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1.  Extra-medical stimulant dependence among recent initiates 
Drug and alcohol dependence  2009;104(0):147-155.
New estimates for the risk of becoming stimulant dependent within 24 months after first extra-medical (EM) use of a stimulant drug compound are presented, with a focus on subgroup variations in this risk (e.g., alcohol dependence, male–female differences). The study estimates are derived from a representative sample of United States residents ages 12 and older (n = 166,737) obtained from the 2003 to 2005 National Surveys on Drug Use and Health. A total of 1700 respondents were found to have used stimulants extra-medically for the first time within 24 months prior to assessment. Approximately 5% of these recent-onset EM users had become stimulant dependent since onset of EM use. As hypothesized, alcohol dependence cases were found to have experienced an excess risk of becoming stimulant dependent soon after onset of stimulant drug use; there was no robust male–female difference in risk. Independently, initiates who had used multiple types of stimulants extra-medically, and methamphetamine users, were more likely to have become stimulant dependent soon after onset of use; by comparison, EM users of methylphenidate (Ritalin®) were less likely to have developed rapid-onset dependence. These epidemiologic findings help quantify a continuing public health burden associated with new onsets of extra-medical stimulant use in the 21st century.
PMCID: PMC4327814  PMID: 19515516
Stimulants; Dependence; Methylphenidate; Logistic regression; Epidemiology; Recent-onset
2.  Who Is Becoming Hallucinogen Dependent Soon After Hallucinogen Use Starts?1 
Drug and alcohol dependence  2006;87(0):153-163.
This study, based upon epidemiological survey data from the United States (U.S.) National Household Surveys on Drug Abuse (NHSDA) from 2000–2001, presents new estimates for the risk of developing a hallucinogen dependence syndrome within 24 months after first use of any hallucinogen (median elapsed time ~ 12 months). Subgroup variations in risk of becoming hallucinogen dependent also are explored. Estimates are derived from the NHSDA representative samples of non-institutionalized U.S. residents ages 12 and older (n = 114,241). A total of 2,035 respondents had used hallucinogens for the first time within 24 months prior to assessment. An estimated 2%–3% of these recent-onset hallucinogen users had become dependent on hallucinogens, according to the NHSDA DSM-IV computerized diagnostic algorithm. Controlling for sociodemographic and other drug use covariates, very early first use of hallucinogens (age 10–11 years) is associated with increased risk of hallucinogen dependence (p < 0.01). Excess risk of developing hallucinogen dependence was found in association with recent-onset use of mescaline; excess risk also was found for recent onset users of ecstasy and of PCP. This study’s evidence is consistent with prior evidence on a tangible but quite infrequent dependence syndrome soon after the start of hallucinogen use; it offers leads that can be confirmed or disconfirmed in future investigations.
PMCID: PMC4327824  PMID: 16987612
hallucinogen; dependence; logistic regression; epidemiology; recent-onset
3.  Gender, violence and brief interventions for alcohol in the emergency department 
Drug and alcohol dependence  2012;127(0):115-121.
The impact of gender and violence on brief interventions (BIs) for alcohol use in the emergency department (ED) has not been studied. Our objective was to examine the effectiveness of alcohol BIs in an ED population stratified by gender and violence.
This was a secondary analysis of datasets pooled from three ED-based randomized controlled studies of alcohol BIs. AUDIT-C was the primary outcome measure; secondary outcomes were binge drinking and achievement of NIAAA safe drinking levels. We conducted univariate comparisons and developed generalized linear models (GLM) for the primary outcome and generalized estimating equation (GEE) models for secondary outcomes to examine the intervention effect on the whole study group, gender-stratified subgroups, and gender- and violence-stratified subgroups.
Of 1219 participants enrolled, 30% were female; 31% of women and 42% of men reported violence involvement at baseline. In univariate analysis, no differences in outcomes were found between intervention and control groups for any subgroup. However, in multivariable models, men demonstrated an intervention effect for likelihood of safe drinking limits. Stratifying further by violence, only men without violence involvement demonstrated a positive intervention effect for safe drinking limits. There was no evidence of an intervention effect on women.
Analyzing the overall effect of ED-based BI may mask its ability to improve alcohol-related outcomes in a subset of the population. Alternatively, interventions may need to be significantly improved in subsets of the ED population, e.g., in women and in men with involvement in violence.
