The effect of clozapine and risperidone on attentional bias in patients with schizophrenia and a cannabis use disorder: An fMRI study Cannabis use and cannabis use disorders and their relationship to mental disorders: a 10-year prospective-longitudinal community study in adolescents. The relevance of age at first alcohol and nicotine use for initiation of cannabis use and progression to cannabis use disorders. Cannabis use disorders in schizophrenia: Effects on cognition and symptoms Subjective Cannabis Effects as Part of a Developing Disorder in Adolescents and Emerging Adults A randomized placebo-controlled trial of N-acetylcysteine for cannabis use disorder in adults. CANDIS treatment program for cannabis use disorders: findings from a randomized multi-site translational trial. Spatial working memory in heavy cannabis users: a functional magnetic resonance imaging study Age‐varying effects of cannabis use frequency and disorder on symptoms of psychosis, depression and anxiety in adolescents and adults Cannabis abuse and the course of recent onset schizophrenic disorders Transitions from first substance use to substance use disorders in adolescence: is early onset associated with a rapid escalation? The temporal dynamics of relationships between cannabis, psychosis and depression among young adults with psychotic disorders: findings from a 10-month prospective study. The impact of substance use on brain structure in people at high risk of developing schizophrenia. Verbal learning and memory in adolescent cannabis users, alcohol users and non-users Cannabis cue-induced brain activation correlates with drug craving in limbic and visual salience regions: Preliminary results Effects of cannabis use status on cognitive function, in males with schizophrenia A randomized controlled trial of a brief motivational enhancement for non-treatment-seeking adolescent cannabis users. Cue-induced striatal activity in frequent cannabis users independently predicts cannabis problem severity three years later Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study Clinical profile of participants in a brief intervention program for cannabis use disorder. Cannabis abuse and serious suicide attempts. Mechanisms Underlying the Link between Cannabis Use and Prospective Memory A randomized controlled trial of brief cognitive-behavioral interventions for cannabis use disorder. Cannabis use and transition to psychosis in people at ultra-high risk. Cannabis use and risk of schizophrenia: a Mendelian randomization study Internet-based prevention for alcohol and cannabis use: final results of the Climate Schools course. Delivering prevention for alcohol and cannabis using the Internet: a cluster randomised controlled trial. A cross-validation trial of an Internet-based prevention program for alcohol and cannabis: Preliminary results from a cluster randomised controlled trial Course of cannabis use and clinical outcome in patients with non-affective psychosis: a 3-year follow-up study. Individual and combined effects of acute delta-9-tetrahydrocannabinol and cannabidiol on psychotomimetic symptoms and memory function
Cannabis use disorders ( CUDs ) are highly comorbid in patients with schizophrenia and are associated with poor outcome . Clozapine has been put forward as the first choice antipsychotic in this comorbid group . However , little is known about the mechanisms underlying the assumed superiority of clozapine . We compared the effects of clozapine and risperidone on attentional bias , subjective craving and associated regional brain activity in patients with schizophrenia and CUD . Overall , 36 patients with schizophrenia and 19 healthy controls were included . Patients were r and omised to antipsychotic treatment with clozapine or risperidone . At baseline and after 4 weeks of medication use , regional brain responses were measured during a classical Stroop and a cannabis word Stroop using functional magnetic resonance imaging . Clozapine-treated CUD patients showed a larger reduction in craving and in activation of the insula during the cannabis word Stroop , while risperidone-treated patients showed a larger decrease in activation of the right anterior cingulate cortex during the classical Stroop . A significant association was found between decreases in subjective craving and decreases in insula activation during the cannabis word Stroop . These findings strongly suggest that clozapine may be a better treatment choice in patients with schizophrenia and CUD than risperidone BACKGROUND Whereas the role of externalizing disorders is relatively well established in predicting the onset of cannabis use ( CU ) or cannabis use disorder ( CUD ) , the status of anxiety and mood disorders in predicting CU and CUD remains controversial . OBJECTIVE ( 1 ) To examine cross-sectional and prospect i ve associations of CU and CUD with a range of mental disorders and whether anxiety and mood disorders are associated with CU/CUD after adjusting for externalizing disorders . METHODS N=1395 community subjects aged 14 - 17 at baseline were followed-up at three waves prospect ively over 10 years . Substance use , substance disorders and mental disorders were assessed using the DSM-IV/M-CIDI . RESULTS ( 1 ) The baseline prevalence rates where 19.3 % at t(0 ) for CU and 2.6 % for CUD . Cumulative incidence rates at t(3 ) were 54.3 % for CU and 13.7 % for CUD . ( 2 ) In cross-sectional and prospect i ve analyses other substance use disorders , mood and anxiety disorders were associated with CU and CUD . ( 3 ) Associations of panic-anxiety with CU and of depressive and bipolar disorders with CU and CUD were significant after controlling for externalizing disorders . CONCLUSION A range of psychopathological conditions , including depressive , bipolar and less consistently anxiety disorders as well as the degree of their comorbidity are significantly associated with incident CU and progression to CUD , even when controlling for externalising disorders . A better underst and ing of this complex interplay may