Serving Substance Abuse Professionals Since 1993

Last Update: 27.11.11

C O R K O N L I N E

powerpoint presentations
CORK database search
resource materials
bibliographies
clinical tools
user services
newsletters
about cork
home

CORK Bibliography: Marijuana and Psychosis

93 citations. January 2003 to present

Prepared: December 2011

Arendt M; Rosenberg R; Foldager L; Perto G; Munk-Jorgensen P. Cannabis-induced psychosis and subsequent schizophrenia-spectrum disorders: Follow-up study of 535 incident cases. British Journal of Psychiatry 187: 510-515, 2005. (25 refs.)

Background Few studies have examined samples of people with cannabis-induced psychotic symptoms. Aims To establish whether cannabis-induced psychotic disorders are followed by development of persistent psychotic conditions, and the timing of their onset. Method Data on patients treated for cannabis-induced psychotic symptoms between 1994 and 1999 were extracted from the Danish Psychiatric Central Register. Those previously treated for any psychotic symptoms were excluded. The remaining 535 patients were followed for at least 3 years. In a separate analysis, the sample was compared with people referred for schizophrenia-spectrum disorders for the first time, but who had no history of cannabis-induced psychosis. Results Schizophrenia-spectrum disorders were diagnosed in 44.5% of the sample. New psychotic episodes of any type were diagnosed in 77.2%. Male gender and young age were associated with increased risk. Development of schizophrenia-spectrum disorders was often delayed, and 47.1% of patients received a diagnosis more than a year after seeking treatment for a cannabis-induced psychosis. The patients developed schizophrenia at an earlier age than people in the comparison group (males, 24.6 v. 30.7 years, females, 28.9 v. 33.1 years). Conclusions Cannabis-induced psychotic disorders are of great clinical and prognostic importance.

Arseneault L; Cannon M; Witton J; Murray RM. Causal association between cannabis and psychosis: Examination of the evidence. (review). British Journal of Psychiatry 184: 110-117, 2004. (44 refs.)

Background: Controversy remains as to whether cannabis acts as a causal risk factor for schizophrenia or other functional psychotic illnesses. Aims: To examine critically the evidence that cannabis causes psychosis using established criteria of causality. Method: We identified five studies that included a well-defined sample drawn from population-based registers or cohorts and used prospective measures of cannabis use and adult psychosis. Results On an individual level, cannabis use confers an overall twofold increase in the relative risk for later schizophrenia. At the population level, elimination of cannabis use would reduce the incidence of schizophrenia by approximately 8%, assuming a causal relationship. Cannabis use appears to be neither a sufficient nor a necessary cause for psychosis. It is a component cause, part of a complex constellation of factors leading to psychosis. Conclusions: Cases of psychotic disorder could be prevented by discouraging cannabis use among vulnerable youths. Research is needed to understand the mechanisms by which cannabis causes psychosis.

Atakan Z. Cannabis and psychosis: How important is the link? (commentary). Addiction 99(4): 513-515, 2004. (12 refs.)

Barkus E; Lewis S. Schizotypy and psychosis-like experiences from recreational cannabis in a non-clinical sample. Psychological Medicine 38(9): 1267-1276, 2008. (30 refs.)

Background. The relationship between cannabis use and psychosis is still a matter for debate. Accounting for the individual differences in subjective experiences to recreational cannabis use in the general population may hold some clues to the aetiological relationship between cannabis and psychotic symptoms. We hypothesized that schizotypy would account for the individual differences in subjective experiences after cannabis use but not in patterns of use. Method. In a sample of 532 young people who had used cannabis at least once, we examined the relationship between the Cannabis Experiences Questionnaire (CEQ) and the Schizotypal Personality Questionnaire (SPQ). Additionally, we examined the psychometric properties of the CEQ. Results. We replicated our previously reported findings that schizotypy was associated with increased psychosis-like experiences and after-effects, but also found that high-scoring schizotypes reported more pleasurable experiences when smoking cannabis. Using new subscales derived from principal components analysis (PCA), we found that the psychosis-like items were most related to varying rates of schizotypy both during the immediate use of cannabis and in the after-effects of cannabis use. High-scoring schizotypes who used cannabis experienced more psychosis-like symptoms during and after use. Conclusions. Our results suggest that cannabis use may reveal an underlying vulnerability to psychosis in those with high schizotypal traits.

Barnes TRE; Mutsatsa SH; Hutton SB; Watt HC; Joyce EM. Comorbid substance use and age at onset of schizophrenia. British Journal of Psychiatry 188: 237-242, 2006. (50 refs.)

Background: Substance use may be a risk factor for the onset of schizophrenia. Aims: To examine the association between substance use and age at onset in a UK, inner-city sample of people with recent-onset schizophrenia. Method The study sample consisted of 152 people recruited to the West London First-Episode Schizophrenia Study Self-reported data on drug and alcohol use, as well as information on age at onset of psychosis, were collected. Mental state, cognition (IQ, memory and executive function) and social function were also assessed. Results: In total, 60% of the participants were smokers, 27% reported a history of problems with alcohol use, 35% reported current substance use (not including alcohol), and 68% reported lifetime substance use (cannabis and psychostimulants were most commonly used). Cannabis use and gender had independent effects on age at onset of psychosis, after adjusting for alcohol misuse and use of other drugs. Conclusions: The strong association between self-reported cannabis use and earlier onset of psychosis provides further evidence that schizophrenia may be precipitated by cannabis use and/or that the early onset of symptoms is a risk factor for cannabis use.

Barnett JH; Werners U; Secher SM; Hill KE; Brazil R; Masson K et al. Substance use in a population-based clinic sample of people with first-episode psychosis. British Journal of Psychiatry 190(515-520), 2007. (33 refs.)

Background Substance use is implicated in the cause and course of psychosis. Aims To characterise substance and alcohol use in an epidemiologically representative treatment sample of people experiencing a first psychotic episode in south Cambridgeshire. Method Current and lifetime substance use was recorded for 123 consecutive referrals to a specialist early intervention service. Substance use was compared with general population prevalence estimates from the British Crime Survey Results Substance use among people with first-episode psychosis was twice that of the general population and was more common in men than women. Cannabis abuse was reported in 51% of patients (n=62) and alcohol abuse in 43% (n=53). More than half (n=68, 55%) had used Class A drugs, and 38% (n=43) reported polysubstance abuse. Age at first use of cannabis, cocaine, ecstasy and amphetamine was significantly associated with age at first psychotic symptom. Conclusions Substance misuse is present in the majority of people with first-episode psychosis and has major implications for management. The association between age at first substance use and first psychotic symptoms has public health implications.

Ben Amar M. Cannabis and psychosis: What is the link? Journal of Psychoactive Drugs 39(2): 131-142, 2007. (95 refs.)

Growing evidence supports the hypothesis that cannabis consumption is a risk factor for the development of psychotic symptoms. Nonetheless, controversy remains about the causal nature of the association. This review takes the debate further through a critical appraisal of the evidence. An electronic search was performed, allowing to identify 622 studies published until June 1st 2005. Longitudinal studies and literature reviews were selected if they addressed specifically the issues of the cannabis/psychosis relationship or possible mechanisms involved. Ten epidemiological studies were relevant: three supported a causal relationship between cannabis use and diagnosed psychosis; five suggested that chronic cannabis intake increases the frequency of psychotic symptoms, but not of diagnosed psychosis; and two showed no causal relationship. Potential neurobiological mechanisms were also identified, involving dopamine, endocannabinoids, and brain growth factors. Although there is evidence that cannabis use increases the risk of developing psychotic symptoms, the causal nature of this association remains unclear. Contributing factors include heavy consumption, length and early age of exposure, and psychotic vulnerability. This conclusion should be mitigated by uncertainty arising from cannabis use assessment, psychosis measurement, reverse causality and control of residual confounding.

Boydell J; Dean K; Dutta R; Giouroukou E; Fearon P; Murray R. A comparison of symptoms and family history in schizophrenia with and without prior cannabis use: Implications for the concept of cannabis psychosis. Schizophrenia Research 93(1-3): 203-210, 2007. (35 refs.)

Background: There is considerable interest in cannabis use in psychosis. It has been suggested that the chronic psychosis associated with cannabis use, is symptomatically distinct from idiopathic schizophrenia. Several studies have reported differences in psychopathology and family history in people with schizophrenia according to whether or not they were cannabis users. We set out to test the hypotheses arising from these studies that cannabis use is associated with more bizarre behaviour, more thought disorder, fewer negative symptoms including blunted affect, more delusions of reference, more paranoid delusions and a stronger family history of schizophrenia. Method: We used a case register that contained 757 cases of first onset schizophrenia, 182 (24%) of whom had used cannabis in the year prior to first presentation, 552 (73%) had not and 3% had missing data. We completed the OPCRIT checklist on all patients and investigated differences in the proportion of people with distractibility, bizarre behaviour, positive formal thought disorder, delusions of reference, well organised delusions, any first rank symptom, persecutory delusions, abusive/accusatory hallucinations, blunted affect, negative thought disorder, any negative symptoms (catatonia, blunted affect, negative thought disorder, or deterioration), lack of insight, suicidal ideation and a positive family history of schizophrenia, using chi square tests. Logistic regression modelling was then used to determine whether prior cannabis use affected the presence of the characteristics after controlling for age, sex and ethnicity. Results: There was no statistically significant effect of cannabis use on the presence of any of the above. There remained however a non-significant trend towards more insight (OR 0.65 p = 0.055 for "loss of insight") and a finding of fewer abusive or accusatory hallucinations (OR 0.65 p = 0.049) of borderline significance amongst the cannabis users. These were in the hypothesised direction. There was no evidence of fewer negative symptoms or greater family history amongst cannabis users. Conclusion: We found few appreciable differences in symptomatology between schizophrenic patients who were or were not cannabis users. There were no differences in the proportion of people with a positive family history of schizophrenia between cannabis users and non-users. This argues against a distinct schizophrenia-like psychosis caused by cannabis.

Broome MR; Woolley JB; Tabraham P; Johns LC; Bramon E; Murray GK et al. What causes the onset of psychosis? Schizophrenia Research 79(1): 23-34, 2005. (100 refs.)

it has become increasingly clear that the simple neurodevelopmental model fails to explain many aspects of schizophrenia including the timing of the onset, and the nature of the abnormal perceptions. Furthermore, we do not know why some members of the general population have anomalous experiences but remain well, while others enter the prodrome of psychosis, and a minority progress to frank schizophrenia. We suggest that genes or developmental damage result in individuals vulnerable to dopamine deregulation. In contemporary society, this is often compounded by abuse of drugs such as amphetamines and cannabis, which then propel the individual into a state of dopamine-induced misinterpretation of the environment. Certain types of social adversity such as migration and social isolation, as well as affective change can also contribute to this. Thereafter, biased cognitive appraisal processes result in delusional interpretation of the abnormal perceptual experiences. Thus, a plausible model of the onset of psychosis needs to draw not only on neuroscience, but also on the insights of social psychiatry and cognitive psychology.

Caspi A; Moffittt TE; CAnnon M; McClay J; Murray R; Harrington H et al. Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: Longitudinal evidence of a gene X environment interation. Biological Psychiatry 57(10): 1117-1127, 2005. (63 refs.)

Background: Recent evidence documents that cannabis use by young people is a modest statistical risk factor for psychotic symptoms in adulthood, such as hallucinations and delusions, as well as clinically significant schizophrenia. The vast majority of cannabis users do not develop psychosis, however, prompting us to hypothesize that some people are genetically vulnerable to the deleterious effects of cannabis. Methods: In a longitudinal study of a representative birth cohort followed to adulthood, we tested why cannabis use is associated with the emergence of psychosis in a minority of users, but not in others. Results: A functional polymorphism in the catechol-O-methyltransferase (COMT) gene moderated the influence of adolescent cannabis use on developing adult psychosis. Carriers of the COMT valine(158) allele were most likely to exhibit psychotic symptoms and to develop schizophreniform disorder if they used cannabis. Cannabis use had no such adverse influence on individuals with two copies of the methionine allele. Conclusions: These findings provide evidence of a gene X environment interaction and suggest that a role of some susceptibility genes is to influence vulnerability to environmental pathogens.

Clough AR; d'Abbs P; Cairney S; Gray D; Maruff P; Parker R et al. Adverse mental health effects of cannabis use in two indigenous communities in Arnhem Land, Northern Territory, Australia: Exploratory study. Australian and New Zealand Journal of Psychiatry 39(7): 612-620, 2005. (53 refs.)

Objective: We investigated adverse mental health effects and their associations with levels of cannabis use among indigenous Australian cannabis users in remote communities in the Northern Territory. Method: Local indigenous health workers and key informants assisted in developing 28 criteria describing mental health symptoms. Five symptom clusters were identified using cluster analysis of data compiled from interviews with 103 cannabis users. Agreement was assessed (method comparison approach, kappa-statistic) with a clinician's classification of the 28 criteria into five groups labelled: 'anxiety', 'dependency', 'mood', 'vegetative' and 'psychosis'. Participants were described as showing 'anxiety', 'dependency' etc., if they reported half or more of the symptoms comprising the cluster. Associations between participants' self-reported cannabis use and each symptom cluster were assessed (logistic regression adjusting for age, sex, other substance use). Results: Agreement between two classifications of 28 criteria into five groups was 'moderate' (64%, kappa = 0.55, p < 0.001). When five clusters were combined into three, 'anxiety-dependency', 'mood-vegetative' and 'psychosis', agreement rose to 71% (kappa = 0.56, p < 0.001). 'Anxiety-dependency' was positively associated with number of 'cones' usually smoked per week and this remained significant when adjusted for confounders (p = 0.020) and tended to remain significant in those who had never sniffed petrol (p = 0.052). Users of more than five cones per week were more likely to display 'anxiety-dependency' symptoms than those who used one cone per week (OR = 15.8, 1.8-141.2, p = 0.013). A crude association between the 'mood-vegetative' symptom cluster and number of cones usually smoked per week (p = 0.014) also remained statistically significant when adjusted for confounders (p = 0.012) but was modified by interactions with petrol sniffing (p = 0.116) and alcohol use (p = 0.276). There were no associations between cannabis use and 'psychosis'. Conclusions: Risks for 'anxiety-dependency' symptoms in cannabis users increased as their level of use increased. Other plausible mental health effects of cannabis in this population of comparatively new users were probably masked by alcohol use and a history of petrol sniffing.

Compton MT; Broussard B; Ramsay CE; Stewart T. Pre-illness cannabis use and the early course of nonaffective psychotic disorders: Associations with premorbid functioning, the prodrome, and mode of onset of psychosis. Schizophrenia Research 126(1-3): 71-76, 2011. (47 refs.)

Introduction: Limited research indicates that pre-illness cannabis use may result in an earlier age at onset of psychosis, though little is known about the influence of prior cannabis use on the premorbid and prodromal phases. This study examined the effects of prior or concurrent cannabis (as well as nicotine and alcohol) use on: (1) early adolescent (12-15 years) premorbid functioning, (2) late adolescent (16-18 years) premorbid functioning, (3) two features of the prodrome, and (4) mode of onset of psychosis. Methods: Participants included 109 well-characterized first-episode patients hospitalized in public-sector settings. Assessments included ages at initiation of first, weekly, and daily use of substances, the Premorbid Adjustment Scale, the Symptom Onset in Schizophrenia inventory, and a consensus-based best estimate of mode of onset. Results: Participants having used cannabis at <= 15 years had better early adolescence social functioning than those who had not used cannabis (p = 0.02). Conversely, those who had used cannabis at <= 18 years had poorer late adolescence academic functioning (p < 0.001). Participants having used cannabis before onset of psychotic symptoms did not differ from those who had not in terms of having had an identifiable prodrome or the number of prodromal symptoms experienced. Whereas 42% of those having used cannabis daily had an acute mode of onset of psychosis, only 20% of those without prior daily cannabis use had an acute onset (p = 0.04). Conclusions: Findings suggest that cannabis use is associated with premorbid social and academic functioning and mode of onset. Further research is warranted to elucidate the complex associations between cannabis use and diverse early-course features.