PMCID: PMC4325369  PMID: 22818512
Alcohol-related disorders; Gender; Violence; Emergency medicine
4.  A new definition of early age at onset in alcohol dependence 
Drug and alcohol dependence  2009;108(0):43-48.
The accurate cut-off of an early onset of alcohol dependence is unknown. The objectives of this analysis are (1) to confirm that ages at onset variability in alcohol dependence is best described as a two sub-groups entity, (2) to define the most appropriate cut-off, and (3) to test the relevancy of such distinction.
Data were drawn the Epidemiologic Survey on Alcohol and Related Conditions (NESARC). This study focused on the 4,782 adults with lifetime alcohol dependence.
The best-fit model distinguished two subgroups of age at onset of alcohol dependence, with a cut-off point at 22 years. Subjects with an earlier onset of alcohol dependence (≤22 years old) reported higher lifetime rates of specific phobia, antisocial behaviors and nearly all addictive disorders.
The early onset of alcohol dependence is best defined as beginning before the age of 22 years.
PMCID: PMC4313551  PMID: 20018459
NESARC; alcohol dependence; admixture test; DSM-V; age at onset
5.  [No title available] 
PMCID: PMC3904106  PMID: 24332802
6.  [No title available] 
PMCID: PMC3915779  PMID: 24200103
7.  [No title available] 
PMCID: PMC3918435  PMID: 24332577
8.  [No title available] 
PMCID: PMC3919662  PMID: 24326203
9.  [No title available] 
PMCID: PMC3919702  PMID: 24332801
10.  [No title available] 
PMCID: PMC3931128  PMID: 24374111
11.  [No title available] 
PMCID: PMC3941002  PMID: 24360650
12.  [No title available] 
PMCID: PMC3943469  PMID: 24342420
13.  [No title available] 
PMCID: PMC3947194  PMID: 24332790
14.  [No title available] 
PMCID: PMC3952562  PMID: 24382362
15.  [No title available] 
PMCID: PMC4040973  PMID: 24331637
16.  Efficacy of Dual Focus Mutual Aid for Persons with Mental Illness and Substance Misuse 
Drug and alcohol dependence  2013;135:78-87.
Previous studies have indicated that persons with co-occurring mental health and substance use problems can benefit by attending dual-focus mutual aid groups. However, to date, a trial to test the efficacy of these groups has not been published.
This study randomly assigned 203 substance misusing clients attending a mental health or dual-diagnosis facility to either a dual-focus 12-step group (Double Trouble in Recovery; DTR) or a waiting list control group. Participants were followed for 3–6 months. The primary outcome was substance use (days used in the past 30 with saliva testing to detect under-reporting); secondary outcomes included psychiatric medication adherence, attendance at traditional (single-focus) 12-step meetings (e.g., AA/NA); and improvement in mental health and substance use problems (quality of life). Multilevel model (MLM) regression was used to analyze the nested effect of participants within 8 facilities (7 in New York City and 1 in Michigan). Regression imputation was used to adjust for drug use under-reporting.
At follow-up 79% of the subjects were interviewed. In intent to treat analysis, DTR subjects compared with control subjects used alcohol (p=.03) and any substances (p=.02) on fewer days. DTR compared with control subjects were also more likely to rate themselves as experiencing better mental health and fewer substance use problems (p=.001). There were no effects for DTR on drug use only, medication adherence or NA/AA attendance.
Findings reported in previous studies on the association between exposure to DTR and reductions in substance use were partially supported in this efficacy trial.
PMCID: PMC4261224  PMID: 24342419
Mutual Aid; 12-Step groups; Recovery; Dual diagnosis; Co-occurring disorders
17.  Positive Affect and Processes of Recovery among Treatment-Seeking Methamphetamine Users 
Drug and alcohol dependence  2013;132(3):624-629.
Revised Stress and Coping Theory proposes that positive affect serves adaptive functions, independent of negative affect. However, scant research has examined whether, how, and under what circumstances positive affect is associated with decreased substance use.
Eighty-eight methamphetamine-using men who have sex with men (MSM) completed the baseline assessment for substance abuse treatment outcome study which included measures of positive and negative affect, cognitive-behavioral change processes (i.e., approach-oriented coping, self-efficacy for managing methamphetamine triggers, and abstinence-related action tendencies), abstinence-specific social support, and self-reported substance use. Participants also provided a urine sample for toxicology screening.
