URJHS Volume 8

A Review of the Relationship Between Cannabis Use and Affective Disorders

Thomas Hugh Richardson
University of Bath

Abstract

This paper examines the relationship between cannabis use and the affective disorders of depression, bipolar disorder, and mania. The literature is reviewed, examining both sides of the debate. The literature suggests that cannabis is most strongly related to depression in heavy use, in particular in adolescents. Cannabis may be used to self-medicate depressive symptoms, though there is little evidence that this is effective. Whilst cannabis may also be used for self-medication in bipolar disorder, it has a number of effects on the emergence, presentation, treatment, and prognosis of the illness. Cannabis use may also increase sub-clinical manic symptoms in non-clinical populations. Future research is then suggested to resolve some of the discrepancies in the literature.

Introduction

Cannabis is the most widely used illegal drug in many countries, in Ireland, cannabis is the most commonly used illegal drug, with an estimated 17 percent of the population using cannabis in their lifetime (NACDD, 2003). There is an increasing body of literature concerning the relationship between cannabis use and a number of psychiatric disorders including schizophrenia and psychosis. There has also been research on cannabis and depression and bipolar disorder, and a smaller body of literature on cannabis and mania. This review will examine the relationship between cannabis use and the three affective disorders: depression, bipolar disorder, and mania. Discrepancies in the literature will be examined, in particular regarding the cause-effect nature of any relationships, in order to draw conclusions about this issue, and suggest further research.

Depression

Whether depression is a predisposing risk factor to substance abuse, with cannabis being used to mediate symptoms (the self-medication hypothesis), or whether cannabis use itself directly exacerbates or induces depression, is a matter of controversial debate in the literature (Frances, 1997). Whilst there is clearly at least a modest statistical relationship between the two, there are opposing views about the nature of the causal relationship (De Irala, Ruiz-Canela & Martinez-Gonzalez, 2005 ).

The Argument for : Cannabis causes depression

Cannabis use and depressive symptoms in the general population

There is an increasing body of evidence that heavy cannabis use is directly related to depression, and may independently cause depression, or exacerbate pre-existing vulnerabilities. Studies have shown that depressive symptomatology cannot predict later cannabis use (Chabrol et al., 2005a) and that cannabis is rarely used for depression (Chabrol et al., 2005b), suggesting that self-medication cannot account for the relationship. One longitudinal study found that in participants with no baseline depressive symptoms, those who used cannabis were four times more likely to have depressive symptoms (Bovasso, 2001). In particular, cannabis users were more prone to anhedonia and suicidal ideation (Bovasso, 2001). Furthermore, depressive symptoms at baseline failed to predict cannabis use at follow up, suggesting that cannabis was not used for self-medication (Bovasso, 2001). Another longitudinal survey concluded that there is a causal relationship, with cannabis use increasing the population prevalence of depression by up to 9 percent (Harder, Morral & Arkes, 2006). One meta-analysis found only a modest association between cannabis use and later depression in cross-sectional and cohort studies (Degenhardt, Hall & Lynskey, 2003 ). However, this association was much stronger with early onset, heavy cannabis use (Degenhardt, Hall & Lynskey, 2003 ). The meta-analysis also found little evidence that depression increased subsequent cannabis use (Degenhardt, Hall & Lynskey, 2003 ). Early-onset cannabis use may be a particularly potent risk factor. One birth cohort study found significantly increased depression and suicidal ideation in those who had early onset cannabis use, before the age of 15 (Fergusson, Lynskey & Horwood, 1996 ). There is considerable evidence for a causal relationship between cannabis use and depression in the general population, independent of self-medication of symptoms.