Compton MT; Whicker NE; Hochman KM. Alcohol and cannabis use in urban, African American, first-episode schizophrenia-spectrum patients: Associations with positive and negative symptoms. Journal of Clinical Psychiatry 68(12): 1939-1945, 2007. (33 refs.)

Objective: On the basis of limited prior research on associations between symptoms and substance use in first-episode psychosis, a retrospective chart review was conducted to test 2 hypotheses: (1) the presence of positive symptoms is associated with alcohol use prior to admission and (2) the absence of prominent negative symptoms is associated with cannabis use prior to admission. Method. Eligible patients included those admitted for a first episode of psychosis in a publicsector, university-affiliated hospital that serves a predominantly African American, socially disadvantaged, urban population. The 72 patients included in the analysis were 18 to 40 years of age, and all were African American. Using a structured data collection instrument, discharge summaries of consecutively admitted patients from January 2002 to March 2005 were reviewed to extract data on basic demographic and clinical characteristics, the presence of I I symptoms, and alcohol and cannabis use within 6 months prior to hospitalization. Results: Alcohol use in the 6 months prior to hospitalization was associated with a higher frequency of positive psychotic symptoms among first-episode patients. Cannabis use was associated with a lower likelihood of having prominent negative symptoms. These associations remained even after controlling for relevant covariates in logistic regression models. Conclusion: Although the direction of causality cannot be established, the association between positive psychotic symptoms and alcohol use may represent a self-medication effect, whereas the association between lesser negative symptoms and cannabis use may result from the fact that interpersonal deficits and reduced hedonic capacity minimize drug-seeking activities.

De Hert M; Wampers M; Jendricko T; Franic T; Vidovic D; De Vriendt N et al. Effects of cannabis use on age at onset in schizophrenia and bipolar disorder. Schizophrenia Research 126(1-3): 270-276, 2011. (94 refs.)

Background: Cannabis use may decrease age at onset in both schizophrenia and bipolar disorder, given the evidence for substantial phenotypic and genetic overlap between both disorders. Methods: 766 patients, aged 16 to 65 years, were assessed with the Composite International Diagnostic Interview (CIDI) for substance abuse/use. 676 subjects were diagnosed with schizophrenia and 90 subjects with bipolar disorder. The influence of cannabis use on age at onset in both schizophrenia and bipolar disorder was examined using regression analysis. Results: Cannabis and other substance use was more frequent in patients with schizophrenia compared to the bipolar group. Both cannabis use and a schizophrenia diagnosis predicted earlier age at onset. There was a significant interaction between cannabis use and diagnosis, cannabis having a greater effect in bipolar patients. Age at onset in users of cannabis was comparable in both diagnostic groups whereas bipolar non-users were significantly older than schizophrenia non-users at onset. Conclusion: Cannabis use may decrease age at onset in both schizophrenia and bipolar patients and reduce the effect of diagnosis. This is consistent with the view that cannabis use may unmask a pre-existing genetic liability that is partly shared between patients with schizophrenia and bipolar disorder.

de Irala J; Ruiz-Canela M; Martinez-Gonzalez MA. Causal relationship between cannabis use and psychotic symptoms or depression. Should we wait and see? A public health perspective. Medical Science Monitor 11(12): RA355-RA358, 2005. (21 refs.)

The aim of this paper is to update and critically analyze the public health relevance of available evidence about the causal relationship between cannabis use and psychosis or depression. There are conflicting views about this causal relationship. Two systematic reviews of existing evidence assessed this association and were published in 2004, but they came to different conclusions. From a public health perspective a thorough discussion is warranted before attributing any observed effect to potential biases. First, the impact of residual confounding in this causal relationship is discussed. We consider that the attenuation of estimates after controlling for confounding factors cannot be interpreted as evidence to support the claim that residual confounding fully explains this link. Secondly, taking into account the results of recent studies, the time-sequence and dose-response criteria of causality are discussed. The fact that unreported or subclinical psychological problems might have preceded and precipitated cannabis use is a very unlikely explanation when the cannabis-psychosis outcome link is assessed from different longitudinal studies. And finally, available evidence is interpreted with a broad view of public health and by taking into account the precautionary principle. We therefore provide reasons to support the case that stronger preventive actions against cannabis are still required in order to avoid the potential increased incidence of psychosocial health problems in the future.

de la Serna E; Mayoral M; Baeza I; Arango C; Andres P; Bombin I et al. Cognitive functioning in children and adolescents in their first episode of psychosis differences between previous cannabis users and nonusers. Journal of Nervous and Mental Disease 198(2): 159-162, 2010. (19 refs.)

To investigate the relationship between cognition and prior cannabis use in children and adolescents presenting a first episode of psychosis. A total of 107 patients with first episode of psychosis and 96 healthy controls, aged 9 to 17 years, were interviewed about their previous substance use and to assess their cognitive functions. Patients were assessed while not using cannabis by means of a comprehensive neuropsychological battery. They were divided into 2 groups depending on the history of prior cannabis use: cannabis users (CU) and cannabis nonusers (CNU). Significant differences were found in all areas evaluated between the 3 groups. Both CU and CNU patients obtained lower scores than controls on verbal learning and memory and working memory. Patients with prior cannabis use performed better on some tests of attention (Continuous performance test (CPT) number of correct responses, p = 0.002; CPT average reaction time, p < 0.001) and executive functions (Trail Making Test, part B (TMT-B) number of mistakes, p < 0.001; Wisconsin Card Sorting Test (WCST) number of categories completed, p < 0.001) than CNU patients. CU patients performed better than CNU subjects on some cognitive measures. This may indicate lower individual vulnerability for psychosis in CU patients in whom cannabis use can be a precipitating factor of psychotic episodes.

Degenhardt L. The link between cannabis use and psychosis: Furthering the debate. (editorial). Psychological Medicine 33(1): 3-6, 2003. (37 refs.)

Degenhardt L; Hall W. Is cannabis use a contributory cause of psychosis? (review). Canadian Journal of Psychiatry 51(9): 556-565, 2006. (86 refs.)

Objective: To assess whether cannabis use in adolescence and young adulthood is a contributory cause of schizophreniform psychosis in that it may precipitate psychosis in vulnerable individuals. Method: We reviewed longitudinal studies of adolescents and young adults that examined the relations between self-reported cannabis use and the risk of diagnosis with a psychosis or of reporting psychotic symptoms. We also reviewed studies that controlled for potential confounders, such as other forms of drug use and personal characteristics that predict an increased risk of psychosis. We assessed evidence for the biological plausibility of a contributory causal relation. Results: Evidence from 6 longitudinal studies in 5 countries shows that regular cannabis use predicts an increased risk of a schizophrenia diagnosis or of reporting symptoms of psychosis. These relations persisted after controlling for confounding variables, such as personal characteristics and other drug use. The relation did not seem to be a result of cannabis use to self-medicate symptoms of psychosis. A contributory causal relation is biologically plausible because psychotic disorders involve disturbances in the dopamine neurotransmitter systems with which the cannabinoid system interacts, as demonstrated by animal studies and one human provocation study. Conclusion: It is most plausible that cannabis use precipitates schizophrenia in individuals who are vulnerable because of a personal or family history of schizophrenia.

Degenhardt L; Hall W; Lynskey M. Testing hypotheses about the relationship between cannabis use and psychosis. Drug and Alcohol Dependence 71(1): 37-48, 2003. (71 refs.)

Aim: To model the impact of rising rates of cannabis use on the incidence and prevalence of psychosis under four hypotheses about the relationship between cannabis use and psychosis. Methods: The study modelled the effects on the prevalence of schizophrenia over the lifespan of cannabis in eight birth cohorts: 1940-1944, 1945-1949, 1950-1954, 1955-1959, 1960-1964, 1965-1969, 1970-1974, 1975-1979. It derived predictions as to the number of cases of schizophrenia that would be observed in these birth cohorts, given the following four hypotheses: (1) that there is a causal relationship between cannabis use and schizophrenia; (2) that cannabis use precipitates schizophrenia in vulnerable persons; (3) that cannabis use exacerbates schizophrenia; and (4) that persons with schizophrenia are more liable to become regular cannabis users. Results: There was a steep rise in the prevalence of cannabis use in Australia over the past 30 years and a corresponding decrease in the age of initiation of cannabis use. There was no evidence of a significant increase in the incidence of schizophrenia over the past 30 years. Data on trends the age of onset of schizophrenia did not show a clear pattern. Cannabis use among persons with schizophrenia has consistently been found to be more common than in the general population. Conclusions: Cannabis use does not appear to be causally related to the incidence of schizophrenia, but its use may precipitate disorders in persons who are vulnerable to developing psychosis and worsen the course of the disorder among those who have already developed it.

Degenhardt L; Hall W; Lynskey M; Coffey C; Patton G. The association between cannabis use and depression: A review of the evidence. IN: Castle D; Murray R, eds. Marijuana and Madness: Psychiatry and Neurobiology. Cambridge: Cambridge University Press, 2004. pp. 54-74. (96 refs.)

The association between cannabis and depression has not received as much attention as the association with psychosis. This is true despite the high prevalence of both cannabis use and depression. It has been suggested that cannabis use may contribute to depression and suicidal behavior, and there is some research supporting this. Toxicological analysis of suicide in California over a two year period found marijuana in16% of cases. A case control study in New Zealand found a higher rate of cannabis abuse/depdendence amoang those who made serious sucide atttempts, a rate of 16%, than among controls (2%). The causal hypothesis wold be consistent with the parallel increases in cannabis use among young adults and in suicide rates in young adults. In light of this,this chapter evaluates the nature of the relationship between cannabis use and depression by examining the following questions: Is there evidence of the association between cannabis us and depression? If so, what the potential explanations? What evidence is needed to test different explanations? What arethe public health implications of the evidence to date? Based on the examination of the data, the authors conclude that the proportion of cases of depression attributable to marijuana use are very modest. Regular marrijuana use explains only a small proportion of depression in the population.

Degenhardt L; Roxburgh A; McKetin R. Hospital separations for cannabis- and methamphetamine-related psychotic episodes in Australia. Medical Journal of Australia 186(7): 342-345, 2007. (25 refs.)

Objective: To examine trends in hospital separations related to "drug-induced" psychosis for cannabis and methamphetamine, in the context of patterns of cannabis and methamphetamine use in the Australian population. Design and setting: Analysis of prospectively collected data from the National Hospital Morbidity Database on hospital separations primarily attributed to drug-induced psychosis (July 1993 - June 2004), and specifically for cannabis and amphetamines (1999-2004). Calculation of Australian population-adjusted rates of drug-induced psychosis hospital separations using estimated resident population data from the Australian Bureau of Statistics (at 30 June each year) and data on cannabis and methamphetamine use from the 2004 National Drug Strategy Household Survey. Main outcome measures: Number of hospital separations due to drug-induced psychosis, and standardised (age-specific) rates per million population and per million users. Results: There have been notable increases in hospital separations due to drug-induced psychosis, which appear to have been driven by amphetamine-related rather than cannabis-related episodes. The rate of hospital separations was higher for amphetamine users than for cannabis users in all age groups, and the rate increased among older amphetamine users. Conclusions: The risk of hospitalisation for a drug-induced psychotic episode associated with amphetamine use appears to be greater than that for cannabls use in all age groups.

Degenhardt L; Tennant C; Gilmour S; Schofield D; Nash L; Hall W et al. The temporal dynamics of relationships between cannabis, psychosis and depression among young adults with psychotic disorders: Findings from a 10-month prospective study. Psychological Medicine 37(7): 927-934, 2007. (31 refs.)

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 prospective 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.

Di Forti M; Morrison PD; Butt A; Murray RM. Cannabis use and psychiatric and cogitive disorders: The chicken or the egg? Current Opinion in Psychiatry 20(3): 228-234, 2007. (48 refs.)

Purpose of review: Cannabis is the world's most commonly used illicit drug. In this review, we consider the recent literature on the effects of cannabis on mental health and on cognition. Recent findings Cannabis use in adolescence increases the risk of later schizophrenia-like psychoses, especially in genetically vulnerable individuals. Not surprisingly, patients already suffering from psychosis who use cannabis have a worse outcome than those who do not. These effects of cannabis may be consequent on its impact on the dopamine system. There is less evidence of cannabis playing an aetiological role in other mental disorders including depression, but there have been far fewer studies. Heavy cannabis use has also been shown to affect memory and learning performance, both in healthy individuals and in patients suffering from psychosis. Combined cognitive-behavioural therapy and motivational interviewing seems a promising psychological intervention to achieve a cessation of cannabis use in patients suffering from schizophrenia. Summary: Further research is needed to understand the biological mechanisms underlying the effects of cannabis on mental health, but intervention strategies to help patients abstain should currently be implemented in psychiatric services, and public education campaigns should be directed at increasing awareness of the health risks of cannabis.

Double DB. Cannabis and psychosis - Let's start from the null hypothesis. (letter). British Medical Journal 332(7536): 303-303, 2006. (5 refs.)

Drewe M; Drewe J; Riecher-Rossler A. Cannabis and risk of psychosis. (review). Swiss Medical Weekly 134(45-46): 659-663, 2004. (43 refs.)

Legalisation of cannabis use in Switzerland has recently been debated by the Swiss Parliament. Although legalisation has not yet been decided upon, it is still the subject of impassioned public discussion. If cannabis use is legalised, an increase in consumption is to be expected. One of the manifold negative consequences for mental health will probably be an increase in the prevalence of psychoses - not only acute, toxic psychosis but also chronic psychoses. Schizophrenic psychoses are expected to be triggered at an earlier age and to be negatively influenced in their course. This eventuality could have deleterious consequences not only for many currently healthy individuals predisposed to psychosis, but also for the disability pension.

D'Souza C; Cho HS; Perry E; Krystal JH. A cannabinoid 'model' psychosis, dopamine-cannabinoid interactions and implications for schizophrenia. IN: Castle D; Murray R, eds. Marijuana and Madness: Psychiatry and Neurobiology. Cambridge: Cambridge University Press, 2004. pp. 142-165. (70 refs.)

This chapter addresses the exogenous hypothesis of cannabis consumption and psychosis. First, it reviews studies from a number of sources, supporting an association between cannabis consumption and the manifestation of psychotic symptoms in human. It then details a recent pharmacological study that assessed the effects of exposure to the principal psychoactive constituent of cannabis, delta-nine-tetrahydrocannabinol in patients with schizophrenia and normal controls. The authors discuss possible mechanisms by which cannabis may induce psychosis and articulate the implications of the findings for a potential endocannabinoid contribution to the pathophysiology of schizophrenia. It is noted that controlled pharmacological studies demonstrate that delta-nine-tetrahydrocannabinol an induce a full range of transient schizophrenia-like positive psychotic symptoms, negative symptoms, and cognitive deficits, among other behavioral effects. Together with other data these data from pharmacological studies suggests that cannabinoid receptor dysfunction may contribute to the pathophysiology of schizophrenia. thus, there is tentative support for both the exogenous and endogenous hypotheses. While preclinical data suggest that dopaminergic systems may play an important role in the pscyhotogenic effects of cannabinoids, preliminary clinical data do not support this. The mechanisms underlying the capacity of cannabinoids to induce psychosis are unclear and warrant further study. Understanding the mechanisms may in addition provide novel therapeutic strategies for the treatment of psychoses.

