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Abstract: 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

Abstract:

Abstinence is rarely achieved in clinical trials for cannabis use disorder (CUD). Cannabis reduction is associated with functional improvement, but reduction endpoints have not been established, indicating a need to identify and validate clinically meaningful reduction endpoints for assessing treatment efficacy.

In this study, data from a 12-week double-blind randomized placebo-controlled medication trial for cannabis cessation (CTN-0053, ACCENT) were analyzed. Participants (N = 225) were treatment-seeking adults, M = 30.6 (8.9) years old, 70.2% male, and 42.2% non-white, with CUD who completed 12 weeks of treatment. Frequency (days of use per week) and quantity (grams per using day) were used to define high-, medium-, and low-risk levels. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale and cannabis-related problems were assessed using the Marijuana Problems Scale. General linear models for repeated measures tested associations between the magnitude of risk reduction and functional outcomes from baseline (BL) to end-of-treatment (EOT).

Results found that cannabis risk levels were sensitive to reductions in use from BL to EOT for frequency- and quantity-based metrics. Magnitude reduction in frequency-based risk level was associated with magnitude decrease in depression, anxiety, and cannabis-related problems. Magnitude reduction in quantity-based risk level was associated with magnitude decrease in anxiety and cannabis-related problems.

Conclusions: Cannabis use risk levels, as operationalized in this study, captured reductions in use during a clinical trial. Risk level reduction was associated with functional improvement suggesting that identifying risk levels and measuring the change in levels over time may be a viable and clinically meaningful endpoint for determining treatment efficacy.

Related protocols: CTN-0053

Abstract:

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

Abstract:

This study examined the associations of polysubstance use, mood disorders, and chronic conditions with the history of anxiety disorder among patients with opioid use disorder (OUD). Researchers performed a secondary analysis of the baseline data from NIDA-CTN-0027 (“Starting Treatment with Agonist Replacement Therapies (START)”), a clinical trial that included 1,645 individuals with OUD, of which 513 had anxiety disorder. Substance use disorder (SUDs) included alcohol, amphetamines, cannabis, cocaine, and sedative use disorders. Mood disorders included major depressive disorder (MDD) and bipolar disorder (BD). Chronic conditions were allergies, gastrointestinal problem(s), skin problem(s), and hypertension. Sedative use disorder, MDD, BD, skin problems, and hypertension were significantly associated with anxiety disorder. Additionally, more than two SUDs, two mood disorders, and more than two chronic conditions were significantly associated with anxiety disorder.

Conclusions: These findings highlight the comorbid mental health and physical health problems in individuals with OUD, as well as the need for integrated multidisciplinary treatment plans. Future areas of research should focus on not only OUD, but also patients presenting with other comorbidities to identify more vulnerable groups, discover effective solutions, and reduce the prevalence of OUD.

Related protocols: CTN-0027

Abstract:

Individuals treated for opioid use disorder (OUD) have high rates of psychiatric disorders potentially diminishing treatment outcomes. This study examined long-term treatment experiences and outcomes by type of psychiatric disorder among participants in the NIDA Clinical Trials Network Starting Treatment with Agonist Replacement Therapies (START) study (CTN-0027) and its follow-up study (CTN-0050).

Researchers categorized the 593 participants who completed the Mini-International Neuropsychiatric Interview (MINI) during the START follow-up study into four mutually exclusive groups to indicate current psychiatric diagnosis: 1) bipolar disorder (BPD; n=51), 2) major depressive disorder (MDD; n=85), 3) anxiety disorder (AXD; n=121), and 4) no comorbid mental disorder (NMD; n=336). Participants’ baseline characteristics and treatment outcomes were then compared.

Groups with mental disorders had worse substance use outcomes and poorer psychosocial functioning than the NMD group. Participants with BPD had significantly more self-reported days using opioids (mean: 8.6 for BPD vs. 3.4 days for NMD) and heroin (mean: 6.4 for BPS vs. 2 for MDD, 3.1 days for NMD) in the 30 days prior to the final interview. Compared to patients without mental disorders, patients with MDD spent more time engaged with OUD pharmacotherapy during the ~16 month period between MINI and final interview (mean: 71.6% vs. 50.6%).

