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: OBJECTIVE We sought to examine the relation between cannabis abuse and the symptomatic course of recent-onset schizophrenia and related disorders . DESIGN A prospect i ve cohort study over a year using monthly Brief Psychiatric Rating Scale assessment s. PARTICIPANTS  Cannabis-abusing patients ( n = 24 ) were compared with nonabusers ( n = 69 ) . Eleven patients were mild and 13 were heavy cannabis-abusing patients . RESULTS Significantly more and earlier psychotic relapses occurred in the cannabis-abusing group ( P = .03 ) . This association became stronger when mild and heavy cannabis abuse were distinguished ( P = .002 ) . No confounding effect of other variables , eg , other street drugs , was found . In all but one patient , cannabis abuse preceded the onset of the first psychotic symptoms for at least 1 year . CONCLUSIONS Cannabis abuse and particularly heavy abuse can be considered a stressor eliciting relapse in patients with schizophrenia and related disorders and possibly a premorbid precipitant BACKGROUND Cannabis use is a major problem in inner cities and has been causally implicated in psychosis . Very few of the available hospital-based studies of the implication s of cannabis usage have involved psychiatric intensive care units ( PICU ) ; but PICU receive many of the most challenging and re source -hungry- and incompletely understood- patients in the mental health system . AIMS To study the clinical impact of cannabis abuse in a PICU , and to compare the use of atypical and typical antipsychotics in this setting . METHOD 115 patients admitted to a PICU consented to take part in an open label naturalistic study .  BPRS , TCI-240 , weight , length of admission and routine bloods were evaluated in all participants . RESULTS There was a high rate of cannabis abuse ( 71.3 % ) in the PICU population . Patients who abused cannabis spent longer in PICU because their psychoses were more severe . They were younger at first hospital admission . Cannabis also had metabolic implication s , with higher blood glucose levels at admission and greater weight increase .  Atypical antipsychotics were effective in treating psychosis in patients positive to cannabis at admission . CONCLUSION Our findings suggest that cannabis abusers had a more severe psychotic illness , especially in schizophrenia . There are additional complications in terms of weight gain for cannabis users OBJECTIVE Relapse is a frequently used outcome measure in schizophrenia research . However , difficulties in reliably measuring relapse diminish its usefulness . Hospitalization is a potential alternative , but its relationship to relapse has not been assessed . METHODS This study used data from a two-year , prospect i ve study to examine associations between  relapse  and  hospitalization  in a cohort of 200 Canadian patients with first-episode psychosis . First , the relationship between relapse and  hospitalization  was assessed by cross-tabulating relapse and hospitalization . Next , survival curves of time to first relapse or hospitalization were compared . Finally , to examine the convergent validity of relapse and  hospitalization  , the predictive capacity of three predictors were examined : a substance use disorder diagnosis , prior hospitalization , and medication adherence . RESULTS Rates of both relapse and hospitalization were similar . During the two-year follow-up , 37 % of the patients experienced a relapse , and 26 % were hospitalized . As an indicator of relapse , hospitalization had a low sensitivity ( 47 % ) and high specificity ( 87 % ) . A higher risk of hospitalization and relapse was associated with prior hospitalization , a substance use disorder diagnosis , and medication nonadherence . CONCLUSIONS Results indicated that relapse and hospitalization are separate but related outcome measures . They had similar frequencies and were found to have similar relationships with some predictors . Relapse is a more useful outcome measure in smaller clinical studies in which routine st and ardized clinical measures can be used .  Hospitalization  is more relevant in larger studies or as a quality indicator for studies using administrative data bases , and it serves as a good measure for quality management in health systems Objective To determine whether use of cannabis in adolescence increases the risk for psychotic outcomes by affecting the incidence and persistence of sub clinical expression of psychosis in the general population ( that is , expression of psychosis below the level required for a clinical diagnosis ) . Design Analysis of data from a prospect i ve population based cohort study in Germany ( early developmental stages of psychopathology study ) . Setting Population based cohort study in Germany . Participants 1923 individuals from the general population , aged 14 - 24 at baseline . Main outcome measure Incidence and persistence of subthreshold psychotic symptoms after use of cannabis in adolescence .  