D'Souza DC. Cannabinoids and psychosis. (review). Integrating the Neurobiology of Scizophrenia 78: 289-+, 2007. (162 refs.)

Recent epidemiological studies and advances in understanding of brain cannabinoid function have renewed interest in the long-recognized association between cannabinolds and psychosis. This chapter presents evidence supporting and refuting the association between cannabinoids and psychosis. Cannabinoids can induce acute transient psychotic symptoms or an acute psychosis in some individuals. What makes some individuals vulnerable to cannabinoid-related psychosis is unclear. Also clear is that cannabinoids can also exacerbate psychosis in individuals with an established psychotic disorder, and these exacerbations may last beyond the peniod of intoxication. Less clear is whether cannabis causes a persistent de novo psychosis. The available evidence meets many but not all the criteria for causality, including dose-response, temporality, direction, specificity, and biological plausibility. On the other hand, the large majority of individuals exposed to cannabinoids do not experience psychosis or develop schizophrenia and the rates of schizophrenia have not increased commensurate with the increase in rates of cannabis use. Similar to smoking and lung cancer, it is more likely that cannabis exposure is a component cause that interacts with other factors, for example, genetic risk, to "cause" schizophrenia. Nevertheless, in the absence of known causes of schizophrenia, the role of component causes such as cannabis exposure (exogenous hypothesis) is important and warrants further study. There is also tantalizing evidence from postmortem, neurochemical, and genetic studies suggesting CB I receptor dysfunction (endogenous hypothesis) in schizophrenia that warrants further investigation. Further work is necessary to identify those factors that place individuals at higher risk for cannabinold-related psychosis, to identify the biological mechanisms underlying the risks and to further study whether CBI receptor dysfunction contributes to the pathophysiology of psychotic disorders.

D'Souza DC; Abi-Saab WM; Madonick S; Forselius-Bielen K; Doersch A et al. Delta-9-tetrahydrocannabinol effects in schizophrenia: Implications for cognition, psychosis, and addiction. (review). Biological Psychiatry 57(6): 594-608, 2005. (158 refs.)

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, randomized, 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.

D'Souza DC; Perry E; MacDougall L; Ammerman Y; Cooper T; Wu YT et al. The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: Implications for psychosis. (review). Neuropsychopharmacology 29(8): 1558-1572, 2004. (148 refs.)

Recent advances in the understanding of brain cannabinoid receptor function have renewed interest in the association between cannabinoid compounds and psychosis. In a 3-day, double-blind, randomized, and counterbalanced study, the behavioral, cognitive, and endocrine effects of 0, 2.5, and 5 mg intravenous delta-9-tetrahydrocannabinol (Delta-9-THC) were characterized in 22 healthy individuals, who had been exposed to cannabis but had never been diagnosed with a cannabis abuse disorder. Prospective safety data at 1, 3, and 6 months poststudy was also collected. Delta-9-THC (1) produced schizophrenia-like positive and negative symptoms; (2) altered perception; (3) increased anxiety; (4) produced euphoria; (5) disrupted immediate and delayed word recall, sparing recognition recall; (6) impaired performance on tests of distractibility, verbal fluency, and working memory (7) did not impair orientation; (8) increased plasma cortisol. These data indicate that Delta-9-THC produces a broad range of transient symptoms, behaviors, and cognitive deficits in healthy individuals that resemble some aspects of endogenous psychoses. These data warrant further study of whether brain cannabinoid receptor function contributes to the pathophysiology of psychotic disorders.

Edwards J; Elkins K; Hinton M; Harrigan SM; Donovan K; Athanasopoulos O et al. Randomized controlled trial of a cannabis-focused intervention for young people with first-episode psychosis. Acta Psychiatrica Scandinavica 114(2): 109-117, 2006. (41 refs.)

Objective: To evaluate a cannabis-focused intervention (cannabis and psychosis therapy: CAP) for patients continuing to use cannabis following initial treatment for first-episode psychosis (FEP). Method: Consecutive admissions to an early psychosis program were screened and consenting individuals using cannabis in the 4 weeks prior to assessment participated. A single-blind randomized controlled trial compared CAP (n = 23) with a clinical control condition (psychoeducation, PE; n = 24). Results: There were no significant differences between the CAP and PE groups on cannabis use at end of treatment and 6 months post-intervention. There were no significant group differences on psychopathology and functional ratings at follow-up. A significant reduction in cannabis use was observed for both groups over time. Conclusion: PE and specific cannabis-focused intervention are associated with similar reductions in cannabis use in an FEP cohort. Simple interventions may therefore be worth considering prior to intensive psychotherapeutic efforts with this population.

Estrada G; Fatjo-Vilas M; Munoz MJ; Pulido G; Minano MJ; Toledo E et al. Cannabis use and age at onset of psychosis: Further evidence of interaction with COMT Val158Met polymorphism. Acta Psychiatrica Scandinavica 123(6): 485- 492, 2011. (69 refs.)

Objective: To examine, in a sample of young psychiatric patients, (n = 157, mean age 17.01 years (SD = 3.6)) whether i) age at first cannabis use and age at emergence of psychiatric disorders are related and ii) such a relationship is modulated by the Val158Met polymorphism in the COMT gene. Method: Cannabis use profiles and COMT Val158Met genotypes were obtained from 80 inpatients with schizophrenia-spectrum disorders and 77 inpatients with other non-psychotic disorders. Results: First, age at first cannabis use correlates with age at onset in both schizophrenia-spectrum and other psychiatric disorder groups: those who started using cannabis earlier had an earlier age at onset of psychiatric disorders. Second, the distribution of the Val158Met genotypes was not different either between diagnosis groups or between cannabis users and non-users. Third, an interaction between Val158Met genotypes and cannabis use was observed specifically on age at emergence of psychotic disorders, with Val/Val genotype carriers showing an earlier age at onset than Met carriers. Conclusion: Our results suggest the importance of brain maturation timing in which exposure to cannabis occurs. The COMT Val158Met genotype seems to modulate the association between cannabis and age at onset of psychotic disorders. These results are consistent with previous studies.

Every-Palmer S. Synthetic cannabinoid JWH-018 and psychosis: An explorative study. Drug and Alcohol Dependence 117(2-3): 152-157, 2011. (53 refs.)

Background: Aroma, Spice, K2 and Dream are examples of a class of new and increasingly popular recreational drugs. Ostensibly branded "herbal incense", they have been intentionally adulterated with synthetic cannabinoids such as JWH-018 in order to confer on them cannabimimetic psychoactive properties while circumventing drug legislation. JWH-018 is a potent cannabinoid receptor agonist. Little is known about its pharmacology and toxicology in humans. This is the first research considering the effects of JWH-018 on a psychiatric population and exploring the relationship between JWH-018 and psychotic symptoms. Method: This paper presents the results of semi-structured interviews regarding the use and effects of JWH-018 in 15 patients with serious mental illness in a New Zealand forensic and rehabilitative service. Results: All 15 subjects were familiar with a locally available JWH-018 containing product called "Aroma" and 86% reported having used it. They credited the product's potent psychoactivity, legality, ready availability and non-detection in drug testing as reasons for its popularity, with most reporting it had replaced cannabis as their drug of choice. Most patients had assumed the product was "natural" and "safe". Anxiety and psychotic symptoms were common after use, with 69% of users experiencing or exhibiting symptoms consistent with psychotic relapse after smoking JWH-018. Although psychological side effects were common, no one reported becoming physically unwell after using JWH-018. Three subjects described developing some tolerance to the product, but no one reported withdrawal symptoms. Conclusion: It seems likely that JWH-018 can precipitate psychosis in vulnerable individuals. People with risk factors for psychosis should be counseled against using synthetic cannabinoids.

Ferdinand RF; Sondeijker F; van der Ende J; Selten JP; Huizink A; Verhulst FC. Cannabis use predicts future psychotic symptoms, and vice versa. Addiction 100(5): 612-618, 2005. (37 refs.)

Aims: To assess if cannabis use is a risk factor for future psychotic symptoms, and vice versa, in adolescents and young adults from the general population. Design: Cohort study. Setting/participants: 'Zuid Holland' study, a 14-year follow-up study of 1580 initially 4-16-year-olds who were drawn randomly from the Dutch general population. Because cannabis use is generally condoned in the Netherlands, false-negative reports of cannabis use may occur less frequently than in countries with stricter drug policies, which supports the value of the present study. Measurements: Life-time cannabis use and psychotic symptoms, assessed with the Composite International Diagnostic Interview (CIDI). Findings: Cannabis use, in individuals who did not have psychotic symptoms before they began using cannabis, predicted future psychotic symptoms (hazard ratio = 2.81; 95% confidence interval = 1.79-4.43). However, psychotic symptoms in those who had never used cannabis before the onset of psychotic symptoms also predicted future cannabis use (hazard ratio = 1.70; 95% confidence interval = 1.13-2.57). Conclusions: The results imply either a common vulnerability with varying order of onset or a bi-directional causal relationship between cannabis use and psychosis. More research on patterns and timings of these relationships is needed to narrow down the possibilities.

Fergusson DM. Cannabis and psychosis: Two kinds of limitations which attach to epidemiological research. (letter). Addiction 99(4): 512-513, 2004. (10 refs.)

Fergusson DM; Horwood J; Ridder EM. Mirkin refuted: Reasons for believing that the association between cannabis use and risk of psychosis is probably causal. (letter). Addiction 100(5): 715, 2005. (9 refs.)

Fergusson DM; Horwood LJ; Ridder EM. Tests of causal linkages between cannabis use and psychotic symptoms. Addiction 100(3): 354-366, 2005. (44 refs.)

Aim: To examine possible causal linkages between cannabis use and psychosis using data gathered over the course of a 25-year longitudinal study. Design: A 25-year longitudinal study of the health, development and adjustment of a birth cohort of 1265 New Zealand children (635 males, 630 females). Setting: The Christchurch Health and Development Study, a general community sample. Participants A total of 1055 participants from the Christchurch Health and Development Study (CHDS) cohort for whom data on cannabis use and psychotic symptoms were available on at least one occasion from 18, 21 and 25 years. Measurements: As part of this study, data were gathered on frequency of cannabis use and psychotic symptoms at ages 18, 21 and 25 years. Findings: Regression models adjusting for observed and non-observed confounding suggested that daily users of cannabis had rates of psychotic symptoms that were between 1.6 and 1.8 times higher (P < 0.001) than non-users of cannabis. Structural equation modelling suggested that these associations reflected the effects of cannabis use on symptom levels rather than the effects of symptom levels on cannabis use. Conclusions: The results of the present study add to a growing body of evidence suggesting that regular cannabis use may increase risks of psychosis. The present study suggests that: (a) the association between cannabis use and psychotic symptoms is unlikely to be due to confounding factors; and (b) the direction of causality is from cannabis use to psychotic symptoms.

Fergusson DM; Poulton R; Smith PF; Boden JM. Drugs: Cannabis and psychosis. British Medical Journal 332(7534): 172-175, 2006. (23 refs.)

The United Kingdom is considering reclassifying cannabis because of concerns about links with mental health problems. This column deals with what the evidence does and does not show. It considers two areas of extensive research which have not been integrated. One is the link between cannabis and psychosis and the other is how cannabis affects neurochemical functioning. Among the evidence noted are (1) all studies have found that the use of cannabis is associated with increased risks of psychosis or psychotic symptoms and there is a dose-response relationship; and this relationship has been found with different measures for outcome and when confounded variables are controlled, as well as reverse causality. (2) The neurological pathways that link cannabis use and increased psychotic symptoms are not wholly clear. the most likely involve the effects of dealt-9-terthydocannabiono on the regulation of dopamine and serotonin, both of which are known to have a role in maintaining the psychotic state. It is noted that the use of cannabis accounts for about 10% of the cases of psychosis. At a policy level this leads to the confronting "a choice of evils: in which the rights of the majoring who use cannabis without problem, are balanced against the risk for a minority who may incur serious health consequences.

Flanders SE. Delusions incorporating cannabis use in dually diagnosed patients with a primary psychotic disorder. Australian and New Zealand Journal of Psychiatry 41(11): 934-936, 2007. (5 refs.)

Objective: To describe and discuss the implications for treatment of 3 cases of dually diagnosed patients with a primary psychotic disorder who have developed persisting, cannabis-oriented delusional systems. Method: Psychiatric assessment and daily observation on an acute inpatient psychiatric unit. Results: Abstinence appears to be particularly difficult to attain for a patient with psychosis who hold delusional beliefs that cannabis is a conduit for supernormal experiences with positive affective content, grandiose themes and a sense of enhanced self-efficacy. Conclusion: This phenomenon poses special challenges in the treatment of dual diagnosis patients. Modifications to existing CBT protocols for the treatment of substance abuse in psychosis might be useful in such patients.

Foti DJ; Kotov R; Guey LT; Bromet EJ. Cannabis use and the course of schizophrenia: 10-year follow-up after first hospitalitalization. American Journal of Psychiatry 167(8): 987-993, 2010. (40 refs.)

Objective: The authors examined the relationship between cannabis use and the course of illness in schizophrenia over 10 years of follow-up after first psychiatric hospitalization. Method: The authors assessed 229 patient S with a schizophrenia spectrum disorder five times: during the first admission and 6 months, 2 years, 4 years, and 10 years later. Ratings of cannabis use and psychiatric symptoms (psychotic, negative, disorganized, and depressive) were made at each assessment. Results: The lifetime rate of cannabis use was 66.2%, and survival analysis revealed that lifetime use was associated with an earlier onset of psychosis. The rates of current use ranged from 10% to 18% across assessments. Cannabis status was moderately stable, with tetrachoric correlation coefficients between waves ranging from 0.48 to 0.78. Mixed-effects logistic regression revealed that changes in cannabis use were associated with changes in psychotic symptoms over time even after gender, age, socioeconomic status, other drug use, antipsychotic medication use, and other symptoms were controlled for. Structural equation modeling indicated that the association with psychotic symptoms was bidirectional. Conclusions: Cannabis use is associated with an adverse course of psychotic symptoms in schizophrenia, and vice versa, even after taking into account other clinical, substance use, and demographic variables.

Gentil V. Cannabis psychosis, smoke and fire. (editorial). Stress and Health 19(5): 249-251, 2003

Compared to the many other adverse effects of cannabis, chronic psychosis may be relatively uncommon. Helping or living with someone with the dual diagnosis of psychosis and drug addiction are among the most stressful challenges that one may face. Causation deserves special attention here because treatment efficacy is low, and primary prevention depends on knowledge of the main causal factors. The debate regarding this subject has recently been heated by new research findings of a much denied causal relationship between cannabis abuse and schizophrenia. In the US and in other countries, the co-morbidity of substance abuse and psychosis is about 50%, and an interaction of acute cannabis effects and vulnerability is well demonstrated. In addition, clinical reports and research findings of a causal link between cannabis and psychosis have repeatedly been dismissed on methodological grounds. In a convergence of epidemics, the academic argument about independent causation versus interaction with vulnerabilities has limited public health relevance. Liberal attitudes increasing exposure will surely increase risks. Given that there is no reliable way to detect specific vulnerability and no effective treatment, it is better to avoid the fire.

