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The Trier Social Stress Test (TSST) is a standard laboratory stressor comprised of a speech and arithmetic tasks that reliably induces physiological and psychological stress. It is traditionally administered in a room where the participant takes part in the TSST in front of two "committee" members. However, due to the recent Coronavirus disease (COVID-19) pandemic, in-person research study procedures have been limited due to potential exposure risks. Since stress reactivity is associated with drug use and the TSST reliably increases stress reactivity among cannabis users, the present pilot study examined a "remote" version of the TSST using the cloud-based virtual video communications platform, Zoom, among cannabis-using individuals (N = 15). The use of a remote platform such as Zoom allowed the participant and the committee to interact in real time while limiting in-person contact. The primary aim of this study was to test the feasibility of a remote version of the TSST in producing an increase in subjective stress response, cannabis craving, and cardiovascular stress in individuals who use cannabis. Participants completed subjective effects questionnaires and had blood pressure (BP) assessed before (baseline) and at various time points after the TSST. Heart rate (HR) was continuously measured throughout the session. This remote version of the TSST significantly and robustly increased State Anxiety and Perceived Stress scores, BP, and HR compared to baseline. There was no effect of the remote TSST on cannabis craving. Overall, the remote version of the TSST appears to be an effective laboratory stressor for future stress reactivity studies. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Cannabis and synthetic cannabinoids are abused in spite of possible adverse health consequences. The current study investigated the reinforcing effects of an ecologically relevant mode of administration (inhalation) of delta-9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis, and three synthetic cannabinoids detected in synthetic cannabinoid products (JWH-018, JWH-073, and HU-210) in non-human primates (NHPs). Male and female (N = 4 each) rhesus macaques were trained to inhale warm air via a metal stem to receive a candy reinforcer, an alcohol aerosol vehicle was then paired with the candy. Dose-dependent responding for inhaled aerosols of THC (2.0-16.0 μg/kg/inhalation), JWH-018 (0.2-1.6 μg/kg/inhalation), JWH-073 (2.0-8.0 μg/kg/inhalation), and HU-210 (1.0-8.0 μg/kg/inhalation) was established using a fixed-ratio five schedule of reinforcement and compared to vehicle (alcohol) self-administration. Dose-dependent responding for inhaled heroin (25.0-100.0 μg/kg/inhalation), a known reinforcer in NHPs, was also established. Responding approximated vehicle levels for many drug doses tested, but at least half of the monkeys responded for ≥ one dose of each cannabinoid and heroin above vehicle, with the exception of THC. Drug deliveries calculated as percent vehicle followed a prototypical inverted-U shaped dose-response curve for cannabinoids and heroin except for THC and JWH-018 (in males). Grouped data according to sex demonstrated that peak percent of vehicle reinforcers earned for THC was greater in males than females, whereas peak percent of vehicle reinforcers earned for JWH-018, HU-210, and heroin were greater in females than males. These findings indicate minimal reinforcing effects of CB1 receptor agonists when self-administered by NHPs via aerosol inhalation. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Women with a history of childhood sexual abuse (CSA) are at greater risk to develop alcohol use disorders. Whereas impulsivity has been postulated as a behavioral mechanism linking childhood trauma and alcohol use, few studies have comprehensively examined impulsivity in women with CSA. We compared women with a history of CSA (n = 21) and control women who did not endorse CSA or other major traumas (CON; n = 21) on self-report measures of impulsivity and risk taking. Additionally, performance on behavioral impulsivity and subjective response to alcohol were examined before and after acute alcohol (0.00, 0.50, 0.75 g/kg) administration. Overall, women with CSA responded more impulsively than CON women on the immediate and delayed-memory tasks (measures of response initiation) and the GoStop task (a measure of response inhibition). Whereas alcohol produced dose-related increases in impulsive responding on the immediate memory task in both groups, alcohol-induced increases in response inhibition on the GoStop task were evident only in the CSA group. In contrast, women with CSA exhibited less risk taking than the CON group on the balloon analogue risk task. Alcohol produced dose-related increases on several subjective response measures (e.g., alcohol liking) in both groups; however, these ratings tended to be greater in women with CSA. These preliminary data suggest that women with CSA may be more impulsive. Importantly, impulsivity can lead to hazardous drinking, and alcohol consumption can further increase impulsivity, putting women with CSA at increased risk for sexual revictimization, particularly in the context of alcohol use. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The psycholinguistic analysis of client– counselor interactions indicates that how individuals talk about their substance use is associated with treatment outcome. However, the processes by which client speech influences out-of-session behaviors have not been clearly delineated. This study investigated the relationships between deriving relations–a key behavioral process by which language and cognition may come to influence behavior, shifts in the strength of client talk in favor of change, and treatment outcome among 75 cocaine-dependent participants (23% Female). Participants were trained to relate cocaine words, nonsense syllables, and negative-consequence words and were then assessed for a derived relation of equivalence before starting treatment. The DARN-C coding system was used to quantify the strength of participant speech during an early cognitive behavior therapy counseling session. Cocaine use during treatment was the outcome of interest. The analyses (a) characterized the process of deriving relations among individuals seeking help for their misuse of cocaine, (b) tested the relationships between shifts in the strength of participants’ speech in favor of change and treatment outcome, and (c) tested if deriving equivalence relations moderated the relationship between shifts in the strength of in-session speech and treatment response. Results indicated that a minority of participants derived equivalence relations, however increases in the strength of commitment language predicted less cocaine use during treatment only among those who did. The findings suggest deriving relations may be an important process by which changes in the strength of commitment language comes to influence substance use.

