Cannabis use and the course and outcome of major depressive disorder: A population based longitudinal study
Introduction
Following tobacco and alcohol, cannabis is the most widely used drug in the world (United Nations Office on Drugs and Crime, 2012) with an estimated 5% prevalence of past-year use, representing up to 200 million annual users worldwide (Degenhardt et al., 2011). Research in the past decade has pointed to the contribution of the human endo-cannabinoid system to the onset and course of various psychiatric disorders (Carvalho and Van Bockstaele, 2012). Extensive epidemiological research has supported the notion that cannabis use, and especially heavy use, may be associated with an increased risk for developing a psychotic disorder including schizophrenia (Moore et al., 2007, WHO, 2016). Moreover, it has been reported that cannabis use may affect the course of such disorders, leading to earlier onset, higher severity and longer persistence of psychotic disorders as well as more frequent psychotic relapses over time (Foti et al., 2010, Grech et al., 2005, Linszen et al., 1994, Whiteford et al., 2013).
Cannabis use may also alter the course of additional psychiatric disorders. Individuals who used cannabis were more prone to have earlier onset of panic attacks (Zvolensky et al., 2006), elevated intensity of anxiety symptoms during panic attacks (Szuster et al., 1988) and increased sensitivity to anxiety symptoms (Buckner et al., 2009). A meta-analysis suggested that among individuals diagnosed with bipolar disorder, cannabis users were approximately three-times more prone to experience a recurring manic episode compared to nonusers (Gibbs et al., 2014). Furthermore, individuals diagnosed with bipolar disorder and co-occurring cannabis use were reported to have more depressive and manic/hypomanic episodes per year (Lev-Ran et al., 2013a), longer duration of mixed and manic episodes (Strakowski et al., 2007) and poorer life functioning (Agrawal et al., 2011) compared to nonusers. However, the effect of cannabis use on the course and outcome of depression is less clear.
Major depressive disorder (MDD) is a common psychiatric disorder which contributes significantly to the global burden of disease (Whiteford et al., 2013). Several cross-sectional studies revealed strong co-occurrence between cannabis use and psychopathology (such as post-traumatic stress disorder (Kevorkian et al., 2015)), and specifically between cannabis use and depression, indicating high prevalence of cannabis use among individuals with depression and vice-versa (Chen et al., 2002, Grant, 1995). Longitudinal studies have reported conflicting results; while several longitudinal studies reported that cannabis users were more prone to develop depression at follow-up compared to nonusers (Bovasso, 2001, Gage et al., 2015, Pacek et al., 2013), others reported no significant association (Danielsson et al., 2015). An integrative study conducted by Horwood et al. (2012) explored the extent to which cannabis use consistently predicts the onset of depressive symptoms in four Australian cohorts. Controlling for possible confounding effects, analyses revealed a significant dose-response effect between cannabis use and latter onset of depressive symptoms, with evidence indicating that this effect may be strongest in mid-adolescence and weaker in mature adulthood. In a meta-analysis conducted by Lev-Ran et al. (2013) the authors concluded that cannabis use, and particularly heavy use, may be associated with moderate yet significant increased risk for developing depression.
It has been argued that the discrepancy in longitudinal evidence concerning cannabis use and depression is caused by inconsistent measuring of cannabis use and depression as well as lack of sufficient control for confounding factors (Lev-Ran et al., 2013c). In addition, CUDs may be associated with MDD in a substantially different way than cannabis use per se, as Substance Use Disorders (SUDs) and MDD presumably share common mechanisms and manifestations, including clinical similarities and neurobiological pathways and abnormalities (Brady and Sinha, 2005). Recently Feingold et al. (2015) reported that after controlling for various confounding factors, including sociodemographic variables and additional psychiatric and substance use disorders among individuals without lifetime MDD, baseline cannabis use, even daily use, was not associated with increased risk for onset of MDD at follow-up compared to nonusers. Inversely, after controlling for confounding variables among lifetime cannabis abstainers, individuals with baseline MDD were at a significantly increased risk to initiate cannabis use at follow-up (Feingold et al., 2015). However specific effects of cannabis use on the outcome of MDD are not clear.
It has been reported that among individuals with MDD cannabis use may be associated with a significantly elevated feeling of dysphoria (Ablon and Goodwin, 1974) and an incline in number of depressive symptoms (Otten and Engels, 2013). There is evidence suggesting that cannabis use, and particularly frequent use, may reduce the efficiency of pharmacological treatment for depressive symptoms (Bricker et al., 2007). Additional cross-sectional research indicates potentially lower self-reported quality of life (QoL) among individuals with MDD who use cannabis frequently, compared to nonusers (Aspis et al., 2015). Nevertheless, longitudinal data on the effect of cannabis use on the severity and course of depression is lacking.
In this study we sought to explore the effect of cannabis use and Cannabis Use Disorders (CUDs) on the course and outcome of MDD over a three-year period. Course of illness and outcome were assessed using rates of remission, depressive symptomology, suicidality measures, treatment utilization, measures of impairment in social, occupational and educational functioning and self-reported mental QoL. We hypothesized that cannabis use and CUD are associated with poorer outcome of MDD, as manifested by increased depressive symptoms, more significant impairment and lower QoL.
Section snippets
Participants
We used data from the National Epidemiologic survey on Alcohol and Related Conditions (NESARC), a national representative survey designed by the National Institute on Alcohol Abuse and Alcoholism (Grant et al., 2008). The NESARC is a longitudinal survey which targeted non-institutionalized adults living in the United States, including military personnel living off-base and those in group housing (e.g. college dormitories, shelters). Wave 1 of the NESARC was conducted at 2001–2002 including a
Results
Among individuals with baseline MDD, 7.5% reported using cannabis throughout the study period without qualifying for a CUD, and 4.7% qualified for a diagnosis of a CUD throughout the same time-frame ("CUD"). In the twelve months prior to Wave 1, daily or almost daily use of cannabis was reported by 16.3% and 39.9% of cannabis users and individuals with CUD, respectively. Compared to nonusers, both groups of cannabis users differed significantly in several sociodemographic variables (Table 1)
Discussion
In this study we explored the effect of cannabis use and CUDs on the course and outcome of MDD over a three-year period. Results indicate that cannabis users and individuals with CUDs did not differ from nonusers in rates of remission from MDD. Levels of cannabis use (no use, users without a CUD and those with a CUD) were associated with increased number of depressive symptoms at follow-up, particularly differences in prevalence ofanhedonia, change in body weight, insomnia or hypersomnia and
Conflict of interest
The Authors have declared that there are no conflicts of interest in relation to the subject of this study.
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