Combination Treatment With Varenicline and Nicotine Patch on Smoking Cessation Outcomes in Heavy Drinkers at 26-Week Follow-up.

PURPOSE/BACKGROUND: People who smoke cigarettes and drink alcohol heavily are less likely to quit smoking compared with those who do not drink heavily. The current study examined the effects of a 12-week treatment phase of combination varenicline and nicotine patch compared with placebo and nicotine patch on smoking cessation (primary outcome) and alcohol consumption (secondary outcome) in heavy drinking smokers at 26-week follow-up. METHODS/PROCEDURES: Participants were daily smokers who met heavy drinking criteria. They were randomly assigned to receive either varenicline and nicotine patch (n = 61) or placebo and nicotine patch (n = 61) for 12 weeks. At week 26, self-reports of point prevalence cigarette abstinence were biochemically confirmed, and past-month alcohol drinking days and heavy drinking days were assessed. FINDINGS/RESULTS: At week 26, smoking quit rates did not differ by treatment group (25% varenicline and 26% placebo). Relative to week 12 outcomes, week 26 quit rates significantly dropped off in the varenicline group but not in the placebo group. Alcohol drinking reductions for the whole sample that were previously observed from baseline to week 12 were sustained at week 26, although they did not differ between treatment groups. IMPLICATIONS/CONCLUSIONS: In heavy drinking smokers, smoking cessation success was evident in a quarter of the total sample at 3 months postmedication discontinuation. At this time, quit rates were the same between those who received varenicline and nicotine patch and those who received nicotine patch alone. Future research is warranted to examine what may aid in longer-term smoking quit rates in heavy drinking smokers.

Effect of continuous positive airway pressure helmet on respiratory function following surgical procedures in brachycephalic dogs: A randomized controlled trial.

OBJECTIVE: To evaluate the effect of continuous positive airway pressure (CPAP) on respiratory function in the early postoperative period of brachycephalic dogs. STUDY DESIGN: Prospective, randomized clinical trial. ANIMALS: A total of 32 dogs. METHODS: Dogs were assigned to recover with or without CPAP (control) and assessed at specific time points over 1 h. Treatment was discontinued for dogs with a CPAP tolerance score of 3 or more (from a range of 0-4). The primary outcome was pulse oximetry (SpO2). Secondary outcomes were arterial O2 pressure (PaO2)/FiO2 ratio (PaO2/FiO2), arterial CO2 pressure (PaCO2), and rectal temperature. For dogs that reached a CPAP tolerance score of 3 or more, only the data collected up to the time point before discontinuation were included in the analysis. The treatment effect (ß) was analyzed using random effects models and the results were reported with 95% confidence intervals. RESULTS: Dogs were assigned randomly to each protocol. Baseline characteristics in both groups were comparable. Arterial blood gases were obtained in seven control group dogs and nine CPAP group dogs. Treatment did not affect SpO2 (ß = -0.1, -2.1 to 2.0) but affected the PaO2/FiO2 ratio (ß = 58.1, 2.6 to 113.6), with no effects on PaCO2 (ß = -4.3, -10.5 to 1.9) or temperature (ß = 0.4, -0.8 to 1.6). CONCLUSION: In postoperative brachycephalic dogs, CPAP had no effect on SpO2 but improved the PaO2/FiO2 ratio in brachycephalic dogs postoperatively. CLINICAL SIGNIFICANCE: Continuous positive airway pressure offers a valuable solution to improve gas exchange efficiency, a prevalent concern in postoperative brachycephalic dogs, with the potential to enhance overall outcomes.

Cue Reactivity Effects of Heated Tobacco Product Use in Current, Former, and Never Smokers in the United States.

