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Background: Depression and substance use disorders, including cannabis dependence, arise during adolescence, are frequently comorbid, and represent major health burdens in the general US population. Yet little is known about the association of depression symptoms with cannabis and other substance use and use disorders in Native American adolescents.

Objective: To investigate the comorbidity of cannabis use and depression symptoms in Native American adolescents.

Methods: This study used the Children's Semi-Structured Assessment for the Genetics of Alcoholism (Adolescent Version) to obtain lifetime DSM-III-R diagnoses from a community sample of 202 (98 boys, 104 girls) American Indian adolescents living on contiguous reservations.

Results: Thirteen percent of boys and 38% of girls had a lifetime DSM-III-R major depression disorder (MDD) independent of substance use. Fifteen percent of boys and 41% of girls had a major depression episode (MDE) either coincident with or independent of cannabis use. MDE and several individual depression symptoms were significantly associated with cannabis dependence in boys but not in girls. The median ages of onset of MDE were the same in the boys and girls who had experienced both depression and cannabis use.

Conclusions: These findings suggest that the association of depression with cannabis dependence is more significant in boys than girls in this population of adolescents.

Scientific Significance: Understanding comorbidity between depression and cannabis use is important in order to disentangle the etiological relationship between the two and also for designing more effective treatment and prevention strategies, particularly in Native Americans who are at high risk for both disorders. (Am J Addict 2012;21:536–543)