Conclusions: Results show that treatment outcomes in individuals with OUD vary by psychiatric comorbidity groups, which supports the need for mental health assessment and treatment for psychiatric conditions in the context of pharmacotherapy for patients with OUD.

Related protocols: CTN-0027, CTN-0050

Abstract:

Sleep disturbance may play a role in cocaine use outcomes and, hence, may be a potential therapeutic target for cocaine use disorder (CUD). Research in this area, which has largely relied on resource-intensive polysomnography, would be facilitated by identifying a self-report sleep measure predictive of CUD outcomes and by a better understanding of the mechanisms by which sleep may impact CUD outcomes.

This study, a secondary analysis of CTN-0046 (Smoking Cessation and Stimulant Treatment), tested the predictive validity of the Pittsburgh Sleep Quality Index (PSQI), a self-report assessment of past-month sleep quality. To better understand potential mechanisms, mediation models relating sleep disturbance to CUD outcomes were evaluated.

The PSQI was collected at baseline; the outcomes of interest were cocaine and drug abstinence at end-of-treatment (weeks 9-10). Potential mediators, measured in weeks 1-8, were: cocaine craving (Brief Substance Craving Scale); and anxiety and depression symptoms (Hospital Anxiety and Depression Scale). Mediation techniques were used to evaluate mediation effects separately and jointly.

The majority of participants (58.3%) had baseline sleep disturbance. Sleep disturbance was not a significant predictor of end-of-treatment abstinence when regressed without consideration of mediators. Cocaine craving, anxiety, and depression were significant mediators, both separately and jointly, of an effect of baseline sleep disturbance on end-of-treatment abstinence.

Conclusions: This exploratory analysis suggests that there may be an indirect relationship between self-reported sleep quality and substance use outcomes in cocaine-dependent patients, mediated by craving, anxiety, and depression.

Related protocols: CTN-0046

Abstract:

This study examined the longitudinal association between reductions in cannabis use and changes in anxiety, depression, sleep quality, and quality of life. Secondary analyses were conducted based on data from a cannabis use disorder medication trial in 302 adults, NIDA Clinical Trials Network protocol CTN-0053, Achieving Cannabis Cessation: Evaluating N-Acetylcysteine Treatment (ACCENT). Changes in symptoms of anxiety and depression, sleep quality, and quality of life were assessed in relation to changes in cannabis use during the 12-week trial of treatment.

Based on the slope of individual cannabis use trajectory, the sample was classified into two groups (Cannabis Use Reduction, n=152 vs. Cannabis Use Increase, n=150) which was included as a binary covariate in subsequent modeling. Controlling for demographics (age, gender, race/ethnicity), treatment condition, and time-varying tobacco and alcohol use, separate latent growth curve models showed a significant association between the Cannabis Use Reduction group and improvement (i.e., lower values in slope) in anxiety, depression, and sleep quality over the observation period, but not in quality of life.

Conclusions: These results indicate a longitudinal relationship between reductions in cannabis use and improvements in anxiety, depression, and sleep quality. Clinicians treating patients with co-occurring cannabis use and problems with anxiety, depression, or sleep quality should attend to cannabis use reduction as a component of treatment.

