Cannabis and Mood Disorders

By Kaylee Martig

Mood disorders are a category of psychiatric disorders characterized by changes in affect. Two common mood disorders are depression and bipolar disorder. Symptoms of depression include “depressed mood” or “loss of interest or pleasure,” which may be accompanied by an increase or decrease in appetite, insomnia or hypersomnia, psychomotor agitation or retardation, fatigue, feelings of worthlessness, or suicidal ideation (1). Symptoms of bipolar disorder include mania, which is described in the DSM-5 as “a distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased activity and energy,” that may cycle with depressive symptoms. Although multiple classifications of bipolar disorder exist, it will be discussed as a single inclusive disorder in this paper.

There is accumulating research demonstrating the influential role of the endocannabinoid system in mood disorders. As previously described, the endocannabinoid system is comprised of CB1 and CB2 receptors which are activated by endogenous cannabinoid neurotransmitters. While it is not known exactly how the endocannabinoid system is related to mood disorders, two hypotheses include inhibition/excitation and regulation of the serotoninergic system. It is well established that the endocannabinoid system regulates inhibition and excitation in the brain; and when this system is dysfunctional, extreme inhibition or excitation of the brain may lead, respectively, to depression or mania (2, 3). Furthermore, CB1 receptors may play a role in the regulation of the serotoninergic system, which is dysregulated in depression (4).

Dysregulation of inhibition/excitation in the brain is associated with many psychiatric disorders, including schizophrenia, anxiety, and depression (2, 3). In a postmortem investigation, researchers found lower concentrations of CB1 receptors in the anterior cingulate cortex of individuals with unipolar depression than in healthy brains (5). Clinical observations suggest the endocannabinoid system and CB1 receptors may be similarly implicated in depression associated with bipolar disorder (2). The association between reduced CB1 activity and depression suggests drugs which increase CB1 activation may compensate for decreased CB1 activity and improve depressive symptoms. Animal studies have found that cannabinoids which increase CB1 activation elicit antidepressant effects in small doses, although they actually appear to have the opposite effect in high doses, with the potential to worsen depressive symptoms (6, 7). This supports the utility of cannabinoids as treatment for depression through the regulation of inhibition/excitation of the endocannabinoid system, although more research is needed to identify optimal dosing.

Conventional treatments for depression, including SSRI and tricyclic antidepressants, work in the brain by increasing the availability of serotonin. A number of studies in mouse models of depression found the administration of CBD increased serotonin levels, and CBD, THC, and other phyto-cannabinoids reversed depressive behaviors (7, 8, 9). In humans, THC (5-10mg) administered through smoking herbal cigarettes has been shown to decrease subjective ratings of depression and improve sleep under placebo-controlled conditions (2). The endocannabinoid system may be implicated through the activation of CB1 receptors and through regulation of the serotoninergic system. Clinical studies are needed to establish efficacy and determine a therapeutic dosing window, however anecdotal evidence indicates that a number of patients have found cannabis useful in treating symptoms of both depression and mania, sometimes more so than conventional treatments (10).

Still, there are risks associated with cannabis use, particularly in bipolar disorder. Cannabis use disorders are frequently diagnosed in people with bipolar disorder, with yearly incidence of 7.2% in people with bipolar disorder, compared to 1.2% in the general population (11). This may result from self-medication practices. The self-medication theory is supported by slightly worse symptomology in people with bipolar disorder who used cannabis compared to those with bipolar disorder who did not use cannabis, including higher levels of depressive and manic symptoms (12). The symptomology was worse prior to cannabis use, and improved within several hours of cannabis use. While anecdotal evidence has endorsed cannabis use in mania, research suggests THC use may induce or exacerbate mania. Those who used cannabis recreationally or for self-medication exhibit higher levels of illness severity, mania, and psychosis compared with nonusers (11; 13).

One of the major concerns about cannabis use is that it can trigger mania in people who are diagnosed with or are predisposed to bipolar disorder. High doses or rapid administration of THC, common in recreational use, can induce acute psychosis with hypomanic features in subjects without a mood disorder (2). One study found that intravenous administration of THC (2.5mg) induced positive psychotic symptoms in healthy adults (14). However, in people with bipolar disorder, cannabis use is associated with the onset and exacerbation of manic symptoms, as well as younger age of onset of mania and more frequent manic and depressive episodes (15, 16). These effects are likely caused by THC. CBD has antipsychotic properties and may actually lower the risk of cannabis-related psychosis (17). Therefore, psychotic and manic symptoms may be reduced by using cannabis products with substantial CBD levels.

Intriguingly, a study of adults found those with bipolar disorder who were also diagnosed with a cannabis use disorder demonstrated better neurocognitive performance than those without a diagnosis of a cannabis use disorder (18). Bipolar disorder, especially during manic episodes, is associated with neurocognitive deficits including deficits in attention, working memory, verbal learning, delayed verbal and nonverbal memory, and executive function (19). Results from the aforementioned research included better performance on measures of attention, working memory, verbal learning, processing speed, and executive functioning in cannabis users (18, 20). Cannabis (CBD alone and 1:1 CBD:THC) is known to have some neuroprotective properties against neurodegenerative conditions, such as Huntington’s disease (21). These areas of improved neurocognitive performance suggest cannabis use may also counteract some of the neurocognitive deficits associated with bipolar disorder. The information regarding recreational use of cannabis for people with bipolar disorder is inconclusive, and individuals with this disorder should use caution when deciding whether to use cannabis.

It is important to note that the use of cannabis for mood disorders have only been studied in adults, and cannot be directly generalized to children and adolescents. While cannabis appears to have some benefits for adults with mood disorders, it is unknown whether the neuroprotective properties of CBD would apply to children and adolescents, or whether cannabis would be an effective treatment for mood disorders in children. Furthermore, recreational cannabis use, specifically the use of THC, during adolescent development has been shown in numerous studies to increase the risk of psychiatric disorders including mood and psychotic disorders (22). Even adult recreational use may be unwise for people with bipolar disorder, due to the risk of psychosis. To date, research regarding the safety and efficacy of cannabis use in bipolar disorder is inconclusive, and may be impacted by factors including dose, mode of ingestion, and personal factors (12). As a whole, more research is needed to demonstrate long-term safety and efficacy of cannabis use, particularly in children.

References

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