Gonzalez-Pinto A; Vega P; Ibanez B; Mosquera F; Barbeito S; Gutierrez M et al. Impact of cannabis and other drugs on age at onset of psychosis. Journal of Clinical Psychiatry 69(8): 1210-1216, 2008. (40 refs.)

Objective: The aim of this study was to investigate the relationship between age and cannabis use in patients with a first psychotic episode, and to analyze the mediating effect of comorbid use of other drugs and sex on age at onset of psychosis. Method: All consenting patients (aged 15 to 65 years) with a first psychotic episode needing inpatient psychiatric treatment during a 2-year period between February 1997 and January 1999 were considered, confirming a total of 131 patients. Subjects were interviewed using the Structured Clinical Interview for DSM-IV Axis I Disorders, and clinical and demographic data were collected. We used general linear models with age at onset as the response variable and survival Cox models to confirm the results. Both a multivariate linear model and the corresponding Cox model were fitted with a covariate that summarizes the most significant contributors that seemed to decrease age at onset. Results: Regarding the effect of cannabis use, a significant gradual reduction on age at onset was found as dependence on cannabis increased, consisting in a decrement of 7, 8.5, and 12 years for users, abusers, and dependents, respectively, with respect to nonusers (p = .004, p < .001, and p < .001, respectively). Multivariate analysis showed a clear effect of cannabis use on age at onset, which was not explained by the use of other drugs or by gender. The finding was similar in the youngest patients, suggesting that this effect was not due to chance. Conclusion: The major contribution of this investigation is the independent and strong link between cannabis use and early age at onset of psychosis, and the slight or nonexistent effect of sex and comorbid substance abuse in this variable. These results point to cannabis as a dangerous drug in young people at risk of developing psychosis.

Gorelick DA; Heishman SJ. Methods for clinical research involving cannabis administration. IN: Onaivi ES, ed. Marijuana and Cannabinoid Research: Methods and Protocols. Totowa NJ: Humana Press, 2005. pp. 235-253

Better scientific understanding of cannabis effects and the development of treatments for cannabis dependence require clinical studies involving cannabis administration. Cannabis can be administered by smoking a plant-derived cigarette or by oral or intravenous administration of ?9-tetrahydrocannabinol (THC), the primary psychoactive chemical in cannabis. The smoked route is most commonly used outside the laboratory, but is subject to wide variation in absorbed dose. Oral synthetic THC is a legally marketed medication (dronabinol), also subject to wide pharmacokinetic variation, but offering a greater safety margin because of slower onset of action and lower potency. Intravenous THC offers precise investigator control of dose and timing. Acute adverse effects of cannabis administration include tachycardia, orthostatic hypotension, pulmonary irritation (if smoked), motor incoordination, cognitive impairment, anxiety, paranoia, and psychosis. Screening of research subjects should identify and exclude those with risk factors for such events, e.g., a history of significant cardiovascular, pulmonary, or psychiatric disorders. Monitoring of subjects during cannabis administration should include heart rate, blood pressure, and mental status. Subjects should not be discharged from research participation until reevaluation has shown that they have returned to baseline status.

Grech A; Van Os J; Jones PB; Lewis SW; Murray RM. Cannabis use and outcome of recent onset psychosis. European Psychiatry 20(4): 349-353, 2005. (30 refs.)

Purpose. - To test the hypothesis that recent onset psychotic patients who use cannabis will have psychotic symptoms that are more severe and more persistent than those who do not use cannabis. Subjects and methods. - We carried out a 4-year follow-up study of a cohort of 119 patients with recent onset of psychosis. The patients were divided into four groups according to duration of cannabis use, taking index admission and follow-up as reference points. Results. - Those subjects who persisted in the use of cannabis had more positive (but not negative) symptoms and a more continuous illness at follow-up. Limitations. - The main limitations of the study were: the relatively small sample size, and that the excess of male subjects and the presence of cannabis induced psychosis could have a confusing impact on the interpretation of the results. Conclusion. - It is possible that psychotic patients who use cannabis are at a greater risk of a more continuous illness with more positive symptoms than those who do not.

Green AI; Tohen MF; Hamer RM; Strakowski SM; Lieberman JA; Glick I et al. First episode schizophrenia-related psychosis and substance use disorders: Acute response to olanzapine and haloperidol. Schizophrenia Research 66(2-3): 125-135, 2004. (57 refs.)

Background: Co-occurring substance use disorders, mostly involving alcohol, cannabis or cocaine, occur commonly in patients with schizophrenia and are associated with increased morbidity and mortality. Available but limited data suggest that substance use disorders (especially cannabis use disorders) may also be common in first-episode patients and appear linked to a poor outcome in these patients. Strategies to curtail substance use form an important dimension of the treatment program for both first-episode and chronic patients. We report on rates of co-occurring substance use disorders in patients within their first episode of schizophrenia-related psychosis from a multicenter, international treatment trial of olanzapine vs. baloperidol. Methods: The study involved 262 patients (of 263 who were randomized and who returned for a post-randomization evaluation) within their first episode of psychosis (schizophrenia, schizoaffective disorder or schizophreniform disorder) recruited from 14 academic medical centers in North America and Western Europe. Patients with a history of substance dependence within I month prior to entry were excluded. Results: Of this sample, 97 (37%) had a lifetime diagnosis of substance use disorder (SUD); of these 74 (28% of the total) had a lifetime cannabis use disorder (CUD) and 54 (21%) had a lifetime diagnosis of alcohol use disorder (AUD). Patients with SUD were more likely to be men. Those with CUD had a lower age of onset than those without. Patients with SUD had more positive symptoms and fewer negative symptoms than those without SUD, and they had a longer duration of untreated psychosis. The 12-week response data indicated that 27% of patients with SUD were responders compared to 35% of those without SUD. Patients with AUD were less likely to respond to olanzapine than those without AUD. Discussion: These data suggest that first-episode patients are quite likely to have comorbid substance use disorders, and that the presence of these disorders may negatively influence response to antipsychotic medications, both typical and atypical antipsychotics, over the first 12 weeks of treatment.

Green B; Kavanagh DJ; Young RM. Predictors of cannabis use in men with and without psychosis. Addictive Behaviors 32(12): 2879-2887, 2007. (32 refs.)

Background: Factors associated with cannabis use among people with psychosis are not well understood. Aims: To examine whether people with psychosis and age-matched controls modified cannabis use in response to recent experiences. Method: This study predicted 4 weeks of cannabis use prospectively, using expectancies derived from recent occasions of use. Results: People with psychosis used cannabis less frequently than controls, but had more cannabis-related problems. More negative cannabis expectancies resulted in less frequent cannabis use over Follow-up. The psychosis group was more likely to moderate cannabis use after negative effects than controls. Conclusions: Results offer optimism about abilities of people with psychosis to moderate cannabis use in the short term.

Green B; Kavanagh DJ; Young RMCD. Reasons for cannabis use in men with and without psychosis. Drug and Alcohol Review 23(4): 445-453, 2004. (34 refs.)

Psychoses are relatively low prevalence disorders that have a disproportionately negative impact on individuals and society. Cannabis use is one factor that can exacerbate the negative consequences associated with psychotic disorders. Relatively few studies have examined the effects or reasons for using cannabis self-reported by individuals with psychosis. The present study is the first known to compare directly such factors in individuals with and without psychosis, within a single study. At baseline and follow-up participants with psychosis most commonly reported using cannabis for positive mood alteration (36% and 42%), coping with negative affect (27% and 29%) and for social activity reasons (38% and 29%). The control group most commonly reported using cannabis for relaxation (34% and 43%) and social activity reasons (49% and 51%). Participants with psychosis were less likely to report relaxation as the most important effect after use (27%) or expect it at follow-up (49%) compared to the control group (53% and 70%). In both groups, addiction and positive affect enhancement were the composite variable scores correlated most consistently with concurrent amount and frequency of use.

Hall W; Degenhardt L. Cannabis and the increased incidence and persistence of psychosis. (editorial). British Medical Journal 342: article d719, 2011. (12 refs.)

Hall W; Degenhardt L. Is there a specific 'cannabis psychosis'? IN: Castle D; Murray R, eds. Marijuana and Madness: Psychiatry and Neurobiology. Cambridge: Cambridge University Press, 2004. pp. 89-100. (61 refs.)

The existence of a discrete 'cannabis psychosis' is still a matter for debate. In its favour are case series of 'cannabis psychosis' and a small number of controlled studies that compare the characteristics of 'cannabis psychosis' with those of psychoses in individuals who were not using cannabis at the time of manifestation of symptoms. Critics of the hypothesis emphasize the fallibility of clinical judgments about etiology, the poorly specified criteria used in diagnosis these psychoses, the dearth of controlled studies and the striking variations in the clinical features of 'cannabis psychosis.' It is a plausible hypothesis that high doses of cannabis can produce psychotic symptoms. There is no compelling evidence, however, that there is a specific syndrome that is identifiable as a 'cannabis psychosis.' It these exist, they are rare or they only rarely receive medical intervention in western societies.

Hall W; Degenhardt L. Prevalence and correlates of cannabis use in developed and developing countries. Current Opinion in Psychiatry 20(4): 393-397, 2007. (51 refs.)

Purpose of review: The aim of this article is to review recent research on the prevalence, antecedents and correlates of cannabis use in young adults in developed and developing countries. Recent findings Cannabis is the most widely used illicit drug globally and its use appears to be increasing in developed and developing countries. In developed countries rebelliousness, antisocial behaviour, poor school performance, and affiliation with drug-using peers are risk factors for early and regular cannabis use. Similar antecedents are now being reported in developing countries. Dependence is an underappreciated risk of cannabis that affects one in six to seven adolescents who use cannabis in developed countries. Adolescent cannabis dependence is correlated with an increased risk of using other illicit drugs, symptoms of depression, and symptoms of psychosis. The plausibility of cannabis playing a contributory causal role has increased for symptoms of psychosis in longitudinal studies but remains contentious. In the case of other illicit drug use and mood disorders common causal explanations remain difficult to exclude. Summary: Early and regular cannabis use in adolescence predicts an increased risk of cannabis dependence which in turn predicts an increased risk of using other illicit drugs, and reporting symptoms of mood and psychotic disorders.

Hall W; Degenhardt L. What are the policy implications of the evidence on cannabis and psychosis? (review). Canadian Journal of Psychiatry 51(9): 566-574, 2006. (82 refs.)

Objective: To explore the implications for mental health services, for health education about the risks of cannabis use, and for public policy toward cannabis use of observational evidence that cannabis use is a contributory cause of psychosis. Method: Using comparative analyses of similar evidence for the harmful effects of alcohol, tobacco, and amphetamine use, we considered the relation between observational evidence and action on cannabis. We examined arguments on the grounds of public health prudence for discouraging cannabis use by young individuals. With the assumption that the relation may be causal, we considered recommendations for policy in mental health services, health education, and public policy toward cannabis. Results: The observational evidence and biological plausibility of the hypothesis that cannabis is a contributory cause of psychosis is at least as strong as evidence for causal relations between heavy alcohol and amphetamine use and psychosis. On public health grounds, there is a good case for discouraging cannabis use among adolescents and young adults. It remains uncertain how best to discourage use and at whom campaigns to reduce cannabis use should be targeted. Conclusions: We should discourage young adults seeking treatment in mental health services from using cannabis and inform them of the probable mental health risks of cannabis use, especially of early and frequent use. We must exercise caution in liberalizing cannabis laws in ways that may increase young individuals' access to cannabis, decrease their age of first use, or increase their frequency of cannabis use. We should consider the feasibility of reducing the availability of high-potency cannabis products.

Hall W; Degenhardt L; Teesson M. Cannabis use and psychotic disorders: An update. Drug and Alcohol Review 23(4): 433-443, 2004. (86 refs.)

This paper evaluates three hypotheses about the relationship between cannabis use and psychosis in the light of recent evidence from prospective epidemiological studies. These are that: (1) cannabis use causes a psychotic disorder that would not have occurred in the absence of cannabis use; (2) that cannabis use may precipitate schizophrenia or exacerbate its symptoms; and (3) that cannabis use may exacerbate the symptoms of psychosis. There is limited support for the first hypothesis. As a consequence of recent prospective studies, there is now stronger support for the second hypothesis. Four recent prospective studies in three countries have found relationships between the frequency with which cannabis had been used and the risk of receiving a diagnosis of schizophrenia or of reporting psychotic symptoms. These relationships are stronger in people with a history of psychotic symptoms and they have persisted after adjustment for potentially confounding variables. The absence of any change in the incidence of schizophrenia during the three decades in which cannabis use in Australia has increased makes it unlikely that cannabis use can produce psychoses that would not have occurred in its absence. It seems more likely that cannabis use can precipitate schizophrenia in vulnerable individuals. There is also reasonable evidence for the third hypothesis that cannabis use exacerbates psychosis.

Hall W; Degnhardt L. Cannabis use and the risk of developing a psychotic disorder. World Psychiatry 7(2): 68-71, 2008. (53 refs.)

We briefly review the evidence that cannabis use in adolescence and young adulthood is a contributory cause of schizophreniform psychoses, by summarising longitudinal studies that: a) have examined relationships between cannabis use and the risk of psychosis or psychotic symptoms; and b) have controlled for potential confounders, such as other forms of drug use and personal characteristics that predict an increased risk of psychosis. There is now reasonable evidence from longitudinal studies that regular cannabis use predicts an increased risk of schizophrenia and of reporting psychotic symptoms. These relationships have persisted after controlling for confounding variables such as personal characteristics and other drug use. The relationships did not seem to be explained by cannabis being used to self-medicate symptoms of psychosis. A contributory causal relationship is biologically plausible because psychotic disorders involve disturbances in the dopamine neuro transmitter system with which the cannabinoid system interacts, as has been shown by animal studies and a human provocation study. We briefly explore the clinical and public health implications of the most plausible hypothesis, that cannabis use precipitates schizophrenia in persons who are vulnerable because of a personal or family history of schizophrenia.

Hall W; Pacula RL. Cannabis Use and Dependence: Public Health and Public Policy. Melbourne: Cambridge University Press, 2003. (960 refs.)

The use of cannabis in the late twentieth and this century is an area of medical and moral controversy. Despite its illegality, cannabis is the most widely used drug after alcohol and tobacco among young adults in Australia, the USA and Europe. This book explores the relationship between health policy, public health and the law regarding cannabis use. The book is organized into 8 sections. The first section describes cannabis as a drug and the ways in which it is typically used. Section 2 (chapters 3-5) reviews the evidence of adverse health effects associated with cannabis use including acute effects, chronic effects on cellular, immunological, and reproductive functioning, and cardiovascular, respiratory and gastrointestinal system. Section 3 (Chapters 7-9) examines the psychological effects of chronic use. These include effects on motivation and the risk of dependence, effects on cognitive function and risk of developing psychosis. The fourth section (chapters 10-11) deals with the most contentious issues in the debate on cannabis, effects on adolescents. The gateway hypothesis is reviewed as well as the effects of cannabis on psychosocial outcomes of adolescence. The fifth sections (chapters 11-12) considers the harms and benefits of cannabis use, the latter which are generally not considered. Section six discusses the cannabis policy debate, This includes two central claims of strategic significance to the case for legal reform, whether prohibition has any deterrent effects and the economic costs of enforcing the current prohibitions. There is also a summary of some of the tangible costs of cannabis prohibition that have been identified by its critics, including the loss of liberty to use marijuana, the creation of a black market, disrespect for a widely broken and minimally enforced law, harm to users' reputations, impaired health education about marijuana and other drugs, the loss of benefits from marijuana including medical use, and the inefficient use of law enforcement resources. Section seven explores, in detail, alternative cannabis policy. There is a discussion of variations of prohibition that have been proposed and trialled in a number of countries. There is also discussion of the possibility for a legal market in which cannabis could be legally produced, sold and used. The nature of a heavily regulated legal cannabis market is set forth. The final chapter summarizes the arguments that have been put forth about the harms of cannabis use and the costs and effectiveness of prohibition. The authors argue that marijuana policies need to be more responsive to evidence on both the adverse health effects of marijuana and the costs and effectiveness of marijuana control policies. The do suggest ways to move the policy debate forward by developing support for incremental policy changes - the costs and effects of which could be systematically evaluated.

