Search

Studies conducted in rodents indicate a crucial role of the opioid circuit in mediating objective hedonic reactions to primary rewards. However, it remains unclear whether opioid transmission is also essential to experience pleasure with more abstract rewards, such as music. We addressed this question using a double-blind within-subject pharmacological design in which opioid levels were up- and downregulated by administering an opioid agonist (oxycodone) and antagonist (naltrexone), respectively, before healthy participants (n = 21) listened to music. Participants also performed a monetary incentive delay (MID) task to control for the effectiveness of the treatment and the specificity of the effects. Our results revealed that the pharmacological intervention did not modulate subjective reports of pleasure, nor the occurrence of chills. On the contrary, psychophysiological (objective) measures of emotional arousal, such as skin conductance responses (SCRs), were bidirectionally modulated in both the music and MID tasks. This modulation specifically occurred during reward consumption, with greater pleasure-related SCR following oxycodone than naltrexone. These findings indicate that opioid transmission does not modulate subjective evaluations but rather affects objective reward-related psychophysiological responses. These findings raise new caveats about the role of the opioidergic system in the modulation of pleasure for more abstract or cognitive forms of rewarding experiences, such as music.

Inflammatory bowel disease (IBD) is a chronic health condition exacerbated by negative emotional stress experiences. In the current study, we examined whether the outbreak of the COVID‐19 pandemic coincided with an increase in stress experiences and accordingly an aggravation of disease activity in IBD patients. Sixty‐three IBD patients (30 Crohn's disease or CD, 33 ulcerative colitis) completed an online survey during the COVID‐19‐related lockdown, assessing clinical disease activity, disease‐related quality of life, presence of functional gastrointestinal symptoms, social isolation and stress experiences. Scores were then compared to pre‐lockdown baseline screening. The pandemic yielded a significant baseline‐to‐lockdown increase in emotional stress and social isolation. Stress increments, particularly those occasioned by interpersonal tension and excessive interpersonal proximity, were associated with a worsening of functional gastrointestinal symptoms. Exacerbations of loneliness coincided with an escalation of CD activity, functional gastrointestinal symptoms and a decline in subjective health. Lastly, COVID‐19 anxiety was significantly related to CD symptom severity and social dysfunction. The findings show that shifts in IBD expression are closely linked to changes in emotional stress experiences and interpersonal relatedness. As such, they contribute to a better understanding of inter‐individual differences in IBD progression and provide leads for therapeutic interventions.

Music listening provides one of the most significant abstract rewards for humans because hearing music activates the dopaminergic mesolimbic system. Given the strong link between reward, dopamine, and memory, we aimed here to investigate the hypothesis that dopamine-dependent musical reward can drive memory improvements. Twenty-nine healthy participants of both sexes provided reward ratings of unfamiliar musical excerpts that had to be remembered following a consolidation period under three separate conditions: after the ingestion of a dopaminergic antagonist, a dopaminergic precursor, or a placebo. Linear mixed modeling of the intervention data showed that the effect of reward on memory-i.e., the greater the reward experienced while listening to the musical excerpts, the better the memory recollection performance-was modulated by both dopaminergic signaling and individual differences in reward processing. Greater pleasure was consistently associated with better memory outcomes in participants with high sensitivity to musical reward, but this effect was lost when dopaminergic signaling was disrupted in participants with average or low musical hedonia. Our work highlights the flexibility of the human dopaminergic system, which can enhance memory formation not only through explicit and/or primary reinforcers but also via abstract and aesthetic rewards such as music.

There is widespread belief in the legal system that alcohol impairs witness testimony. Nevertheless, most laboratory studies examining the effects of alcohol on witness testimony suggest that alcohol may affect the number of correct but not incorrect details recalled. However, it is difficult to draw conclusions because sample sizes, testing paradigms, and recall measures vary between individual studies. We conducted a meta-analysis to address this issue. We found alcohol intoxication had a significant and moderate sized effect on the number of correct details recalled (g=0.40). The effect of alcohol on the number of incorrect details recalled was not significant. Further, the effect of alcohol on the recall of correct details was significantly moderated by multiple factors like intoxication level, the retention interval length between encoding and recall, and the types of questions asked (i.e., free recall vs. cued recall). We discuss the applied implications of the results.