INTRODUCTION: Heated tobacco products (HTPs) share similar characteristics as combustible cigarettes and electronic nicotine delivery systems (ENDS) and thus may serve as cues for smoking and vaping. While HTP familiarity is low in the United States, HTPs may be perceived as a less harmful alternative to cigarettes. AIMS AND METHODS: The present study examined if visual exposure to HTP use influenced cigarette and e-cigarette craving in a large national sample of adults with varied smoking patterns. Current, former, and never cigarette smokers (N = 515; Mage = 40) were recruited from online crowd-sourcing panels throughout the United States from January to April 2020. Participants completed surveys before and after watching a video depicting the use of an HTP, cigarette, or bottled water. Main outcomes were changes in cigarette craving after exposure to the video cue. Secondary outcomes included changes in e-cigarette craving. RESULTS: Relative to the water cue, the HTP and cigarette cues increased cigarette craving in current smokers. The HTP cue also increased e-cigarette craving (desire for a mod or vape pen and JUUL) across all subgroups. CONCLUSIONS: Current smokers demonstrated cue reactivity to the use of an HTP as they reported increases in both cigarette and e-cigarette craving after exposure. All smoking groups reported e-cigarette reactivity to the HTP cue. As HTPs gain traction globally, it is crucial to consider how their use may influence active users and passive viewers to inform future health policies. IMPLICATIONS: Noncombustible nicotine delivery systems are known cues for cigarette smoking and e-cigarette vaping, and this study examined whether relatively novel heated tobacco products (HTPs) may also act as a smoking or vaping cue in adults across varied smoking backgrounds. Results showed that passive exposure to HTP use increased desire for both a cigarette and an e-cigarette in current smokers and also increased desire for an e-cigarette in former and nonsmokers. Thus given its similarity to smoking and vaping, HTP use may affect passive observers and could play a role in perpetuating the dual use of cigarettes and vape products.

The Impact of the COVID-19 Pandemic on Tobacco Treatment Program Implementation at National Cancer Institute-Designated Cancer Centers.

INTRODUCTION: The COVID-19 pandemic disrupted cancer screening and treatment delivery, but COVID-19's impact on tobacco cessation treatment for cancer patients who smoke has not been widely explored. AIMS AND METHODS: We conducted a sequential cross-sectional analysis of data collected from 34 National Cancer Institute (NCI)-designated cancer centers participating in NCI's Cancer Center Cessation Initiative (C3I), across three reporting periods: one prior to COVID-19 (January-June 2019) and two during the pandemic (January-June 2020, January-June 2021). Using McNemar's Test of Homogeneity, we assessed changes in services offered and implementation activities over time. RESULTS: The proportion of centers offering remote treatment services increased each year for Quitline referrals (56%, 68%, and 91%; p = .000), telephone counseling (59%, 79%, and 94%; p = .002), and referrals to Smokefree TXT (27%, 47%, and 56%; p = .006). Centers offering video-based counseling increased from 2020 to 2021 (18% to 59%; p = .006), Fewer than 10% of centers reported laying off tobacco treatment staff. Compared to early 2020, in 2021 C3I centers reported improvements in their ability to maintain staff and clinician morale, refer to external treatment services, train providers to deliver tobacco treatment, and modify clinical workflows. CONCLUSIONS: The COVID-19 pandemic necessitated a rapid transition to new telehealth program delivery of tobacco treatment for patients with cancer. C3I cancer centers adjusted rapidly to challenges presented by the pandemic, with improvements reported in staff morale and ability to train providers, refer patients to tobacco treatment, and modify clinical workflows. These factors enabled C3I centers to sustain evidence-based tobacco treatment implementation during and beyond the COVID-19 pandemic. IMPLICATIONS: This work describes how NCI-designated cancer centers participating in the Cancer Center Cessation Initiative (C3I) adapted to challenges to sustain evidence-based tobacco use treatment programs during the COVID-19 pandemic. This work offers a model for resilience and rapid transition to remote tobacco treatment services delivery and proposes a policy and research agenda for telehealth services as an approach to sustaining evidence-based tobacco treatment programs.

Smoking Status, Nicotine Medication, Vaccination, and COVID-19 Hospital Outcomes: Findings from the COVID EHR Cohort at the University of Wisconsin (CEC-UW) Study.