Related protocols: CTN-0053

Abstract:

This study aimed to determine if current comorbid psychiatric disorders differ in adults with cocaine use disorder, other stimulant (primarily methamphetamine) use disorder, or both, and identify demographic and clinical characteristics in those with increasing numbers of comorbid disorders. Baseline data from participants enrolled in the NIDA Clinical Trials Network’s “Stimulant Reduction Intervention using Dosed Exercise” (STRIDE) study, a multisite randomized controlled trial that compared the efficacy of high intensity exercise and health education, both augmented to substance abuse treatment as usual in adults with stimulant use disorders entering residential treatment settings (N=302). Mood disorders were present in 33.6%, and anxiety disorders in 29.6%, with no differences among stimulant use disorder groups. Panic disorder was more frequently present with other stimulant use disorder. Those with two or more comorbid psychiatric disorders were more often female, white, had more symptoms of depression, greater propensity and risk for suicidal behavior, lower functioning in psychiatric and family domains, lower quality of life, more symptoms with stimulant abstinence and greater likelihood of marijuana dependence. Those with one or more comorbid disorders had more medical disorder burden, lower cognitive and physical functioning, greater pain, and higher rates of other drug dependence.

With current comorbid psychiatric disorders, the morbidity of stimulant use disorders increases. Use of validated assessments near treatment entry, and a treatment plan targeting not only substance use and comorbid psychiatric disorders, but functional impairments, medical disorder burden and pain, may be useful.

Related protocols: CTN-0037

Abstract:

Already the most commonly used illicit drug worldwide, cannabis continues to rise in popularity as the perception of its harmfulness decreases and evidence of its deleterious developmental effect increases. While internalizing distress and suicide risk have been linked with cannabis use problems (DSM-5 cannabis use disorder (CUD); DSM-IV cannabis abuse and dependence) it remains unclear how this association varies over the course of development in treatment-seeking men and women.

The current study utilized the NIDA Clinical Trials Network (CTN) to conduct a cross-sectional comparison of internalizing distress and suicide risk among men (n=437) and women (n=163) spanning ages 18-50 who met DSM-5 criteria for CUD (the sample was comprised of participants who had been screened for participation in CTN-0053). Interactions between gender and developmental stage (i.e., late adolescent, early adulthood, and middle adulthood) were observed for suicide risk and anxiety but not depression problems. Specifically, women seeking CUD treatment in late adolescence and middle adulthood exhibited significantly higher rates of anxiety and suicide risk compared to men seeking treatment during the same developmental stage. Internalizing distress and suicide risk did not differ between treatment-seeking men and women in the early adult stage.

Conclusions: This study is the first to utilize a gender differences framework to estimate how concurrent psychosocial problems associated with CUD may be moderated by development stage in those presenting for care. Results suggest that the structure of risk for CUD may differ in men and women across the lifespan and that women presenting for CUD treatment during late adolescence and middle adulthood may uniquely benefit from intervention designed to address these elevations in anxiety and suicide risk.

Related protocols: CTN-0053

Abstract:

Eating disorders (ED) and substance use disorders (SUD) commonly co-occur, especially in conjunction with posttraumatic stress disorder (PTSD), yet little is known about ED and ED symptoms in women presenting to addiction treatment programs. This study examined the association between ED symptoms and substance use frequency and severity in a sample of women with a DSM IV diagnosis of current SUD and PTSD enrolled in SUD treatment. Participants were 122 women from four substance abuse treatment sites who participated in a multi-site clinical trial through NIDA’s Clinical Trials Network (CTN). The Eating Disorder Examination-Questionnaire (EDE-Q), the Clinician Administered PTSD Scale (CAPS), and the Addiction Severity Index (ASI) were administered at baseline and correlational analyses were performed. Variables that significantly correlated with EDE-Q total and subscale scores were entered into a linear regression analysis. Results found that scores on the EDE-Q Global scale, as well as the Eating Concern, Weight Concern, and Shape Concern subscales of the EDE-Q were significantly associated with Caucasian race/ethnicity, past 30 day opiate use, higher ASI Psychiatric Subscale score, and lower ASI Employment Subscale score.

Conclusions: Women in recovery from SUD and PTSD reported concerns about weight, shape, and eating at a higher rate than in the general US population of women. The finding that past 30 day opiate use was associated with EDE scores may indicate that opiates also play a substantial role in disordered eating symptoms. Though exploratory, these findings suggest that there may be a relationship between addiction severity, use of certain drugs of abuse, and eating disorder symptoms, particularly those involving weight and shape concerns in women with comorbid PTSD and SUD. Comprehensive and integrated treatment approaches need to be developed to address this complex but common comorbidity.

