Jennifer McLaren

Mortality among regular or dependent users of heroin and other opioids: a systematic review and meta‐analysis of cohort studies

AIMS To review the literature on mortality among dependent or regular users of opioids across regions, according to specific causes, and related to a number of demographic and clinical variables. METHODS Multiple search strategies included searches of Medline, EMBASE and PsycINFO, consistent with the methodology recommended by the Meta-analysis of Observational Studies in Epidemiology (MOOSE) group; grey literature searches; and contact of experts for any additional unpublished data from studies meeting inclusion criteria. Random-effects meta-analyses were conducted for crude mortality rates (CMRs) and standardized mortality ratios (SMRs), with stratified analyses where possible. Meta-regressions examined potentially important sources of heterogeneity across studies. RESULTS Fifty-eight prospective studies reported mortality rates from opioid-dependent samples. Very high heterogeneity across studies was observed; pooled all-cause CMR was 2.09 per 100 person-years (PY; 95% CI; 1.93, 2.26), and the pooled SMR was 14.66 (95% CI: 12.82, 16.50). Males had higher CMRs and lower SMRs than females. Out-of-treatment periods had higher mortality risk than in-treatment periods (pooled RR 2.38 (CI: 1.79, 3.17)). Causes of death varied across studies, but overdose was the most common cause. Multivariable regressions found the following predictors of mortality rates: country of origin; the proportion of sample injecting; the extent to which populations were recruited from an entire country (versus subnational); and year of publication. CONCLUSIONS Mortality among opioid-dependent users varies across countries and populations. Treatment is clearly protective against mortality even in non-randomized observational studies. Study characteristics predict mortality levels; these should be taken into account in future studies.

Cannabis potency and contamination: a review of the literature

AIMS Increased potency and contamination of cannabis have been linked in the public domain to adverse mental health outcomes. This paper reviews the available international evidence on patterns of cannabis potency and contamination and potential associated harms, and discusses their implications for prevention and harm reduction measures. METHODS A systematic literature search on cannabis potency and contamination was conducted. RESULTS Cannabis samples tested in the United States, the Netherlands, United Kingdom and Italy have shown increases in potency over the last 10 years. Some countries have not shown significant increases in potency, while other countries have not monitored potency over time. While there are some grounds to be concerned about potential contaminants in cannabis, there has been no systematic monitoring. CONCLUSION Increased potency has been observed in some countries, but there is enormous variation between samples, meaning that cannabis users may be exposed to greater variation in a single year than over years or decades. Claims made in the public domain about a 20- or 30-fold increase in cannabis potency and about the adverse mental health effects of cannabis contamination are not supported currently by the evidence. Systematic scientific testing of cannabis is needed to monitor current and ongoing trends in cannabis potency, and to determine whether cannabis is contaminated. Additionally, more research is needed to determine whether increased potency and contamination translates to harm for users, who need to be provided with accurate and credible information to prevent and reduce harms associated with cannabis use.

A systematic review of research examining benzodiazepine-related mortality

This paper will review literature examining the association of benzodiazepine use and mortality.

Assessing evidence for a causal link between cannabis and psychosis: a review of cohort studies.

Over the past five years, the release of cohort studies assessing the link between cannabis and psychosis has increased attention on this relationship. Existing reviews generally conclude that these cohort studies show cannabis has a causal relationship to psychosis, or at least that one cannot be excluded. Few studies have evaluated the relative strengths and limitations of these methodologically heterogeneous cohort studies, and how their relative merits and weaknesses might influence the way the link between cannabis use and psychosis is interpreted. This paper reviews the methodological strengths and limitations of major cohort studies which have looked at the link between cannabis and psychosis, and considers research findings against criteria for causal inference. Cohort studies that assessed the link between cannabis and psychosis were identified through literature searches using relevant search terms and MEDline, PsycINFO and EMBASE. Reference lists of reviews and key studies were hand searched. Only prospective studies of general population cohorts were included. Findings were synthesised narratively. A total of 10 key studies from seven general population cohorts were identified by the search. Limitations were evident in the measurement of psychosis, consideration of the short-term effects of cannabis intoxication, control of potential confounders and the measurement of drug use during the follow-up period. Pre-existing vulnerability to psychosis emerged as an important factor that influences the link between cannabis use and psychosis. Whilst the criteria for causal association between cannabis and psychosis are supported by the studies reviewed, the contentious issue of whether cannabis use can cause serious psychotic disorders that would not otherwise have occurred cannot be answered from the existing data. Further methodologically robust cohort research is proposed and the implications of how evidence informs policy in the case of uncertainty is discussed.

