Validation of serotonin transporter mRNA as a quantitative biomarker of heavy drinking and its comparison to ethyl glucuronide/ethyl sulfate: A randomized, double-blind, crossover trial.

BACKGROUND: The serotonin transporter (SERT) mRNA was previously reported to be a quantitative and pathophysiology-based biomarker of heavy drinking in 5HTTLPR:LL genotype-carriers treated with ondansetron. Here, we validated the potential use of SERT mRNA for quantitative prediction of recent alcohol consumption (in the absence of treatment) and compared it with the known biomarkers ethyl glucuronide (EtG) and ethyl sulfate (EtS). METHODS: Binge drinking men and women of European ancestry aged 21 to 65 years were enrolled in a 12-day, in-patient, randomized, double-blind, crossover study, where they were administered three beverage doses (placebo, 0.5 g/kg [0.4 g/kg] ethanol, and 1 g/kg [0.9 g/kg] ethanol for men [women]) individually in three 4-day periods (experiments), separated by minimum 7-day washout period. Diet, sleep, and physical activity were controlled throughout the inpatient experiments. Twenty-nine participants were randomized to receive beverage doses counterbalancing the sequence of treatment and gender within subgroups stratified by SERT genotypes 5HTTLPR:LL+rs25531:AA (LA LA ) versus 5HTTLPR:LS/SS. Peripheral venous blood was collected daily for (1) quantification of SERT mRNA (the primary outcome measure) using qRT-PCR and (2) plasma EtG and EtS levels using tandem mass-spectrometry. RESULTS: The association between administered beverage dose and SERT mRNA from completers of at least one 4-day experiment (N = 18) assessed by a linear mixed model was not statistically significant. Significant positive associations were found with beverage dose and plasma EtG, EtS and EtG/EtS ratio (ß = 5.8, SE = 1.2, p < 0.0001; ß = 1.3, SE = 0.6, p = 0.023; and ß = 3.0, SE = 0.7, p < 0.0001, respectively; the C-statistics for discriminating outcomes were 0.97, 0.8, and 0.92, respectively). Additionally, we observed a sequence effect with a greater placebo effect on SERT mRNA when it was administered during the first experiment (p = 0.0009), but not on EtG/EtS measures. CONCLUSION: The findings do not validate the use of SERT as a biomarker of heavy drinking. Larger and more innovative studies addressing the effects of placebo, race, gender, and response to treatment with serotonergic agents are needed to fully assess the utility of SERT as a biomarker of heavy and binge drinking.

Trends and risk markers of student hazardous drinking: a comparative analysis using longitudinally linked datasets in a public university.

Aims: This study compares the incidence and risk-markers of student alcohol intoxication-related emergency department (ED) visits and alcohol-related incidents reported to student affairs. Methods: Enrollment data were linked to ED visits with alcohol intoxication and to alcohol-related incidents reported to campus authorities within one year following the first (index) annual enrollment. Incidence, annual trends and associated risk markers were analyzed. Results: The cohort consisted of 204,423 students aged 16-49. Incidence rates of first ED visit with alcohol intoxication and alcohol-related incidents were 59/10,000 and 311/10,000 person-years, respectively. Both outcomes shared common risk-markers including age, gender, race/ethnicity, fraternity and sorority (FSL) membership, an existing diagnosis of depression, etc. Being an athlete was associated with a lower risk of alcohol-related ED visits, and transfer students were at lower risk for alcohol-related incidents. Conclusion: Linking enrollment data with hazardous drinking events can help in better monitoring of student hazardous drinking and targeting interventions.HighlightsFirst longitudinal study documenting the incidence of extreme student alcohol misuse.There were rising trends in student risky drinking based on two independent datasets.Analysis identified a range of risk markers predictive of risky drinking behaviors.Linking multiple student datasets can timely identify high risk students.

A randomized, double-blind, placebo-controlled trial of ondansetron for the treatment of cocaine use disorder with post hoc pharmacogenetic analysis.

