title: Cannabis abuse and the course of recent onset schizophrenic disorders Is cannabis an anti-antipsychotic? The experience in psychiatric intensive care. Relationship between relapse and hospitalization in first-episode psychosis. Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study Does change in cannabis use in established psychosis affect clinical outcome? Effects of illicit drug use in an inpatient psychiatric population. Modulation of mediotemporal and ventrostriatal function in humans by Delta9-tetrahydrocannabinol: a neural basis for the effects of Cannabis sativa on learning and psychosis. The impact of cannabis use on clinical outcomes in recent onset psychosis. Marijuana effects on human forgetting functions. Substance misuse in first-episode psychosis: 15-month prospective follow-up study. The temporal dynamics of relationships between cannabis, psychosis and depression among young adults with psychotic disorders: findings from a 10-month prospective study. Effects of cannabis use status on cognitive function, in males with schizophrenia Continued cannabis use and outcome in first-episode psychosis: data from a randomized, open-label, controlled trial. Course of cannabis use and clinical outcome in patients with non-affective psychosis: a 3-year follow-up study. Effect of cannabis use on the course of schizophrenia in male patients: A prospective cohort study Delta-9-tetrahydrocannabinol effects in schizophrenia: Implications for cognition, psychosis, and addiction
abstract: 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 cannabinoid system on delayed matching procedures , and the data help illuminate one behavioral mechanism through which marijuana alters memory performance BACKGROUND Well- design ed prospect i ve studies of substance misuse in first-episode psychosis can improve our underst and ing of the risks associated with comorbid substance misuse and psychosis . AIMS To examine the potential effects of substance misuse on in-patient admission and remission and relapse of positive symptoms in first-episode psychosis . METHOD The study was a prospect i ve 15-month follow-up investigation of 103 patients with first-episode psychosis recruited from three mental health services . RESULTS Substance misuse was independently associated with increased risk of in-patient admission , relapse of positive symptoms and shorter time to relapse of positive symptoms after controlling for potential confounding factors . Substance misuse was not associated with remission or time to remission of positive symptoms . Heavy substance misuse was associated with increased risk of in-patient admission , relapse and shorter time to relapse . CONCLUSIONS Substance misuse is an independent risk factor for a problematic recovery from first-episode psychosis BACKGROUND The aim was to examine the temporal relationships over 10 months between cannabis use and symptoms of psychosis and depression in people with schizophrenia and related disorders . The design was a prospect i ve study of 101 patients with schizophrenia and related disorders who were assessed monthly over 10 months on medication compliance , cannabis and other drug use , symptoms of depression and symptoms of psychosis . METHOD Linear regression methods to assess relationships between cannabis use and symptoms of psychosis and depression while adjusting for serial dependence , medication compliance and other demographic and clinical variables . RESULTS Cannabis use predicted a small but statistically significant increase in symptoms of psychosis , but not depression , after controlling for other differences between cannabis users and non-users . Symptoms of depression and psychosis did not predict cannabis use . CONCLUSION Continued cannabis use by persons with schizophrenia predicts a small increase in psychotic symptom severity but not vice versa Cognitive impairment and cannabis use are common among patients with schizophrenia . However , the moderating role of cannabis on cognition remains unclear . We sought to examine cognitive performance as a function of cannabis use patterns in schizophrenia . A secondary aim was to determine the effects of cumulative cannabis exposure on cognition . Cognition was assessed in male out patients with current cannabis dependence ( n=18 ) and no current cannabis use disorders ( n=29 ) . We then parsed non-current users into patients with lifetime cannabis dependence ( n=21 ) and no lifetime cannabis dependence ( n=8 ) . Finally , as an exploratory analysis , we examined relationships between cumulative cannabis exposure and cognition in lifetime dependent patients . Cross-sectional comparisons suggest that lifetime cannabis users demonstrate better processing speed than patients with no lifetime dependence . Exploratory analyses indicated that patients with current dependence exhibited robust negative relationships between cumulative cannabis exposure and cognition ; these associations were absent in former users . Cannabis status has minimal effects on cognition in males with schizophrenia . However , cumulative cannabis exposure significantly impairs cognition in current , but not former users , suggesting that the state dependent negative effects of cannabis may be reversed with sustained abstinence . Prospect i ve studies are needed to confirm these findings OBJECTIVE Cannabis use has been found to increase the risk of psychosis .  