INTRODUCTION: Available evidence is mixed concerning associations between smoking status and COVID-19 clinical outcomes. Effects of nicotine replacement therapy (NRT) and vaccination status on COVID-19 outcomes in smokers are unknown. METHODS: Electronic health record data from 104 590 COVID-19 patients hospitalized February 1, 2020 to September 30, 2021 in 21 U.S. health systems were analyzed to assess associations of smoking status, in-hospital NRT prescription, and vaccination status with in-hospital death and ICU admission. RESULTS: Current (n = 7764) and never smokers (n = 57 454) did not differ on outcomes after adjustment for age, sex, race, ethnicity, insurance, body mass index, and comorbidities. Former (vs never) smokers (n = 33 101) had higher adjusted odds of death (aOR, 1.11; 95% CI, 1.06-1.17) and ICU admission (aOR, 1.07; 95% CI, 1.04-1.11). Among current smokers, NRT prescription was associated with reduced mortality (aOR, 0.64; 95% CI, 0.50-0.82). Vaccination effects were significantly moderated by smoking status; vaccination was more strongly associated with reduced mortality among current (aOR, 0.29; 95% CI, 0.16-0.66) and former smokers (aOR, 0.47; 95% CI, 0.39-0.57) than for never smokers (aOR, 0.67; 95% CI, 0.57, 0.79). Vaccination was associated with reduced ICU admission more strongly among former (aOR, 0.74; 95% CI, 0.66-0.83) than never smokers (aOR, 0.87; 95% CI, 0.79-0.97). CONCLUSIONS: Former but not current smokers hospitalized with COVID-19 are at higher risk for severe outcomes. SARS-CoV-2 vaccination is associated with better hospital outcomes in COVID-19 patients, especially current and former smokers. NRT during COVID-19 hospitalization may reduce mortality for current smokers. IMPLICATIONS: Prior findings regarding associations between smoking and severe COVID-19 disease outcomes have been inconsistent. This large cohort study suggests potential beneficial effects of nicotine replacement therapy on COVID-19 outcomes in current smokers and outsized benefits of SARS-CoV-2 vaccination in current and former smokers. Such findings may influence clinical practice and prevention efforts and motivate additional research that explores mechanisms for these effects.

Sleep and circadian differences between light and heavy adult alcohol drinkers.

BACKGROUND: Numerous studies have reported that eveningness is associated with increased alcohol consumption. However, biological markers of circadian timing, such as dim light melatonin onset (DLMO) and circadian photoreceptor responsivity (post-illumination pupil response, PIPR), have rarely been assessed in the context of habitual alcohol consumption. This study aimed to examine sleep, circadian timing, and photoreceptor responsivity in adult alcohol drinkers. METHODS: Participants (21 to 45 years) included 28 light and 50 heavy drinkers. The 8-day study consisted of a week of ad lib sleep monitored with wrist actigraphy, followed by a 9-h laboratory session with a photoreceptor responsivity and circadian phase assessment. RESULTS: The heavy drinkers obtained on average 28 more minutes of sleep (p = 0.002) and reported more eveningness than the light drinkers (p = 0.029). There was a trend for a shorter DLMO-midsleep interval (p = 0.059) in the heavy drinkers, reflecting a tendency for them to sleep at an earlier circadian phase. The PIPR in the heavy drinkers was significantly smaller than in the light drinkers (p = 0.032), suggesting reduced circadian photoreceptor responsivity in the heavy drinkers. A larger PIPR was significantly associated with a later DLMO in the light drinkers (r = 0.44, p = 0.019), but this relationship was absent in the heavy drinkers (r = -0.01, p = 0.94). CONCLUSIONS: These results are consistent with earlier reports of more eveningness and a shorter DLMO-midsleep interval being associated with heavier alcohol drinking. The novel finding of reduced circadian photoreceptor responsivity in heavy drinkers is consistent with prior rodent studies. Future studies should explore the impact of habitual alcohol consumption on other measures of circadian photoreceptor responsivity.

Blunted opioid regulation of the HPA stress response during nicotine withdrawal: therapeutic implications.

Endogenous opioids regulate pain, drug reward, and stress responses. We have previously shown reduced hypothalamic-pituitary-adrenal (HPA) responses to psychological stress and to opioid blockade among dependent smokers. In this study, we examined the extent to which biologically confirmed nicotine withdrawal alters endogenous opioid regulation of HPA axis functioning during rest and in response to acute stress. Smokers were randomly assigned to one of two conditions; 24 h withdrawal from all nicotine-containing products (n = 62) or smoking ad libitum (n = 44). A nonsmoking comparison group (n = 43) was also included. Participants (85 males and 64 females) completed two acute stress sessions during which a placebo or 50 mg of naltrexone (opioid antagonist) were administered using a double-blind design. Blood and saliva samples (assayed for cortisol and adrenocorticotropic hormone, i.e. ACTH) and mood measures were obtained during a resting absorption period, after acute stress (public speaking, mental arithmetic, and cold pressor tasks), and during an extended recovery period. Results indicated that opioid blockade (naltrexone) was associated with increased ACTH and cortisol responses to stress, and tobacco withdrawal was associated with blunted hormonal responses. A pattern of sex differences also emerged, with women exhibiting reduced ACTH responses to stress and higher ACTH and plasma cortisol responses to opioid blockade. These results indicated that compared to ad libitum smoking, nicotine withdrawal is associated with blunted opioid modulation of the HPA axis. Sex may modulate these effects. Blunted endogenous opioid regulation may underlie an incentive process that reinforces smoking behavior and may warrant therapeutic attention.

