Acute analgesic effect of nicotine vaping using three experimental pain induction tasks: a randomized, placebo-controlled laboratory study.

RATIONALE: Pain and nicotine use are co-occurring conditions with a significant impact on health. Experimental evidence supports an acute analgesic effect of nicotine which may reinforce nicotine use among those with chronic pain. Evidence for nicotine analgesia have primarily been gathered in combustible cigarette users and have not been extended to electronic nicotine delivery systems (ENDS or vaping). Furthermore, the mechanisms of nicotine analgesia in humans are not well understood. OBJECTIVES: Assess the effect of acute vaped nicotine on subjective and behavioral indices of pain sensitivity using three tasks designed to probe distinct mechanisms of analgesia. METHODS: This study recruited ENDS users (N = 86) to undergo a paced vaping protocol followed by pain tasks in counterbalanced order. Across four sessions, participants vaped e-liquid containing nicotine or placebo, and flavor or no-flavor in a 2 × 2 within-subject design. Assessments included cold pressor, submaximal effort tourniquet to induce ischemic pain, and temporal summation of heat pain, an index of central sensitization. RESULTS: Compared to placebo, nicotine increased cold pressor pain tolerance (ηp2 = 0.031), ischemic pain threshold (ηp2 = 0.073) and tolerance (ηp2 = 0.056) but had no effect on temporal summation of pain. Flavor did not affect pain sensitivity. Females reported greater ischemic pain sensitivity (ηp2 = 0.027) and greater reductions in craving (ηp2 = 0.086). CONCLUSIONS: Consistent with research from tobacco smoking, analgesia may be reinforcing and contribute to nicotine dependence among ENDS users. More research on sex differences is warranted.

Prospective associations of behavioral economic demand for cannabis and alcohol with simultaneous cannabis and alcohol use among young adults.

Behavioral economic demand for cannabis and alcohol is robustly associated with cannabis use and alcohol use, respectively. However, few studies have examined the contributions of cannabis and alcohol demand to simultaneous cannabis and alcohol use, which is common among young adults. We examined prospective associations of cannabis demand and alcohol demand with propensity for simultaneous use (broadly defined as using both cannabis and alcohol in the same day) and with cannabis and alcohol consumption during simultaneous use days among young adults. Young adults reporting simultaneous use (N = 107) completed a Marijuana Purchase Task assessing cannabis demand and an Alcohol Purchase Task assessing alcohol demand. They then completed daily smartphone surveys over 21 days assessing cannabis and alcohol use. Multilevel models revealed that higher cannabis demand (i.e., higher Omax, Pmax, and intensity; lower elasticity) was uniquely associated with greater propensity for simultaneous use relative to nonuse. In addition, higher alcohol demand (lower elasticity) was uniquely associated with greater propensity for simultaneous use relative to cannabis-only use, and higher cannabis demand (higher break point and intensity, lower elasticity) was uniquely associated with greater propensity for simultaneous use relative to alcohol-only use. Furthermore, in models limited to simultaneous use days, greater cannabis demand (higher Omax, lower elasticity) and lower alcohol demand (higher elasticity) were uniquely associated with greater overall cannabis flower consumption, and higher alcohol demand (higher Omax, lower elasticity) was uniquely associated with greater overall alcohol consumption. Results suggest that individual differences in cannabis and alcohol demand may contribute to simultaneous cannabis and alcohol use behaviors in a substance-specific pattern. Furthermore, cannabis demand may more strongly drive the tendency to engage in simultaneous use (vs. nonuse) relative to alcohol demand. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

How Much THC Is in That Joint? A Daily Diary Study of Young Adults' Knowledge of the Cannabinoid Content of Cannabis Products.

