Effect of setting on the reinforcing and subjective effects of ethanol in social drinkers

The reinforcing and subjective effects of two doses of ethanol [0.5 g/kg (LOW) and 0.8 g/kg (HIGH)] were evaluated under two conditions, a social condition (SOC), in which subjects were tested with two or three other subjects, and a socially isolated condition (ISO), in which subjects were tested alone. Forty-one social drinkers participated in a double-blind, seven-session choice procedure. Subjects were randomly assigned to one of four experimental groups: SOC-LOW, SOC-HIGH, ISO-LOW, or ISO-HIGH. On the first four sessions, subjects sampled ethanol (0.5 or 0.8 g/kg) on two occasions and placebo on the other two occasions. On the three remaining sessions, subjects selected and consumed whichever of the two previously sampled substances they preferred. The number of sessions on which they chose ethanol was the primary measure of the reinforcing effects of ethanol. Standardized self-report questionnaires and a psychomotor test were used to measure subjective and objective drug effects. Subjects in the SOC condition chose ethanol over placebo on significantly more sessions than subjects in the ISO condition. Ethanol produced positive subjective effects (e.g., increased ratings of drug liking and euphoria) for subjects in the SOC condition, but for subjects in the ISO condition, it produced apparently negative effects (e.g., increased ratings of dysphoria). These results extend previous reports that the behavioral effects of ethanol depend upon the social condition in which it is consumed.     

Predictors of success in smoking cessation among Italian adults motivated to quit

We examined the role of sexual gender, age, working status, education, cigarettes per day, Fagerström test, age of onset, pharmacologic intervention (bupropion or varenicline), 10 sessions of cognitive–behavioral group counseling therapy (GCT) conducted over 6 weeks, and level of attendance of the counseling program as predictors of smoking cessation on 1282 Italian adult smokers. Results of a multi-variate forward stepwise conditional logistic analysis, at the first step, indicate that subjects who attended the program from 4 to 6 sessions and from 1 to 3 sessions, respectively, resulted about 3 times and 24 times more likely to smoke than those attending from 7 to 10 sessions; at the second step, subjects with high Fagerström score were 2 times more likely to smoke than subjects with low/middle Fagerström; at the third step, subjects treated only with GCT were 2 times more likely to smoke than subjects with combined pharmacologic interventions and GCT; at the fourth step, subjects with age of onset less than 17 years were 1.5 times more likely to smoke than subjects with a higher age of onset; eventually, at the fifth step women resulted 1.5 times more likely to smoke than men. In conclusion, we found that a steady attendance of the cognitive behavioral program, as well as the addition of pharmacologic interventions to counseling, remarkably increased the probability of the smoking cessation behavior to be determined. Nevertheless, FTQ was a valid measure in predicting the smoking cessation, and women revealed to be more likely to keep the smoking behavior, as well as subjects who declared an age of onset less than 17 years.     

Neuropsychological Measurement of Drug Effects: Polydrug Research

Abstract

This study examined the impact of treatment intensity on cocaine use. Seventy-seven cocaine-using methadone patients were enrolled in a six-month, structured, manual-driven, cognitive behavioral treatment program. Sessions consisted of five individual and/or group sessions per week. At intake subjects showed extensive polydrug abuse, psychiatric comorbidity, criminal histories, and HIV risk behaviors. Treatment intensity was measured by dividing number of sessions attended into quartiles. Paired comparisons, within treatment quartiles, were made between subjects' intake and six-month self-reports of cocaine use. Subjects in quartiles two through four showed significant reductions in frequency of cocaine use at follow-up, with subjects who received the most treatment showing the greatest reductions in cocaine use. Bivariate and multivariate analyses showed that treatment sessions attended remained a strong predictor of reduction in cocaine use at follow-up, even after controlling for drug use at intake and background variables. The results indicate that there is a substantial treatment dose-response relationship.     

