The Acute Effects of a Dopamine D3 Receptor Preferring Agonist on Motivation for Cigarettes in Dependent and Occasional Cigarette Smokers.

This is the final version of the article. Available from OUP via the DOI in this record.Background: Dopaminergic functioning is thought to play critical roles in both motivation and addiction. There is preliminary evidence that dopamine agonists reduce the motivation for cigarettes in smokers. However, the effects of pramipexole, a dopamine D3 receptor preferring agonist, have not been investigated. The aim of this study was to examine the effects of an acute dose of pramipexole on the motivation to earn cigarettes and nondrug rewards. Methods: Twenty dependent and 20 occasional smokers received 0.5 mg pramipexole using a double-blind, placebo-controlled crossover design. Motivation for cigarettes and consummatory nondrug rewards was measured using the DReaM-Choice task, in which participants earned, and later "consumed," cigarettes, music, and chocolate. Demand for cigarettes was measured using the Cigarette Purchase Task (CPT). Self-reported craving, withdrawal, and drug effects were also recorded. Results: Dependent smokers chose (p < .001) and button-pressed for (p < .001) cigarettes more, and chose chocolate less (p < .001), than occasional smokers. Pramipexole did not affect the number of choices for or amount of button-pressing for any reward including cigarettes, which was supported by a Bayesian analysis. The dependent smokers had greater demand for cigarettes than occasional smokers across all CPT outcomes (ps < .021), apart from elasticity. Pramipexole did not affect demand for cigarettes, and this was supported by Bayesian analyses. Pramipexole produced greater subjective "feel drug" and "dislike drug" effects than placebo. Conclusions: Dependent and occasional cigarette smokers differed in their motivation for cigarettes but not for the nondrug rewards. Pramipexole did not acutely alter motivation for cigarettes. These findings question the role of dopamine D3 receptors in cigarette-seeking behavior in dependent and occasional smokers. Implications: This study adds to the growing literature about cigarette versus nondrug reward processing in nicotine dependence and the role of dopamine in cigarette-seeking behavior. Our results suggest nicotine dependence is associated with a hypersensitivity to cigarette rewards but not a hyposensitivity to nondrug rewards. Furthermore, our results question the importance of dopamine D3 receptors in motivational processing of cigarettes in occasional and dependent smokers.This study was funded by BBSRC PhD funding

The effects of cannabidiol on impulsivity and memory during abstinence in cigarette dependent smokers

This is the final version of the article. Available from Springer Nature via the DOI in this record.The dataset generated during the current study are available from the corresponding author on reasonable request.Acute nicotine abstinence in cigarette smokers results in deficits in performance on specific cognitive processes, including working memory and impulsivity which are important in relapse. Cannabidiol (CBD), the non-intoxicating cannabinoid found in cannabis, has shown pro-cognitive effects and preliminary evidence has indicated it can reduce the number of cigarettes smoked in dependent smokers. However, the effects of CBD on cognition have never been tested during acute nicotine withdrawal. The present study therefore aimed to investigate if CBD can improve memory and reduce impulsivity during acute tobacco abstinence. Thirty, non-treatment seeking, dependent, cigarette smokers attended two laboratory-based sessions after overnight abstinence, in which they received either 800 mg oral CBD or placebo (PBO), in a randomised order. Abstinence was biologically verified. Participants were assessed on go/no-go, delay discounting, prose recall and N-back (0-back, 1-back, 2-back) tasks. The effects of CBD on delay discounting, prose recall and the N-back (correct responses, maintenance or manipulation) were null, confirmed by a Bayesian analysis, which found evidence for the null hypothesis. Contrary to our predictions, CBD increased commission errors on the go/no-go task. In conclusion, a single 800 mg dose of CBD does not improve verbal or spatial working memory, or impulsivity during tobacco abstinence.This research was funded by a PhD Studentship from the Medical Research Council (MRC) to the C.H. and an MRC DPFS award (MR/K015524/1) to HVC and CJAM.TPF is funded by a Senior Academic Fellowship from the Society for the Study of Addiction

