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Background: Craving is a core clinical feature of cannabis use disorder (CUD) and a predictor of treatment outcomes, yet its temporal course during treatment is not well characterized. This study aimed to identify latent classes of cannabis craving trajectories among adults with CUD and examine associated baseline predictors and cannabis use outcomes.

Methods: This was a secondary analysis of the National Drug Abuse Treatment Clinical Trials Network’s CTN-0053 trial, a 12-week, multisite randomized controlled trial of N-acetylcysteine versus placebo for adults with CUD (N = 302). Cannabis craving was measured using the Marijuana Craving Questionnaire–Short Form at six treatment timepoints (weeks 1–5, 9 and 12) and one 5-week post-treatment follow-up (week 17). Urine cannabinoid tests were conducted twice weekly throughout treatment and follow-up. Latent class growth analysis identified craving trajectories. The present study aimed to identify latent classes of cannabis craving over 12 weeks of treatment and examine baseline predictors of class membership.

Results: A four-class solution provided the best fit: low craving (41%), moderate-decreasing craving (38%), moderate-stable craving (11%), and high craving (10%). Participants in higher craving classes exhibited greater baseline anxiety, depression, and obsessive-compulsive symptoms related to cannabis use. The high craving class had the greatest proportion of cannabis positive urine tests (96%) and the lowest urine test completion rate.

Conclusions: Craving follows heterogeneous trajectories during CUD treatment and is associated with co-occurring mental health symptoms and poorer outcomes. Dynamic craving assessment may support personalized treatment and strategies to prevent return to use.

Related protocols: CTN-0053

Over the past two decades, the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) has made major contributions to progress in substance use treatment research. However, contributions to research addressing the considerable medical and mental health comorbidities of substance use, which can impede treatment efficacy and compromise health, have been emphasized less. In this Commentary, we review the contributions of CTN studies focused on medical comorbidities, initially centered on the HIV epidemic in people who use drugs, and subsequently broadening to address hepatitis C and life-threatening bacterial infections; as well as mental health comorbidities, especially post-traumatic stress disorder, attention-deficit/hyperactivity disorder, and suicidality. These studies demonstrate that comorbidities assessments and treatment can be feasibly implemented in substance use treatment programs and, conversely, that substance use assessments and treatments can be feasibly implemented in clinical care sites. We highlight the NIDA CTN Data Share as an invaluable resource for secondary analyses of comorbidities using data from CTN substance use treatment protocols and provide examples of its use. We describe the work of the CTN Comorbidities of Substance Use Special Interest Group (SIG), formerly known as the HIV SIG, as an example of the role that SIGs can play in facilitating CTN research in areas of emerging significance. We emphasize the importance of implementing a “whole person” approach—one that integrates both substance use and comorbidities outcomes. We identify promising opportunities for conducting this research by studying strategies for integrating prevention, screening, linkage, treatment, adherence, and retention support for comorbidities into substance use disorder (SUD) treatment venues; as well as strategies for integrating SUD treatment into primary care venues, hospitals, and other non-SUD clinical settings.

Adolescent substance use (SU) presents a distinct public health challenge, as this developmental stage carries heightened vulnerability for progression to problematic use. Early SU—before age 18—is a major risk factor for later Substance Use Disorders (SUD), with long-term neurobiological and psychosocial consequences. National surveillance data show a continued decline in alcohol and cigarette use, yet persistent concerns around cannabis (including synthetic variants) and sharp increases in vaping. The frequent occurrence of polysubstance use further complicates prevention and intervention efforts.

The intersection of SU and mental health conditions, such as anxiety and depression, compounds these challenges. The 2024 National Survey on Drug Use and Health data reveal that nearly one-third (27.9%) of adolescents aged 12–17 with both SUD and a Major Depressive Episode receive no treatment for either condition. Despite promising evidence-based interventions, their implementation remains limited, revealing a critical translational gap between research efficacy and real-world effectiveness.

To close this gap, the National Drug Abuse Treatment Clinical Trials Network (CTN) is leveraging its multi-site research infrastructure to conduct pragmatic clinical trials that emphasize the inclusion of adolescents from all backgrounds. The CTN’s agenda identifies six priorities to advance scalable, impactful solutions:

• Implementation Science and Real-World Effectiveness – embedding interventions into existing systems of care.
• Precision Medicine and Personalized Interventions – integrating biological, psychological, and social data to tailor treatments.
• Family and Environmental Contexts – expanding family-based and peer-supported models.
• Digital Innovations and Technology Integration – evaluating technology-assisted and AI-driven interventions.
• Longitudinal Outcomes and Lifespan Perspective – assessing developmental, academic, and quality-of-life outcomes over time.
• Community-Led and Co-Designed Research – engaging community partners and individuals with lived experience as co-researchers.