Cannabis use and clinical depression

Clinically depressed patients with co-morbid cannabis use have considerably poorer long-term outcomes from treatment. For example, cannabis use may reduce the effectiveness of cognitive behavioural therapy for depression ( Bricker et al., 2007 ). The co-morbidity of major depression and cannabis use is high, particularly among adolescent inpatients (Grilo et al., 1997). This suggests that clinically depressed adolescents may be especially vulnerable to the adverse effects of cannabis use. Cannabis use and dependence are particularly frequent in adolescence (Poulton et al., 1997), as are depressive symptoms and depressive disorder (AACAP, 1998). Cannabis use is very high in clinically depressed adolescents, and use increases depressive symptoms in this population (Rey et al., 2002). However, depressed adolescent patients who use cannabis are less likely to self-refer themselves to mental health services (Rey et al., 2002). The prevalence of clinical depression is higher in patients who use cannabis alone compared to those who use cannabis and harder drugs such as cocaine (Arendt & Munk-Jørgensen, 2004). This suggests that cannabis and clinical depression is co-morbid in a unique way. One review concluded that clinical depression does not cause cannabis use and patients with life-time Major Depressive Disorder (MDD) use cannabis for the same reasons as users without depression (Kalant, 2004). This suggests that the relationship is not due to the self-medication of clinical symptoms. Clinically depressed cannabis users often reported increased depression whilst under the influence and may experience an increase in specific depressive symptoms (Arendt et al., 2007). Cannabis-induced clinical depression may differ from classic MDD, having more psychotic symptoms (Pattern, 2004). One study of heavy cannabis users seeking treatment found that users were significantly younger and more depressed, more so than for harder drug users seeking treatment (Arendt & Munk-Jørgensen, 2004). Cannabis use may contribute to clinical depression considerably, independent of self-medication, in particular in adolescent depression.

Gender differences

There are important gender differences in the adverse effects of cannabis use on depression. Depressive disorders are more common in girls than in boys (AACAP, 1998), but substance abuse is more common in boys (Fergusson, Lynskey & Horwood, 1996). Gender differences in motives for use and initial depressive symptoms may be linked to the presence of comorbid depression (Chabrol et al., 2005b), and susceptibility to the adverse effects of cannabis on depressive symptoms (Compton et al., 2005). The relationship between cannabis use and depression, suicidal ideation, and suicide attempts is especially strong in adolescent girls (Wilcox & Anthony, 2004). Whilst cannabis can increase depressive symptoms in boys, it has a much stronger effect on depressive symptoms in girls (Poulin et al., 2005). Female adolescents who use cannabis are at a greater risk of subsequent depression than their male peers (McGee et al., 2000). Females, in particular adolescent females are particularly at risk of developing depression from cannabis use, even though they may not use as heavily as their male peers (McGee et al., 2000). These gender differences in the relationship between cannabis use and depression may be due to differences in use for self-medication (Chabrol et al., 2005b). However, they suggest a causal link, as cannabis has a greater adverse effect on adolescent girls who have a greater pre-existing vulnerability to depression.

Cannabis use and pre-dispositions

There is an ongoing debate as to whether cannabis itself can cause depression, or whether it brings underlying genetic predispositions to the surface (Patton et al., 2002). One twin study examined twins discordant for cannabis dependence, finding that cannabis dependent individuals were at a 2.5 times higher risk of suicidal ideation and suicide attempt (Lynskey et al., 2004). Cannabis dependence was associated with increased risk of MDD in dizygotic but not monozygotic twins, suggesting that the effect of cannabis use on depression may be independent of genetic predispositions. However, early MDD was significantly associated with the risk of cannabis dependence in discordant dizygotic but not monozygotic twins (Lynskey et al., 2004). This suggests that the co-morbidity between cannabis dependence and MDD is due to shared genetic and environmental factors that predispose towards both. Cannabis may be a significant risk factor for MDD in those who already have a pre-existing vulnerability (Lynskey et al., 2004 ).