OBJECTIVE: Many young adults report frequent cannabis use and are at risk for cannabis harms. Knowledge of the tetrahydrocannabinol (THC) and cannabidiol (CBD) concentrations of cannabis products may promote harm reduction, but few studies have characterized cannabinoid concentration knowledge in this population. This study used day-level data to examine predictors of cannabinoid concentration knowledge and associations of cannabinoid concentration knowledge with substance-related consequences among young adults. METHOD: Participants (n = 131; mean age = 22.11 years; 64.12% female) from a larger study of cannabis and alcohol co-use completed daily surveys over 21 days assessing knowledge of the cannabinoid concentrations of cannabis used, forms of cannabis used, motives for cannabis use (medicinal, nonmedicinal, both), and substance-related consequences. RESULTS: On average, participants reported at least some knowledge of the THC and CBD concentrations of their cannabis on 48% and 32% of their cannabis use days, respectively. Generalized linear mixed models revealed that participants with a greater propensity to use nonflower (relative to flower) cannabis products and to report medicinal (relative to exclusively nonmedicinal) motives for cannabis use reported greater cannabinoid concentration knowledge overall across days, controlling for sociodemographic factors and level of cannabis involvement. Participants with greater overall cannabinoid concentration knowledge reported positive substance-related consequences more often. In addition, participants were more likely to report negative substance-related consequences on days during which cannabinoid concentrations were known versus unknown. CONCLUSIONS: Findings suggest that cannabinoid concentration knowledge may be higher among young adults who report primarily nonflower and medicinally motivated cannabis use, although cannabinoid concentration knowledge, alone, may not protect against negative substance-related consequences at the day level.

Effects of Nicotine Content and Preferred Flavor on Subjective Responses to E-cigarettes: A Randomized, Placebo-controlled Laboratory Study.

INTRODUCTION: Evidence suggests that e-liquid flavor and nicotine concentration are important factors in the initiation and maintenance of e-cigarette use (vaping). Flavors may increase the initiation and maintenance of vaping, and nicotine content is a factor in e-cigarette dependence and the efficacy of e-cigarettes for cigarette smoking cessation. Few human laboratory studies have assessed the joint and interactive effects of flavor and nicotine on subjective responses to e-cigarettes. METHODS: Regular e-cigarette users (N = 89) completed a multi-session study involving a paced vaping procedure with e-liquid cartridges containing their preferred flavor (berry, menthol, or tobacco) or no flavor, with or without nicotine (18 mg). Subjective effects of vaping (satisfaction, reward, aversion, airway sensations, and craving relief) were assessed. RESULTS: Nicotine significantly increased psychological reward and craving relief, whereas flavor significantly increased vaping satisfaction and taste. Nicotine dependence severity moderated the effect of nicotine on reward, such that those with the greatest dependence severity reported the greatest reward. CONCLUSIONS: These findings support differential and noninteractive effects of e-liquid nicotine content and flavor on reinforcing effects of e-cigarettes. IMPLICATIONS: E-liquid flavor and nicotine content have independent, non-interactive effects on subjective responses to vaping under controlled laboratory conditions. Among regular e-cigarette users, vaping a preferred flavor increased taste and satisfaction, but did not interact with nicotine to alter reward or craving. Further research on the ways in which these subjective effects may motivate vaping behavior among different populations of e-cigarette users would be useful to inform regulatory policy of ENDS products.

Cannabis self-administration in the human laboratory: a scoping review of ad libitum studies.

Cannabis self-administration studies may be helpful for identifying factors that influence cannabis consumption and subjective response to cannabis. Additionally, these paradigms could be useful for testing novel pharmacotherapies for cannabis use disorder. This scoping review aims to summarize the findings from existing ad libitum cannabis self-administration studies to determine what has been learned from these studies as well as their limitations. We examined studies that specifically examined cannabis smoking, focusing on subjective response and self-administration behavior (e.g., smoking topography). A systematic search was conducted using PubMed and Embase from inception to October 22, 2022. Our search strategy identified 26 studies (total N = 662, 79% male) that met our eligibility criteria. We found that tetrahydrocannabinol (THC) concentration significantly affected subjective response to cannabis in some but not all studies. In general, cannabis self-administration tended to be most intense at the beginning of the laboratory session and decreased in later parts of the session. There was limited data on cannabis self-administration in adults older than 55. Data on external validity and test-retest reliability were also limited. Addressing these limitations in future ad libitum cannabis self-administration studies could lead to more valid and generalizable paradigms, which in turn could be used to improve our understanding of cannabis use patterns and to help guide medication development for cannabis use disorder.