BACKGROUND: Cocaine use disorder (CUD) has significant consequences and there remain no FDA-approved pharmacotherapies. Ondansetron is an indirect dopaminergic modulator that has shown efficacy in alcohol use disorder, particularly in phenotypic and genotypic subgroups, and was found to be efficacious in a pilot dose-finding trial for CUD. METHODS: One-hundred eight (108) adults with CUD were randomized to ondansetron 4 mg twice daily or placebo for 9 weeks and assessed up to thrice weekly to evaluate self-reported cocaine use and urine benzoylecgonine. Participants received cognitive-behavioral therapy and brief behavioral compliance enhancement therapy. Consenting participants (N = 79) provided blood samples for exploratory pharmacogenetic analyses. RESULTS: Participants in both arms reduced cocaine use over time, but there was no statistically significant difference on percentage of cocaine-free days (PCFD; p = 0.972) or percentage of cocaine-free urine samples (PCFU; p = 0.909). Participants with early-onset CUD had greater improvement regardless of study arm (p = 0.002). Post hoc pharmacogenetic analyses demonstrated an interaction effect between treatment and rs1176713 SNP on PCFU in the total sample (p = 0.040) and African ancestry subset (p = 0.03). Constipation, fatigue, and somnolence were more common among ondansetron-treated participants (Fisher exact p < 0.05). Those who developed constipation were mostly rs1176713:GG carriers (Fisher exact p = 0.029). CONCLUSIONS: Ondansetron did not demonstrate efficacy in the treatment of CUD. However, these preliminary results suggest a genotype-based variance in response to ondansetron in African ancestry individuals with CUD. Further studies are needed to validate findings for developing a personalized genomic approach for CUD treatment in racially and ethnically diverse populations.

Addiction among women and sexual minority groups.

Gender-related alcohol and drug abuse problems are related not only to biologic differences but also to social and environment factors, all of which can influence the clinical presentation, consequences of use, and treatment approaches. The number of women becoming addicted to alcohol or drugs of abuse has significantly increased with women becoming the fastest-growing group of substance abusers in the United States. Given that women experience a more rapid progression of their addiction than men, it is important that we understand and address the differences to help develop prevention and treatment programs that are tailored for women, incorporating trauma assessment and management, comorbidities, financial independence, pregnancy, and child care.

Epidemiology of pediatric buprenorphine and methadone exposures reported to the poison centers.

BACKGROUND: Buprenorphine prescriptions have increased dramatically within the United States, whereas methadone continues to be used widely. We investigated the trends and characteristics of buprenorphine and methadone exposures in the pediatric population. METHODS: We identified pediatric exposures to buprenorphine and methadone using the National Poison Data System from 2013 to 2016. We descriptively assessed characteristics of the exposures. Trends in exposures were evaluated using generalized linear mixed models. RESULTS: Pediatric buprenorphine exposures increased from 2013 (1097) to 2016 (1226) while methadone calls decreased (486 to 396). After adjusting for the random effects of the geographical region, the mean number of pediatric buprenorphine exposures (per 100,000 pediatric population) increased from 1.3 to 1.5 (P = .05). Conversely, the mean number of methadone exposures decreased from 0.6 to 0.4 (P = .03). Children aged ≤3 years constituted the highest percentage of both exposures. Unintentional exposures accounted for most of the buprenorphine (86.9%) and methadone (62.4%) exposures. Major clinical effects were demonstrated in 2.3% of buprenorphine exposures and were more frequent with methadone (13%). West Virginia and Maryland demonstrated the highest incidence of buprenorphine and methadone exposures, respectively. CONCLUSIONS: Pediatric buprenorphine exposures increased but demonstrated less severe effects compared to methadone exposures, which decreased during the study period.

Epidemiology of severe buprenorphine exposures reported to the U.S. Poison Centers.