Hall W; Solowij N. The adverse health and psychological consequences of cannabis dependence. IN: Roffman RA; Stephens RS, eds. Cannabis Dependence: Its Nature, Consequences and Treatment. London: Cambridge University Press, 2006. pp. 106-132

This chapter considers morbidity associated with chronic marijuana use. Among the conidtions addressed are the respiratory risks of smoking marijuana, respiratory cancers associated with long term use, brain function and cognitivie impairment associated with chronic use, and the role of cannabis in accidental injury. The cardiovascular effects of cannabis use are reviewed. In addition psychological/behavioral related effects are addressed, such as the impact of different levels of marijuana use on school performance,the relationsip of cannabis use ato psychosis and schizophrenia, and the "gateway hypothesis", as well as special populations of cannabis-dependent persons.

Hall WD. Cannabis use and the mental health of young people. (review). Australian and New Zealand Journal of Psychiatry 40(2): 105-113, 2006. (98 refs.)

Objective: To review the evidence on the mental health and psychosocial consequences of rising rates of cannabis use among young people in developed countries. Method: This paper critically reviews epidemiological evidence on the following psychosocial consequences of adolescent cannabis use: cannabis dependence; the use of heroin and cocaine; educational underachievement; and psychosis. Leading electronic databases such as PubMed have been searched to identify large-scale longitudinal studies of representative samples of adolescents and young adults conducted in developed societies over the past 20 years. Results: Cannabis is a drug of dependence, the risk of which increases with decreasing age of initiation. Cannabis dependence in young people predicts increased risks of using other illicit drugs, underperforming in school, and reporting psychotic symptoms. Uncertainty remains about which of these relationships are causal although the evidence is growing that cannabis is a contributory cause of psychotic symptoms. Conclusions: We face major challenges in communicating with young people about the most probable risks of cannabis use (dependence, educational underachievement and psychosis) given uncertainties about these risks and polarized community views about the policies that should be adopted to reduce them.

Harley M; Kelleher I; Clarke M; Lynch F; Arseneault L; Connor D et al. Cannabis use and childhood trauma interact additively to increase the risk of psychotic symptoms in adolescence. Psychological Medicine 40(10): 1627-1634, 2010. (54 refs.)

Background. Adolescent cannabis use has been shown in many studies to increase the risk of later psychosis. Childhood trauma is associated with both substance misuse and risk for psychosis. In this study our aim was to investigate whether there is a significant interaction between cannabis use and childhood trauma in increasing the risk for experiencing psychotic symptoms during adolescence. Method. Psychiatric interviews using the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) semi-structured instrument were carried out with 211 adolescents aged between 12 and 15 years and their parents as part of a population-based study. The interview enquired about early traumatic events, cannabis use and psychiatric symptoms in adolescence. Results. In separate analyses both cannabis use and childhood trauma were significantly associated with risk of experiencing psychotic symptoms. However, the presence of both childhood trauma and early cannabis use significantly increased the risk for psychotic symptoms beyond the risk posed by either risk factor alone, indicating that there was a greater than additive interaction between childhood trauma and cannabis use. Conclusion. Our finding of a greater than additive interaction between childhood trauma and cannabis use may have implications for the identification of individuals at high risk of experiencing psychotic symptoms. For example, measures to actively discourage or intensively treat cannabis use in children and adolescents who have experienced abuse may help to prevent the development of psychosis in this vulnerable group. Our findings require replication in larger samples to confirm this interaction effect.

Henquet C; Di Forti M; Morrison P; Kuepper R; Murray RM. Gene-environment interplay between cannabis and psychosis. (review). Schizophrenia Bulletin 34(6): 0586-7614, 2008. (104 refs.)

Cannabis use is considered a contributory cause of schizophrenia and psychotic illness. However, only a small proportion of cannabis users develop psychosis. This can partly be explained by the amount and duration of the consumption of cannabis and by its strength but also by the age at which individuals are first exposed to cannabis. Genetic factors, in particular, are likely to play a role in the short- and the long-term effects cannabis may have on psychosis outcome. This review will therefore consider the interplay between genes and exposure to cannabis in the development of psychotic symptoms and schizophrenia. Studies using genetic, epidemiological, experimental, and observational techniques will be discussed to investigate gene-environment correlation gene-environment interaction, and higher order interactions within the cannabis-psychosis association. Evidence suggests that mechanisms of gene-environment interaction are likely to underlie the association between cannabis and psychosis. In this respect, multiple variations within multiple genes-rather than single genetic polymorphisms-together with other environmental factors (eg, stress) may interact with cannabis to increase the risk of psychosis. Further research on these higher order interactions is needed to better understand the biological pathway by which cannabis use, in some individuals, may cause psychosis in the short- and long term.

Henquet C; Murray R; Linszen D; van Os J. The environment and schizophrenia: The role of cannabis use. Schizophrenia Bulletin 31(3): 608-612, 2005. (31 refs.)

Cannabis use is associated with poor outcome in existing schizophrenia and may precipitate psychosis in individuals with preexisting liability. To investigate the overall effect size and consistency of the association between cannabis and psychosis, a meta-analysis from prospective studies was carried out. The pooled odds ratio was 2.1 (95% CI: 1.7-2.5) and could not be explained by confounding or reverse causality. Evidence suggests that cannabis is a component cause in the development and prognosis of psychosis, in which mechanisms of gene-environment interaction are most likely to explain this association. Potential new methods to directly link genetic liability to the effects of cannabis are discussed.

Hides L; Dawe S; Kavanagh DJ; Young RM. Psychotic symptom and cannabis relapse in recent-onset psychosis: Prospective study. British Journal of Psychiatry 189: 137-143, 2006. (40 refs.)

Background: Cannabis use appears to exacerbate psychotic symptoms and increase risk of psychotic relapse. However, the relative contribution of cannabis use compared with other risk factors is unclear. The influence of psychotic symptoms on cannabis use has received little attention. Aims: To examine the influence of cannabis use on psychotic symptom relapse and the influence of psychotic symptom severity on relapse in cannabis use in the 6 months following hospital admission. Method: At baseline, 84 participants with recent-onset psychosis were assessed and 81 were followed up weekly for 6 months, using telephone and face-to-face interviews. Results: A higher frequency of cannabis use was predictive of psychotic relapse, after controlling for medication adherence, other substance use and duration of untreated psychosis. An increase in psychotic symptoms was predictive of relapse to cannabis use, and medication adherence reduced cannabis relapse risk. Conclusions: The relationship between cannabis use and psychosis may be bidirectional, highlighting the need for early intervention programmes to target cannabis use and psychotic symptom severity in this population.

Hides L; Dawe S; Young RM; Kavanagh DJ. The reliability and validity of the Severity of Dependence Scale for detecting cannabis dependence in psychosis. Addiction 102(1): 35-40, 2007. (31 refs.)

To determine the reliability and validity of the Severity of Dependence Scale (SDS) for detecting cannabis dependence in a large sample of in-patients with a schizophrenia spectrum disorder. Cross-sectional study. Participants were 153 in-patients with a schizophrenia spectrum disorder in Brisbane, Australia. Participants were administered the SDS for cannabis dependence in the past 12 months. The presence of Diagnostic and Statistical Manual Version-IV (DSM-IV) cannabis dependence in the previous 12 months was assessed using the Comprehensive International Diagnostic Interview (CIDI). The SDS had high levels of internal consistency and strong construct and concurrent validity. Individuals with a score of >= 2 on the SDS were nearly 30 times more likely to have DSM-IV cannabis dependence. The SDS was the strongest predictor of DSM-IV cannabis dependence after controlling for other predictor variables. The SDS is a brief, valid and reliable screen for cannabis dependence among people with psychosis.

Houston JE; Murphy J; Shevlin M; Adamson G. Cannabis use and psychosis: Re-visiting the role of childhood trauma. Psychological Medicine 41(11): 2339-2348, 2011. (54 refs.)

Background. Cannabis consumption continues to be identified as a causal agent in the onset and development of psychosis. However, recent findings have shown that the effect of cannabis on psychosis may be moderated by childhood traumatic experiences. Method. Using hierarchical multivariate logistic analyses the current study examined both the independent effect of cannabis consumption on psychosis diagnosis and the combined effect of cannabis consumption and childhood sexual abuse on psychosis diagnosis using data from the Adult Psychiatric Morbidity Survey 2007 (n=7403). Results. Findings suggested that cannabis consumption was predictive of psychosis diagnosis in a bivariate model; however, when estimated within a multivariate model that included childhood sexual abuse, the effect of cannabis use was attenuated and was not statistically significant. The multivariate analysis revealed that those who had experienced non-consensual sex in childhood were over six times [odds ratio (OR) 6.10] more likely to have had a diagnosis of psychosis compared with those who had not experienced this trauma. There was also a significant interaction. Individuals with a history of non-consensual sexual experience and cannabis consumption were over seven times more likely (OR 7.84) to have been diagnosed with psychosis compared with those without these experiences; however, this finding must be interpreted with caution as it emerged within an overall analytical step which was non-significant. Conclusions. Future studies examining the effect of cannabis consumption on psychosis should adjust analyses for childhood trauma. Childhood trauma may advance existing gene-environment conceptualisations of the cannabis-psychosis link.

Iqbal N. Recoverable hearing loss with amphetamines and other drugs. Journal of Psychoactive Drugs 36(2): 285-288, 2004. (17 refs.)

Prolonged and sustained consumption of alcohol, heroin and volatiles had been reported to impair hearing. Amphetamine related hearing loss is clinically different from the hearing loss seen with other agents. It seems that illicit drug use could result in two clinically different types of hearing losses. In May and June of 2001, 183 men aged 18 and above who met DSM-IV criteria for substance dependence were studied in a hospital in Saudia Arabia. The purpose of the study was to ascertain the prevalence of amphetamine-related recoverable hearing loss, establish whether similar hearing loss also occurred with other drugs of abuse and determine if drug-related psychosis was more prevalent in those amphetamine users who developed this type of hearing loss. Recoverable type of hearing loss was not just seen in amphetamine users but also occurred with cannabis, heroin, alcohol, dextromethorphan and glue use. Drug-induced psychosis was three and a half times more common in those amphetamine users who developed a hearing loss. Major depression and suicidality was also more common in these individuals. This association of major depression and subsequent development of hearing loss was also found in those using other type of drugs. It was concluded that a history of major depression was a good predictor of later development of both drug-induced psychosis and hearing loss in amphetamine users, and hypoperfusion was proposed as the possible explanation.

Isaac M; Isaac M; Holloway F. Is cannabis an anti-antipsychotic? The experience in psychiatric intensive care. Human Psychopharmacology. Clinical and Experimental 20(3): 207-210, 2005. (27 refs.)

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 implications of cannabis usage have involved psychiatric intensive care units (PICU); but PICU receive many of the most challenging and resource-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 implications, with higher blood glucose levels at admission and greater weight increase. Atypical antipsychotics were effective in treating psychosis inpatients 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.

James W. Addressing cannabis abuse in people with psychosis. IN: Castle D; Murray R, eds. Marijuana and Madness: Psychiatry and Neurobiology. Cambridge: Cambridge University Press, 2004. pp. 186-197. (46 refs.)

As discussed elsewhere in the book, cannabis use is common among those with schizophrenia and regular use, even at low levels, can have a negative impact on illness course. The effective management of this clinical problem is increasingly the focus of psychiatric practice and research. This chapter reviews a number of important areas that deserve consideration when developing an effective response. Aspects such as screening, assessment and models of service delivery are covered. The chapter concludes by outlining a number of psychosocial treatment interventions. There is a paucity of research evidence in terms of treatment interventions solely for cannabis use amongst people with schizophrenia, and thus studies considering other drugs are also included in the review.

Kohler S; van Os J; de Graaf R; Vollebergh W; Verhey F; Krabbendarn L. Psychosis risk as a function of age at onset: A comparison between early- and late-onset psychosis in a general population sample. Social Psychiatry and Psychiatric Epidemiology 42(4): 288-294, 2007. (69 refs.)

Background: Little is known about lateonset psychosis (onset after the age 45 years) and how it relates to early-onset psychosis (before age 45 years). The aims of this study were to calculate the incidence of non-affective, non-organic psychotic symptoms across the life span and to explore the contribution of different sets of risk factors in relation to age at onset. Methods: Data were obtained from the three measurements of the Netherlands Mental Health Survey and Incidence Study. Symptoms of psychosis were assessed in individuals aged 18-64 years using the Composite International Diagnostic Interview. All individuals reporting first-onset of psychotic symptoms within a three-year interval were included. The degree to which sets of risk factors affected the psychosis outcome similarly across age groups was assessed. Results The number of subjects displaying incident psychotic symptoms was similar across age groups. Cumulative incidence rates ranged from 0.3% to 0.4%. Age differences were found for life-time depressive symptoms (risk difference = 5%, 95% CI = 1%, 9%) and baseline neuroticism (risk difference = 3%, 95% CI = 0%, 696), indicating that late-onset psychosis was less often preceded by these. In contrast, no effect modification by age was observed for female sex, hearing impairment, being single, or life-time cannabis use. Conclusions: Onset of psychotic symptoms in late life is no rare event. Compared to early onset psychosis, the late-onset counterpart less often arises in a context of emotional dysfunction and negative affectivity, suggesting qualitative differences in aetiology and more effective premorbid coping styles.

Konings M; Henquet C; Maharajh HD; Hutchinson G; Van Os J. Early exposure to cannabis and risk for psychosis in young adolescents in Trinidad. Acta Psychiatrica Scandinavica 118(3): 209-213, 2008. (35 refs.)

Objective: Cannabis use increases the risk for psychosis, but psychotogenic effects of cannabis may be restricted to exposure during early adolescence. Method: Four hundred and seventy-two participants (aged 12-23 years), randomly selected from the general population in Trinidad, completed questionnaires on past and current cannabis use and psychotic symptoms (using the Community Assessment of Psychic Experiences). Results: Cannabis use increased the risk of experiencing psychotic symptoms and this effect was conditional on early exposure, defined around the mean age of onset of cannabis use. Thus, exposure before but not after the age of 14 years predicted psychotic symptoms (respectively beta: 0.71, 95% CI 0.22; 1.19, P = 0.004 and beta: -0.11, 95% CI -0.57; 0.36, P = 0.66). The developmental effect of cannabis use was independent of use of other drugs or current use of cannabis. Conclusion: Early adolescence may be a critical period with regard to the psychotogenic effect of cannabis across geographical settings and ethnic groups.

Kristensen K; Cadenhead KS. Cannabis abuse and risk for psychosis in a prodromal sample. Psychiatry Research 151(1-2): 151-154, 2007. (20 refs.)