Extent of use and severity

The relationship between cannabis use and later depression is related to the extent of abuse. One study found that weekly use doubled the risk of depression, whereas daily use increased it five-fold (Patton et al., 2002). Around 10 percent of cannabis users will become dependent (Hall, Solowij & Lemon, 1994), and whether users are dependent appears to be important in its relationship to depression. One longitudinal study found that cannabis use was associated with a 14 percent prevalence of MDD, but this increased to 29 percent with subjects who were dependent (Grant & Pickering, 1998). The strength of cannabis may also be related to subsequent risk of depression (Arendt & Munk-Jørgensen, 2004). This research implies a causal link, suggesting a dose-effect relationship, with heavier and more problematic cannabis use increasing the strength of the relationship with depression.

The argument against: Cannabis does not cause depression

A body of the literature refutes the causal link between cannabis use and depression, based on three arguments. Firstly, the link exists because depressed patients use cannabis to help control their symptoms (the self-medication hypothesis). Secondly, the link exists because shared genetic, environmental and socio-economic factors predispose individuals both to develop depression and to abuse cannabis. Thirdly, there is no link between the two, and cannabis may in fact have antidepressant effects.

The self-medication hypothesis

It has been suggested that whilst there is a link between cannabis use and depression, this is due to self-medication of depressive symptoms. Studies of psychiatric inpatients have found that cannabis is often used as an attempt to reduce depression (Schofield et al., 2006). Other studies have suggested that depression alleviation is a common reason for cannabis use (Mueser, Drake & Wallach, 1998). A study of adolescents with comorbid MDD and substance abuse found that out of a number of substances, cannabis use was significantly more prevalent in those who had suffered depression before abuse (Libby et al., 2005). Recreational users often report that using cannabis increases euphoria (Velez, Johnson & Cohen, 1989). However, studies have shown that cannabis does not improve mood in the clinically depressed (Pond, 1948), and longitudinal population studies have often shown no relationship between initial depressive symptoms and later cannabis use (Brook et al., 2002). Self-medication may be a factor in the relationship between cannabis use and depression, but this still does not rule out the possibility of cannabis use increasing the risk of initial depression.

Common factors create co-morbidity

There is also an argument that the relationship between cannabis use and depression is caused by third variables that are often missed by studies. Shared factors may increase the likelihood both of suffering from depression, and of using cannabis. Longitudinal data suggests that there are common factors that are related to depression and cannabis use (Degenhardt, Hall & Lynskey, 2001). A birth cohort study found that many of the associations between cannabis use and depression could be explained by socio-economic status, early adjustment problems and delinquent peers (Fergusson, Lynskey & Horwood, 1996 ). It has also been found that whilst cannabis is statistically related to depression, once demographic variables and personality characteristics are controlled for, this relationship disappears (Degenhardt, Hall & Lynskey, 2001) . Other research has suggested that cannabis is not related to depression once other substance abuse is controlled (Degenhardt, Hall & Lynskey, 2005) and when education, marital status, alcohol, and tobacco use are accounted for (Green & Ritter, 2000). Cannabis-dependent patients have been found to hold marginalized positions in society, suggesting that cannabis dependence may correlate with social problems (Kalant, 2004). Heavy cannabis users also often come from socially disadvantaged families (Kendel, 1984). It is also possible that genetic factors may be responsible for the link, as a genetic overlap has been found between depression and cannabis dependence (Fu et al., 2002). Such findings suggest that there are common factors which