OBJECTIVE: This study aims to evaluate the trends and risk factors of severe buprenorphine outcomes (SBO) reported to the U.S. Poison Centers (PCs). METHODS: We queried the National Poison Data System for exposures to buprenorphine from 2011 to 2016. SBO cases were defined as exposures that resulted in either a death or major clinical outcomes. Trends were tested using Poisson regression. Characteristics of the exposures were descriptively assessed. Logistic regression was used to evaluate the risk factors of SBO. RESULTS: SBO cases (967) reported to the PCs increased by 66.6% during this period (114-190, p < 0.001). While adults between 20 and 39 years were more frequent in the SBO group (50.4%) compared to the non-SBO group (38.7%), cases under 6 years (29.6% vs 13.8%) were more common among the non-SBO group. Intentional abuse (20.1% vs 24.9%) and suspected suicides (13.7% vs 37.5%) were significantly higher among the SBO group. Multisubstance exposures were more frequent among the SBO cases (36.4% vs 71.4%). SBO risk increased with age, with cases above 60 years (AOR: 1.66, 95% CI: 1.14-2.42) demonstrating significantly increased odds. Suspected suicide (AOR: 1.87, 95% CI: 1.53-2.28) and abuse (AOR: 1.40, 95% CI: 1.13-1.73) cases were more likely to result in a SBO. Multisubstance exposures significantly increased the risk of a SBO. CONCLUSIONS: This study reflected an increase in the cases of SBO paralleling the rise in the buprenorphine prescriptions. Age, reasons for exposure and multi-substance exposures significantly increased the risk of SBO.

Women and Addiction: An Update.

Gender-related alcohol and drug abuse problems are related not only to biological differences, but also to social and environmental factors, which can influence the clinical presentation, consequences of use, and treatment approaches. Women are becoming the fastest-growing population of substance abusers in the United States. Given that women experience a more rapid progression of their addiction than men, it is important that we understand and address the differences to help develop prevention and treatment programs that are tailored for women, incorporating trauma assessment and management, identification and intervention for medical and psychiatric comorbidities, financial independence, pregnancy, and child care.

Development and validation of a risk predictive model for student harmful drinking-A longitudinal data linkage study.

BACKGROUND: This study aimed to develop a predictive model to quantify the risk of student harmful drinking associated with emergency department (ED) visits and/or campus-wide incidents reported to campus authorities in a U.S. public university. METHODS: Six-year (2010/11-2015/16) student enrollment data were linked to subsequent harmful drinking events defined as either alcohol intoxication associated with ED visits or alcohol-related incidents reported to authorities within 1 year following the annual (index) enrollment. Multivariable logistic regression analysis was used to develop a risk predictive model based on the first 3-year student cohort (n = 93,289), which was then validated in the following 3-year student cohort (n = 85,876). RESULTS: A total of 2609 students in the derivation cohort and 2617 students in the validation cohort had at least 1 harmful drinking event within 1 year following the index enrollment, providing an incidence of 2.8% and 3.1%, respectively. Student demographics (gender, age, ethnicity, parental tax dependency), academic level, Greek life member, transfer students, first-time enrolled students, having been diagnosed with depression or injury, and violence involvement were statistically significant predictors. C-statistics of the model were 0.86 in both cohorts, with excellent calibration and no evidence of over- or under-prediction observed from calibration plots. CONCLUSIONS: By linking routinely collected student data, a robust risk predictive model was developed and validated to quantify absolute risk of harmful drinking for every student. This model can provide a useful tool for clinicians or health educators to make real time decision to plan target interventions for students at elevated risk.

Impulsiveness as a predictor of topiramate response for cocaine use disorder.

