Background:Prenatal alcohol exposure can cause neurodevelopmental injury, but the cellular events linking altered inhibitory signalling to apoptotic changes in the developing spinal dorsal horn remain incompletely understood. Methods:C57BL/6J mice received two subcutaneous ethanol injections (2.5 g/kg each, 2 h apart) on postnatal day 7 (PD7). Dorsal horn injury and GABAergic changes were assessed by histology, immunostaining, and whole-cell patch-clamp recording. Intracellular Ca2+ signalling, CaMKII and GSK-3β regulation, mitochondrial apoptosis-related markers, oxidative stress, and cell viability were examined using calcium imaging, flow cytometry, Western blotting, and co-immunoprecipitation. Tetraethylammonium chloride (TEAC) and Bay K8644 were used to explore the contribution of membrane excitability and voltage-gated Ca2+ entry. Results:Ethanol exposure was associated with altered dorsal horn neuronal morphology, increased cleaved caspase-3, and prominent involvement of GAD67-positive neurons. It was also associated with increased GABA staining and mIPSC frequency, without a clear change in mIPSC amplitude; reduced intracellular Ca2+ signals; lower CaMKII Thr286 phosphorylation and CaMKII-GSK-3β association; decreased inhibitory GSK-3β Ser9 phosphorylation; and mitochondrial apoptosis-related changes, increased ROS, reduced cell viability, and caspase-3 activation. TEAC attenuated several ethanol-associated molecular and cellular injury markers, whereas Bay K8644 moderated selected Ca2+- and mitochondrial/oxidative stress-related outcomes. Conclusion:Acute PD7 ethanol exposure was associated with neuronal injury in the developing mouse spinal dorsal horn and with coordinated changes in GABAergic signalling, Ca2+-CaMKII regulation, GSK-3β activity, and apoptosis-related markers. These findings support a candidate membrane-potential/Ca2+-sensitive GABAergic and Ca2+-CaMKII-GSK-3β/BAX signalling framework, but do not establish a fixed causal sequence or behavioural consequence.
Yuting Wang,1,2,* Zhaoyang Cheng,1,2,* Zizhuo Wang,3 Xihui Ding,3 Xiaoxiang Xu,3 Shuaichen Sun,3 Yingying Zheng,3 Min Liu,3 Jianguang Xu,4 Xiang Nan,3 Jinyong Xu,3,5 Xiaohui Li,3,5 Zhenhua Ren,1,2,4 Kai Zhang1,2,5,61Department of Psychiatry, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, People’s Republic of China; 3Department of Anatomy, Anhui Medical University, Hefei, People’s Republic of China; 4College and Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, People’s Republic of China; 5Anhui Provincial Key Laboratory for Brain Bank Construction and Resource Utilization, Hefei, People’s Republic of China; 6Anhui Psychiatric Center, Hefei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenhua Ren, College and Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, 81 Meishan Road, Hefei, 238000, People’s Republic of China, Tel/Fax +86-0551-65161053, People’s Republic of China, Email renzhenhua@ahmu.edu.cn Kai Zhang, Department of Psychiatry, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, 238000, People’s Republic of China, Tel/Fax +86-551-82324114, Email zhangkai@ahmu.edu.cnBackground: Prenatal alcohol exposure can cause neurodevelopmental injury, but the cellular events linking altered inhibitory signalling to apoptotic changes in the developing spinal dorsal horn remain incompletely understood.Methods: C57BL/6J mice received two subcutaneous ethanol injections (2.5 g/kg each, 2 h apart) on postnatal day 7 (PD7). Dorsal horn injury and GABAergic changes were assessed by histology, immunostaining, and whole-cell patch-clamp recording. Intracellular Ca2+ signalling, CaMKII