Mediational pathways among drug use initiation, use-related consequences, and quit attempts.

Background: Factors that predict attempts to discontinue drug use are clinically relevant and may inform treatment. This study investigated drug use-related consequences as a predictor of drug quit attempts and treatment seeking among two cohorts of persons who use drugs. Methods: Drug use and clinical characteristics were assessed among persons who use cocaine (N=176; urine-verified; 'Cocaine Cohort') and among those who use heroin (N=166; urine-verified; 'Heroin Cohort'). Mediation analyses assessed relationships among age at initial drug use, adverse drug-specific use-related consequences, and drug-specific quit attempts, separately for each cohort. Forward conditional logistic regression models evaluated drug use and clinical symptom scores as predictors of drug-specific treatment seeking. Results: Controlling for age, mediation models showed that drug use consequences fully mediated the relationship between age at initial drug use and number of drug-specific quit attempts for the 'Cocaine Cohort' and 'Heroin Cohort' (R2=0.30, p<.001; R2=0.17, p<.001; respectively). Reporting more consequences predicted more quit attempts in each cohort, accounting for duration of use (ps<.001). Reporting more consequences also predicted greater likelihood of seeking drug use treatment (ps<.001) and was associated with more severe clinical symptoms in each cohort (ps<.05). Conclusions: Using a parallel analysis design, we showed that reporting more drug-specific use-related consequences predicted more drug-specific quit attempts and greater likelihood to seek treatment in two cohorts: persons who use cocaine and those who use heroin. Our findings suggest that experiencing more drug use consequences predicts more attempts to seek drug abstinence and that assessment of consequences may be informative for treatment.

Attention-deficit/hyperactivity disorder combined subtype exacerbates opioid use disorder consequences: Mediation by impulsive phenotypes.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is highly prevalent and associated with opioid use disorder (OUD). Yet, little is known about the mechanisms by which ADHD (which is a heterogeneous construct/diagnosis) might alter the trajectory of OUD outcomes in persons who use heroin. AIM: We examined whether ADHD subtypes are related to heroin-use consequences and the extent to which the effects of ADHD on lifetime heroin-use consequences are mediated by two impulsivity factors that may be partly independent of ADHD: foreshortened time perspective and drug-use impulsivity. METHODS: Individuals who reported regular heroin use (N=250) were screened using the Assessment of Hyperactivity and Attention (AHA), Impulsive Relapse Questionnaire (IRQ), Stanford Time Perception Inventory (STPI), and a comprehensive assessment of lifetime and current substance use and substance-related consequences. This secondary analysis examined whether ADHD or intermediate phenotypes predicted heroin-use consequences. RESULTS: Relative to participants whose AHA scores indicated lifetime absence of ADHD (n=88), those with scores indicating persistent ADHD (childhood and adult, n=62) endorsed significantly more total lifetime heroin-use consequences despite comparable heroin-use severity. Likewise, there was a significant indirect effect of the combined ADHD subtype in childhood on lifetime heroin-use consequences. This effect was mediated by STPI scores indicating less future (and more hedonism in the present) temporal orientation and by IRQ scores indicating less capacity for delaying drug use. CONCLUSION: The combined ADHD subtype is significantly associated with lifetime heroin-use consequences, and this effect is mediated through higher drug-use impulsivity (less capacity for delay) and lower future temporal orientation.

Development and validation of a reasons for electronic cigarette use questionnaire.

People use electronic cigarettes (e-cigarettes) for many reasons, but currently there are no comprehensive assessments of the motivations for tobacco vaping. The aim of the present study is to develop and test the initial construct validity of a new measure to assess reasons for e-cigarette use. We developed a 56-item measure based on the e-cigarette literature. This measure, along with demographic and tobacco use questions, was administered to adults who self-identified as past or present e-cigarette users on the Prolific crowdsourcing platform. The sample (n = 965) was randomly assigned into two analytic groups for exploratory factor analysis (EFA; n = 484) and confirmatory factor analysis (CFA; n = 481). The sample ranged from 19 to 77 (M = 36.6; SD = 11.5) years old, and 42.2% identified as women, 74.6% as White, 7.2% as African American, 4.7% as Asian/Pacific Islander, and 5.1% Hispanic/Latino. After removing highly correlated items and nonloading items on the EFA, the 56-item scale was reduced to 47 items across eight factors. The eight subscales assessing various motivation domains of e-cigarette use included social influence, alternative to cigarettes, pleasurable effects, harm reduction, dependence, cessation, weight/appetite, and smell/flavor domains. Cronbach's α coefficients and preliminary analyses of differential motivation based on sex, age, and daily smoker status are presented. This study demonstrates the construct validity for the first comprehensive measure tested to assess reasons for e-cigarette use. This measure has potential to become a valuable assessment for researchers examining factors contributing to tobacco vaping among a variety of populations and settings. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The First "Hit" to the Endocannabinoid System? Associations Between Prenatal Cannabis Exposure and Frontolimbic White Matter Pathways in Children.