Cannabis use and psychotic symptoms were assessed at three time points ( baseline , T2 ( 3.5 years ) , T3 ( 8.4 years ) ) over a 10 year follow-up period with the Munich version of the composite international diagnostic interview ( M-CIDI ) . Results In individuals who had no reported lifetime psychotic symptoms and no reported lifetime cannabis use at baseline , incident cannabis use over the period from baseline to T2 increased the risk of later incident psychotic symptoms over the period from T2 to T3 ( adjusted odds ratio 1.9 , 95 % confidence interval 1.1 to 3.1 ; P=0.021 ) . Furthermore , continued use of cannabis increased the risk of persistent psychotic symptoms over the period from T2 to T3 ( 2.2 , 1.2 to 4.2 ; P=0.016 ) . The incidence rate of psychotic symptoms over the period from baseline to T2 was 31 % ( 152 ) in exposed individuals versus 20 % ( 284 ) in non-exposed individuals ; over the period from T2 to T3 these rates were 14 % ( 108 ) and 8 % ( 49 ) , respectively . Conclusion Cannabis use is a risk factor for the development of incident psychotic symptoms . Continued cannabis use might increase the risk for psychotic disorder by impacting on the persistence of symptoms BACKGROUND Cannabis use has been identified as a potent predictor of the earlier onset of psychosis , but meta- analysis has not indicated that it has a clear effect in established psychosis . AIM To assess the association between cannabis and outcomes , including whether change in cannabis use affects symptoms and functioning , in a large sample of people with established nonaffective psychosis and comorbid substance misuse . METHODS One hundred and sixty participants whose substance use included cannabis were compared with other substance users ( n = 167 ) on baseline demographic , clinical , and substance use variables . The cannabis using subgroup was examined prospect ively with repeated measures of substance use and psychopathology at baseline , 12 months , and 24 months . We used generalized estimating equation models to estimate the effects of cannabis dose on subsequent clinical outcomes and whether change in cannabis use was associated with change in outcomes . RESULTS Cannabis users showed cross-sectional differences from other substances users but not in terms of positive symptoms . Second , cannabis dose was not associated with subsequent severity of positive symptoms and change in cannabis dose did not predict change in positive symptom severity , even when patients became abstinent . However , greater cannabis exposure was associated with worse functioning , albeit with a small effect size . CONCLUSIONS We did not find evidence of an association between cannabis dose and psychotic symptoms , although greater cannabis dose was associated with worse psychosocial functioning , albeit with small effect size . It would seem that within this population , not everyone will demonstrate durable symptomatic improvements from reducing cannabis All 533 patients in the acute and subacute psychiatric wards of a VA psychiatric facility were evaluated by nursing staff for substance abuse history and for illicit drug use . Eighteen percent had a history of either drug or combined drug and alcohol problems , 40 % had a history of alcohol abuse , and only 42 % had no substance abuse problems . Fifty-six of the patients with a history of drug problems ( 58 % ) were illicitly using drugs in the hospital . They were compared with a group of 64 r and omly chosen patients with no substance abuse history . Drug users were much younger and tended to be black ; they had more re-admissions , even though their original hospital admission was much more recent . Eighty-three percent of both groups had a primary diagnosis of schizophrenia , but drug users were more likely to be diagnosed paranoid schizophrenic . The groups did not differ significantly in treatment status and progress , except that drug users were more likely to exhibit marked mood changes . Half of the drug users were taking drugs three or more times weekly . Marijuana use was by far the most common substance observed . Ten consequences of drug use occurred in at least one-third of the users on a regular basis , the most common effects being negative attitudes toward treatment , cliquishness , secretiveness , and a need for greater supervision . The treatment problems and effects of drug use were much more serious for about half of the drug users than for the others CONTEXT Cannabis sativa use can impair verbal learning , provoke acute psychosis , and increase the risk of schizophrenia . It is unclear where C. sativa acts in the human brain to modulate verbal learning and to induce psychotic symptoms . OBJECTIVES To investigate the effects of 2 main psychoactive constituents of C. sativa , Delta9-tetrahydrocannabinol ( Delta9-THC ) and cannabidiol , on regional brain function during verbal paired