result in better aetiological models and intervention strategies BACKGROUND A younger age at onset of use of a specific substance is a well-documented risk-factor for a substance use disorder ( SUD ) related to that specific substance . However , the cross-substance relationship between a younger age at onset of alcohol use ( AU ) and nicotine use ( NU ) and the risk of cannabis use disorders ( CUD ) in adolescence and early adulthood remains unclear . AIMS To identify the sequence of and latency between initial AU/NU and initial cannabis use ( CU ) . To investigate whether younger age at AU- and NU-onset is associated with any and earlier CU-onset and a higher risk of transition from first CU to CUD , taking into account externalizing disorders ( ED ) and parental substance use disorders as putative influential factors . METHODS Prospect ive-longitudinal community study with N=3021 subjects ( baseline age 14 - 24 ) and up to four assessment waves over up to ten years with additional direct parental and family history information .  Substance use and CUD were assessed with the DSM-IV/M-CIDI . RESULTS Most subjects with CU reported AU ( 99 % ) and NU ( 94 % ) . Among users of both substances , 93 % reported AU prior to CU ( 87 % for NU ) . After adjustment for ED and parental substance use disorders younger age at AU-onset was associated with any CU . Younger age at NU-onset was associated with earlier CU initiation . Younger age at AU- and NU-onset was not associated with a higher risk of CUD . CONCLUSIONS The cross-substance relevance of younger age at first AU and NU for the risk of CUD is limited to early CU involvement OBJECTIVE Despite the controversy surrounding the possible causal link between cannabis use and the onset of schizophrenia ( SZ ) , data seeking to eluci date the effect of cannabis use disorders ( CUDs ) on the clinical presentation of SZ have produced mixed results . Although several studies have suggested that CUD in patients with SZ may be associated with variation in cognitive function , clinical presentation and course of illness , the effects have been inconsistent . METHODS We retrospectively ascertained a large cohort ( N=455 ) of SZ patients with either no history of a CUD ( CUD- ; N=280 ) or a history of CUD ( CUD+ ; N=175 ) . The groups were initially compared on key demographic variables including sex , race , age , age at onset of SZ , parental socioeconomic status , premorbid IQ , education level and global assessment of functioning . Covarying for any observed differences in demographic variables , we then compared groups on lifetime measures of psychotic symptoms as well as a brief battery of neurocognitive tests . RESULTS Compared to the CUD- group the CUD+ group demonstrated significantly better performance on measures of processing speed ( Trail Making Tests A and B ) , verbal fluency ( animal naming ) and verbal learning and memory ( California Verbal Learning Test ) . Moreover , the CUD+ group had better GAF scores than the CUD group . CONCLUSIONS Collectively , these findings suggest that SZ patients with comorbid CUD may represent a higher functioning subgroup of SZ . Future prospect i ve studies are needed to eluci date the nature of this relationship In light of exp and ing legalization of cannabis and swelling debate about the potential risks , particularly for younger users , underst and ing acute cannabis effects among adolescents and emerging adults is more important than ever . Contemporary models of addiction development identify subjective drug responses as central to the developmental unfolding of drug use disorders . Despite this , surprisingly little is known about cannabis ’s acute subjective effects in human youths . This research utilized ecological momentary assessment ( EMA ) in the natural environment to identify the typical situational context of cannabis use among 85 frequent cannabis users , ages 15–24 years ( M = 19.8 , SD = 2.0 ; 48.2 % female ) . Study aims were to ( a ) characterize momentary changes in several subjective states ( i.e. , stimulation , sedation , tension , craving , and high ) when not using , just before cannabis use , and after use , and ( b ) evaluate whether cannabis responses varied with cannabis use disorder ( CUD ) severity or across the transition from adolescence to emerging adulthood in a correlational manner . Use of cannabis produced measurable reductions in craving and tension , as well as increases in stimulation , sedation , and “ high . ” Participants with more CUD symptoms reported greater relief of craving and increased stimulatory response and high following use . In contrast , emerging adults reported diminished stimulatory response and high following use , relative to adolescents . Results highlight the utility of EMA for characterizing cannabis response as this behavior unfolds in daily life , during a key developmental timeframe in the pathogenesis of cannabis-use pathology BACKGROUND Cannabis use disorder ( CUD ) is a prevalent and impairing condition , and established psychosocial treatments convey limited efficacy . In light of recent findings supporting the efficacy of N-acetylcysteine ( NAC ) for CUD in adolescents , the objective of this trial was to evaluate its efficacy in adults . METHODS In a 12-week double-blind r and omized placebo-controlled trial , treatment-seeking adults ages 18 - 50 with CUD ( N=302 ) , enrolled across six National Drug Abuse Treatment Clinical Trials Network-affiliated clinical sites , were r and omized in a 1:1 ratio to a 12-week course of NAC 1200 mg ( n=153 ) or placebo ( n=149 ) twice daily . All participants received contingency management ( CM ) and medical management . The primary efficacy measure was the odds of negative urine cannabinoid tests during treatment , compared between NAC and placebo participants . RESULTS There was not statistically significant evidence that the NAC and placebo groups differed in cannabis abstinence ( odds ratio=1.00 , 95 % confidence interval 0.63 - 1.59 , p=0.984 ) . Overall , 22.3 % of urine