Background: Cannabis is the most used federally illicit substance among pregnant people in the United States. However, emerging preclinical data show that a significant portion of cannabis constituents, such as Δ9-tetrahydrocannabinol and its bioactive metabolites, readily cross the placenta and accumulate in the fetal brain, disrupting neurodevelopment. Recent research using the Adolescent Brain Cognitive Development (ABCD) Study cohort has linked prenatal cannabis exposure (PCE) to greater neurobehavioral problems and lower total gray and white matter volume in children. Here, we examined the impact of PCE on frontolimbic white matter pathways that are critical for cognitive- and emotion-related functioning, show a high density of cannabinoid receptors, and are susceptible to cannabis exposure during other periods of rapid neurodevelopment (e.g., adolescence). Methods: This study included 11,530 children (mean ± SD age = 118.99 ± 7.49 months; 47% female) from the ABCD Study cohort. Linear mixed-effects models were used to examine the effects of caregiver-reported PCE on fractional anisotropy of 10 frontolimbic pathways (5 per hemisphere). Results: PCE was associated with lower fractional anisotropy of the right (ß = -0.005, p < .001) and left (ß = -0.003, p = .007) fornix, and these results remained significant after adjusting for a variety of covariates, multiple comparisons, fractional anisotropy of all fibers, and using a quality-control cohort only. Conclusions: In sum, we demonstrated small, yet reliable, effects of PCE on white matter integrity during childhood, particularly in the fornix, which plays a crucial role in emotion- and memory-related processes. Future studies are needed to understand the impacts of small changes in brain structure or function on neurodevelopment and risk of neurobehavioral problems.

Effects of Two Cannabidiol Oil Products on Self-Reported Stress Relief: A Quasi-Experimental Study.

Introduction: Estimated rates of past-month cannabidiol (CBD) use in the general public are 13-26% and emerging research examines CBD as a potential adjunct treatment for several medical conditions, including stress-related disorders (e.g., depression, anxiety, and chronic pain). However, little is known about the effects of different CBD products on self-reported stress. The present study compared the effects of two delta-9-tetrahydrocannabinol (THC)-free CBD tincture products - (1) an isolate CBD oil and (2) a broad spectrum CBD oil - on self-ratings of effectiveness of the product and ability to manage stress. Methods: This quasi-experimental study reports on a total of 374 participants who completed either a 30- or 60-day regimen. Participants were instructed to use a 1,000 mg CBD isolate product at will, and then switch over to a 1,000 mg broad spectrum product for the remainder of the regimen (i.e., next 15 or 30 days). Self-reported effectiveness of the product and its ability to help manage stress was compared between the isolate and broad spectrum products. We also examined overall impression, quality, taste, and adverse effects of each product. Results: Overall, both products were rated to be highly effective and able to assist with stress management. Participants reported that the broad spectrum product's effectiveness (p < 0.001) and ability to reduce stress (p < 0.001) as greater than the isolate product across both regimens. However, participants preferred the taste of the isolate product over that of the broad spectrum across regimens (p < 0.05). For the 30-day regimen, participants reported a more positive overall impression of the isolate as compared to the broad spectrum (p < 0.001); however, overall impression did not differ between the products in the 60-day regimen. There was no difference in adverse effects or quality between the products, across both regimens. Conclusion: These results fit with prior studies suggesting anti-stress effects of CBD. Ratings were higher for the broad spectrum as compared to the isolate product, which is consistent with prior data suggesting that cannabinoids can work synergistically to maximize benefits. Nonetheless, more controlled studies are needed to explore these effects in nonclinical and clinical populations.

