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The present study determined whether: (1) the response to alcohol varied as a function of menstrual cycle phase and (2) women with a paternal history of alcoholism (FHP) were less sensitive to the effects of alcohol compared to women without a family history of alcoholism (FHN). The behavioral effects of alcohol (0.00, 0.25, and 0.75 g/kg) were evaluated in 21 FHN and 24 FHP women; each dose was tested during both the midfollicular and late luteal phases of the menstrual cycle. Baseline negative mood was increased during the luteal phase compared to the follicular phase (increased Beck Depression scores and decreased Vigor, Arousal, and Friendly scores). Alcohol increased ratings of Drug Liking and Good Drug Effect more in the luteal phase than the follicular phase. FHP women had greater negative mood during the luteal phase and some of these dysphoric effects were increased by alcohol more in FHP women than FHN women. Alcohol impaired performance, with no group or menstrual cycle differences. However, consistent with previous studies, FHP women were less impaired by alcohol than FHN women on the balance task. These data indicate that (1) the differences in response to alcohol across the menstrual cycle are subtle, although alcohol is liked more during the luteal phase; (2) increases in dysphoric mood during the luteal phase are more pronounced in FHP women compared to FHN women, particularly after alcohol; and (3) the differences observed in response to alcohol between FHP and FHN women are less pronounced than previously shown in men.

The purpose of this double-blind 14-week trial was to compare the efficacy of sustained-release methylphenidate (MPH) to placebo (PBO) in treating adult attention deficit hyperactivity disorder (ADHD) symptoms in current cocaine dependent (CD) treatment seekers. The randomized sample consisted of 106 participants who were predominately male (83%) and 60% Caucasian, 14% Hispanic, 20% African-American and 6% other. All participants met DSM-IV criteria for ADHD and CD. There were no significant demographic differences between the two treatment groups. All participants received weekly individual cognitive behavioral therapy. There was no difference in retention rate based on treatment group (p=.91). The majority of the PBO group and the MPH group reported >30% improvement in their ADHD symptoms (55% versus 47%), with no significant difference between the two groups (p=.44). Using a combined outcome measure (>30% reduction in ADHD symptoms and CGI

Background Effective treatments for cocaine use disorders remain elusive. Two factors that may be related to treatment failures are route of cocaine used and impulsivity. Smoked cocaine users are more likely to have poorer treatment outcomes compared to intranasal cocaine users. Further, cocaine users are impulsive and impulsivity is associated with poor treatment outcomes. While stimulants are used to treat Attention Deficit Hyperactivity Disorder (ADHD) and attenuate certain cocaine-related behaviors, few studies have comprehensively examined whether stimulants can reduce behavioral impulsivity in cocaine users, and none examined route of cocaine use as a factor. Methods The effects of immediate release oral d -amphetamine (AMPH) were examined in 34 cocaine users (13 intranasal, 21 smoked). Participants had three separate sessions where they were administered AMPH (0, 10, or 20 mg) and completed behavioral measures of impulsivity and risk-taking and subjective measures of abuse liability. Results Smoked cocaine users were more impulsive on the Delayed Memory Task, the GoStop task and the Delay Discounting Task than intranasal cocaine users. Smoked cocaine users also reported more cocaine craving and negative mood than intranasal cocaine users. AMPH produced minimal increases on measures of abuse liability (e.g., Drug Liking). Conclusions Smoked cocaine users were more impulsive than intranasal cocaine users on measures of impulsivity that had a delay component. Additionally, although AMPH failed to attenuate impulsive responding, there was minimal evidence of abuse liability in cocaine users. These preliminary findings need to be confirmed in larger samples that control for route and duration of cocaine use.

Background Alcohol effects in humans involve gamma-amino butyric acid (GABA) neurotransmission. It has been proposed that GABAergic medications may be effective in the treatment of alcohol dependence. This study evaluated the acute effects of gabapentin, an anticonvulsant that increases extracellular GABA, on the subjective, physiological, and performance effects of alcohol in heavy (mean 34 drinks per week) alcohol drinkers. Methods Seventeen volunteers without alcohol dependence were tested using a double-blind design with three 3-day long inpatient phases, each separated by at least a 1-week wash-out period. Each phase, gabapentin (0, 1000, or 2000 mg) was administered 4 h before alcohol (0.75 g/kg), which was given in four divided doses every 20 min. Results Gabapentin impaired the ability to balance without producing changes in subjective, physiological or other performance measures. Pretreatment with gabapentin did not significantly alter subjective and performance effects of alcohol and did not alter alcohol craving. Gabapentin, dose-dependently enhanced alcohol-induced tachycardia. Conclusions Acute gabapentin administration was well tolerated in combination with alcohol, but did not alter the effects of alcohol.