Project ASPIRE: An Interactive,Multimedia Smoking Prevention and Cessation Curriculum for Culturally Diverse High School Students

A Smoking Prevention Interactive Experience (ASPIRE) is an innovative, computer-based smoking prevention and cessation intervention delivered to a culturally diverse population of high school students. Founded in the Transtheoretical Model of Change, five main and two “booster” sessions comprise the interactive intervention. Here we describe the intervention and the baseline characteristics from our study sample of 1,574 10th graders from 16 high schools in Houston, Texas. Environmental and behavioral smoking risk factors were assessed, and the two intervention groups were comparable with respect to most measured variables. The intervention program holds considerable promise in its ability to reduce smoking among teens.     

Persistent anxiety-like behavior in marmosets following a recent predatory stress condition: reversal by diazepam

Initial investigations indicated the use of the Marmoset Predator Confrontation Test (MPCT) as an experimental procedure to measure fear/anxiety-related behaviors in non-human primates. However, possible long-term habituation effects and re-use of experimental subjects need to be verified. This study, therefore, compared the behavioral response of experienced versus na?ve adult black tufted-ear marmosets (Callithrix penicillata) in the MPCT, with/without diazepam administrations. Subjects were tested in the figure-8 maze and confronted with a taxidermized wild-cat predator stimulus. After four initial 20-min maze habituation sessions, each subject was submitted to two randomly-assigned 20-min predator confrontation sessions: vehicle and 2 mg/kg of diazepam. Confrontation with the predator induced significant behavioral changes; i.e., proximic avoidance and tsik-tsik alarm call. Diazepam administration, concomitant to predator exposure, reversed the behavioral changes observed. In both the experienced and na?ve marmosets a similar behavioral profile and response pattern to diazepam was detected, corroborating the important selective pressure that felines seem to have on marmoset behavioral ecology. Therefore, during a more naturalistic-like regimen--i.e., recurring intermittent predator encounters--the general response pattern remains highly consistent, regardless of prior experience. One may consider the re-use of marmoset subjects in the MPCT, particularly under these specific conditions (i.e. repeated 20-min confrontations, 72-h apart).     

Lack of effect of social context on the reinforcing effects of diazepam in humans.

The reinforcing effects of diazepam (DZP) were compared under two conditions in human volunteers using a cumulative dose procedure. Under the social (SOC) condition, groups of two to four subjects participated concurrently whereas in the solitary (SOL) condition subjects participated individually. During the first four sessions of each condition, subjects received 20 mg DZP in five divided doses (4 mg) in two of the sessions and placebo (PL) in the other two sessions. Each drug (DZP or PL) was administered in a distinctively colored capsule and labeled by letter code. During the last three choice sessions, subjects chose which capsule they wished to self-administer and were allowed to choose up to a maximum of seven capsules (28 mg DZP) during each session. Subjects also filled out questionnaires that assessed momentary mood. Overall, DZP was chosen on 33% of choice sessions and there were no differences across conditions. There was a tendency for choice to be correlated with levels of weekly alcohol consumption and liking scores, and as well the latter two measures were correlated. DZP produced sedative-like subjective effects that did not appear to be related to setting, choice of drug in the study, or alcohol drinking history. These results partially confirm previous reports of a relationship between DZP preference and alcohol consumption, but differ from previously reported studies in the overall lower level of DZP choice.     

Assessing pentobarbital preference in normal volunteers using a cumulative dosing procedure

Preference for pentobarbital was assessed in 12 normal healthy volunteers using a seven-session cumulative dosing choice procedure. On the first four sessions subjects sampled the drug and a placebo, and on the last three sessions they chose the substance they preferred. During each of the sampling sessions they ingested, at 30-min intervals, five capsules containing either pentobarbital (30 mg per dose) or placebo. During the choice sessions subjects first chose which capsules they preferred to take (drug or placebo), and then took from one to seven of these capsules, separated by 30 min between ingestions. Self-report measures of subjective effects were obtained at regular intervals during each session. Subjects chose the pentobarbital-containing capsules on average 52% of choice sessions, and ingested an average total dose of 132 mg. Although the drug produced only modest, sedative-like subjective and behavioral effects and there was little evidence of euphoric effects in the group as a whole, individual differences in drug liking and choice were observed. The results are discussed in terms of variables that affect the reinforcing effects of pentobarbital in normal volunteers, and they are contrasted to previous findings using this procedure with other sedative drugs.     

