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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.

This presentation was delivered as part of a symposium at the 2024 CPDD conference entitled, “Two-Eyed Seeing for Opioid Use Disorder Treatment and Recovery with American Indian and Alaska Native Communities,” moderated by Aimee Campbell and Carmen Rosa. In this section of the symposium, Dr. Patten discussed the development and testing of a novel, moderated, private Facebook group intervention to support AI/AN women in opioid use disorder recovery. The intervention was developed through feedback from key partners and beta tested and refined with AI/AN women in recovery.

Related protocols: CTN-0123

This is the primary outcomes article for Aim 1 of CTN-0123.

The ongoing opioid misuse epidemic has had a marked impact on American Indian/Alaska Native (AI/AN) communities. Culture- and gender-specific barriers to medically assisted recovery from opioid use disorder (OUD) have been identified, exacerbating its impact for AI/AN women. Wiidookaage’win is a community-based participatory research study that aims to develop a culturally tailored, moderated, private Facebook group intervention to support Minnesotan AI/AN women in medically assisted recovery from OUD. The current study, NIDA Clinical Trials Network study CTN-0123, assessed the preliminary feasibility and acceptability of the intervention in a beta-test to inform refinements before conducting a pilot randomized controlled trial (RCT).

The intervention was beta-tested for 30 days. Moderators were trained prior to delivering the intervention. Study assessments were conducted at baseline and post-intervention. The post-intervention assessments included substance use (self-report and urine drug screen), treatment acceptability, mental health, and spirituality outcomes. We examined intervention engagement patterns using Facebook metrics and qualitatively explored common topics that emerged in participant posts and comments.

Ten AI/AN women taking medication for OUD (MOUD) were recruited (age range 25–62 years). Participants had been in opioid recovery a mean of 15.2 months (SD = 16.1; range = 3–60). The study participation rate (accrued/eligible) was 91%. Nine participants completed the post-intervention survey assessment and eight completed a UDS. Acceptability was high based on the mean treatment satisfaction score (M = 4.8, SD = 0.2 out of a possible 5.0), Facebook group engagement, and positive qualitative feedback. All participants retained at post-intervention continued their MOUD treatment, and none had returned to opioid use.

Conclusions: The beta-test indicated that the Facebook platform and study procedures generally worked as intended and that the intervention was largely acceptable to study participants. The results of this study phase provided valuable insights to inform refinements prior to conducting a pilot RCT to further assess the feasibility, acceptability, and potential efficacy of the intervention.

Related protocols: CTN-0123

The purpose of this study, NIDA Clinical Trials Network protocol CTN-0123 was to develop a culturally-tailored American Indian/Alaska Native (AI/AN) women’s Facebook group supporting opioid recovery as an adjunct to medication. Participants were AI/AN women in Minnesota in opioid recovery, interested parties, and a Community Advisory Committee (CAC) of AI/AN women with lived experience, health care providers, and community members.

For the intervention, the study team developed evidence-based content focusing on stress/trauma and substance use, mindfulness, responding to triggers, and supportive community resources. Additional content centered on AI/AN culture was also selected.

Interviews were conducted by two women, then transcribed and coded using content analysis with NVivo software. Results were presented to CAC for further content refinement.

CAC members (n = 10) guided study methods, intervention development, and dissemination activities. 14 AI/AN women (mean age 36.4 years; mean 6.7 months opioid abstinence) and 12 interested parties (7 men, 5 women) were receptive to an AI/AN gender-specific Facebook group, preferring content with AI/AN people and/or text resonating with AI/AN culture (e.g., Native traditions, family, personal stories, historical trauma). Recommendations included (1) protect confidentiality, (2) retain positivity, (3) incorporate resources and exercises to build coping skills, and (4) moderators should be authentic and relatable to build trust.

Conclusions: This approach provides a model for developing culturally tailored, appealing and effective social media interventions to support AI/AN women in recovery from opioid use disorder.

Related protocols: CTN-0123

This is the Results Article for CTN-0084-A-2.

Multiple digital data sources can capture moment-to-moment information to advance a robust understanding of opioid use disorder (OUD) behavior, ultimately creating a digital phenotype for each patient. This information can lead to individualized interventions to improve treatment for OUD.

