Association between ADORA2A and DRD2 polymorphisms and caffeine-induced anxiety.

Caffeine produces mild psychostimulant and sometimes anxiogenic effects by antagonizing adenosine at A(1) and A(2A) receptors, and perhaps through interactions with other transmitter systems. Adenosine receptors are colocalized and functionally interact with dopamine receptors in the brain. Thus, functional polymorphisms in the genes for either adenosine or dopamine receptors may affect responses to caffeine.

Enhanced mood and psychomotor performance by a caffeine-containing energy capsule in fatigued individuals.

Caffeine produces mild psychostimulant effects that may be particularly evident in individuals whose mood or performance is impaired by sleep restriction or caffeine withdrawal. Caffeinated energy drinks have been shown to improve energy and cognition but expectancy effects cannot be ruled out in these studies. Very few studies have examined the effects of caffeine-containing energy capsules upon behavioral and subjective measures.

Effects of low to moderate acute doses of pramipexole on impulsivity and cognition in healthy volunteers.

The neurotransmitter dopamine is integrally involved in the rewarding effects of drugs, and it has also been thought to mediate impulsive behaviors in animal models. Most of the studies of drug effects on impulsive behaviors in humans have involved drugs with complex actions on different transmitter systems and different receptor subtypes. The present study was designed to characterize the effect of single doses of pramipexole, a D2/D3 agonist, on measures of cognitive and impulsive behavior, as well as on mood in healthy volunteers.

Personality and gender differences in effects of d-amphetamine on risk taking.

The effects of stimulant drugs on risk-taking behavior vary across individuals, even in healthy samples. These differences could relate to personality, which may share common mechanisms with drug effects or impulsive, risk-taking behavior. The current study investigated the role of temperament and gender in the effects of amphetamine on risk taking.

Effects of sleep deprivation on impulsive behaviors in men and women.

The purpose of this study was to examine the effects of sleep deprivation on impulsive behavior. Patients with impulse control disorders often report sleep problems, and sleep deprivation even in healthy individuals impairs cognition, decision-making, and perhaps impulse control. To characterize the effects of sleep loss on specific forms of impulsive behavior, we tested the effects of overnight, monitored sleep deprivation on measures of impulsivity and cognition in healthy volunteers.

Norepinephrine transporter gene variation modulates acute response to D-amphetamine.

Background: Individual differences in subjective responses to stimulant drugs such as amphetamine may influence risk of abuse as well as clinical-treatment response to these drugs. Because the effects of amphetamine are mediated in part by the norepinephrine transporter (SLC6A2), we examined interindividual differences in mood response to amphetamine in relation to SLC6A2 gene polymorphisms.

Methods: Ninety-nine healthy volunteers participated in three sessions in which they randomly received either placebo or D-amphetamine (10 mg or 20 mg) under double-blind conditions.

Preference for immediate over delayed rewards is associated with magnitude of ventral striatal activity.

Discounting future outcomes as a function of their deferred availability underlies much of human decision making. Discounting, or preference for immediate over delayed rewards of larger value, is often associated with impulsivity and is a risk factor for addictive disorders such as pathological gambling, cigarette smoking, and drug and alcohol abuse. The ventral striatum (VS) is involved in mediating behavioral responses and physiological states associated with reward, and dysregulation of the VS contributes to addiction, perhaps by affecting impulsive decision-making.

Efficacy of naltrexone in smoking cessation: a preliminary study and an examination of sex differences.

This double-blinded, placebo-controlled trial evaluated the efficacy of naltrexone as an adjunct to standard smoking cessation treatment. Participants (N = 110) were adult male and female nicotine-dependent smokers who expressed interest in quitting smoking. All subjects received six sessions of behavioral counseling (1 hr/session for 6 weeks), and 1 month of the nicotine patch (21 mg for the first 2 weeks, 14 mg the third week, 7 mg the fourth week).

Serotonin transporter genotype and acute subjective response to amphetamine.

The authors have previously shown an effect of dopamine transporter genotype on acute subjective responses to d-amphetamine, which may affect risk of addiction. They now report the results of an evaluation of the role of the serotonin transporter gene (HTT) using a double-blind, placebo-controlled, crossover design in which subjects (N = 101) completed self-report measures of subjective effect. The separate and combined analyses of the gene-linked polymorphic region (5-HTTLPR) and the Intron 2 VNTR suggest that these two HTT polymorphisms may contribute to acute subjective responses to d-amphetamine with a small effect.

Cortisol effects of D-amphetamine relate to traits of fearlessness and aggression but not anxiety in healthy humans.

Unlabelled: The current study utilized personality measures thought to relate to noradrenergic and catecholamine function (i.e., sensation seeking, anxiety and aggression) to investigate individual differences in amphetamine-induced increases in cortisol.

Does stress reactivity or response to amphetamine predict smoking progression in young adults? A preliminary study.

Recent studies with laboratory animals indicate that a constellation of behavioral factors predict progression to self-administer drugs. Relatively little is known about behavioral or biological factors that predict the progression in drug use from initial experimentation to regular use in human drug users. The present exploratory study examined reactivity to an acute stressor and reactivity to a single dose of a dopaminergic drug as predictors in progression to heavier smoking in young cigarette smokers over a 6-month period.