associate learning . DESIGN Subjects were studied on 3 separate occasions using a block design functional magnetic resonance imaging paradigm while performing a verbal paired associate learning task . Each imaging session was preceded by the ingestion of Delta9-THC ( 10 mg ) , cannabidiol ( 600 mg ) , or placebo in a double-blind , r and omized , placebo-controlled , repeated- measures , within-subject design . SETTING University research center . PARTICIPANTS Fifteen healthy , native English-speaking , right-h and ed men of white race/ethnicity who had used C. sativa 15 times or less and had minimal exposure to other illicit drugs in their lifetime . MAIN OUTCOME MEASURES Regional brain activation ( blood oxygen level-dependent response ) , performance in a verbal learning task , and objective and subjective ratings of psychotic symptoms , anxiety , intoxication , and sedation . RESULTS Delta9-Tetrahydrocannabinol increased psychotic symptoms and levels of anxiety , intoxication , and sedation , whereas no significant effect was noted on these parameters following administration of cannabidiol .  Performance in the verbal learning task was not significantly modulated by either drug . Administration of Delta9-THC augmented activation in the parahippocampal gyrus during blocks 2 and 3 such that the normal linear decrement in activation across repeated encoding blocks was no longer evident . Delta9-Tetrahydrocannabinol also attenuated the normal time-dependent change in ventrostriatal activation during retrieval of word pairs , which was directly correlated with concurrently induced psychotic symptoms . In contrast , administration of cannabidiol had no such effect . CONCLUSION The modulation of mediotemporal and ventrostriatal function by Delta9-THC may underlie the effects of C. sativa on verbal learning and psychotic symptoms , respectively BACKGROUND There are inconsistencies in findings as to whether cannabis use has a negative impact on clinical outcomes for people with established psychosis . Effects may be more evident on patients with recent onset psychosis . AIM To investigate the relationship between cannabis use and clinical outcome , including whether change in cannabis use affects psychotic symptoms , affective symptoms , functioning and psychotic relapse in a sample of people in early psychosis with comorbid cannabis abuse or dependence . METHODS One hundred and ten participants were examined prospect ively with repeated measures of substance use antecedent to psychopathology at baseline , 4.5 , 9 , and 18 months . We used r and om intercept models to estimate the effects of cannabis dose on subsequent clinical outcomes and whether change in cannabis use was associated with change in outcomes . RESULTS There was no evidence of a specific association between cannabis use and positive symptoms , or negative symptoms , relapse or hospital admissions . However , a greater dose of cannabis was associated with subsequent higher depression and anxiety . Change in the amount of cannabis used was associated with statistically significant corresponding change in anxiety scores , but not depression . Additionally , reductions in cannabis exposure were related to improved patient functioning . CONCLUSIONS Reducing cannabis may be directly associated with improvements in anxiety and functioning , but not other specific symptoms It has long been known that acute marijuana administration impairs working memory ( e.g. , the discrimination of stimuli separated by a delay ) . The determination of which of the individual components of memory are altered by marijuana is an unresolved problem . Previous human studies did not use test protocol s that allowed for the determination of delay-independent ( initial discrimination ) from delay-dependent ( forgetting or retrieval ) components of memory . Using methods developed in the experimental analysis of behavior and signal detection theory , we tested the acute effects of smoked marijuana on forgetting functions in 5 humans . Immediately after smoking placebo , a low dose , or a high dose of marijuana ( varying in delta9-THC content ) , subjects completed delayed match-to- sample testing that included a range of retention intervals within each test session ( 0.5 , 4 , 12 , and 24 s ) . Performances ( discriminability ) at each dose were plotted as forgetting functions , as described and developed by White and colleagues ( White , 1985 ; White & Ruske , 2002 ) . For all 5 subjects , both delta9-THC doses impaired delay-dependent discrimination but not delay-independent discrimination . The outcome is consistent with current nonhuman studies examining the role of the 
    Output:
    
agent
INTERPRETATION Continued cannabis use after onset of psychosis predicts adverse outcome , including higher relapse rates , longer hospital admissions , and more severe positive symptoms than for individuals who discontinue cannabis use and those who are non-users .