Related protocols: CTN-0015, CTN-0015-A-1

Abstract:

A preponderance of relevant research has indicated reduction in anxiety and depressive symptoms following smoking abstinence. This secondary analysis of data from the National Drug Abuse Treatment Clinical Trials Network study CTN-0029 investigated whether the phenomenon extends to smokers with attention deficit hyperactivity disorder (ADHD). The study setting was an 11-week double-blind placebo-controlled randomized trial of osmotic release oral system methylphenidate (OROS-MPH) as a cessation aid when added to nicotine patch and counseling. Participants were 255 adult smokers with ADHD. The study outcomes were: anxiety (measured by the Beck Anxiety Inventory (BAD)) and depressed mood (Beck Depression Inventory II (BDI)), measured 1 week and 6 weeks after a target quit day (TQD). The main predictor was point-prevalence abstinence measured at weeks 1 and 6 after TQD. Covariates were treatment (OROS-MPH vs. placebo), past major depression, past anxiety disorder, number of cigarettes smoked daily, demographics (age, gender, education, marital status) and baseline scores on the BAI, BDI, and DSM-IV ADHD Rating Scale.

Results found that abstinence was significantly associated with lower anxiety ratings throughout the post-quit period (p<0.001). Depressed mood was lower for abstainers than non-abstainers at week 1 (p<0.05), but no longer at week 6 (p=0.83). Treatment with OROS-MPH relative to placebo showed significant reductions at week 6 after TQD for both anxiety (p<0.05) and depressed mood (p<0.001), but not at week 1. Differential abstinence effects of gender were observed. Anxiety and depression ratings at baseline predicted increased ratings of corresponding measures during the post-quit period.

Conclusions: Stopping smoking yielded reductions in anxiety and depressed mood in smokers with ADHD treated with nicotine patch and counseling. Treatment with OROS-MPH produced better outcomes on the post-cessation mood ratings compared to placebo, albeit in a delayed manner, suggesting that OROS-MPH could be an important adjunct for achieving smoking abstinence in this population. Validation of findings from this secondary analysis could advance discovery and development of treatments for persons dually diagnosed with nicotine dependence and ADHD.

Related protocols: CTN-0029

Abstract:

Comorbid psychiatric and substance use disorders are common and associated with poorer treatment engagement, retention, and outcomes. This study examines the presence of depressive symptoms and demographic and clinical correlates in a diverse sample of substance abuse treatment-seekers to better characterize patients with co-occurring depressive symptoms and substance use disorders and understand potential treatment needs. Baseline data from a randomized clinical effectiveness trial of a computer-assisted, web-delivered psychosocial intervention were analyzed (CTN-0044, Web Delivery of Evidence-Based, Psychosocial Treatment for Substance Use Disorders). Participants (N=507) were recruited from 10 geographically diverse outpatient drug treatment programs. Assessments included the self-report Patient Health Questionnaire, and measures of coping strategies, social functioning, physical health status, and substance use.

One-fifth (21%; n=106) of the sample screened positive for depression; those screening positive for depression were significantly more likely to screen positive for anxiety (66.9%) and PTSD (42.9%). After controlling for anxiety and PTSD symptoms, presence of depressive symptoms remained significantly associated with fewer coping strategies (p=.001), greater impairment in social adjustment (p<.001), and poorer health status (p<.001), but not to days of drug use in the last 90 days (p=.14).

Conclusions: Depression is a clinically significant problem among substance abusers and, in this study, patients who screened positive for depression were more likely to have co-occurring symptoms of anxiety and PTSD. Additionally, the presence of depressive symptoms was associated with fewer coping strategies and poorer social adjustment. Coping skills are a significant predictor of addiction outcomes and it may be especially important to screen for and enhance coping among depressed patients. Evidence-based interventions that target coping skills and global functioning among substance abusers with depressive symptoms may be important adjuncts to usual treatment. Understanding the factors that might affect outcomes is important for the planning and implementation of substance abuse treatment.