This is an introduction to the special issue, "Animal Models of Neuropsychiatric Disorders and Substance Use Disorders: Progress and Gaps." This issue presents 6 original research reports describing the use of mice and rats to model neurodevelopmental disorders, depressive disorders, anxiety disorders, and substance use disorders. Collectively, these studies demonstrate the progress of the field and the gaps and challenges that remain. They also illustrate the range of conditions that are informed by animal models and identify the clinical populations that stand to benefit from their use in preclinical research. (PsycINFO Database Record

Background The hypocretin/orexin system is involved in regulating arousal, and much recent work demonstrates that decreasing hypocretin receptor-1 (HCRTr1) activity using antagonists decreases appetitive behavior, including stimulant drug self-administration and reinstatement. Methods The present study determined the effects of hypocretin-1 and HCRTr1 antagonists on responding reinforced by intravenous (i.v.) cocaine self-administration (0.0125 – 0.05 mg/kg/infusion) in 5 female rhesus monkeys. Responding was examined using 3 schedules of reinforcement: 1) a Fixed interval 1 min, Fixed ratio 10 Chain schedule [FI 1-min (FR10:S)], 2) a Progressive Ratio (PR) schedule, and 3) a cocaine vs. candy. Results Choice schedule: the HCRTr1 antagonist SB-334867 (8–24 mg/kg, i.m.) decreased cocaine taking under the Chain schedule and PR schedule in all 5 monkeys and in 4 of the 5 monkeys under the Choice schedule. d- Amphetamine (0.06 – 0.25 mg/kg, i.m.), tested as a control manipulation, decreased cocaine taking in all 5 monkeys under the Chain schedule. The peptide hypocretin-1 (0.072 mg/kg, i.v.) increased cocaine taking in the monkeys with low rates of cocaine taking under the Chain (3/4) and Choice (4/5) schedules. Reinstatement of extinguished cocaine responding following response-independent delivery of a large dose of cocaine (0.3 mg/kg) was attenuated in 3 of the 5 monkeys by the HCRTr1 antagonist SB-334867. Conclusions These data expand upon work accomplished in predominantly male rodents suggesting that the hypocretin system modulates the response to appetitive stimuli. A better understanding of this system offers promise as a novel approach in medication development for appetitive disorders.

The anorexigenic effects of intramuscular d-amphetamine HCl (0.06-0.50 mg/kg) and dexfenfluramine HCl (0.25-2.0 mg/kg) were determined in experimentally naive baboons. A group of 8 adult male baboons was tested prior to a group of 7 adult female baboons. A 120-min session occurred at 9:00 a.m. during which baboons could respond for food pellets. Drug was given 30 min prior to the 9:00 a.m. morning session. Beginning at 11:00 a.m., baboons had a 6-hr multiple-meal session during which they could have up to 4 food pellet meals. Food was not available overnight, but food was available for 90 min upon awakening such that drug effects were evaluated in non-food-deprived animals. Under baseline conditions baboons earned between 30 and 70 pellets during the morning session and another 175-225 pellets during the remainder of the day. Amphetamine and dexfenfluramine produced dose-dependent decreases in food pellet intake during both the morning food session and the later multiple-meal session. Whereas there were minimal sex differences in the effects of dexfenfluramine, many of the amphetamine doses produced greater decreases in pellet intake in males than females. These results are discordant with much of the rodent literature on abuse-related drug effects that generally reports greater effects of amphetamine in females than males. Additional work is needed to replicate the current findings in nonhuman primates. (PsycINFO Database Record

Heavy drinking has increased in recent years and has been linked to numerous health-related risks, particularly in women. A number of factors may play a role in exacerbating the risks linked to heavy drinking, such as impulsivity, which itself is related to a number of risky behaviors. The present study investigated the effects of alcohol (0, 0.5, 0.75 g/kg) on impulsivity in female heavy drinkers (n = 23) and female light drinkers (n = 23) using a double-blind, placebo-controlled outpatient design; all women were tested during follicular phase of the menstrual cycle. Each session, participants completed a range of tasks including subjective measures of abuse liability, cognitive performance tasks, three behavioral impulsivity tasks, and a risk-taking task. Alcohol increased impulsivity on the Immediate and Delayed Memory Task (IMT and DMT) and Delay Discounting task. Heavy drinkers scored higher on impulsivity self-reports and were more impulsive on the IMT and the GoStop task than light drinkers. The high dose of alcohol further increased impulsive performance on the IMT and DMT in heavy drinkers. There were no group differences or alcohol effects on the Balloon Analogue Risk Task. Alcohol increased sedative-like effects more in light drinkers and increased stimulant-like effects and alcohol liking more in heavy drinkers. In summary, female heavy drinkers are less sensitive to the negative effects of alcohol, report more positive effects of alcohol, and are more impulsive than female light drinkers. Moreover, impulsive responding was exacerbated by alcohol drinking among female heavy drinkers, indicating that women who drink at this level are at increased risk for developing alcohol use disorders and engaging in other risky behaviors, particularly after drinking. (PsycINFO Database Record (c) 2012 APA, all rights reserved). Language: en

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.

