Prize-based Incentives for Smoking Cessation Among People with HIV: A Sequential Multiple Assignment Randomized Trial (SMART).

INTRODUCTION: Contingency management (CM) is an incentive-based approach that has demonstrated efficacy for smoking cessation in various populations. There is an unmet need for feasible and effective smoking cessation interventions in people with HIV (PWH). The study purpose is to assess efficacy of prize-based CM for smoking cessation in PWH using a Sequential Multiple Assignment Randomization Trial (SMART) design selected to tailor intervention intensity based on early treatment response. METHODS: During phase 1, 129 participants were randomly assigned to high-magnitude prize CM (HM-CM) or standard of care (SoC) for 4 weeks. Participants who did not reduce smoking were randomized in Phase 2 to continued counseling with HM-CM plus monitoring support or only continued monitoring support for 8 weeks. Participants who reduced smoking were randomized to booster monitoring with low-magnitude CM or no additional care. Outcomes were biochemically-verified smoking reduction and 7-day abstinence prevalence at post-treatment, 6-month and 12-month follow-up. RESULTS: Phase 1 responders (based on biochemical indicators of smoking reduction) were significantly less likely to return to smoking (during treatment and at 6- and 12-months) if they received low-magnitude incentives. Notably, initial exposure to CM vs. SoC did not increase rate of phase 1 response, and high-magnitude incentives later in treatment did not lead to greater smoking cessation for early treatment non-responders. CONCLUSION: Weekly CM sessions in the first four weeks of smoking cessation intervention did not perform significantly better than SoC. However, brief booster CM sessions aimed at maintaining early smoking cessation hold clinical promise and warrant further investigation. IMPLICATIONS: This represents the first trial to examine the use of contingency management for smoking cessation among people with HIV within the context of a Sequential Multiple Assignment, Randomized Trial (SMART) design.

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).

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.

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.

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.

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.

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.

Beyond the Bud: Emerging Methods of Cannabis Consumption for Youth.

Cannabis continues to be the most widely used illicit substance among youth, as many teens view the risks of cannabis consumption to be low. With cannabis laws becoming lax and dispensaries becoming more prevalent throughout the United States, highly concentrated Δ-9-tetrahydrocannibinol (THC) is becoming readily available. This article examines the available literature on consumption of concentrated THC, focusing on potential consequences of concentrate use among youth. Various methods for consuming concentrated THC, including ingestion of edibles, vaping, and dabbing, are discussed, along with associated risks of each consumption method. Recommendations for health professionals are provided.

Factors associated with sedative use and misuse among heroin users.

BACKGROUND: Rates of both opioid and sedative use and misuse are rising. Comorbid opioid and sedative use is associated with especially severe consequences (e.g., overdose and poor health outcomes). Heroin users report multiple motivations for sedative use, including self-medication. We aimed to understand differences in lifetime substance use characteristics between heroin users with different sedative use histories. METHODS: Substance use data were collected from 385 non-treatment seeking heroin users. Subjects were divided into four lifetime sedative-use groups: no use, medical use only, non-medical use only, and mixed medical and non-medical use. We examined patterns of use of various substances of abuse (tobacco, alcohol, marijuana, cocaine, heroin, and sedatives) and individual characteristics associated with each. RESULTS: Non-medical sedative use (alone or in addition to medical use) was associated with more negative consequences from using all substances. Medical sedative use alone was not related to increased overdose or emergency room visits associated with heroin use. Non-medical sedative use was associated with increases in 15 of the 21 measured heroin consequences and only one of those - health problems - was also associated with medical sedative use. CONCLUSIONS: Concomitant non-medical sedative use and heroin use is associated with significantly greater negative outcomes than those experienced by heroin users who report use of sedatives only as prescribed. Understanding these differences offers insight into risks related to using both substances and may help treatment providers create targeted harm reduction interventions for this population.

Developing a scale of domains of negative consequences of chronic heroin use.

