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Cannabinoids in Bipolar disorder

The role of cannabis (marijuana) in psychiatric disorders remains controversial. In bipolar disorder, it is known that many people use cannabis for various reasons. There are some reports that people use cannabis for help in alleviating mania and others report its use for relieving depression. However, these reports are anecdotal and no systematic research has ever been done to see if these effects apply to the population in general. Additionally, there are reports that indicate that cannabis can have a detrimental and potentially causative role in the development of psychosis and paradoxically, can induce mania. The authors of this paper conducted a literature search to identify what has been published regarding the relationship between cannabis and bipolar disorder. Additionally, they looked at other ways of ingesting cannabinoids (the type of molecule that is the active ingredient in marijuana). The active ingredient in marijuana is called delta-9 tetrahydracannabinol but there are other similar cannabinoid molecules that can be utilized to harbor similar effects.

When marijuana is ingested, the active ingredient triggers a receptor in the brain called the CB-1 receptor. CB-1 receptors are part of what is called the "endocannabinoid" system which broken down means "endo" or endogenous (naturally present in the body) cannabinoid system. The evolution of this system indicates that our bodies naturally produce cannabinoid-type molecules, which in fact is the case. CB-1 receptors are plentiful in the areas of the brain considered to be involved with bipolar disorder with the highest levels in the basal ganglia, cerebellum and hippocampus. There are similar receptors in the peripheral body, called CB-2 receptors. They are seen primarily in immune cells. It is not known precisely what effect the CB-2 receptors have with the effects of cannabis.

Unfortunately, no controlled trials of THC have been done in bipolar disorder. Anecdotal evidence is fraught with peril in terms of making major judgments because it is not controlled and there is no objective comparison to understand the benefit due to the drug itself versus other effects associated with taking the drug or placebo effect. Additionally, it is seen that the effects of THC are often "bidirectional" which means that it is possible that in some people THC will relax, often in similar effectiveness as benzodiazepine (valium for example) medications, but in other people will cause anxiety and change physiologic parameters that leads to furthering of anxiety. It may make people tired or in others increase alertness and in some it may lead to depressed feelings while others feel a high and levels of euphoria.

Because there is evidence, particularly in certain genetically susceptible individuals, of psychosis being related to usage of cannabis, it should be with extreme caution that one uses such a drug if they have a diagnosis of bipolar disorder. Additionally, as it can provoke mania in some people, extreme caution should be used before one takes this drug if they have a diagnosis of bipolar disorder. THC also can interfere with the action of psychiatric medications, primarily the atypical antipsychotics which are frequently used as anti-manic agents. Lastly, it has been shown that the effects of marijuana are often more severe in people already diagnosed with psychiatric disorders.

However, given the anecdotal evidence, it does appear that for some people marijuana is beneficial. Any decision to use it should be well considered and best discussed with physician and should be done under very careful supervision. Before an evidence-based recommendation can be made regarding marijuana, a double-blind, randomized controlled trial will need to be conducted both for safety and effectiveness. The authors are advocating for such research to be conducted and one can only feel that to know the results of this kind of research would be beneficial. Additionally, if such research were to show a positive benefit, more standardized methods of taking the THC, such as a sublingual spray, could be created such that it could be given in a therapeutic dose. Inhalational THC, smoked marijuana for example, varies in potency and in the depth of inhalation by the consumer and can lead to different effects even with the same product. Standardized dosing would also allow for a lower dose to be taken which may be equally effective but with fewer risks, (psychosis, mania, or hypomania in particular) than conventional inhalational means allow for. Additionally, a commercially prepared medication could include a similar cannabinoid called cannabidiol to further help temper the drug to lower side effects.

Ashton CH, Moore PB, Gallagher P, Young AH.
Cannabinoids in bipolar affective disorder: a review and discussion of their therapeutic potential.
J Psychopharmacol. 2005 Sep;19(3):293-300.