Through this coordinated agenda, the CTN aims to build an equitable, evidence-informed framework that bridges discovery and practice, drives innovation, and informs policies that foster resilient, healthy futures for adolescents nationwide.

Introduction: Hospitalizations are common among people with opioid use disorder (OUD). While hospitalizations represent opportunities to engage patients and offer treatment, they are also destabilizing events associated with an increased risk of death in the post-hospitalization period.

Methods: We conducted a retrospective cohort study within the Veterans Health Administration including all Veterans with OUD who experienced at least one medical hospitalization between January 2011 and December 2021 (part of CTN-0087). We examined which patient-level clinical and demographic factors were associated with all-cause and opioid-related mortality within 0-30 and 0-365 days following an index medical hospitalization.

Results: The cohort included 90,920 Veterans with OUD who experienced one or more medical hospitalizations during the study period. Median age was 58 years, and 93% were male. Older age (adjusted Odds Ratio [aOR] range 30d: 1.50-2.66; 1y: 1.58-3.28), higher medical complexity (aOR range 30d: 2.11-6.23; 1y: 1.96-7.34), multiple substance use disorders (SUD; aOR 30d: 1.81 (95% CI 1.44, 2.27) 1y: 1.48 [95% CI 1.36, 1.62]), and length of hospitalization (aOR 30d: 6.78 [95% CI 4.85, 9.47] 1y: 3.45 [95% CI 2.96, 4.01]) were associated with increased all-cause mortality following hospitalization. Homelessness (aOR 30d: 0.75 [95% CI 0.63, 0.90]; 1y: 0.85 [95 % CI 0.80, 0.91]), depression (aOR 1y: 0.89 [95 % CI 0.84, 0.95]), bipolar disorder (aOR 1y: 0.88 [95% CI 0.82, 0.94]), buprenorphine receipt (aOR 1y: 0.79 [95% CI 0.69, 0.91]), and service connection (aOR 30d: 0.76 [95% CI 0.60, 0.97] 1y: 0.64 [95 % CI 0.59, 0.70]) were associated with reduced all-cause mortality. Younger age (aOR range 30d: 3.21-5.24; 1y: 2.71-2.38), homelessness (aOR 1y: 1.40 [95% CI 1.20, 1.63]), and multiple SUD (aOR 1y: 1.78 [95% CI 1.33, 2.38]) were among factors associated with increased opioid-related mortality after hospitalization. Black race (aOR 1y: 0.61 [95% CI 0.50, 0.74]) and higher service connection (aOR 30d: 0.41 [95 % CI 0.21, 0.81]; 1y: 0.53 [95% CI 0.43-0.66]) were associated with reduced opioid-related mortality after hospitalization.

Conclusions: Several patient-level factors were associated with increased all-cause mortality (e.g., length of hospital stay), reduced all-cause mortality (e.g., homelessness), increased opioid-related mortality (e.g., multiple SUD), and reduced opioid-related mortality (e.g., service connection) after hospitalization. This information provides a roadmap for future development and study of tailored supports and risk stratification tools to enhance post-hospitalization transitional care for patients with OUD.

Related protocols: CTN-0087

Buprenorphine and other medication treatments for opioid use disorder (OUD) in general medical settings are effective in preventing drug overdoses related to opioid use, although treatment retention is often challenging. Real-world data indicate high medication discontinuation rates at 6 months or greater following treatment initiation, partially indicative of a common failure to optimize medication dosing to minimize side effects, maximize therapeutic effects, and sustain treatment engagement and adherence. These barriers hinder the achievement of optimal clinical outcomes in managing conditions like OUD, which is often a chronic relapsing condition and frequently associated with mood disorders. Measurement-based care (MBC) may be defined as an evidence-based healthcare approach in which systematic outcome monitoring of disease severity and symptomatology over time yields actionable feedback to providers to guide their clinical decision-making on how to customize medication dosing promptly to improve patients’ treatment outcomes.

