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

> **NIH NIH F31** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2022 · $46,752

## Abstract

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 develo...

## Key facts

- **NIH application ID:** 10533526
- **Project number:** 1F31DA057051-01
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Erin Lindsey Martin
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10533526

## Citation

> US National Institutes of Health, RePORTER application 10533526, Evaluating Contributors to Relapse in Comorbid Major Depressive Disorder and Cannabis Use Disorder (1F31DA057051-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10533526. Licensed CC0.

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