Alcohol use is frequently involved in crime, making it crucial to understand the role of alcohol in facial recognition to maximize correct perpetrator identifications. Although the majority of the alcohol and face recognition research has investigated recognition with retrospective confidence judgments, we examined the effects of alcohol intoxication on face recognition with prospective metacognitive judgments. Participants (N=54 university students without a history of hazardous alcohol/substance use) consumed either alcohol (mean breath alcohol concentration of 0.06 at pretest and 0.07 at post-test) or a non-alcoholic placebo drink. Participants then studied unfamiliar male and female faces and made judgments of learning (JOLs) for each face (i.e., predicted the likelihood of recognizing that face on a future memory test). After a brief distractor task, participants completed an old-new recognition test on which they attempted to distinguish the studied faces from new faces. It was found that the alcohol manipulation had minimal effect on face recognition performance or judgments of learning. Our results suggest that theory-based cues about the effects of alcohol might play a greater role in retrospective judgments than prospective judgments. Although not a primary focus of the study, face recognition was better for male faces than female faces, and this occurred for both female and male participants. Limitations and implications of the research are discussed.

AIMS: The present study assessed the acute effects of methadone and buprenorphine on actual on-road driving performance and neurocognitive function.METHODS: Methadone (5 and 10 mg per oral) and buprenorphine (0.2 and 0.4 mg sublingual) were administered to 22 healthy volunteers in a five-way, double-blind, randomized, placebo-controlled, double-dummy, cross-over study. Driving performance was assessed with an on-road driving test. The primary outcome measure was standard deviation of lateral position (SDLP), a measure of road tracking control. Laboratory tests were used to measure cognitive function (e.g. reaction time and attention) and questionnaires were used to assess subjective measures of mood and sedation.RESULTS: There was no significant main effect of treatment on SDLP. Yet, analysis of individual drug-placebo contrast data revealed that buprenorphine 0.4 mg significantly increased SDLP. Driving impairment was mild and below the impairment threshold of a blood alcohol concentration of 0.5 mg ml-1. Four participants stopped their driving test while under the influence of either opioid due to sleepiness. Both opioids produced impairments of cognitive task performance and increased sleepiness particularly at the highest dose.CONCLUSIONS: Analgesic doses of buprenorphine produced mild impairing effects on driving and related cognitive skills, while methadone impaired cognitive task performance but not driving performance. Large individual variations were observed for both drugs. Patients should be informed about the possibility of driving impairment when initiating opioid treatment.

Sleep and physical activity are both modifiable behavioural factors that are associated with better health and are potentially related. Following traumatic brain injury, damage to the brain caused by an external force, sleep disturbances are common. Exploring bidirectional relationships between sleep and physical activity might provide insight into whether increasing physical activity could decrease these sleep disturbances. The current study, therefore, examined inter‐ and intra‐individual temporal associations between sleep and daytime physical activity in 64 people with traumatic brain injury reporting sleep problems or fatigue (47 males; mean age, 40 years). Sleep and physical activity were measured using actigraphy with corroborating sleep diaries over 14 consecutive days. Multilevel models were used to examine inter‐ and intra‐individual associations between physical activity and sleep. Inter‐individual variations showed that earlier bedtimes, earlier wake‐up times and lower sleep efficiency were associated with more physical activity. Intra‐individual temporal variations showed no significant association of daytime physical activity with sleep duration or continuity. However, shorter sleep time and less wake after sleep onset than usual were associated with more time spent in light‐intensity activity the next day. Therefore, sleep may have more of an influence on physical activity than physical activity has on sleep in people with traumatic brain injury. In conclusion, the results do not confirm a potential beneficial effect of physical activity on sleep but suggest that improving sleep quality might be relevant to support of a physically active lifestyle in people with traumatic brain injury. Further research is necessary to confirm these results.