HIV chronicity as a predictor of hippocampal memory deficits in daily cannabis users living with HIV.

Background: Antiretroviral medications have increased the lifespan of persons living with HIV (PLWH) thereby unmasking memory decline that may be attributed to chronological age, HIV symptomatology, HIV disease chronicity, and/or substance use (especially cannabis use which is common among PLWH). To date, few studies have attempted to disentangle these effects. In a sample of daily cannabis-using PLWH, we investigated whether hippocampal memory function, assessed via an object-location associative learning task, was associated with age, HIV chronicity and symptom severity, or substance use. Methods: 48 PLWH (12.9 ± 9.6 years since HIV diagnosis), who were 44 years old on average (range: 24-64 years; 58 % male) and reported daily cannabis use (recent use confirmed by urinalysis) completed the study. We assessed each participant's demographics, substance use, medical history, current HIV symptoms, and hippocampal memory function via a well-validated object-location associative learning task. Results: Multiple regression analyses found that living more years since HIV+ diagnosis predicted significantly worse associative learning total score (r=-0.40) and learning rate (r=-0.34) whereas chronological age, cannabis-use characteristics, and recent HIV symptom severity were not significantly related to hippocampal memory function. Conclusions: In daily cannabis-using PLWH, HIV chronicity was related to worse hippocampal memory function independent from cannabis use, age, and HIV symptomatology. Object-location associative learning performance could serve as an 'early-warning' metric of cognitive decline among PLWH. Future research should examine longitudinal changes in associative learning proficiency and evaluate interventions to prevent hippocampal memory decline among PLWH. ClinicalTrials.gov: NCT01536899.

Response to health warnings on cigarette packs as a predictor of future smoking among current tobacco smokers.

The United States (US) Food and Drug Administration (FDA) requires health warning labels on all cigarette packages as part of a campaign to reduce tobacco smoking. Prior research has revealed the mixed effectiveness of these health warning labels. The present study used nationally representative, longitudinal data from the Population Study of Tobacco and Health (PATH) Study to assess whether reported reactions to health warning labels on cigarette packs predict smoking frequency and smoking cessation two years later. We hypothesized that individuals who reported strong reactions to health warnings at Wave 1 of the PATH Study would engage in less frequent smoking behavior and would be more likely to have completely quit cigarette smoking two years later (Wave 3), compared with individuals who did not report strong reactions. Multinomial and binary logistic regressions were used to estimate the associations between attitudes toward health warning labels and later smoking frequency and smoking cessation. Our hypotheses were partially supported; results indicated that several attitudes toward health warnings predict later smoking behaviors. These findings indicate general effectiveness of health warning labels and support the FDA's initiative to require more attention-grabbing health warning labels on cigarette packs.

Prenatal alcohol exposure and attention-deficit/hyperactivity disorder independently predict greater substance use in young adulthood.

BACKGROUND: The degree to which prenatal alcohol exposure (PAE) may influence alcohol and drug use in adulthood is difficult to determine. That is because PAE is highly correlated with environmental factors, including low socioeconomic status and exposure to parental drinking, and with behavioral problems, such as, attention-deficit/hyperactivity disorder (ADHD), which are correlated with alcohol use and abuse. METHODS: Participants were 121 young adults from our Detroit Longitudinal Cohort study. Mothers were recruited during pregnancy and interviewed about their alcohol consumption using a timeline follow-back procedure. At 19 years, their offspring were interviewed regarding current and past use of alcohol, cigarettes, and other illicit drugs. RESULTS: PAE was associated with greater alcohol, cannabis, and cigarette use. PAE, assessed using overall alcohol intake during pregnancy and alcohol dose per occasion, was associated with larger quantities of alcohol per occasion and greater alcohol tolerance in early adulthood. These effects persisted after control for demographic background, sex, age and education of participant, home environment, other prenatal drug exposure, and postnatal alcohol and drug use by the primary caregiver. Whereas ADHD predicted average alcohol consumed/month during young adulthood, PAE predicted alcohol dose/drinking occasion, and the effect on dose/occasion was not mediated by ADHD. CONCLUSIONS: The effects of PAE on alcohol and cannabis use in young adulthood are not attributable to being reared in an environment that is socioeconomically disadvantaged or in one in which there is extensive maternal drinking. Furthermore, PAE was related to enhanced alcohol tolerance in young adults, a risk factor for alcohol use disorder later in life. Although ADHD was associated with greater alcohol consumption in early adulthood, it did not mediate the effect of PAE on offspring's alcohol use.