This aim of this study, CTN-0084-A-2, was to examine patient engagement with multiple digital phenotyping methods among patients receiving buprenorphine medication for OUD.

The study enrolled 65 patients receiving buprenorphine for OUD between June 2020 and January 2021 from 4 addiction medicine programs in an integrated health care delivery system in Northern California. Ecological momentary assessment (EMA), sensor data, and social media data were collected by smartphone, smartwatch, and social media platforms over a 12-week period. Primary engagement outcomes were meeting measures of minimum phone carry (=8 hours per day) and watch wear (=18 hours per day) criteria, EMA response rates, social media consent rate, and data sparsity. Descriptive analyses, bivariate, and trend tests were performed.

The participants’ average age was 37 years, 47% of them were female, and 71% of them were White. On average, participants met phone carrying criteria on 94% of study days, met watch wearing criteria on 74% of days, and wore the watch to sleep on 77% of days. The mean EMA response rate was 70%, declining from 83% to 56% from week 1 to week 12. Among participants with social media accounts, 88% of them consented to providing data; of them, 55% of Facebook, 54% of Instagram, and 57% of Twitter participants provided data. The amount of social media data available varied widely across participants. No differences by age, sex, race, or ethnicity were observed for any outcomes.

Conclusions: To our knowledge, this is the first study to capture these 3 digital data sources in this clinical population. Our findings demonstrate that patients receiving buprenorphine treatment for OUD had generally high engagement with multiple digital phenotyping data sources, but this was more limited for the social media data.

Related protocols: CTN-0084-A-2

Presented by: Marina Toulu-Shams, PhD, Professor, Dept of Psychiatry and Behavioral Sciences, Weill Institute of Infant, Child and Adolescent Psychiatry, Dept of Psychiatry, University of California, San Francisco

Dr. Marina Tolou-Shams, trained as a pediatric and forensic psychologist, is a clinician-scientist. She leads the UCSF Juvenile Justice Behavioral Health lab whose mission is to improve behavioral health outcomes for youth who come into contact with the juvenile justice, child welfare, and foster care systems (https://jjbh.org/). Her NIH-funded research focuses on improving youths’ physical, mental, and emotional health, reducing drug and alcohol use, reducing HIV/STI risk behaviors, and increasing access to evidence-based care with particular emphasis on leveraging technology to achieve these outcomes. One study is a pilot trial of SMS text-messaging platform to engage court-involved youth in substance use or dual diagnosis treatment services. A second developmental study takes a mixed-methods, multi-informant participatory research approach to developing and testing a Foster Care Family Navigator model to improve youth mental health outcomes.

The objectives of the presentation are to:

1. understand the substance use and mental health intervention needs of justice-involved youth;
2. identify barriers to behavioral health care access and engagement; and,
3. discuss ways that technology may hold promise for improving justice-involved youth’s behavioral health and legal outcomes.

This is the primary outcomes article for CTN-0083.

Social media sites, dating apps, and information search sites have been used to reach individuals at high risk for HIV infection. However, it is not clear which platform is the most efficient in promoting home HIV self-testing, given that the users of various platforms may have different characteristics that impact their readiness for HIV testing.

This study, CTN-0083, “Using Social Media to Deliver HIV Self-Testing Kits and Link to Online PrEP Services,” aimed to compare the relative effectiveness of social media sites, dating apps, and information search sites in promoting HIV self-testing among minority men who have sex with men (MSM) at an increased risk of HIV infection. Test kit order rates were used as a proxy to evaluate promotion effectiveness. In addition, researchers assessed differences in characteristics between participants who ordered and did not order an HIV test kit.

Culturally appropriate advertisements were placed on popular sites of three different platforms: social media sites (Facebook, Instagram), dating apps (Grindr, Jack’D), and information search sites (Google, Bing). Advertisements targeted young (18-30 years old) and minority (Black or Latinx) MSM at risk of HIV exposure. Recruitment occurred in 2 waves, with each wave running advertisements on 1 platform of each type over the same period. Participants completed a baseline survey assessing sexual or injection use behavior, substance use including alcohol, psychological readiness to test, attitudes toward HIV testing and treatment, and HIV-related stigma. Participants received an electronic code to order a free home-based HIV self-test kit. Follow-up assessments were conducted to assess HIV self-test kit use and uptake of pre-exposure prophylaxis (PrEP) at 14 and 60 days post enrollment.