Disentangling Medicinal and Recreational cannabis Use Among People Living with HIV: An Ecological Momentary Assessment Study.

This study examined the feasibility of using ecological momentary assessment (EMA) to disentangle medicinal cannabis use (MCU) from recreational cannabis use (RCU) among people living HIV (PLWH). Over a 14-day period, PLWH (N = 29) who engaged in both MCU and RCU completed a smartphone-based survey before and after every cannabis use event assessing general motivation for cannabis use (MCU-only, RCU-only, or mixed MCU/RCU), cannabis use behavior, and several antecedents and outcomes of cannabis use. A total of 739 pre-cannabis surveys were completed; 590 (80%) of the prompted post-cannabis surveys were completed. Motives for cannabis use were reported as MCU-only on 24%, RCU-only on 30%, and mixed MCU/RCU on 46% of pre-cannabis surveys. Mixed effects models examined within-person differences across MCU-only, RCU-only, and mixed MCU/RCU events. Results showed that relative to RCU-only events, MCU-only events were more likely to involve symptom management and drug substitution motives, physical and sleep-related symptoms, solitary cannabis use, and use of cannabis oils and sprays; MCU-only events were less likely to involve relaxation, happiness, and wellness motives, cannabis flower use, and positive cannabis consequences. Differences between mixed MCU/RCU and RCU-only events were similar, except that mixed MCU/RCU events were additionally associated with stress reduction motives and symptoms of anxiety and depression. Findings support the feasibility of partially disentangling MCU and RCU behavior among PLWH who engage in concurrent MCU and RCU. This study highlights the need for more EMA studies isolating MCU from RCU to inform ongoing changes to cannabis policies.

Effects of varenicline and bupropion on laboratory smoking outcomes: Meta-analysis of randomized, placebo-controlled human laboratory studies.

Human laboratory studies are widely used to evaluate behavioural mechanisms of pharmacotherapy effects. Results from human laboratory studies examining smoking cessation pharmacotherapies have not been examined in aggregate. The current meta-analysis aimed to synthesize data from randomized, placebo-controlled human laboratory studies on the effects of non-nicotine pharmacotherapies on outcomes relevant for smoking cessation. Literature searches identified 15 human laboratory studies of varenicline (n = 697) and 9 studies of bupropion (n = 313) with sufficient data for inclusion. Studies involved acute or subacute pharmacotherapy treatment with administration durations ranging from a single dose to 8 weeks. Primary outcomes examined were craving, withdrawal and behavioural indices of smoking. Varenicline significantly reduced craving (Hedge's g = -0.36[-0.54,-0.17], p < 0.001), withdrawal (g = -0.25[-0.41,-0.09], p = 0.003) and behavioural indices of smoking (g = -0.36[-0.63,-0.08], p = 0.01) relative to placebo. In contrast, results were inconclusive regarding bupropion's effects on craving (g = -0.13[-0.32,0.05], p = 0.15), withdrawal (g = -0.15[-0.44,0.14], p = 0.31) and behavioural indices of smoking (g = -0.05[-0.35,0.24], p = 0.73) relative to placebo. Findings provide meta-analytic support that short-term varenicline treatment decreases craving, withdrawal symptoms and smoking behaviour under controlled laboratory conditions. However, findings also suggest the ability of human laboratory paradigms to detect pharmacotherapy effects may differ by treatment type. Pharmacotherapy discovery and evaluation efforts utilizing human laboratory methods should aim to align study designs and laboratory procedures with presumed therapeutic mechanisms when possible.

Therapeutic Potential of Histamine H3 Receptors in Substance Use Disorders.