Laboratory studies in which drugs of abuse are self- or experimenter-administered to non-treatment-seeking research volunteers provide valuable data about new pharmacotherapies for substance use disorders, as well as behavioral and performance data for understanding the neurobiology of drug abuse. This paper analyzed follow-up data from six smoked cocaine self-administration laboratory studies, in order to determine whether changes in substance use occurred 1 and 3 months after study participation compared to pre-study baseline.Ninety-eight healthy, non-treatment-seeking cocaine users were admitted to inpatient and combined inpatient/outpatient studies lasting from 12 to 105 days. The studies allowed participants to self-administer repeated doses of smoked cocaine (0, 6, 12, 25, and/or 50mg per dose) on multiple occasions. Participants returned for follow-up at 1 and 3 months, at which time self-reported consumption of cocaine, alcohol, marijuana, and nicotine was assessed.Compared to baseline ($374.04/week, S.D. $350.09), cocaine use significantly decreased at 1 month ($165.13/week, S.D. $165.56) and 3 months ($118.59/week, S.D. $110.48) after study participation (p0.001; results based on the 39 participants who completed all 3 time points). This decrease was not accompanied by a change in other drug use, e.g., a compensatory increase in alcohol, marijuana or nicotine use.Study participation was not associated with increased post-study cocaine, alcohol, marijuana, or nicotine use. Thus, human laboratory models of cocaine self-administration, conducted in non-treatment-seeking research volunteers, are relatively safe, and study participation does not exacerbate ongoing drug use.

Attention deficit hyperactivity disorder (ADHD) is prevalent in adult cocaine abusers. Yet, it remains to be determined how the response to cocaine differs in cocaine abusers with ADHD compared to cocaine abusers without ADHD. Further, since ADHD is commonly treated with stimulants, such as methylphenidate (MPH), it is important to examine whether MPH maintenance alters the response to cocaine in cocaine abusers with ADHD. Thus, the first phase of this study compared the response to cocaine in adult cocaine abusers with ADHD to those without ADHD. The second phase assessed the effects of oral sustained-release methylphenidate (MPH-SR) maintenance (40 and 60 mg) on the response to cocaine only in those with ADHD. Cocaine abusers with ADHD (N=7) and without ADHD (N=7) who were not seeking treatment remained inpatient initially for 1 week, when the effects of cocaine alone were tested (Phase 1). Cocaine abusers with ADHD remained inpatient for an additional 3 weeks, during which the effects of cocaine during oral MPH-SR maintenance were tested (Phase 2). During cocaine fixed dosing sessions, participants received four injections of i.v. cocaine (0, 16 or 48 mg/70 kg), spaced 14 min apart. During cocaine choice sessions, participants had a choice between receiving i.v. cocaine (16 or 48 mg/70 kg) or two tokens, each exchangeable for 2 US dollars. Subjective effects related to ADHD symptoms (e.g. ratings of "Able to Concentrate") were significantly lower in cocaine abusers with ADHD compared to those without ADHD when placebo cocaine was administered. Active cocaine produced similar increases in cardiovascular and positive subjective effects in both groups and there was no difference in cocaine choice between the two groups. These data suggest that the response to cocaine is not different between cocaine abusers with ADHD compared to those without ADHD. When the cocaine abusers with ADHD were maintained on MPH-SR, cardiovascular effects were increased, however, this did not warrant termination of any test session. Maintenance on MPH-SR decreased some of the positive subjective effects of cocaine. Further, maintenance on a high dose of MPH-SR decreased cocaine choice. Thus, oral MPH-SR is safe in combination with repeated cocaine doses and decreases some of the positive and reinforcing effects of cocaine in cocaine abusers with ADHD.

