within the left parahippocampal gyrus were associated with the use of ecstasy , but not amphetamine , during the follow-up period . However , there were no significant differences in memory performance . Conclusions The current findings suggest specific effects of ecstasy use on memory-related hippocampal functioning . However , alternative explanations such as (sub-)acute cannabis effects are conceivable Drug addiction is a chronic , relapsing brain disorder . The identification of biomarkers that render individuals vulnerable for the transition from occasional drug use to addiction is of key importance to develop early intervention strategies . The aim of the present study was to prospect ively assess brain structural markers for escalating drug use in two independent sample s of occasional amphetamine-type stimulant users . At baseline occasional users of amphetamine and 3,4-methylenedioxymethamphetamine ( cumulative lifetime use ≤10 units ) underwent structural brain imaging and were followed up at 12 months and 24 months ( Study 1 , n = 38 ; Study 2 , n = 28 ) . Structural vulnerability markers for escalating amphetamine-type drug use were examined by comparing baseline grey matter volumes of participants who increased use with those who maintained or reduced use during the follow-up period . Participants in both sample s who subsequently increased amphetamine-type drugs use displayed smaller medial prefrontal cortex volumes and , additionally , in the basolateral amygdala ( Study 1 ) and dorsal striatum ( Study 2 ) . In both sample s the baseline volumes were significantly negatively correlated with stimulant use during the subsequent 12 and 24 months . Additional multiple regression analyses on the pooled data sets revealed some evidence of a compound-specific association between the baseline volume of the left basolateral amygdala and the subsequent use of amphetamine . These findings indicate that smaller brain volumes in fronto-striato-limbic regions implicated in impulsivity and decision-making might render an individual vulnerable for the transition from occasional to escalating amphetamine-type stimulant use Previous studies have suggested toxic effects of recreational ecstasy use on the serotonin system of the brain . However , it can not be excluded that observed differences between users and non-users are the cause rather than the consequence of ecstasy use . As part of the Netherl and s XTC Toxicity ( NeXT ) study , we prospect ively assessed sustained effects of ecstasy use on the brain in novel ecstasy users using repeated measurements with a combination of different neuroimaging parameters of neurotoxicity . At baseline , 188 ecstasy-naive volunteers with high probability of first ecstasy use were examined . After a mean period of 17 months follow-up , neuroimaging was repeated in 59 incident ecstasy users and 56 matched persistent ecstasy-naives and their outcomes were compared . Neuroimaging included [(123)I]beta-carbomethoxy-3beta-(4-iodophenyl)tropane ( CIT ) SPECT to measure serotonin transporter densities as indicators of serotonergic function ; (1)H-MR spectroscopy ( (1)H-MRS ) to measure brain metabolites as indicators of neuronal damage ; diffusion tensor imaging ( DTI ) to measure the apparent diffusion coefficient and fractional anisotropy ( FA ) of the diffusional motion of water molecules in the brain as indicators of axonal integrity ; and perfusion weighted imaging ( PWI ) to measure regional relative cerebral blood volume ( rrCBV ) which indicates brain perfusion . With this approach , both structural ( (1)H-MRS and DTI ) and functional ( [(123)I]beta-CIT SPECT and PWI ) aspects of neurotoxicity were combined . Compared to persistent ecstasy-naives , novel low-dose ecstasy users ( mean 6.0 , median 2.0 tablets ) showed decreased rrCBV in the globus pallidus and putamen ; decreased FA in thalamus and frontoparietal white matter ; increased FA in globus pallidus ; and increased apparent diffusion coefficient in the thalamus . No changes in serotonin transporter densities and brain metabolites were observed . These findings suggest sustained effects of ecstasy on brain microvasculature , white matter maturation and possibly axonal damage due to low dosages of ecstasy . Although we do not know yet