***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: OBJECTIVE We sought to examine the relation between cannabis abuse and the symptomatic course of recent-onset schizophrenia and related disorders . DESIGN A prospect i ve cohort study over a year using monthly Brief Psychiatric Rating Scale assessment s. PARTICIPANTS  Cannabis-abusing patients ( n = 24 ) were compared with nonabusers ( n = 69 ) . Eleven patients were mild and 13 were heavy cannabis-abusing patients . RESULTS Significantly more and earlier psychotic relapses occurred in the cannabis-abusing group ( P = .03 ) . This association became stronger when mild and heavy cannabis abuse were distinguished ( P = .002 ) . No confounding effect of other variables , eg , other street drugs , was found . In all but one patient , cannabis abuse preceded the onset of the first psychotic symptoms for at least 1 year . CONCLUSIONS Cannabis abuse and particularly heavy abuse can be considered a stressor eliciting relapse in patients with schizophrenia and related disorders and possibly a premorbid precipitant BACKGROUND Cannabis use is a major problem in inner cities and has been causally implicated in psychosis . Very few of the available hospital-based studies of the implication s of cannabis usage have involved psychiatric intensive care units ( PICU ) ; but PICU receive many of the most challenging and re source -hungry- and incompletely understood- patients in the mental health system . AIMS To study the clinical impact of cannabis abuse in a PICU , and to compare the use of atypical and typical antipsychotics in this setting . METHOD 115 patients admitted to a PICU consented to take part in an open label naturalistic study .  BPRS , TCI-240 , weight , length of admission and routine bloods were evaluated in all participants . RESULTS There was a high rate of cannabis abuse ( 71.3 % ) in the PICU population . Patients who abused cannabis spent longer in PICU because their psychoses were more severe . They were younger at first hospital admission . Cannabis also had metabolic implication s , with higher blood glucose levels at admission and greater weight increase .  Atypical antipsychotics were effective in treating psychosis in patients positive to cannabis at admission . CONCLUSION Our findings suggest that cannabis abusers had a more severe psychotic illness , especially in schizophrenia . There are additional complications in terms of weight gain for cannabis users OBJECTIVE Relapse is a frequently used outcome measure in schizophrenia research . However , difficulties in reliably measuring relapse diminish its usefulness . Hospitalization is a potential alternative , but its relationship to relapse has not been assessed . METHODS This study used data from a two-year , prospect i ve study to examine associations between  relapse  and  hospitalization  in a cohort of 200 Canadian patients with first-episode psychosis . First , the relationship between relapse and  hospitalization  was assessed by cross-tabulating relapse and hospitalization . Next , survival curves of time to first relapse or hospitalization were compared . Finally , to examine the convergent validity of relapse and  hospitalization  , the predictive capacity of three predictors were examined : a substance use disorder diagnosis , prior hospitalization , and medication adherence . RESULTS Rates of both relapse and hospitalization were similar . During the two-year follow-up , 37 % of the patients experienced a relapse , and 26 % were hospitalized . As an indicator of relapse , hospitalization had a low sensitivity ( 47 % ) and high specificity ( 87 % ) . A higher risk of hospitalization and relapse was associated with prior hospitalization , a substance use disorder diagnosis , and medication nonadherence . CONCLUSIONS Results indicated that relapse and hospitalization are separate but related outcome measures . They had similar frequencies and were found to have similar relationships with some predictors . Relapse is a more useful outcome measure in smaller clinical studies in which routine st and ardized clinical measures can be used .  Hospitalization  is more relevant in larger studies or as a quality indicator for studies using administrative data bases , and it serves as a good measure for quality management in health systems Objective To determine whether use of cannabis in adolescence increases the risk for psychotic outcomes by affecting the incidence and persistence of sub clinical expression of psychosis in the general population ( that is , expression of psychosis below the level required for a clinical diagnosis ) . Design Analysis of data from a prospect i ve population based cohort study in Germany ( early developmental stages of psychopathology study ) . Setting Population based cohort study in Germany . Participants 1923 individuals from the general population , aged 14 - 24 at baseline . Main outcome measure Incidence and persistence of subthreshold psychotic symptoms after use of cannabis in adolescence .  