Control of alcohol tolerance by reinforcement in nonalcoholics

The development of tolerance to alcohol was examined in two experiments with nonalcoholic drinkers. In both experiments, male undergraduates received pretraining on a pursuit rotor task and were then randomly assigned to either alcohol or placebo conditions. In the first experiment, monetary and performance feedback reinforcement for pursuit rotor performance were provided to both groups over four drinking sessions. In the second experiment, two final drinking sessions were added where no reinforcement was provided to either the alcohol or placebo subjects, and an additional alcohol group received no reinforcement throughout the six drinking sessions. Tolerance to the impairing effects of alcohol on pursuit rotor performance developed only for the reinforced alcohol subjects; withdrawal of reinforcement from tolerant subjects resulted in a return of impaired performance, i.e. tolerance was extinguished. Impairment remained consistently high in the non-reinforced alcohol subjects throughout all six drinking sessions. The results provide support for the learning hypothesis of behavioural tolerance by demonstrating that its acquisition and extinction may be controlled by reinforcement.     

Non-specific effect of naltrexone on ethanol consumption in social drinkers

Rationale: Clinical studies have shown that the opioid antagonist naltrexone is effective in the treatment of alcoholism. However, the mechanism by which it produces this effect is not understood. Objective: This study was designed to investigate the effect of acute naltrexone on consumption of ethanol in healthy, non-problem social drinkers. Methods: Subjects (n=24) participated in an eight-session, within-subject, placebo-controlled choice procedure which measured ethanol preference and consumption. The procedure consisted of two blocks of four sessions in which subjects received either naltrexone (50 mg oral) or placebo 1 h before consuming an ethanol or placebo beverage. On the first two sessions of each block, subjects received a color-coded beverage containing ethanol (0.75 g/kg) or placebo, in five equal portions at 15-min intervals. On the next two sessions of each block, subjects chose which beverage they preferred (i.e., placebo or ethanol) and how much they wished to take, in unit doses (placebo or ethanol 0.15 g/kg/dose). The primary behavioral measures were (1) the number of times subjects chose ethanol over placebo, and (2) the number of doses they consumed. Subjects rated their mood states and subjective drug effects at regular intervals during each session. Results: Naltrexone did not alter the frequency of ethanol (versus placebo) choice. Although naltrexone did decrease the total number of ethanol doses subjects took (mean 2.7 doses after naltrexone; 3.4 doses after placebo), it also decreased the number of placebo ”doses” subjects took on sessions when they chose the placebo beverage (mean 1.6 placebo doses after naltrexone; 2.8 doses after placebo). Ethanol produced its prototypic subjective effects (e.g., increased ratings of ”feel drug”, ”like drug” and ”high”), and these effects were not altered by naltrexone. Naltrexone produced mild sedative-like effects, and several subjects reported adverse effects such as nausea. Conclusions: These findings show that naltrexone reduces ethanol consumption in healthy volunteers, as it does in alcoholics. However, this reduction was not specific to alcohol; subjects also consumed less of a non-alcoholic, placebo beverage. These findings suggest that naltrexone may reduce alcohol consumption by a non-specific mechanism. Received: 17 September 1998 / Final version: 14 April 1999     

Acute effects of d-amphetamine during the early and late follicular phases of the menstrual cycle in women

Recent preclinical evidence indicates that ovarian hormones, such as estrogen and progesterone, may influence the behavioral effects of psychoactive drugs by interacting directly with neurotransmitter systems in the central nervous system. However, few studies have examined the effects of ovarian hormones on subjective or behavioral responses to psychoactive drugs in humans. In the present study, we assessed the subjective and physiological effects of d-amphetamine during the early and late follicular phases of the menstrual cycle. Nineteen healthy, regularly-cycling women participated in four sessions receiving doses of d-amphetamine (AMPH; 15 mg oral) or placebo during the early and late follicular phases of two menstrual cycles. During the early follicular phase levels of both estrogen and progesterone are low, whereas during the late follicular phase estrogen levels are higher while progesterone remains low. Dependent measures included self-report questionnaires, physiological measures and plasma hormone levels. Most of the subjective and physiological effects of AMPH were not affected by menstrual cycle phase. However, subjects reported greater Unpleasant Stimulation after AMPH, and less Unpleasant Sedation, during the late follicular phase than during the early follicular phase. These results provide limited evidence that higher levels of estrogen during the late follicular phase alter the subjective effects of AMPH in normal, healthy women.     