It is unclear whether , after a first psychotic episode has occurred , continued cannabis use is associated with poor functional outcome of psychosis . METHOD As part of a r and omized , open-label , controlled trial , the association of cannabis use and measures for psychopathology and social role functioning after 2 years of follow-up and for the recently proposed outcome measures of symptomatic remission , functional remission , and clinical recovery was explored in a group of 124 patients suffering from nonaffective first-episode psychosis ( diagnosed according to DSM-IV and included from a catchment area in the Netherl and s of 3.1 million inhabitants from October 2001 through December 2002 ) . Other patient characteristics that were expected to be independently associated with outcome , among them alcohol and other drug use , were assessed at baseline . RESULTS Continued cannabis use was not associated with symptomatic or functional remission or clinical recovery . After 2 years , cannabis use was related to certain aspects of social role functioning ( economic and social activities ; explained variance 5.6 % and 8.4 % , respectively ) but not to psychopathology ( Positive and Negative Syndrome Scale Positive , Negative , or General symptoms ) . CONCLUSIONS Our findings support the notion that continued cannabis use after the onset of a first-episode psychosis is correlated with worse social outcome and should be discouraged whenever possible , but its role in outcome is modest in comparison to other factors . TRIAL REGISTRATION Nederl and s Trial Register : http://www.trialregister.nl ( ID : NTR 374 ) BACKGROUND Prospect i ve studies on the relationship between course of cannabis use and clinical outcome in patients with non-affective psychotic disorders are inconclusive . The current study examined whether ( 1 ) persistent , recently started , discontinued and non-cannabis-using patients with a psychotic disorder differed with regard to illness outcome at 3-year follow-up , and ( 2 ) whether timing of cannabis discontinuation was associated with course of clinical outcome . METHOD This 3-year follow-up study was part of a multi-center study in the Netherl and s and Belgium ( Genetic Risk and Outcome of Psychosis ; GROUP ) . We used mixed-model analyses to investigate the association between pattern of cannabis use and symptoms , global functioning and psychotic relapse . RESULTS In our sample of 678 patients , we found persistent users to have more positive and general symptoms , worse global functioning and more psychotic relapses compared with non-users and discontinued users [ Positive and Negative Syndrome Scale ( PANSS ) positive , p < 0.001 ; PANSS general , p < 0.001 ; Global Assessment of Functioning ( GAF ) symptoms , p = 0.017 ; GAF disability , p < 0.001 ; relapses , p = 0.038 ] . Patients who started using cannabis after study onset were characterized by worse functioning at baseline and showed an increase in general symptoms ( including depression and anxiety ) at the 3-year follow-up ( p = 0.005 ) . Timing of cannabis discontinuation was not associated with clinical outcome . CONCLUSIONS These findings suggest that cannabis use in patients with a psychotic disorder has a long-lasting negative effect on illness outcome , particularly when persistent . Treatment should focus on discouraging cannabis use BACKGROUND Findings on the impact of cannabis use on the course of schizophrenia are inconsistent and not conclusive . AIMS To study the effect of cannabis use on the course of schizophrenia taking into account the effects of the quantity of cannabis use and important confounders . METHODS Prospect i ve cohort study with assessment s of symptoms , confounders and hospitalizations at baseline , 6 month and 12 month follow up . RESULTS In a representative cohort of 145 male patients with schizophrenia , 68 ( 46.9 % ) used cannabis .  Mean age at onset of schizophrenia in cannabis using patients was significantly lower than in non-cannabis using patients . No other cross-sectional demographic or clinical differences were observed between users and non-users . In a series of longitudinal analyses , cannabis use was not associated with differences in psychopathology , but relapse in terms of the number of hospitalizations was significantly higher in cannabis using patients compared to non-cannabis using patients . CONCLUSIONS Patients with schizophrenia using cannabis are more frequently hospitalized than non-cannabis using patients but do not differ with respect to psychopathology . Possible explanations for these findings are discussed BACKGROUND Recent advances in the neurobiology of cannabinoids have renewed interest in the association between cannabis and psychotic disorders . METHODS In a 3-day , double-blind , r and omized , placebo-controlled study , the behavioral , cognitive , motor , and endocrine effects of 0 mg , 2.5 mg , and 5 mg intravenous Delta-9-tetrahydrocannabinol ( Delta-9-THC ) were characterized in 13 stable , antipsychotic-treated schizophrenia patients . These data were compared with effects in healthy subjects reported elsewhere . RESULTS Delta-9-tetrahydrocannabinol transiently increased 1 ) learning and recall deficits ; 2 ) positive , negative , and general schizophrenia symptoms ; 3 ) perceptual alterations ; 4 ) akathisia , rigidity , and dyskinesia ; 5 ) deficits in vigilance ; and 6 ) plasma prolactin and cortisol .  Schizophrenia patients were more vulnerable to Delta-9-THC effects on recall relative to control subjects . There were no serious short- or long-term adverse events associated with study participation . CONCLUSIONS Delta-9-tetrahydrocannabinol is associated with transient exacerbation in core psychotic and cognitive deficits in schizophrenia . These data do not provide a reason to explain why schizophrenia patients use or misuse cannabis . Furthermore , Delta-9-THC might differentially affect schizophrenia patients relative to control subjects . Finally , the enhanced sensitivity to the cognitive effects of Delta-9-THC warrants further study into whether brain cannabinoid receptor dysfunction contributes to the pathophysiology of the cognitive deficits associated with schizophrenia
target: 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 .
background: BACKGROUND Although the link between cannabis use and development of psychosis is well established , less is known about the effect of continued versus discontinued cannabis use after the onset of psychosis .
  We aim ed to summarise available evidence focusing on the relationship between continued and discontinued cannabis use after onset of psychosis and its relapse .