Anhedonia modulates benzodiazepine and opioid demand among persons in treatment for opioid use disorder.

Background: Benzodiazepine (BZD) misuse is a significant public health problem, particularly in conjunction with opioid use, due to increased risks of overdose and death. One putative mechanism underlying BZD misuse is affective dysregulation, via exaggerated negative affect (e.g., anxiety, depression, stress-reactivity) and/or impaired positive affect (anhedonia). Similar to other misused substances, BZD consumption is sensitive to price and individual differences. Although purchase tasks and demand curve analysis can shed light on determinants of substance use, few studies have examined BZD demand, nor factors related to demand. Methods: This ongoing study is examining simulated economic demand for alprazolam (among BZD lifetime misusers based on self-report and DSM-5 diagnosis; n = 23 total; 14 male, 9 female) and each participant's preferred-opioid/route using hypothetical purchase tasks among patients with opioid use disorder (n = 59 total; 38 male, 21 female) who are not clinically stable, i.e., defined as being early in treatment or in treatment longer but with recent substance use. Aims are to determine whether: (1) BZD misusers differ from never-misusers on preferred-opioid economic demand, affective dysregulation (using questionnaire and performance measures), insomnia/behavioral alertness, psychiatric diagnoses or medications, or urinalysis results; and (2) alprazolam demand among BZD misusers is related to affective dysregulation or other measures. Results: Lifetime BZD misuse is significantly (p < 0.05) related to current major depressive disorder diagnosis, opioid-negative and methadone-negative urinalysis, higher trait anxiety, greater self-reported affective dysregulation, and younger age, but not preferred-opioid demand or insomnia/behavioral alertness. Alprazolam and opioid demand are each significantly positively related to higher anhedonia and, to a lesser extent, depression symptoms but no other measures of negative-affective dysregulation, psychiatric conditions or medications (including opioid agonist therapy or inpatient/outpatient treatment modality), or sleep-related problems. Conclusion: Anhedonia (positive-affective deficit) robustly predicted increased BZD and opioid demand; these factors could modulate treatment response. Routine assessment and effective treatment of anhedonia in populations with concurrent opioid and sedative use disorder may improve treatment outcomes. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT03696017, identifier NCT03696017.

Cannabis and complementary/alternative self-treatment approaches for symptom management among African American persons living with HIV.

Persons living with HIV (PLWH) experience symptoms from disease progression and side effects of antiretroviral treatment. This study examines in African American PLWH (N = 259) commonly-endorsed symptoms, types and self-rated efficacy of therapies for symptom alleviation. Analyses were stratified by gender (n = 178 males, n = 81 females) and cannabis use typology: non-users (n = 90), mostly recreational use (n = 46), mixed recreational/therapeutic use (n = 51), or mostly therapeutic use (n = 72). Females reported greater severity for pain, fatigue, depression, weight change and tingling in extremities, but there were no gender differences for ratings of poor sleep, anxiety, poor appetite, or headache. Both marijuana (used therapeutically by females more than males) and medication(s) were among the 3 top methods for managing pain, poor sleep, anxiety, and headache. Marijuana was most often used for poor appetite, and medications for depression. Perceived efficacy of self-treatment approaches was moderately good. Among African American PLWH, symptom severity was higher for females and for therapeutic users of cannabis. Marijuana and medicine were often used to self-treat symptoms, but many participants did nothing. These results highlight the need for careful evaluation and management of symptoms in this underserved population.

Impact of prenatal cannabis exposure on functional connectivity of the salience network in children.