Assessing individual differences in ethanol preference using a cumulative dosing procedure

Preference for ethanol versus a placebo was assessed in 12 normal volunteers using a cumulative dosing preference test. The test consisted of four sampling sessions followed by three choice sessions. During the sampling sessions subjects received either five cumulating oral doses of ethanol (0.1g/kg per dose) or equal volumes of placebo, at 15-min intervals. Subjective and observer-rated drug effects, psychomotor performance, drug liking ratings, and breath ethanol levels were measured at regular intervals. During choice sessions, subjects first chose which of the two substances (drug or placebo) they wished to take and ingested one unit dose. Then, at 15-min intervals throughout the session, they could ingest up to ten additional unit doses of the same substance (i.e., up to 1.1 g/kg ethanol). On average, the subjects chose the ethanol-containing beverage on 75% of the choice sessions, and they self-administered a mean total dose of 0.8g/kg per session. Subjects varied in the amount of ethanol ingested on choice sessions, and the amount they chose was related to their subjective responses to the drug during sampling. Subjects who chose the most ethanol reported experiencing stimulant-like effects from the ethanol, whereas the subjects who chose ethanol less frequently and ingested lower doses reported primarily sedative-like effects from the drug. The results demonstrate that the cumulative dosing procedure can be used effectively to evaluate drug preferences and dose preferences in normal volunteers.     

Evaluation of an alternative program for MMTP drop-outs: impact on treatment re-entry

INTRODUCTION: Retention in a Methadone Maintenance Treatment Program (MMTP) is predictive of abstaining from heroin and has other benefits. Many individuals leave treatment before they experience these positive outcomes. OBJECTIVE: This research project targeted MMTP drop-outs with an intervention designed to assist them in returning to drug treatment. METHODS: Subjects who had left MMTP within the prior 12 months were randomly assigned to intervention or comparison groups. The 3-month long intervention consisted of street outreach, cognitive behavioral groups, and individual counseling. Data were analyzed for 175 subjects who were out of treatment at baseline and who returned for a 6-month follow-up interview (Intervention group, N=111; Comparison group, N=64). RESULTS: A total of 87% of subjects assigned to the intervention condition participated in at least one component. Intervention subjects who attended two or more cognitive behavioral group sessions were more likely than those who attended 0-1 sessions or those in the comparison group to have returned to treatment during the 6 month follow up time period (72 vs. 53 vs. 50%, respectively, P<0.05, chi square test). CONCLUSION: MMTP drop-outs need not be lost to the drug treatment system if special efforts are made to engage them in interventions developed to encourage treatment re-entry.     

Efficacy of counselor vs. computer-delivered intervention with mandated college students

The purpose of this study was to evaluate the efficacy of two brief interventions and the inclusion of a 1-month booster session with college students who were referred to attend alcohol education following an alcohol-related incident. Participants (N=225; 48.9% male) were randomly assigned to receive one session of a Brief Motivational Interview (BMI) or computer-delivered intervention (CDI) with the Alcohol 101 CD-ROM. Participants were also randomly assigned to booster/no booster. At 3-month follow up, participants in BMI reported greater help seeking and use of behavioral strategies to moderate drinking. At 12-month follow up, BMI participants were drinking more frequently and CDI participants were consuming a greater number of drinks per occasion than at baseline. Mediation analyses showed that the use of specific behavioral strategies mediated the effect of the BMI condition on drinking volume. There was no intervention effect on alcohol problems, and the booster condition did not significantly affect outcomes. Promoting specific behaviors in the context of in-person brief interventions may be a promising approach to reducing drinking volume among identified at-risk students.     

