Background The conditioned place preference procedure is a widely used animal model of rewarding drug effects that, to date, has not been tested in humans. In this study, we sought to demonstrate ...that humans, like nonhumans, would exhibit a preference for a place previously associated with amphetamine. Further, we investigated the relationship between conditioned place preference and the mood-altering effects of the drug. Methods Thirty-one healthy individuals participated in a five-session procedure during which they experienced the effects of d -amphetamine (20 mg) or placebo on two occasions in two distinctive environments (sessions 1–4). One group of subjects (paired group, n = 19) received amphetamine consistently in one room and placebo in another room, whereas a second group (unpaired group, n = 12) received amphetamine and placebo without regard to room. During the sessions, participants completed questionnaires to rate their mood. On the fifth session, they rated their preference for the two rooms. Results Individuals in the paired group rated their liking of the amphetamine-paired room significantly higher than the placebo-associated room, whereas there was no difference between ratings of the two rooms for individuals in the unpaired group. In the paired group, drug-liking ratings during the conditioning sessions positively predicted preference for the drug-associated room, whereas reports of amphetamine-induced anxiety and dysphoria negatively predicted room-liking scores. Conclusions This study demonstrates that humans, like nonhumans, prefer a place associated with amphetamine administration. These findings support the idea that subjective responses to a drug contribute to its ability to establish place conditioning.
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. In this study, we examined associations between self-reported anxiogenic effects of caffeine and variation in the genes for A(2A) (ADORA2A) and DRD(2) (DRD2) receptors. Healthy male and female individuals (n=102), who consumed less than 300 mg caffeine per week, ingested capsules containing 0, 50, 150, and 450 mg caffeine under double-blind conditions in four separate experimental sessions. Subjective anxiety was measured before and at repeated times after capsules were consumed. At the 150 mg dose of caffeine, we found a significant association between caffeine-induced anxiety (Visual Analog Scales, VAS) and ADORA2A rs5751876 (1976C/T), rs2298383 (intron 1a) and rs4822492 (3'-flank), and DRD2 rs1110976 (intron 6). Caffeine-induced anxiety (VAS) was also associated with two-loci interactions of selected ADORA2A and DRD2 polymorphisms. The lowest dose of caffeine did not increase ratings of anxiety while the highest dose increased anxiety in the majority of subjects. These findings provide support for an association between an ADORA2A polymorphism and self-reported anxiety after a moderate dose of caffeine. It is likely that other ADORA2A and DRD2 polymorphisms also contribute to responses to caffeine.
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.
This study investigated the physiological, subjective, and behavioral effects of 0, 50, 150, and 450 mg caffeine in 102 light, nondependent caffeine users.
Using a within-subjects design, subjects participated in four experimental sessions, in which they received each of the four drug conditions in random order under double blind conditions. Participants completed subjective effects questionnaires and vital signs were measured before and at repeated time points after drug administration. Forty minutes after the capsules were ingested, subjects completed behavioral tasks that included tests of sustained attention, short-term memory, psychomotor performance, and behavioral inhibition.
Caffeine significantly increased blood pressure, and produced feelings of arousal, positive mood, and high. Caffeine increased the number of hits and decreased reaction times in a vigilance task, but impaired performance on a memory task.
We confirm that acute doses of caffeine, at levels typically found in a cup of coffee, produce stimulant-like subjective effects and enhance performance in light, nondependent caffeine users. These findings support the idea that the drug has psychoactive effects even in the absence of withdrawal.
Background
Theobromine, a methylxanthine related to caffeine and present in high levels in cocoa, may contribute to the appeal of chocolate. However, current evidence for this is limited.
Objectives
...We conducted a within-subjects placebo-controlled study of a wide range of oral theobromine doses (250, 500, and 1,000 mg) using an active control dose of caffeine (200 mg) in 80 healthy participants.