Cannabis use among pregnant people has increased over the past decade. This is of concern as prenatal cannabis exposure (PCE) is associated with cognitive, motor, and social deficits among offspring. Here, we examined resting-state functional connectivity (rsFC) of the salience network (SN)-a core neurocognitive network that integrates emotional and sensory information-in children with (vs. without) PCE. Using neuroimaging and developmental history data collected from 10,719 children (M ± SD = 9.92 ± 0.62 years; 47.9% female) from the Adolescent Brain Cognitive Development study, we assessed the impact of parent-reported PCE (before or after knowledge of pregnancy) on rsFC within and between the SN and five other core neurocognitive networks. We also evaluated whether SN rsFC mediated the association between PCE and child psychopathology. Results showed that PCE before (but not after) knowledge of pregnancy was associated with lower SN-ventral attention network (VAN) rsFC. Furthermore, psychotic-like experiences mediated the association between PCE and SN-VAN rsFC, and reversal of the model was also significant, such that SN-VAN rsFC mediated the association between PCE and psychotic-like symptoms. However, these mediation effects were no longer significant after the inclusion of covariates. Taken together, these findings suggest that developmental alterations in SN-VAN interactions may explain the previously reported association between PCE and elevated risk of child psychopathology.

Michigan Model for HealthTM Learning to Enhance and Adapt for Prevention (Mi-LEAP): protocol of a pilot randomized trial comparing Enhanced Replicating Effective Programs versus standard implementation to deliver an evidence-based drug use prevention curriculum.

BACKGROUND: School-based drug use prevention programs have demonstrated notable potential to reduce the onset and escalation of drug use, including among youth at risk of poor outcomes such as those exposed to trauma. Researchers have found a robust relationship between intervention fidelity and participant (i.e., student) outcomes. Effective implementation of evidence-based interventions, such as the Michigan Model for HealthTM (MMH), is critical to achieving desired public health objectives. Yet, a persistent gap remains in what we know works and how to effectively translate these findings into routine practice. The objective of this study is to design and test a multi-component implementation strategy to tailor MMH to meet population needs (i.e., students exposed to trauma), and improve the population-context fit to enhance fidelity and effectiveness. METHODS: Using a 2-group, mixed-method randomized controlled trial design, this study will compare standard implementation versus Enhanced Replicating Effective Programs (REP) to deliver MMH. REP is a theoretically based implementation strategy that promotes evidence-based intervention (EBI) fidelity through a combination of EBI curriculum packaging, training, and as-needed technical assistance and is consistent with standard MMH implementation. Enhanced REP will tailor the intervention and training to integrate trauma-informed approaches and deploy customized implementation support (i.e., facilitation). The research will address the following specific aims: (1) design and test an implementation strategy (Enhanced REP) to deliver the MMH versus standard implementation and evaluate feasibility, acceptability, and appropriateness using mixed methods, (2) estimate the costs and cost-effectiveness of Enhanced REP to deliver MMH versus standard implementation. DISCUSSION: This research will design and test a multi-component implementation strategy focused on enhancing the fit between the intervention and population needs while maintaining fidelity to MMH core functions. We focus on the feasibility of deploying the implementation strategy bundle and costing methods and preliminary information on cost input distributions. The substantive focus on youth at heightened risk of drug use and its consequences due to trauma exposure is significant because of the public health impact of prevention. Pilot studies of implementation strategies are underutilized and can provide vital information on designing and testing effective strategies by addressing potential design and methods uncertainties and the effects of the implementation strategy on implementation and student outcomes. TRIAL REGISTRATION: NCT04752189-registered on 8 February 2021 on ClinicalTrials.gov PRS.

A mixed methods investigation of implementation determinants for a school-based universal prevention intervention.