Alcohol subjective responses in heavy drinkers: Measuring acute effects in the natural environment versus the controlled laboratory setting.

BACKGROUND: For decades, laboratory alcohol challenges have been the "gold standard" for measuring individual differences in alcohol's subjective effects. However, these approaches are expensive and labor-intensive, making them impractical for large-scale use. This study examined the reliability and validity of a new high-resolution EMA (HR-EMA) ambulatory approach to assessing alcohol use and subjective responses in drinkers' natural environments. METHODS: Participants were 83 young adult heavy social drinkers (58% male; mean ± SD age = 25.4 ± 2.6 years) who completed up to two smartphone-based, 3-h HR-EMA assessments of alcohol use and related subjective responses in their typical drinking environments. Reported alcohol consumption during the HR-EMA periods was used to calculate estimated blood alcohol concentration (eBAC). Subjective effects were measured using the Brief Biphasic Alcohol Effects Scale (B-BAES) and Drug Effects Questionnaire (DEQ). All participants also completed identical measures during a separate, 4 to 5-h laboratory session in which they received a 0.8 g/kg alcohol challenge. RESULTS: Most natural environment drinking episodes (87%) met or exceeded the threshold for binge drinking (final mean eBAC = 0.12 g/dl). Associations between reported alcohol use and subjective responses on the B-BAES and DEQ were strongest earlier in the drinking events, with fair reliability of reported subjective effects across two HR-EMA episodes (intraclass correlation [ICC] range = 0.46-0.49). There was fair-to-good correspondence between HR-EMA- and laboratory-derived subjective responses (ICC range = 0.49-0.74), even after accounting for differences in alcohol consumption and drinking context. Reported stimulating and rewarding alcohol effects were higher in the ambulatory than laboratory setting, and vice versa for sedating effects. CONCLUSIONS: This study supports the reliability and validity of smartphone-based HR-EMA to measure alcohol use and subjective responses in heavy drinkers' natural environments. These findings lend support to the use of ambulatory HR-EMA as a measure of alcohol subjective responses in risky drinkers when a laboratory protocol is not practical, feasible, or safe.

The future of translational research on alcohol use disorder.

In March 2019, a scientific meeting was held at the University of California, Los Angeles (UCLA) Luskin Center to discuss approaches to expedite the translation of neurobiological insights to advances in the treatment of alcohol use disorder (AUD). A guiding theme that emerged was that while translational research in AUD is clearly a challenge, it is also a field ripe with opportunities. Herein, we seek to summarize and disseminate the recommendations for the future of translational AUD research using four sections. First, we briefly review the current landscape of AUD treatment including the available evidence-based treatments and their uptake in clinical settings. Second, we discuss AUD treatment development efforts from a translational science viewpoint. We review current hurdles to treatment development as well as opportunities for mechanism-informed treatment. Third, we consider models of translational science and public health impact. Together, these critical insights serve as the bases for a series of recommendations and future directions. Towards the goal of improving clinical care and population health for AUD, scientists are tasked with bolstering the clinical applicability of their research findings so as to expedite the translation of knowledge into patient care.

Learning-induced mRNA alterations in olfactory bulb mitral cells in neonatal rats.

