Journal of addiction research & therapy最新文献

Objective: To evaluate the effectiveness of ceftriaxone treatment in attenuating relapse-like ethanol drinking behavior in male P rats following 14-weeks of continuous ethanol consumption.

Methods: After 14-weeks of continuous access to free choice of 15% and 30% ethanol, male P rats were deprived of ethanol for two weeks. On the last five days of abstinence period, P rats were treated, once a day, with either saline or ceftriaxone (50 or 200 mg/kg; i.p.). This was followed by re-exposure to ethanol for the next 10 days to simulate the relapse-like ethanol drinking behavior.

Results: Ceftriaxone treatment (during abstinence) reduced ethanol intake upon re-exposure to ethanol, compared to the saline treated P rats. This statistically significant reduction in ethanol consumption in P rats following treatment with ceftriaxone (200 mg/kg/day) was observed from Day 2 to Day 9. Similarly, water consumption in P rats treated with ceftriaxone was significantly higher than the saline treated group between Day 2 and Day 7. Importantly, ceftriaxone treatment at both doses did not cause any significant changes in body weight compared to saline treated group.

Conclusions: We report here that ceftriaxone at higher dose has been found to be effective in the attenuation of relapse-like ethanol-drinking behavior in chronic ethanol intake model. This is in accordance with previous data from our lab in cocaine animal model demonstrating that only higher dose of ceftriaxone has been effective in attenuating cocaine relapse.

The endemic of legal opioid iatrogenic induced prescription drug abuse is of major world-wide concern. Understanding pain pathways and the role of dopaminergic tone in the neurophysiology of pain relief provides potential therapeutic solutions. A 2011 NIDA report indicated that approximately 8.7% of the entire US population above the age of 12 years has used a psychoactive drug within the past 30 days. It has been reported that the overall genetic contribution to the variance of Substance Use Disorder (SUD) was approximately 60% but each candidate gene evaluated by GWAS was relatively small. In an attempt to combat this global endemic we are proposing a number of alternative strategies. Prevention of death due to opioid overdose and attenuation of prescription abuse should focus on strategies that target 1) high-dosage medical users; 2) persons who seek care from multiple doctors; 3) persons involved in "drug diversion"; 4) genetic testing for addiction liability and severity indices; 5) non-pharmacolgical analgesic treatments such as electrotherapy.

Addictions to smoking, alcohol, illicit drugs, and certain behaviors like gambling, overeating, and sex, are prevalent worldwide. These behaviors are highly destructive and costly to individuals and society due to health consequences, criminality and lost productivity. The genetic vulnerability, environmental exposures, and individual behaviors that contribute to the brain dysfunction and compulsive tendencies that mark addiction make it one of the most complicated diseases to study and treat. Although much has been learned about the genetic basis of and biochemical imbalances associated with the addictions, research leading to effective treatments has been slow. Addictions are often accompanied by an inner sense of disintegration, enslavement and meaninglessness that can be viewed in terms of a spiritual craving for wholeness, freedom, and transformation. Arguably, progress towards effective treatment has been retarded by insufficient attention being paid to understanding the role of spirituality in helping to heal addicts. Assuming one accepts the belief that the brain mediates all conscious and unconscious experiences- including spiritually experiences -healing, like addictions, can be related to the processes by which the human brain is organized for controlling pleasure and pain. Here we hypothesize that a healthy spirituality may come more naturally to some individuals because of the unique interaction of their genes and their environments, and we review the evidence in support of this view.

Background: Economic conditions and drinking norms have been in considerable flux over the past 10 years. Accordingly, research is needed to evaluate both overall trends in alcohol problems during this period and whether changes within racial/ethnic groups have affected racial/ethnic disparities.

Methods: We used 3 cross-sectional waves of National Alcohol Survey data (2000, 2005, and 2010) to examine a) temporal trends in alcohol dependence and consequences overall and by race/ethnicity, and b) the effects of temporal changes on racial/ethnic disparities. Analyses involved bivariate tests and multivariate negative binomial regressions testing the effects of race/ethnicity, survey year, and their interaction on problem measures.