Background: Effective implementation of evidence-based prevention interventions in schools is vital to reducing the burden of drug use and its consequences. Universal prevention interventions often fail to achieve desired public health outcomes due to poor implementation. One central reason for suboptimal implementation is the limited fit between the intervention and the setting. Research is needed to increase our understanding of how intervention characteristics and context influence intervention implementation in schools to design implementation strategies that will address barriers and improve public health impact. Methods: Using a convergent mixed methods design we examined qualitative and quantitative data on implementation determinants for an evidence-based health curriculum, the Michigan Model for HealthTM (MMH) from the perspective of health teachers delivering the curriculum in high schools across the state. We examined data strands independently and integrated them by investigating data alignment, expansion, and divergence. Results: We identified three mixed methods domains: (1) Acceptability, (2) intervention-context fit, and (3) adaptability. We found alignment across data strands as teachers reporting low acceptability also reported low fidelity. The fit between student needs and the curriculum predicted fidelity (expansion). Teachers mentioned instances of poor intervention-context fit (discordance), including when meeting the needs of trauma-exposed youth and keeping updated on youth drug use trends. Teachers reported high adaptability (concordance) but also instances when adaptation was challenging (discordance). Conclusions: This investigation advances implementation research by deepening our understanding of implementation determinants for an evidence-based universal prevention intervention in schools. This will support designing effective implementation strategies to address barriers and advance the public health impact of interventions that address important risk and protective factors for all youth. Plain Language Summary: (1) What is Already Known About the Topic? While many evidence-based interventions (EBIs) exist to address key health issues among youth including substance use and mental health, few of these interventions are effectively implemented in community settings, such as schools. Notable multilevel barriers exist to implement universal prevention in schools. Researchers identify that misalignment between the intervention and the context is a key reason why many implementation efforts do not achieve desired outcomes. (2) What Does This Paper Add? This paper combines the strengths of qualitative and quantitative research methods to identify and understand challenges to intervention-context fit for a comprehensive health curriculum, the Michigan Model for HealthTM (MMH) which is widely adopted throughout Michigan, from the perspective of end users. This paper also utilizes the consolidated framework for implementation research and implementation outcomes framework to guide our understanding of implementing complex interventions and key barriers to implementation in schools. This research provides a foundation to design effective strategies that will balance curriculum fidelity and adaptation to achieve public health objectives. (3) What are the Implications for Practice, Research, or Policy? We need implementation strategies that guide flexibility and fidelity in EBI delivery in schools. While overall teachers felt the curriculum was adaptable and met student needs, they also mentioned specific instances when they would benefit from additional implementation support, such as making adaptations to meet the needs of trauma-exposed youth and keeping up-to-date with emerging drugs. Implementation strategies designed to address these challenges can improve fidelity and ultimately student well-being.

Electronic cigarette use among sexual minority and heterosexual young adults in a U.S. national sample: Exploring the modifying effects of advertisement exposure.

Sexual minorities demonstrate disparities in traditional cigarette use and nicotine-related health consequences. Electronic cigarette (e-cigarette) use is increasing, particularly among adolescents and young adults. Sexual minorities have been found to use e-cigarettes at higher rates than heterosexuals, but little is known about reasons for this disparity. The present study examined characteristics of current and lifetime e-cigarette use between sexual minority and heterosexual young adults (18-34; N = 14,174) using a U.S. national sample from the Population Assessment of Tobacco and Health (PATH) Survey-Wave 3. Sexual minority young adults were hypothesized to have higher rates of current and lifetime e-cigarette use and higher rates of exposure to e-cigarette advertisements. These exposures were hypothesized to moderate the relationship between sexual minority status and current e-cigarette use. Results revealed that sexual minority respondents demonstrated greater risk of current e-cigarette use after adjusting for several covariates (e.g., sex, age, lifetime cigarette use). However, advertisement exposures did not moderate the relationship between sexual minority status and current e-cigarette use. In contrast, sexual minority status was not associated with lifetime e-cigarette use after controlling for covariates. Post-hoc tests revealed that sexual minority status was associated with heightened risk of current and lifetime e-cigarette use only among females. This is the first study to examine the impact of e-cigarette advertising across expanded settings, including point of sale locations (e.g., retail, bars, festivals), while exploring differences in current and lifetime e-cigarette use among sexual minority and heterosexual males and females.

Long-term effects of opioid overdose prevention and response training on medical student knowledge and attitudes toward opioid overdose: A pilot study.