The goal of the present study was to examine the rate of cannabis use among participants in the Cognitive Assessment and Risk Evaluation (CARE) Program, a longitudinal program for individuals who are "at risk" for developing a psychotic disorder. Cannabis abuse was assessed in 48 individuals identified as at risk for psychosis based on subsyndromal psychotic symptoms and/ or family history. At I year follow-up, 6 of the 48 (12.5%) at risk subjects had made the transition to psychosis. Of the 32 subjects who had no use or minimal cannabis use, one subject (3.1%) converted to psychosis. Of the 16 subjects who met criteria for cannabis abuse/dependence, five (3 1.3%) converted to psychosis. The results show a significant association between cannabis abuse and conversion to psychosis in this sample. Nicotine use was also found to be significantly associated with later conversion. The significant associations between cannabis and nicotine abuse and conversion to psychosis in individuals at risk for schizophrenia suggest that early identification and intervention programs should screen for and provide education about the deleterious effects of these substances.

Kuepper R; van Os J; Lieb R; Wittchen HU; Henquet C. Do cannabis and urbanicity co-participate in causing psychosis? Evidence from a 10-year follow-up cohort study. Psychological Medicine 41(10): 2121-2129, 2011. (49 refs.)

Background. Cannabis use is considered a component cause of psychotic illness, interacting with genetic and other environmental risk factors. Little is known, however, about these putative interactions. The present study investigated whether an urban environment plays a role in moderating the effects of adolescent cannabis use on psychosis risk. Method. Prospective data (n = 1923, aged 14-24 years at baseline) from the longitudinal population-based German Early Developmental Stages of Psychopathology cohort study were analysed. Urbanicity was assessed at baseline and defined as living in the city of Munich (1562 persons per km(2); 4061 individuals per square mile) or in the rural surroundings (213 persons per km(2); 553 individuals per square mile). Cannabis use and psychotic symptoms were assessed three times over a 10-year follow-up period using the Munich version of the Composite International Diagnostic Interview. Results. Analyses revealed a significant interaction between cannabis and urbanicity [10.9% adjusted difference in risk, 95% confidence interval (CI) 3.2-18.6, p = 0.005]. The effect of cannabis use on follow-up incident psychotic symptoms was much stronger in individuals who grew up in an urban environment (adjusted risk difference 6.8%, 95% CI 1.0-12.5, p = 0.021) compared with individuals from rural surroundings (adjusted risk difference -4.1%, 95% CI -9.8 to 1.6, p = 0.159). The statistical interaction was compatible with substantial underlying biological synergism. Conclusions. Exposure to environmental influences associated with urban upbringing may increase vulnerability to the psychotomimetic effects of cannabis use later in life.

Latt N; Jurd S; Tennant C; Lewis J; Macken L; Joseph A et al. Alcohol and substance use by patients with psychosis presenting to an emergency department: Changing patterns. Australasian Psychiatry 19(4): 354-359, 2011. (14 refs.)

Objectives: The aim of this study was to determine the incidence of alcohol and other substance use in patients presenting to an emergency department with acute psychiatric illnesses and to clarify the role of urine drug screens. Method: This was an unblinded prospective (observational) cohort study incorporating retrospective review of patient medical records, history of alcohol and substance use, results of urine drug screens and blood alcohol concentrations. Results: Of 196 acute psychotic patients, 104 were diagnosed with schizophrenia and 92 with "other psychosis". Results of urine drug screens were consistent with self-reported use of substances and only identified an additional 5% of substance users. Cannabis was the commonest illicit substance used by both groups of patients, followed by psychostimulants, mainly amphetamines. Younger males were more likely to use psychostimulants and to present with violence. Conclusions: Patients with co-existing mental health problems and substance use present a major problem for our emergency departments. Cannabis was the most common substance used. Youth, male gender and psychostimulant use are associated with violent presentations. A comprehensive history of alcohol and substance use is important to implement appropriate dual diagnosis treatment. Urine drug screening is recommended for patients who do not admit to substance use.

Leweke FM; Gerth CW; Klosterkotter J. Cannabis-associated psychosis: Current status of research. (review). CNS Drugs 18(13): 895-910, 2004. (143 refs.)

Cannabis has been used for recreational, medicinal and religious purposes in different cultures since ancient times. There have been various reports of adverse effects due to or associated with cannabis consumption, including psychotic episodes. Historically, our understanding of these clinical observations has been significantly hindered by a lack of knowledge regarding their underlying neurobiological and pharmacological processes. However, the discovery of the endogenous cannabinoid system has allowed a greater understanding of these adverse effects to develop. From a clinical perspective, toxic or transient psychotic reactions to the administration of herbal cannabis preparations or specific cannabinoid compounds have to be differentiated from longer-lasting, persistent schizophrenia-like disorders associated with the use of cannabis/cannabinoids. The latter are most likely to be associated with a predisposition or vulnerability to schizophrenia. Interestingly, the recently suggested role of the endogenous cannabinoid system in schizophrenia not related to previous cannabinoid consumption introduces an additional perspective on the mechanism underlying cannabis-associated schizophrenia-like disorders, as well as on the effects of cannabis consumption in schizophrenia. At present, acute psychopharmacological treatment options for cannabis-associated transient and persistent schizophrenia-like psychotic episodes are similar and are based on the use of benzodiazepines and antipsychotics. However, new pharmacological strategies using the endogenous cannabinoid system as a primary target are under development. Long-term psychotherapeutic treatment options involve case management strategies and are mainly based on specialised psychotherapeutic programmes to encourage cannabis users to stop their use of the drug.

Linszen D van; Amelsvoort T. Cannabis and psychosis: An update on course and biological plausible mechanisms. Current Opinion in Psychiatry 20(2): 116-120, 2007. (48 refs.)

Purpose of review: Cannabis use is the most commonly abused illicit substance. Its relation with psychosis remains a topic of debate. Epidemiological studies suggest that cannabis is a component cause accounting for approximately 10% of cases. An increasing number of studies have been published on neurobiological effects of cannabis and vulnerability of psychosis. Recent findings: Acute cannabis administration can induce memory impairments, sometimes persisting months following abstinence. There is no evidence that residual effects on cognition remain after years of abstinence. The scarce literature on neuro-imaging mainly done in nonpsychotic populations, show little evidence that cannabis has effects on brain anatomy. Acute effects of cannabis include increases of cerebral blood flow, whereas long-term effects of cannabis include attenuation of cerebral blood flow. In animals Delta 9-tetrahydrocannabinol enhances neurotransmission in brain regions known to be implicated in psychosis. Studies in humans show that genetic vulnerability may add to increase risk of developing psychosis and cognitive impairments following cannabis consumption. Delta 9-tetrahydrocannabinol induces psychotic like states and memory impairments in healthy volunteers. Summary: Simultaneously with increasing understanding of neurobiological cannabis effects, there is a lack of studies in people with psychosis. There are plausible mechanisms that might explain the psychotogenic effects of cannabis.

Lubman DI; Hides L; Jorm AF. Beliefs of young people and their parents about the harmfulness of alcohol, cannabis and tobacco for mental disorders. Medical Journal of Australia 187(5): 266-269, 2007. (18 refs.)

Objective: To ascertain the beliefs of young people and their parents about the role of alcohol, tobacco and marijuana in the prevention and treatment of mental disorders. Design, setting and participants: Between May and August 2006, a national computer-assisted telephone survey was conducted on a representative sample of Australian youths aged 12-25 years. 3746 young people and 2005 of their parents were presented with a case vignette portraying psychosis, depression, depression with alcohol misuse, or social phobia in a young person. Main outcome measures: Participants' beliefs regarding the role of substance use in preventing or dealing with mental disorders in young people. Results: Over 85% of participants agreed that alcohol, tobacco and marijuana were harmful for the young people in the vignettes, and over 80% of youths agreed that not using marijuana or drinking alcohol in excess would reduce the risk of developing a similar problem. Conclusion: Young people and their parents are fully aware of the negative impact of substance use on mental disorders. Translating this knowledge into behavioural change will be a major challenge for future public health campaigns.

Macdonald AJ. Cannabis and psychosis - Does cannabis really cause psychosis? (letter). British Medical Journal 332(7536): 303-303, 2006. (1 refs.)

Mackie CJ; Castellanos-Ryan N; Conrod PJ. Developmental trajectories of psychotic-like experiences across adolescence: Impact of victimization and substance use. Psychological Medicine 41(1): 47-58, 2011. (65 refs.)

Background. Research suggests that psychotic-like experiences (PLEs) in the general population are common, but can reflect either transitory or persistent developmental phenomena. Using a general adolescent population it was examined whether different developmental subtypes of PLEs exist and whether different trajectories of PLEs are associated with certain environmental risk factors, such as victimization and substance use. Method. Self-reported PLEs were collected from 409 adolescents (mean age 14 years 7 months) at four time points, each 6 months apart. General growth mixture modelling was utilized to identify classes of adolescents who followed distinct trajectories of PLEs across this period. Predictors of class membership included demographics, personality, victimization, depression, anxiety and substance use. Results. We identified the following three developmental subgroups of PLEs: (1) persistent; (2) increasing; (3) low. Adolescents on the persistent trajectory reported frequent victimization and consistent elevated scores in depression and anxiety. Adolescents on the increasing trajectory were engaging in cigarette use prior to any increases in PLEs and were engaging in cocaine, cannabis and other drug use as PLEs increased at later time points. Conclusions. The findings suggest that different developmental subgroups of PLEs exist in adolescence and are differentially related to victimization and substance use.

Macleod J. Cannabis use and symptom experience amongst people with mental illness: A commentary on Degenhardt et al. (editorial). Psychological Medicine 37(7): 913-916, 2007. (23 refs.)

The article by Degenhart is in this issue, "The temporal dynamics of relationships between cannabis, psychosis and depression among young adults with psychotic disorders: Findings from a 10-month prospective study."

Macleod J; Hickman M; Vickerman P; Kirkbride J; Jones PB. Response to the commentaries. Addiction 102(4): 516-518, 2007. (19 refs.)

This is the response to commentaries by others to the authors article in this issue "Cannabis and schizophrenia: model projections of the impact of the rise in cannabis use on historical and future trends in schizophrenia in England and Wales. Addiction 2007; 102: 597-606." The question being addressed is the extent to which cannabis use causes clinically significant and enduring psychosis. Among the points addressed by commentaries is the genetic dimension, the type of evidence required to confirm a causative impact of mairjuana use.

Maki P; Veijola J; Jones PB; Murray GK; Koponen H; Tienari P et al. Predictors of schizophrenia: A review. (review). British Medical Bulletin 73-74: 1-15, 2005. (88 refs.)

Schizophrenia is an aetiologically heterogeneous syndrome that usually becomes overtly manifest in adolescence and early adulthood, but in many cases subtle impairments in neurointegrative function are present from birth; hence it is considered to be a disorder with a neurodevelopmental component. The strongest risk factor that has been identified is familial risk with genetic loading. Other risk factors include pregnancy and delivery complications, infections during pregnancy, disturbances of early neuromotor and cognitive development and heavy cannabis use in adolescence. Unfortunately, to date it has not been possible to utilize the predictors of the disorder that have been identified in primary preventative interventions in a general population. However, some authors have claimed that in future it might be possible to reduce the risk for developing schizophrenia through general health policy. In clinical settings, it is helpful to map out possible early risk factors, at least familial risk for psychosis, especially in child, adolescent and young adult mental patients. Furthermore, in the future we may have predictive models combining data from genetic factors for schizophrenia, antenatal risk factors, childhood and adolescent development and clinical symptomatology, as well as brain structural and functional abnormalities.

Malcolm CP; Picchioni MM; DiForti M; Sugranyes G; Cooke E; Joseph C et al. Pre-morbid Conduct Disorder symptoms are associated with cannabis use among individuals with a first episode of psychosis. Schizophrenia Research 126(1-3): 81-86, 2011. (39 refs.)

Background: Early cannabis use has consistently been associated with an increased risk for the later development of psychosis. Studies suggest that Conduct Disorder (CD) is more common amongst young people who later go on to develop psychosis. CD has been associated with greater and earlier cannabis use in general population samples. Based on this evidence, we hypothesised that among patients experiencing their first episode of psychosis, the presence of CD symptoms prior to age 15 would be associated with cannabis use. Method: 102 patients experiencing a first episode of psychosis were interviewed to assess CD symptoms prior to age 15 and use of cannabis and other substances. Results: The number of CD symptoms was significantly associated with lifetime cannabis use (odds ratio = 5.41 (1.76-16.57), p = 0.03) and with first use of cannabis before age 14 (odds ratio = 1.46 (1.12-1.92), p = 0.006), after controlling for stimulant/hallucinogen use and level of education. Conclusions: Among patients experiencing a first episode of psychosis, CD symptoms were significantly associated with use of cannabis and with use by age 14. Among individuals vulnerable for psychosis, CD symptoms may independently increase the likelihood of cannabis use which in turn increases the risk of psychosis.

Maremmani I; Lazzeri A; Pacini M; Lovrecic M; Placidi GF; Perugi G. Diagnostic and symptomatological features in chronic psychotic patients according to cannabis use status. Journal of Psychoactive Drugs 36(2): 235-241, 2004. (36 refs.)

The prevalence and the clinical meaning of cannabis use in patients with chronic psychosis has not been systematically explored. The authors have compared the diagnostic and symptomatological characteristics of I1sdI male patients affected by chronic psychosis with and without past or current use of cannabis. Sixty-six patients were still using or had used cannabis; in all cases the use preceded the onset of psychotic symptoms. Forty-three patients were cannabis-positive on urinary screening at the moment of hospitalization and 23 were currently cannabis-free but reported the use of cannabis in the past. Forty-five patients were negative on urinary screening and reported no past history of cannabis use. In evaluating the psychopathological features, the Brief Psychiatric Rating Scale (BPRS) and the Overt Aggression Rating Scale (AORS) were used. The three groups showed similar demographic data, except for age, which was lower in current cannabis users than in nonusers; no differences were found between current and past users. As regards diagnostic features, "mood cluster" was significantly better represented in cannabis users and "schizophrenic cluster" in nonusers; bipolar spectrum disorders were more frequently reported than unipolar ones. When past and current users were grouped together, only blunted affect score was significantly higher in nonusers than in users, while clastic violence showed higher scores in users. These data indicate that chronic psychosis, whether associated with past or with current use of cannabis, is frequently associated with bipolar spectrum disorders and tends to display less blunted affect and more clastic behavior.

Mata I; Rodriguez-Sanchez JM; Pelayo-Teran JM; Perez-Iglesias R; Gonzalez-Blanch C; Ramirez-Bonilla M et al. Cannabis abuse is associated with decision-making impairment among first-episode patients with schizophrenia-spectrum psychosis. Psychological Medicine 38(9): 1257-1266, 2008. (70 refs.)

Background. Cannabis use appears to be a risk factor for schizophrenia. Moreover, cannabis abusers show impaired decision-making capacities, linked to the orbitofrontal cortex (OFC). Although there is substantial evidence that first-episode schizophrenia patients show impairments in cognitive tasks associated with the dorsolateral prefrontal cortex (DLPFC), it is not clear whether decision making is impaired at schizophrenia onset. In this Study, we examined the association between antecedents of cannabis abuse and cognitive impairment in cognitive tasks associated with the DLPFC and the OFC in a sample of first-episode patients with schizophrenia-spectrum disorders. Method. One hundred and thirty-two patients experiencing their first episode of a schizophrenia-spectrum psychosis were assessed with a cognitive battery including DLPFC-related tasks [backward digits, verbal fluency (FAS) and the Trail Making Test (TMT)] and an OFC-related task [the Iowa Gambling Task (GT)]. Performance on these tasks was compared between patients who had and had not abused cannabis before their psychosis onset. Results. No differences were observed between the two groups on the performance of any of the DLPFC-related tasks. However, patients who had abused cannabis before their psychosis onset showed a poorer total performance on the gambling task and a lower improvement on the performance of the task compared to no-abusers. Conclusions. Pre-psychotic cannabis abuse is associated with decision-making impairment, but not working memory and executive function impairment, among first-episode patients with a schizophrenia-spectrum psychosis. Further studies are needed to examine the direction of causality of this impairment; that is, does the impairment make the patients abuse cannabis, or does cannabis abuse cause the impairment?