Using the Belgian Drugs and Driving procedure, 36% of the cocaine-positive oral fluid (OF) screening results were not confirmed in plasma. This study investigates the impact of the choice of screening devices and confirmation matrix on the detection of cocaine use. An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method quantifying cocaine, benzoylecgonine (BZE), and other basic drugs in OF was developed and validated. This method monitored OF samples obtained either from a roadside (n = 12) or a double-blind controlled study with cocaine users (n = 10) who were given either a capsule containing 300 mg of cocaine-HCl or a placebo. The OF data were compared to plasma concentrations to obtain concentration-time profiles. In addition, the sensitivity and accuracy of the Drugwipe5S® was assessed. A significant difference between the OF volume collected at baseline/placebo (median 0.93 mL [range 0.43-1.92 mL]) or after cocaine-HCL intake (0.79 mL [0.30-1.21 mL]) was observed. The median OF/Plasma at the 3 collection time points were 10.7, 13.8, 6.7 for cocaine and 0.8, 1.7, 0.8 for BZE, respectively. The Drugwipe5S® detected cocaine use until at least 4 hours after intake. When applying the Belgian legal confirmation decision limit of 10 ng/mL in OF, an accuracy of 75%-98% was observed, depending on the study setting. Cocaine concentrations in OF were much higher and were detected longer as compared to plasma, when applying the same decision limit. From a toxicological viewpoint, the longer detection window with the higher sensitivity of Cocaine and BZE is beneficial to detect drivers in the crash/fatigue phase.

OBJECTIVES: 4-Fluoroamphetamine (4-FA) is a novel psychoactive substance with a pharmacological profile and reported subjective effects (e.g., empathy) intermediate between 3,4-methylenedioxymethamphetamine (MDMA) and amphetamine. Studies have shown that MDMA and amphetamine increase emotional empathy without affecting cognitive empathy; MDMA simultaneously leads to elevated levels of oxytocin, unrelated to its behavioral effects. The aim of the present study was to assess the reported enhancement of empathy by 4-FA, to assess its effects on oxytocin, and to test potential associations between both.METHODS: Twelve healthy poly-drug users were included in a double-blind placebo-controlled two-way crossover study. Treatments were 4-FA (100 mg) and placebo; empathy was assessed by means of the multifaceted empathy test, and blood samples were taken before and after treatment administration to determine oxytocin concentrations.RESULTS: 4-FA reduced cognitive empathy, whereas emotional empathy was left unaffected. One hour after treatment, plasma oxytocin levels were significantly increased compared with placebo. Behavioral and hormonal effects were unrelated.CONCLUSION: Although 4-FA shares its pharmacological mechanism with MDMA and amphetamine, current findings seem to indicate that it affects empathy differently. The 4-FA-induced increase in oxytocin levels was independent of behavioral effects, which confirms previous findings that drug-induced effects on peripheral oxytocin levels are not associated with empathy.

Summary Background Allergic rhinitis (AR) reduces quality of life as a result of impaired psychological well-being and perceived impaired cognitive functioning. Few studies have measured cognitive functions objectively and it remains uncertain whether AR leads to an objective reduction in cognitive functions. Objective The present study investigated whether AR is associated with a decrement in several aspects of cognitive functioning. Furthermore, the study investigated whether AR patients invest more ‘mental effort’ in order to achieve the same cognitive performances as healthy controls. Methods Twenty five patients with seasonal allergic rhinitis (SAR) and 26 healthy controls, matched for age, education and sex, were tested on a battery of time-demanding and strenuous objective cognitive tests and subjective questionnaires, both before and after nasal provocation (NP). The cognitive functions assessed were sustained attention, short- and long-term memory and speed of information processing. Mental effort was assessed using visual rating scales. Results Sustained but not short cognitive performance was impaired in patients after NP. Patients showed an increased effort on short cognitive tests. Conclusion SAR patients suffer from cognitive performance decrements that can be compensated by additional mental effort for short tasks only.

Objective Memory complaints in the absence of objective test impairments are common. Only a subset of these subjects seeks medical attention for these complaints. The aim of the present study was to investigate which factors determine why people with subjective memory complaints (SMC) seek medical attention. Methods Thirty-three cases with SMC from a memory clinic were compared to 85 control subjects with SMC from a population-based study who did not seek help for their complaints. We investigated whether cases differed from controls with respect to the following: depressive and anxiety symptoms (SCL-90), extraversion and neuroticism (EPQ), meta-memory (MIA), quality of life (SF-36), changes in memory and daily functioning according to a relative (DECO), life-changing events, and a family history of dementia. Results Cases with SMC who seek medical attention, scored lower on memory self-efficacy and quality of life. They were more often worried due to a positive family history of dementia by comparison to the control subjects. Relatives of cases reported more deterioration in daily functioning than relatives of controls. Both the cases and control subjects had similar levels of depressive and anxiety symptoms, as well as levels of extraversion and neuroticism. Conclusion Lower memory self-efficacy and quality of life, deterioration in daily functioning, and worries due to a positive family history for dementia are factors that determine why subjects with SMC seek medical attention. This information may be useful for the development of interventions for these subjects. Copyright © 2008 John Wiley & Sons, Ltd.

