Evaluating Contributors to Relapse in Comorbid Major Depressive Disorder and Cannabis Use Disorder

点击翻译按钮获取中文摘要

Nearly one-fifth of individuals that have used cannabis in the past year have Cannabis Use Disorder (CUD), and nearly one-third of individuals with CUD have comorbid Major Depressive Disorder (MDD). Comorbid MDD/CUD is associated with greater rates of addiction treatment-seeking and worse treatment outcomes relative to CUD alone. However, there is no available pharmacotherapy for CUD and the few clinical trials targeting comorbid MDD/CUD have been unsuccessful. One potential explanation for worsened clinical outcomes in comorbid MDD/CUD is that two major contributors to relapse in CUD, cannabis withdrawal symptoms and stress, may be enhanced by the addition of MDD. This is hypothesized due to the overlap across cannabis withdrawal and MDD symptoms and the enhanced stress response observed in people with MDD alone relative to neurotypical individuals. Both cannabis withdrawal and stress response are regulated by the endocannabinoid (eCB) system; evidence of this has been observed both centrally (in brain) and peripherally (in blood). Because the eCB system has been associated with these major contributors to relapse, it presents a potential target for the development of addiction pharmacotherapy. Furthermore, eCB dysregulation observed in people with MDD compared to neurotypical individuals suggests eCB modulation may have additional utility in people with comorbid MDD/CUD relative to CUD alone. However, it is currently unknown if the eCB system is uniquely dysregulated in comorbid MDD/CUD relative to CUD alone (Aim 1), if cannabis withdrawal severity is enhanced in comorbid MDD/CUD relative to CUD alone (Aim 2), or if comorbid MDD/CUD is associated with enhanced stress responding relative to CUD alone (Aim 3). To address these aims, thirty adults (15 CUD, 15 MDD/CUD) will be recruited to complete four in-person laboratory visits over one week. The first visit will be completed during cannabis use-as-usual and the remaining three visits will occur during acute withdrawal. Blood samples will be collected at three time points during each visit to assess eCB tone and participants will complete cannabis withdrawal symptom assessments at multiple time points over the week. On the final day of study participation, participants will be subjected to a social stress test. Subjective experiences of stress and drug craving, objective biomarkers of stress such as blood cortisol and heart rate, and blood eCBs will be collected prior to stress exposure and at four time points thereafter. Outcomes from the proposed project will be used to determine the relevance of eCB modulation as a pharmacotherapeutic strategy for comorbid MDD/CUD in the context of future clinical trial development. Over the course of the proposed project, the applicant (Erin Martin) will receive mentorship in key aspects of translational research including study design and implementation, scientific communication, and advanced statistical analysis. This training will be applied to the development of a future independent research program examining addiction in people with psychiatric comorbidities.