cannabinoid tests in the NAC group were negative , compared with 22.4 % in the placebo group . Many participants were medication non-adherent ; exploratory analysis within medication-adherent subgroups revealed no significant differential abstinence outcomes by treatment group . CONCLUSIONS In contrast with prior findings in adolescents , there is no evidence that NAC 1200 mg twice daily plus CM is differentially efficacious for CUD in adults when compared to placebo plus CM . This discrepant finding between adolescents and adults with CUD may have been influenced by differences in development , cannabis use profiles , responses to embedded behavioral treatment , medication adherence , and other factors BACKGROUND In a recent paper , we reported the efficacy of a modular cognitive-behavioral intervention for treating adolescents and adults with cannabis use disorders ( CUD ) . In this study , we examine the outcome of this intervention after translating it into clinical practice . METHODS A multi-site , r and omized controlled trial of 279 treatment seekers with ICD-10 cannabis use disorders aged 16- 63 years was conducted in 11 outpatient addiction treatment centers in Germany . Patients were r and omly assigned to an Active Treatment ( AT , n=149 ) or Delayed Treatment Control ( DTC , n=130 ) . Treatment consisted of 10 sessions of fully manualized individual psychotherapy that combined Cognitive-Behavioral Therapy , Motivational EnhancementTherapy and problem-solving training . Assessment s were conducted at baseline , during each therapy session , at post-treatment and at three and six month follow-ups . RESULTS At post assessment 53.3 % of AT patients reported abstinence ( 46.3 % negative urine screenings ) compared to 22 % of DTC patients ( 17.7 % negative drug screenings ) ( p<0.001 , Intention-to-treat analysis ) . AT patients improved in the frequency of cannabis use , number of cannabis dependence criteria , severity of dependence , as well as number and severity of cannabis-related problems . Effect sizes were moderate to high . While abstinence rates in the AT group decreased over the 3-month ( negative urine screenings : 32.4 % ) and 6-month ( negative urine screenings : 35.7 % ) follow-up periods , the effects in secondary outcomes were maintained . CONCLUSIONS The intervention can successfully be translated to and applied in clinical practice . It has the potential to improve access to evidence -based care for chronic CUD patients Rationale Many neuropsychological studies have documented deficits in working memory among recent heavy cannabis users . However , little is known about the effects of cannabis on brain activity . Objective We assessed brain function among recent heavy cannabis users while they performed a working memory task . Methods Functional magnetic resonance imaging was used to examine brain activity in 12 long-term heavy cannabis users , 6–36 h after last use , and in 10 control subjects while they performed a spatial working memory task .  Regional brain activation was analyzed and compared using statistical parametric mapping techniques . Results Compared with controls , cannabis users exhibited increased activation of brain regions typically used for spatial working memory tasks ( such as prefrontal cortex and anterior cingulate ) . Users also recruited additional regions not typically used for spatial working memory ( such as regions in the basal ganglia ) . These findings remained essentially unchanged when re-analyzed using subjects ’ ages as a covariate . Brain activation showed little or no significant correlation with subjects ’ years of education , verbal IQ , lifetime episodes of cannabis use , or urinary cannabinoid levels at the time of scanning . Conclusions Recent cannabis users displayed greater and more widespread brain activation than normal subjects when attempting to perform a spatial working memory task . This observation suggests that recent cannabis users may experience subtle neurophysiological deficits , and that they compensate for these deficits by “ working harder”—calling upon additional brain regions to meet the dem and s of the task Abstract Aims We tested the age‐varying associations of  cannabis use ( CU ) frequency and disorder ( CUD ) with  psychotic , depressive and anxiety symptoms in adolescent and adult sample s. Moderating effects of early onset ( ≤ 15 years ) and sex were tested . Design Time‐varying effect models were used to assess the significance of concurrent associations between CU and CUD  and symptoms of psychosis , depression and anxiety at each age . Setting and Participants Adolescent data ( V‐HYS ; n = 662 ) were collected from a r and omly recruited sample of adolescents in Victoria , British Columbia , Canada during a 10‐year period ( 2003–13 ) . Adult cross‐sectional data ( NESARC‐III ; n = 36 309 ) were collected from a representative sample from the United States ( 2012–13 ) .  Measurements Mental health symptoms were assessed using self‐report measures of diagnostic symptoms . CU was based on frequency of past‐year use . Past‐year CUD was based on DSM‐5 criteria . Findings For youth in the V‐HYS , CU was associated with psychotic symptoms following age 22 [ b = 0.13 , 95 % confidence interval ( CI ) = 0.002 , 0.25 ] , with depressive symptoms from ages 16–19 and following age 25 ( b = 0.17 , 95 % CI = 0.003 , 0.34 ) , but not with anxiety symptoms . CUD was associated with psychotic symptoms following age 23 ( b = 0.51 , 95 % CI = 0.01 , 1.01 ) , depressive symptoms at ages 19–20 and following age 25 ( b = 0.71 , 95 % CI = 0.001 , 1.42 ) and anxiety symptoms ages 26–27 only . For adults in the NESARC‐III , CU was associated with mental health symptoms at most ages [ e.g. psychotic symptoms ; age 18 ( b = 0.22 , 95 % CI = 0.10 , 0.33 ) to age 65 ( b = 0.36 , 95 % CI = 0.16 , 0.56 ) ] . CUD was associated with all mental health symptoms across most ages [ e.g. depressive symptoms ; age 18 ( b = 0.96 , 95 % CI = 0.19 , 1.73 ) to age 61 ( b = 1.11 , 95 % CI = 0.01 , 2.21 ) ] . Interactions with sex show stronger associations for females than males in young adulthood [ e.g. V‐HYS  : CUD × sex interaction on psychotic symptoms significant after age 26 ( b = 1.12 , 95 % CI = 0.02 , 2.21 ) ] . Findings were not moderated by early‐onset CU . Conclusions Significant associations between cannabis use ( CU ) frequency and disorder ( CUD ) and psychotic and depressive symptoms in late adolescence and young adulthood extend across adulthood , and include anxiety 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 Early substance use ( SU ) in adolescence is known to be associated with an elevated risk of developing substance use disorders ( SUD ) ; it remains unclear though whether early SU is associated with more rapid transitions to SUD . OBJECTIVE To examine the risk and speed of transition from first SU ( alcohol , nicotine , cannabis ) to SUD as a function of age of first use . METHODS N=3021 community subjects aged 14 - 24 years at baseline were followed-up prospect ively over 10-years . SU and SUD were assessed using the DSM-IV/M-CIDI . RESULTS ( 1 ) The conditional probability of substance-specific SU-SUD transition was the greatest for nicotine ( 36.0 % ) and the least for cannabis ( 18.3 % for abuse , 6.2 % for dependence ) with alcohol in between ( 25.3 % for abuse ; 11.2 % for dependence ) . ( 2 ) In addition to confirming early SU as a risk factor for SUD we find : ( 3 ) higher age of onset of any SU to be associated with faster transitions to SUD , except for cannabis dependence . ( 4 ) Transitions from first cannabis use ( CU ) to cannabis use disorders ( CUD ) occurred faster than for alcohol and nicotine . ( 5 ) Use of other substances co-occurred with risk and speed of transitions to specific SUDs . CONCLUSION Type of substance and concurrent use of other drugs are of importance for the association between age of first use and the speed of transitions to substance use disorders . Given that further research will identify moderators and mediators affecting these differential associations , these findings may have important implication s for design ing early and targeted interventions to prevent disorder progression 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 Ventricular enlargement and reduced prefrontal volume are consistent findings in schizophrenia . Both are present in first episode subjects and may be detectable before the onset of clinical disorder . Substance misuse is more common in people with schizophrenia and is associated with similar brain abnormalities . We employ a prospect i ve cohort study with nested case control comparison design to investigate the association between substance misuse , brain abnormality , and subsequent schizophrenia . Substance misuse history , imaging data , and clinical information were collected on 147 subjects at high risk of schizophrenia and 36 controls . Regions exhibiting a significant relationship between level of use of alcohol , cannabis or tobacco , and structure volume were identified . Multivariate regression then eluci date d the relationship between level of substance use and structure volumes while accounting for correlations between these variables and correcting for potential confounders . Finally , we established whether substance misuse was associated with later risk of schizophrenia . Increased ventricular volume was associated with alcohol and cannabis use in a dose-dependent manner . Alcohol consumption was associated with reduced frontal lobe volume . Multiple regression analyses found both alcohol and cannabis were significant predictors of these abnormalities when simultaneously entered into the statistical model . Alcohol and cannabis misuse were associated with an increased subsequent risk of schizophrenia . We provide prospect i ve evidence that use of cannabis or alcohol by people at high genetic risk of schizophrenia is associated with brain abnormalities and later risk of psychosis . A family history of schizophrenia may render the brain particularly sensitive to the risk-modifying effects of these substances Rationale Long-term heavy cannabis use can result in memory impairment .  Adolescent users may be especially vulnerable to the adverse neurocognitive effects of cannabis . Objectives and methods In a cross-sectional and prospect i ve neuropsychological study of 181 adolescents aged 16–20 ( mean 18.3 years ) , we compared performance indices from one of the most widely used measures of learning and memory — the Rey Auditory Verbal Learning Test — between cannabis users ( n = 52 ; mean 2.4 years of use , 14 days/month , median abstinence 20.3 h ) , alcohol users ( n = 67 ) and non-user controls ( n = 62 ) matched for age , education and premorbid intellectual ability ( assessed prospect ively ) , and alcohol consumption for cannabis and alcohol users . Results Cannabis users performed significantly worse than alcohol users and non-users on all performance indices . They recalled significantly fewer words overall ( p < 0.001 ) , demonstrating impaired learning ( p < 0.001 ) , retention ( p < 0.001 ) and retrieval ( p < 0.05 ) ( Cohen ’s d 0.43–0.84 ) . The degree of impairment was associated with the duration , quantity , frequency and age of onset of cannabis use , but was unrelated to alcohol exposure or other drug use . No gender effects were detected and the findings remained after controlling for premorbid intellectual ability . An earlier age of onset of regular cannabis use was associated with worse memory performance after controlling for extent of exposure to cannabis . Conclusions Despite relatively brief exposure , adolescent cannabis users relative to their age-matched counterparts demonstrated similar memory deficits to those reported in adult long-term heavy users . The results indicate that cannabis adversely affects the developing brain and reinforce concerns regarding the impact of early exposure Craving is a major motivator underlying drug use and relapse but the neural correlates of cannabis craving are not well understood . This