BACKGROUND/OBJECTIVES: Topiramate has been studied in the treatment of substance use disorders and is often used off-label in the treatment of other disorders with impaired impulse control. We sought to determine whether impulsiveness could predict topiramate treatment response in individuals with cocaine use disorder (CUD). METHODS: In a post-hoc analysis of a 12-week, double-blind, randomized, placebo-controlled trial of topiramate for CUD, we examined the relationship between response to treatment and participants' baseline score on the Barrett Impulsiveness Scale (BIS-11). During the original trial, topiramate was titrated up to 300 mg/day over 6 weeks and maintained for 6 weeks. All participants received weekly cognitive behavioral therapy. RESULTS: Individuals with total BIS-11 scores above the median had 11.2% more cocaine-free days with topiramate versus placebo (Bonferroni corrected p = 0.047). Individuals with first-order factor scores above the median in self-control (Bonferroni corrected p = 0.020) and at or below the median in attention (Bonferroni corrected p = 0.022), and second-order factor scores at or below the median in attentional (Bonferroni corrected p = 0.024) and motor impulsiveness (Bonferroni corrected p = 0.046) were all associated with a greater improvement with topiramate. DISCUSSION/CONCLUSION: The results indicate an association between higher within-group impulsiveness and response to topiramate for CUD. The subscore findings may suggest a complex interaction between effectiveness and known cognitive side effects. The finding that trait impulsiveness is associated with treatment response is a promising discovery that may help guide treatment for CUD. SCIENTIFIC SIGNIFICANCE: This analysis suggests a possible endophenotype based on impulsiveness that can predict treatment response to topiramate. (Am J Addict 2019;XX:1-6).

Impact of Coping and Communication Skills Program on Physician Burnout, Quality of Life, and Emotional Flooding.

BACKGROUND: Physician behaviors that undermine a culture of safety have gained increasing attention as health-care organizations strive to create a culture of safety and reduce medical errors. We developed, implemented, and assessed a course to teach physicians skills regarding effective coping and interpersonal communication skills and present our results regarding outcomes. METHODS: We examined a professional development program specifically designed to address unprofessional or distressed behaviors of physicians, and we evaluated the impact on burnout, quality of life, and emotional flooding scores of the physicians. Assessments of burnout, quality of life, and emotional flooding were assessed preintervention and postintervention. RESULTS: Results demonstrated statistically significant reductions over time in physicians' emotional flooding and emotional exhaustion (EE). Specifically, using a Wilcoxon Signed-Rank test, results revealed that flooding scores at follow-up were statistically significantly lower than at baseline, V = 590, p < 0.05, and EE and personal accomplishment distributions were found to significantly deviate from normal as indicated by Shapiro-Wilks tests (p < 0.05). A Wilcoxon signed-rank test indicated that EE scores were significantly higher at baseline compared to follow-up 1, V = 285, p < 0.05. CONCLUSION: We conclude that the physician participants who enrolled in the educational skills training program improved scores on emotional flooding and EE and that this may be indicative of improved skills related to their experiences and learning in the program. These improved skills in physicians may have a positive impact on the overall culture of safety in the health system setting.

Trends and characteristics of naloxone therapy reported to US poison centers.

BACKGROUND AND AIMS: In the United States, access to naloxone has been expanded as a measure to address growing opioid overdose mortality. The study aimed to describe the national trends in naloxone use as reported to the US poison centers (PCs). METHODS: The National Poison Data System (NPDS) was queried for cases reporting naloxone therapy from 1 January 2001 to 31 December 2016. Demographic and clinical characteristics were assessed descriptively. Trends in naloxone reports were evaluated by using generalized linear mixed models that were adjusted for age, gender and random effects of the geographical census region. Cumulative incidence rates (CIR) of naloxone reports at the state- and national-level were calculated. RESULTS: There were 304 249 cases reporting naloxone therapy during the study period. The frequency of naloxone reports increased from 9498 in 2000 to 26 826 in 2016. The proportion of cases where naloxone was used prior to PC recommendation increased from 59.8% in 2000 to 81.5% in 2016. The mean number of NPDS naloxone reports per 100 000 human exposures increased from 9.6 [95% confidence interval (CI) = 6.4-14.2] to 31.7 (95% CI = 21.4-46.9, P < 0.001). Among the cases, 52.4% were female and the most frequent age group was 20-39 years (39.1%). The principal reason for a toxic exposure resulting in a naloxone report was suspected suicide (55.0%). Life-threatening symptoms were seen in one-fifth of the cases, with 53.9% cases being admitted to critical care units. Opioids (59.7% cases), were the most commonly reported exposure agents, with hydrocodone being most frequently reported. The national CIR of naloxone reports to the US PCs was 6.3 cases per 100 000 population, with West Virginia demonstrating the highest incidence. CONCLUSIONS: Analysis of calls to the United States poison centers indicates an increasing trend of naloxone use from 2000 to 2016.