Effects of sublingually given naloxone in opioid-dependent human volunteers

To determine whether sublingual naloxone could precipitate withdrawal in opioid-dependent subjects, naloxone was administered in increasing doses (0-8 mg in four or six sessions conducted over 2 days) to six heroin abusers and three methadone (30 mg/day, p.o.) maintenance patients. Two or three sessions were conducted per day with 2- to 2.5-h intervals between same-day sessions. Naloxone precipitated withdrawal in two of six heroin abusers and in all three methadone subjects. Naloxone is sufficiently absorbed sublingually to precipitate abstinence in dependent subjects, but naloxone doses up to 1-2 mg can be administered sublingually to opioid abusers/addicts without precipitating withdrawal.     

Effects of acute tiagabine administration on aggressive responses of adult male parolees

Experimental and clinical studies have supported a relationship between gamma-aminobutyric acid (GABA) and aggressive behavior in non-humans and humans. Tiagabine is a GABA uptake inhibitor that has been shown to produce acute behavioral effects in animals. In addition, tiagabine has been shown to decrease aggression in agitated patients when administered chronically. The present study was designed to investigate the effects of acute administration of tiagabine on aggressive responding on a laboratory task in adult humans. Ten adult males participated in experimental sessions on the Point Subtraction Aggression Paradigm (PSAP), which provided subjects with aggressive, escape, and monetary-reinforced response options. All subjects received four acute oral doses of Tiagabine (4, 8, 12 and 16 mg) separated by placebo sessions. Tiagabine decreased aggression at doses that either did not affect, or affected to a lesser extent, monetary-reinforced responding. The results are consistent with some prior research using the PSAP showing a possible unique role for GABA in the regulation of human aggression. A possible behavioral mechanism for the rate-decreasing effects on aggressive responding produced in the present study is that tiagabine may modify aggressive responding by suppressing reactions to aversive stimuli.     

Immunogenicity and safety of a virosomal hepatitis A vaccine (Epaxal) in the elderly

BACKGROUND: Protection against hepatitis A virus (HAV) in the elderly is becoming more important as more senior travelers visit areas of high HAV endemicity, and less have protective antibodies acquired after natural infection during childhood. This study assessed the immunogenicity and safety of hepatitis A vaccine in elderly compared to young adults. METHODS: In this open, uncontrolled study, subjects of 18 to 45 years or < or = 50 years of age received two doses of aluminum-free, virosomal HAV vaccine, Epaxal (Berna Biotech Ltd, formerly Swiss Serum and Vaccine Institute, Bern, Switzerland) 12 months apart. RESULTS: After both the basic and the booster doses, geometric mean titers (GMT) for anti-HAV antibodies were 1.7-fold higher in subjects younger than 45 years compared with those < or = 50 years of age. The proportional increase in GMT after the booster dose, however, was similar in younger and older subjects. Seroprotection (< or = 20 mIU/mL) rates in the younger and older subjects were 100 and 65%, respectively, after the first vaccination and 100 and 97%, respectively, after the booster dose. Systemic and local adverse events were mainly mild and short-lived. CONCLUSION: These data show that HAV virosomal vaccine (Epaxal) is well tolerated and immunogenic in elderly subjects. The clinical relevance of lower seroconversion rates after the primary dose is unknown in this population of travelers.     

Acute behavioral effects and abuse potential of trazodone, zolpidem and triazolam in humans