Results: Both women and men overall showed significant increases in dependence symptoms in 2010 (vs. 2000); women also reported increases in alcohol-related consequences in 2010 (vs. 2000). (Problem rates were equivalent across 2005 and 2000.) However, increases in problems were most dramatic among Whites, and dependence symptoms actually decreased among Latinos of both genders in 2010. Consequently, the long-standing disparity in dependence between Latino and White men was substantially reduced in 2010. Post-hoc analyses suggested that changes in drinking norms at least partially drove increased problem rates among Whites.

Conclusions: Results constitute an important contribution to the literature on racial/ethnic disparities in alcohol problems. Findings are not inconsistent with the macroeconomic literature suggesting increases in alcohol problems during economic recession, but the pattern of effects across race/ethnicity and findings regarding norms together suggest, at the least, a revised understanding of how recessions affect drinking patterns and problems.

Alcohol use disorders are pervasive in society and their impact affects quality of life, morbidity and mortality, as well as individual productivity. Alcohol has detrimental effects on an individual's physiology and nervous system, and is associated with disorders of many organ and endocrine systems impacting an individual's health, behavior, and ability to interact with others. Youth are particularly affected. Unfortunately, adolescent usage also increases the probability for a progression to dependence. Several areas of research indicate that the deleterious effects of alcohol abuse may be exacerbated by mixing caffeine with alcohol. Some behavioral evidence suggests that caffeine increases alcohol drinking and binge drinking episodes, which in turn can foster the development of alcohol dependence. As a relatively new public health concern, the epidemiological focus has been to establish a need for investigating the effects of caffeinated alcohol. While the trend of co-consuming these substances is growing, knowledge of the central mechanisms associated with caffeinated ethanol has been lacking. Research suggests that caffeine and ethanol can have additive or synergistic pharmacological actions and neuroadaptations, with the adenosine and dopamine systems in particular implicated. However, the limited literature on the central effects of caffeinated ethanol provides an impetus to increase our knowledge of the neuroadaptive effects of this combination and their impact on cognition and behavior. Research from our laboratories indicates that an established rodent animal model of alcoholism can be extended to investigate the acute and chronic effects of caffeinated ethanol.

Background: Emerging evidence suggests that neuroadaptations to alcohol may result from chronic alcohol consumption-induced expression changes of microRNAs (miRNAs) and their target genes. Studies with animal or cell culture models have demonstrated that ethanol exposure leads to miRNA expression alterations. However, there is limited information on miRNA expression in the brains of subjects with alcohol use disorders (AUDs). The present study aimed to analyze expression changes of miRNAs and their target genes in postmortem prefrontal cortex (PFC) of AUD subjects.

Methods: Genome-wide miRNA and mRNA expression was examined in postmortem PFC of 23 European Australia AUD cases and 23 matched controls using the Illumina HumanHT-12 v4 Expression BeadChip array, which targets 43,270 coding transcripts and 3,961 non-coding transcripts (including 574 miRNA transcripts). Multiple linear regression analysis and permutation test were performed to identify differentially expressed miRNAs and their target mRNAs. Target gene prediction, Gene Set Enrichment Analysis (GESA), and DAVID functional annotation clustering analysis were applied to identify AUD-associated gene sets and biological modules.

Results: Two miRNAs and 787 coding genes were differentially expressed in the PFC of AUD cases [miR-130a (downregulated): P_permutation=0.023, miR-604 (upregulated): P_permutation=0.019, coding genes: 1.6×10^-5≤P_permutation≤0.05; but all P values did not survive multiple-testing correction]. GESA showed that the 202 predicted target genes of miR-130a were highly enriched in differentially expressed genes (P_nominal<0.001), but not the 116 predicted target genes of miR-604 (P_nominal=0.404). DAVID functional clustering further revealed that the hub target genes (e.g., ITPR2 and ATP1A2) of miRNA130a were mainly responsible for regulating ion channel function.

Conclusion: This study provides evidence that downregulation of miR-130a may lead to altered expression of a number of genes in the PFC of AUD subjects. Further studies are warranted to confirm these findings in replication samples and other reward-related brain regions.