Trends in incidence and risk markers of student emergency department visits with alcohol intoxication in a U.S. public university-A longitudinal data linkage study.

BACKGROUND: To examine the trends in incidence and socio-demographic, organizational, academic, and clinical risk markers of student alcohol intoxication associated with emergency department (ED) visits. METHODS: Student admission data from 2009 to 2015 were linked to primary healthcare data and subsequent ED visits with alcohol intoxication identified using ICD-9 codes within one year following the first (index) enrollment each year. Incidence rate per 10,000 person-years was calculated. Cox proportional hazard regression provided adjusted hazard ratios (HR) (95 % CIs) for the association between student characteristics and subsequent ED visits with alcohol intoxication. RESULTS: Of 177,128 students aged 16-49 enrolled, 889 had at least one ED visit with alcohol intoxication, resulting in an incidence rate of 59/10,000 person-years. Incidence increased linearly from 45/10,000 person-years in 2009-10 to 71/10,000 person-years in the 2014-15 academic year (p < 0.001). HRs (95%CIs) of student characteristics associated with this outcome were: males (versus females): 1.38 (1.21-1.58); below 20 years of age (versus 25-30 years): 3.36 (1.99-5.65); Hispanic (versus Asian) students: 1.61 (1.16-2.25); parental tax dependency: 1.49 (1.16-1.91); Greek life member: 1.96 (1.69-2.26); member of an athletic team: 0.51 (0.36-0.72); undergraduate (versus graduate) students: 2.65 (1.88-3.74). Past year alcohol use or having been diagnosed with depression or anxiety were also significant predictors. Adjustments for campus-related factors strongly attenuated the associations between student socio-demographic characteristics with this outcome. CONCLUSIONS: Linking student admission data with ED clinical data can help monitor student alcohol intoxication associated with ED visits and identify student groups at higher risk who subsequently can be targeted for intervention efforts.

A Review of Alprazolam Use, Misuse, and Withdrawal.

: Alprazolam is one of the most widely prescribed benzodiazepines for the treatment of generalized anxiety disorder and panic disorder. Its clinical use has been a point of contention as most addiction specialists consider it to be highly addictive, given its unique psychodynamic properties which limit its clinical usefulness, whereas many primary care physicians continue to prescribe it for longer periods than recommended. Clinical research data has not fully shed light on its "abuse liability," yet it is one of the most frequently prescribed benzodiazepines. "Abuse liability" is the degree to which a psychoactive drug has properties that facilitate people misusing it, or becoming addicted to it, and is commonly used in the literature. We have replaced it in our manuscript with "misuse liability" as it reflects a more updated terminology consistent with the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). In this paper, we have reviewed alprazolam's indications for use, its effect on pregnant women, misuse liability, withdrawal syndrome, pharmacodynamic properties, and suggest better clinical prescription practice of alprazolam by presenting an indepth theory of its clinical effects with use and withdrawal.

Differentials and trends in emergency department visits due to alcohol intoxication and co-occurring conditions among students in a U.S. public university.

BACKGROUND: Few studies have explored the epidemiology of students presenting to the emergency department (ED) as a consequence of hazardous drinking. This study examined differentials and trends in ED visits following alcohol intoxication and co-occurring conditions among students presenting to a major U.S. university health system. METHODS: The ED electronic medical records from academic years 2010-2015 were queried for student visits and their records were linked to the university's student admission datasets. Student alcohol-related visits were identified based on ICD-9 codes. Student characteristics and trends in the rate of alcohol intoxication per 100 ED student visits were analyzed. A random sample of 600 student clinical records were reviewed to validate diagnostic codes. RESULTS: There were 9616 student ED visits (48% males) to the ED of which 1001 (10.4%) visits involved alcohol intoxication. Two thirds of ED visits with alcohol intoxication had a co-occurring diagnosis, with injuries (24%) being the most common condition. The rate of alcohol intoxication varied greatly by student demographics and campus-related factors. There was a linear increase in the rate of alcohol intoxication from 7.9% in 2009-10 to 12.3% in 2014-15 (p<0.01). The increase was greater among female students, students below 20 years of age, Asian students, and student athletes. In the sample reviewed, only two thirds of ED visits with alcohol intoxication were recorded by diagnostic codes. CONCLUSION: The rate of ED visits following alcohol intoxication varied by student demographic characteristics and campus-related factors with a rising trend over the study period.