In total, 271 participants were enrolled, and 254 were included in the final analysis. Among these 254 participants, 177 (69.7%) ordered a home HIV self-test kit. Most of the self-test kits were ordered by participants enrolled from dating apps. Due to waves with low enrollment, between wave statistical comparisons were not feasible. Within wave comparison revealed that Jack’D showed higher order rates (3.29 kits/day) compared to Instagram (0.34 kits/day) and Bing (0 kits/day). There were no associations among self-test kit ordering and HIV-related stigma, perceptions about HIV testing and treatment, and mistrust of medical organizations.

Conclusions: These findings show that using popular dating apps might be an efficient way to promote HIV self-testing. Stigma, perceptions about HIV testing and treatment, or mistrust of medical organizations may not affect order rates of HIV test kits promoted on the internet.

Related protocols: CTN-0083

Presented by: Michael Dennis, PhD

Dr. Dennis describes the trends in smartphone interventions for substance users, how they vary by age, and their significance for adolescent treatment. He also discusses how his research examines the findings of several recent clinical trials, including which parts of the smartphone interventions best predict outcomes. Further, he discusses what it means to adapt smartphones to better target adolescents and young adults.

This is the primary outcomes article for CTN-0073-Ot.

As digital technology increasingly informs clinical trials, novel ways to collect study data in the natural field setting have the potential to enhance the richness of research data. Cocaine use in clinical trials is usually collected via self-report and/or urine drug screen results, both of which have limitations. This article examines the feasibility of developing a wrist-worn device that can detect sufficient physiological data (i.e., heart rate and heart rate variability) to detect cocaine use. This study, CTN-0073-Ot, “Towards Detecting Cocaine Use Using Smartwatches in the NIDA Clinical Trials Network,” aimed to develop a wrist-worn device that can be used in the natural field setting among people who use cocaine to collect reliable data (determined by data yield, device wearability, and data quality) that is less obtrusive than chest-based devices used in prior research. The study also aimed to further develop a cocaine use detection algorithm used in previous research with an electrocardiogram on a chestband by adapting it to a photoplethysmography sensor on the wrist-worn device which is more prone to motion artifacts.

Results indicate that wrist-based heart rate data collection is feasible and can provide higher data yield than chest-based sensors, as wrist-based devices were also more comfortable and affected participants’ daily lives less often than chest-based sensors.

Conclusions: This study developed a wrist-worn device that can be used in the natural field setting among people who use cocaine to collect reliable heart rate data that is less obtrusive than chest-based devices. When properly worn, the wrist-based sensor produced similar quality of heart rate and heart rate variability features to chest-based sensors and matched their performance in automated detection of cocaine use events.

Related protocols: CTN-0073-Ot

Telemedicine (TM) enabled by digital health technologies to provide medical services has been considered a key solution to increasing health care access in rural communities. With the immediate need for remote care due to the COVID-19 pandemic, many health care systems have rapidly incorporated digital technologies to support the delivery of remote care options, including medication treatment for individuals with opioid use disorder (OUD). In responding to the opioid crisis and the COVID-19 pandemic, public health officials and scientific communities appear to strongly support and advocate for greater use of TM-based medication treatment for opioid use disorder (MOUD) to improve access to care and have suggested that broad use of TM during the pandemic should be sustained. Nevertheless, research on the implementation and effectiveness of TM-based MOUD has been limited.

To address this knowledge gap, the National Drug Abuse Treatment Clinical Trials Network (CTN) funded (via the NIH HEAL Initiative) a study on Rural Expansion of Medication Treatment for Opioid Use Disorder (Rural MOUD; CTN-0102) to investigate the implementation and effectiveness of adding TM-based MOUD to rural primary care for expanding access to MOUD. In preparation for this large-scale, randomized controlled trial incorporating TM in rural primary care, a feasibility study is being conducted to develop and pilot test implementation procedures.

