Dopamine, urges to smoke, and the relative salience of drug versus non-drug reward

When addicted individuals are exposed to drug-related stimuli, dopamine release is thought to mediate incentive salience attribution, increasing attentional bias, craving and drug seeking. It is unclear whether dopamine acts specifically on drug cues versus other rewards, and if these effects correspond with craving and other forms of cognitive bias. Here, we administered the dopamine D 2 /D 3 agonist pramipexole (0.5 mg) to 16 tobacco smokers in a double-blind placebo-controlled crossover design. Visual fixations on smoking and money images were recorded alongside smoking urges and fluency tasks. Pramipexole attenuated a marked bias in initial orienting towards smoking relative to money but did not alter a maintained attentional bias towards smoking. Pramipexole decreased urges to smoke retrospectively after the task but not on a state scale. Fewer smoking words were generated after pramipexole but phonological and semantic fluency were preserved. Although these treatment effects did not correlate with each other, changes in initial orienting towards smoking and money were inversely related to baseline scores. In conclusion, pramipexole can reduce the salience of an addictive drug compared with other rewards and elicit corresponding changes in smoking urges and cognitive bias. These reward-specific and baseline-dependent effects support an ‘inverted-U’ shaped profile of dopamine in addiction

A comparison of emotion regulation strategies in response to craving cognitions: Effects on smoking behaviour, craving and affect in dependent smokers

AIM: The effects of three emotion regulation strategies that targeted smoking-related thoughts were compared on outcomes relevant to smoking cessation. METHOD: Daily smokers applied defusion (n = 25), reappraisal (n = 25) or suppression (n = 23) to thoughts associated with smoking during a cue-induced craving procedure. Smoking behaviour, approach/avoidance behavioural bias, and subjective measures of experiential avoidance, craving, and affect were assessed during the experimental session, with additional behavioural and subjective outcomes assessed at 24 h and seven day follow-up. The influence of baseline group differences in smoking level and nicotine dependence were explored statistically. RESULTS: Defusion and reappraisal were associated with greater restraint in smoking behaviour in the immediate post-session period as well as reduction in smoking at seven day follow-up compared to suppression. Relative to suppression, reduced subjective craving was seen in the reappraisal group, and reduced experiential avoidance in the defusion group. Differences in approach/avoidance responses to smoking and neutral cues were observed only between the suppression and reappraisal groups. Although suppression was rated as lower in both credibility and strategy-expectancy compared to defusion and reappraisal, neither credibility nor expectancy mediated the effect of any strategy on changes in levels of smoking. CONCLUSION: Defusion and reappraisal produced similar benefits in smoking-related behavioural outcomes but, relative to suppression, were associated with distinctive outcomes on experiential avoidance and craving. The effects appear to be independent of perceived expectancy and credibility of the different strategies. Overall, the results suggest a role for reappraisal and defusion strategies in the development of psychological treatments for addiction-related disorders

Nuclear quadrupole resonance as a non-destructive testing tool

Nuclear pure quadrupole resonance (NQR) is a resonance technique that provides distinctly different information from that provided by nuclear magnetic resonance (NMR). In NMR the splitting of the energy levels, and therefore the frequency observed, occurs because of the interaction of the nuclear magnetic moment with an external magnetic field. Information about the system under study comes from perturbations on this magnetic interaction. These perturbations lead to a broadening of the line, or to relaxation effects on the interchange of energy between the spins and the lattice, and among the spins. In NQR the primary interaction is between the electric quadrupole moment of a nucleus and the electric field gradient at that nucleus. The field gradient is provided by internal interactions in the sample itself, arising from the chemical bonds, rather than by an external field. Anything that changes the bonding environment, such as tensile stress, will cause shifts in the quadrupole resonance frequency. All nuclei with spin greater than 1/2 have a nuclear quadrupole moment, in addition to their magnetic moment. The nucleus used as an example in this paper is 75As, which has spin 3/2

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

Grain refinement in a AlZnMgCuTi alloy by intensive melt shearing: A multi-step nucleation mechanism

This is a post-print version of the article. Copyright @ 2010 Elsevier B.V.Direct chill (DC) cast ingots of wrought Al alloys conventionally require the deliberate addition of a grain refiner to provide a uniform as-cast microstructure for the optimisation of both mechanical properties and processability. Grain refiner additions have been in widespread industrial use for more than half a century. Intensive melt shearing can provide grain refinement without the need for a specific grain refiner addition for both magnesium and aluminium based alloys. In this paper we present experimental evidence of the grain refinement in an experimental wrought aluminium alloy achieved by intensive melt shearing in the liquid state prior to solidification. The mechanisms for high shear induced grain refinement are correlated with the evolution of oxides in alloys. The oxides present in liquid aluminium alloys, normally as oxide films and clusters, can be effectively dispersed by intensive shearing and then provide effective sites for the heterogeneous nucleation of Al3Ti phase. As a result, Al3Ti particles with a narrow size distribution and hence improved efficiency as active nucleation sites of alpha-aluminium grains are responsible for the achieved significant grain refinement. This is termed a multi-step nucleation mechanism.Funding was obtained from the EPRSC

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

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

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