Alcoholism is a major public health problem in the United States, such that approximately 15.6 million people meet criteria for alcohol abuse or dependence, and over 800,000 received treatment for alcohol abuse or dependence in 2006 (SAMHSA, 2007). Despite the enormous impact of this disease on society, there are only three medications (disulfiram, naltrexone, and acamprosate) currently approved by the FDA for the treatment of alcohol dependence (e.g., Bouza et al., 2004; Heilig and Egli, 2006; Kiefer and Mann, 2005; Kranzler and Van Kirk, 2001) and given their limited efficacy there is a need for additional pharmacotherapies for alcohol dependence. The interaction of alcohol with the gamma-amino butyric acid (GABA)-ergic neurotransmitter system is well known (Grant and Lovinger, 2005) and targeting GABA-ergic neurotransmission has been considered as a potential treatment strategy for alcohol dependence (Johnson et al., 2005; Heilig and Egli, 2006). Baclofen, a GABA-B receptor agonist, has attracted considerable attention as a potential medication not only for alcoholism (Addolorato et al., 2006a; Colombo et al., 2004; Heilig and Egli, 2006; Johnson et al., 2005; Kranzler, 2000), but also for other addictive disorders (Cousins et al., 2002). There is encouraging preclinical evidence in laboratory rodents that baclofen decreases 1) alcohol withdrawal symptoms (Colombo et al., 2000; Knapp et al., 2007), 2) acquisition and maintenance of voluntary alcohol consumption (Colombo et al., 2000, 2002; Daoust et al., 1987), 3) alcohol consumption associated with alcohol deprivation (Colombo et al., 2003a, 2006), 4) alcohol self-administration (Anstrom et al., 2003; Besheer et al., 2004; Liang et al., 2006; Walker and Koob, 2007), and 5) responding for alcohol during extinction, suggestive of decreased motivation to obtain alcohol (Colombo et al., 2003b; Maccioni et al., 2008). However, not all preclinical studies have reported that baclofen produces a reduction in alcohol consumption or self-administration (e.g., Colombo et al., 2005; Czachowski et al., 2006; Moore et al., 2007; Petry, 1997; Smith et al., 1999; Tomkins and Fletcher, 1996). Nonetheless, the preclinical literature suggests that baclofen may have therapeutic efficacy for alcoholism. Several studies have been conducted in humans to evaluate the efficacy of baclofen for the treatment of patients with alcohol problems. One of the first studies used an open-label design in 10 alcohol-dependent patients (Addolorato et al., 2000) and found that maintenance on 30 mg/day of baclofen for 4 weeks decreased alcohol craving in the 9 patients who completed the study, with 7 patients maintaining total abstinence. Similar positive findings were obtained in two subsequent studies, both of which maintained alcohol-dependent patients on 30 mg/day of baclofen (Addolorato et al., 2002a; Flannery et al., 2004). These findings were recently extended and confirmed in a larger randomized clinical trial among alcohol-dependent patients with liver cirrhosis who were treated with either baclofen (30 mg/day) or placebo for 12 weeks (Addolorato et al., 2007). In all of these studies, side effects of baclofen were minimal and retention was excellent. Further, there have been two case reports showing that high doses of baclofen (100–140 mg/day) were effective in reducing alcohol craving and consumption (Ameisen, 2005; Buckman, 2007). Lastly, several small pilot studies have reported that baclofen (30 mg/day) reduces alcohol withdrawal symptoms in alcohol-dependent patients (Addolorato et al., 2002b, 2003, 2006b). Despite the promising preclinical and clinical findings to date suggesting that baclofen may be effective for treating alcohol dependence, there is a paucity of human laboratory studies assessing the interaction of baclofen and alcohol. Human behavioral laboratory studies can play an important role in the early stages of the medication development process for drug and alcohol abuse (Cousins et al., 2002; O’Brien and Gardner, 2005), particularly for assessing the safety of a candidate medication when administered alone and in combination with alcohol, as well as to elucidate the therapeutic mechanism. Baclofen is a centrally acting muscle relaxant approved by the FDA for the alleviation of signs and symptoms of spasticity; while the usual dose range is between 40–80 mg daily in divided doses, much higher doses have been used for the treatment of spasticity with a good safety profile (Aisen et al., 1992). Baclofen is also known to have anxiolytic effects (Breslow et al., 1989; Drake et al., 2003; Jamous et al., 1994), even among a population of alcoholic patients (Krupitsky et al.,1993), and these anxiolytic effects have been hypothesized to reduce alcohol craving and drinking. In fact, several studies have observed a reduction in anxiety in baclofen-treated alcohol-dependent patients (Addolorato et al., 2002a, 2006b, 2007;Flannery et al., 2004). Alternatively, baclofen may reduce alcohol craving and drinking by reducing the positive effects of alcohol, including the stimulant effects (Cousins et al., 2002), or by enhancing the negative effects of alcohol, including sedation. Despite these potential benefits, the sedative and anxiolytic effects of baclofen also raise concerns about the safety of baclofen in combination with alcohol and its abuse liability (Heilig and Egli, 2006). The purpose of the present study was to comprehensively assess the acute behavioral and physiological effects of baclofen (0, 40, 80 mg) alone, and in combination with an intoxicating dose of alcohol (0.75 g/kg) in non-treatment seeking heavy social drinkers. Specifically, we wanted to address the issues related to the safety profile of baclofen alone and in combination with alcohol, as well as the behavioral effects of baclofen that might elucidate the nature of its putative pharmacotherapeutic effect.

Background: There is growing evidence that N-methyl-d-aspartate (NMDA) receptor antagonists may have potential for the treatment of alcohol disorders. Memantine is a selective noncompetitive NMDA receptor antagonist that has been shown to decrease alcohol craving in moderate drinkers. This 16-week double-blind outpatient pilot clinical trial determined if memantine was more effective than placebo at reducing alcohol use in actively drinking alcohol-dependent patients. Methods: Forty-four treatment-seeking alcohol-dependent individuals were enrolled, with 34 patients stratified to either the memantine group (n=19; maximum dose of 40 mg/d) or the placebo (PBO; n=15) group. The primary outcome measures were related to alcohol use (average drinks per day, average drinks per drinking day, percentage of heavy drinking days, and percentage of days abstinent) based on the timeline follow-back (TLFB). Secondary outcome measures included the Obsessive Compulsive Drinking Scale, Clinical Global Impression ratings, and γ-glutamyltransferase (GGT), a biomarker of recent alcohol use. To enhance retention, patients received voucher incentives for clinic attendance. Results: Of those randomized, approximately 80% (27) completed the entire 16-week trial. Longitudinal analysis of drinks per day and drinks per drinking day showed a significant reduction in alcohol use, but no difference between the 2 groups. Further, the percentage of heavy drinking days indicated that both groups showed a significant decrease in drinking behavior, but there was significant treatment effect in favor of the PBO group. Similarly, for the percentage of days abstinent, the PBO group achieved a significantly greater percentage of days abstinent at a faster rate than the memantine group. Lastly, the memantine group reported a greater number of side effects compared with the PBO group, such that 26% of patients had their drug dose decreased or discontinued due to memantine-related side effects. Conclusions: The results of this double-blind placebo-controlled pilot trial do not support the use of memantine for the treatment of actively drinking alcohol-dependent patients. However, voucher incentives did facilitate retention.