Recovery after single-breath halothane induction of anaesthesia in daycase patients

A single-breath technique of inhalational induction of anaesthesia allows intravenous induction agents to be avoided. We have investigated recovery from anaesthesia in 40 daycase patients, using tests of psychomotor function. Patients anaesthetised with inhalational induction awaken earlier than those who receive thiopentone, but not significantly earlier. There were no significant differences in postoperative psychomotor function between patients who received thiopentone and those who had inhalational inductions. Single-breath halothane, nitrous-oxide, oxygen induction is an alternative to intravenous induction in cooperative adults, but does not confer significant benefits in terms of recovery.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75757/1/j.1365-2044.1988.tb06685.x.pd

Factors associated with crisis pregnancies in Ireland: Findings from three nationally representative sexual health surveys

Background: Findings on the demographic and sexual health characteristics associated with the experience of a crisis pregnancy is important to inform the public health policy of a country, including Ireland. Findings from other jurisdictions have suggested that certain demographic groups are at risk for unintended pregnancies and the disparity between the groups have been growing in recent years. Ireland is a country which experienced much economic and societal change in the first decade of the 21st century, changes which are likely to have affected demographic variables pertaining to sexual health. The current study had two aims: to investigate changes in the socioeconomic characteristics associated with crisis pregnancies over a seven year period [2003 to 2010], and to investigate the recent [2010] socioeconomic risk factors associated with crisis pregnancies in Ireland. Methods: The study compared the results from 18-45 year old women using data from three broadly similar nationally representative Irish sexual health surveys carried out in 2003, 2004-2006 and 2010. Chi square analysis compared of the socioeconomic characteristics across the seven year period and found that a higher proportion of women with two or more children and women for whom religion was not important reported a crisis pregnancy in 2010 compared with earlier years. A logistic regression then investigated the sexual health history and socioeconomic factors associated with the experience of a recent crisis pregnancy using the most recent 2010 data. Results: Receipt of sex education and contraception use at first sex significantly predicted the experiencing of a recent crisis pregnancy. Younger women and those with a lower level of education were more likely to report having experienced a recent crisis pregnancy. Conclusion: Similar demographic groups are at risk for experiencing a crisis pregnancy in Ireland compared with international research, yet the disparities between demographic groups who have experienced a crisis pregnancy appear to be decreasing rather than increasing over a seven year period. Recommendations are made with regard to the provision of continued sex education throughout the lifespan, particularly for those women who are at an increased risk of experiencing a crisis pregnancy

Which biological and self-report measures of cannabis use predict cannabis dependency and acute psychotic-like effects?

This is the final version. Available from the publisher via the DOI in this record.BACKGROUND: Changes in cannabis regulation globally make it increasingly important to determine what predicts an individual's risk of experiencing adverse drug effects. Relevant studies have used diverse self-report measures of cannabis use, and few include multiple biological measures. Here we aimed to determine which biological and self-report measures of cannabis use predict cannabis dependency and acute psychotic-like symptoms. METHOD: In a naturalistic study, 410 young cannabis users were assessed once when intoxicated with their own cannabis and once when drug-free in counterbalanced order. Biological measures of cannabinoids [(Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN) and their metabolites)] were derived from three samples: each participant's own cannabis (THC, CBD), a sample of their hair (THC, THC-OH, THC-COOH, CBN, CBD) and their urine (THC-COOH/creatinine). Comprehensive self-report measures were also obtained. Self-reported and clinician-rated assessments were taken for cannabis dependency [Severity of Dependence Scale (SDS), DSM-IV-TR] and acute psychotic-like symptoms [Psychotomimetic State Inventory (PSI) and Brief Psychiatric Rating Scale (BPRS)]. RESULTS: Cannabis dependency was positively associated with days per month of cannabis use on both measures, and with urinary THC-COOH/creatinine for the SDS. Acute psychotic-like symptoms were positively associated with age of first cannabis use and negatively with urinary THC-COOH/creatinine; no predictors emerged for BPRS. CONCLUSIONS: Levels of THC exposure are positively associated with both cannabis dependency and tolerance to the acute psychotic-like effects of cannabis. Combining urinary and self-report assessments (use frequency; age first used) enhances the measurement of cannabis use and its association with adverse outcomes

Which biological and self-report measures of cannabis use predict cannabis dependency and acute psychotic-like effects?