In the olfactory bulb, a cAMP/PKA/CREB-dependent form of learning occurs in the first week of life that provides a unique mammalian model for defining the epigenetic role of this evolutionarily ancient plasticity cascade. Odor preference learning in the week-old rat pup is rapidly induced by a 10-min pairing of odor and stroking. Memory is demonstrable at 24 h, but not 48 h, posttraining. Using this paradigm, pups that showed peppermint preference 30 min posttraining were sacrificed 20 min later for laser microdissection of odor-encoding mitral cells. Controls were given odor only. Microarray analysis revealed that 13 nonprotein-coding mRNAs linked to mRNA translation and splicing and 11 protein-coding mRNAs linked to transcription differed with odor preference training. MicroRNA23b, a translation inhibitor of multiple plasticity-related mRNAs, was down-regulated. Protein-coding transcription was up-regulated for Sec23b, Clic2, Rpp14, Dcbld1, Magee2, Mstn, Fam229b, RGD1566265, and Mgst2. Gng12 and Srcg1 mRNAs were down-regulated. Increases in Sec23b, Clic2, and Dcbld1 proteins were confirmed in mitral cells in situ at the same time point following training. The protein-coding changes are consistent with extracellular matrix remodeling and ryanodine receptor involvement in odor preference learning. A role for CREB and AP1 as triggers of memory-related mRNA regulation is supported. The small number of gene changes identified in the mitral cell input/output link for 24 h memory will facilitate investigation of the nature, and reversibility, of changes supporting temporally restricted long-term memory.

The Feasibility, Tolerability, and Safety of Administering a Very High Alcohol Dose to Drinkers with Alcohol Use Disorder.

INTRODUCTION: There remains a paucity of research quantifying alcohol's effects in drinkers with alcohol use disorder (AUD), particularly responses to very high alcohol doses (≥0.8 g/kg). As drinkers with AUD frequently engage in very heavy drinking (8 to 10 drinks/occasion), doses of ≤0.8 g/kg may lack ecological validity. The present study examined the feasibility, tolerability, and safety of administering a very high alcohol dose (1.2 g/kg) to non-treatment-seeking AUD participants. METHODS: Sixty-one young adult AUD drinkers enrolled in the Chicago Social Drinking Project and completed 3 laboratory sessions at which they consumed a beverage with 1.2, 0.8, and 0.0 g/kg alcohol. Physiological responses (vital signs, nausea and vomiting, breath alcohol concentrations [BrAC]) were monitored throughout the sessions. After each session, participants completed a next-day survey of substance use, engagement in risky behaviors, and related consequences. RESULTS: Overall, the sample demonstrated good compliance with study procedures; 93% of participants adhered to presession alcohol abstinence requirements (indicated by BrAC < 0.003 g/dl), with no participants exhibiting serious alcohol withdrawal symptoms at arrival to study visits. The 1.2 g/kg alcohol dose achieved an expected mean peak BrAC of 0.13 g/dl at 60 minutes after drinking, which was well tolerated; the majority of the sample did not experience nausea (70%) or vomiting (93%), and dose effects on vital signs were not clinically significant. Finally, we demonstrated that the 1.2 g/kg alcohol dose is safe and not associated with postsession consequences, including reduced sleep time, atypical substance use, accidents or injuries, and severe hangovers. CONCLUSION: Results support the feasibility, tolerability, and safety of administering a very high alcohol dose to young adult drinkers with AUD within the context of a well-validated laboratory alcohol challenge paradigm. Utilizing an alcohol dose more consistent with naturalistic drinking patterns may foster greater ecological validity of laboratory paradigms for persons with moderate to severe AUD.

Substance use behaviors in adolescent and young adult cancer patients: Associations with mental and physical health.

OBJECTIVE: Cancer diagnosis in adolescents and young adults (AYAs) coincides with the developmental initiation of substance use and emergence of affective disturbance. We examined substance use behaviors and risk-stratified associations with mental and physical health, as well as objective indicators of tobacco and cannabis use and concordance with self-report and medical records. METHODS: AYAs were 15 to 39 years at cancer diagnosis and ≥18 years and ≥6 months postdiagnosis at study enrollment. Risk-stratified groups included nonsmoker/nondrinker, nonsmoker/drinker, smoker/drinker. Assessments included demographics, past year tobacco, alcohol, and cannabis use, depression, anxiety, sleep, and physical activity. Urine analysis provided biochemical verification of tobacco and cannabis use. RESULTS: Participants included 100 AYAs (60% male) with primarily hematological cancers (88%). Past year alcohol, tobacco, and cannabis use prevalence rates were 80%, 15%, and 33%, respectively. A minority (non-users) refrained from both alcohol and tobacco (20%), while most were exclusively alcohol users (65%) or alcohol and tobacco co-users (15%). Relative to other sub-groups, co-users reported more depressive and anxious symptoms, while non-users reported more physical activity. More frequent tobacco and cannabis use were associated with more depressive and anxious symptoms, while more frequent alcohol use was associated with lower physical activity. There were no group differences or associations with sleep quality. There was considerable discordance between tobacco use self-report, biochemical verification, and medical record documentation. CONCLUSIONS: Substance use among AYAs is common and detrimental to mental and physical health, especially among more frequent users and co-users, highlighting the need for early assessment and intervention.