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

Although stimulant abuse is a growing problem among women, few studies have focused on factors that may be implicated in potential sex differences. Numerous preclinical studies have indicated that female rodents are more sensitive than male rodents to the behavioral effects of stimulants and that the hormone estradiol is involved in these sex differences. In humans, the subjective response to stimulants is greater in the follicular phase (characterized by moderate estradiol levels and minimal progesterone levels) than in the luteal phase (characterized by elevated estradiol levels and elevated progesterone levels). Differences between men and women emerge only when men are compared with women in the luteal phase; the subjective response to stimulants is similar in men and women in the follicular phase. In contrast to rodents, there is minimal evidence that estradiol enhances the subjective response to stimulants in humans. Rather, the hormone progesterone has been shown to attenuate the subjective response to stimulants, particularly in women. Recent preclinical data confirm that progesterone reduces the behavioral response to stimulants. In summary, there is converging evidence from studies in humans that (a) men and women do differ in their subjective response to stimulants; (b) these sex differences are evident when women are in the luteal phase, when progesterone levels are elevated; and (c) progesterone administration attenuates the subjective response to stimulants. Therefore, the menstrual cycle should be addressed in mixed-gender studies. Moreover, the modulatory effects of progesterone on reducing the positive effects of cocaine may have some clinical utility in treating stimulant abusers.

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.

The purpose of this study was to determine if methadone-maintained patients (MMP) with cocaine dependence (CD) and/or adult Attention Deficit Hyperactivity Disorder (ADHD) exhibited compounded cognitive dysfunction associated with their poly-substance use and/or co-morbid psychiatric diagnoses. The sample consisted of 79 MMP (59% male, 51% Caucasian), maintained on methadone doses ranging from 40-130 mg/day, who were placed into one of four diagnostic categories: (1) a control group (no ADHD, no CD) (n = 24), (2) CD alone (n = 18), (3)ADHDalone (n = 18), and (4)ADHD+ CD(n = 19). The California Computerized Assessment Package (CalCAP) was administered to assess cognitive functioning requiring focused and sustained attention in a standardized fashion. There were no group differences on Simple Reaction tasks. Compared to the control group, the ADHD+ CD group was slower and less accurate on 33% of the Choice Reaction (CR) tasks. Specifically, individuals in the ADHD + CD group and the ADHD alone group performed significantly worse on tasks measuring attention and psychomotor responding. These tasks are associated with broader cognitive skills in working memory, language discrimination and flexibility of cognitive sets that may have implications for treatment outcome. Diagnostic services capable of identifying cognitive deficits among MMP with ADHD and/or CD are needed to maximize the likelihood of treatment success and to serve as an indicator for the efficacy of therapeutic approaches.

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.

In a previous study, we showed that the positive subjective effects of cocaine were higher during the follicular phase compared to the luteal phase of the menstrual cycle. The purpose of the present study was to determine if exogenously administered progesterone during the follicular phase in females would attenuate the response to cocaine compared to the normal follicular phase, thus making the response to cocaine similar to the luteal phase. To address the role of sex differences, males were also administered exogenous progesterone during one inpatient stay. In all, 11 female and 10 male non-treatment-seeking cocaine smokers participated. Females had three inpatient stays: one during a normal follicular phase, one during a normal luteal phase, and one during a follicular phase when exogenous progesterone was administered. Males had two inpatient stays: one when exogenous progesterone was administered and the other when placebo was administered. During each inpatient admission, there were four smoked cocaine administration sessions: participants were administered six doses of cocaine (0, 6, 12, or 25 mg cocaine base) at 14 min intervals. Smoked cocaine increased heart rate, blood pressure and several subjective effects such as 'good drug effect' and 'drug quality' cluster scores. Administration of progesterone during the follicular phase in women attenuated the positive subjective effects of cocaine, whereas only minimal changes were observed in men. These results indicate that progesterone modulates the response to cocaine in women and suggests that fluctuations in endogenous progesterone levels account for some of the sex differences observed in humans.

Several studies in rodents suggest that there are sex differences in response to cocaine that are related to fluctuations in the ovarian hormones of females. Female rhesus monkeys have menstrual cycles that are remarkably similar to human menstrual cycles in both duration and hormonal variations. Therefore, data obtained in monkeys should be an ideal model for assessing the effects of cocaine across the menstrual cycle in humans. The present study assessed the acute effects of intravenous cocaine (0, 0.25, 0.50, and 1.00 mg/kg) in five female rhesus monkeys during four phases of the menstrual cycle: menses, midfollicular, periovulatory, and midluteal. To reduce the effects of stress that can occur from sedation, all animals were trained to enter primate chairs so that repeated blood samples could be obtained in awake animals. Hormone levels for estradiol and progesterone were measured each session before cocaine administration. Cocaine and cocaine metabolite plasma levels were measured at 5, 15, 30, 45, 60, and 90 min after cocaine administration. Similarly, levels of luteinizing hormone (LH) were measured before, 15, 30, 45, 60, and 90 min after cocaine administration. Within 5 min of cocaine administration, cocaine plasma levels peaked and dose-dependent behavioral changes (ie increased motor activity, mydriasis, and refusal of treats) were observed. These effects typically resolved in 15-30 min. There were few differences in the pharmacokinetic profile of cocaine across the menstrual cycle. However, the cocaine metabolites, BZE and EME, did vary across the menstrual cycle, with both being increased in the luteal phase, particularly following the highest dose of cocaine. In addition, unlike previous studies, cocaine did not produce consistent increases in LH levels. Rather, the change in LH levels depended on menstrual cycle phase and cocaine dose. In summary, there is little evidence that the pharmacokinetics of cocaine vary as a function of menstrual cycle phase.