study sought to determine whether visual cannabis cues increase cannabis craving and whether cue-induced craving is associated with regional brain activation in cannabis-dependent individuals . Cannabis craving was assessed in 16 cannabis-dependent adult volunteers while they viewed cannabis cues during a functional MRI ( fMRI ) scan . The Marijuana Craving Question naire was administered immediately before and after each of three cannabis cue-exposure fMRI runs . FMRI blood-oxygenation-level-dependent ( BOLD ) signal intensity was determined in regions activated by cannabis cues to examine the relationship of regional brain activation to cannabis craving . Craving scores increased significantly following exposure to visual cannabis cues . Visual cues activated multiple brain regions , including inferior orbital frontal cortex , posterior cingulate gyrus , parahippocampal gyrus , hippocampus , amygdala , superior temporal pole , and occipital cortex . Craving scores at baseline and at the end of all three runs were significantly correlated with brain activation during the first fMRI run only , in the limbic system ( including amygdala and hippocampus ) and paralimbic system ( superior temporal pole ) , and visual regions ( occipital cortex ) . Cannabis cues increased craving in cannabis-dependent individuals and this increase was associated with activation in the limbic , paralimbic , and visual systems during the first fMRI run , but not subsequent fMRI runs . These results suggest that these regions may mediate visually cued aspects of drug craving . This study provides preliminary evidence for the neural basis of cue-induced cannabis craving and suggests possible neural targets for interventions targeted at treating cannabis dependence 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 Evidence for negative effects of early-onset cannabis use has led to a need for effective interventions targeting adolescent cannabis users . A r and omized controlled trial of an Australian two-session intervention based on motivational interviewing ( the ACCU , or Weed-Check in Dutch ) was replicated in a larger Dutch sample of 119 non-treatment-seeking adolescent cannabis users . Outcome measures at the 3-month follow-up were quantity and frequency of cannabis use , symptoms of dependence , stage of change , and psychosocial functioning . Changes in all measures were in the expected direction , yet not significant . In moderation analyses , heavier cannabis users at baseline receiving the Weed-Check had greater reductions in cannabis use than those in the control condition . These results suggest that the Weed-Check might be beneficial for heavier cannabis-using adolescents . Further research is needed to confirm these results in a sample of adolescent heavy cannabis users and to examine the relationship between MI skills of prevention workers and outcome Cannabis is the most frequently used illicit drug worldwide , but little is known about the mechanisms underlying continued cannabis use . Cue-reactivity ( the physical , psychological , behavioural and neural reaction to substance-related cues ) might be related to continued cannabis use . In this 3-year prospect i ve neuroimaging study we investigated whether cannabis cue-induced brain activity predicted continued cannabis use and associated problem severity 3 years later . In addition , baseline brain activations were compared between dependent and non-dependent cannabis users at follow-up . Analyses were focussed on brain areas known to be important in cannabis cue-reactivity : anterior cingulate cortex , orbitofrontal cortex , ventral tegmental area , amygdala and striatum . At baseline , 31 treatment-naive frequent cannabis users performed a  cue-reactivity functional magnetic resonance imaging task . Of these participants , 23 completed the 3-year follow-up . None of the cue-induced region of interest activations predicted the amount of cannabis use at follow-up . However , cue-induced activation in the left striatum ( putamen ) significantly and independently predicted problem severity at follow-up ( p < 0.001 ) as assessed with the Cannabis Use Disorder Identification Test . Also , clinical ly dependent cannabis users at follow-up showed higher baseline activation at trend level in the left striatum compared with non-dependent users . This indicates that neural cue-reactivity in the dorsal striatum is an independent predictor of cannabis use-related problems . Given the relatively small sample size , these results are preliminary and should be replicated in larger sample s of cannabis users Papers pp 1195 , 1199 The strongest evidence that cannabis use may be a risk factor for later psychosis  comes from a Swedish cohort study which found that heavy cannabis use at age 18 increased the risk of later schizophrenia sixfold . 1 2 This study could not establish whether adolescent cannabis use was a consequence of pre-existing psychotic symptoms rather than a cause . We present the first prospect i ve longitudinal study of adolescent cannabis use as a risk factor for  adult schizophreniform disorder  , taking into account childhood psychotic symptoms3 antedating cannabis use . View this table : Association between  cannabis use in adolescence and schizophrenia and depressive symptoms and disorders at age 26 ( n=759 ) , controlling for childhood psychotic symptoms and use of other drugs in adolescence The Dunedin multidisciplinary health and development study ( a study of a general population birth cohort of 1037 individuals born in Dunedin , New Zeal and , in 1972 - 3)4 has a 96 % follow up rate at age 26 . It obtained information on psychotic symptoms at age 11 and drug use at ages 15 and 18 from self reports and assessed The increasing dem and for cannabis dependence treatment has led to the identification of significant gaps in the knowledge of effective interventions . A r and omized controlled trial of brief cognitive-behavioral interventions ( CBT ) for cannabis dependence was undertaken to address this issue . A