This opinion piece describes a proposed research agenda evaluating measurement-based care for opioid use disorder among patients with co-occurring depressive disorders that emphasizes pragmatic, multisite effectiveness-implementation trials to operationalize MBC in real-world, community-based, and primary care settings. The National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) is positioned as a potential platform for advancing this agenda, leveraging its experience in bridging research and practice.

Objectives: Assessment and counseling are recommended for individuals with prenatal cannabis use. We examined characteristics that predict prenatal substance use assessment and counseling among individuals who screened positive for prenatal cannabis use in prenatal settings.

Methods: Electronic health record data from Kaiser Permanente Northern California’s Early Start perinatal substance use screening, assessment, and counseling program was used to identify individuals with =1 pregnancies positive for prenatal cannabis use. Outcomes included completion of a substance use assessment and among those assessed, attendance in Early Start counseling only or Addiction Medicine Recovery Services (AMRS) treatment. Predictors included demographics and past-year psychiatric and substance use disorder diagnoses evaluated with GEE multinomial logistic regression.

Results: The sample included 17,782 individuals with 20,398 pregnancies positive for cannabis use (1/2011-12/2021). Most pregnancies (80.3%) had an assessment. Individuals with Medicaid, anxiety, depression and tobacco use disorders, compared to those without, had higher odds and those with greater parity, older age (=35) and in later trimesters, had lower odds of assessment. Among 64% (n = 10,469) pregnancies needing intervention based on assessment, most (88%) attended Early Start counseling only or AMRS (with or without Early Start). Greater parity and later trimester assessment was associated with lower odds, while Medicaid was associated with higher odds of Early Start counseling. Nearly all diagnosed psychiatric and substance use disorders were associated with higher odds of AMRS treatment.

Conclusions: A comprehensive prenatal substance use program engaged most pregnant individuals with prenatal cannabis use in substance use assessment and counseling. Opportunities to improve care gaps remain.

Related protocols: CTN-0140

The goal of this study, part of CTN-0140 (Cannabis Use Among Pregnant Women with Polysubstance Use and Psychiatric Problems), was to estimate the strength of association between psychiatric disorders and substance use disorders (SUD), and cannabis use and cannabis use disorder (CUD) during early pregnancy. Participants were 299,496 pregnancies from 227,555 individuals screened for cannabis use by self-report and a urine toxicology test at entrance to prenatal care in Kaiser Permanente Northern California during January 2011-December 2021 (excepting year 2020). The sample was 62.5% non-White, with a mean (standard deviation) age of 31.1 (5.5) years; 6.8% used cannabis; 0.2% had a CUD.

Exposure variables included electronic health record-based psychiatric diagnoses of attention deficit hyperactivity, anxiety, bipolar, depressive, personality, posttraumatic stress and psychotic disorders; and alcohol, opioid, stimulant and tobacco use disorders, during the two years prior to pregnancy up to the day before the prenatal substance use screening date. Outcome variables were any cannabis use, frequency of self-reported cannabis use and CUD during early pregnancy.

Psychiatric disorder prevalence ranged from 0.2% (psychotic) to 14.3% (anxiety), and SUD ranged from 0.3% (stimulant/opioid) to 3.8% (tobacco). Psychiatric disorders were associated with cannabis use and CUD, with the strongest association for any use found for bipolar disorder (adjusted odds ratio [aOR] = 2.83; 95% confidence interval [CI] = 2.53-3.17) and the strongest association for CUD found for psychotic disorders (aOR = 10.01, 95% CI = 6.52-15.37). SUDs were associated with cannabis use and CUD, with the strongest association for any use found for tobacco use disorder (aOR = 4.03, 95% CI = 3.82-4.24) and the strongest association for CUD found for stimulant use disorder (aOR = 21.99, 95% CI = 16.53-29.26). Anxiety, bipolar, depressive disorders and tobacco use disorder were associated with greater odds of daily than monthly or less cannabis use.

Conclusions: Psychiatric disorders and substance use disorders appear to be associated with elevated odds of any and frequent cannabis use as well as cannabis use disorder during early pregnancy. In most cases, the associations with cannabis outcomes were stronger for substance use disorders than other psychiatric disorders.