and GSK-3β regulation, mitochondrial apoptosis-related markers, oxidative stress, and cell viability were examined using calcium imaging, flow cytometry, Western blotting, and co-immunoprecipitation. Tetraethylammonium chloride (TEAC) and Bay K8644 were used to explore the contribution of membrane excitability and voltage-gated Ca2+ entry.Results: Ethanol exposure was associated with altered dorsal horn neuronal morphology, increased cleaved caspase-3, and prominent involvement of GAD67-positive neurons. It was also associated with increased GABA staining and mIPSC frequency, without a clear change in mIPSC amplitude; reduced intracellular Ca2+ signals; lower CaMKII Thr286 phosphorylation and CaMKII-GSK-3β association; decreased inhibitory GSK-3β Ser9 phosphorylation; and mitochondrial apoptosis-related changes, increased ROS, reduced cell viability, and caspase-3 activation. TEAC attenuated several ethanol-associated molecular and cellular injury markers, whereas Bay K8644 moderated selected Ca2+- and mitochondrial/oxidative stress-related outcomes.Conclusion: Acute PD7 ethanol exposure was associated with neuronal injury in the developing mouse spinal dorsal horn and with coordinated changes in GABAergic signalling, Ca2+-CaMKII regulation, GSK-3β activity, and apoptosis-related markers. These findings support a candidate membrane-potential/Ca2+-sensitive GABAergic and Ca2+-CaMKII-GSK-3β/BAX signalling framework, but do not establish a fixed causal sequence or behavioural consequence.Keywords: fetal alcohol spectrum disorders, developmental ethanol exposure, spinal dorsal horn, apoptosis, CaMKII, GSK-3β
Background:Sleep-related symptoms are common among people receiving medications for opioid use disorder (OUD), including buprenorphine. In outpatient addiction treatment, nighttime sleep complaints are often evaluated alongside active medication lists and recent substance exposures. This short report described patient-reported nighttime sleep symptoms and sleep-relevant medication class documentation among adults receiving buprenorphine for OUD. Methods:This cross-sectional study used survey data and medical-record abstraction from adults receiving buprenorphine for OUD at an academic addiction clinic from February 2022 to September 2023. Nighttime sleep symptoms were characterized using Insomnia Severity Index items 1-3: difficulty falling asleep, difficulty staying asleep, and waking too early. Participants were categorized as No-Sx, Single-Sx, or Multi-Sx. Sleep-relevant medications documented on the active outpatient medication list were grouped into eight classes. Sample characteristics, nighttime symptom groups, medication class documentation, and urine drug testing results within 30 days were summarized descriptively. Results:Among study participants (n = 136), 72.1% endorsed at least one nighttime sleep symptom. Symptom group distribution was No-Sx (27.9%), Single-Sx (11.0%), and Multi-Sx (61.0%). In the Multi-Sx group, gabapentinoids were most frequently documented (34.9%), followed by sedating antidepressants (26.5%), sedating antihistamines (22.9%), and adrenergic agents (22.9%). Cannabinoids were detected in 46.2% of participants with available urine drug testing results. Conclusion:Nighttime sleep symptoms and sleep-relevant medication documentation were common in this outpatient buprenorphine-treated OUD sample. Findings support routine nighttime sleep symptom assessment, together with medication review and consideration of recent substance exposure, to help identify clinically relevant sleep concerns and inform safer outpatient buprenorphine care.