Individuals who are moderate drinkers are at increased risk to abuse alcohol. Moreover, women are more vulnerable than men to the adverse consequences of alcohol consumption and recent data indicate that the drinking pattern in women is becoming more similar to that of men. However, few studies have determined whether female moderate drinkers (MD) show a differential response to the subjective and performance effects of alcohol, compared to female light drinkers (LD). Fifteen female MD who consumed an average of 34.7 drinks/month were compared to 15 female LD who consumed an average of 6.7 drinks/month. None of the participants had a first-degree family history of alcoholism or substance abuse. The acute effects of alcohol (0, 0.25, 0.50, 0.75 mg/kg) were evaluated using a double-blind, placebo-controlled outpatient design. Drug effects were assessed using a full range of performance measures, subjective-effects questionnaires and observer ratings. Alcohol impaired performance in a dose-related manner on all performance tasks for both groups of females. However, MD were less impaired than LD on balance and Digit Symbol Substitution Test (DSST). This reduced response was also evident from the observer ratings, with MD being viewed as less impaired by alcohol than LD. While ratings of Drug Liking increased in both groups of women on the ascending limb of the breath alcohol curve, alcohol was disliked by LD on the descending limb and LD reported increased ratings of Bad Drug Effects following the high dose of alcohol. The reduced performance impairment, coupled with the positive subjective effects and relative absence of adverse subjective effects, suggestive of behavioral tolerance, could result in a progression towards increased alcohol consumption among moderate female social drinkers.

There is a noticeable lack of targeted treatment options for marijuana dependence, in particular pharmacologic approaches. This is the first study evaluating a targeted pharmacologic approach for marijuana dependence. The goals of the study were to determine if such patients would seek pharmacologic treatment, whether these patients could be retained in treatment using a design previously developed for cocaine-dependent patients, and especially whether divalproex sodium showed promise as a treatment agent for marijuana dependence. We found that marijuana-dependent patients will seek treatment, and such patients can be adequately maintained in a pharmacologic trial. Regardless of treatment group, patients reported a significant reduction in their frequency and amount of marijuana use as well as a reduction in irritability. Given the lack of proven effective treatments for marijuana dependence, pharmacotherapies should be sought. The design of a preliminary clinical trial should include a psychosocial/behavioral intervention emphasizing motivation and medication compliance and a placebo control group.

This is an introduction to the special issue "50th Anniversary of APA Division 28: The Past, Present, and Future of Psychopharmacology and Substance Abuse." Taken together, the scholarly contributions included in this special issue serve as a testament to the important work conducted by our colleagues over the past five decades. Division 28 and its members have advanced and disseminated knowledge on the behavioral effects of drugs, informed efforts to prevent and treat substance abuse, and influenced education and policy issues more generally. As past and current leaders of the division, we are excited to celebrate 50 years of Division 28 and look forward to many more successful decades for our division and its members. (PsycINFO Database Record

A small, controlled study was conducted to assess whether pergolide mesylate has clinical promise as a treatment for cocaine abuse prior to embarking on a larger, randomized, double-blind, controlled trial. Fourteen individuals were placed on placebo for 2 weeks, followed by a 24-week single-blind study in which they were placed on pergolide for 12 weeks, followed by placebo for 12 weeks. Another 14 patients received single-blind placebo for two weeks and then were randomized into a 24-week double-blind, placebo-controlled, multiple baseline design. Initially, patients enrolled in the study were placed on risperidone (n = 9) or placebo (n = 5). During the first 12 weeks, retention was worse for those receiving pergolide compared to risperidone or placebo. Neither risperidone nor pergolide were more efficacious in reducing cocaine use than placebo. Although earlier open studies found pergolide to show promise as a treatment for cocaine abuse, this study did not support these earlier findings. Comparing an agent to both an active control and placebo group may better predict whether a promising new agent will have clinical utility compared to the standard open trial.

There are three purposes for this study: (1) To extend the laboratory study of heavy smoked cocaine use to women, (2) to assess cocaine withdrawal symptoms and (3) to assess the utility of voucher incentives for achieving and maintaining cocaine and other drug abstinence in female cocaine abusers. Methods: Ten non-treatment seeking female cocaine smokers resided inpatient for 4–5 days and could smoke up to 6 doses of cocaine base (50 mg each) twice a day (at 1200 h and again at 1600 h) for 2 consecutive days. During the following 2-week outpatient phase, women were given US$40 in merchandise vouchers if urinalysis indicated lower drug levels from the previous day. Results: Women self-administered 20.4 out of 24 possible doses. Compared to the 1200 session, heart rate and blood pressure, but not subjective effects, were still significantly increased prior to the 1600 session. Nine women completed the outpatient phase, attending 98% of their appointments. Using the One-Half Rule, 56% of urines indicated no new cocaine or other drug use. Implications: Although a US$40 voucher incentive for a “clean” urine was not sufficient to eliminate cocaine use, the possibility of earning the voucher was sufficient to maintain nearly perfect attendance.