Cannabis use and psychotic symptoms were assessed at three time points ( baseline , T2 ( 3.5 years ) , T3 ( 8.4 years ) ) over a 10 year follow-up period with the Munich version of the composite international diagnostic interview ( M-CIDI ) . Results In individuals who had no reported lifetime psychotic symptoms and no reported lifetime cannabis use at baseline , incident cannabis use over the period from baseline to T2 increased the risk of later incident psychotic symptoms over the period from T2 to T3 ( adjusted odds ratio 1.9 , 95 % confidence interval 1.1 to 3.1 ; P=0.021 ) . Furthermore , continued use of cannabis increased the risk of persistent psychotic symptoms over the period from T2 to T3 ( 2.2 , 1.2 to 4.2 ; P=0.016 ) . The incidence rate of psychotic symptoms over the period from baseline to T2 was 31 % ( 152 ) in exposed individuals versus 20 % ( 284 ) in non-exposed individuals ; over the period from T2 to T3 these rates were 14 % ( 108 ) and 8 % ( 49 ) , respectively . Conclusion Cannabis use is a risk factor for the development of incident psychotic symptoms . Continued cannabis use might increase the risk for psychotic disorder by impacting on the persistence of symptoms BACKGROUND Cannabis use has been identified as a potent predictor of the earlier onset of psychosis , but meta- analysis has not indicated that it has a clear effect in established psychosis . AIM To assess the association between cannabis and outcomes , including whether change in cannabis use affects symptoms and functioning , in a large sample of people with established nonaffective psychosis and comorbid substance misuse . METHODS One hundred and sixty participants whose substance use included cannabis were compared with other substance users ( n = 167 ) on baseline demographic , clinical , and substance use variables . The cannabis using subgroup was examined prospect ively with repeated measures of substance use and psychopathology at baseline , 12 months , and 24 months . We used generalized estimating equation models to estimate the effects of cannabis dose on subsequent clinical outcomes and whether change in cannabis use was associated with change in outcomes . RESULTS Cannabis users showed cross-sectional differences from other substances users but not in terms of positive symptoms . Second , cannabis dose was not associated with subsequent severity of positive symptoms and change in cannabis dose did not predict change in positive symptom severity , even when patients became abstinent . However , greater cannabis exposure was associated with worse functioning , albeit with a small effect size . CONCLUSIONS We did not find evidence of an association between cannabis dose and psychotic symptoms , although greater cannabis dose was associated with worse psychosocial functioning , albeit with small effect size . It would seem that within this population , not everyone will demonstrate durable symptomatic improvements from reducing cannabis All 533 patients in the acute and subacute psychiatric wards of a VA psychiatric facility were evaluated by nursing staff for substance abuse history and for illicit drug use . Eighteen percent had a history of either drug or combined drug and alcohol problems , 40 % had a history of alcohol abuse , and only 42 % had no substance abuse problems . Fifty-six of the patients with a history of drug problems ( 58 % ) were illicitly using drugs in the hospital . They were compared with a group of 64 r and omly chosen patients with no substance abuse history . Drug users were much younger and tended to be black ; they had more re-admissions , even though their original hospital admission was much more recent . Eighty-three percent of both groups had a primary diagnosis of schizophrenia , but drug users were more likely to be diagnosed paranoid schizophrenic . The groups did not differ significantly in treatment status and progress , except that drug users were more likely to exhibit marked mood changes . Half of the drug users were taking drugs three or more times weekly . Marijuana use was by far the most common substance observed . Ten consequences of drug use occurred in at least one-third of the users on a regular basis , the most common effects being negative attitudes toward treatment , cliquishness , secretiveness , and a need for greater supervision . The treatment problems and effects of drug use were much more serious for about half of the drug users than for the others CONTEXT Cannabis sativa use can impair verbal learning , provoke acute psychosis , and increase the risk of schizophrenia . It is unclear where C. sativa acts in the human brain to modulate verbal learning and to induce psychotic symptoms . OBJECTIVES To