Results
Caffeine had the expected effects on mood including feelings of alertness and cardiovascular parameters. Theobromine responses differed according to dose; it showed limited subjective effects at 250 mg and negative mood effects at higher doses. It also dose-dependently increased heart rate. In secondary analyses, we also examined individual differences in the drug’s effects in relation to genes related to their target receptors, but few associations were detected.
Conclusions
This study represents the highest dose of theobromine studied in humans. We conclude that theobromine at normal intake ranges may contribute to the positive effects of chocolate, but at higher intakes, effects become negative.
•Ethinyl estradiol was associated with increased alcohol use in women using oral contraceptives.•Progestin levels were not associated with alcohol consumption.•Oral contraceptive pill phase did not ...impact alcohol use.
Alcohol use is highly prevalent in young adult women and rates of alcohol use disorder are rising rapidly in this population. Further, emerging evidence suggests that circulating levels of ovarian hormones influence alcohol consumption, with increased consumption associated with higher estradiol and lower progesterone levels. However, less is known about the influence of synthetic hormones (contained in oral contraceptive (OC) pills) on alcohol use. The current study examined the influence of OC pill phase, ethinyl estradiol (EE) levels, and progestin levels on self-reported alcohol consumption in healthy female drinkers. Young adult female drinkers using OCs (N = 21) reported alcohol use across one OC pill pack using the Timeline Followback and provided blood samples during both pill phases to measure synthetic hormone levels. We compared alcohol use between OC pill phases (active vs. inactive) using linear mixed effects models for repeated measures and examined correlations between alcohol use and EE and progestin levels. Results showed that women with higher EE levels reported increased alcohol consumption (r = 0.56, p = 0.01) and binge drinking (r = 0.45, p = 0.04) in the active pill phase. Progestin levels and pill phase were not significantly associated with alcohol consumption. These findings provide preliminary data suggesting increased levels of EE from OC pills are associated with excessive alcohol consumption in women. Further research is needed to determine if EE plays a causal role in increased alcohol consumption. This line of research could inform female-specific AUD prevention and treatment strategies among the large subpopulation of women using hormonal contraceptives.
Sales of energy products have grown enormously in recent years. Manufacturers claim that the products, in the form of drinks, shots, supplements, and gels, enhance physical and cognitive performance, ...while users believe the products promote concentration, alertness, and fun. Most of these products contain caffeine, a mild psychostimulant, as their foremost active ingredient. However, they also contain additional ingredients, e.g., carbohydrates, amino acids, herbal extracts, vitamins, and minerals, often in unspecified amounts and labeled as an “energy blend.” It is not clear whether these additional ingredients provide any physical or cognitive enhancement beyond that provided by caffeine alone. This article reviews the available empirical data on the interactive effects of these ingredients and caffeine on sleep and cognitive performance and suggests objectives for future study.
IntroductionThe effectiveness of antibiotics for treating gonococcal infections is compromised due to escalating antibiotic resistance; and the development of an effective gonococcal vaccine has been ...challenging. Emerging evidence suggests that the licensed meningococcal B (MenB) vaccine, 4CMenB is effective against gonococcal infections due to cross-reacting antibodies and 95% genetic homology between the two bacteria, Neisseria meningitidis and Neisseria gonorrhoeae, that cause the diseases. This project aims to undertake epidemiological and genomic surveillance to evaluate the long-term protection of the 4CMenB vaccine against gonococcal infections in the Northern Territory (NT) and South Australia (SA), and to determine the potential benefit of a booster vaccine doses to provide longer-term protection against gonococcal infections.Methods and analysesThis observational study will provide long-term evaluation results of the effectiveness of the 4CMenB vaccine against gonococcal infections at 4–7 years post 4CMenB programme implementation. Routine notifiable disease notifications will be the basis for assessing the impact of the vaccine on gonococcal infections. Pathology laboratories will provide data on the number and percentage of N. gonorrhoeae positive tests relative to all tests administered and will coordinate molecular sequencing for isolates. Genome sequencing results will be provided by SA Pathology and Territory Pathology/New South Wales Health Pathology, and linked with notification data by SA Health and NT Health. There are limitations in observational studies including the potential for confounding. Confounders will be analysed separately for each outcome/comparison.Ethics and disseminationThe protocol and all study documents have been reviewed and approved by the SA Department for Health and Well-being Human Research Ethics Committee (HREC/2022/HRE00308), and the evaluation will commence in the NT on receipt of approval from the NT Health and Menzies School of Health Research Human Research Ethics Committee. Results will be published in peer-reviewed journals and presented at scientific meetings and public forums.