The purpose of this double-blind, three-arm, 12-week trial was to compare the efficacy of sustained-release methylphenidate or sustained-release bupropion to placebo in treating adult attention deficit hyperactivity disorder (ADHD) symptoms. The randomized sample consisted of 98 methadone-maintained patients who were predominately male (57%) and 40% Caucasian, 40% Hispanic and 20% African American. All participants met DSM-IV criteria for adult ADHD, with 53% meeting DSM-IV criteria for cocaine dependence/abuse. In addition to medication and treatment as usual at a methadone program, individuals received weekly individual cognitive behavioral treatment. Other than current employment status, there were no significant demographic differences across the three treatment groups. Seventy percent completed the 12-week trial. There were no differences in retention rate based on treatment group. A reduction in ADHD symptoms using the adult ADHD rating scale was observed in all three groups, but there were no significant differences in outcome between treatments. The placebo response rate was high, with 46% of the placebo group self-reporting substantial improvement in their ADHD symptoms (>30% reduction in adult ADHD rating scale). Using other ADHD outcome measures, the placebo response and medication response rates were substantially lower. There was no evidence of misuse of medication or worsening of cocaine use among those randomized to methylphenidate. Taken together, sustained-release methylphenidate or sustained-release bupropion did not provide a clear advantage over placebo in reducing ADHD symptoms or additional cocaine use in methadone-maintained patients.

Studies have shown that alcohol expectancies are positively associated with drinking and alcohol abuse and dependence symptoms among alcohol users. This study looked at the relationship of alcohol expectancies, family history of alcoholism, menstrual cycle and drinking behavior. The present study compared alcohol expectancies using the Alcohol Expectancy Questionnaire (AEQ) in 85 women ranging from 18 to 35 years of age. Forty-one women had a confirmed parental history of alcoholism (family history positive, FHP) and 44 women had no parental history of alcoholism (family history negative, FHN). Participants' mood, alcohol consumption, and daily consequences of alcohol use were prospectively tracked across one menstrual cycle. Alcohol expectancies at screening were significantly greater in FHP women in four of the six AEQ subscales, as well as the composite score. Alcohol expectancies correlated significantly with drinking behavior among FHN women. In FHP women, alcohol expectancies were elevated regardless of their drinking level. Alcohol expectancies decreased among FHP women, but not FHN women, after prospectively tracking their drinking behavior and consequences of drinking. Negative outcomes of drinking were increased among the FHP women who were heavy drinkers. Irrespective of family history status, alcohol use in moderate drinkers increased significantly during menses compared to the follicular and luteal phases of the menstrual cycle. These findings suggest that menstrual cycle may also play a role in alcohol consumption. Thus, the results of the present study indicate that issues related to the level of alcohol consumption, menstrual cycle phase and family history of alcoholism should be considered when addressing alcohol abuse in women.

s / Drug and Alcohol Dependence 140 (2014) e169–e251 e231 chopathology (dissociation, suicidality, depression) indicates a need to attend to these areas. Third, the PSES shows strong initial psychometric properties, showing potential utility as a brief, clinically relevant instrument for implementation in a wide variety of medical/specialty settings. Future research should further explore gender in substance expectancies given known gender differences in PTSD/SUD etiology/clinical presentation (e.g., women more likely to suffer sexual violence). Financial support: None. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.638 Oral d-amphetamine increases sensitivity to negative consequences on an associative learning task in cocaine users N.P. Vadhan1, S.M. Evans1, C.E. Myers3, M.A. Gluck2, S.C. Reed1 1 Columbia University & NYS Psychiatric Institute, New York, NY, United States 2 Rutgers University, Newark, NJ, United States 3 VA New Jersey Health Care System & New Jersey Medical School, East Orange, NJ, United States Aims: Thepurposeof this studywas to examine the acute effects of d-amphetamine (AMPH) on sensitivity to positive and negative consequences in cocaine users. Methods: Thirteen intranasal cocaine users (12male, 1 female), reporting 3.7 days (SD=1.2) of cocaine use ($228.9, SD=115.4) per week, participated in this 3-session outpatient study to date. Participants completed a computerized stimulus classification task at 180min following administration of oral AMPH (0, 10, 20mg); dose order was randomized and double-blind. On some task trials, correct responses were followed by a gain of 25 points (+$0.10) but incorrect responses were not followed by any feedback (positive consequence trials). For other task trials, incorrect responses were followed by a loss of 25 points (−$0.10), but correct responses were not followed by any feedback (negative consequence trials). The primary outcome measure was % optimal responses made on positive and negative consequence trials. Results: For the positive consequences condition, optimal responding increased as a function of trial block (p 0.05). Under the negative consequences condition, optimal responding did not increase as a function of trial block (p>0.05), but the 10mg dose of AMPH increased overall optimal responding by about 8% relative to placebo (p

