Cannabis and depression: An integrative data analysis of four Australasian cohorts☆
Introduction
In recent years, there has been growing interest in the association between the use of cannabis and mental health. An increasing number of studies have shown that the use of cannabis, and particularly the heavy use of cannabis, is associated with increased risks of: major depression (Arseneault et al., 2002, Bovasso, 2001, Chen et al., 2002, Cheung et al., 2010, Degenhardt et al., 2003a, Fergusson et al., 2002, Hayatbakhsh et al., 2007, Lynskey et al., 2004, Marmorstein and Iacono, 2011, McGee et al., 2000, Patton et al., 2002, Rey et al., 2002, van Laar et al., 2007); psychosis/psychotic symptoms (Andreasson et al., 1987, Arseneault et al., 2002, Fergusson et al., 2005, Henquet et al., 2005, Jablensky et al., 2000, Kuepper et al., 2011, Large et al., 2011, van Os et al., 2002, Zammit et al., 2002); anxiety disorders (Han et al., 2010, Hayatbakhsh et al., 2007, Patton et al., 2002, Rey et al., 2002, Zvolensky et al., 2010); and suicidal behaviours (Beautrais et al., 1999, Borges et al., 2000, Fergusson and Horwood, 1997, Lynskey et al., 2004, Pedersen, 2008). These findings clearly raise the possibility that, by various routes, cannabis may act to increase susceptibility to mental health problems.
However, the view that cannabis use may play a causative role in depression and other mental health problems has been questioned (Degenhardt et al., 2003b, Harder et al., 2008, Macleod et al., 2004, Pedersen, 2008). Several studies have not supported a causal association linking cannabis use problems with depression (Harder et al., 2008, Pedersen, 2008). Specifically, it has been suggested that the observed associations between cannabis use and depression may be due to uncontrolled sources of residual confounding (Macleod et al., 2004). Moreover, the possibility that common individual, social and contextual factors increase the risks of both heavy cannabis use and depression cannot be ruled out (Degenhardt et al., 2003a). For example, there is evidence that a substantial component of the association between cannabis dependence and depression is attributable to shared genetic vulnerabilities (Lynskey et al., 2004).
A further complication concerns the direction of any causal relationship. In particular, it can be argued that any association between cannabis and depression may arise by two quite different sets of causal processes. First, cannabis use may by various mechanisms act to provoke or precipitate the onset of mental health problems. It is biologically plausible that cannabis use may lead to depression as neuropsychological studies in animals (Hill et al., 2006, Tsou et al., 1999) and humans (Dean et al., 2001, Leroy et al., 2001) suggest that cannabis has multiple effects on brain chemistry. Animal studies have demonstrated that serotonin (5HT)-2A receptors are up-regulated and 5HT-1A receptors are down-regulated following long term administration of cannabinoids (Hill et al., 2006). These findings provide a potential neurochemical explanation for the association between cannabis dependence and depression as changes in serotonin regulation have been linked with depression and suicidal behaviour in humans (Bhagwager et al., 2004, Drevets et al., 1999, Sargent et al., 2000). Heavy cannabis use may also contribute to depression indirectly by impairing psychosocial adjustment, from which mental health problems could arise (Degenhardt et al., 2003a). The adverse psychosocial consequences of cannabis use disorders, such as educational under-achievement, unemployment and criminal offending, have been shown to partly explain the observed association between heavy cannabis use and later depression (Marmorstein and Iacono, 2011). Cannabis use may also give rise to depression and other mental health problems through cognitive impairment which persists beyond acute cannabis intoxication (Solowij and Battisti, 2008).
Second, the development of mental health disorders may increase the likelihood that the individual will use cannabis heavily or regularly. This hypothesis proposes that people with depression may use cannabis to relieve their symptoms (Klien and Riso, 1994). Although the self-reported effects of cannabis use support its use for symptomatic relief (Green et al., 2003), the evidence from empirical studies generally does not support a self-medication hypothesis (Arendt et al., 2007, Fergusson et al., 2005, Hayatbakhsh et al., 2007, Patton et al., 2002).
A final issue concerns the effects of age on the relationship between cannabis use and mental health problems. There is growing evidence to suggest that any adverse effects of cannabis use are greatest during adolescence and tend to decline with increasing age (Arseneault et al., 2002, Fergusson et al., 2002, Fergusson et al., 2008, Stefanis et al., 2004). This effect of age on the relationship between cannabis and mental health has been attributed to the possible adverse effects of cannabis on brain structure and functioning during adolescence (Eggan et al., 2010, Malone et al., 2010, Schneider, 2008).