After controlling for demographic characteristics and negative affect, higher positive affect was independently associated with greater approach-oriented coping, abstinence-related action tendencies, and abstinence-specific social support. Positive affect was also independently associated with greater self-efficacy for managing methamphetamine triggers, but only at lower levels of negative affect. Through these cognitive-behavioral and social pathways, positive affect was indirectly associated with lower frequency of stimulant use in the past 30 days, lower odds of reporting stimulant use two or more days in a row, and lower odds of providing a urine sample that was reactive for stimulant metabolites. On the other hand, negative affect was not indirectly associated with any measure of stimulant use.
Clinical research is needed to examine the pathways whereby positive affect may predict better substance abuse treatment outcomes.
PMCID: PMC4302392  PMID: 23684632
Cocaine; Coping; HIV; Methamphetamine; Negative Affect; Positive Affect; Self-Efficacy; Social Support
18.  Gender Differences in Circumstances Surrounding First Injection Experience of Rural Injection Drug Users in the United States 
Drug and alcohol dependence  2013;134:10.1016/j.drugalcdep.2013.10.013.
Research has demonstrated that there can be substantial gender differences in circumstances surrounding initiation of injection drug use; however, little is known about the gendered dynamics of first injection in rural areas where syringe exchange is inaccessible or among those who predominantly inject prescription medications. The present study examines gender differences in first injection experience among rural residents who predominantly inject prescription opioids.
Interview-administered questionnaires collected data from a sample of injection drug users (n=394) recruited from Appalachian Kentucky using respondent-driven sampling.
Women were more likely to have initiated injection due to social-pressure (p=0.001), received the drugs as a gift (p=0.011), initiated in their partner’s home (p=0.004) and in their partner’s presence (p<0.001), been injected by their partner (p<0.001), used an unclean syringe (p=0.026), and received the syringe from their partner (p<0.001). Women were also more likely to report having engaged in sexual intercourse before or after initiation (p<0.001). Men were more likely to have personally purchased the drugs (p=0.002), to have acquired the syringe from a pharmacy/clinic (p=0.004), and to have injected with a friend (p=0.001) or family member (p=0.020). Men were also more likely to have a friend administer the first injection (p=0.007).
In this population of rural drug users, notable gender differences in injection initiation were observed. Social pressure played a more substantial role in women’s first injection experience, and male partners had an integral role in women’s initiation.
PMCID: PMC3874445  PMID: 24216393
gender; injection drug use; nonmedical use of prescription drugs; risk behavior; rural
19.  Modafinil restores methamphetamine induced object-in-place memory deficits in rats independent of glutamate N-methyl d-aspartate receptor expression 
Drug and alcohol dependence  2013;134:10.1016/j.drugalcdep.2013.09.018.
Chronic methamphetamine (meth) abuse in humans can lead to various cognitive deficits, including memory loss. We previously showed that chronic meth self-administration impairs memory for objects relative to their location and surrounding objects. Here, we demonstrate that the cognitive enhancer, modafinil, reversed this cognitive impairment independent of glutamate N-methyl d-aspartate (GluN) receptor expression.
Male, Long-Evans rats underwent a noncontingent (Experiment 1) or contingent (Experiment 2) meth regimen. After one week of abstinence, rats were tested for object-in-place recognition memory. Half the rats received either vehicle or modafinil (100 mg/kg) immediately after object familiarization. Rats (Experiment 2) were sacrificed immediately after the test and brain areas that comprise the key circuitry for object in place performance were manually dissected. Subsequently, glutamate receptor expression was measured from a crude membrane fraction using western blot procedures.
Saline-treated rats spent more time interacting with the objects in changed locations, while meth-treated rats distributed their time equally among all objects. Meth-treated rats that received modafinil showed a reversal in the deficit, whereby they spent more time exploring the objects in the new locations. GluN2B receptor subtype was decreased in the perirhinal cortex, yet remained unaffected in the prefrontal cortex and hippocampus of meth rats. This meth-induced down regulation occurred whether or not meth experienced rats received vehicle or modafinil.
These data support the use of modafinil for memory impairment in meth addiction. Further studies are needed to elucidate the neural mechanisms of modafinil reversal of cognitive impairments.
PMCID: PMC3874857  PMID: 24120858
glutamate; memory; methamphetamine; perirhinal cortex; self-administration; object recognition
20.  Correlated Outcomes of a Pilot Intervention for People Injecting Drugs and Their Family Members in Vietnam 
Drug and alcohol dependence  2013;134:10.1016/j.drugalcdep.2013.11.004.
