Cannabidiol tempers alcohol intake and neuroendocrine and behavioural correlates in alcohol binge drinking adolescent rats. Focus on calcitonin gene-related peptide's brain levels.

Alcohol binge drinking is common among adolescents and may challenge the signalling systems that process affective stimuli, including calcitonin gene-related peptide (CGRP) signalling. Here, we employed a rat model of adolescent binge drinking to evaluate reward-, social- and aversion-related behaviour, glucocorticoid output and CGRP levels in affect-related brain regions. As a potential rescue, the effect of the phytocannabinoid cannabidiol was explored. Adolescent male rats underwent the intermittent 20% alcohol two-bottle choice paradigm; at the binge day (BD) and the 24 h withdrawal day (WD), we assessed CGRP expression in medial prefrontal cortex (mPFC), nucleus accumbens (NAc), amygdala, hypothalamus and brainstem; in addition, we evaluated sucrose preference, social motivation and drive, nociceptive response, and serum corticosterone levels. Cannabidiol (40 mg/kg, i.p.) was administered before each drinking session, and its effect was measured on the above-mentioned readouts. At BD and WD, rats displayed decreased CGRP expression in mPFC, NAc and amygdala; increased CGRP levels in the brainstem; increased response to rewarding- and nociceptive stimuli and decreased social drive; reduced serum corticosterone levels. Cannabidiol reduced alcohol consumption and preference; normalised the abnormal corticolimbic CGRP expression, and the reward and aversion-related hyper-responsivity, as well as glucocorticoid levels in alcohol binge-like drinking rats. Overall, CGRP can represent both a mediator and a target of alcohol binge-like drinking and provides a further piece in the intricate puzzle of alcohol-induced behavioural and neuroendocrine sequelae. CBD shows promising effects in limiting adolescent alcohol binge drinking and rebalancing the bio-behavioural abnormalities.

Magnesium-L-threonate alleviate colonic inflammation and memory impairment in chronic-plus-binge alcohol feeding mice.

Magnesium-l-threonate (MgT) is considered a food supplement. Alcohol-mediated diseases (AMD) are accompanied by inflammation and memory impairment. The purpose of this study is to investigate the function of MgT in AMD. Hence, chronic-plus-binge alcohol feeding mice model and multiply bioinformatics analysis were performed. Consequently, the expression of inflammatory cytokines downregulated, while the activities of antioxidases decreased in serum, colon, and brain. Interestingly, MgT relieved gut barrier dysfunction and reshaped microbiota. The relative abundance of Akkermansia, Odoribacter, and Blautia were increased, while that of Alloprevotella and Clostridium were decreased. Metabolic analysis elucidated amino acids and glutamate metabolism were enhanced in MgT-treated mice. Furthermore, morris water maze test confirmed memory ability was enhanced. Inflammation cytokines were negatively correlated with Blautia, and Akkermansia. Collectively, MgT relieved inflammation in gut-brain axis of mice, reshaped gut microbiota, and enhanced the amino acids and glutamate metabolism. MgT may be used as a food supplement to prevent inflammation and memory impairment induced by alcohol abuse.

Early Signs of Emotional Recognition Deficits in Adolescent High-Binge Drinkers.

Background: Emotional dysregulation, measured with face recognition tasks, is prevalent in alcohol use disorders (AUD), constituting a risk factor for alcohol use and relapse. It is not clear however whether emotional dysregulation is a by-product of alcohol consumption, or if it can act as a predisposing factor for AUD. Objective: Our aim was to examine early signs of emotional dysregulation in adolescent drinkers. Method: Twenty-four high-school students and 24 university students completed two tasks. On the first one, participants had to gradually increment the emotional content of different faces until they could perceive an emotional expression (emotion perception threshold task). We also examined the propensity to perceive fearful expressions in an emotion identification task. Participants were semantically primed with emotion words (i.e., "fear"), and they then had to indicate whether a neutral-fearful facial composite matched the prime. Results: Using repeated-measures ANOVAS, in the emotion perception threshold task, "happy" faces were the easiest to detect and "sad" ones the hardest. For high school students there was a differential response pattern depending on binge scores, such that High-binge drinkers found it easier to detect a sad face but harder to detect a happy one compared to Low-binge drinkers. In the facial emotion identification task, Low-binge drinkers observed more fearful expressions compared to High-binge drinkers. Conclusions: Differences in emotional processing in young adolescents depending on drinking habits point towards the relevance of emotional dysregulation as an early sign of AUD. These findings could help develop novel diagnostic and treatment tools for young populations.