To Infuse or Ingest in Human Laboratory Alcohol Research.

Human alcohol laboratory studies use two routes of alcohol administration: ingestion and infusion. The goal of this paper was to compare and contrast these alcohol administration methods. The work summarized in this report was the basis of a 2019 Research Society on Alcoholism Roundtable, "To Ingest or Infuse: A Comparison of Oral and Intravenous Alcohol Administration Methods for Human Alcohol Laboratory Designs." We review the methodological approaches of each and highlight strengths and weaknesses pertaining to different research questions. We summarize methodological considerations to aid researchers in choosing the most appropriate method for their inquiry, considering exposure variability, alcohol expectancy effects, safety, bandwidth, technical skills, documentation of alcohol exposure, experimental variety, ecological validity, and cost. Ingestion of alcohol remains a common and often a preferable, methodological practice in alcohol research. Nonetheless, the main problem with ingestion is that even the most careful calculation of dose and control of dosing procedures yields substantial and uncontrollable variability in the participants' brain exposures to alcohol. Infusion methodologies provide precise exposure control but are technically complex and may be limited in ecological validity. We suggest that alcohol ingestion research may not be the same thing as alcohol exposure research; investigators should be aware of the advantages and disadvantages that the choice between ingestion and infusion of alcohol invokes.

Exposure to JUUL use: cue reactivity effects in young adult current and former smokers.

BACKGROUND: Exposure to the use of first, second and third generations of electronic cigarettes (e-cigarettes) elicits the desire to vape and smoke among observers, as well as facilitates smoking behaviour. Given the rapid rise in the popularity of the pod mod JUUL, we examined whether observing the use of this device would elicit similar responses in smokers. Exploratory analyses were also conducted to determine whether JUUL can act as a smoking cue for former smokers. METHODS: The sample consisted of 82 young adult participants (62 current smokers and 20 former smokers approximately 1 year smoke free). The study examined their response to observing use of bottled water (control cue) and JUUL (active cue) in a controlled laboratory paradigm. Both cues were delivered by a trained study confederate under the guise of a social interaction task, and participants completed mood and desire and urge surveys precue and postcue exposures. RESULTS: In current smokers, exposure to the JUUL cue increased smoking urge and desire for a cigarette, mod/vape pen and JUUL, and two-thirds chose to smoke in the behavioural analogue task. In former smokers, the JUUL cue evoked modest and transient increases in desire for a cigarette and JUUL. CONCLUSIONS: The use of JUUL affects the user and elicits responses in observers; this study is the first to demonstrate that exposure to JUUL use may act as a smoking cue and exposure to JUUL use may affect tobacco control efforts.

Mechanisms of Alcohol Addiction: Bridging Human and Animal Studies.

AIM: The purpose of this brief narrative review is to address the complexities and benefits of extending animal alcohol addiction research to the human domain, emphasizing Allostasis and Incentive Sensitization, two models that inform many pre-clinical and clinical studies. METHODS: The work reviewed includes a range of approaches, including: a) animal and human studies that target the biology of craving and compulsive consumption; b) human investigations that utilize alcohol self-administration and alcohol challenge paradigms, in some cases across 10 years; c) questionnaires that document changes in the positive and negative reinforcing effects of alcohol with increasing severity of addiction; and d) genomic structural equation modeling based on data from animal and human studies. RESULTS: Several general themes emerge from specific study findings. First, positive reinforcement is characteristic of early stage addiction and sometimes diminishes with increasing severity, consistent with both Allostasis and Incentive Sensitization. Second, evidence is less consistent for the predominance of negative reinforcement in later stages of addiction, a key tenant of Allostasis. Finally, there are important individual differences in motivation to drink at a given point in time as well as person-specific change patterns across time. CONCLUSIONS: Key constructs of addiction, like stage and reinforcement, are by necessity operationalized differently in animal and human studies. Similarly, testing the validity of addiction models requires different strategies by the two research domains. Although such differences are challenging, they are not insurmountable, and there is much to be gained in understanding and treating addiction by combining pre-clinical and clinical approaches.