The interrelationship between the well-being of injecting drug users (IDUs) and their family environment has been widely documented. However, few intervention programs have addressed the needs of both IDUs and their family members.
This study describes a randomized intervention pilot targeting 83 IDUs and 83 of their family members from four communes in Phú Thọ province, Vietnam. The IDUs and family members in the intervention condition received multiple group sessions, with the intent to improve psychological well-being and family relationships. The intervention outcomes (depressive symptoms and family relations) were evaluated at baseline, 3-month and 6-month follow-up assessments.
Depressive symptoms and family relations reported by IDUs were found to be correlated to those reported by their family members. Overall, significant intervention effects on depressive symptoms and family relations were observed for both IDUs and family members. A similar improvement pattern in family relations emerged for both the IDU and family member samples, although the intervention effect of reducing depressive symptoms was more sustainable for family members at the 6-month assessment when compared to the IDU sample.
The intervention pilot addressed challenges faced by IDUs and their family members and revealed correlated outcomes for the two groups. Findings suggest a vital need to include family members in future drug prevention and harm reduction intervention efforts.
PMCID: PMC3881285  PMID: 24305572
IDU; family members; intervention outcome; Vietnam
21.  Excessive state switching underlies reversal learning deficits in cocaine users 
Drug and alcohol dependence  2013;134:10.1016/j.drugalcdep.2013.09.029.
Markers of chronic cocaine exposure on neural mechanisms in animals and humans is of great interest. The probabilistic reversal-learning task may be an effective way to examine dysfunction associated with cocaine addiction. However the exact nature of the performance deficits observed in cocaine users has yet to be disambiguated.
Data from a probabilistic reversal-learning task performed by 45 cocaine users and 41 controls was compared and fit to a Bayesian hidden Markov model (HMM).
Cocaine users demonstrated the predicted performance deficit in achieving the reversal criterion relative to controls. The deficit appeared to be due to excessive switching behavior as evidenced by responsivity to false feedback and spontaneous switching. This decision-making behavior could be captured by a single parameter in an HMM and did not require an additional parameter to represent perseverative errors.
Cocaine users are characterized by excessive switching behavior on the reversal-learning task. While there may be a compulsive component to behavior on this task, impulsive decision-making may be more relevant to observed impairment. This is important in building diagnostic tools to quantify the degree to which each type of dysfunction is present in individuals, and may play a role in developing treatments for those dysfunctions.
PMCID: PMC3881558  PMID: 24176201
reinforcement learning; Bayesian hidden Markov model; reversal learning; decision making; reward; state switching; cocaine; impulsivity; compulsivity
22.  The Impact of Lifetime Drug Use on Hepatitis C Treatment Outcomes in Insured Members of an Integrated Health Care Plan 
Drug and alcohol dependence  2013;134:222-227.
The relation of drug use to HCV treatment outcome in an insured household population has not been previously reported.
Lifetime frequencies of marijuana use and non-medical use of stimulants, sedatives, and opioids; hallucinogens; and inhalants were retrospectively assessed in 259 privately insured members of an integrated health care plan treated for chronic hepatitis C virus infection (HCV+) with pegylated interferon alpha and ribavirin and examined with respect to rates of sustained virological response (SVR).
The majority of patients reported chronic use of multiple illegal drugs; 61.6% reported injection drug use (IDU); 79.5% abstained from drug use during the six months prior to HCV treatment. Total frequency of individual drugs, multiple drugs, and length of abstention from drugs prior to HCV treatment were not related to impaired SVR rates. Sustained viral responses were obtained in 80.2% of patients with HCV genotype 2/3 and 45.1% of patients with genotype 1/4/6. Marijuana use during HCV treatment, reported by 8.5% of patients, was associated with higher treatment adherence (95.5% compared with 78.9%, p=0.045), but lower SVR rates (40.9% compared with 62.5%, p=0.041). In addition, drug use during HCV treatment was associated with significantly higher relapse rates, 18.8% compared with 7.7% (p=.053).
A history of chronic illegal drug use should not be considered a deterrent to HCV treatment in members of an integrated health care plan who are motivated to seek treatment and closely monitored, but drug use during HCV treatment, including marijuana use, should be discouraged.
PMCID: PMC3888084  PMID: 24262649
Lifetime drug use; hepatitis C; retrospective cohort study; intravenous drug use; marijuana
23.  Achieving smoking abstinence is associated with decreased cocaine use in cocaine-dependent patients receiving smoking-cessation treatment 
Drug and alcohol dependence  2013;134:391-395.