Related protocols: CTN-0044

Abstract:

Current U.S. population surveys indicate more general drug use and higher rates of illicit drug dependence for men than women, however studies also suggest that, for stimulant use, female users exceed males on the severity of dependence, and addiction severity at treatment entry for drug abuse has been linked to poorer outcomes in clinical samples.

This secondary analysis of a stimulant abusing or dependent residential treatment sample (N=302) participating in the National Drug Abuse Treatment Clinical Trials Network study CTN-0037 ( Stimulant Reduction Intervention using Dosed Exercise (STRIDE)) examined gender-specific factors associated with stimulant abstinence severity.

Bivariate statistics tested gender differences in stimulant abstinence symptoms, measured by participant-reported experiences of early withdrawal. Multivariate linear regression examined gender and other predictors of stimulant abstinence symptom severity. Women compared to men reported greater stimulant abstinence symptom severity. Anxiety disorders and individual anxiety-related abstinence symptoms accounted for this difference. African American race/ethnicity was also predictive of lower stimulant abstinence severity.

Conclusions: This study identified differences between men and women on measures of stimulant use and associated disorders, finding greater stimulant abstinence symptom severity in women compared to men. This study also suggests anxiety-related withdrawal experiences as salient topics for clinicians to address in treatment to reduce abstinence symptoms and potentially the risk for relapse to stimulant use.

Related protocols: CTN-0037

Abstract:

Severe stimulant abstinence symptoms have been shown to predict early substance abuse treatment termination. This study explored gender-specific factors associated with addiction severity, craving, and abstinence symptoms in a residential treatment seeking sample. The study analyzed data collected from stimulant abusing or dependent participants enrolled in the National Drug Abuse Treatment Clinical Trials Network’s “Stimulant Reduction Intervention using Dosed Exercise (STRIDE)” trial. Women participating in STRIDE reported greater addiction severity problems in employment, family/social, and psychiatric domains compared to men (this is consistent with similar studies). More severe abstinence symptoms in women than men appear to be associated with anxiety-related symptoms (e.g., anxiety, tension, irritability, difficultly concentrating, and panic disorder) and to be correlated with race/ethnicity. It is unknown if anxiety associated with stimulant abstinence affects treatment attrition.

Conclusions: Interventions that address gender-related abstinence may improve treatment for stimulant dependence.

Related protocols: CTN-0037

Abstract:

Research shows that interventions for substance use disorders may be helpful in reducing internalizing disorders in adolescents. This paper examines the prevalence and reductions of anxiety and depression symptoms among youth receiving substance use treatment. Four hundred and eighty adolescents ages 12-17 who received treatment for substance abuse as part of the Brief Strategic Family Therapy (BSFT) effectiveness trial in the National Drug Abuse Treatment Clinical Trials Network (protocol CTN-0014) were screened for anxiety and depression using the Diagnostic Interview Schedule for Children-Predictive Scales (DISC-PS). Twelve-month post-randomization assessments were completed by 327 parents and 315 youth. Sixty-five percent of the sample was found to have probability of at least one anxiety disorder or depression diagnosis. Significant reductions of anxiety and depressive symptoms and significant reductions in probable anxiety and depression diagnoses were observed at follow-up. Few differences by treatment type and ethnic group were noticed.

Conclusions: This article makes a novel contribution to the literature by showing that community-based drug abuse treatments may help reduce the prevalence of anxiety and depression symptoms and probability of diagnoses among adolescents. Adolescents with comorbid substance use and mental health problems constitute a unique clinical population at a very high risk for comorbid problems into adulthood to the extent that it has become one of the most pressing issues in developing and testing effective interventions for drug abuse. Results of this study suggest there were significant reductions in symptoms after treatment, even when controlling for other services that these adolescents might have received for these problems, a discovery with important clinical implications.

Related protocols: CTN-0014