BACKGROUND: Medical settings provide ideal opportunities to identify patients with substance use disorders and provide harm reduction and treatment resources. Medical students often volunteer in the community and can spend substantial time with patients, serving as touchpoints. Accordingly, medical schools have begun training in harm reduction. Initial studies show such training acutely improves knowledge, but sustained effects remain unclear. This pilot study explored longer-term impacts of Opioid Overdose Prevention and Response Training (OOPRT) on medical student knowledge about opioids, overdose, and naloxone. METHODS: Students completed a survey about knowledge of opioid use disorder, overdoses, and attitudes towards patients. This included Opioid Overdose Knowledge (OOKS) and Opioid Overdose Attitudes (OOAS) scales. A subset of students was invited to attend OOPRT and complete a post-training survey. All who completed the baseline survey were invited to complete a 6-month follow-up. We analyzed long-term training effects on OOKS and OOAS scores. RESULTS: 89 students completed baseline and 6-month follow-up surveys; of these, 22 received training. OOPRT yielded significant improvements in knowledge of signs of opioid overdose (F(2,38) = 18.04, P < .001), actions to take during overdose (F(2,38) = 8.32, P = .001), and naloxone use (F(2,38) = 35.46, P < .001), along with attitudes regarding overdose competencies (F(2,38) = 99.40, P < .001) and concerns (F(2,38) = 8.86, P < .001). When comparing over time, students who attended OOPRT retained significantly higher competency scores than those who did not attend F(1,87) = 40.82, P < .001). No other significant differences were observed. CONCLUSIONS: This study demonstrates immediate efficacy of OOPRT in improving opioid overdose knowledge and attitudes and sustained changes at 6 months, compared to standard undergraduate medical curricula alone. Future research with larger sample sizes is underway to validate these preliminary findings and examine the difference in attitudes and knowledge retention over time. Given that students report interest in receiving OOPRT and consider it worthwhile, systematic study is warranted.

Effects of cocaine and/or heroin use on resting cardiovascular function.

BACKGROUND: Regular cocaine and/or heroin use is associated with major health risks, especially cardiovascular disease, but confounded by other factors. We examined effects of chronic (years regular use) and recent (past-month) cocaine and heroin use, controlling for other factors, on resting cardiovascular function. METHODS: In a sample of 292 cocaine and/or heroin users, we assessed demographics, body mass index (BMI), substance use history, electrocardiogram, heart rate (HR) and blood pressure (BP). Three-block (1: demographics, BMI; 2: tobacco, alcohol, cannabis; 3: cocaine, heroin) regression analyses were conducted to predict cardiovascular measures. RESULTS: Higher BMI predicted increased systolic and diastolic BP (as did older age), increased supine HR, and longer QRS duration, QTc interval, PR interval, and P-wave duration. Past-month cannabis-use days predicted higher systolic BP, lower supine HR, and greater likelihood of early repolarization and ST elevation; average daily cannabis use predicted shorter QTc interval. Average daily alcohol use predicted higher diastolic BP, higher supine HR and lower likelihood of sinus bradycardia (HR < 60 bpm). Past-month tobacco-use days predicted shorter QTc interval and lower lower likelihood of profound bradycardia (HR < 50 bpm). Past-month heroin-use days predicted lower seated HR, greater likelihood of sinus bradycardia and lower likelihood of left ventricular hypertrophy. More years of regular cocaine use and past-month cocaine-use days predicted longer QTc interval. CONCLUSIONS: Cocaine and heroin use incrementally predicted modest variance in resting bradycardia and QTc interval. Clinicians should first consider demographics and recent use of tobacco, alcohol and cannabis before assuming cocaine and heroin affect these measures.

COVID-19 and Substance Use in Adolescents.

Studies have yielded mixed findings regarding changes in adolescent substance use during the COVID-19 pandemic; some report increased alcohol and cannabis use, others show less binge drinking and vaping behaviors, and others no change. In 2019, only 8.3% of the 1.1 million adolescents with a substance use disorder received specialized treatment. Treatment rates for 2020 have not yet been published. Stay-at-home orders and social distancing guidelines put into place in March 2020 caused the partial closure of many outpatient substance use clinics. The implications of this treatment suspension and special considerations for working with adolescents during stay-at-home orders are discussed.

Demand curve analysis of marijuana use among persons living with HIV.