total of 229 participants were assessed and allocated to either a 6-session CBT program , a single-session brief intervention , or a delayed-treatment control group . This paper demonstrates that individuals with cannabis use disorder will present for a brief intervention program . While they report similar patterns of cannabis use to nontreatment sample s , they report a range of serious health and psychosocial consequences . While they appear relatively socially stable , they typically demonstrated severe cannabis dependence and significantly elevated levels of psychological distress , with the most commonly cited reason for cannabis use being stress relief . There were clinical ly relevant gender differences among the sample . This study provides more evidence of the dem and for , and nature of issues relevant to , interventions for cannabis use disorders , and supports the need for further research into how best to assist individuals with these disorders AIMS To compare the relationship between cannabis abuse/dependence and risk of medically serious suicide attempts  in individuals making serious suicide attempts and r and omly selected comparison subjects . DESIGN Case-control comparison . SETTING Cases , a general hospital ; controls , the local community . PARTICIPANTS Cases were 302 consecutive individuals making medically serious suicide attempts ; 1028 r and omly selected control subjects . MEASUREMENTS DSM-III-R mental disorder diagnoses ; measures of socio-demographic characteristics and childhood and family experiences . FINDINGS Of those making serious suicide attempts , 16.2 % met DSM-III-R criteria for cannabis abuse/dependence at the time of the attempt , compared with 1.9 % of comparison subjects ( OR = 10.3 ; 95%CI , 5.95 - 17.8 , p < 0.0001 ) . Risks of serious suicide attempt were significantly related to a series of socio-demographic and childhood characteristics , and to mental disorders that were co-morbid with cannabis abuse/dependence . When the association between cannabis abuse/dependence and suicide attempt risk was controlled for socio-demographic factors , childhood factors and concurrent psychiatric morbidity , there was a marginally significant association ( OR = 2.0 ; 95%CI , 0.97 - 5.3 , p < 0.06 ) between cannabis abuse/dependence and serious suicide attempt risk . CONCLUSIONS These results suggested that much of the association between cannabis abuse/dependence and suicide attempt risk arose because : ( a ) individuals who develop cannabis abuse/dependency tend to come from disadvantaged socio-demographic and childhood background s which , independently of cannabis abuse , are associated with higher risk of suicide attempt , or ( b ) because cannabis abuse/dependence is co-morbid with other mental disorders which are independently associated with suicidal behaviour . Nevertheless , the possibility remains that cannabis abuse/dependence may make an independent contribution to risk of serious suicide attempt , both directly and through the possible effects of cannabis abuse on risk of other mental disorders While the effects of cannabis use on retrospective memory have been extensively examined , only a limited number of studies have focused on the links between cannabis use and prospect i ve memory . We conducted two studies to examine the links between cannabis use and both time-based and event-based prospect i ve memory as well as potential mechanisms underlying these links . For the first study , 805 students completed an online survey design ed to assess cannabis consumption , problems with cannabis use indicative of a disorder , and frequency of experiencing prospect i ve memory failures . The results showed small to moderate sized correlations between cannabis consumption , problems with cannabis use , and prospect i ve memory . However , a series of mediation analyses revealed that correlations between problems with cannabis use and prospect i ve memory were driven by self-reported problems with retrospective memory . For the second study , 48 non-users ( who had never used cannabis ) , 48 experimenters ( who had used cannabis five or fewer times in their lives ) , and 48 chronic users ( who had used cannabis at least three times a week for one year ) were administered three objective prospect i ve memory tests and three self-report measures of prospect i ve memory . The results revealed no objective deficits in prospect i ve memory associated with chronic cannabis use . In contrast , chronic cannabis users reported experiencing more internally-cued prospect i ve memory failures . Subsequent analyses revealed that this effect was driven by self-reported problems with retrospective memory as well as by use of alcohol and other drugs . Although our sample s were not fully characterized with respect to variables such as neurological disorders and family history of substance use disorders , leaving open the possibility that these variables may play a role in the detected relationships , the present findings indicate that cannabis use has a modest effect on self-reported problems with prospect i ve memory , with a primary problem with retrospective memory appearing to underlie this relationship The increasing dem and for treatment for cannabis dependence in Australia and internationally has led to the identification of significant gaps in knowledge of effective interventions . A r and omized controlled trial of brief cognitive-behavioral interventions ( CBT ) for cannabis dependence was undertaken to address this issue . A total of 229 participants were assessed and r and omly assigned to either a six-session CBT program ( 6CBT ) , a single-session CBT intervention ( 1CBT ) , or a delayed-treatment control ( DTC ) group . Participants were assisted in acquiring skills to promote cannabis cessation and maintenance of abstinence . Participants were followed-up a median of 237 days after last attendance . Participants in the treatment groups reported better treatment outcomes than the DTC group . They were more likely to report abstinence , were significantly less concerned about their control over cannabis use , and reported significantly fewer cannabis-related problems than those in the DTC group . Those in the 6CBT group also reported more significantly reduced levels of cannabis consumption than the DTC group . While the therapist variable had no effect on any outcome , a secondary analysis of the 6CBT and 1CBT groups showed that treatment compliance was significantly associated with decreased dependence and cannabis-related problems . This study supports the attractiveness and effectiveness of individual CBT interventions for cannabis use disorders and the need for multisite replication trials BACKGROUND Cannabis use is associated with an increased risk of developing a psychotic disorder but the temporal relationship between cannabis use and onset of illness is unclear . The objective of this study was to assess prospect ively the influence of cannabis use on transition to psychosis in people at ultra-high risk ( UHR ) for the disorder . METHOD Lifetime and continued cannabis use was assessed in a consecutively ascertained sample of 182 people ( 104 male , 78 female ) at UHR for psychosis . Individuals were then followed clinical ly for 2 years to determine their clinical outcomes . RESULTS Lifetime cannabis use was reported by 134 individuals ( 73.6 % ) . However , most of these individuals had stopped using cannabis before clinical presentation ( n=98 , 73.1 % ) , usually because of adverse effects . Among lifetime users , frequent use , early-onset use and continued use after presentation were all associated with an increase in transition to psychosis . Transition to psychosis was highest among those who started using cannabis before the age of 15 years and went on to use frequently ( frequent early-onset use : 25 % ; infrequent or late-onset use : 5 % ; χ(2)1=10.971 , p=0.001 ) . However , within the whole sample , cannabis users were no more likely to develop psychosis than those who had never used cannabis ( cannabis use : 12.7 % ; no use : 18.8 % ; χ(2)1=1.061 , p=0.303 ) . CONCLUSIONS In people at UHR for psychosis , lifetime cannabis use was common but not related to outcome . Among cannabis users , frequent use , early-onset use and continued use after clinical presentation were associated with transition to psychosis Cannabis use is observationally associated with an increased risk of schizophrenia  , but whether the relationship is causal is not known . Using a genetic approach , we took 10 independent genetic variants previously identified to associate with cannabis use in 32 330 individuals to determine the nature of the association between cannabis use and risk of schizophrenia . Genetic variants were employed as instruments to recapitulate a r and omized controlled trial involving two groups (  cannabis users vs nonusers ) to estimate the causal effect of cannabis use on risk of schizophrenia  in 34 241 cases and 45 604 controls from predominantly European descent . Genetically-derived estimates were compared with a meta- analysis of observational studies reporting ever use of cannabis and risk of schizophrenia or related disorders . Based on the genetic approach , use of cannabis was associated with increased risk of schizophrenia ( odds ratio ( OR ) of schizophrenia for users vs nonusers of cannabis : 1.37 ; 95 % confidence interval ( CI ) , 1.09–1.67 ; P-value=0.007 ) . The corresponding estimate from observational analysis was 1.43 ( 95 % CI , 1.19–1.67 ; P-value for heterogeneity = 0.76 ) . The genetic markers did not show evidence of pleiotropic effects and accounting for tobacco exposure did not alter the association ( OR of schizophrenia for users vs nonusers of cannabis , adjusted for ever vs never smoker : 1.41 ; 95 % CI , 1.09–1.83 ) . This adds to the substantial evidence base that has previously identified cannabis use to associate with increased risk of schizophrenia , by suggesting that the relationship is causal . Such robust evidence may inform public health messages about cannabis use , especially regarding its potential mental health consequences AIMS To establish the long-term efficacy of a universal internet-based alcohol and cannabis prevention programme in schools . METHODS A cluster-r and omized controlled trial was conducted to assess the effectiveness of the Climate Schools : Alcohol and Cannabis Course . The evidence -based course , aim ed at reducing alcohol and cannabis use , is facilitated by the internet and consists of 12 novel and curriculum consistent lessons delivered over 6 months . PARTICIPANTS A total of 764 year 8 students ( 13 years ) from 10 Australian secondary schools were allocated r and omly to the  internet-based prevention programme  ( n = 397 , five schools ) , or to their usual health classes  ( n = 367 , five schools ) . MEASURES Participants were assessed at baseline , immediately post , and 6 and 12 months following completion of the intervention , on measures of alcohol and cannabis knowledge , attitudes , use and related harms . RESULTS This paper reports the final results of the intervention trial , 12 months following the completion of the Climate Schools : Alcohol and Cannabis Course . The effectiveness of the course 6 months following the intervention has been reported previously . At the 12-month follow-up , compared to the control group , students in the intervention group showed significant improvements in alcohol and cannabis knowledge , a reduction in average weekly alcohol consumption and a reduction in frequency of drinking to excess . No differences between groups were found on alcohol expectancies , cannabis attitudes or alcohol- and cannabis-related harms . The course was found to be acceptable by teachers and students as a means of delivering drug education in schools . CONCLUSIONS Internet-based prevention programs for school-age children can improve student 's  knowledge about alcohol and cannabis , and may also reduce alcohol use twelve months after completion OBJECTIVE To establish the efficacy of an