Austin M Jones,1 Michelle Eglovitch,2 Pablo Soto,2 Amber R Green,1 Madison M Marcus,1 Joseph M Dzierzewski,3 Maha Alattar,4 Caitlin E Martin1,51Institute for Drug and Alcohol Studies, Virginia Commonwealth University, Richmond, VA, USA; 2Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA; 3National Sleep Foundation, Washington, DC, USA; 4Department of Neurology, Virginia Commonwealth University, Richmond, VA, USA; 5Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USACorrespondence: Austin M Jones, Institute for Drug and Alcohol Studies, Virginia Commonwealth University, 203 E. Cary St, Richmond, VA, 23219, USA, Tel +1 (804) 828-3639, Email jonesam32@vcu.eduBackground: Sleep-related symptoms are common among people receiving medications for opioid use disorder (OUD), including buprenorphine. In outpatient addiction treatment, nighttime sleep complaints are often evaluated alongside active medication lists and recent substance exposures. This short report described patient-reported nighttime sleep symptoms and sleep-relevant medication class documentation among adults receiving buprenorphine for OUD.Methods: This cross-sectional study used survey data and medical-record abstraction from adults receiving buprenorphine for OUD at an academic addiction clinic from February 2022 to September 2023. Nighttime sleep symptoms were characterized using Insomnia Severity Index items 1– 3: difficulty falling asleep, difficulty staying asleep, and waking too early. Participants were categorized as No-Sx, Single-Sx, or Multi-Sx. Sleep-relevant medications documented on the active outpatient medication list were grouped into eight classes. Sample characteristics, nighttime symptom groups, medication class documentation, and urine drug testing results within 30 days were summarized descriptively.Results: Among study participants (n = 136), 72.1% endorsed at least one nighttime sleep symptom. Symptom group distribution was No-Sx (27.9%), Single-Sx (11.0%), and Multi-Sx (61.0%). In the Multi-Sx group, gabapentinoids were most frequently documented (34.9%), followed by sedating antidepressants (26.5%), sedating antihistamines (22.9%), and adrenergic agents (22.9%). Cannabinoids were detected in 46.2% of participants with available urine drug testing results.Conclusion: Nighttime sleep symptoms and sleep-relevant medication documentation were common in this outpatient buprenorphine-treated OUD sample. Findings support routine nighttime sleep symptom assessment, together with medication review and consideration of recent substance exposure, to help identify clinically relevant sleep concerns and inform safer outpatient buprenorphine care.Keywords: opioid use disorder, buprenorphine, sleep disturbance, insomnia, sedating medications
Purpose of Review:Kratom (Mitragyna speciosa Korth) is a tree that belongs to the coffee family (Rubiaceae) and is native to Southeast Asia. This review article focuses on the diversification of kratom products, differentiating between native leaf, extracts and isolates based on use patterns and conceptualization of kratom for self-treatment of disorders. Findings:The dried powdered native leaf and its extract derivatives are primarily used as kratom products in the US and Europe. Diversification of kratom products has increased since 2021 following the global COVID-19 pandemic. There has been a rise in chemically altered kratom products, including enriched extracts, edibles, resins, and isolates. Most prominent among them is the oxidative metabolite of mitragynine, 7-hydroxymitragynine. Summary:The total alkaloid content is lowest in native kratom leaf products (2-5% by weight) which is associated with a lower potential for adverse effects and dependence compared to concentrated products, where extracts can contain five to 50 times the alkaloid content of the native leaf. Purified compounds, predominantly mitragynine and semi-synthetic 7-hydroxymitragynine, are likely to be associated with a higher risk for dependence and overdose potential.
Individuals with substance use disorders (SUDs) access care through emergency departments (EDs) more frequently than the general population, representing a critical opportunity for addiction treatment linkage. Peer recovery support services (PRSS) utilize individuals with lived recovery experience to provide peer support for those struggling with addiction. This service may be particularly helpful in the ED, where prior negative experiences can erode patient trust and care often involves extended waiting periods during which motivation can fluctuate. PRSS may enhance engagement in this setting by offering relationship-based support from someone who patients can identify with and who can provide practical information on service navigation. We conducted a systematic review of comparative studies evaluating ED-based PRSS for individuals with SUDs versus a non-PRSS comparator (eg, usual care). A medical librarian searched the literature through 8/2025; 1,801 citations were retrieved, 708 duplicates were removed, 1,093 records were screened, and 127 studies underwent full-text review. Nine studies published between 2011 and 2025, representing 14,883 unique individuals, met inclusion criteria. Most (seven) were considered moderate regarding global risk of bias. Types of substance and outcomes varied by study; opioids (n=7) were the most commonly evaluated substance, while overdose (n=6), all-cause hospital return (n=3), all-cause mortality (n=3), and SUD treatment linkage (n=3) were the most commonly evaluated outcomes. The findings were mixed; PRSS has not yet demonstrated clear superiority over non-PRSS comparators, though this may evolve as research continues. Consisting solely of quantitative studies, the present review fails to capture the qualitative patient experience of working with a peer, which may have been a positive, recovery-promoting encounter, even in the absence of statistical significance. While ED-based PRSS interventions are individualized services that promote connection and may increase patient comfort, the current evidence base remains heterogeneous, limited in comparative studies, and subject to bias.