whether these effects are reversible or not , we can not exclude that ecstasy even in low doses is neurotoxic to the brain Rationale Neurotoxic effects of 3,4-methylenedioxymethamphetamine ( MDMA , “ ecstasy ” ) on the serotonin ( 5-HT ) system have been described in animals and humans , but little is known about long-term effects of ecstasy use on mood . Objectives To investigate short-term and long-term effects of ecstasy use on mood and its association with 5-HT neurotoxicity , dose , and gender in humans . Methods Fifteen moderate ecstasy users , 23 heavy ecstasy users , 16 former heavy ecstasy users and 15 drug-using , but ecstasy-naive controls were included .  Mood was assessed using the Composite International Diagnostic Interview ( CIDI ) and the Beck Depression Inventory ( BDI ) . Outcomes were correlated with 5-HT transporter ( SERT ) density , assessed with [123I]β-CIT single photon emission computed tomography ( SPECT ) . Results The prevalence of mood disorders assessed by CIDI did not differ between all groups . The overall test for differences in BDI scores between groups was near significance ( P=0.056 ) , with BDI scores higher in former heavy ecstasy users than in ecstasy-naive controls ( P=0.045 ) . BDI scores were correlated with the total number of ecstasy tablets used ( r=0.310 ; P=0.021 ) . No associations between CIDI or BDI outcomes and SERT density or gender were observed . Conclusions These results suggest that ecstasy use is not associated with clinical depression ( CIDI ) . However , the number of ecstasy tablets taken lifetime was associated with higher BDI scores for depressive mood , and this relationship seemed to persist after ecstasy use had stopped . We did not find that depressed mood in ecstasy users was associated with decrease in SERT density . Prospect i ve studies are needed to establish the causal relationship between ecstasy use and depressed mood OBJECTIVE To determine incidence and patterns of natural course of ecstasy/stimulant/hallucinogen ( ESH ) use and disorders as well as cohort effects in a community sample of adolescents and young adults . METHOD Cumulative incidence and patterns of ecstasy use and disorders were examined in a prospect i ve longitudinal design ( mean follow-up period=42 months ) in a representative sample ( N=2446 ) aged 14 - 24 years at the outset of the study . Patterns of DSM-IV defined ESH use , abuse and dependence were assessed with the Munich Composite International Diagnostic Interview ( M-CIDI ) . RESULTS ( 1 ) Cumulative lifetime incidence for use of ESH at second follow-up : 9.1 % , 1.0 % for abuse , 0.6 % for dependence ; ( 2 ) men used and abused ESH more often than women ; ( 3 ) the younger birth cohort ( 1977 - 81 ) tended to start earlier with substance (ab)use compared to the older birth cohort ( 1970 - 77 ) ; ( 4 ) use of ESH was associated with increasing rates of concomitant use of other licit and illicit drugs ; ( 5 ) the majority of the lifetime ESH users without disorder had stopped to use these substances and not consumed them during the 12 months preceding the second follow-up ; ( 6 ) those who had stopped to take ecstasy and related drugs at follow-up also took other illicit drugs  less often than those who continued to consume ESH . CONCLUSIONS Use of design er drugs is widespread in our sample , but the probability of developing use disorders is fairly low ( 1.6 % ) . The majority of the ESH users stopped their use spontaneously in their twenties ( 80 % of the prior users without disorder , 67 % of the prior abusers ) , but 50 % of those that once had fulfilled DSM-IV criteria of dependence continued to use these substances 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 It is debated whether ecstasy use has neurotoxic effects on the human brain and what the effects are of a low dose of ecstasy use . We prospect ively studied sustained effects ( > 2 weeks abstinence ) of a low dose of ecstasy on the brain in ecstasy-naive volunteers using a combination of advanced MR techniques and self-report question naires on psychopathology as part of the NeXT ( Netherl and s XTC Toxicity ) study . Outcomes of  proton magnetic resonance spectroscopy ( 1H-MRS ) , diffusion tensor imaging ( DTI ) , perfusion-weighted imaging ( PWI 
    Output:
    