Evaluation of a Randomized Clinical Trial Comparing the Effectiveness of a Culturally Targeted and Nontargeted Smoking Cessation Intervention for Lesbian, Gay, Bisexual, and Transgender Smokers.

PURPOSE: To examine the benefits of a culturally targeted compared with a nontargeted smoking cessation intervention on smoking cessation outcomes among lesbian, gay, bisexual, and transgender (LGBT) smokers. METHODS: A prospective randomized design was used to evaluate the added benefits of an LGBT culturally targeted Courage to Quit (CTQ-CT) smoking cessation treatment (N = 172) compared with the standard intervention (CTQ; N = 173). The smoking cessation program consisted of six treatment sessions combined with 8 weeks of nicotine replacement therapy. The primary smoking cessation outcome was 7-day point prevalence quit rates. Secondary outcomes examined included changes in nicotine dependence, nicotine withdrawal, cigarettes per day, smoking urges, self-efficacy, and readiness to quit. RESULTS: Overall quit rates were 31.9% at 1 month, 21.1% at 3 months, 25.8% at 6 months, and 22.3% at 12 months. Quit rates did not differ between treatment groups [1 month OR = 0.81 (0.32, 2.09), 3 months OR = 0.65 (0.23, 1.78), 6 months OR = 0.45 (0.17, 1.21), 12 months OR = 0.70 (0.26, 1.91)]. Compared with baseline levels, all secondary smoking cessation outcomes measured were improved at 1 month and were maintained at 12-month follow-up. Compared with the CTQ, the CTQ-CT intervention was more highly rated on program effectiveness (d = 0.2, p = .011), intervention techniques (d = 0.2, p = .014), the treatment manual (d = 0.3, p < .001), and being targeted to the needs of LGBT smokers (d = 0.5, p < .0001). CONCLUSIONS: LGBT smokers receiving the CTQ intervention achieved smoking cessation outcomes in the range reported for other demographic groups. Cultural targeting improved the acceptability of the intervention but did not confer any additional benefit for smoking cessation outcomes. IMPLICATIONS: Study results have implications for understanding the benefits of culturally targeted compared with nontargeted smoking cessation interventions for improving smoking cessation outcomes among LGBT smokers. Shorter and longer term 7-day point prevalence quit rates associated with the targeted and nontargeted interventions were modest but comparable with other group-based interventions delivered in a community setting. Although cultural targeting improved the overall acceptability of the intervention, no added benefits were observed for the culturally targeted intervention on either the primary or secondary outcomes.

E-cigarette use (vaping) is associated with illicit drug use, mental health problems, and impulsivity in university students.

BACKGROUND: This study examined the prevalence of e-cigarette use ("vaping") among university students and its associations with psychosocial correlates. METHODS: In this study, 9,449 students received a 156-item anonymous online survey assessed the use of e-cigarettes (ever or past year), alcohol and drug use, mental health issues, and impulsive and compulsive traits. RESULTS: In total, 3,572 university students (57.1% female) responded to the survey. The prevalence of past 12-month e-cigarette use was 9.2%, with 9.8% reporting having used more than 12 months ago. E-cigarette use was associated with the use of multiple other drugs (eg, alcohol, opiates). Those who used e-cigarettes were significantly more likely to have mental health histories of attention-deficit/hyperactivity disorder, posttraumatic stress disorder, gambling disorder, and anxiety, to report low self-esteem, and to endorse traits of impulsivity. CONCLUSIONS: Use of e-cigarettes is common in university students and appears to be associated with a variety of mental health and drug use problems. Clinicians should be aware that certain mental health conditions are more common in e-cigarette users. This study indicates the need for longitudinal research into the effects of chronic nicotine consumption on brain function and mental health, especially in young people, since such effects would be common to conventional tobacco smoking and vaping.

Lack of Association between Opioid-Receptor Genotypes and Smoking Cessation Outcomes in a Randomized, Controlled Naltrexone Trial.