Background: Most patients with opioid use disorder have experienced traumatic events; however, sex differences in trauma exposure, its timing, and its association with treatment outcomes remain unclear. Methods: Of the 1194 patients admitted to a methadone maintenance treatment (1993-2025), 923 completed an intake questionnaire assessing traumatic events and their timing relative to substance use (before, during, "always", or "never"). Predictors of long-term retention were examined using Kaplan-Meier analyses and a Cox multivariate model. Results: Of 923 participants, 23.5% were female, and 74.4% reported trauma. Males (35.7%) more often reported trauma during substance use than females (27.6%), whereas females more frequently reported trauma occurring "always" (31.3%) than males (22.2%; p=0.024). Interpersonal trauma category was more prevalent in females (59% vs. 40.2%, p<0.001) with no differences in physical trauma (50.8%) and self-directed harm (38.8%). The age of opioid initiation was comparable between sexes but females were admitted to MMT younger. Substance use at admission was comparable between sexes, as were one-year and long-term retention (mean=9.8 years, 95% CI 9.1-10.6). Long-term retention between trauma timing groups and trauma categories were comparable, also when stratified by sex. Sex-specific differences emerged only when trauma type and timing were considered. Specifically rape history was associated with shorter retention among males but not females. Conclusion: Traumatic experiences differed between sexes but were not associated with long-term retention and did not change the comparable outcomes between sexes. A bigger sample is needed to confirm the findings of shorter retention in male who experienced rape.
Purpose:Approach bias modification (ApBM), a cognitive training intervention that reduces "alcohol approach bias" (impulses to approach alcohol-related stimuli), reduces post-treatment relapse rates when delivered during residential alcohol use disorder (AUD) treatment. However, few residential treatment services provide ApBM to their clients. Smartphone app-delivered ApBM may circumvent barriers to implementation within services by allowing clients to self-administer ApBM after discharge instead. This double-blind RCT tested whether providing a personalised ApBM smartphone app to people discharging from residential AUD treatment increased alcohol abstinence rates. Participants and Methods:Participants were recruited while attending residential AUD treatment programs. 171 participants were sent app download instructions following discharge, of whom 134 installed it (61 receiving the ApBM version; 73 sham-training controls), providing only 39% power for primary outcome analysis. App notifications reminded participants to complete training tasks each week for 4 weeks. Alcohol use and other secondary outcomes were measured post-intervention and at 1-month, 3-month, and 6-month follow-ups. The primary outcome was past-month abstinence from alcohol at the 3-month follow-up. Results:Abstinence rates at 3-month follow-up were 55% [95% CI: 40%, 70%] in controls and 52% [95% CI: 36%, 67%] in ApBM participants. This difference was non-significant (contrast: -3% [95% CI: -25%, 18%], p = 0.758). All secondary outcomes analyses also found non-significant effects of group. Exploratory post-hoc analyses suggested that duration of residential treatment and number of ApBM sessions completed may moderate ApBM's effects on abstinence. Conclusion:Findings did not support the efficacy of post-discharge, personalised, app-delivered ApBM for relapse prevention in residential AUD treatment clients. These findings should be treated with caution due to this trial's low statistical power. Exploratory analyses suggest that future trials may be more likely to find evidence of efficacy for this approach if they focus on clients with shorter admissions and deliver a more sustained, structured ApBM intervention.