Little is known about whether the duration of cocaine use or an individual's age may influence the acute effects of cocaine, patterns of use, and specific treatment needs.This post hoc analysis determined whether the duration of cocaine use or current age influenced the acute subjective response to cocaine. Data from four smoked cocaine self-administration laboratory studies were combined and analyzed to determine whether the subjective effects of a 25-mg smoked cocaine dose varied as a function of years of cocaine use or current age.Thirty-six nontreatment-seeking healthy cocaine users (ages 32-49) were admitted to studies lasting from 12 to 105 days. Participants rated the subjective effects of each cocaine dose from 0 to 100 by completing a computerized self-report visual analogue scale (VAS). The main outcome measures were the change in VAS ratings between a baseline placebo dose and the first 25-mg dose of smoked cocaine.No significant relationship was found between the subjective effects of cocaine and years of cocaine use (mean 20.9, range 5-30) or current age (mean 41.1, range 32-49).Among long-term cocaine users between the ages of 32 and 49, the acute subjective effects of cocaine did not vary as a function of years of cocaine use or current age.These data fail to support the incentive sensitization theory for addiction by Robinson and Berridge, as cocaine "liking" and "wanting" remained the same regardless of age or years of cocaine use.

Tolerance to the analgesic effects of opioids has been demonstrated in laboratory animals after repeated drug administration; yet, this effect has been studied less frequently under controlled laboratory conditions in humans. This within-subject, double-blind, placebo-controlled study was designed to determine whether tolerance developed to the analgesic, subjective, and physiological effects of the commonly prescribed opioid oxycodone when it was administered daily for 5 days. The effects of oxycodone (0, 5, and 20 mg/70 kg, orally) were compared, using a within-session cumulative dosing procedure, on the first and fifth days of the 'daily' dosing phase to assess for tolerance; active oxycodone was administered on the second and fourth days of the daily dosing phase. Changes in the effects of oxycodone were also compared when the medication was only administered on the first and the fifth day of a 5-day 'intermittent' dosing phase; placebo medication was administered on the second and fourth days of the intermittent dosing phase. A 9-day 'washout' period occurred between phases during which no medication was administered. Healthy volunteers (N=10) with no history of drug dependence or current drug use participated in this outpatient study. Analgesia was assessed using the cold pressor test, pain and drug effects were measured using a variety of questionnaires, and pupil diameter was monitored as an index of physiological effects. When administered daily, no differences were observed in oxycodone-induced analgesia between the first and the fifth days, but tolerance did develop to some of the positive subjective effects of oxycodone. In contrast, oxycodone-induced analgesia and participant ratings of some positive subjective drug effects were greater on the fifth compared with the first day of the intermittent dosing phase. No differences in the miotic effects of oxycodone between the first and the fifth days of either dosing phase were detected. Although obtained under limited experimental conditions, these findings suggest that tolerance may not develop to the analgesic effects of therapeutic doses of oxycodone under short-term daily dosing conditions, even though some of its subjective effects may decrease. These data also suggest that intermittent administration may enhance the analgesic effects of oxycodone, while also increasing some of the drug's positive subjective effects related to abuse liability.

Previous research suggests that women who report dietary restraint tend to consume alcohol in greater quantities, however most studies use retrospective data collection, which is often unreliable, and no studies have accounted for this relationship with respect to potential changes in alcohol consumption across the menstrual cycle. Therefore, the present study investigated the relationship between prospectively monitored drinking patterns and dietary restraint across the menstrual cycle among females from the general population whose drinking level (7–20 drinks/week) places them at-risk for developing alcohol use disorders. Restrained eaters (RES; N = 51) and unrestrained eaters (UN-RES; N = 55), per the cognitive restraint scale scores from the Three-Factor Eating Questionnaire, provided prospective ratings measuring mood, alcohol consumption, and consequences of alcohol use across one full menstrual cycle. Dysphoric mood increased during the late luteal and menstrual phases in both groups. Although overall the RES group did not drink more than the UN-RES group, the RES group drank less than the UN-RES group during the follicular phase, suggesting that among RES women alcohol consumption may be modulated by hormonal fluctuations across the menstrual cycle. The differences between the present findings and previous research may be due to the cohorts sampled; the majority of previous studies sampled college students, where binge drinking and dietary restraint are more common, whereas this study sampled the general population. Future research should replicate prior studies in a college-aged population using the current design of prospective data collection for greater accuracy of self-reported alcohol consumption.

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.

This paper provides a methodological survey of research of 1253 experiments on the acute effects of drugs used for non-medical purposes on human performance. 305 different tasks were tested, but only 118 tasks were used in more than two experiments. While the majority of experiments did have control conditions and measured drug effects at more than one time point after drug administration, they varied widely on other protocol details: (1) subject populations, (2) training on the tasks prior to drug administration, and (3) number of active test doses that were tested. Administration of stimulants either had no effect, or improved performance. In contrast, administration of marijuana, alcohol, or benzodiazepines had no effect, or impaired performance. In order to maximize comparability and utility, future protocols should use control groups, train subjects prior to participation, test more than one drug dose, and test performance before, and several times after, drug administration. A greater range of subject populations should also be studied. Finally, task standardization including type of instructions to subjects, duration of performance testing, feedback to subjects, motivational conditions, and inclusion of a benchmark task should also be used to enhance comparisons across studies.