internet based prevention program to reduce alcohol and cannabis use  in adolescents . METHOD A cluster r and omised controlled trial was conducted with 764 13-year olds from ten Australian secondary schools in 2007 - 2008 . Half the schools were r and omly allocated to the computerised prevention program ( n=397 ) , and half to their usual health classes ( n=367 ) . The Climate Schools : Alcohol and Cannabis prevention course is facilitated by the internet and consists of novel , evidence -based , curriculum consistent lessons aim ed at reducing alcohol and cannabis use . Participants were assessed at baseline , immediately post , and at six months following the intervention . RESULTS Compared to the control group , students in the intervention group showed significant improvements in alcohol and cannabis knowledge at the end of the course and the six month follow-up . In addition , the intervention group showed a reduction in average weekly alcohol consumption and frequency of cannabis use at the six month follow-up . No differences between groups were found on alcohol expectancies , cannabis attitudes , or alcohol and cannabis related harms . CONCLUSIONS The course is acceptable , scalable and fidelity is assured . It increased knowledge regarding alcohol and cannabis , and decreased use of these drugs Objective : Replication is an important step in evaluating evidence -based preventive interventions and is crucial for establishing the generalizability and wider impact of a program . Despite this , few replications have occurred in the prevention science field . This study aims to fill this gap by conducting a cross-validation trial of the Climate Schools : Alcohol and Cannabis course , an Internet-based prevention program , among a new cohort of Australian students . Method : A cluster r and omized controlled trial was conducted among 1103 students ( Mage : 13.25 years ) from 13 schools in Australia in 2012 . Six schools received the Climate Schools course  and 7 schools were r and omized to a control group ( health education as usual ) . All students completed a self-report survey at baseline and immediately post-intervention . Mixed-effects regressions were conducted for all outcome variables . Outcomes assessed included alcohol and cannabis use , knowledge and intentions to use these substances . Results : Compared to the control group , immediately post-intervention the intervention group reported significantly greater alcohol ( d = 0.67 ) and cannabis knowledge ( d = 0.72 ) , were less likely to have consumed any alcohol ( even a sip or taste ) in the past 6 months ( odds ratio = 0.69 ) and were less likely to intend on using alcohol in the future ( odds ratio = 0.62 ) . However , there were no effects for binge drinking , cannabis use or intentions to use cannabis . Conclusion : These preliminary results provide some support for the Internet-based Climate Schools : Alcohol and Cannabis course as a feasible way of delivering alcohol and cannabis prevention . Intervention effects for alcohol and cannabis knowledge were consistent with results from the original trial ; however , analyses of longer-term follow-up data are needed to provide a clearer indication of the efficacy of the intervention , particularly in relation to behavioral changes 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 The main active ingredient in cannabis , delta-9-tetrahydrocannabinol ( THC ) , can acutely induce psychotic symptoms and impair episodic and working memory . Another major constituent , cannabidiol ( CBD ) , may attenuate these effects . This study aim ed to determine the effects of THC and CBD , both alone and in combination on psychotic symptoms and memory function . A r and omised , double-blind crossover design compared the effects of ( i ) placebo , ( ii ) THC 8 mg , ( iii ) CBD 16 mg and ( iv ) THC 8 mg + CBD 16 mg administered by inhalation through a vaporiser . Using an experimental medicine approach to predict treatment sensitivity , we selected 48 cannabis users from the community on the basis of ( 1 ) schizotypal personality question naire scores ( low , high ) and ( 2 ) frequency of cannabis use ( light , heavy ) . The Brief Psychiatric Rating Scale ( BPRS ) , Psychotomimetic States Inventory ( PSI ) , immediate and delayed prose recall ( episodic memory ) , 1- and 2-back ( working memory ) were assessed on each day . Results indicated that THC increased overall scores on the PSI , negative symptoms on BPRS , and robustly impaired episodic and working memory . Co-administration of CBD did not attenuate these effects . CBD alone reduced PSI scores in light users only . At a ratio of 2:1 , CBD does not attenuate the acute psychotic and memory impairing effects of vaporised THC . Frequent cannabis users may show a blunted anti- psychotic response to CBD , which is of concern due to the high rates of cannabis use disorders in patients with schizophrenia
RESULTS Although causality is unclear , heavy and dependent cannabis use is consistently associated with a high prevalence of comorbid psychiatric disorders and learning and memory impairments that seem to recover after a period of abstinence .
Evidence regarding other cognitive domains and neurological consequences including cerebrovascular events is limited and inconsistent .
Abstinence after treatment is only achieved in a minority of cases ; treatment targeted at reduction in use appears have some success .
Potential moderators of the impact of CUD on the brain include age of onset , heaviness of use , CUD severity , the ratio of ∆9-tetrahydrocannabinol to cannabidiol , and severity of comorbid disorders .
Current evidence of long-term effects of daily cannabis use and cannabis use disorder on brain-related outcomes is suggestive rather than conclusive but use is associated with psychiatric morbidity and with cognitive impairments that recover after a period of abstinence
AIMS To summarize and evaluate our knowledge of the relationship between heavy cannabis use , Cannabis Use Disorder ( CUD ) , and the brain .