BACKGROUND: Chronic use of heroin typically leads to numerous negative life consequences and serious clinical impairment. Increased negative consequences can result in poor treatment outcomes as well as adverse health effects and impaired social functioning. Certain risk factors, including early substance use initiation, concurrent use of other illicit substances, and injection drug use are associated with an increase in negative consequences. This study examined whether there are unique domains of heroin consequences and, if so, whether these domains are related to specific substance use characteristics. METHODS: Data regarding substance use characteristics were collected from 370 non-treatment seeking, heroin-using, 18 to 55year-old participants from the Detroit metropolitan area. Principal component analysis (PCA) was used to analyze the factor structure of 21 negative heroin consequence items. RESULTS: PCA demonstrated that heroin consequences could be divided into 5 unique domains. These unique domains were related to specific substance use characteristics and heroin consequence domains. Injection heroin use was significantly associated with increased Factor 1 consequences (primarily acute medical problems) but not with consequences in other domains. Certain substance use characteristics, such as injection status and earlier onset of marijuana use, were associated with increased consequences in specific domains. CONCLUSIONS: These findings support the existence of unique domains of negative consequences, and indicate that some risk factors (e.g. injection use) may be specific to these domains. Potential tailored-treatment strategies aimed at improving treatment engagement and reducing harm for heroin use based on person-specific risks and negative consequences are discussed.

Magnitude and duration of cue-induced craving for marijuana in volunteers with cannabis use disorder.

AIMS: Evaluate magnitude and duration of subjective and physiologic responses to neutral and marijuana (MJ)-related cues in cannabis dependent volunteers. METHODS: 33 volunteers (17 male) who met DSM-IV criteria for Cannabis Abuse or Dependence were exposed to neutral (first) then MJ-related visual, auditory, olfactory and tactile cues. Mood, drug craving and physiology were assessed at baseline, post-neutral, post-MJ and 15-min post MJ cue exposure to determine magnitude of cue- responses. For a subset of participants (n=15; 9 male), measures of craving and physiology were collected also at 30-, 90-, and 150-min post-MJ cue to examine duration of cue-effects. RESULTS: In cue-response magnitude analyses, visual analog scale (VAS) items craving for, urge to use, and desire to smoke MJ, Total and Compulsivity subscale scores of the Marijuana Craving Questionnaire, anxiety ratings, and diastolic blood pressure (BP) were significantly elevated following MJ vs. neutral cue exposure. In cue-response duration analyses, desire and urge to use MJ remained significantly elevated at 30-, 90- and 150-min post MJ-cue exposure, relative to baseline and neutral cues. CONCLUSIONS: Presentation of polysensory MJ cues increased MJ craving, anxiety and diastolic BP relative to baseline and neutral cues. MJ craving remained elevated up to 150-min after MJ cue presentation. This finding confirms that carry-over effects from drug cue presentation must be considered in cue reactivity studies.

Heroin delay discounting: Modulation by pharmacological state, drug-use impulsivity, and intelligence.

Delay discounting (DD) refers to how rapidly an individual devalues goods based on delays to receipt. DD usually is considered a trait variable but can be state dependent, yet few studies have assessed commodity valuation at short, naturalistically relevant time intervals that might enable state-dependent analysis. This study aimed to determine whether drug-use impulsivity and intelligence influence heroin DD at short (ecologically relevant) delays during two pharmacological states (heroin satiation and withdrawal). Out-of-treatment, intensive heroin users (n = 170; 53.5% African American; 66.7% male) provided complete DD data during imagined heroin satiation and withdrawal. Delays were 3, 6, 12, 24, 48, 72, and 96 hours; maximum delayed heroin amount was thirty $10 bags. Indifference points were used to calculate area under the curve (AUC). We also assessed drug-use impulsivity (subscales from the Impulsive Relapse Questionnaire [IRQ]) and estimated intelligence (Shipley IQ) as predictors of DD. Heroin discounting was greater (smaller AUC) during withdrawal than satiation. In regression analyses, lower intelligence and IRQ Capacity for Delay as well as higher IRQ Speed (to return to drug use) predicted greater heroin discounting in the satiation condition. Lower intelligence and higher IRQ Speed predicted greater discounting in the withdrawal condition. Sex, race, substance use variables, and other IRQ subscales were not significantly related to the withdrawal or satiation DD behavior. In summary, heroin discounting was temporally rapid, pharmacologically state dependent, and predicted by drug-use impulsivity and estimated intelligence. These findings highlight a novel and sensitive measure of acute DD that is easy to administer.

Functional mu opioid receptor polymorphism (OPRM1 A(118) G) associated with heroin use outcomes in Caucasian males: A pilot study.