Rates of tobacco use among adolescents in China and other lower and middle-income countries remain high despite notable prevention and intervention programs. One reason for this may be the lack of theory-based research in tobacco use prevention in these countries. In the current study, a culturally appropriate 21-item measurement scale for cigarette smoking was developed based on the core constructs of Protection Motivation Theory (PMT). The scale was assessed among a sample of 553 Chinese vocational high school students. Results from correlational and measurement modeling analysis indicated adequate measurement reliability for the proposed PMT scale structure. The two PMT Pathways and the seven PMT constructs were significantly correlated with adolescent intention to smoke and actual smoking behavior. This study is the first to evaluate a PMT scale for cigarette smoking among Chinese adolescents. The scale provides a potential tool for assessing social cognitive processes underlying tobacco use. This is essential for understanding smoking behavior among Chinese youth and to support more effective tobacco use prevention efforts. Additional studies are needed to assess its utility for use with Chinese youth in other settings.

It is well established that inherited human aldehyde dehydrogenase 2 (ALDH-2) deficiency reduces the risk for alcoholism. Kudzu plants and extracts have been used for 1,000 years in traditional Chinese medicine to treat alcoholism. Kudzu contains daidzin, which inhibits ALDH-2 and suppresses heavy drinking in rodents. Decreased drinking due to ALDH-2 inhibition is attributed to aversive properties of acetaldehyde accumulated during alcohol consumption. However not all of the anti-alcohol properties of diadzin are due to inhibition of ALDH-2. This is in agreement with our earlier work showing significant interaction effects of both pyrozole (ALDH-2 inhibitor) and methyl-pyrozole (non-inhibitor) and ethanol's depressant effects. Moreover, it has been suggested that selective ALDH 2 inhibitors reduce craving for alcohol by increasing dopamine in the nucleus accumbens (NAc). In addition there is significant evidence related to the role of the genetics of bitter receptors (TAS2R) and its stimulation as an aversive mechanism against alcohol intake. The inclusion of bitters such as Gentian & Tangerine Peel in Declinol provides stimulation of gut TAS2R receptors which is potentially synergistic with the effects of Kudzu. Finally the addition of Radix Bupleuri in the Declinol formula may have some protective benefits not only in terms of ethanol induced liver toxicity but neurochemical actions involving endorphins, dopamine and epinephrine. With this information as a rationale, we report herein that this combination significantly reduced Alcohol Use Disorders Identification Test (AUDIT) scores administered to ten heavy drinkers (M=8, F=2; 43.2 ± 14.6 years) attending a recovery program. Specifically, from the pre-post comparison of the AUD scores, it was found that the score of every participant decreased after the intervention which ranged from 1 to 31. The decrease in the scores was found to be statistically significant with the p-value of 0.00298 (two-sided paired test; p-value = 0.00149 for one-sided test). Albeit this being a small pilot, we are encouraged about these significant results, and caution any interpretation until larger controlled studies are executed.

Background: We tested predictors of interest in a clinical trial of naltrexone plus counseling for heavy drinking reduction in young adults using a web survey. Respondents could indicate interest in the clinical trial at the conclusion of the survey.

Methods: A random sample of university students completed the survey (N = 584, 60% female). Data were collected in October-November 2010.

Results: Among past-year drinkers (n = 411), 22.6% (n =93) indicated interest. Equivalent levels of interest were found among past-year heavy drinkers. Non-white race and current cigarette smoking predicted interest. Alcohol-related negative consequences score was a trend-level predictor in the full regression model, but a significant predictor in a reduced model.

Conclusions: Non-white students, smokers and those with a high number of negative consequences may be more amenable to drinking reduction via medication and counseling. These findings could facilitate efforts of researchers, administrators, counselors and other professionals to tailor drinking reduction messages and facilitate treatment engagement by undergraduates.

This study explored predictors of engagement with specific video game genres, and degree of problem play experienced by players of specific genres, during the early life course. Video game players ages 18-29 (n = 692) were recruited in and around video game retail outlets, arcades, conventions, and other video game related contexts in New York City. Participants completed a Computer-Assisted Personal Interview (CAPI) of contemporaneous demographic and personality measures and a Life-History Calendar (LHC) measuring video gaming, school/work engagement, and caffeine and sugar consumption for each year of life ages 6 - present. Findings were that likelihood of engagement with most genres rose during childhood, peaked at some point during the second decade of life, and declined through emerging adulthood. Cohorts effects on engagement also emerged which were probably attributable to changes in the availability and popularity of various genres over the 12-year age range of our participants. The relationship between age and problem play of most genres was either negative or non-significant. Sensation-seeking was the only consistent positive predictor of problem play. Relationships between other variables and engagement with and problem play of specific genres are discussed in detail.