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Cannabis use and the development of depression symptoms have been linked in prospective research. However, no research has examined how depression symptoms might change relative to reductions in cannabis use. One group at risk for comorbid cannabis-use disorders and clinical depression is female emerging adults (those aged 18–25 years old) as cannabis use peaks during this period, depression is the most common psychiatric disorder among emerging adults, and females are at increased risk for depression relative to males. This study examined the longitudinal association between reductions in cannabis use and existing depression symptoms.Secondary analyses from a cannabis intervention trial for 332 female emerging adults were conducted. Changes in depression symptoms (categorized as minimal, mild, and moderate or more severe depression) were assessed in relation to changes in cannabis use at 3- and 6-months postbaseline assessment.After controlling for alcohol use, the association between change in cannabis-use frequency and change in depression (measured by Beck Depression Inventory-II) was significantly stronger for those with mild depression (b = −0.26; 95% CI: −0.44, −0.08; P = .004), and for those with moderate or more severe depression (b = −0.50; 95% CI: −0.68, −0.33; P < .001) relative to those with minimal depression.These results indicate a relationship between reductions in cannabis use and reductions in depression symptoms among female emerging adults who report at least mild depression symptoms. This represents a clinically meaningful effect for clinicians treating patients with co-occurring cannabis use and depressive disorders.