investigate the effects of 2 main psychoactive constituents of C. sativa , Delta9-tetrahydrocannabinol ( Delta9-THC ) and cannabidiol , on regional brain function during verbal paired associate learning . DESIGN Subjects were studied on 3 separate occasions using a block design functional magnetic resonance imaging paradigm while performing a verbal paired associate learning task . Each imaging session was preceded by the ingestion of Delta9-THC ( 10 mg ) , cannabidiol ( 600 mg ) , or placebo in a double-blind , r and omized , placebo-controlled , repeated- measures , within-subject design . SETTING University research center . PARTICIPANTS Fifteen healthy , native English-speaking , right-h and ed men of white race/ethnicity who had used C. sativa 15 times or less and had minimal exposure to other illicit drugs in their lifetime . MAIN OUTCOME MEASURES Regional brain activation ( blood oxygen level-dependent response ) , performance in a verbal learning task , and objective and subjective ratings of psychotic symptoms , anxiety , intoxication , and sedation . RESULTS Delta9-Tetrahydrocannabinol increased psychotic symptoms and levels of anxiety , intoxication , and sedation , whereas no significant effect was noted on these parameters following administration of cannabidiol .  Performance in the verbal learning task was not significantly modulated by either drug . Administration of Delta9-THC augmented activation in the parahippocampal gyrus during blocks 2 and 3 such that the normal linear decrement in activation across repeated encoding blocks was no longer evident . Delta9-Tetrahydrocannabinol also attenuated the normal time-dependent change in ventrostriatal activation during retrieval of word pairs , which was directly correlated with concurrently induced psychotic symptoms . In contrast , administration of cannabidiol had no such effect . CONCLUSION The modulation of mediotemporal and ventrostriatal function by Delta9-THC may underlie the effects of C. sativa on verbal learning and psychotic symptoms , respectively BACKGROUND There are inconsistencies in findings as to whether cannabis use has a negative impact on clinical outcomes for people with established psychosis . Effects may be more evident on patients with recent onset psychosis . AIM To investigate the relationship between cannabis use and clinical outcome , including whether change in cannabis use affects psychotic symptoms , affective symptoms , functioning and psychotic relapse in a sample of people in early psychosis with comorbid cannabis abuse or dependence . METHODS One hundred and ten participants were examined prospect ively with repeated measures of substance use antecedent to psychopathology at baseline , 4.5 , 9 , and 18 months . We used r and om intercept models to estimate the effects of cannabis dose on subsequent clinical outcomes and whether change in cannabis use was associated with change in outcomes . RESULTS There was no evidence of a specific association between cannabis use and positive symptoms , or negative symptoms , relapse or hospital admissions . However , a greater dose of cannabis was associated with subsequent higher depression and anxiety . Change in the amount of cannabis used was associated with statistically significant corresponding change in anxiety scores , but not depression . Additionally , reductions in cannabis exposure were related to improved patient functioning . CONCLUSIONS Reducing cannabis may be directly associated with improvements in anxiety and functioning , but not other specific symptoms It has long been known that acute marijuana administration impairs working memory ( e.g. , the discrimination of stimuli separated by a delay ) . The determination of which of the individual components of memory are altered by marijuana is an unresolved problem . Previous human studies did not use test protocol s that allowed for the determination of delay-independent ( initial discrimination ) from delay-dependent ( forgetting or retrieval ) components of memory . Using methods developed in the experimental analysis of behavior and signal detection theory , we tested the acute effects of smoked marijuana on forgetting functions in 5 humans . Immediately after smoking placebo , a low dose , or a high dose of marijuana ( varying in delta9-THC content ) , subjects completed delayed match-to- sample testing that included a range of retention intervals within each test session ( 0.5 , 4 , 12 , and 24 s ) . Performances ( discriminability ) at each dose were plotted as forgetting functions , as described and developed by White and colleagues ( White , 1985 ; White & Ruske , 2002 ) . For all 5 subjects , both delta9-THC doses impaired delay-dependent discrimination but not delay-independent discrimination . The outcome is consistent with current nonhuman studies examining the role of the 
    Output:
    