Aims: This study evaluated the efficacy of oral micronized progesterone (PROG) for reducing cocaine use in women. Methods: A 10-week double-blind treatment trial compared PROG (up to 400mg/day, b.i.d.) to placebo (PBO) in cocaine-dependent women who were cocaine abstinent before randomization. Voucher incentives for attendance were used to enhance retention. Primary outcome measures included time to relapse, days of consecutive cocaine abstinence and retention. Response to a laboratory stressor, the Trier Social Stress Test (TSST) and treatment outcome was also explored. Results: Out of 227 women assessed, 25 women entered the trial, with 10 stratified to the PBOGroup and 11 to the PROGGroup. Thirteen women (62%) completed the entire 10-week trial. Five patients (2 in the PROG group and 3 in the PBO group) did not relapse, i.e., remained cocaine abstinent, during the trial. Two other women, one in each group, also did not relapse, but did not complete the trial. For the remainingwomen, themean number of days to relapse was 2.0 for the PROG group and 2.3 for the PBO group (p>0.05). Themean number of consecutive days of abstinence was 7.5 for the PROG group and 9.0 days for the PBO group (p>0.05). Among the 14 women who completed the TSST before randomization, increases in heart rate (r=−.33), anxiety scores (r=−.37) and cocaine craving (r=−.34) in response to stress were negatively correlated with the percentage of cocaine negative urines. Conclusions: PROG was well tolerated, but due to the small sample size it was not possible to adequately determine if PROG may be an effective treatment for cocaine-dependent women. Although cocaine-abstinence rates were low, they could be potentially improved using voucher incentives contingent on cocaine abstinence. Lastly, the preliminary findings showing that increased stress reactivity was related to low rates of cocaine abstinence suggest that stress-reduction techniques could improve treatment outcome. Financial support: NIDA grants RO1 DA022218 (SME), K24 DA029647 (FRL) and KO1 DA022282 (SCR). Medication was provided by the Women’s International Pharmacy.

In this study, 281 cocaine abusers seeking treatment were assessed for adult attention-deficit hyperactivity disorder (ADHD). Structured assessments included the SCID for DSM-IV, a SCID-like module for ADHD, and a pattern of drug use questionnaire. The sample consisted of 82% men, 67% African-Americans, 19% Hispanics, and 14% Caucasians identified at several treatment sites. Average age was 33.7±.4 years. Twelve percent (n=34) of the sample met DSM-IV criteria for childhood ADHD. Of the entire sample, 10% (n=27), or 79% of the patients diagnosed with childhood ADHD, had adult ADHD. A history of conduct disorder and antisocial personality disorder were prevalent among those with adult ADHD (63% and 52%, respectively). This subpopulation of cocaine abusers may be one of the most difficult-to-treat cocaine-abusing groups, particularly if the ADHD remains undetected. To provide effective treatment for cocaine abusers, clinicians may need to identify subpopulations of patients, such as those with ADHD, and target both pharmacologic and nonpharmacologic interventions for these groups.

Pigeons trained to discriminate (+)-amphetamine (AMPH) from saline in a two-key food-maintained drug discrimination paradigm, were used to investigate the discriminative stimulus (DS) effects of two structural analogues of amphetamine, namely (±)-3,4-methylenedioxymethamphetamine (MDMA) and (±)-3,4-methylenedioxyamphetamine (MDA). After discrimination performance was stable (90% injection-appropriate responding), test sessions with various doses of AMPH were conducted and a dose-dependent relationship for AMPH-appropriate responding was obtained. Both MDMA (3.0 mg/kg) and MDA (3.0 or 5.6 mg/kg) substituted for AMPH; however, at these doses MDA produced a greater decrease in response rate compared to AMPH and MDMA. Furthermore, while MDMA and MDA were similar in potency in producing drug-appropriate responding, both were less potent than AMPH. These results indicate that MDMA and MDA have DS effects similar to AMPH in pigeons.