BACKGROUND: Changes in cannabis regulation globally make it increasingly important to determine what predicts an individual's risk of experiencing adverse drug effects. Relevant studies have used diverse self-report measures of cannabis use, and few include multiple biological measures. Here we aimed to determine which biological and self-report measures of cannabis use predict cannabis dependency and acute psychotic-like symptoms. METHOD: In a naturalistic study, 410 young cannabis users were assessed once when intoxicated with their own cannabis and once when drug-free in counterbalanced order. Biological measures of cannabinoids [(Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN) and their metabolites)] were derived from three samples: each participant's own cannabis (THC, CBD), a sample of their hair (THC, THC-OH, THC-COOH, CBN, CBD) and their urine (THC-COOH/creatinine). Comprehensive self-report measures were also obtained. Self-reported and clinician-rated assessments were taken for cannabis dependency [Severity of Dependence Scale (SDS), DSM-IV-TR] and acute psychotic-like symptoms [Psychotomimetic State Inventory (PSI) and Brief Psychiatric Rating Scale (BPRS)]. RESULTS: Cannabis dependency was positively associated with days per month of cannabis use on both measures, and with urinary THC-COOH/creatinine for the SDS. Acute psychotic-like symptoms were positively associated with age of first cannabis use and negatively with urinary THC-COOH/creatinine; no predictors emerged for BPRS. CONCLUSIONS: Levels of THC exposure are positively associated with both cannabis dependency and tolerance to the acute psychotic-like effects of cannabis. Combining urinary and self-report assessments (use frequency; age first used) enhances the measurement of cannabis use and its association with adverse outcomes

Cross-polarized photon-pair generation and bi-chromatically pumped optical parametric oscillation on a chip

Nonlinear optical processes are one of the most important tools in modern optics with a broad spectrum of applications in, for example, frequency conversion, spectroscopy, signal processing and quantum optics. For practical and ultimately widespread implementation, on-chip devices compatible with electronic integrated circuit technology offer great advantages in terms of low cost, small footprint, high performance and low energy consumption. While many on-chip key components have been realized, to date polarization has not been fully exploited as a degree of freedom for integrated nonlinear devices. In particular, frequency conversion based on orthogonally polarized beams has not yet been demonstrated on chip. Here we show frequency mixing between orthogonal polarization modes in a compact integrated microring resonator and demonstrate a bi-chromatically pumped optical parametric oscillator. Operating the device above and below threshold, we directly generate orthogonally polarized beams, as well as photon pairs, respectively, that can find applications, for example, in optical communication and quantum optics

Acute and chronic effects of cannabinoids on effort-related decision-making and reward learning: an evaluation of the cannabis 'amotivational' hypotheses