Mattick RP; McLaren J. Cannabis and psychosis put in perspective. (editorial). Canadian Journal of Psychiatry 51(9): 554-555, 2006. (5 refs.)

Mechoulam R; Hanu L. The cannabinoid system: From the point of view of a chemist. IN: Castle D; Murray R, eds. Marijuana and Madness: Psychiatry and Neurobiology. Cambridge: Cambridge University Press, 2004. pp. 1-18. (93 refs.)

This book is about cannabis (marijuana) and psychotic illnesses; more specifically, it outlines how our increasing understanding of cannabis itself, the effects of cannabis on the brain and psychic functions of the cannabinoid system can inform our understanding of the relationships between cannabis and psychosis. This chapter serves as an introduction to the topic, with a brief historical oveview of the psychic effects of cannabis, followed by an exposition on the cannabinoid system.

Mirkin B; Earleywine M. The cannabis and psychosis connection questioned: A comment on Fergusson et al. 2005. (letter). Addiction 100(5): 714, 2005. (4 refs.)

Mushtaq F; Mondelli V; Pariante CM. The metabolic implications of long term cannabis use in patients with psychosis. Journal for Epidemiology and Psychiatric Sciences 17(3): 221-226, 2008. (44 refs.)

Aims - The aim of this paper is to summarise the effects of cannabis use on appetite and energy balance, and to subsequently investigate the possible implications this may have in patients with psychosis, in whom a high prevalence of cannabis use has been reported. Methods - A narrative review based on the recent literature regarding cannabis use in the general population and patients with psychosis. Results - The short-term abilities of cannabis to increase appetite and body weight, through actions on the endogenous endocannabinoid system, have been well characterised throughout the literature. The long term effects of cannabis use are however unclear and only a minority of studies have been conducted in the genera. population with overall conflicting results. In terms of the effects of cannabis in patients with psychosis, there has only been one study to date that has investigated this and interestingly found cannabis use to be associated with increased body weight and blood glucose levels, thus providing evidence that cannabis use may be an important contributing factor to the reduced life expectancy, as is Currently observed in this vulnerable patient group. Conclusions - It is clear from the literature that patients with psychosis are at a high risk of metabolic and cardiovascular disease in comparison to the general population. However the contribution of cannabis use to this risk is as of yet undetermined and further long term studies are need to confirm current findings and evaluate hypothesised mechanisms.

Myin-Germeys I; Krabbendam L; van Os J. Continuity of psychotic symptoms in the community. Current Opinion in Psychiatry 16(4): 443-449, 2003. (83 refs.)

Purpose of review: This review explores recent evidence relating to the hypothesis that the psychosis phenotype exists as a continuous distribution in nature. Recent findings: Several studies demonstrate that psychosis-like symptoms and experiences are prevalent in the general population, which is suggestive of a symptomatic continuum of psychosis between normal subjects and subjects with psychotic disorder. In addition, there is new evidence that psychotic disorders are related to the same underlying aetiological influences as psychosis-like experiences and schizotypy, i.e. aetiological continuity may exist in addition to phenotypic continuity. The evidence extends from demographic risk factors, such as gender and age, to environmental risk factors such as trauma, influenza and urbanicity, cannabis use and personality characteristics (neuroticism). All these factors are related not only to psychotic disorder in patients, but also to psychosis-like experiences and schizotypy in the general population. In addition, patterns of genetic transmission of symptom dimensions may be comparable for psychotic disorder and non-clinical psychosis. Finally, a number of neuropsychological and psychophysiological risk factors involved in the development of both psychosis and schizotypy and psychosis-like experiences are discussed. Summary: There is credible evidence that is compatible with the suggestion of a continuity model of psychosis. It is attractive to hypothesize that psychosis-like experiences and psychotic disorders are situated, at least in part, on an aetiological continuum underlying the observed phenotypic continuity.

Pollack HA; Reuter P. The implications of recent findings on the link between cannabis and psychosis. Addiction 102(2): 173-176, 2007. (23 refs.)

This is a commentary on a report in this issue, "Cannabis and schizophrenia: model projections of the impact of the rise in cannabis use on historical and future trends in schizophrenia in England and Wales." This commentary raises questions about both the clinical and policy implications. Assuming the posited relationship exists, then the social costs of marijuana use are substantially greater.

Roncero C; Collazos F; Valero S; Casas M. Cannabis consumption and development of psychosis: State of the art. (review). Actas Esponolas de Psiquiatria 35(3): 182-189, 2007. (30 refs.)

Cannabis is the most widely used illegal drug in Spain. Currently, its use is on the rise as risk perception is decreasing, primarily among young people. It is well known that cannabis negatively influences course and prognosis in schizophrenic patients. However, the relationship between cannabis use and development of a psychotic or schizophrenic disorder remains controversial. The study of this topic has been approached using longitudinal cohort studies, which study cannabis use and psychotic or schizophrenic disorders. In addition to the classic Swedish conscript study published by Andreasson et al. 1987, during the past years, six more longitudinal cohort studies have been published. The data demonstrate that there are both temporal and dose-response relationships, and that early initiation of cannabis use is highly correlated with the development of psychotic symptoms. Cannabis consumption can increase the risk of developing schizophrenia in a vulnerable population twofold, to the extent that some studies suggest a causal relationship. The current knowledge base makes it necessary to warn the population about the relationship between cannabis use and the development of psychosis.

Roxburgh A; Degenhardt L. Hospital stays related to illicit drugs in Australia, 1993-2004. NDARC Technical Report No. 261. Sydney: National Drug and Alcohol Research Centre (Australia), 2006. (45 refs.)

This report examines trends in drug-related hospital separations (including use,

Schofield D; Tennant C; Nash L; Degenhardt L; Cornish A; Hobbs C et al. Reasons for cannabis use in psychosis. Australian and New Zealand Journal of Psychiatry 40(6-7): 570-574, 2006. (14 refs.)

To examine the reasons for cannabis use among individuals with psychotic disorders. Forty-nine people with psychotic disorders in treatment with community health centres in Northern Sydney were interviewed to collect information about their experience of antipsychotic side-effects and their influence on cannabis use. Other information collected on cannabis use included: amount and frequency, effects of use and other general reasons given for use. It was found that boredom, social motives, improving sleep, anxiety and agitation and symptoms associated with negative psychotic symptoms or depression were the most important motivators of cannabis use. Positive symptoms of psychosis and antipsychotic side-effects that were not associated with anxiety, were not important motivators of cannabis use. As cannabis use may precipitate relapse in this population, it is important to reduce these motivators of use. Clinician's must assess and treat these problems, thus reducing the need for patients to self-medicate with cannabis, and therefore reducing the risk of relapse.

Schubart CD; van Gastel WA; Breetvelt EJ; Beetz SL; Ophoff RA; Sommer IEC et al. Cannabis use at a young age is associated with psychotic experiences. Psychological Medicine 41(6): 1301- 1310, 2011. (60 refs.)

Background. Cannabis use is associated with psychosis and a range of subclinical psychiatric symptoms. The strength of this association depends on dosage and age at first use. The current study investigates whether level of cannabis exposure and starting age are associated with specific profiles of subclinical symptoms. Method. We collected cross-sectional data from a young adult population sample by administering an online version of the Community Assessment of Psychic Experiences (CAPE). Cannabis exposure was quantified as the amount of Euros spent on cannabis per week and the age of initial cannabis use. The primary outcome measure was the odds ratio (OR) to belong to the highest 10% of scores on the total CAPE and the positive-, negative- and depressive symptom dimensions. Results. In 17 698 adolescents (mean age 21.6, S.D. = 4.2 years), cannabis use at age 12 years or younger was strongly associated with a top 10% score on psychotic experiences [OR 3.1, 95% confidence interval (CI) 2.1-4.3] and to a lesser degree with negative symptoms (OR 1.7, 95% CI 1.1-2.5). The OR of heavy users (>(sic)25/week) for negative symptoms was 3.4 (95% CI 2.9-4.1), for psychotic experiences 3.0 (95% CI 2.4-3.6), and for depressive symptoms 2.8 (95% CI 2.3-3.3). Conclusions. Early start of cannabis use is strongly associated with subclinical psychotic symptoms and to a lesser degree with negative symptoms, while smoking high amounts of cannabis is associated with increased levels of all three symptom dimensions : psychotic, negative and depressive. These results support the hypothesis that the impact of cannabis use is age specific.

Selten JP; Veen ND; Hoek HW; Laan W; Schols D; van der Tweel I et al. Early course of schizophrenia in a representative Dutch incidence cohort. Schizophrenia Research 97(1-3): 79-87, 2007. (34 refs.)

Purpose: To describe the early course of psychotic disorders in general and to examine whether certain variables can predict the early course of schizophrenic disorders (DSM-IV: schizophrenia, schizophreniform or schizoaffective disorder), Subjects and method: Follow-up and re-diagnosis of a highly representative Dutch incidence cohort (N= 181), thirty months after first contact with a physician for a psychotic disorder. Poor course was defined as a continuous psychotic illness or a score of less than 39 on the Global Assessment of Functioning scale. Results: The follow-up rate was 92%. 125 Subjects were diagnosed with a schizophrenic disorder. Poor course was present in 70 of these subjects (56%). Univariable analysis showed that male sex, heavy cannabis use during the follow-up period (sometimes or often more than one joint a day) and long duration of dysfunctioning before psychosis onset (> 1 month) were predictors of poor course, while age at onset, ethnicity, socioeconomic status and duration of untreated psychosis (trend, p=0.08) were not. The effect of cannabis was confounded by sex. Multivariable analysis showed that male sex was the sole significant and independent predictor of poor course and explained 13% of the variation. The odds ratio for males, adjusted for duration of pre-psychotic dysfunctioning and cannabis use during the follow-up period, was 3.0 (95% CI, 1.0-8.9). Strengths and limitations: This is the first study to examine the influence of cannabis in an epidemiological, highly representative sample. A limitation was the sample size. Conclusion: Male sex is an independent risk factor for an unfavorable early course in schizophrenia.

Semple DM; McIntosh AM; Lawrie SM. Cannabis as a risk factor for psychosis: Systematic review. (review). Journal of Psychopharmacology 19(2): 187-194, 2005. (44 refs.)

Various kinds of evidence suggest an association between cannabis and psychosis. Five years ago, the only significant case-control study addressing this question was the Swedish Conscript Cohort. Within the last few years, other studies have emerged, allowing the evidence for cannabis as a risk factor to be more systematically reviewed and assessed. Using specific search criteria on Embase, PsychINFO and Medline, all studies examining cannabis as an independent risk factor for schizophrenia, psychosis or psychotic symptoms, published between January 1966 and January 2004, were examined. Additional studies were also reviewed from references found in retrieved articles, reviews, and a cited reference search (ISI-Web of Science). Studies selected for meta-analysis included: (i) case-control studies where exposure to cannabis preceded the onset of schizophrenia or schizophrenia-like psychosis and (ii) cohort studies of healthy individuals recruited before the median age of illness onset, with cannabis exposure determined prospectively and blind to eventual diagnosis. Studies of psychotic symptoms were also tabulated for further discussion. Eleven studies were identified examining the relationship between cannabis use and psychosis. Seven were included in the meta-analysis, with a derived odds ratio (fixed effects) of 2 (.) 9 (95% confidence interval = 2.4-3.6). No evidence of publication bias or heterogeneity was found. Early use of cannabis did appear to increase the risk of psychosis. For psychotic symptoms, a dose-related effect of cannabis use was seen, with vulnerable groups including individuals who used cannabis during adolescence, those who had previously experienced psychotic symptoms, and those at high genetic risk of developing schizophrenia. In conclusion, the available evidence supports the hypothesis that cannabis is an independent risk factor, both for psychosis and the development of psychotic symptoms. Addressing cannabis use, particularly in vulnerable populations, is likely to have beneficial effects on psychiatric morbidity.

Shapiro GK; Buckley-Hunter L. What every adolescent needs to know: Cannabis can cause psychosis. Journal of Psychosomatic Research 69(6): 533-539, 2010. (73 refs.)

Objective: Cannabis is a widely used substance that may be becoming more socially accepted, legally tolerated, and utilized by younger individuals. This review explores the relationship between cannabis and the onset of psychosis as well as the policy ramifications of current research. Method: This article synthesizes published work that was considered by the author to be relevant to the discussion of cannabis and the onset of psychosis. Results: The evidence suggests that, along with other harms, cannabis is a significant risk factor in the etiology of psychosis. Adolescents are more vulnerable to using cannabis, and because of their stage of mental development, the cognitive effects are more pronounced. The mechanism for this change is thought to be neuro-chemical with a stronger effect in those with a diathesis for psychosis. Conclusion: The risk that cannabis poses to adolescent health should not be neglected. Policy measures should use a multifaceted and strategic perspective in order to prevent adolescents from using this drug.

Solowij N; Michie PT. Cannabis and cognitive dysfunction: Parallels with endophenotypes of schizophrenia? (review). Journal of Psychiatry & Neuroscience 32(1): 30-52, 2007. (312 refs.)

Currently, there is a lot of interest in cannabis use as a risk factor for the development of schizophrenia. Cognitive dysfunction associated with long-term or heavy cannabis use is similar in many respects to the cognitive endophenotypes that have been proposed as vulnerability markers of schizophrenia. In this overview, we examine the similarities between these in the context of the neurobiology underlying cognitive dysfunction, particularly implicating the endogenous cannabinoid system, which plays a significant role in attention, learning and memory, and in general, inhibitory regulatory mechanisms in the brain. Closer examination of the cognitive deficits associated with specific parameters of cannabis use and interactions with neurodevelopmental stages and neural substrates will better inform our understanding of the nature of the association between cannabis use and psychosis. The theoretical and clinical significance of further research in this field is in enhancing our understanding of underlying pathophysiology and improving the provision of treatments for substance use and mental illness.

Spencer C. Motives that maintain cannabis use among individuals with psychotic disorders. IN: Castle D; Murray R, eds. Marijuana and Madness: Psychiatry and Neurobiology. Cambridge: Cambridge University Press, 2004. pp. 166-185. (57 refs.)

Beyond the issue of the relationship of marijuana use and psychosis is the question whether long-term heavy cannabis users experience residual deficits in cognition, even if they stop using cannabis for a substantial period. The question is not easily answered, for example, given the difficulty in defining "residual", and the time from use to evaluation. In the discussion, there is a distinction between short-term residual and long-term residual effects, and the relationship of each to lifetime duration of cannabis use. The author concludes that although short-term effects are related to heavy cannabis use, there is little evidence to suggest that these deficits persist for prolonged periods after discontinuation of use. However, several studies have suggested an association between lifetime duration of cannabis use or age of onset of use and cognitive deficits, which can not be explained by short-term residual effects. While research continues, this possibility must be regarded with caution due to confounding factors. Thus it is still uncertain whether heavy cannabis use causes long-term residual neuropsychological deficits in some individuals or under certain conditions.

Stefanis NC; Delespaul P; Henquet C; Bakoula C; Stefanis CN; Van Os J. Early adolescent cannabis exposure and positive and negative dimensions of psychosis. Addiction 99(10): 1333-1341, 2004. (38 refs.)