The present study examined the acute behavioral effects and abuse potential of three drugs commonly used to treat sleep disorders, trazodone, zolpidem and triazolam, and placebo in ten male volunteers with histories of alcohol and drug abuse. Trazodone (100, 200 and 300 mg), a triazolopyridine antidepressant, was included because antidepressants are being used more frequently to treat sleep disorders, but it is unclear whether they have a distinct behavioral pharmacologic profile relative to benzodiazepine hypnotics. Zolpidem (15, 30 and 45 mg), an imidazopyridine hypnotic, was tested because it is the most commonly prescribed hypnotic and purportedly has a unique benzodiazepine-receptor binding profile. Triazolam (0.25, 0.5 and 0.75 mg), a triazolobenzodiazepine hypnotic, was included as the standard component because previous laboratory studies have demonstrated that it has at least some abuse potential. Trazodone, zolpidem and triazolam generally produced comparable dose-related increases in scores on the PCAG scale of the ARCI, which suggests the doses tested were equivalent on some behavioral dimension. The effects of trazodone on subject-rated items thought to measure abuse potential (e.g., subject ratings of Willing to Take Again) were less than those observed with triazolam. Zolpidem and triazolam produced comparable effects on these measures. The highest dose of zolpidem, but not triazolam, increased ratings of Like Drug, Happy, Good Effects, Friendly, Elated, Carefree and Bad Effects. Triazolam and zolpidem produced dose-dependent impairment on all of the performance tasks. Trazodone impaired performance on some, but not all, of these tasks. Consistent with the pharmacokinetics of these compounds, the time-action functions of trazodone, zolpidem and triazolam were similar on these measures. These data suggest that trazodone has less abuse potential than triazolam, and may be a viable alternative to benzodiazepine hypnotics in individuals with histories of alcohol or drug abuse. By contrast, despite its unique neuropharmacological profile, the acute behavioral effects and abuse potential of zolpidem are comparable to those of triazolam. Received: 20 June 1998 / Final version: 4 November 1998     

Demonstration of naturalistic methods for cocaine smoking by human volunteers

Five, healthy, adult, male research volunteers participated in up to four daily laboratory sessions while residing on a Clinical Research Unit. Two subjects were tested twice. Fifty milligrams of cocaine base was smoked one, two or four times each session with a 14-min interval between doses. Two subjects smoked cocaine placed in 'smoke-free' cigarettes, while the remaining subjects smoked cocaine placed in a modified tobacco pipe. Significant and biologically relevant cocaine venous blood levels were engendered most consistently using the modified tobacco pipe. Large, transient increases in heart rate, blood pressure and self-reported 'stimulated' scores were observed during single dosing sessions. During multiple dose sessions, cardiovascular activity either increased, returning to near baseline levels between doses, or were sustained, while reported 'stimulated' scores peaked after the first dose and were lower following subsequent doses. Both cardiovascular and subjective effects were greater on the ascending limb than on the descending limb of the cocaine blood level curve suggesting acute tolerance. Although preliminary, these results demonstrate the usefulness of this relatively simple procedure requiring subjects to smoke in the manner they are accustomed, and suggest the importance of further research in this area.     

Preference for diazepam,but not buspirone,in moderate drinkers

The purpose of the present study was to determine the preference for buspirone, an anxiolytic predicted to have minimal abuse potential, in comparison with diazepam in moderate drinkers. Preference for diazepam and buspirone was assessed in 55 moderate drinkers using a seven-session procedure consisting of four sampling sessions followed by three choice sessions. On each sampling session subjects ingested five capsules, one every 30 min. Color-coded capsules contained placebo on two sessions and drug on two sessions. Each drug capsule contained diazepam (4 mg) for 30 subjects and buspirone (5 mg) for 25 subjects. On choice sessions subjects chose whichever of the two color-coded capsules, i.e., drug or placebo, they wished to take. After ingesting one capsule, every 30 min they had the option of ingesting another capsule of the same color and content, for a maximum of seven capsules over the session (maximum of 28 mg diazepam or 35 mg buspirone). In the diazepam group 70% of subjects chose diazepam over placebo on at least two of the three choice sessions, whereas in the buspirone group only 24% of subjects chose buspirone over placebo on at least two sessions. Both diazepam and buspirone increased measures of sedation. Only diazepam increased ratings of liking and impaired performance, whereas only buspirone decreased ratings of feeling Friendly. These results replicate previous findings indicating that diazepam has reinforcing effects in moderate drinkers. Further, these results demonstrate the pharmacological specificity of this effect by showing that buspirone did not function as a reinforcer under these same conditions.