Rationale: Anecdotally, both acute and chronic cannabis use have been associated with apathy, amotivation, and other reward processing deficits. To date, empirical support for these effects is limited, and no previous studies have assessed both acute effects of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as associations with cannabis dependence. Objectives: The objectives of this study were (1) to examine acute effects of cannabis with CBD (Cann + CBD) and without CBD (Cann-CBD) on effort-related decision-making and (2) to examine associations between cannabis dependence, effort-related decision-making and reward learning. Methods: In study 1, 17 participants each received three acute vaporized treatments, namely Cann-CBD (8 mg THC), Cann + CBD (8 mg THC + 10 mg CBD) and matched placebo, followed by a 50 % dose top-up 1.5 h later, and completed the Effort Expenditure for Rewards Task (EEfRT). In study 2, 20 cannabis-dependent participants were compared with 20 non-dependent, drug-using control participants on the EEfRT and the Probabilistic Reward Task (PRT) in a non-intoxicated state. Results: Cann-CBD reduced the likelihood of high-effort choices relative to placebo (p = 0.042) and increased sensitivity to expected value compared to both placebo (p = 0.014) and Cann + CBD (p = 0.006). The cannabis-dependent and control groups did not differ on the EEfRT. However, the cannabis-dependent group exhibited a weaker response bias than the control group on the PRT (p = 0.007). Conclusions: Cannabis acutely induced a transient amotivational state and CBD influenced the effects of THC on expected value. In contrast, cannabis dependence was associated with preserved motivation alongside impaired reward learning, although confounding factors, including depression, cannot be disregarded. This is the first well powered, fully controlled study to objectively demonstrate the acute amotivational effects of THC

Acute effects of delta-9-tetrahydrocannabinol, cannabidiol and their combination on facial emotion recognition: A randomised, double-blind, placebo-controlled study in cannabis users

Acute administration of the primary psychoactive constituent of cannabis, Δ-9-tetrahydrocannabinol (THC), impairs human facial affect recognition, implicating the endocannabinoid system in emotional processing. Another main constituent of cannabis, cannabidiol (CBD), has seemingly opposite functional effects on the brain. This study aimed to determine the effects of THC and CBD, both alone and in combination on emotional facial affect recognition. 48 volunteers, selected for high and low frequency of cannabis use and schizotypy, were administered, THC (8 mg), CBD (16 mg), THC+CBD (8 mg+16 mg) and placebo, by inhalation, in a 4-way, double-blind, placebo-controlled crossover design. They completed an emotional facial affect recognition task including fearful, angry, happy, sad, surprise and disgust faces varying in intensity from 20% to 100%. A visual analogue scale (VAS) of feeling ‘stoned’ was also completed. In comparison to placebo, CBD improved emotional facial affect recognition at 60% emotional intensity; THC was detrimental to the recognition of ambiguous faces of 40% intensity. The combination of THC+CBD produced no impairment. Relative to placebo, both THC alone and combined THC+CBD equally increased feelings of being ‘stoned’. CBD did not influence feelings of ‘stoned’. No effects of frequency of use or schizotypy were found. In conclusion, CBD improves recognition of emotional facial affect and attenuates the impairment induced by THC. This is the first human study examining the effects of different cannabinoids on emotional processing. It provides preliminary evidence that different pharmacological agents acting upon the endocannabinoid system can both improve and impair recognition of emotional faces

Polar vortex formation in giant-planet atmospheres due to moist convection

A strong cyclonic vortex has been observed on each of Saturn’s poles, coincident with a local maximum in observed tropospheric temperature. Neptune also exhibits a relatively warm, although much more transient, region on its south pole. Whether similar features exist on Jupiter will be resolved by the 2016 Juno mission. Energetic, small-scale storm-like features that originate from the water-cloud level or lower have been observed on each of the giant planets and attributed to moist convection, suggesting that these storms play a significant role in global heat transfer from the hot interior to space. Nevertheless, the creation and maintenance of Saturn’s polar vortices, and their presence or absence on the other giant planets, are not understood. Here we use simulations with a shallow-water model to show that storm generation, driven by moist convection, can create a strong polar cyclone throughout the depth of a planet’s troposphere. We find that the type of shallow polar flow that occurs on a giant planet can be described by the size ratio of small eddies to the planetary radius and the energy density of its atmosphere due to latent heating from moist convection. We suggest that the observed difference in these parameters between Saturn and Jupiter may preclude a Jovian polar cyclone.National Science Foundation (U.S.). Graduate Research FellowshipNational Science Foundation (U.S.) (ATM-0850639)National Science Foundation (U.S.) (AGS-1032244)National Science Foundation (U.S.) (AGS-1136480)United States. Office of Naval Research (N00014-14-1-0062