Women and Addiction.

Gender-related alcohol and drug abuse problems are related not only to biological differences, but also to social and environmental factors, which can influence the clinical presentation, consequences of use, and treatment approaches. Women are becoming the fastest-growing population of substance abusers in the United States. Given that women experience a more rapid progression of their addiction than men, it is important that we understand and address the differences to help develop prevention and treatment programs that are tailored for women, incorporating trauma assessment and management, identification and intervention for medical and psychiatric comorbidities, financial independence, pregnancy, and child care.

A Phase 2, Double-Blind, Placebo-Controlled Randomized Trial Assessing the Efficacy of ABT-436, a Novel V1b Receptor Antagonist, for Alcohol Dependence.

Alcohol use disorder has been linked to dysregulation of the brain stress systems, producing a negative emotional state leading to chronic relapsing behavior. Vasopressin receptors appear to have a regulatory role in stress, anxiety, and alcohol. This study evaluated the novel compound, ABT-436, a V1b receptor antagonist, in alcohol-dependent participants in a 12-week clinical trial. Men and women (n=150) who met criteria for DSM-IV alcohol dependence were recruited across four sites. Participants received double-blind ABT-436 or placebo, and a computerized behavioral intervention. ABT-436 was titrated to 800 mg/day during weeks 2-12. Although the primary outcome, percentage of heavy drinking days, was lower in participants receiving ABT-436 compared with placebo, this difference was not statistically significant (31.3 vs 37.6, respectively; p=0.172; d=0.20). However, participants receiving ABT-436 had significantly greater percentage of days abstinent than those receiving placebo (51.2 vs 41.6, respectively; p=0.037; d=0.31). No significant differences were found between treatment groups on any other measures of drinking, alcohol craving, or alcohol-related consequences. Smokers receiving ABT-436 smoked significantly fewer cigarettes per week than those receiving placebo (p=0.046). ABT-436 was well tolerated, with diarrhea (mild-to-moderate severity) being the most common side effect. In subgroup analyses, participants with relatively higher baseline levels of stress responded better to ABT-436 than placebo on select drinking outcomes, suggesting there may be value in testing medications targeting the vasopressin receptor in high stress, alcohol-dependent patients.

Pharmacotherapy for Alcohol Use Disorders: Physicians' Perceptions and Practices.

BACKGROUND AND OBJECTIVES: Alcohol use disorders (AUDs) are an important cause of morbidity and mortality. Despite the National Institute on Alcohol Abuse and Alcoholism (NIAAA) recommendations that medications be considered for patients with alcohol dependence, the mainstay of treatment has been counseling. We designed a survey to assess the treatment practices of psychiatrists and family medicine (FM) physicians in an effort to identify barriers to the use of pharmacotherapy and develop strategies to increase physician knowledge and utilization of these medications. METHODS: An anonymous online survey was sent to FM physicians and psychiatrists nationwide. The survey collected demographic information and assessed prescription of medications in treating AUDs, including FDA-approved medications and other medications used off-label for this purpose. We also examined factors that would lead to an increase in AUDs pharmacotherapy. RESULTS: A total of 491 surveys were completed, with 475 responses included in the final analyses. 45.5% of participants were psychiatrists vs. 54.5% FM physicians. The 74.7% respondents had used medications to treat AUDs, with psychiatrists more likely to have prescribed acamprosate, naltrexone, and several off-label medications. FM physicians were more likely to report efficacy concerns. A majority of all physicians sampled would increase pharmacotherapy of AUDs with increased training. DISCUSSION: In our sample, most physicians have used medications to treat AUDs. There were concerns about efficacy with all non-FDA-approved medications, but limited treatment success even with FDA-approved medications. Greater education about pharmacotherapy, including predictors for treatment response amongst patients, should help alleviate some of the uncertainties reported with medications' efficacy and lead to a more individualized treatment approach.