Past research suggests that a significant relationship exists between cigarette smoking and illicit-stimulant abuse. The present study evaluated the association between achieving smoking abstinence in response to smoking-cessation treatment (SCT) and illicit-stimulant abstinence in cocaine- and/or methamphetamine-dependent participants.
Secondary analysis of a randomized, 10-week trial conducted at 12 substance use disorder (SUD) treatment programs. Two hundred and sixty seven adults, meeting DSM-IV-TR criteria for cocaine and/or methamphetamine-dependence and interested in quitting smoking were randomized to SUD treatment as usual plus SCT consisting of weekly individual smoking cessation counseling, extended-release (XL) bupropion (300 mg/day), nicotine inhaler, and contingency management for smoking abstinence. Illicit-stimulant-abstinence was measured by self-report and urine drug screens. Smoking abstinence was assessed via self-report and carbon monoxide levels.
A significant effect was found for the cocaine-dependent subsample (N=147) in which participants who stopped smoking were abstinent for illicit stimulants an average of 78.2% of the post-smoking-quit weeks (weeks 4-10) relative to 63.6% in participants who continued smoking (X2(1)=8.55, p<.01, d=0.36). No significant effects were found for the sample as a whole (N=249) or for the methamphetamine-dependent subsample (N=102).
The present results suggest that cocaine-dependent patients achieving smoking abstinence in response to SCT might evidence not only improved smoking outcomes but improved cocaine-use outcomes as well. Future research to replicate this finding appears warranted.
PMCID: PMC3889710  PMID: 24128381
cocaine; smoking cessation; methamphetamine
Drug and alcohol dependence  2013;134:167-177.
Cue triggered relapse during the postpartum period can negatively impact maternal care. Given the high reward value of pups in maternal rats, we designed an fMRI experiment to test whether offspring presence reduces the neural response to a cocaine associated olfactory cue.
Cocaine conditioned place preference was carried out before pregnancy in the presence of two distinct odors that were paired with cocaine or saline (+Cue and −Cue). The BOLD response to +Cue and −Cue was measured in dams on postpartum days 2–4. Odor cues were delivered to dams in the absence and then the presence of pups.
Our data indicate that several limbic and cognitive regions of the maternal rat brain show a greater BOLD signal response to a +Cue versus −Cue. These include dorsal striatum, prelimbic cortex, parietal cortex, habenula, bed nucleus of stria terminalis, lateral septum and the mediodorsal and the anterior thalamic nucleus. Of the aforementioned brain regions, only the parietal cortex of cocaine treated dams showed a significant modulatory effect of pup presence. In this area of the cortex, cocaine exposed maternal rats showed a greater BOLD activation in response to the +Cue in the presence than in the absence of pups.
Specific regions of the cocaine exposed maternal rat brain are strongly reactive to drug associated cues. The regions implicated in cue reactivity have been previously reported in clinical imaging work, and previous work supports their role in various motivational and cognitive functions.
PMCID: PMC3908547  PMID: 24183499
cocaine; olfactory; cue; memory; pups; maternal rat; fMRI
25.  Parental Separation and Early Substance Involvement: Results from Children of Alcoholic and Cannabis Dependent Twins 
Drug and alcohol dependence  2013;134:78-84.
Risks associated with parental separation have received limited attention in research on children of parents with substance use disorders. We examined early substance involvement as a function of parental separation during childhood and parental alcohol and cannabis dependence.
Data were drawn from 1,318 adolescent offspring of monozygotic (MZ) or dizygotic (DZ) Australian twin parents. Cox proportional hazards regression analyses were conducted predicting age at first use of alcohol, first alcohol intoxication, first use and first regular use of cigarettes, and first use of cannabis, from parental separation and both parent and cotwin substance dependence. Parent and cotwin alcohol and cannabis dependence were initially modeled separately, with post-hoc tests for equality of effects.
With few exceptions, risks associated with parental alcohol versus cannabis dependence could be equated, with results largely suggestive of genetic transmission of risk from parental substance (alcohol or cannabis) dependence broadly defined. Controlling for parental substance dependence, parental separation was a strong predictor for all substance use variables, especially through age 13.
Together, findings underscore the importance of parental separation as a risk-factor for early substance involvement over and above both genetic and environmental influences specific to parental alcohol and cannabis dependence.
PMCID: PMC3908916  PMID: 24120074
adolescent substance use; parental separation; parental substance dependence; children of twins

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