In this commentary, the authors share some of their experiences, which include several challenges, during the initial two-month period of the feasibility study phase. While these challenges could be due, at least in part, to adjusting to the COVID-19 pandemic and new workflows to accommodate the study, they are notable and could have a substantial impact on the larger, planned pragmatic trial and on TM-based MOUD more broadly. Challenges include low rates of identification of risk for OUD from screening, low rates of referral to TM, digital device and internet access issues, workflow and capacity barriers, and insurance coverage. These challenges also highlight the lack of empirical guidance for best TM practice and quality remote care models. With TM expanding rapidly, understanding implementation and demonstrating what TM approaches are effective are critical for ensuring the best care for persons with OUD.

Related protocols: CTN-0102

The application of digital technologies to better assess, understand, and treat substance use disorders (SUDs) is a particularly promising and vibrant area of scientific research. The National Drug Abuse Treatment Clinical Trials Network (CTN), launched in 1999 by the U.S. National Institute on Drug Abuse, has supported a growing line of research that leverages digital technologies to glean new insights into SUDs and provide science-based therapeutic tools to a diverse array of persons with SUDs.

This article provides an overview of the breadth and impact of research conducted in the realm of digital health within the CTN. This work has included the CTN’s efforts to systematically embed digital screeners for SUDs into general medical settings to impact care models across the nation. This work has also included a pivotal multi-site clinical trial conducted on the CTN platform, whose data led to the very first “prescription digital therapeutic” authorized by the U.S. Food and Drug Administration (FDA) for the treatment of SUDs. Further CTN research includes the study of telehealth to increase capacity for science-based SUD treatment in rural and under-resourced communities. In addition, the CTN has supported an assessment of the feasibility of detecting cocaine-taking behavior via smartwatch sensing. And, the CTN has supported the conduct of clinical trials entirely online (including the recruitment of national and hard-to-reach/under-served participant samples online, with remote intervention delivery and data collection). Further, the CTN is supporting innovative work focused on the use of digital health technologies and data analytics to identify digital biomarkers and understand the clinical trajectories of individuals receiving medications for opioid use disorder (OUD).

This paper concludes by outlining the many potential future opportunities to leverage the unique national CTN research network to scale-up the science on digital health to examine optimal strategies to increase the reach of science-based SUD service delivery models both within and outside of healthcare.

Related protocols: CTN-0044, CTN-0059, CTN-0073-Ot, CTN-0076, CTN-0083, CTN-0084-A-2, CTN-0090, CTN-0095, CTN-0101, CTN-0102

The TAPS Tool is a substance use screening and brief assessment instrument that was developed for use in primary care medical settings. It is one of the first screening instruments to provide rapid assessment of all commonly used substance classes, including illicit and prescription opioids, and is one of the only available screeners designed and validated in an electronic self-administered format (myTAPS). This secondary analysis of data from the TAPS Tool validation study (CTN-0059) describes the feasibility and acceptability of the myTAPS among primary care patients.

Adult patients (N=2000) from five primary care clinics completed the TAPS Tool on a tablet computer (myTAPS) and in an interviewer-administered format. Requests for assistance and time required were tracked, and participants completed a survey on ease of use, utilization of audio guidance, and format preference. Logistic regression was used to examine outcomes in defined subpopulations, including groups that may have greater difficulty completing an electronic screener and those that may prefer an electronic self-administered approach.

Almost all participants (98.3%) reported that the myTAPS was easy to use. The median time to complete myTAPS screening was 4 minutes (mean 4.48, standard deviation 2.57). More time was required by participants who were older, Hispanic, Black, or reported non-medical prescription drug use, while less time was required by women. Assistance was requested by 25% of participants and was more frequently requested by those with lower education or who were over the age of 65. Audio guidance was used by 18.3% and was more frequently used by participants with lower education, who were over 65, or of Black race. The myTAPS format was preferred by women and individuals with drug use, while participants with lower education preferred the interviewer-administered format.

Conclusions: Overall, myTAPS screening was feasible and well accepted by adult primary care patients. Clinics adopting electronic screening should be prepared to offer assistance to some patients, particularly those who are older or less educated, and should have the capacity to use an interviewer-administered approach when required. Future studies should assess the acceptability and the feasibility of myTAPS screening when it is implemented in routine practice.

Related protocols: CTN-0059

Cocaine use in clinical trials is often measured via self-report, which can be inaccurate, or urine drug screens, which can be intrusive and burdensome. Devices that can automatically detect cocaine use and can be worn conveniently in daily life may provide several benefits. AutoSense is a wearable, physiological-monitoring suite that can detect cocaine use, but it may be limited as a method for monitoring cocaine use because it requires wearing a chestband with electrodes.

