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Genes, childhood sexual abuse may influence marijuana dependence

Analysis of three separate study cohorts suggests the rs604300 genotype in the monoacylglycerol lipase gene moderates the relationship between childhood sexual abuse and marijuana dependence symptoms.

“In this study, we investigated whether variation in genes within the endocannabinoid system may be particularly important in setting the stage for cannabis dependence, especially in the context of childhood trauma,” Caitlin E. Carey, a PhD student at Washington University, St. Louis, said in a press release.

Caitlin E. Carey

Carey and colleagues conducted three analyses to determine the role of genes and childhood sexual abuse in development of marijuana dependence.

The first analysis included data from the Comorbidity and Trauma Study (CATS) on childhood sexual abuse and marijuana use for 1,558 Australian adults. The majority of study participants were opioid-dependent.

Results from the CATS analysis indicated that only a single variant within the monoacylglycerol lipase gene, rs604300, exhibited significant interaction with childhood sexual abuse and later marijuana dependence (P = .0002).

Within the full rs604300 model, increasing exposure to childhood sexual abuse was associated with a higher number of dependence symptoms among individuals who were homozygous for the more common G allele (P < .001). There was no association among heterozygous individuals.

Data indicated a negative relationship between childhood sexual abuse and marijuana dependence symptoms among individuals homozygous for the A allele.

The rs604300 genotype did not have a main effect on marijuana dependence symptoms or childhood sexual abuse.

The second analysis included data from the Study of Addiction: Genetics and Environment (SAGE) for 859 alcohol-dependent or healthy European American adults.

Researchers found that interaction between rs604300 genotype and childhood abuse was significantly associated with marijuana dependence symptoms (P = .026).

Similar to CATS results, childhood abuse was associated with more dependence symptoms, though this was only observed among individuals homozygous for the G allele (P < .001).

There was no association between childhood abuse and marijuana dependence symptoms among carriers of the minor A allele.

Divergent from CATS results, there was a significant main effect of genotype on marijuana dependence symptoms, with greater symptoms among A allele carriers.

The third analysis included functional MRI and genetic data from the Duke Neurogenetics Study (DNS), which assessed numerous behavioral, experimental and biological phenotypes among young adults aged 18 to 22 years. Data was available for 325 participants.

Researchers found an association between increased right basolateral amygdala habituation and increased early life stress among A allele carriers but not individuals homozygous for the G allele.

“Here, we found evidence that rs604300 genotype in [monoacylglycerol lipase gene] moderates the relationship between [childhood sexual abuse] and cannabis dependence symptoms. Those who carried two copies of the major G allele were at increased risk for cannabis dependence as a function of increasing exposure to [childhood sexual abuse] events. This finding was not surprising, as [childhood sexual abuse] has been widely documented as a potent contributor to the etiology of a host of addictive behaviors, including cannabis dependence,” Carey and colleagues wrote. “What was particularly intriguing was that rs604300 minor A allele carriers did not demonstrate increased vulnerability to cannabis dependence symptoms in the presence of [childhood sexual abuse] exposure. This alludes to the potential buffering effects of the A allele in rs604300 on the pathogenic effects of [childhood sexual abuse].” – by Amanda Oldt

Disclosure: Please see the full study for a list of all authors’ relevant financial disclosures.