BACKGROUND: Heroin's analgesic, euphoric and dependence-producing effects are primarily mediated by the mu opioid receptor (MOR). A single gene, OPRM1, encodes the MOR. The functional polymorphism A(118)G, located in exon 1 of the OPRM1 gene, results in anatomically-specific reductions in MOR expression, which may alter an individual's response to heroin. In prior studies 118G (rare allele) carriers demonstrated significantly greater opioid tolerance, overdose vulnerability, and pain sensitivity than 118AA homozygotes. Those findings suggest OPRM1 genotype may impact characteristics of heroin use. METHODS: The present pilot study characterized the impact of OPRM1 genotype (rs1799971, 118G allele carriers vs. 118AA homozygotes) on heroin-use phenotypes associated with heroin dependence severity in a sample of male, Caucasian chronic heroin users (n = 86). RESULTS: Results indicate that 118G allele carriers reported significantly more heroin use-related consequences and heroin-quit attempts, and were more likely to have sought treatment for their heroin use than 118AA homozygotes. CONCLUSIONS: These preliminary findings, consistent with extant data, illustrate a role for OPRM1 allelic variation on heroin use characteristics, and provide support for considering genotype in heroin treatment and relapse prevention.

Progression to regular heroin use: examination of patterns, predictors, and consequences.

BACKGROUND: The present study retrospectively evaluated the chronology and predictors of substance use progression in current heroin-using individuals. METHODS: Out-of-treatment heroin users (urinalysis-verified; N=562) were screened for laboratory-based research studies using questionnaires and urinalysis. Comprehensive substance use histories were collected. Between- and within-substance use progression was analyzed using stepwise linear regression models. RESULTS: The strongest predictor of onset of regular heroin use was age at initial heroin use, accounting for 71.8% of variance. The strongest between-substance predictors of regular heroin use were ages at regular alcohol and tobacco use, accounting for 8.1% of variance. Earlier onset of regular heroin use (≤20 years) vs. older onset (≥30 years) was associated with a more rapid progression from initial to regular use, longer duration of heroin use, more lifetime use-related negative consequences, and greater likelihood of injecting heroin. The majority of participants (79.7%) reported substance use progression consistent with the gateway hypothesis. Gateway-inconsistent individuals were more likely to be African-American and to report younger age at initial use, longer duration of heroin use, and more frequent past-month heroin use. CONCLUSIONS: Our findings demonstrate the predictive validity and clinical relevance of evaluating substance use chronology and the gateway hypothesis pattern of progression.

Gender-specific predictors of retention and opioid abstinence during methadone maintenance treatment.

AIMS: Retention in methadone maintenance treatment (MMT) for 1 year is associated with positive outcomes including opioid abstinence, however, most studies have not investigated gender differences. We hypothesized that predictors of retention and opioid abstinence would differ between men and women, and aimed to determine which factors best predict retention and abstinence for each gender. METHODS: Data were available for 290 patients (173 M, 117 F) admitted to outpatient MMT. Regression analyses, stratified by gender, were conducted to identify unique predictors of MMT retention (<1 vs. >1 year) and opioid abstinence rate (proportion of opioid-free urine samples up to 1 year retention). RESULTS: Gender did not significantly predict treatment retention (mean = 231 days, 39% retained > 1 year) or opioid abstinence (49% overall). For males, significant predictors of > 1-year retention were urine samples negative for opioids (odds ratio [OR] = 6.67) and cannabinoids (OR = 5.00) during the first month, and not cocaine dependent (OR = 2.70). Significant predictors of higher long-term opioid abstinence were first-month urine samples negative for opioids and cocaine metabolites. For females, significant predictors of >1-year retention were first-month urine samples negative for cocaine metabolites (OR = 4.00) and cannabinoids (OR = 9.26), and no history of sexual victimization (OR = 3.03). The only significant predictor of higher opioid abstinence rate was first-month opioid-free urine samples. CONCLUSIONS: These findings indicate gender-specific predictors of MMT retention and opioid abstinence. Future studies on MMT outcomes should examine each gender separately, and consider unique pathways by which females and males adhere to, and benefit from MMT.

Exploration of the telescoping effect among not-in-treatment, intensive heroin-using research volunteers.