The epidemiology of cannabis use and cannabis-related harm in Australia 1993-2007.

AIMS To examine trends in patterns of cannabis use and related harm in the Australian population between 1993 and 2007. DESIGN Analysis of prospectively collected data from: (1) the National Drug Strategy Household Survey (NDSHS) and Australian Secondary Student Alcohol and Drug Survey (ASSADS); (2) the National Hospital Morbidity Database (NHMD); and (3) the Alcohol and Other Drug Treatment Services National Minimum Dataset (AODTS-NMDS). PARTICIPANTS Australians aged 14 years and over from the general population; students aged 12-17 years; public and private hospital in-patients; public and private in-patients and out-patients attending for drug treatment. MEASUREMENT Prevalence of 12-month cannabis use among the general population and secondary students. Proportions in the general population by age group reporting: daily cannabis use; difficulties in controlling cannabis use; and heavy cannabis use on each occasion. Number of hospital and treatment presentations for cannabis-related problems. FINDINGS Prevalence of past-year cannabis use has declined in the Australian population since the late 1990s. Among those reporting past-year use, daily use is prevalent among 40-49-year-olds, while heavy patterns of use are prevalent among 14-19-year-olds. Hospital presentations for cannabis-related problems reflect similar trends. Past-year cannabis use has decreased among the 10-19-year age group, but those who are daily users in this age group report using large quantities of cannabis. CONCLUSIONS Despite declines in the prevalence of cannabis use, continued public health campaigns warning of the harms associated with cannabis use are essential, aimed particularly at users who are already experiencing problems. The increasing demand for treatment for cannabis problems in Australia suggests the need for more accessible and more effective interventions for cannabis use disorders.

Should Burden of Disease Estimates Include Cannabis Use as a Risk Factor for Psychosis

Louise Degenhardt and colleagues discuss the evidence and the debate about whether Global Burden of Disease estimates should include cannabis use as a risk factor for psychosis.

Impaired physical health among methamphetamine users in comparison with the general population: The role of methamphetamine dependence and opioid use

AIM To examine the extent of physical health impairment among a community sample of methamphetamine users in comparison with the general population, and factors associated with impairment among this group. METHOD A cross-sectional survey of 309 regular methamphetamine users from Sydney. The Physical Component Scale of the Short Form 12 (SF-12) was used to measure impairment in physical health (score < 40). Age-matched general population data for the SF-12 were derived from the Australian National Survey of Mental Health and Well-Being. RESULTS Participants had a higher prevalence of impaired physical health compared to the Australian general population (20% vs. 10%, p<0.05), but this effect occurred among only dependent methamphetamine users over 24 years of age (25 - 34 years, 23% vs. 10%; 35 - 44 years, 41% vs. 12%). Methamphetamine dependence remained significantly predictive of impaired physical health after adjusting for age and other confounding factors. Opioid pharmacotherapy was also related strongly to poor physical health, accounting for 63% of participants with physical impairment. Other factors associated with impaired physical health were being female, having less than 10 years of schooling, and having been diagnosed previously with an anxiety disorder (p<0.05). CONCLUSION Methamphetamine users are more likely to report impaired physical health than the general population, but this impairment is specific to older methamphetamine users who are dependent on the drug, particularly those who are enrolled in opioid pharmacotherapy.

Hostility among methamphetamine users experiencing psychotic symptoms

The aim of the study was to provide empirical data on the severity of hostility among methamphetamine users experiencing psychotic symptoms. Participants were 71 methamphetamine users from the general community who had experienced positive psychotic symptoms in the past year. Psychotic symptoms were defined as a score of 4 or greater on the Brief Psychiatric Rating Scale (BPRS) subscales of suspiciousness, unusual thought content, or hallucinations. The BPRS hostility subscale was used to measure hostility during the most severe symptom episode during the preceding year. Pathological hostility (BPRS score of 4+) was reported by 27% of participants during their most severe episode of psychotic symptoms. Hostility was significantly more common among participants experiencing severe psychotic symptoms (BPRS score 6-7, 42% vs. 15%) or where the psychotic symptoms continued for at least two days (43% vs. 20%). Daily heroin use and low levels of schooling were also correlated with hostility. Clinically significant hostility co-occurs with psychotic symptoms in around one-quarter of methamphetamine users who experience psychosis, and it is more common with severe psychotic symptoms that persist for longer than two days.