Related protocols: CTN-0140

This secondary analysis of CTN-0049 and CTN-0064 aimed to determine whether endorsement patterns of psychosocial symptoms revealed distinct subgroups, or latent classes, of people living with HIV who use substances (PLWH-SU), and to assess whether these classes demonstrated differential health outcomes over time. It uses data from 801 PLWH-SU initially enrolled across 11 US hospitals during 2012–2014 (CTN-0049) and followed up in 2017 (CTN-0064). Latent class analysis included 28 psychosocial items. Regression analysis examined class membership as a predictor of viral suppression. Survival analysis examined class as a predictor of all-cause mortality. The selected model identified five unique classes. Individuals in classes characterized by more severe and more numerous psychosocial symptoms at baseline had lower likelihoods of viral suppression and survival.

Conclusions: The study demonstrated the importance of considering patterns of overlapping psychosocial symptoms to identify subgroups of PLWH-SU and reveal their risks for adverse outcomes. Integration of primary, mental health, and substance use care is essential to address the needs of this population.

Related protocols: CTN-0049, CTN-0064

Suicide is the tenth leading cause of death in the United States and continues to be a major public health concern. Suicide risk is highly prevalent among individuals with co-occurring substance use disorders (SUD) and mental health disorders, making them more prone to adverse substance use related outcomes including overdose. Identifying individuals with SUD who are suicidal, and therefore potentially most at risk of overdose, is an important step to address the synergistic epidemics of suicides and overdose fatalities in the United States. The current study assesses whether patterns of suicidality endorsement can indicate risk for substance use and overdose.

Latent class analysis (LCA) was used to assess patterns of item level responses to the Concise Health Risk Tracking Self-Report (CHRT-SR), which measures thoughts and feelings associated with suicidal propensity. We used data from 2,541 participants with SUD who were enrolled across 8 randomized clinical trials in the National Drug Abuse Treatment Clinical Trials Network from 2012 to 2021 (CTN-0037, -0049, -0051, -0053, -0054, -0064, -0067, -0068). Characteristics of individuals in each class were assessed, and multivariable logistic regression was performed to examine class membership as a predictor of overdose. LCA was also used to analyze predictors of substance use days.

Three classes were identified and discussed: Class (1) Minimal Suicidality, with low probabilities of endorsing each CHRT-SR construct; Class (2) Moderate Suicidality, with high probabilities of endorsing pessimism, helplessness, and lack of social support, but minimal endorsement of despair or suicidal thoughts; and Class (3) High Suicidality with high probabilities of endorsing all constructs. Individuals in the High Suicidality class comprise the highest proportions of males, Black/African American individuals, and those with a psychiatric history and baseline depression, as compared with the other two classes. Regression analysis revealed that those in the High Suicidality class are more likely to overdose as compared to those in the Minimal Suicidality class (p = 0.04).

Conclusions: Suicidality is an essential factor to consider when building strategies to screen, identify, and address individuals at risk for overdose. The integration of detailed suicide assessment and suicide risk reduction is a potential solution to help prevent suicide and overdose among people with SUD.

Related protocols: CTN-0037, CTN-0049, CTN-0051, CTN-0053, CTN-0054, CTN-0064, CTN-0067, CTN-0068

Co-occurring substance use disorders (SUDs) among individuals with opioid use disorder (OUD) are associated with additional impairment, overdose, and death. This study, a secondary analysis of data from CTN-0102, examined characteristics of patients who have OUD with and without co-occurring SUDs in rural primary care clinics.

Researchers analyzed data from six rural primary care clinics, including demographics, diagnoses, encounters, and prescriptions of medication for OUD (MOUD), as well as EHR data from an external telemedicine vendor that provided MOUD to some clinic patients. The study population included all adult patients who had a visit to the participating clinics from October 2019 to January 2021.

The authors identified 1164 patients with OUD; 72.6 % had OUD only, 11.5 % had OUD and stimulant use disorder (OUD + StUD), and 15.9 % had OUD and other non-stimulant substance use disorder (OUD + Other). The OUD + StUD group had the highest rates of hepatitis C virus (25.4 % for OUD + StUD, 17.8 % for OUD + Other, and 7.5 % for OUD Only; p < 0.001) and the highest rates of mental health disorders (78.4 %, 69.7 %, and 59.9 %, respectively; p < 0.001). Compared to the OUD Only group, patients in the OUD + StUD and OUD + Other groups were more likely to receive telehealth services provided by clinic staff, in-clinic behavioral health services, and in-clinic MOUD. The OUD + StUD group had the highest proportion of referrals to the external telemedicine vendor.