A randomized clinical trial evaluating the efficacy of a brief alcohol intervention supplemented with a substance-free activity session or relaxation training.

OBJECTIVE: Behavioral economic theory suggests that a reduction in alcohol use is most likely when there is an increase in rewarding substance-free activities. Anxiety has also been linked to heavy drinking, and strategies to reduce anxiety may enhance alcohol interventions. The goal of this 2-site randomized controlled clinical trial was to evaluate the efficacy of a brief alcohol intervention that was supplemented with either a behavioral economic substance-free activity session (SFAS) or a relaxation training (Relaxation training [RT]) session. METHOD: Participants were 393 college students (61% female, mean age = 18.77 years) who reported 2 or more past-month heavy drinking episodes. Participants were randomized to 1 of 3 conditions: (a) assessment; (b) alcohol brief motivational intervention (BMI) plus SFAS; or (c) BMI plus RT. Both treatment conditions included 2 in-person sessions plus a phone booster session. Outcomes were evaluated 1-, 6-, 12-, and 16-months postintervention. RESULTS: Generalized linear mixed models indicated that the combination of a BMI plus either the SFAS or RT was associated with significant reductions in alcohol use and problems across the 16-month follow-up compared with assessment only. There were no significant differences between the two active treatment conditions. Changes in proportional reinforcement from substance-related activities, and protective behavioral strategies mediated treatment effects. CONCLUSION: Two-session (plus booster) interventions that combine BMI and either substance-free activity enhancement or RT can result in enduring reductions in alcohol misuse among college drinkers. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The combination of swimming and curcumin consumption may improve spatial memory recovery after binge ethanol drinking.

Helping the return of people with social disorders, including ethanol consumption, are important research topics in the field of biological sciences, and there are many uncertainties about the efficacy of drug interventions and exercise training. The aim of this study was to investigate the effects short-term combination of curcumin and swimming on the improvement of spatial memory. Male Wistar rats (200-250 g) were randomly assigned into ethanol or dextrose groups. After 4 days of gavage, and withdrawn of consumption, they were affected by swimming intervention or curcumin supplementation within 2 weeks. Spatial memory was assessed in Morris Water Maze (MWM) apparatus by a single training session of eight trials. Furthermore, levels of BDNF were measured in hippocampal tissue by doing real time PCR. The results showed that binge ethanol drinking had no significant effect on the traveled distance [F(1,14) = 0.024; P > .05] and escape latency [F(1,14) = 0.648; P > .05] of reaching the platform. In the probe test, both the percentage of swimming time [t(14) = -4.621; P < .001] and distance [t(14) = -4.989; P < .001] in the target quadrant was significantly lower in the ethanol group than the dextrose group. On the other hand in reviewing the effect of curcumin and swimming exercise on learning and spatial memory, The percentage of swimming time was significantly higher in the swim+curcumin [P < .01], training [P < .05] and curcumin [P < .05] subgroups then the control subgroup. The percentage of distance traveled in the swim+curcumin subgroup [P < .001] and curcumin subgroup [P < .05] was significantly higher than the control subgroup. In addition, in the group of binge ethanol drinking, the percentage of swimming time and distance traveled in the target quadrant in the swim+curcumin subgroup was significantly higher than the control subgroup [P < .001]. There was a positive correlation between BDNF gene expression and the percentage of swimming time [P < .01] and the distance traveled in the target quadrant [P < .001] was observed. In conclusion, Binge ethanol drinking causes spatial memory deficiency by reduction of BDNF, and the combination of curcumin and swimming training improves impaired spatial memory after binge ethanol drinking.