Purpose: To examine the effectiveness of the Functional-Cognitive and Sensory Treatment (F-CaST) for individuals with Substance Use Disorder (SUD), in supporting daily functioning and reducing dropout from the therapeutic community. Patients and Methods: A single-blind randomized controlled trial was conducted in a therapeutic community. Participants were randomly allocated to either the F-CaST group or a control group receiving standard care. The F-CaST consisted of 16 sessions (eight group and eight individual sessions) delivered over eight weeks and focused on teaching strategies individually tailored for executive function deficits and sensory modulation dysfunction linked to participants' personal occupational goals. Assessments were conducted at pre (T1), immediately post-intervention (T2), and at 1- and 3-month follow-ups (T3-T4). Primary outcomes included occupational performance and satisfaction measured by the Canadian Occupational Performance Measure (COPM), dropout rates, and length of stay in the therapeutic community. Results: Thirty-three participants were randomized to F-CaST (n=20) or standard care (n=13). Both groups demonstrated significant improvements in COPM performance and satisfaction over time; however, the F-CaST group showed a more favorable pattern of improvement and higher rates of clinically meaningful change (72% vs. 39% at 3 months). Dropout rates were significantly lower in the F-CaST group at T2 (22% vs. 62%). No significant between-group differences were found in length of stay. Conclusion: F-CaST appears to be a feasible and promising intervention that may support improvements in occupational performance, satisfaction, and early treatment retention among individuals with SUD in therapeutic communities.
Drug abuse has emerged as a pressing concern worldwide and is increasingly affecting developing countries like Pakistan, particularly their university students. Stress and peer pressure are major driving factors, further exacerbated by limited awareness and inadequate counseling services. In a country where the majority of the population comprises young people, this surge is a serious public concern that requires urgent and coordinated action from policymakers. Although efforts are being made to address this issue, there remains a significant need for improvements, especially in prevention, early intervention, and student support mechanisms. This article highlights the need for strengthened initiatives and support systems to guide and counsel students, addressing this growing concern.
The consumption of cannabinoids is highly prevalent and has been associated with altered structural, functional, and metabolic brain integrity, measured using PET and neuroimaging tools. However, the current neuroimaging evidence has been summarized by distinct modalities that measure different metrics of brain integrity, precluding a comprehensive understanding of the underlying neurobiology. A non-systematic narrative review method was used to summarize the multimodal neuroimaging evidence on brain integrity from experimental studies of cannabinoid intoxication and observational studies in non-intoxicated cannabis users. Consistent evidence showed that acute intoxication with delta-9-tetrahydrocannabinol (THC) was associated with greater brain activity in fronto-striatal pathways. For regular cannabis users compared to controls, there was consistent cross-sectional evidence of lower hippocampal volumetry and white matter microstructure of the superior longitudinal fasciculus, and of different fronto-striatal activity and connectivity during cue-reactivity tasks and resting-state. In cannabis users, there was emerging evidence from Positron Emission Tomography studies of altered neurochemistry in fronto-striatal pathways (eg, lower N-acetyl aspartate); lower glucose metabolism in the frontal cortex; and lower density of cannabinoid receptors, which may reverse with abstinence. Longitudinal multimodal neuroimaging studies are required to confirm if brain differences predate or follow the onset of cannabis use or cannabis use disorder, and whether changes in brain integrity in people who use cannabis dissipate with abstinence.