Substance use disorders are a leading cause of morbidity and mortality, and available pharmacological treatments are of modest efficacy. Histamine is a biogenic amine with four types of receptors. The histamine H3 receptor (H3R) is an autoreceptor and also an heteroreceptor. H3Rs are highly expressed in the basal ganglia, hippocampus and cortex, and regulate a number of neurotransmitters including acetylcholine, norepinephrine, GABA and dopamine. Its function and localization suggest that the H3R may be relevant to a number of psychiatric disorders and could represent a potential therapeutic target for substance use disorders. The purpose of the present review is to summarize preclinical studies investigating the effects of H3R agonists and antagonists on animal models of alcohol, nicotine and psychostimulant use. At present, the effects of H3R antagonists such as thioperamide, pitolisant or ciproxifan have been investigated in drug-induced locomotion, conditioned place preference, drug self-administration, reinstatement, sensitization and drug discrimination. For alcohol and nicotine, the effects of H3R ligands on two-bottle choice and memory tasks, respectively, have also been investigated. The results of these studies are inconsistent. For alcohol, H3R antagonists generally decreased the reward-related properties of ethanol, which suggests that H3R antagonists may be effective as a treatment option for alcohol use disorder. However, the effects of H3R antagonists on nicotine and psychostimulant motivation and reward are less clear. H3R antagonists potentiated the abuse-related properties of nicotine, but only a handful of studies have been conducted. For psychostimulants, evidence is mixed and suggests that more research is needed to establish whether H3R antagonists are a viable therapeutic option. The fact that different drugs of abuse have different brain targets may explain the differential effects of H3R ligands.

Acute effects of a very low nicotine content cigarette on laboratory smoking lapse: Impacts of nicotine metabolism and nicotine dependence.

Reducing cigarette nicotine content to nonaddictive levels facilitates smoking cessation; however, very low nicotine content cigarettes (VLNCs) may not be equally effective across heterogeneous smokers. We evaluated the impact of acute VLNC smoking versus control (sham puffs) on craving, withdrawal and smoking lapse behaviour and whether genetically influenced differences in nicotine metabolism and individual differences in nicotine dependence moderate observed effects. Thirty-three overnight-abstinent smokers (15 slow vs. 17 normal nicotine metabolizers; 17 low vs. 16 high nicotine dependence) smoked a 0.05-mg nicotine VLNC during one session and took sham VLNC puffs during another session, in a counterbalanced order. Craving and withdrawal were assessed before and after smoking and sham puffing. Next, participants completed the McKee Smoking Lapse Task, which measures ability to resist smoking and quantity of ad libitum smoking. VLNC (vs. sham) reduced craving and withdrawal, increased ability to resist smoking and reduced ad libitum smoking. VLNC-induced reduction in craving for positive reinforcement was greater in slow (vs. normal) metabolizers. Nicotine metabolism did not moderate any other VLNC responses. High-dependence (vs. low-dependence) participants engaged in greater ad lib smoking across VLNC and sham conditions. Nicotine dependence did not moderate VLNC responses. VLNC reduced craving, withdrawal and smoking lapse behaviour. Individual differences in nicotine metabolism and dependence had a minimal impact on VLNC responses; however, VLNCs were less effective at reducing craving for positive reinforcement among normal (vs. slow) metabolizers. These findings suggest that desirable VLNC effects may extend across heterogeneous groups of smokers.

Personalized dosing of nicotine replacement therapy versus standard dosing for the treatment of individuals with tobacco dependence: study protocol for a randomized placebo-controlled trial.

BACKGROUND: Medications for smoking cessation are currently only effective in helping a minority of smokers quit. Drug development is slow and expensive; as such, there is much interest in optimizing the effectiveness of existing treatments and medications. Current standard doses of nicotine replacement therapy are not effective for many smokers, and in many cases, the amount of nicotine provided is much less than when a smoker is smoking their usual number of cigarettes. The proposed study will test if titrating the dose of the nicotine patch (up to 84 mg) will improve quitting success compared to those receiving a 21-mg nicotine patch with increasing doses of placebo patch. METHODS: This is a multicenter, pragmatic, two-arm, placebo-controlled, block randomized controlled trial. We will recruit participants who smoke at least 10 cigarettes daily and are interested in making a quit attempt. After 2 weeks of usual treatment with a 21-mg patch, participants who fail to quit smoking (target n = 400) will be randomized to receive escalating doses of a nicotine patch vs matching placebo patches for an additional 10 weeks or up to a maximum dose of 84 mg per day. Those who stop smoking during the first 2 weeks of usual treatment will continue with 21 mg patch treatment for 10 weeks and will form an additional comparison arm. In addition to the medication, participants will receive brief behavioral counseling at each study visit. The primary outcome will be biochemically confirmed continuous abstinence from smoking during the last 4 weeks of treatment (weeks 9 to 12). DISCUSSION: Research evidence supporting the effectiveness of personalized doses of nicotine replacement therapy could change current practice in a variety of healthcare settings. Given the evidence that quitting smoking at any age diminishes the risk of tobacco-related morbidity and mortality, even small increases in absolute quit rates can have a substantial population-level impact on reducing smoking-related disease, mortality rates, and associated healthcare costs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03000387 . Registered on 22 December 2016.