BACKGROUND: Despite medicalization and legalization of marijuana use, factors influencing demand for marijuana among persons living with HIV (PLWH) are incompletely understood. This knowledge gap undermines effective clinical management and policies. This study used demand curve simulation methods to address these issues. METHODS: Marijuana-using PLWH (N = 119) completed experimental tasks to simulate amount of marijuana purchasing/use across different costs (money or time), and likelihood of reselling marijuana or marijuana therapeutic-use registration card in relation to profits. Additional simulations assessed purchasing of marijuana relative to other drug and non-drug goods. RESULTS: Simulated marijuana use decreased as money and time costs increased. Consumption was greater for participants with more severe Cannabis Use Disorder (CUD) and anxiety, intermediate pain levels, and past 90-day opioid use. Whereas few participants chose to sell their registration card, marijuana resale (diversion) steeply increased with profit. Likelihood of seeking marijuana therapeutic-use certification decreased in relation to registration card money cost, having to visit more physicians to get a signature, and delay to receiving the card, and increased with duration of certification. Participants who reported recent opioid use were more likely to seek certification. Consumption of several commodities assessed was independent of marijuana. CONCLUSIONS: Simulated marijuana use was related to participants' clinical profile (CUD, anxiety and pain symptoms, recent opioid use), and unrelated to purchasing other goods. Likelihood of seeking marijuana therapeutic-use registration was affected by several types of costs and recent opioid use. Participants were unlikely to divert registration cards. We discuss clinical and policy implications of these findings.

Contingency management for individuals with chronic health conditions: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Contingency management (CM) interventions involve providing reinforcement for engaging in a desired behavior, and have been shown to increase treatment adherence and promote abstinence in the treatment of substance use disorders. This review was conducted to systematically review the literature on the effectiveness of CM when applied to a range of medical conditions outside of substance use disorders. METHOD: The authors identified a total of 24 randomized studies examining the effects of CM on four outcomes: weight change, physical activity, medication/device adherence, and viral load that were included in the qualitative summary, and 20 studies included in the meta-analysis. RESULTS: CM was associated with positive outcomes for physical activity and medication/device adherence compared to control conditions. Findings with weight loss and viral load were more mixed, and evidence for publication bias was found for both outcomes. The effects of CM tend to dissipate when the contingency is removed. Heterogeneity was observed across most outcomes. LIMITATIONS AND CONCLUSIONS: This review provides preliminary support for the use of CM in increasing physical activity and improving adherence to medication for chronic health conditions while reinforcement is ongoing. Future studies should examine potential moderators and identify strategies to maintain these changes over time.

N-acetylcysteine reduces cocaine-seeking behavior and anterior cingulate glutamate/glutamine levels among cocaine-dependent individuals.

N-acetylcysteine (NAC) is a cystine prodrug shown to reduce cocaine- and cue-primed reinstatement of cocaine-seeking behavior in preclinical studies. In this inpatient study, the effects of NAC maintenance versus placebo on cocaine-seeking behavior were examined during cocaine-primed and unprimed self-administration sessions among non-treatment-seeking, cocaine-dependent individuals. Twelve participants completed this double-blind, placebo-controlled, within-subject crossover study. Each participant was maintained for 1 week (Sat-Fri) on NAC (1200-mg TID; 3600 mg/day total) and 1 week on placebo (0-mg TID); medication order was randomized. A subset of participants underwent proton magnetic resonance spectroscopy scans (n = 8) on the third day of medication (Mon) to assess neurochemistry in the rostral anterior cingulate (rACC; voxel = 4.5 cm3 ). In four randomized sessions (Tue-Fri) each week, each participant could earn unit amounts of cocaine (10 mg, fixed) versus money ($0.50 vs. $1.50) on a choice, progressive ratio schedule after insufflating active versus placebo cocaine-priming doses (110 mg vs. 4 mg). Relative to the placebo priming dose, the active cocaine priming dose (110 mg) increased cocaine-seeking behavior (p = .003). NAC reduced cocaine-primed cocaine-seeking behavior compared with placebo levels (p = .044) but did not alter placebo-primed cocaine-seeking behavior. The larger money alternative ($1.50) suppressed cocaine-seeking behavior relative to the smaller money alternative ($0.50; p = .011). Compared with placebo levels, NAC significantly decreased rACC glutamate + glutamine levels (p = .035) and numerically decreased rACC glutamate levels (p = .085). These preliminary findings indicate that NAC suppresses cocaine-seeking behavior in some, but not all, experimental scenarios. Further, our findings suggest NAC may exert its therapeutic effects by modulating excitatory tone in the rACC.