Background: Using English-only assessment tools with Spanish-speaking patients can lead to miscommunication and inadequate care. The current study translates the commonly used Clinical Opiate Withdrawal Scale (COWS) into La Escala Clinica de Sindrome Abstinencia de Opi & aacute;ceos (ECAO) for use by healthcare workers to use with Spanish-speaking patients. Methods: First, the COWS was translated using standard forward/backward methods. Next attitudes and feedback about the ECAO were assessed via a mixed-methods pilot study. Results: The translation went according to plan. The final sample size of the pilot study was N=107 healthcare providers (Mage = 40.00 years; woman = 58.88%; master's degree = 42.06%). The translation was rated as accurate (M=7.83; SD = 1.71; range 4-10) with a majority (62.62%) of participants rating it at an 8 or above. Ratings of acceptability, appropriateness, feasibility, understandability, and actionability were also quite high, with agreement across questions in these sections ranging from 72.09-95.33%. Qualitative results highlighted favorability toward the ECAO such as its accurate and culturally sensitive translation with areas of improvement including use of overly medical terms. Conclusion: Based on the results of this pilot study, the ECAO appears to be an accurate, feasible, useful tool for Spanish-speaking healthcare workers who treat patients struggling with opioid withdrawal. The free availability of the Spanish-language ECAO will help patients and providers communicate adequately in order to determine the extent of opioid withdrawal accuracy as well as develop appropriate treatment plans.
Purpose: People who use methamphetamine can experience significant barriers to access treatment, care, and support. This study aimed to explore the experiences of access to care using a conceptual model, for this population. Patients and Methods: This descriptive qualitative study was embedded within an Australian telephone-delivered intervention trial for methamphetamine use problems. Twenty-seven participants were interviewed about their experiences of access to care (prior to enrolment in the trial). Interview transcripts were analysed using framework analysis, and data mapped to a patient-centred access to care framework. Results: Three themes were identified: (1) the "problem" of methamphetamine use; (2) beliefs about treatment; and, (3) the impact of stigma. These themes were aligned to relevant determinants of access to care. Access to care was experienced through participant perceptions about the need for care, the ability to engage in the care process, and the acceptability of service providers. Conclusion: Stigma and beliefs about problematic use, and knowledge of treatment options dominated participants' experiences of access. Clear information about available treatment options, particularly to address fears of engaging in treatment that is viewed as stigmatising, are important considerations for policy makers and service providers.
Introduction: Cannabis legalization has expanded rapidly across high-income jurisdictions, altering patterns of cannabis use, product potency, and commercial markets. Although surveillance systems increasingly quantify cannabis exposure, clinically meaningful harm is more difficult to detect. Cannabis use disorder (CUD) represents a key construct linking exposure to sustained impairment, yet its epidemiologic visibility depends heavily on diagnostic frameworks and measurement design. Aim: This review examines how contemporary surveillance systems detect cannabis-related harm and evaluates the implications of diagnostic classification, epidemiologic measurement, and treatment capacity for understanding and responding to CUD in the postlegalization era. Methods: We conducted a narrative review synthesizing literature on cannabis legalization, psychiatric epidemiology, and treatment of CUD. Evidence was identified from biomedical databases, epidemiologic surveys, systematic reviews, randomized trials, and policy analyses. Sources were examined across three domains: (1) post-legalization surveillance of cannabis exposure and harm, (2) diagnostic evolution and measurement of CUD in population surveys, and (3) current evidence for treatment interventions and treatment system responses. Results: Population surveillance systems measure cannabis exposure with increasing precision but show limited sensitivity for persistent or clinically meaningful harm. Transitions from DSM-IV's hierarchical abuse-dependence framework to the dimensional DSM-5 model expanded detection of mild and moderate disorder and altered prevalence estimates across epidemiologic surveys. International studies using DSM-5-aligned instruments generally report past-year CUD prevalence of approximately 2-3% in the general population, with substantially higher conditional risk among frequent users. However, surveillance systems relying on legacy diagnostic modules or restrictive assessment logic may underestimate disorder prevalence despite rising cannabis exposure and increasing acute health-care encounters. Evidence for CUD treatment indicates modest but consistent benefits from psychosocial interventions-including motivational, cognitive-behavioral, and contingency-based approaches-while no pharmacotherapies are currently approved, and treatment engagement remains low relative to estimated prevalence. Conclusion: Apparent uncertainty in post-legalization health outcomes often reflects limitations in measurement rather than absence of harm. Aligning surveillance systems with contemporary diagnostic frameworks and strengthening treatment pathways are essential for translating exposure monitoring into effective public health response. As legalization continues to expand, CUD provides an important test of whether addiction treatment systems can adapt to legalized substances whose harms are diffuse, chronic, and frequently under-recognized.