Can the AUDIT consumption items distinguish lower severity from high severity patients seeking treatment for alcohol use disorder?

Brief screening tools based on the Alcohol Use Disorders Identification Test (AUDIT) consumption items (e.g., AUDIT-C and AUDIT-3) are commonly used in general medical settings to identify at-risk drinkers who may benefit from alcohol interventions. Conversely, in specialty alcohol treatment settings with a high volume of self-referrals, there may be a need for brief screening tools that can help to identify patients who are unlikely to require intensive treatments, but there has been little research on the use of AUDIT-C or AUDIT-3 in this context. The current study examined the utility of brief screeners comprised of the AUDIT consumption items for distinguishing lower-severity patients from high severity patients in a cohort of individuals self-referring to specialty alcohol treatment. Participants were adults seeking treatment for alcohol problems (N = 853) at a large public psychiatric hospital in Toronto, Canada, who completed the full 10-item AUDIT as part of an initial telephone screening with hospital staff. Results of receiver operating characteristic curve analyses showed that both the AUDIT-C and the AUDIT-3 demonstrated adequate accuracy (area under the curve; AUC > 0.85) for distinguishing lower-severity patients (defined as those in AUDIT zones I, II, and III) from high-severity patients (defined as those in AUDIT zone IV). Exploratory analyses showed that the addition of AUDIT item 4 (impaired control) to the AUDIT-C and AUDIT-3 significantly improved classification accuracy (AUCs = 0.95; ps < .001), and the resulting brief screeners had cut-points with good sensitivity and specificity (i.e., >80%). Results support the potential utility of brief screeners comprised of the AUDIT consumption items for distinguishing lower-severity from high severity individuals seeking specialty alcohol treatment services, which may assist with the initial screening and triage process. The addition of AUDIT item 4 improved the performance of the AUDIT-C and AUDIT-3 in this context. Future research validating these findings against external criteria, including comprehensive diagnostic information, is required.

A review of performance indicators of single-item alcohol screening questions in clinical and population settings.

Screening and brief intervention (SBI) for unhealthy alcohol use is recommended as a routine clinical procedure for adults in primary care settings. However, implementation of SBI remains suboptimal, in part reflecting time constraints in clinical settings. Single Item Screening Questions (SISQ) have increasingly been studied as a means of minimizing assessment burden. Although the ability of SISQ to accurately detect unhealthy alcohol use (i.e., at-risk drinking or alcohol use disorder) has been studied in various clinical and population settings, results have not been summarized in aggregate. This descriptive summarizes SISQ performance metrics across various clinical settings and populations. Based on results from 40 identified studies, there is consistent support that SISQ have good sensitivity as screeners for unhealthy drinking, with performance generally being comparable to longer validated instruments. Collectively, these results justify further efforts to evaluate SISQ as a means of maximizing SBI uptake and efficiency in various clinical settings.

Changes in Nicotine Metabolite Ratio Among Daily Smokers Receiving Treatment for Alcohol Use Disorder.

