Family History of Bipolar Disorder Linked to Increased Risk of Cannabis Use Disorder, Study Finds

Cannabis Use Disorder (CUD) is the most common illicit drug use disorder in the United States and is believed to affect around 22 million people worldwide. The disorder is hallmarked by cravings and other physical withdrawal symptoms when cannabis is not used.

Evidence suggests that CUD rates are increasing over time, and that the condition may also be associated with other psychiatric conditions such as major depressive disorder (MDD) or bipolar disorders.

Now, a new study published in JAMA Psychiatry has found that there is an increased risk of developing CUD among relatives of people with bipolar type-II disorder (BP-II), but not bipolar type-I (BP-I) or MDD. Identifying such associations and clarifying the potential shared mechanisms between such disorders is important, the researchers say, as this can help to direct efforts towards CUD prevention and treatment.

CUD and bipolar II may share common underlying link

To examine the co-occurrence of CUD and mood disorders in individuals and their families, core study participants (also known as probands) took part in a semi-structured diagnostic interview designed to collect information on any mood disorders or substance use disorders. Each proband also gave consent for up to two of their adult first-degree relatives to be contacted and interviewed as part of the study. In total, 586 probands and 698 relatives consented to be interviewed for the study, which took place within a community in Washington, DC.

The researchers found that BP-II in probands was associated with an increased risk of CUD in first degree relatives, suggesting that there may be a common familial vulnerability to both of these conditions. Furthermore, comorbid CUD and BP-II in probands was found to be associated with more than twice the risk of CUD in first-degree relatives. Rates of CUD were highest among relatives with both a familial and individual history of BP-II.

Interestingly, the study did not find any similar association between familial CUD and probands with BP-I or MDD alone.

Generally, BP-I and BP-II are distinguished by the intensity of their manic episodes and the presence of depressive episodes. A BP-II diagnosis tends to reflect less severe episodes of mania (hypomania) but does require at least one lifetime major depressive episode, whereas BP-I does not.

“Findings demonstrating that BP-II but not BP-I was associated with CUD have important implications for nosology and the ongoing debate concerning the validity of the bipolar spectrum,” the researchers wrote.

Mood disorder diagnosis tends to pre-date CUD

To further investigate this relationship between mood disorders and CUD, the researchers looked at the age of onset for CUD and the symptoms of each three main mood disorders examined here, BP-I, BP-II, and MDD.

They found that in around two-thirds of cases, the onset of the mood disorder preceded the onset of CUD. However, this pattern only met the threshold for statistical significance when considering major depressive episode (MDE) symptoms, a limitation that the researchers say is “likely because of the greater number of MDE cases compared with mania or hypomania.”

The researchers also suggested that some of the comorbidity between CUD and mood disorders could be explained by individuals self-medicating with cannabis initially, before this escalated to cannabis misuse.

“...[T]he possibility that self-medication may explain CUD comorbidity with mood disorders remains valid and may extend to hypomania as well,” the researchers wrote. “Taken together with our finding that each mood disorder subtype mostly preceded CUD in both probands and relatives (a finding that was statistically significant for individuals with MDE and CUD), CUD may be a result of these preexisting conditions.”

Despite having a relatively large overall sample size, this study was still limited by the fact the small number of probands and relatives who met the criteria for CUD. According to the researchers, this limited the study’s statistical power when it came to assessing the influence of other comorbidities.

For example, comorbid anxiety disorder in probands and relatives was consistently found to not be associated with CUD in relatives. However, the association seen between BP-II in probands and CUD in relatives diminished when anxiety was included in an adjusted model. Future work with a larger sample size of individuals with CUD could help to determine the true effect of such comorbid disorders.

Treatments for CUD

It may seem counterintuitive, but one of the most well-researched avenues for CUD treatment involves the use of cannabinoids.

THC-based treatment strategies can be thought of as being similar to nicotine-replacement therapies for smokers. So a pharmaceutical formulation that includes THC or some mixture of THC and CBD should help people with CUD to address some of the withdrawal cravings.

A recent review of CUD treatment strategies concluded that some THC-based formulations can decrease withdrawal symptoms and relapses when given in moderate doses, though evidence supporting their effectiveness in reducing cannabis use was more mixed.

Another recent study involving the use of non-intoxicating CBD also found that high doses of this cannabinoid could increase the number of abstinence days from cannabis in a group of individuals with moderate CUD.

Alternative cannabinoid-free treatment avenues are also being investigated, particularly for treating more vulnerable groups. The non-invasive brain stimulation technique transcranial magnetic stimulation (rTMS) was recently studied by researchers as a possible way of addressing CUD in people with schizophrenia. The method was found to be effective at reducing self-reported cannabis use; those who received rTMS treatment also trended towards greater reductions in craving compared to the placebo group. 

“People with schizophrenia have very high rates of cannabis use disorder compared to the general population, and there is strong evidence that cannabis use worsens psychiatric symptoms and quality of life in these people,” senior author Dr Tony George said in a press release at the time.

“Despite the known harmful effects, there is currently no approved treatment for CUD with or without schizophrenia. These results indicate rTMS may be a safe and effective way to reduce cannabis among people with schizophrenia.”