In this paper we address some of these issues by reporting a multiple cohort study of the relationships between the use of cannabis and the development of symptoms of depression in four Australasian cohorts that have gathered data on cannabis use and symptoms of depression over the period from adolescence to young adulthood. These studies include: the Victorian Adolescent Health Cohort Study (Patton et al., 2007); the Personality and Total Health (PATH) study (Anstey et al., 2011); the Australian Temperament Project (ATP; Prior et al., 2000); and the Christchurch Health and Development Study (CHDS; Fergusson and Horwood, 2001, Fergusson et al., 1989). The availability of four data sets gathered by independent investigators in different centres offers the advantages of testing for robust and general associations between the use of cannabis and the development of depressive symptoms.
The paper aims to address three questions regarding the linkages between cannabis and depression using data from these cohorts.
- 1.
Association: To what extent are there consistent dose/response relationships between the extent of cannabis use and the development of depressive symptoms? This stage of the analysis will use random effects regression methods and integrative data analysis to estimate the linkages between cannabis use and depressive symptoms for each study and pooled across studies.
- 2.
Confounding: To what extent can any association between cannabis use and the development of depressive symptoms be explained by third or confounding factors? This stage of the analysis will use fixed effects regression models to control for non-observed fixed sources of confounding. Estimates from the four studies will be combined using integrative data analysis models.
- 3.
Age: To what extent does any association between the use of cannabis and rates of depressive symptoms vary with age? This question will be addressed by extending the statistical models described in 2 to test for age × cannabis use interactions.
Section snippets
The Victorian Adolescent Health Cohort Study (VAHCS)
The VAHCS is a longitudinal study of a representative sample of mid-secondary school adolescents resident in Victoria, Australia (Patton et al., 2007). In 1992, participants were recruited at the end of Year 9 (wave 1) or the start of Year 10 (wave 2), and were reviewed on four occasions during adolescence (waves 3–6), with a further three follow-ups in young adulthood (waves 7–9). The present analysis is based on data collected during the first seven waves of the study. Of the sample of 2032
Associations between frequency of cannabis use and mean depression scores
Table 2 shows the associations between frequency of cannabis use and mean depression scores for each wave in each study. The table also reports estimates of the pooled mean data for each study. The pooled data represent the mean depression scores averaged over all data waves for all levels of cannabis use. Depression scores have been scaled to a mean of 100 and standard deviation of 10 to ensure comparability across studies. For each cohort a test of the significance of the association between
Discussion
This study has used an integrative data analysis framework to examine the associations between frequency of cannabis use and depressive symptoms in four large Australasian cohorts. The combined data comprised a total of more than 6900 participants assessed repeatedly on measures of cannabis use and depression over the period from mid-adolescence to mature adulthood.
Role of funding source
The VAHCS was funded by grants from the Australian National Health and Medical Research Council (NHMRC) and the Australian Government Department of Health and Ageing. The PATH study has been funded by Unit Grant 973302, Program Grant 179805 and Project Grant 157125 from the NHMRC, a grant from the Australian Rotary Health Research Fund and a grant from the Alcohol-Related Medical Research Grant Scheme of the Australian Brewers’ Foundation. The ATP data used in the present analyses was funded by
Contributors
LJH and DMF designed the study, conducted the analysis and drafted the manuscript; CC and GCP provided oversight of the analysis and interpretation of the data for the VAHCS; RT provided oversight of the analysis and interpretation of the data for PATH; DS and PL provided oversight of the analysis and interpretation of the data for the ATP; ES managed the literature searches and referencing. DH provided feedback on drafts of the manuscript. All authors contributed to, and have approved, the
Conflict of interest
All authors have no conflicts of interest to declare.
Acknowledgements
We thank Kaarin Anstey, Anthony Jorm, Bryan Rodgers, Simon Easteal, Peter Butterworth, Nicolas Cherbuin, Andrew McKinnon, Trish Jacomb, Karen Maxwell and the PATH interviewing team for their contribution to the PATH Through Life Project. We thank Christina O’Loughlin, Craig Olsson, John Carlin and Helen Romaniuk for their contributions to the Victorian Adolescent Health Cohort. GP is supported by an NH&MRC Senior Principal Research Fellowship. We acknowledge all collaborators who have
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Supplementary material can be found by accessing the online version of this paper at http://dx.doi.org.