The market for crystalline methamphetamine in Sydney, Australia

The market for domestically produced methamphetamine in Australia (sold as ‘speed’ and ‘base’) has been recently supplemented with imported crystalline methamphetamine (‘ice’ or ‘crystal’), the supply of which is thought to involve different organized crime groups than those involved with domestic supply. The existence, or otherwise, of distinct retail markets for these different forms of methamphetamine has important implications for police and public health strategies. The aim of this study was to examine whether there was evidence of distinct retail markets for crystalline methamphetamine and domestically produced forms of the drug. A cross-sectional survey of regular methamphetamine users (n = 309) was undertaken in Sydney, Australia to assess the characteristics of the retail market (consumption, price, perceived purity, availability, purchase location and sale from dealers) for crystalline methamphetamine compared with domestically produced forms of the drug (i.e. speed and base). We did not find any clear evidence of a segregated retail market for crystalline methamphetamine. Only 3% of participants were exclusive crystalline methamphetamine users, and both crystalline methamphetamine and other domestically produced forms of the drug were readily available to consumers, being typically purchased from the same dealers, in the same location and at the same price.

Cannabis and psychosis put in perspective.

In this issue, Louisa Degenhardt and Wayne Hall provide an insightful and accessible overview of the literature on the relation between cannabis use and psychosis. They also present some of the policy implications of this relation. The first paper reviews the evidence for a causal relation between cannabis use during adolescence and early adulthood and subsequent diagnosis of a psychotic disorder or experience of psychotic symptoms (1). The authors present research that has established an association between cannabis use and psychosis that cannot be explained by chance. They then focus on recent longitudinal studies that have investigated the causal direction of the association and that have attempted to rule out other explanations for the association by controlling for potential confounders, such as other drug use and personal characteristics. Degenhardt and Hall conclude that these studies suggest that among vulnerable individuals cannabis use does predict an increased risk of experiencing psychotic symptoms or of developing a psychotic disorder. Self-medication is rejected as a likely explanation for the relation. Given the evidence of the involvement of the cannabinoid system in psychosis, Degenhardt and Hall also argue that the causal relation between cannabis and psychosis is biologically plausible. The second paper places this evidence in a broader context by comparing it with the evidence for the health effects of other drug use (2). In light of the evidence presented, the authors discuss the implications for public policy. They conclude that young people with mental health problems should be discouraged from using cannabis and that all young people should be informed of the mental health risks of cannabis use. Hall and Degenhardt examine the controversial topic of how evidence for harms, in this case the risk of developing psychosis as a result of cannabis use, should affect the laws and penalties associated with cannabis. The authors argue that, while we should ensure that legislation and penalties do not make it easier for young people to begin using cannabis, there are many other issues, such as the social harm associated with personal cannabis use being a criminal offence, to consider with respect to cannabis laws and penalties. It is clear from the research literature that, if an individual is prone to serious psychotic illness, the use of cannabis may trigger an episode. The extent of the problem in terms of psychiatric cases must be clarified and put into perspective. Internationally, cannabis use is increasingly prevalent, and it now attracts a great amount of attention from the public, from families of users, from concerned policy-makers, and from mental health clinicians who are increasingly aware of cannabis use among their patients. One of the consequences of focusing on cannabis and psychosis is that other harms associated with cannabis use are overshadowed. The lack of recognition of the mental health effects associated with other drug use (such as alcohol, cocaine, opioids, and amphetamines) is another consequence. Hall and Degenhardt clearly point to the much larger problem of amphetamine psychosis presentations, despite the comparatively fewer users of amphetamine (2). Degenhardt and Hall discuss important cannabis-related harms that include the prevalence of cannabis dependence in the community, the social harms associated with cannabis use, cognitive dysfunction, educational and vocational failure, and the large amount of money spent on cannabis by its regular users. A myopic view will focus on cannabis’ relation to psychosis and will miss the larger picture of the effects of cannabis on general health and well-being. The recent development of an Australian National Cannabis Strategy (3) demonstrates the need for public education on the harms associated with cannabis use; however, the public and professional communities need a broader understanding, from credible sources, of the range of harms that cannabis use brings and not a single focus on psychosis symptoms and disorders. When read carefully, Degenhardt and Hall’s contributions can create an understanding of the strength of evidence and provide some credible ways to deal with the continued growth of cannabis use in many Western countries. Their call for the