Conclusions: More than 27 % of patients with OUD in rural primary care clinics had other co-occurring SUDs, and these patients received more healthcare services than those with OUD only. Future studies should examine variations in outcomes associated with these other services among patients with OUD and co-occurring SUDs.

Related protocols: CTN-0102

To inform clinical practice, researchers identified subgroups of adults based on levels of depression symptomatology over time during opioid use disorder (OUD) treatment. Participants were 474 adults in a 24-week treatment trial for OUD. Depression symptoms were measured using the 17-item Hamilton Depression Rating Scale (HAM-D) at nine-time points. This was a secondary analysis of the Clinical Trials Network Extended-Release Naltrexone versus Buprenorphine for Opioid Treatment (X:BOT, CTN-0051) trial using a growth mixture model.

Three distinct depression trajectories were identified: Class 1 High Recurring-10% with high HAM-D with initial partial reductions (of HAM-D across time), Class 2 Persistently High-5% with persistently high HAM-D, and Class 3 Low Declining-85% of the participants, with low HAM-D with early sustained reductions. The majority (low declining) had levels of depression that improved in the first 4 weeks and then stabilized across the treatment period. In contrast, 15% (high recurring and persistently high) had high initial levels that were more variable across time. The persistently high class had higher rates of opioid relapse.

Conclusions: In this OUD sample, most depressive symptomatology was mild and improved after medication treatment for opioid use disorder (MOUD). Smaller subgroups had higher depressive symptoms that persisted or recurred after the initiation of MOUD. Depressive symptoms should be followed in patients initiating treatment for OUD, and when persistent, should prompt further evaluation and consideration of antidepressant treatment. This study is the first to identify three distinct depression trajectories among a large clinical sample of individuals in MOUD treatment.

Related protocols: CTN-0051

In this study, the researchers sought to characterize the 3-year prevalence of mental disorders and non-nicotine substance use disorders among male and female primary care patients with documented opioid use disorder across large U.S. health systems.

This retrospective study used 2014–2016 data (from CTN-0074) from patients ages =16 years in six health systems. Diagnoses were obtained from electronic health records or claims data; opioid use disorder treatment with buprenorphine or injectable extended-release naltrexone was determined through prescription and procedure data. Adjusted prevalence of comorbid conditions among patients with opioid use disorder (with or without treatment), stratified by sex, was estimated by fitting logistic regression models for each condition and applying marginal standardization.

Females (53.2%, N=7,431) and males (46.8%, N=6,548) had a similar prevalence of opioid use disorder. Comorbid mental disorders among those with opioid use disorder were more prevalent among females (86.4% vs. 74.3%, respectively), whereas comorbid other substance use disorders (excluding nicotine) were more common among males (51.9% vs. 60.9%, respectively). These differences held for those receiving medication treatment for opioid use disorder, with mental disorders being more common among treated females (83% vs. 71%) and other substance use disorders more common among treated males (68% vs. 63%). Among patients with a single mental health condition comorbid with opioid use disorder, females were less likely than males to receive medication treatment for opioid use disorder (15% vs. 20%, respectively).

Conclusions: The high rate of comorbid conditions among patients with opioid use disorder indicates a strong need to supply primary care providers with adequate resources for integrated opioid use disorder treatment.

Related protocols: CTN-0074

Black women are at heightened risk for trauma exposure, post-traumatic stress disorder (PTSD), and substance use disorders (SUDs) compared to white women and the general population. However, disparities in treatment engagement and retention persist, particularly for Black women with co-occurring PTSD and SUD. Although therapeutic alliance is an important predictor and mediator of treatment retention and outcomes, we know little about predictors of alliance and the mediating role of alliance for PTSD+SUD outcomes among Black women.

This study used data previously collected for the National Drug Abuse Treatment Clinical Trials Network (CTN) Women and Trauma Study (CTN-0015), which compared Seeking Safety (a cognitive-behavioral intervention for PTSD+SUD) to Women’s Health Education (control). It includes 88 Black/African American women from both arms of the original trial. Measures included the Helping Alliance Questionnaire, Addiction Severity Index-Lite, and Clinician Administered PTSD Scale. Women in the intervention arm also completed the Seeking Safety Feedback Questionnaire.