Risk profiles for heavy drinking in adolescence: differential effects of gender.

Abnormalities across different domains of neuropsychological functioning may constitute a risk factor for heavy drinking during adolescence and for developing alcohol use disorders later in life. However, the exact nature of such multi-domain risk profiles is unclear, and it is further unclear whether these risk profiles differ between genders. We combined longitudinal and cross-sectional analyses on the large IMAGEN sample (N ≈ 1000) to predict heavy drinking at age 19 from gray matter volume as well as from psychosocial data at age 14 and 19-for males and females separately. Heavy drinking was associated with reduced gray matter volume in 19-year-olds' bilateral ACC, MPFC, thalamus, middle, medial and superior OFC as well as left amygdala and anterior insula and right inferior OFC. Notably, this lower gray matter volume associated with heavy drinking was stronger in females than in males. In both genders, we observed that impulsivity and facets of novelty seeking at the age of 14 and 19, as well as hopelessness at the age of 14, are risk factors for heavy drinking at the age of 19. Stressful life events with internal (but not external) locus of control were associated with heavy drinking only at age 19. Personality and stress assessment in adolescents may help to better target counseling and prevention programs. This might reduce heavy drinking in adolescents and hence reduce the risk of early brain atrophy, especially in females. In turn, this could additionally reduce the risk of developing alcohol use disorders later in adulthood.

Craving, cortisol and behavioral alcohol motivation responses to stress and alcohol cue contexts and discrete cues in binge and non-binge drinkers.

Alcohol use disorders are associated with high craving and disruption of stress biology, but their role in behavioral alcohol motivation is less clear. We examined the effects of craving and cortisol responses on behavioral alcohol motivation to stress, alcohol cue and neutral-relaxing context cues, in addition to discrete alcohol cues, in demographically matched binge/heavy (BH) and moderate (MD) social drinkers. Subjects participated in a 3-day laboratory experiment of provocation by three personalized guided imagery contexts and discrete alcohol cues followed by the 'alcohol taste test' (ATT) to assess behavioral motivation, as measured by ATT intake. Post-ATT alcohol effects on craving and cortisol responses were also examined. Results indicate BH consumed significantly more alcohol than MD in the ATT. Stress and alcohol cue contexts, relative to neutral, led to significantly greater ATT intake across both groups, which also correlated positively with self-reported alcohol use in past 30 days. Stress and alcohol context and discrete alcohol cues each significantly increased alcohol craving, more so in the BH than MD, and significantly predicted greater ATT intake in BH only. The BH showed significantly lower cortisol responses than MD overall and blunted cortisol responses to cues predicted significantly greater ATT intake in the stress condition for BH and in the alcohol cue condition for MD. Higher ATT intake predicted greater cortisol response and higher craving post-ATT, and these effects were moderated by group status. In sum, findings suggest a role for sensitized context-induced craving and blunted cortisol responses in increased behavioral motivation for alcohol.

Stress vulnerability and alcohol use and consequences: From human laboratory studies to clinical outcomes.

It is well known that vulnerability to stress is a risk factor for alcohol use disorder (AUD). Chronic alcohol use can result in neuroadaptations in cortico-striatal pathways and hypothalamic pituitary adrenal (HPA) axis function that are manifested in altered behavioral and cognitive control functions contributing to alcohol craving, compulsive motivation, consumption, and consequences. This symposium brings together studies utilizing novel approaches to help improve our understanding of stress - past, acute, and chronic - on alcohol seeking and consumption and related outcomes using a combination of human laboratory models, neuroimaging, and clinical measures. Examining factors that determine vulnerability as well as resilience to stress are of particular interest in the study of AUD because, in addition to increasing our understanding of the risk factors for AUD, such knowledge can be used to develop more effective treatments. Dr. Stangl presented a novel human experimental model that demonstrates, for the first time, stress-induced increases in alcohol self-administration in binge drinkers using a guided imagery paradigm combined with intravenous alcohol self-administration (IV-ASA). Dr. Blaine presented data demonstrating that glucocorticoid response to stress drives compulsive alcohol motivation and intake in binge/heavy drinkers. Dr. Plawecki presented data examining sex differences in the effect of two distinct stress paradigms - mood induction and abstinence - on IV-ASA in moderate drinkers. Dr. Schwandt presented clinical data providing a new perspective on the relationship between childhood trauma and AUD by suggesting possible underlying mechanisms that confer resilience, rather than vulnerability, to severe early life stress exposure.