Transcriptome profiling and pathway analysis of genes expressed differentially in participants with or without a positive response to topiramate treatment for methamphetamine addiction.

BACKGROUND: Developing efficacious medications to treat methamphetamine dependence is a global challenge in public health. Topiramate (TPM) is undergoing evaluation for this indication. The molecular mechanisms underlying its effects are largely unknown. Examining the effects of TPM on genome-wide gene expression in methamphetamine addicts is a clinically and scientifically important component of understanding its therapeutic profile. METHODS: In this double-blind, placebo-controlled clinical trial, 140 individuals who met the DSM-IV criteria for methamphetamine dependence were randomized to receive either TPM or placebo, of whom 99 consented to participate in our genome-wide expression study. The RNA samples were collected from whole blood for 50 TPM- and 49 placebo-treated participants at three time points: baseline and the ends of weeks 8 and 12. Genome-wide expression profiles and pathways of the two groups were compared for the responders and non-responders at Weeks 8 and 12. To minimize individual variations, expression of all examined genes at Weeks 8 and 12 were normalized to the values at baseline prior to identification of differentially expressed genes and pathways. RESULTS: At the single-gene level, we identified 1054, 502, 204, and 404 genes at nominal P values < 0.01 in the responders vs. non-responders at Weeks 8 and 12 for the TPM and placebo groups, respectively. Among them, expression of 159, 38, 2, and 21 genes was still significantly different after Bonferroni corrections for multiple testing. Many of these genes, such as GRINA, PRKACA, PRKCI, SNAP23, and TRAK2, which are involved in glutamate receptor and GABA receptor signaling, are direct targets for TPM. In contrast, no TPM drug targets were identified in the 38 significant genes for the Week 8 placebo group. Pathway analyses based on nominally significant genes revealed 27 enriched pathways shared by the Weeks 8 and 12 TPM groups. These pathways are involved in relevant physiological functions such as neuronal function/synaptic plasticity, signal transduction, cardiovascular function, and inflammation/immune function. CONCLUSION: Topiramate treatment of methamphetamine addicts significantly modulates the expression of genes involved in multiple biological processes underlying addiction behavior and other physiological functions.

A survey of synthetic cannabinoid consumption by current cannabis users.

BACKGROUND: Despite growing concern about the increased rates of synthetic cannabinoid (SC) use and their effects, only limited data are available that addresses these issues. This study assessed the extent of SC product use and reported effects among a cohort of adult marijuana and tobacco users. METHODS: A brief telephone interview was conducted with individuals who had given permission to be contacted for future research while screening for a cannabis/nicotine dependence medication development study (NCT01204723). RESULTS: Respondents (N = 42; 88% participation rate) were primarily young adults, male, racially diverse, and high school graduates. Nearly all currently smoked tobacco and cannabis, with 86% smoking cannabis on 5 or more days per week. Nearly all (91%) were familiar with SC products, half (50%) reported smoking SC products previously, and a substantial minority (24%) reported current use (i.e., past month). Despite a federal ban on 5 common SCs, which went into effect on March 1, 2011, a number of respondents reported continued SC product use. Common reasons reported for use included, but were not limited to, seeking a new "high" similar to that produced by marijuana and avoiding drug use detection via a positive urine screen. The primary side effects were trouble thinking clearly, headache, dry mouth, and anxiety. No significant differences were found between synthetic cannabinoid product users (ever or current) and nonusers by demographics or other characteristics. CONCLUSIONS: Among current marijuana and tobacco users, SC product consumption was common and persisted despite a federal ban. The primary reasons for the use of SC-containing products seem to be to evade drug detection and to experience a marijuana-like high.