Objective Development of a rational and enforceable basis for controlling the impact of cannabis use on traffic safety. Methods An international working group of experts on issues related to drug use and traffic safety evaluated evidence from experimental and epidemiological research and discussed potential approaches to developing per se limits for cannabis. Results In analogy to alcohol, finite (non-zero) per se limits for delta-9-tetrahydrocannabinol (THC) in blood appear to be the most effective approach to separating drivers who are impaired by cannabis use from those who are no longer under the influence. Limited epidemiological studies indicate that serum concentrations of THC below 10 ng/ml are not associated with an elevated accident risk. A comparison of meta-analyses of experimental studies on the impairment of driving-relevant skills by alcohol or cannabis suggests that a THC concentration in the serum of 7-10 ng/ml is correlated with an impairment comparable to that caused by a blood alcohol concentration (BAC) of 0.05%. Thus, a suitable numerical limit for THC in serum may fall in that range. Conclusions This analysis offers an empirical basis for a per se limit for THC that allows identification of drivers impaired by cannabis. The limited epidemiological data render this limit preliminary.

Objectives Effects of escitalopram 10-20 mg/day and mirtazapine 30-45 mg/day on verbal memory of 18 healthy participants were assessed in a randomized, double-blind, placebo-controlled, three-way crossover trial. Method Each treatment period lasted for 15 days and was separated from the next period by a washout period of at least 13 days. Participants received an evening dose of escitalopram 10 mg, mirtazapine 30 mg, or placebo from days 1 to 7 and an evening dose of escitalopram 20 mg, mirtazapine 45 mg, or placebo from days 8 to 15. On days 2, 9, and 16 a visual verbal memory task was performed measuring drug effects during the acute phase, after dose increase and at steady state. Results Escitalopram did not affect immediate or delayed verbal memory score throughout treatment. During mirtazapine treatment, participants performed less well in the overall immediate recall score compared to placebo. This impairment was most pronounced in the final trial of the visual verbal learning task. Conclusion Verbal memory was not affected by acute and subchronic escitalopram treatment in healthy participants. Overall immediate verbal memory was slightly but significantly impaired throughout mirtazapine treatment, probably due to a general reduction in overall arousal caused by H1 blockade.

BACKGROUND: Mequitazine is a so-called 'non-sedative' second-generation antihistamine even though it has never been firmly established that this drug's sedative potential actually differs from that of the 'sedative' first-generation antihistamines. OBJECTIVE: The present study compares the sedative effects of three doses of mequitazine on actual driving, psychomotor performance and memory with those of a first- and a second-generation antihistamine. METHODS: Eighteen healthy volunteers received on separate days a single dose of 5, 10 and 15 mg mequitazine, 10 mg cetirizine, 6 mg dexchlorpheniramine and placebo. Drug effects were assessed using two actual driving tests (highway-driving test and car-following test), cognitive and psychometric tests (tracking, divided attention, memory, reasoning and critical flicker fusion), pupil size and questionnaires. RESULTS: Highway-driving data revealed an overall effect of Treatment on the standard deviation of lateral position (SDLP). Dexchlorpheniramine impaired driving performance as indicated by a significant rise in SDLP. Mequitazine significantly increased SDLP in a dose-related manner, but the separate dose effects failed to reach statistical significance. Divided attention performance was also affected by Treatment. Reaction time (RT) during mequitazine treatments increased in a dose-related manner and significantly differed from placebo at the highest dose. Subjects reported to be less alert after treatment with dexchlorpheniramine. Cetirizine did not affect performance in any of the tasks. CONCLUSION: It was concluded that mequitazine is mildly sedating. The effects of mequitazine are comparable to those of other second-generation antihistamines, in that it causes mild driving impairment, particularly at higher doses. Language: en