Mindfulness as a mediator of the association between adverse childhood experiences and alcohol use and consequences.

One-third of college students report past-year heavy episodic drinking, making college student alcohol use an important area for continued research. Research has consistently linked early experiences of adversity to problematic substance use in adolescence and adulthood. Given the negative health consequences associated with heavy episodic drinking, it is imperative to identify mechanisms that contribute to this relation. Low levels of mindfulness have been linked to early adversity as well as impulsivity and alcohol use, therefore, the current study aims to examine the mediating role of mindfulness in the relation between early adversity and current alcohol use and consequences. Undergraduate students (N = 385) at a Midwestern university completed an online questionnaire assessing experiences of childhood adversity, trait mindfulness, and current alcohol use and related consequences. Results indicated that increased adverse experiences and lower levels of mindfulness predicted both increased alcohol consumption and consequences (ps < 0.025), with mindfulness mediating the relationships. Mindfulness is a predictor of alcohol outcomes and appears to mediate the relation between early adversity and alcohol use and consequences. Findings suggest that students with a history of adversity are more likely to exhibit lower levels of mindfulness, which may lead to an increase in alcohol consumption and consequences in early adulthood. Targeted alcohol intervention efforts that incorporate mindfulness skills may be particularly beneficial for those who have experienced early adversity.

Toxicological evaluation of 5-methoxy-2-aminoindane (MEAI): Binge mitigating agent in development.

5-Methoxy-2-aminoindane (MEAI) is a psychoactive compound of the aminoindane class, which in recent years has been recreationally used by many people, who reported of a mild euphoric, alcohol-like tipsy experience and reduced desire to consume alcoholic beverages. In the light of these observations it was decided to progress MEAI through a preliminary drug development route and evaluate the acute and subacute toxicity of MEAI administrated orally to Sprague Dawley rats, as well as to determine potential in-vitro cytotoxic and mutagenic effects using state-of-the-art protocols. Furthermore, the interaction of MEAI at the highest non-toxic concentration (100mg/L) with ethanol at cytotoxic levels of 6% and 7.5% was explored, in order to identify possible additive or synergistic effects. MEAI showed a good safety profile in rats at 10 and 30mg/kg body weight, corresponding to the human doses of 1.6mg/kg and 4.8mg/kg body weight, respectively. Cytotoxic effect was demonstrated using concentrations of 500 and 1000mg/L with calculated IC50 value of 368.2mg/L for rat brain striatum primary neurons and 403.1mg/L for human primary healthy hepatocytes. The combination of 6% or 7.5% ethanol with 100mg/L MEAI revealed no statistically significant increase of cytotoxic effect. Further studies, especially long term chronic and addictive behavior studies, are required in-order to assess MEAI safety profile.

Different forms of spirituality and heavy episodic drinking among college students.

OBJECTIVE: The current study examined prospective, bidirectional relationships between 3 measures of spirituality (Daily Spiritual Experiences, Positive Religious Coping, and Negative Religious Coping) and frequency of heavy episodic drinking. PARTICIPANTS: Three hundred ninety-one students attending a large, public university in the Midwest. METHODS: Electronic surveys assessing predictors of college alcohol use were sent to participants in the winter of their freshman and sophomore years. Structural equation modeling was used to analyze data. RESULTS: A latent factor comprised of Daily Spiritual Experiences and Positive Religious Coping (ie, "positive spirituality") was negatively related to future frequency of heavy episodic drinking. Negative Religious Coping was unrelated to heavy episodic drinking. Additionally, heavy episodic drinking did not prospectively predict any measures of spirituality. CONCLUSIONS: Data are supportive of continued efforts to integrate positive spirituality into interventions for collegiate heavy episodic drinking.