Aims: To investigate the effect of exposure to cannabis early in adolescence on subclinical positive and negative symptoms of psychosis. Design: Cross-sectional survey in the context of an ongoing cohort study. Setting: Government-supported general population cohort study. Participants: A total of 3,500 representative 19-year olds in Greece. Measurements: Subjects filled in the 40-item Community Assessment of Psychic Experiences, measuring subclinical positive (paranoia, hallucinations, grandiosity, first-rank symptoms) and negative psychosis dimensions and depression. Drug use was also reported on. Findings Use of cannabis was associated positively with both positive and negative dimensions of psychosis, independent of each other, and of depression. An association between cannabis and depression disappeared after adjustment for the negative psychosis dimensions. First use of cannabis below age 16 years was associated with a much stronger effect than first use after age 15 years, independent of life-time frequency of use. The association between cannabis and psychosis was not influenced by the distress associated with the experiences, indicating that self-medication may be an unlikely explanation for the entire association between cannabis and psychosis. Conclusions: These results add credence to the hypothesis that cannabis contributes to the population level of expression of psychosis. In particular, exposure early in adolescence may increase the risk for the subclinical positive and negative dimensions of psychosis, but not for depression.

Stirling J; Barkus EJ; Nabosi L; Irshad S; Roemer G; Schreudergoidheijt B et al. Cannabis-induced psychotic-like experiences are predicted by high schizotypy. Psychopathology 41(6): 371-378, 2008. (37 refs.)

Background: Cannabis use has been identified as a possible risk factor for developing schizophrenia. In a previous paper we reported preliminary evidence that cannabis use increases the likelihood of psychosis-like experiences in non-clinical respondents who scored highly on a measure of schizotypy. We now present findings from pooled data from 3 new follow-up studies comprising a sample of 477 respondents, of whom 332 reported using cannabis at least once. Sampling and Methods: As in our previous study, the psychological effects of cannabis were assessed with the Cannabis Experiences Questionnaire, from which 3 subscales can be derived; encompassing pleasurable experiences, psychosis-like experiences and after-effects. The respondents also completed the brief Schizotypal Personality Questionnaire. Results: Cannabis use was reported by 70% of the sample. Use per se was not significantly related to schizotypy. However, high scoring schizotypes were more likely to report both psychosis-like experiences and unpleasant after-effects of cannabis use were not related to schizotypy. Exploratory factor analysis of the pooled data from this study and our previous report (providing a sample of >400 cannabis users) suggested a 3-factor solution. These were characterised as a psychotic-dysphoric index (factor 1), an expansive index (factor 2) and an intoxicated index (factor 3). Schizotypy was highly correlated with factors 1 and 3, though not with factor 2. Conclusion: High scoring schizotypes who use cannabis are more likely to experience psychotic-dysphoric phenomena and intoxicating effects during and after use. Our results confirm and expand the findings reported in our previous study. They are consistent with the hypothesis that cannabis use may be a risk factor for full psychosis in this group.

Stirling J; Lewis S; Hopkins R; White C. Cannabis use prior to first onset psychosis predicts spared neurocognition at 10-year follow-up. Schizophrenia Research 75(1): 135-137, 2005. (13 refs.)

A priori cannabis use was recorded at index admission for 112 participants in the Manchester first-episode psychosis cohort. 69 of the 100 surviving (mainly schizophrenia) patients were followed up 10-12 years later and assessed on a battery of clinical, behavioural and neurocognitive measures. Individuals who had not used cannabis before the first episode of illness were generally indistinguishable from cannabis users at follow-up, except that the latter group evinced a marked 'sparing' of neurocognitive functions. These findings are briefly discussed in relation to other casual factors in psychosis.

Teesson, M.; Degenhardt, L.; Hall, W.; Lynskey, M.; Toumbourou, JW; Patton, G. Substance use and mental health in longitudinal perspective. IN: Stockwell, T.; Gruenewald, PJ; Toumbourou, JW; Loxley W, eds. Preventing Harmful Substance Use: The Evidence Base for Policy and Practice. New York: John Wiley & Sons, Ltd, 2005. pp. 43-51. (31 refs.)

Comorbidity between substance use disorders and other psychological disorders has emerged as a major clinical, public health and research issue over the past few decades thanks in large part to population surveys of mental disorders that have highlighted that comorbidity is common. The reasons for comorbidity are complex but longitudinal research has begun to provide insights into the underlying mechanisms. This chapter will give a brief overview of epidemiological research into comorbidity and examines the most recent longitudinal data on patterns and causal pathways of comorbidity. The chapter highlights the increasingly consistent evidence of shared risk factors for both mental disorders and substance use disorders as well as suggesting that causal relationships may operate in both directions, that is from substance use to mental disorders and vice versa. In particular, there is a causal pathway from depression to substance use in males, and from daily cannabis use to depression and anxiety in females. There is also evidence that cannabis use precipitates psychosis in persons who are vulnerable because of a personal or family history of psychosis. Externalizing behavior problems in children, particularly conduct disorder and aggressive behavior emerging prior to age 12, have been shown to predict a greater likelihood of progressing to adolescent poly-drug use and or alcohol use problems in adulthood. The effect of childhood internalizing problems such as anxiety and depression on the subsequent development of substance use problems is less clear. Finally, the chapter addresses the implications of this information for prevention. While we should intervene to prevent or delay the onset of substance use and mental disorders during adolescence, such interventions should not focus solely on substance use or mental disorders alone. They should target a range of potentially health-threatening behaviors including substance use, sexual risk-taking and problems of personal adjustment since many of these behaviors co-occur because of shared risk factors.

Van Mastrigt S; Addington J; Addington D. Substance misuse at presentation to an early psychosis program. Social Psychiatry and Psychiatric Epidemiology 39(1): 69-72, 2004. (41 refs.)

Background Substance misuse is a significant problem in schizophrenia. The purpose of this study was to examine the prevalence and correlates of substance misuse in individuals with a first episode of psychosis at the time they first present for treatment. Method The first 357 consecutive admissions to a comprehensive early psychosis program were included. Assessment measures were the Positive and Negative Syndrome Scale, the Calgary Depression Scale for Schizophrenia, the Quality of Life Scale, the Case Manager Rating Scale and the Premorbid Adjustment Scale. Results Forty-four percent of the sample, the majority of whom used alcohol or cannabis, met diagnostic criteria for substance abuse/dependence. The prevalence was significantly higher than in the general population. Substance misuse was significantly associated with male gender, young age and age of onset. Conclusions This study confirms the high rates of substance misuse, in particular cannabis, in first-episode psychosis. Implications for treatment are addressed.

Van Os J; Henquet C; Stefanis N. Cannabis-related psychosis and the gene-environment interaction: Comments on Ferdinand et al. 2005. (letter). Addiction 100(6): 874, 2005. (9 refs.)

van Os J; Krabbendam L; Myin-Germeys I; Delespaul P. The schizophrenia envirome. Current Opinion in Psychiatry 18(2): 141-145, 2005. (57 refs.)

Purpose of review: To show which aspects of the environment increase the risk for schizophrenia and how they interact with pre-existing liability for psychosis. Recent findings: Not only does cannabis survive as a risk factor for psychosis, but the evidence is showing concrete I synergistic effects between cannabis and pre-existing liability to psychosis. The urban environment is, in terms of attributable risk, the most important proxy environmental risk factor. There is evidence that it interacts with genetic risk and it has been hypothesized that the mechanism involves the cumulative effects of altered social interactions at the individual level and possibly also at the level of the wider social environment, such as the neighbourhood. Early trauma is another aspect of the environment that has recently been linked prospectively to psychosis, and meta-analytic work demonstrates conclusively that minority status is a risk factor, part of which may be mediated by chronic exposure to discrimination. Prenatal environmental effects may involve folate or vitamin D deficiency, viral infections or adverse effects associated with low or high birth weight. The mechanism by which the environment is likely to impact on risk is through cognitive and emotional pathways on the one hand, and biological pathways, possibly involving dopamine sensitization, on the other. Summary: Several synergistic mechanisms involving proxy measures of genes and proxy measures of the environment, such as gene-cannabis, gene-urbanicity and gene-stress interactions, offer concrete avenues to pursue research that stands a good chance of elucidating at least some of the causes of schizophrenia.

Verdoux H. Cannabis and psychosis proneness. IN: Castle D; Murray R, eds. Marijuana and Madness: Psychiatry and Neurobiology. Cambridge: Cambridge University Press, 2004. pp. 75-88. (54 refs.)

In many countries, a large proportion of the general population is exposed to cannabis, as a result of its widespread recreational use. From a public health perspective, this suggests a carefl assessment on the impact on mental health is warranted. Findingsfrom prospective population-based cohort studies suggest that cannabis use may be an independent risk factor for the onset of psychosis. However the nature of the link is far from being elucidated. Studies based on clinical samples have limited value in elucidating the mechanisms underlying this association. as confounding factors linked to clinical status are difficult to control. This chapter provides a review of the studies thaht have investigatedthe relationships between cannabis use and occurrence of psychotic experience in non-clinical populations. The chapter deals with the difficulties in defining "proneless", methodological issues. Based on a review of the literature, it appears that marijuana users are more likely to present with attenuated psychotic systems, suggesting a continuum exists between the incrased prevalence of cannabis use in those with clinical psychosis, and the cross-sectional association between cannabis use and psychosis proneness in those without clinical psychosis. It does appear that cannabis use may be an independent risk factor for psychosis, at least in those with a pre-existing vulnerability, although the mechanisms underlying this are unclear.

Verdoux H; Sorbara F; Gindre C; Swendsen JD; van Os J. Cannabis use and dimensions of psychosis in a nonclinical population of female subjects. Schizophrenia Research 59(1): 77-84, 2003. (35 refs.)

Objective: The aim of the present study was to explore the pattern of associations between cannabis use and dimensions of psychosis in a nonclinical population of female subjects. Method: The Community Assessment of Psychic Experiences (CAPE), a 42-item self-report questionnaire that evolved from the Peters et al. Delusions Inventory [Schizophr. Bull. 25 (1999) 553], was used to measure dimensions of psychosis in a sample of undergraduate female students (n = 571). The participants were also asked to complete a self-report questionnaire collecting information on substance use. Results: Three correlated dimensions of positive, negative and depressive experiences were identified using principal components factor analysis. Frequency of cannabis use was independently associated with the intensity of both positive and negative psychotic experiences. No significant association was found between cannabis use and the depressive dimension, or between alcohol use and any of the three positive, negative and depressive dimensions. Conclusion: This cross-sectional study supports the hypothesis that exposure to cannabis may induce the emergence of positive psychotic symptoms in subjects without clinical psychosis, and additionally suggests that cannabis users exhibit greater levels of negative symptoms. Prospective studies are required to explore the direction of causality and the impact of cannabis on the course of psychotic experiences in subjects from the general population.

Verdoux H; Tournier M; Cougnard A. Impact of substance use on the onset and course of early psychosis. Schizophrenia Research 79(1): 69-75, 2005. (54 refs.)

The strong comorbidity between psychosis and substance use is already identifiable in early psychosis, raising the question of the direction of the association between substance use and psychosis onset. It has long been considered that this association was explained by the self-medication hypothesis. This hypothesis has been recently challenged by several prospective studies carried out in population-based samples, showing a dose-response relationship between cannabis exposure and risk of psychosis. This association was independent from potential confounding factors such as exposure to other drugs and preexistence of psychotic symptoms. As a large percentage of subjects from the general population is now exposed to this drug, even a small increase in the risk of adverse effects may have significant deleterious consequences for the health of the population. Hence, reducing exposure to cannabis may contribute to prevention of some incident cases of psychosis. Regarding prognosis, persistent substance misuse after the onset of psychosis has a deleterious impact on clinical outcome. Therapeutic programs for subjects with dual diagnosis should be implemented early in the course of psychosis to maximise their impact on the course of illness.

Winkelman MJ; Roberts TB, eds. Psychedelic Medicine: New Evidence for Hallucinogenic Substances as Treatments (two volumes). Westport CT: Praeger Perspectives, 2007. (Chapter refs.)

Psychedelic substances present in nature have been used by humans across hundreds of years to produce mind-altering changes in thought, mood, and perception -- changes otherwise only rarely experienced, be it in dreams, religious exaltation, or psychosis. U.S. scientists were studying the practical and therapeutic uses for hallucinogens, including LSD and mescaline, in the 1950s and 1960s. The government took steps to ban all human consumption of hallucinogens, by the 1970s, all human testing was stopped. Medical concerns were less the issue, than social issues and those who advocated free use of hallucinogens by all who desired. The FDA has again begun approving hallucinogenic research using human subjects. In these two volumes, researchers explain the testing and research underway to use - under the guidance of a trained provider - psychedelic substances for better physical and mental health, and their ability to treat disorders ranging from arthritis to post traumatic stress disorder. Spiritual uses are also addressed and the perceived benefits described. Medical and legal issues for therapeutic uses are also presented. The psychedelic drugs described include: LSD, ayahuasca, psilocybin, peyote, MDMA/ecstasy, marijuana. Volume I, deals with the medical use of psychedelic drugs and the social, clinical and legal perspectives. Volume II deals with the use of psychedelics in addiction medicine as well as their use in religious and mystical traditions. Appendices list a sample of sites where medical research with psychedelics is underway, and describe prominent advocates and organizations pushing to further this research.

Zammit S; Moore THM; Lingford-Hughes A; Barnes TRE; Jones PB; Burke M et al. Effects of cannabis use on outcomes of psychotic disorders: Systematic review. (review). British Journal of Psychiatry 193(5): 357-363, 2008. (34 refs.)

Background: It is unclear if research findings support clinical opinion that cannabis use leads to worse outcomes in people with psychosis, or whether this impression is confounded by other factors. Aims: To systematically review the evidence pertaining to whether cannabis affects outcome of psychotic disorders. Method: We searched 10 relevant databases (to November 2006) reference lists of included studies and contacted experts. We included 13 longitudinal studies from 15303 references. Data extraction and quality assessment were conducted independently and in duplicate. Results: Cannabis use was consistently associated with increased relapse and non-adherence. Associations with other outcome measures were more disparate. Few studies adjusted for baseline illness severity, and most made no adjustment for alcohol, or other potentially important confounders. Adjusting for even a few confounders often resulted in substantial attenuation of results. Conclusions: Confidence that most associations reported were specifically due to cannabis is low. Despite clinical opinion, it remains important to establish whether cannabis is harmful, what outcomes are particularly susceptible, and how such effects are mediated. Studies to examine this further are eminently feasible.

dependence, psychosis and withdrawal) in Australia during the period 1993 to 2004. The report presents data on characteristics of those people being treated in hospital for drug-related reasons, details of their hospital stay, analysis of which other drugs co-occur with each drug type, and analysis of the non drug-related treatment received while in hospital in conjunction with drug-related treatment. Opioid-related separations were the most frequent illicit drug-related separations occurring in Australia over the eleven-year period. A substantial proportion (up to 54%) of opioid mentions was accompanied by a broad spectrum of physical health problems, which is indicative of the relatively poor physical health of this group of drug users. Opioid-related separations declined dramatically in 2001/02, the period of the heroin shortage. Despite the dramatic decline in opioid-related separations, they remain the highest across the drug types. Amphetamine-related separations were the next highest in number, and increased over the eleven-year period. Information is provided for other drug classes-- cocaine, marijuana, amphetaminesm, and the numbers treated for withdrawal. Data is presented in 92 tables and figures.