BACKGROUND: Addiction research literature suggests some demographic groups exhibit a later age of substance use initiation, more rapid escalation to dependence, and worse substance use-related outcomes. This 'telescoping' effect has been observed more often in females but has not yet been examined in not-in-treatment heroin users or racial subgroups. METHODS: Not-in-treatment, intensive heroin-using adults screened for laboratory-based research studies (N=554; range 18-55 yr; mean age: 42.5 yr; 60.5% African American [AA]; 70.2% male) were included in this secondary analysis. A comprehensive drug history questionnaire assessed heroin-use characteristics and lifetime adverse consequences. We examined telescoping effects by racial and gender groups: Caucasian males and females; AA males and females. RESULTS: Caucasian males initiated heroin use significantly later than AA males but this difference was not observed for age at intensive heroin use (≥3 times weekly). Caucasian males reported significantly more lifetime heroin use-related consequences, were more likely to inject heroin, and reported more-frequent past-month heroin use, but did not differ from AA males in lifetime heroin quit attempts or prior heroin treatment. Females, compared to males, reported later onset of initial and intensive use, but there was no gender-telescoping effect from initial to intensive heroin-use. CONCLUSIONS: In this not-in-treatment sample, Caucasian males exhibited more rapid heroin-use progression and adverse consequences than AA males, i.e., within-gender, racial-group telescoping. Despite later-onset heroin use among females, there was no evidence of gender-related telescoping. Given the resurgence of heroin use, differential heroin-use trajectories across demographic groups may be helpful in planning interventions.

Predictors of buprenorphine initial outpatient maintenance and dose taper response among non-treatment-seeking heroin dependent volunteers.

BACKGROUND: Buprenorphine (BUP) is effective for treating opioid use disorder. Individuals' heroin-use characteristics may predict their responses to BUP, which could differ during maintenance and dose-taper phases. If so, treatment providers could use pre-treatment characteristics to personalize level of individual care and possibly improve treatment outcomes. METHODS: Non-treatment-seeking heroin-dependent volunteers (N=34) initiated outpatient BUP maintenance (8-mg/day) and submitted urine samples thrice weekly tested for opioids (non-contingent result). After completing three programmatically-related inpatient behavioral pharmacology experiments (while maintained on 8-mg/day BUP), participants were discharged and underwent a double-blind BUP dose taper (4-mg/day, 2-mg/day and 0-mg/day during weeks 1-3, respectively) with an opioid-abstinence incentive ($30 per consecutive opioid-negative urine specimen, obtained thrice weekly). RESULTS: Participants who reported less pre-study (past-month) heroin use and shorter lifetime duration of heroin use were more likely to submit an opioid-negative urine sample during initial outpatient BUP maintenance. Participants who reported more lifetime heroin-quit attempts and provided any opioid-free urine sample during initial outpatient maintenance sustained longer continuous opioid-abstinence during the BUP dose taper. Participants who reported >3 lifetime quit attempts abstained from opioid use nearly one week longer (14 days vs. 8 days to opioid-lapse) and nearly half (46.7%) refrained from opioid use during dose taper. CONCLUSIONS: Number of prior heroin quit attempts may predict BUP dose taper response and provide a metric for stratifying heroin-dependent individuals by relative risk for opioid lapse. This metric may inform personalized relapse prevention care and improve treatment outcomes.

Yohimbine increases opioid-seeking behavior in heroin-dependent, buprenorphine-maintained individuals.

RATIONALE: In laboratory animals, the biological stressor yohimbine (α(2)-noradrenergic autoreceptor antagonist) promotes drug seeking. Human laboratory studies have demonstrated that psychological stressors can increase drug craving but not that stressors alter drug seeking. OBJECTIVES: This clinical study tested whether yohimbine increases opioid-seeking behavior. METHODS: Ten heroin-dependent, buprenorphine-stabilized (8 mg/day) volunteers sampled two doses of hydromorphone [12 and 24 mg IM in counterbalanced order, labeled drug A (session 1) and drug B (session 2)]. During each of six later sessions (within-subject, double-blind, randomized crossover design), volunteers could respond on a 12-trial choice progressive ratio task to earn units (1 or 2 mg) of the sampled hydromorphone dose (drug A or B) vs money ($2) following different oral yohimbine pretreatment doses (0, 16.2, and 32.4 mg). RESULTS: Behavioral economic demand intensity and peak responding (O (max)) were significantly higher for hydromorphone 2 than 1 mg. Relative to placebo, yohimbine significantly increased hydromorphone demand inelasticity, more so for hydromorphone 1-mg units (P (max) = 909, 3,647, and 3,225 for placebo, 16.2, and 32.4 mg yohimbine doses, respectively) than hydromorphone 2-mg units (P (max) = 2,656, 3,193, and 3,615, respectively). Yohimbine produced significant but clinically modest dose-dependent increases in blood pressure (systolic ≈ 15 and diastolic ≈ 10 mmHg) and opioid withdrawal symptoms, and decreased opioid agonist symptoms and elated mood. CONCLUSIONS: These findings concur with preclinical data by demonstrating that yohimbine increases drug seeking; in this study, these effects occurred without clinically significant subjective distress or elevated craving, and partly depended on opioid unit dose.