Sedentary college student drinkers can start exercising and reduce drinking after intervention.

Heavy drinking by college students is exceedingly harmful to the individuals and to the overall college environment. Current interventions to reduce drinking and negative consequences are infrequently utilized. This randomized clinical trial examined an alternative approach that sought to increase exercise behavior, a substance free activity, in sedentary heavy drinking college students. Participants (N = 70) were randomized to an 8-week exercise intervention: (a) motivational interviewing plus weekly exercise contracting (MI + EC) or (b) motivational interviewing and weekly contingency management for exercise (MI + CM). Follow-up evaluations occurred at posttreatment (2 months) and 6 months post baseline. Participants in both interventions significantly increased exercise frequency initially, and the MI + CM participants exercised significantly more than the MI + EC intervention participants during the intervention period (d = 1.70). Exercise behavior decreased during the follow-up period in both groups. Significant reductions in drinking behaviors and consequences were noted over time, but were not related to changes in exercise or the interventions (ds ≤ 0.01). This study underscores the complex nature of promoting 1 specific health behavior change with the goal of changing another. (PsycINFO Database Record

Depressive Symptoms and Alcohol-Related Problems Among College Students: A Moderated-Mediated Model of Mindfulness and Drinking to Cope.

OBJECTIVE: In college student samples, the association between depressive symptoms and alcohol-related problems has been found to be mediated by drinking-to-cope motives. Mindfulness-based interventions suggest that mindfulness may attenuate the conditioned response of using substances in response to negative emotional states, and trait mindfulness has been shown to be a protective factor associated with experiencing fewer alcohol-related problems. In the present study, we examined trait mindfulness as a moderator of the indirect associations of depressive symptoms on alcohol-related problems via drinking-to-cope motives. METHOD: Participants were undergraduate students at a large, southeastern university in the United States who drank at least once in the previous month (n = 448). Participants completed an online survey regarding their personal mental health, coping strategies, trait mindfulness, and alcohol use behaviors. The majority of participants were female (n = 302; 67.4%), identified as being either White non-Hispanic (n = 213; 47.5%) or African American (n = 119; 26.6%), and reported a mean age of 22.74 (SD = 6.81) years. Further, 110 (25%) participants reported having a previous and/or current experience with mindfulness mediation. RESULTS: As hypothesized, the indirect effects from depressive symptoms to alcohol-related problems via drinking-to-cope motives were weaker among individuals reporting higher levels of mindfulness than among individuals reporting lower and average levels of mindfulness. CONCLUSIONS: The present study suggests a possible mechanism through which mindfulness-based interventions may be efficacious among college students: decoupling the associations between depressive symptoms and drinking-to-cope motives.

Substance use and misuse and potential doping behaviour in rugby union players.

The aims of this investigation were to compile evidence on substance-use-and-misuse (SUM) and to identify factors related to potential-doping-behaviour (PDB) in rugby union. The subjects were 105 rugby athletes (all males; 23.4 ± 4.1 years; 99% respondents). The variables included socio-demographic factors, SUM-data, sport-factors, knowledge-on-doping (KD), and PDB. Data showed high alcohol consumption, with more than 30% of the athletes binge drinking at least once per week. Approximately 52% of the subjects used dietary-supplementation (DS) and 23% reported PDB, whereas 55% believed that doping is present in rugby. Forward conditional logistic regression revealed that less rugby experience (OR:1.286; 95%CI:1.058-1.563; p < 0.05), less smoking (OR:2.034; 95%CI:1.100-3.760; p < 0.05), higher DS usage (OR:5.543; 95%CI:1.666-18.444; p < 0.01), and a stronger belief that doping is present in rugby (OR:0.305; 95%CI:0.066-0.638; p < 0.01) were significant predictors of PDB. The high PDB and alcohol consumption warrant a serious intervention on these problems in rugby.