INTRODUCTION: Alcohol may influence the nicotine metabolite ratio (NMR), an index of the rate of nicotine metabolism that is associated smoking level and lapses. We examined if NMR changes during alcohol use disorder (AUD) treatment and how changes in NMR relate to reductions in drinking. METHODS: Using an observational design, 22 daily smokers [63.64% male, Mage = 46.77 (11.37)] receiving AUD treatment completed baseline and follow-up appointments 3 weeks apart. At each appointment, daily alcohol and cigarette use, salivary and urinary NMR, nicotine exposure via urinary total nicotine equivalents, and carbon monoxide were assessed. Multilevel models examined the change over time in NMR and its within-person relations with changes in drinks per week. Sex differences were evaluated. RESULTS: There were significant reductions in both salivary and urinary NMR over time for men (p = .02; p = .01, respectively) but not for women (p = .54; p = .90, respectively). There were no changes over time in total nicotine equivalents (p = .09), carbon monoxide (p = .44), or cigarette use (p = .44) in either sex. Drinks per week were significantly reduced for men (29.12 drink reduction, p < .001) but not for women (2.28 drink reduction, p = .80); however, within-person changes in drinking were not associated with changes in salivary or urinary NMR (p = .99; p = .19). CONCLUSIONS: The reduction in alcohol use and NMR in men provides indirect support for alcohol increasing NMR. In contrast, the low baseline drinking and lack of alcohol reduction likely underlie the lack of change in NMR in females. Reasons for NMR reductions during AUD treatment and its effects on smoking require further study. IMPLICATIONS: Three weeks of alcohol use disorder treatment among daily smokers coincided with a significant reduction in both alcohol use and NMR for men; however, neither drinking level nor NMR changed for women. The findings indirectly support that heavy drinking increases NMR, which is reversed with reduced drinking. Additional research is needed to establish if these changes in NMR correlate with smoking and cessation outcomes.

A review of behavioral alcohol interventions for transplant candidates and recipients with alcohol-related liver disease.

Alcohol-related liver disease (ALD) is a common indication for liver transplantation. Reflecting growing consensus that early transplant (ie, prior to sustained abstinence) can be a viable option for acute alcoholic hepatitis, access to liver transplantation for ALD patients has increased. Prevention of alcohol relapse is critical to pretransplant stabilization and posttransplant survival. Behavioral interventions are a fundamental component of alcohol use disorder treatment, but have rarely been studied in the transplant context. This scoping review summarizes published reports of behavioral and psychosocial alcohol interventions conducted with ALD patients who were liver transplant candidates and/or recipients. A structured review identified 11 eligible reports (3 original research studies, 8 descriptive papers). Intervention characteristics and clinical outcomes were summarized. Interventions varied significantly in orientation, content, delivery format, and timing/duration. Observational findings illustrate the importance of situating alcohol interventions within a multidisciplinary treatment context, and suggest the potential efficacy of cognitive-behavioral and motivational enhancement interventions. However, given extremely limited research evaluating behavioral alcohol interventions among ALD patients, the efficacy of behavioral interventions for pre- and posttransplant alcohol relapse remains to be established.

The effect of a clinical decision support system on prompting an intervention for risky alcohol use in a primary care smoking cessation program: a cluster randomized trial.

BACKGROUND: Clinical decision support systems (CDSSs) may promote practitioner adherence to evidence-based guidelines. This study examined if the addition of a CDSS influenced practitioner delivery of a brief intervention with treatment-seeking smokers who were drinking above recommended alcohol consumption guidelines, compared with practitioners who do not receive a CDSS prompt. METHODS: This was a cluster randomized controlled trial conducted in primary health care clinics across Ontario, Canada, implementing the Smoking Treatment for Ontario Patients (STOP) smoking cessation program. Clinics randomized to the intervention group received a prompt when a patient reported consuming alcohol above the Canadian Cancer Society (CCS) guidelines; the control group did not receive computer alerts. The primary outcome was an offer of an appropriate educational alcohol resource, an alcohol reduction workbook for patients drinking above the CCS guidelines, and an abstinence workbook to patients scoring above 20 points in the AUDIT screening tool; the secondary outcome was patient acceptance of the resource. The tertiary outcome was patient abstinence from smoking, and alcohol consumption within CCS guidelines, at 6-month follow-up. Results were analyzed using a generalized estimation approach for fitting logistic regression using a population-averaged method. RESULTS: Two hundred and twenty-one clinics across Ontario were randomized for this study; 110 to the intervention arm and 111 to the control arm. From the 15,222 patients that enrolled in the smoking cessation program, 15,150 (99.6% of patients) were screened for alcohol use and 5715 patients were identified as drinking above the CCS guidelines. No statistically significant difference between groups was seen in practitioner offer of an educational alcohol resource to appropriate patients (OR = 1.19, 95% CI 0.88-1.64, p = 0.261) or in patient abstinence from smoking and drinking within the CCS guidelines at 6-month follow-up (OR = 0.93, 95% CI 0.71-1.22, p = 0.594). However, a significantly greater proportion of patients in the intervention group accepted the alcohol resource offered to them by their practitioner (OR = 1.48, 95% CI 1.01-2.16, p = 0.045). CONCLUSION: A CDSS may not increase the likelihood of practitioners offering an educational alcohol resource, though it may have influenced patients' acceptance of the resource. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, number NCT03108144 , registered on April 11, 2017, "retrospectively registered".