Physical activity has long been considered beneficial to health and regular exercise is purported to relieve stress. However empirical evidence demonstrating these effects is limited. In this study, ...we compared psychophysiological responses to an acute psychosocial stressor between individuals who did, or did not, report regular physical exercise. Healthy men and women (N = 111) participated in two experimental sessions, one with the Trier Social Stress Test (TSST) and one with a non-stressful control task. We measured heart rate, blood pressure, cortisol, and self-reported mood before and at repeated times after the tasks. Individuals who reported physical exercise at least once per week exhibited lower heart rate at rest than non-exercisers, but the groups did not differ in their cardiovascular responses to the TSST. Level of habitual exercise did not influence self-reported mood before the tasks, but non-exercisers reported a greater decline in positive affect after the TSST in comparison to exercisers. These findings provide modest support for claims that regular exercise protects against the negative emotional consequences of stress, and suggest that exercise has beneficial effects in healthy individuals. These findings are limited by their correlational nature, and future prospective controlled studies on the effects of regular exercise on response to acute stress are needed.
Aims
To test whether non‐dependent drinkers show place preference for a location paired with alcohol, and to test if the amount of time spent in the alcohol‐paired location is related to ...self‐reported subjective alcohol effects experienced in that environment.
Design
Two groups of subjects completed six conditioning sessions: three with alcohol (0.8 g/kg) and three without alcohol. Individuals were assigned randomly to two groups, paired and unpaired, in a 2 : 1 ratio. The paired group (n = 78) received alcohol in one testing room and no‐alcohol in another testing room (biased assignment). The unpaired group (n = 30) received alcohol and no‐alcohol in each testing room.
Setting
Human Behavioral Pharmacology Laboratory, University of Chicago, Chicago, IL, USA (single site).
Participants
Healthy male and female social drinkers (n = 108) aged 21–40 years participated in the study (consisting of 10 separate laboratory visits) between March 2012 and August 2014 (an average of 36 separate subject visits per month).
Measurements
The primary outcome measure was the pre‐ to post‐conditioning change in the percentage of time spent in the least preferred room (obtained during drug‐free exploration tests conducted at separate visits before and after the six conditioning sessions were completed). Secondary measures included self‐reported subjective mood and drug effects obtained during the conditioning sessions.
Findings
The groups differed in the change in the percentage of time spent in the initially least preferred room, from pre‐ to post‐conditioning; paired group = 11.0%, unpaired group = −1.4%, mean difference = 12.4%, 95% confidence interval = 1.9–23.0, P = 0.02. The change in the percentage of time spent in the least‐preferred room was related to the self‐reported sedative effects of alcohol during conditioning sessions among paired group participants only.
Conclusions
Non‐dependent consumers of alcohol appear to develop a behavioral preference for locations paired with alcohol consumption, more so for those who experience sedative effects from alcohol in those locations.
Highlights • We assessed effects of delta-9- tetrahydrocannabinol (THC) on responses to the Trier Social Stress Test (TSST) in healthy volunteers. • THC produced nonlinear dose effects upon emotional ...responses to the TSST. • 7.5 mg THC dampened negative emotional responses without influencing performance. • 12.5 mg THC slightly but significantly increased negative affect overall. • 12.5 mg THC impaired TSST performance and attenuated blood pressure responses.
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