Background: China's drug landscape is rapidly evolving, yet existing research remains fragmented, lacking a comprehensive national perspective. This study analyzes current drug use patterns, trends, and regional differences in China, providing critical insights to guide effective anti-drug policies. Methods: We conducted a comprehensive multilevel analysis of secondary data of drug use data from the China Drug Situation Report (2005-2023) and 34 academic articles (1990-2021). Our analysis includes descriptive statistics, time series, regional differences, and population-specific trends. Results: This study identifies a declining trend in traditional drug use, while the use of new synthetic drugs and new psychoactive substances (NPS) is increasing. Strong negative correlations were found between law enforcement intensity and overall drug use (r: -0.89 to-0.92). Significant regional disparity in NPS use was identified, with prevalence substantially higher in southern China than in the north (p = 0.019). Traditional drugs are more prevalent in the northwest and central regions, while new drugs and NPS are more commonly found in the eastern coastal and central urban areas. The use of NPS is notably higher among adolescents in economically developed regions. Conclusion: The analysis delineates a clear shift in China's drug landscape from traditional drugs to NPS, with concentrations in southern, coastal, and adolescent demographics. These patterns suggest that effective policy responses should be regionally tailored and prioritize youth prevention in economically advanced areas. Future research is needed to verify these associations and explore underlying causal mechanisms.
Mark S Gold,1 Nicole M Avena,2 Rajendra D Badgaiyan,3 Panayotis K Thanos,4,5 Kenneth Blum5,6 1University of Florida, Gainesville, FL, USA; 2Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York City, NY, USA; 3Department of Psychiatry, University of Texas, Long School of Texas, Health Science Center, San Antonio, TX, USA; 4University at Buffalo, Department of Pharmacology and Toxicology, Buffalo, NY, USA; 5Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel, Israel; 6Western University Health Sciences, Pomona, CA, USACorrespondence: Rajendra D Badgaiyan, Email badgaiyan@gmail.com
Background:Substance use disorders (SUDs) are highly prevalent, chronic conditions that often go untreated. Technology-driven interventions, including digital therapeutics, web-based programs, and mobile applications, have expanded treatment access. The COVID-19 pandemic accelerated the adoption of digital approaches, and national policy calls for enhanced use of telehealth and app-based recovery support. However, user engagement with SUD apps remains a challenge. Objective:This narrative review summarizes evidence on digital interventions for SUDs, emphasizing mobile apps. It examines what differentiates effective interventions, drawing on insights from the broader context of general mobile app use. It also proposes strategies to enhance engagement in digital therapeutics. Methods:We reviewed the literature (2013-2025) on SUD digital interventions, including randomized trials, systematic reviews, and large observational studies of SUD-focused apps. Key findings on clinical efficacy and engagement were extracted, along with examining engagement tactics from mobile gaming and other app domains to inform potential improvements. Results:Several apps have demonstrated efficacy in reducing substance use or supporting abstinence, particularly those that integrate evidence-based therapy content, provide personalized feedback, offer craving-management tools, and facilitate connectivity to peer or clinician support. In contrast, apps with minimal interactive content often show no added benefit. A major barrier is sustaining user engagement, as many SUD apps experience a steep drop-off in use after the initial download. Strategies such as gamification, contingency management (utilizing incentives), social networking features, and integration with ongoing care can significantly enhance engagement. Early data suggest that blending these strategies into SUD apps yields higher retention and better clinical results. Conclusion:Mobile apps are emerging as valuable adjuncts for SUD treatment, but their real-world impact depends on users' engagement with compelling content. By incorporating tangible rewards, personalized and timely interventions, social support, and provider involvement, digital therapies for SUDs enhance engagement and, consequently, improve long-term recovery outcomes.
