Background The present study determined if, akin to cocaine, nicotine self-administration in rats induces adaptations in the expression of glutamate transporters and cystine-glutamate exchangers in brain nuclei implicated in reinforcement, and if treating cigarette smokers with a drug that restores cystine-glutamate exchange affected the number of cigarettes smoked. Methods Rats self-administered nicotine intravenously for 12 hours/day or received nicotine through osmotic mini-pumps for 21 days. Somatic signs of withdrawal were measured and immunoblotting performed 12 hours after the last nicotine exposure to determine if the catalytic subunit of the cystine-glutamate exchanger, xCT, or the glial glutamate transporter, GLT-1, were altered in the ventral tegmental area (VTA), nucleus accumbens, prefrontal cortex or amygdala. For the smoking-reduction study in humans, nicotine-dependent smokers were treated for four weeks with N-acetylcysteine (2400 mg/daily) to promote cystine-glutamate exchange or placebo. Participants provided weekly ratings of withdrawal symptoms, craving, CO measurements and logged daily cigarette and alcohol use. Results Rats receiving nicotine via self-administration or minipumps displayed somatic signs of withdrawal, but only nicotine self-administering rats showed decreased xCT expression in the nucleus accumbens and VTA, and decreased GLT-1 expression in the nucleus accumbens. Human smokers treated with N-acetylcysteine reported a reduction in cigarettes smoked, and there was no effect of N-acetylcysteine on estimates of CO levels, craving, or withdrawal. Conclusions These results indicate that the cystine-glutamate exchanger and the glial glutamate transporter are down-regulated after nicotine self-administration, and augmenting exchanger activity with N-acetylcysteine reduced the number of cigarettes smoked in nicotine-dependent individuals.

IntroductionExcessive alcohol consumption is responsible for 88,000 deaths annually and cost the United States $223.5 billion in 2006. It is often assumed that most excessive drinkers are alcohol dependent. However, few studies have examined the prevalence of alcohol dependence among excessive drinkers. The objective of this study was to update prior estimates of the prevalence of alcohol dependence among US adult drinkers. MethodsData were analyzed from the 138,100 adults who responded to the National Survey on Drug Use and Health in 2009, 2010, or 2011. Drinking patterns (ie, past-year drinking, excessive drinking, and binge drinking) were assessed by sociodemographic characteristics and alcohol dependence (assessed through self-reported survey responses and defined as meeting ≥3 of 7 criteria for dependence in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition).ResultsExcessive drinking, binge drinking, and alcohol dependence were most common among men and those aged 18 to 24. Binge drinking was most common among those with annual family incomes of $75,000 or more, whereas alcohol dependence was most common among those with annual family incomes of less than $25,000. The prevalence of alcohol dependence was 10.2% among excessive drinkers, 10.5% among binge drinkers, and 1.3% among non-binge drinkers. A positive relationship was found between alcohol dependence and binge drinking frequency.ConclusionMost excessive drinkers (90%) did not meet the criteria for alcohol dependence. A comprehensive approach to reducing excessive drinking that emphasizes evidence-based policy strategies and clinical preventive services could have an impact on reducing excessive drinking in addition to focusing on the implementation of addiction treatment services.

The inhibition of cocaine cue reactivity is consistent with existing preclinical data and supports the use of N-acetylcysteine as a treatment for cocaine dependence.

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This Phase I trial evaluated the interaction between modafinil steady-state and cocaine. Twelve non-treatment seeking, cocaine dependent volunteers received four sets of randomized blinded infusions of saline, 20 mg IV cocaine, and 40 mg IV cocaine. Modafinil was given open label at 0 mg, 400 mg, or 800 mg. Modafinil combined with IV cocaine did not result in any significant hemodynamic interactions. Modafinil significantly dampened scores on Visual Analog Scale measures as compared to baseline cocaine conditions. No significant alterations in labs occurred. Further outpatient trials of modafinil appear to be warranted.

The use of illegal drugs is common in alcohol dependence and significant psychological and social consequences are associated with the concurrent use of alcohol and illegal drugs. However, little literature has examined the patterns of concurrent drug use in alcohol dependent individuals. A latent class analysis (LCA) was used to determine whether patterns of past year illegal drug use existed in a national sample of 6,059 alcohol dependent respondents of the combined 2005, 2006 and 2007 National Survey on Drug Use and Health. Multinomial logistic regression was then used to determine whether demographic variables, mental health disturbance and social consequences were predictive of drug use classes. Results of the LCA demonstrated a five class solution with optimal fit deduced by Bayesian Information Criterion minima. The five classes included: a close to zero probability of illegal drug use (class 1: 65%), medium marijuana, medium sedatives/tranquilizers and high analgesics (class 2: 7%), high marijuana, medium cocaine use (class 3: 21%), high probabilities of marijuana, cocaine, sedatives and analgesic use (class 4: 6%) and a high concurrent drug use except other hallucinogens (class 5: 1%). Regression results suggest that younger age, comorbidity, engaging in deviant behaviors, sexually transmitted infection and incarceration are associated with concurrent illegal drug use in alcohol dependent individuals. Findings advocate that more intense psychiatric and drug dependence treatment resources may be needed for concurrent drug using alcohol dependent populations and provide evidence for targeted prevention and treatment interventions.

Problem/Condition: Suicidal thoughts and behaviors are important public health concerns in the United States. In 2019, suicide was the 10th leading cause of death among persons aged ≥18 years (adults); in that year, 45,861 adults died as a result of suicide, and an estimated 381,295 adults visited hospital emergency departments for nonfatal, self-inflicted injuries. Regional-and state-level data on self-inflicted injuries are needed to help localities establish priorities and evaluate the effectiveness of suicide prevention strategies.

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