Cannabis has no impact or may help alleviate depression

There is a body of literature that suggests that there is not a significant relationship between cannabis use and depression, and a small body arguing that cannabis may in fact decrease depressive symptoms. Many studies show no link between cannabis and depression despite appropriate statistical power, measurement, and design (Fergusson & Horwood, 1997, Green & Ritter, 2000). Research has concluded that cannabis use is not a strong causal factor in the occurrence of a Major Depressive Episode (Chen, Wagner & Anthony, 2002). Other studies have found that heavy use is associated with externalising problems such as aggressive behaviour and delinquency, but not with internalising problems such as depression, and depressive symptoms such as somatic complaints (Monshouwer et al., 2006). Meta-analyses have shown only a moderate relationship between cannabis use and depression in cohort and cross-sectional studies in non-clinical populations (Degenhardt, Hall & Lynskey, 2003). There is also little relationship between depression and infrequent cannabis use (Degenhardt, Hall & Lynskey, 2003). Longitudinal studies have often been able to account for any statistical relationship once accounting for baseline risk factors for developing depression (Fergusson & Horwood, 1997 ). A review of population studies concluded that cannabis makes only a modest contribution to the overall population prevalence of depression (Degenhardt, Hall & Lynskey, 2003). Population research has also found that cannabis users have a less depressed mood, fewer somatic complaints, and more positive affect than non-users (Denson & Earlywine, 2006). At this stage there seems insufficient evidence to suggest that cannabis use can decrease depression. However, it is clear that many studies fail to find any statistically significant relationship between the two.

Bipolar Disorder

Cannabis use is common in bipolar disorder (Regier et al., 1990). There is a body of evidence examining cannabis use and earlier initial onset, different presentation of symptoms and poorer prognosis, suggesting a causal link between the two. However, a body of literature suggests that cannabis is used for self-medication, and that it may be effective for this purpose.

Cannabis use, susceptibility and prognosis

There is evidence that the use of cannabis in bipolar disorder may not be due to self-medication and may be a risk factor for initial onset, and cause a number of complications. One study found twice the prevalence of bipolar disorder among cannabis users not using hard drugs, compared to cannabis users using hard drugs, and slightly higher than non-cannabis users using hard drugs (Arendt & Munk-Jørgensen, 2004). This suggests that cannabis and bipolar disorder may be co-morbid in a unique way, beyond the co-morbidity often observed with other substances. Bipolar patients with co-morbid substance abuse disorders often have more complex clinical presentations, accelerated relapses, increased depressive features, and elevated suicide risk (Goldberg, 2001). Cannabis use can also complicate the course of bipolar disorder, contributing to mixed states and a poorer prognosis (Goldberg et al., 1999). Remission during hospitalisation is less likely if cannabis is used (Goldberg et al., 1999). Bipolar patients with a history of cannabis use may also respond differently to medication, showing a better response to anticonvulsant mood stabilizers such as carbamazepine and a poorer response to lithium (Goldberg et al., 1999). Patients with general substance abuse disorders have an earlier initial onset ( Brady & Sonne, 1995), and cannabis use can also lead to younger onset (Salloum et al., 2005). Bipolar patients who use cannabis have additional psychiatric co-morbidity and increased frequency of manic phases (Salloum et al., 2005). Cannabis use may also increase the duration of manic cycles (Strakowski et al., 2000). In bipolar disorder, cannabis use can lead to earlier initial onset, and cause a number of complications in the diagnosis, presentation, treatment, and prognosis of the disorder.

Cannabis self-medication in bipolar disorder

There is research suggesting that bipolar patients may use cannabis in an attempt to self-medicate the symptoms of the disorder. A number of bipolar patients find cannabis useful for treating the symptoms of manic and/or depressive cycles (Grinspoon & Bakalar, 1998). Many patients use cannabis as a supplement to lithium, and some describe it as more effective (Grinspoon & Bakalar, 1998). Cannabinoids may have sedative, antidepressant, antipsychotic and anticonvulsant effects which may be useful in managing the disorder (Ashton et al., 2005). In particular, the combined stimulant and sedative properties of cannabis may help to mediate the cycles of mania and depression (Ashton et al., 2005). While it seems probable that a number of bipolar patients use cannabis for self-medication, this does not rule out cannabis use as a causal factor for a number of complications in the disorder. The literature is not yet at a stage to confidently suggest the use of cannabis derivatives in treatment.

Mania

There is limited evidence on cannabis and mania, however, evidence from bipolar and psychotic patients and population epidemiological studies suggests that cannabis use and mania may be related.