This paper describes the design, rationale, and methodology of a project that seeks to build upon and extend previous work in the development of methods to detect cocaine use via wearable, unobtrusive mobile sensor technologies. To this end, a wrist-worn sensor suite (i.e., MotionSense HRV) will be developed and evaluated.

Participants who use cocaine (N=25) will be asked to wear MotionSense HRV and AutoSense for two weeks during waking hours. Drug use will be assessed via thrice-weekly urine drug screens and self-reports, and will be used to isolate periods of cocaine use that will be differentiated from other drug use. The present study will provide information on the feasibility and acceptability of using a wrist-worn device to detect cocaine use.

Related protocols: CTN-0073-Ot

This article describes how smartphones were used to monitor and encourage medication adherence in a pilot study evaluating the potential efficacy of a combination pharmacotherapy for methamphetamine use disorder. It examines the feasibility, utility, and acceptability of using smartphones to capture dosing videos from the perspectives of participants and staff.

The study, CTN-0054 (“Accelerated Development of Additive Pharmacotherapy Treatment (ADAPT) for Methamphetamine Use Disorder”), was an 8-week, open-label evaluation of extended-release bupropion (BRP, Wellbutrin XL, 450mg/day). Participants attended visits twice weekly for observed BRP dosing, assessments, and medical management. BRP was dispensed once weekly for dosing on nonclinic days. Medication adherence was assessed objectively (by observation at the clinic and smartphone videos for dosing at home) and subjectively (self-reports of dosing). Surveys assessing the smartphone component were completed by participants and study staff.

Participants (N=49) reported taking 93.6% of the dispensed BRP doses while 86.6% of dispensed doses were confirmed via dosing video and in-person observations. Most participants who completed the survey agreed that the smartphone was easy to use (92.6%) and that taking the dosing videos helped them remember to take the study medication (80.5%). Staff agreed that the smartphone helped collect accurate dosing data for most (77.5%) participants.

Conclusions: The use of smartphones for video-based oral medication dosing in this study provided a feasible and acceptable mechanism to encourage, monitor, and confirm medication adherence. Video-confirmed dosing adherence provides an objective numerical indicator of the lowest medication adherence rate participants achieve, allowing investigators to more confidently interpret results.

Related protocols: CTN-0054

The Community Reinforcement Approach (CRA) is an evidence-based practice for the treatment of substance use disorders (SUDs) and achieving and maintaining abstinence, but few studies have systematically explored the effect of CRA on secondary, yet also important, outcomes, such as social functioning.

This study was a secondary data analysis of CTN-0044, “Web Delivery of Evidence-Based, Psychosocial Treatment for Substance Use Disorders.” The purpose was to examine whether an internet-based version of CRA plus contingency management (Therapeutic Education System, TES) is associated with improved social functioning of individuals seeking substance use disorder treatment in a multi-site clinical effectiveness trial.

Social functioning was measured using the 54-item Social Adjustment Scale (SAS) assessing role performance in six domains (work, social and leisure activities, extended family relationships, marital relationship, parenting, and immediate family). Generalized linear mixed models tested the effects of treatment, time, sex, baseline abstinence, baseline social functioning and baseline psychological distress on overall social functioning and across social functioning subscales at the end of the 12-week treatment phase and three and six months post treatment.

Results showed no significant association between treatment and total social functioning score or any subscale scores. Being male, however, was significantly associated with better social functioning overall at the end of treatment (p=.024). Additionally, higher levels of psychological distress at baseline predicted significantly worse social functioning at the end of treatment overall (p=.037).

Conclusions: While TES was not associated with improvement in social functioning outcomes among participants when compared to TAU, male participants and those with less psychological distress at baseline experienced greater improvements in social functioning at the end of treatment. When integrating TES into community treatment programs, it may be important to have counselors involved to guide clients when choosing modules; completing home practice is also a critical factor in improving outcomes and should be monitored. In addition, improved measures of social functioning may be needed for studies involving patients with substance use disorders as more traditional secondary outcomes, such as social functioning and quality of life, should be more systematically studied in research involving treatment for substance use disorders.

Related protocols: CTN-0044