Studies using rodents have shown that behavioral responses to a stimulant are enhanced when the stimulant is given within the same context as previous stimulant administrations; this increase in effect related to context is often referred to as sensitization. We examined the role of environmental stimuli in modulating the subjective and cardiovascular effects of cocaine in humans (1) within a daily “binge” and (2) after cocaine abstinence. Ten non-treatment seeking users of smoked cocaine were admitted to the hospital for 17 consecutive days. Participants smoked cocaine (25 mg/dose) under two counterbalanced conditions: paired stimuli (same stimuli presented each session) and unpaired stimuli (varied stimuli presented each session). Under each stimulus condition, participants had cocaine test sessions for three consecutive days, no sessions for the next 3 days, then another cocaine test session on the following day, for a total of eight test days. Stimulus condition had no effect on cardiovascular or subjective effects so data were analyzed as a function of repeated cocaine administration over 2 weeks. Maximal ratings on “good drug” and “drug rating” subjective effects clusters decreased over days of repeated cocaine exposure. In contrast, baseline and peak heart rate and systolic pressure increased over days of repeated cocaine administration. Thus, repeated administration of smoked cocaine to experienced cocaine users resulted in increases in baseline blood pressure and heart rate and modest decreases in positive subjective effects. These data indicate modest tolerance rather than sensitization to the positive subjective effects of cocaine with repeated exposure.

This paper describes the rationale, practical details, and laboratory lore relevant to conducting an acute dose-effect crossover evaluation for abuse liability of a novel anxiolytic/hypnotic compound relative to a standard compound. Basic principles underlying meaningful abuse liability assessments are presented and illustrated with examples from a comparative evaluation of the hypnotics zolpidem and triazolam. These principles include using a double-blind placebo-controlled design, selecting an appropriate comparison compound, evaluating a wide range of doses including supratherapeutic doses, using subjects with histories of sedative drug abuse, and using a range of dependent measures. The dose-effect crossover evaluation is proposed as a crucial first step in any rigorous drug abuse liability evaluation of a novel anxiolytic or hypnotic drug. Such a study can be expected to generate a broad data base which not only provides a prediction about the likelihood of abuse of the novel compound, but provides an assessment of some of the adverse consequences of recreational abuse. The crossover study also establishes parameters for subsequent studies such as direct assessment of reinforcing effects with drug self-administration testing.

With the greater acceptance of adult attention-deficit hyperactivity disorder (ADHD) as a valid clinical diagnosis, this disorder has been increasingly recognized among substance abusers seeking treatment. Because adult ADHD occurs in a substantial minority of substance abusers—from 10 to 30 percent—the question arises of whether individuals identified as having adult ADHD and substance abuse would benefit from targeted treatment interventions. Cocaine abusers with childhood histories of ADHD are more likely to use cocaine at an earlier age and to have more exposure to treatment, but they do less well in treatment (1). Furthermore, Dansereau and associates (2) have found that methadone maintenance patients with “poor attention” do less well in treatment. Thus it seems reasonable to conclude that improving an individual’s difficulties with inattention, hyperactivity, or impulsivity will increase that person’s likelihood of succeeding in substance abuse treatment.

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.

Although there are some data suggesting that individuals with depressive disorders may be more likely to remain in treatment than those without depressive disorders, it is less clear how well other psychiatric subgroups compare to those without psychiatric comorbidity. This sample is a follow-up study of 135 individuals who were admitted into a therapeutic community. Individuals with attention-deficit hyperactivity disorder (ADHD), other Axis I disorders (no ADHD), and no Axis I disorders were compared. Although individuals with other Axis I disorders had a strikingly low early drop-out rate, after a prolonged time in treatment, the drop-out rate increased substantially, such that these individuals were found to complete treatment at a lower rate (17%) than those with no Axis I disorders (29%). Furthermore, individuals with ADHD were less likely to graduate treatment than those with other Axis I or no Axis I disorders (0%, 9%, and 19%, respectively). Future investigations may be useful to determine whether pharmacologic or nonpharmacologic interventions might improve treatment outcome.

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.

Individuals who are moderate/heavy drinkers are at increased risk to abuse benzodiazepines and this risk is increased in women compared to men. However, no studies have determined whether female moderate drinkers (MD) show a differential response to the subjective and performance effects of benzodiazepines compared to female light drinkers (LD). Fourteen female MD who consumed an average of 36 drinks/month were compared to 14 female LD who consumed an average of 4.2 drinks/month. None of the participants had either a first- or second-degree family history of alcoholism. The acute effects of placebo, alprazolam (0.25, 0.50, 0.75 mg) and buspirone (5, 10, 15 mg) were evaluated using a double-blind, placebo-controlled outpatient design. Drug effects were assessed using a full range of performance measures and subjective-effects questionnaires. Alprazolam impaired performance in a dose-related manner on all performance tasks for both groups of females, whereas buspirone had minimal effects on performance. There were few differences between LD and MD with respect to subjective response or performance impairment following either alprazolam or buspirone. Although MD reported greater ratings of Good Drug Effect and Drug Liking than LD, this was neither dose-related, nor specific to alprazolam. The results of the present study suggest that female MD without a family history of alcoholism experience the same level of performance impairment as female LD, although they tend to report greater positive subjective effects from alprazolam.

There are few published studies assessing the efficacy of pharmacologic treatments for attention-deficit hyperactivity disorder (ADHD) among substance abusers seeking treatment. Eleven patients who met DSM-IV diagnostic criteria for cocaine dependence and adult ADHD were entered into a 12-week single-blind trial of divided daily doses of bupropion (BPR). All patients received weekly individual standardized relapse prevention therapy. Treatment compliance and retention were good. Patients reported significant reductions in attention difficulties, hyperactivity and impulsivity. Self-reported cocaine use, cocaine craving, and cocaine positive toxicologies, also decreased significantly. In a previously published trial, 12 patients who met similar diagnostic criteria for adult ADHD and cocaine dependence were entered into a 12-week trial of divided daily doses of sustained-release methylphenidate (MPH). Improvements observed on BPR were similar to, and did not differ from those previously observed with MPH. These preliminary data suggest that BPR may be as effective as sustained-release MPH, when combined with relapse prevention therapy, for cocaine abusers with adult ADHD. However, a future study directly comparing BPR to MPH in a double-blind placebo-controlled trial is needed.