Cannabis and comorbid hypomanic symptomatology

Since the 1970’s, the diagnosis of ‘Cannabis-modified mania’ has been used (Knight, 1976), though cannabis use may be more related to mixed mania than pure mania (Goldberg et al., 1996). Heavy use may induce psychosis with hypomanic features ( Rottanburg et al., 1982), and cannabis dependent subjects have increased manic behaviour (Arendt & Munk-Jørgensen, 2004). In bipolar patients, cannabis use increases the duration of manic cycles (Strakowski et al., 2000). Prenatal exposure to cannabanoids may lead to later symptoms similar to that of hypomania, including hyperactivity and impulsivity (Sundrum, 2006). In bipolar disorder, cannabis use often precedes the initial onset of manic symptoms (Strakowski et al., 2000), and patients often do not resume cannabis use after initial onset (Henquet et al., 2006). This implicates cannabis use as a causal factor for mania rather than a substance used for self-medication. However a number of case studies implicate cannabis use for self-medication of manic symptoms (Grinspoon & Bakalar, 1998). There is little research on cannabis and hypomanic symptomatology in clinical populations independent of bipolar disorder, in particular how the two interact longitudinally and whether the relationship is causal (Strakowski et al., 2000). However it appears that cannabis use may have implications for mania in bipolar disorder, and hypomanic symptoms in other disorders such as psychosis.

Cannabis and manic symptoms in the general population

The first major study of cannabis use and manic symptoms was recently conducted (Henquet et al., 2006). The authors conducted a longitudinal population-based study, assessing substance abuse and manic and psychotic symptoms (Henquet et al., 2006). They found that cannabis use at the baseline significantly increased the risk of manic symptoms during follow up (Henquet et al., 2006). After accounting for demographic variables, neuroticism, alcohol and other drug abuse, and depressive and manic symptoms at baseline, this finding remained significant (Henquet et al., 2006). Furthermore, this increase in manic symptoms was independent of the incidence of psychotic symptoms (Henquet et al., 2006). There was also no evidence for reverse causality in this relationship, as manic symptoms at baseline did not predict cannabis use during follow up (Henquet et al., 2006). The level of use predicted the level of manic symptoms, suggesting a linear relationship, with heavier use increasing symptoms (Henquet et al., 2006). Cannabis use was not related to manic symptoms at follow up, suggesting that manic symptoms are due to the cumulative effects of long-term exposure, rather than the acute effects of intoxication (Henquet et al., 2006). This study was conducted over just 3 years, so the long-term effects of cannabis on outcomes of manic symptoms cannot be determined. Also sub-clinical manic symptoms were studied rather than DSM-IV (Diagnostic and Statistical Manual, 4th Edition) (APA, 1994) symptoms for a manic episode. However, such sub-clinical manic symptoms can increase the risk of a clinical manic episode (Thomas, 2004). This research implies that in terms of sub-clinical definitions, cannabis use may significantly increase manic symptoms.

Conclusion

This paper has reviewed the evidence from the literature examining the relationship between cannabis use and affective disorders. It appears that cannabis use may only be moderately related to depression in the general population. However, adolescents with early onset, in particular girls and those with a pre-existing vulnerability are particularly at risk. Cannabis may be used for self-medication, in particular in bipolar disorder, though this may only be effective for a small proportion of patients. In most bipolar patients, cannabis use complicates diagnosis, compromises treatment outcomes and prognosis, and leads to increased frequency of mixed states and increased duration of manic cycles. Cannabis use may also increase sub-clinical hypomanic symptoms. A preferable design for future research would be a longitudinal study from childhood through to early adulthood, taking account of socio-economic, genetic and demographic variables, as well as drug use and subsequent sub-clinical symptoms and clinical diagnosis. This would help to examine the cause and effect nature of any relationships found, and perhaps account for some of the discrepancies in the literature.

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