AIMS: The present study examined how variation in mu- (OPRM1), kappa- (OPRK), and delta- (OPRD) opioid receptor genes may influence the efficacy of naltrexone in the context of a smoking cessation trial. METHODS: The study's primary objective was to examine the association of the Asn40Asp OPRM1 single nucleotide polymorphism (SNP) with naltrexone's effects on smoking quit rate, weight gain, and heavy drinking behavior during a double-blind, randomized clinical trial in 280 adult DSM-IV nicotine-dependent participants. The secondary goal of the study was to examine the relationship of 20 additional SNPs of OPRM1, OPRK, and OPRD with the aforementioned outcomes. RESULTS: Results indicated a null association between any opioid-receptor gene SNP and naltrexone's effects on smoking quit rate, weight gain, and heavy drinking behavior in this sample of nicotine dependent participants. CONCLUSIONS: In sum, these results do not suggest that genetic variation in opioid-receptors is related to treatment responses to naltrexone in a smoking cessation trial.

The dopamine transporter VNTR polymorphism moderates the relationship between acute response to alcohol and future alcohol use disorder symptoms.

Alcohol use disorder (AUD) is a genetically influenced disease with peak onset in young adulthood. Identification of factors that predict whether AUD symptoms will diminish or persist after young adulthood is a critical public health need. King and colleagues previously reported that acute response to alcohol predicted future AUD symptom trajectory. Genes associated with brain dopamine signaling, which underlies alcohol's rewarding effects, might influence this finding. This study analyzed whether variation at a variable number tandem repeat polymorphism in DAT1/SLC6A3, the gene encoding the dopamine transporter, moderated the predictive relationships between acute response to alcohol and future AUD symptoms among participants enrolled in the Chicago Social Drinking Project (first two cohorts). Heavy-drinking young adults (N = 197) completed an alcohol challenge, in which acute response (liking, wanting, stimulation, and sedation) was measured. Alcohol use disorder symptoms were assessed over the following 6 years. DAT1 genotype significantly moderated the interactions between follow-up time and alcohol liking (P = 0.006) and wanting (P = 0.006) in predicting future AUD symptoms. These predictive effects were strongest among participants who carried the DAT1 9-repeat allele, previously associated with enhanced striatal dopamine tone relative to the 10-repeat allele. Exploratory analyses indicated that DAT1 effects on the relationship between alcohol liking and AUD symptoms appeared stronger for females (n = 79) than males (n = 118) (P = 0.0496). These data suggest that heavy-drinking DAT1 9-repeat allele carriers who display high alcohol-induced reward in young adulthood may be predisposed to persistent AUD symptoms and support combining genotypic and phenotypic information to predict future AUD risk.

Intranasal Oxytocin Does Not Modulate Responses to Alcohol in Social Drinkers.

BACKGROUND: Preclinical and clinical evidence suggest that the neuropeptide oxytocin may be of value in treating alcohol use disorder, by either reducing the rewarding effects of alcohol or reducing negative affect induced by alcohol withdrawal. However, the effect of a single dose of oxytocin on subjective and psychomotor responses to alcohol in social drinkers is not known. METHODS: This study examined the effect of intranasal oxytocin on subjective, behavioral, and physiological responses to a moderate dose of alcohol (0.8 g/kg) in young adult social drinkers. Participants (N = 35) completed 2 study sessions at which they consumed beverages containing alcohol (ALC; N = 20) or placebo (NoALC; N = 15) in combination with intranasal oxytocin (40 IU with a 20 IU booster) or placebo. They received oxytocin at one session and placebo at the other session (order counterbalanced) 20 minutes before consuming beverages. Subjective mood and drug effects ratings, heart rate and blood pressure, and 4 behavioral tasks (flanker task, digit span, go/no-go, and pursuit rotor) were the primary outcome measures. RESULTS: ALC produced its expected subjective and behavioral effects; including feeling intoxicated and impaired performance on the digit span and go/no-go tasks. Oxytocin alone had no significant subjective or physiological effects, and it did not affect responses to alcohol on any measure. CONCLUSIONS: We can conclude that, under these conditions, a single dose of intranasal oxytocin does not alter the effects of acute alcohol in healthy young adult social drinkers. Further research is needed to determine whether oxytocin alters responses to alcohol under different conditions, and to determine its potential as an aid in treatment for substance use disorders.