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.

The subjective and physiological effects of repeated smoked cocaine self-administration were compared in 11 men and 9 women. Twice a day, on 2 consecutive days, participants smoked up to six 50-mg doses of cocaine base, at 14 min intervals. Men and women self-administered a similar number of cocaine doses (21.7 and 21.6, respectively). The most striking sex difference was that women had higher cocaine plasma concentrations than men (632.7 ng/ml vs. 376.7 mg/ml) after the sixth cocaine dose of the first session. After the first cocaine dose, women reported that they would spend significantly less for the dose than men ($1.58 vs. $3.15). Although cocaine produced similar effects in men and women 4 min after each dose, 15 min after the last dose of the session, heart rate and blood pressure remained elevated in women, but ratings of “I want cocaine” were lower in women as compared to men. Thus, smoking cocaine produced similar acute subjective effects in men and women, but prolonged cardiovascular effects and higher cocaine plasma concentrations in women.

This study determined if women with premenstrual dysphoric disorder (PMS) showed impaired mood and performance when they were experiencing their premenstrual symptoms, and if the effects of alprazolam varied as a function of menstrual cycle phase. Under double-blind conditions, the acute effects of placebo and alprazolam (0.25, 0.50, 0.75 mg) were tested during both luteal and follicular phases. Women with confirmed PMS experienced substantial changes in mood as a function of menstrual cycle phase. However, under controlled laboratory conditions, acute doses of alprazolam did not improve negative premenstrual mood, but rather increased negative mood in the follicular phase. Alprazolam impaired task performance, although this impairment was generally similar in both phases when baseline phase differences were taken into consideration. Consistent with the failure of alprazolam to improve mood premenstrually, subjective measures indicative of abuse liability were not increased following alprazolam. Taken together, these data suggest that acute administration of alprazolam doses are not clinically useful for the treatment of PMS.

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.

A mutually exclusive choice procedure was used to evaluate the reinforcing effects of caffeine in eleven normal subjects with histories of regular caffeine consumption (mean 256mg/day). Subjects participated for 24 weeks; each week consisted of three consecutive daily sessions (two sampling days followed by a choice day) during which subjects were required to abstain from dietary sources of caffeine. On each sampling day subjects ingested four capsules, one every 2h. Capsules contained placebo on one sampling day and caffeine (50 or 100mg/capsule) on the other sampling day. Placebo and caffeine were associated with different color-coded capsules. At the beginning of the choice day subjects chose one of the two color-coded capsules they wished to take on that day; they were required to ingest one capsule and, thereafter, they could ingest up to six additional capsules of the same color throughout the day. Across subjects and dose, caffeine was chosen over placebo on 80% of choice occasions; nine of 11 subjects (82%) chose caffeine on more than 70% of choice occasions and caffeine choice was replicable despite changes in capsule colors across blocks. This is the first study in a relatively uncontrolled outpatient context to demonstrate significant caffeine reinforcement in the majority of normal subjects.

DN-2327 (pazinaclone) is a new non-benzodiazepine compound which has high affinity for benzodiazepine receptors. The acute behavioral effects and abuse liability of DN-2327 (2, 4 and 8mg) were compared to those of the benzodiazepine anxiolytic alprazolam (0.25, 0.5 and 1mg) in ten normal adult male volunteers using a double-blind, placebo-controlled, outpatient design. For both drugs, the neck effect occurred approximately 1.5h after drug administration. Both drugs also produced comparable dose-related effects on several measures related to sedation, as well as on subject- and observer-rated strength of drug effect. Both alprazolam and DN-2327 produced dose-related impairments on various performance measures; on some tasks, the impairment was greater for DN-2327. In contrast, there were no differences between DN-2327 and alprazolam on observer-rated measures. Although no measures of drug-taking were made in this study, to the extent that self-reported effects predict reinforcing effects, the data suggest little liability for abuse of the two compounds in this subject population. Ratings of 'drug liking' and 'willing to take the drug again' were not increased following alprazolam. Although DN-2327 did not increase ratings of 'willing to take the drug again', DN-2327 did produce small but significant increases on ratings of 'drug liking'. Overall, these results suggest that the non-benzodiazepine DN-2327 has a pharmacological profile that is similar to that of benzodiazepines.

Two groups of pigeons were trained to discriminate a histamine H(1)-antagonist (chlorpheniramine or promethazine) from saline with responding maintained under a fixed-ratio 30 schedule of food delivery. There was no cross-substitution with these two histamine H(1)-antagonists: that is, promethazine failed to substitute reliably for chlorpheniramine in chlorpheniramine-trained pigeons, and chlorpheniramine failed to substitute reliably for promethazine in promethazine-trained pigeons. Among the other histamine H(1)-antagonists tested, tripelennamine consistently produced greater than 80% responding in chlorpheniramine-trained pigeons but not in promethazine-trained pigeons. In contrast, diphenhydramine consistently produced greater than 80% responding in promethazine-trained pigeons but not in chlorpheniramine-trained pigeons. Similarly, chlorcyclizine partially substituted for promethazine and failed to substitute for chlorpheniramine. d-Amphetamine substituted for chlorpheniramine in 2 of 4 pigeons and partially in a third pigeon, whereas d-amphetamine substituted for promethazine in only 1 of 4 pigeons. Pentobarbital failed to produce greater than 80% responding in either chlorpheniramine- or promethazine-trained pigeons. The results of the present study demonstrate that the histamine H(1)-antagonists, chlorpheniramine and promethazine, have differential discriminative stimulus effects in pigeons. These findings suggest that the discriminative stimulus effects of this class of compounds are not based entirely on their ability to act as antagonists at histamine H(1)-receptors.