Stepwise, hierarchical linear regressions indicted that years of education and previous alcohol/drug treatment attempts significantly predicted early alliance in the second week of therapy, but not late alliance in the last week of therapy. Greater education and more treatment attempts were associated with higher early alliance. Alliance did not mediate relationships between these significant predictors and treatment outcomes (e.g., attendance, post-treatment PTSD and SUD symptoms) or treatment feedback in the Seeking Safety group.

Conclusions: Education and prior treatment attempts predicted early alliance among Black/African American women in PTSD+SUD group treatment, and higher education level was associated with poorer Seeking Safety feedback topic ratings. Educational level and treatment history should be considered during alliance building in therapeutic interventions with Black women. Clinicians may consider the integration of pre-treatment alliance-building strategies with Black female patients who have lower levels of education. This study provides insight into the relative impact of several important factors that influence early alliance among Black women with co-occurring PTSD and SUD.

Related protocols: CTN-0015

Recent studies indicate that sex-based differences exist in co-occurring psychiatric symptoms and disorders among individuals with opioid use disorders (OUD). Whether these associations are present in adolescent samples and change during OUD treatment is poorly understood.

In this study, researchers examined sex-based differences in psychiatric symptoms and relationships among sex, psychiatric symptoms, and opioid use outcomes in youth with OUD receiving buprenorphine/naloxone (Bup/Nal) and psychosocial treatment.

The study randomly assigned 152 youth (15-21 years old) diagnosed with OUD to either 12 weeks of treatment with Bup/Nal or up to 2 weeks of Bup/Nal detoxification with both treatment arms receiving weekly drug counseling as part of a multisite clinical trial (CTN-0010). Researchers compared psychiatric symptoms, assessed via the Youth Self Report (YSR) at baseline and week 12, across male and female OUD participants. The study used logistic regression models to identify sex and psychiatric symptom variables that were predictors of opioid positive urine (OPU) at week 12.

Compared to males, females with OUD had higher mean psychiatric symptom scores at baseline across broad-band and narrow-band symptom domains. The study observed significant reductions in psychiatric symptoms scores in both males and females during treatment, and by week 12, females only differed from males on anxious-depressive symptom scores. Females, in general, and youth of both sexes presenting to treatment with higher anxious depression scores were less likely to have a week-12 OPU.

Conclusions: Clinically significant sex-based differences in psychiatric symptoms are present at baseline among youth with OUD receiving Bup/Nal-assisted treatment and mostly resolve during treatment.

Related protocols: CTN-0010

This study examined the associations of multiple psychiatric and chronic conditions with the self-reported history of major depressive disorder (MDD) among patients with opioid use disorder (OUD) and tested whether the associations differed by gender. Using data from CTN-0027 (START), a clinical trial including 1,646 participants with OUD, of which 465 had MDD, a variable cluster analysis was used to classify chronic medical and psychiatric conditions. Multivariate logistic regression analyses were used to estimate their associations with MDD in subjects with OUD.

Nine variables were divided into three clusters: cluster 1 included heart condition, hypertension, and liver problems; cluster 2 included gastrointestinal (GI) problems and head injury; and cluster 3 included anxiety disorder, bipolar disorder, and schizophrenia. The overall prevalence of MDD in participants with OUD was 28.3% (22.8% for males and 39.5% for females). Gender, anxiety disorder, schizophrenia, liver problems, heart condition, GI problems, and head injury were significantly associated with MDD. Gender-stratified analyses showed that bipolar disorder, liver problems and individuals with one chronic condition were associated with MDD only in males, whereas heart condition, hypertension, and GI problems were associated with MDD only in females. In addition, anxiety disorder, head injury, individuals with one or more than two psychiatric conditions, and individuals with more than two chronic conditions were associated with MDD regardless of gender.

Conclusions: This study showed a high prevalence of MDD in individuals with OUD as compared to the general population. In those with OUD, there is a significant association between MDD and gender, anxiety disorder, liver problems, heart condition, GI problems, and head injury. Furthermore, multiple psychiatric and chronic conditions were significantly associated with MDD. Additionally, gender-stratified analyses showed that bipolar disorder, liver problems and one chronic condition was associated with MDD in males, while heart condition, hypertension, and GI problems were associated with MDD only in females. Treatment plans in patients with OUD should not only address MDD but also co-morbid psychiatric and chronic medical conditions that occur with MDD.

Related protocols: CTN-0027