Is (poly-) substance use associated with impaired inhibitory control? A mega-analysis controlling for confounders.

Many studies have reported that heavy substance use is associated with impaired response inhibition. Studies typically focused on associations with a single substance, while polysubstance use is common. Further, most studies compared heavy users with light/non-users, though substance use occurs along a continuum. The current mega-analysis accounted for these issues by aggregating individual data from 43 studies (3610 adult participants) that used the Go/No-Go (GNG) or Stop-signal task (SST) to assess inhibition among mostly "recreational" substance users (i.e., the rate of substance use disorders was low). Main and interaction effects of substance use, demographics, and task-characteristics were entered in a linear mixed model. Contrary to many studies and reviews in the field, we found that only lifetime cannabis use was associated with impaired response inhibition in the SST. An interaction effect was also observed: the relationship between tobacco use and response inhibition (in the SST) differed between cannabis users and non-users, with a negative association between tobacco use and inhibition in the cannabis non-users. In addition, participants' age, education level, and some task characteristics influenced inhibition outcomes. Overall, we found limited support for impaired inhibition among substance users when controlling for demographics and task-characteristics.

A longitudinal investigation of the association between cannabis use and alcohol use among people living with HIV.

BACKGROUND: Both cannabis use and alcohol use are elevated among people living with HIV, but few studies have investigated the relationship between cannabis use and alcohol use in this population. This study examined the longitudinal association between cannabis use and alcohol use among people living with HIV and explored the moderating role of medicinal vs. recreational cannabis use. METHOD: Participants were cannabis users (N=763) enrolled in the Ontario HIV Treatment Network Cohort Study (67% White, 88% male, 68% gay, median income in the $40,000-$50,000 range). Participants completed assessments of cannabis use, reasons for cannabis use, and alcohol use at baseline and at annual follow-ups (M = 3.42 completed assessments). Multilevel modeling was used to examine between-person and within-person associations between cannabis use and alcohol use over time. RESULTS: Greater average frequency of cannabis use was associated with greater average alcohol consumption across participants. Participants classified as medicinal cannabis users reported more frequent cannabis use and less alcohol use on average than recreational cannabis users. Further, within-person changes in cannabis use over time were positively associated with corresponding changes in alcohol use for recreational cannabis users but not for medicinal users. CONCLUSION: Cannabis use and alcohol use were positively associated over time among people living with HIV, although this association was specific to those using cannabis for recreational reasons. As alcohol use in this population poses significant health risks, more research on the link between cannabis use and alcohol use is needed, particularly in light of recent changes to cannabis regulations.

Does Family History of Alcohol Use Disorder Relate to Differences in Regional Brain Volumes? A Descriptive Review with New Data.