Portrayal of alcohol consumption in movies and drinking initiation in low-risk adolescents.

OBJECTIVES: To investigate the hypothesis that exposure to alcohol consumption in movies affects the likelihood that low-risk adolescents will start to drink alcohol. METHODS: Longitudinal study of 2346 adolescent never drinkers who also reported at baseline intent to not to do so in the next 12 months (mean age 12.9 years, SD = 1.08). Recruitment was carried out in 2009 and 2010 in 112 state-funded schools in Germany, Iceland, Italy, Netherlands, Poland, and Scotland. Exposure to movie alcohol consumption was estimated from 250 top-grossing movies in each country in the years 2004 to 2009. Multilevel mixed-effects Poisson regressions assessed the relationship between baseline exposure to movie alcohol consumption and initiation of trying alcohol, and binge drinking (≥ 5 consecutive drinks) at follow-up. RESULTS: Overall, 40% of the sample initiated alcohol use and 6% initiated binge drinking by follow-up. Estimated mean exposure to movie alcohol consumption was 3653 (SD = 2448) occurrences. After age, gender, family affluence, school performance, TV screen time, personality characteristics, and drinking behavior of peers, parents, and siblings were controlled for, exposure to each additional 1000 movie alcohol occurrences was significantly associated with increased relative risk for trying alcohol, incidence rate ratio = 1.05 (95% confidence interval, 1.02-1.08; P = .003), and for binge drinking, incidence rate ratio = 1.13 (95% confidence interval, 1.06-1.20; P < .001). CONCLUSIONS: Seeing alcohol depictions in movies is an independent predictor of drinking initiation, particularly for more risky patterns of drinking. This result was shown in a heterogeneous sample of European youths who had a low affinity for drinking alcohol at the time of exposure.

Ethnicity as a moderator of motivational interviewing for incarcerated adolescents after release.

Motivational interviewing (MI) has been found to be an effective treatment for substance using populations, including incarcerated adolescents. Although some studies suggest MI is more successful with individuals from minority backgrounds, the research remains mixed. The current study investigated the impact of ethnicity on treatment in reducing alcohol and marijuana use among incarcerated adolescents. Adolescents (14-19 years of age) were recruited from a state juvenile correctional facility and randomly assigned to receive MI or relaxation therapy (RT) (N=147; 48 White, 51 Hispanic, and 48 African American; 126 male; 21 female). Interviews were conducted at admission to the facility and 3 months after release. Results suggest that the effects of MI on treatment outcomes are moderated by ethnicity. Hispanic adolescents who received MI significantly decreased total number of drinks on heavy drinking days (NDHD) and percentage of heavy drinking days (PHDD) as compared to Hispanic adolescents who received RT. These findings suggest that MI is an efficacious treatment for an ethnic minority juvenile justice-involved population in need of evidence-based treatments.

Breaking the cycle of desire: Mindfulness and executive control weaken the relation between an implicit measure of alcohol valence and preoccupation with alcohol-related thoughts.

Stimuli with strong affective valence capture attention. This can impede the self-regulation of impulses. That is, preoccupation with a tempting stimulus such as alcohol may lead to a continued activation of automatic affective responses to that stimulus, increasing the likelihood of approach and consumption. Self-regulation may, thus, benefit from variables that weaken the relation between salient stimuli and cognitive preoccupation with those stimuli. Recent research shows that mindfulness and executive control reduce the link between automatic affective responses to alcohol and alcohol consumption. In this study, the authors examined whether mindfulness and executive control may similarly decouple the relation between automatic affective responses and difficulty in disengaging attention from alcohol-related thoughts. Participants completed measures of trait mindfulness, executive control (a working memory task), automatic alcohol-valence associations, and preoccupation with alcohol-related thoughts. Results showed that (a) both trait mindfulness and executive control are inversely related with alcohol preoccupation, and (b) both mindfulness and executive control weaken a positive relation between automatic alcohol-valence associations and alcohol preoccupation.