Responses to the Trier Social Stress Test (TSST) in single versus grouped participants.

Psychological stress plays an important role in psychopathologies. Laboratory methods have been designed to study stress responses in health and disease. The Trier Social Stress Test is a procedure designed to induce psychosocial stress, but the method is costly in terms of time and personnel requirements.

Nucleus accumbens lesions decrease sensitivity to rapid changes in the delay to reinforcement.

Both humans and non-humans discount the value of rewards that are delayed or uncertain, and individuals that discount delayed rewards at a relatively high rate are considered impulsive. To investigate the neural mechanisms that mediate delay discounting, the present study examined the effects of excitotoxic lesions of the nucleus accumbens (NAC) on discounting of reward value by delay and probability. Rats were trained on delay (n=24) or probability discounting (n=24) tasks.

Diazepam impairs behavioral inhibition but not delay discounting or risk taking in healthy adults.

There are reports that diazepam can increase, decrease, or have no effect on measures of impulsive behavior, which may be related, in part, to differences among the tasks used to measure impulsivity. This study examined the effects of a relatively high dose of diazepam (20 mg) on 5 measures of impulsive behavior in healthy adult men and women. Volunteers (N = 18) participated in a 2-session double-blind randomized design in which they received 20 mg diazepam or placebo.

Evaluation of the abuse potential of pagoclone, a partial GABAA agonist.

This study assessed the abuse potential of pagoclone, a partial agonist at the gamma-aminobutyric acid type A (GABAA) benzodiazepine receptor site, in healthy recreational drug users. Twenty-three young adults, who reported past recreational use of sedative drugs or alcohol, participated in 4 sessions during which capsules containing pagoclone (doses: 1.2 mg, the higher end of the proposed therapeutic dose range, and 4.

Differential effects of nicotine on alcohol consumption in men and women.

Rationale: Nicotine and alcohol are frequently co-used, suggesting that use of one drug may facilitate use of the other. Furthermore, because men and women differ in their responses to both drugs, it is possible that men and women also differ in their responses to the combination of nicotine and alcohol.

Objective: This experiment was designed to investigate the effects of nicotine on consumption and subjective and physiological effects of alcohol in healthy male and female social drinkers.

Subjective, behavioral, and physiological effects of acute caffeine in light, nondependent caffeine users.

Rationale: Caffeine produces mild psychostimulant effects that are thought to underlie its widespread use. However, the direct effects of caffeine are difficult to evaluate in regular users of caffeine because of tolerance and withdrawal. Indeed, some researchers hypothesize that the psychostimulant effects of caffeine are due largely to the reversal of withdrawal and question whether there are direct effects of caffeine consumption upon mood, alertness, or mental performance in nondependent individuals.

Acute-alcohol effects on the Experiential Discounting Task (EDT) and a question-based measure of delay discounting.

Alcohol is widely believed to increase impulsive behavior. However, this has been difficult to demonstrate for impulsive choice using existing measures of delay discounting. We hypothesized a new real-time discounting task would be more sensitive to acute effects of alcohol.

The alcohol clamp: applications, challenges, and new directions--an RSA 2004 symposium summary.

This article summarizes the proceedings of a symposium organized and cochaired by Vijay Ramchandani and Sean O'Connor and presented at the 2004 Research Society on Alcoholism meeting in Vancouver, BC, Canada. The objectives of this symposium were: (1) to provide a rationale for the development and use of the alcohol clamp and the requirements for its use in alcohol challenge studies; (2) to highlight recent studies conducted using the alcohol clamp to identify sources of variation in the pharmacokinetics and pharmacodynamics of alcohol, as well as to address important research questions related to the relationship between the response to alcohol and the risk for alcoholism; and (3) to provide a perspective on progress, address limitations of the clamp, and identify new directions for alcohol challenge research. The symposium began with an introduction and overview of the alcohol clamp, by Vijay Ramchandani.

Menstrual cycle phase and responses to drugs of abuse in humans.

Researchers have recently become aware of the importance of including women in research, including drug abuse research. With this increased awareness has come an increased scientific interest in the potential influence of menstrual cycle phase on responses to drugs. In this review, we discuss recent studies that have examined subjective and physiological responses to drugs of abuse in relation to menstrual cycle phase.

Attenuated cortisol response to alcohol in heavy social drinkers.

Individual differences in response to stress may play a role in the development and maintenance of addictive behaviors. While there is evidence that people with a biological family history for alcoholism have a blunted cortisol response to alcohol, data are lacking in other at-risk subgroups, such as heavy social drinkers. The present study examined salivary cortisol response to administration of 0.

Moderate doses of ethanol fail to increase plasma levels of neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one-like immunoreactivity in healthy men and women.

Rationale: The endogenous GABAergic neuroactive steroid 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP, allopregnanolone) has been proposed to contribute to ethanol actions. Humans synthesize 3alpha,5alpha-THP, but its role in response to systemic administration of ethanol is unclear.

Objective: The present study aims to determine the effect of a moderate dose of ethanol on progesterone and 3alpha,5alpha-THP concentrations in plasma samples of healthy male and female subjects and to determine if these levels are related to the subjective effects of ethanol.