BACKGROUND: Differences in regional brain volumes as a function of family history (FH) of alcohol use disorder (AUD) have been reported, and it has been suggested that these differences might index genetic risk for AUD. However, results have been inconsistent. The aims of the current study were (i) to provide an updated descriptive review of the existing literature and (ii) to examine the association of FH with indices of subcortical volumes and cortical thickness in a sample of youth recruited based on FH status. METHODS: To address aim 1, a literature search located 15 published studies comprising 1,735 participants. Studies were characterized according to population, analytic methods, regions of interest, and primary findings. To address the second aim, we examined volumetric and cortical thickness in a sample of 69 youth (mean age = 19.71 years, SD = 0.79) recruited based on FH status and matched on drinking variables. Associations of sex and alcohol use with volumetric outcomes were also examined. RESULTS: Our descriptive review revealed an inconsistent pattern of results with respect to the presence, direction, and regional specificity of volumetric differences across FH groups. The most consistent finding, significantly smaller amygdala volumes in FH+ participants, was not replicated in all studies. In the current sample of youth, measures of subcortical volumes and cortical thickness did not significantly differ as a function of FH, sex, or their interaction. CONCLUSIONS: Evidence for FH group differences in regional brain volumes is inconsistent, and the current study failed to detect any group differences. Further research is needed to confirm the reproducibility of FH group differences and implications for AUD risk.

Influence of Nicotine Metabolism Ratio on [11C]-(+)-PHNO PET Binding in Tobacco Smokers.

Background: Identifying the biological basis of smoking cessation success is of growing interest. The rate of nicotine metabolism, measured by the nicotine metabolite ratio, affects multiple aspects of nicotine dependence. Fast nicotine metabolizers tend to smoke more, experience more withdrawal and craving, and have lower cessation rates compared with slow metabolizers. The nicotine metabolite ratio predicts treatment response, and differences in brain activation between fast metabolizers and slow metabolizers have been reported in fMRI studies. As reinforcing/rewarding effects of tobacco are associated with dopamine transmission, the purpose of the present study was to study the dopaminergic system in human smokers based on their nicotine metabolite ratio. Methods: The first aim of the study was to explore if there were differences in D2 and D3 receptor binding between fast metabolizers and slow metabolizers during abstinence. The second aim was to explore smoking-induced dopamine release in both groups. Participants underwent 2 [11C]-(+)-PHNO PET scans: one scan during abstinence and the other after smoking a tobacco cigarette. Subjective measures were recorded and blood was drawn for measurement of nicotine and cotinine levels. Results: During abstinence, slow metabolizers (n = 13) had lower [11C]-(+)-PHNO binding potential than fast metabolizers (n = 15) restricted to the D2 regions of the associative striatum and sensorimotor striatum. After smoking a cigarette, [11C]-(+)-PHNO binding potential was decreased in the limbic striatum and ventral pallidum, suggestive of increases in dopamine, but there were no nicotine metabolite ratio differences. Conclusions: Further studies are required to delineate if differences in [11C]-(+)-PHNO binding between slow metabolizers and fast metabolizers at abstinence baseline are preexisting traits or induced by prolonged tobacco use.

Implicit Alcohol and Smoking Associations among Young Adult Heavy Drinkers: Associations with Smoking Status and Alcohol-Cigarette Co-Use.

Implicit memory associations may play a role in motivation to use alcohol and cigarettes, but the relationship between implicit associations and co-use of alcohol and cigarettes is currently unknown. This study provided an initial examination of alcohol and smoking implicit associations among young adult drinkers who were either nonsmokers or relatively light smokers (i.e., 10 or fewer cigarettes per day) as a function of smoking frequency and daily-level alcohol-cigarette co-use. Drinkers (N = 129) completed alcohol-arousal and smoking-valence variants of the Implicit Association Test as well as a daily-level assessment of past 90-day alcohol and cigarette use. Smokers were grouped according to whether they reported daily or nondaily smoking frequency. Results showed that although implicit alcohol-arousal associations did not differ between smokers and nonsmokers, stronger implicit alcohol-arousal associations were observed for nondaily smokers relative to daily smokers after controlling for drinking frequency. Further, implicit positive-smoking associations were stronger for smokers relative to nonsmokers. Within the subgroup of nondaily smokers, more frequent co-use of alcohol and cigarettes was associated with stronger implicit positive-smoking associations when controlling for total drinking and smoking frequency. The findings suggest that implicit alcohol and smoking associations may be linked with smoking patterns (daily vs. nondaily) and co-use of alcohol and cigarettes among young adult drinkers who are not heavy smokers, highlighting the need for more research on the role of implicit associations in the co-use of cigarettes and alcohol.