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Prescription opioid misuse is an unintended consequence of acute pain management. Opioid-induced euphoria (OIE) with first therapeutic opioid exposure may influence opioid misuse. OIE is not assessed in clinical care and self-report measures of OIE have not been validated in adolescents. We (1) determined adolescents' ability to understand existing self-reported OIE measures, (2) revised measures for better understanding by this population, and (3) established initial content validity of revised measures with adolescents. Using runner's euphoria to simulate OIE in Study 1, 29 adolescents' (14 males) understanding of the Drug Effects Questionnaire (DEQ-5), the Addiction Resource Center Inventory Morphine Benzedrine Group scale (ARCI-MBG), and the ARCI Lysergic Acid Diethylamide scale (ARCI-LSD) were tested. In Study 2, 29 additional adolescents (9 males) participated in a modified Delphi study with focus groups to revise survey items to improve understanding by peers. In Study 1, runners understood40% of ARCI-MBG and ARCI-LSD statements. In Study 2, all but 7 survey items were revised. Revised measures of OIE for adolescents may help define at-risk OIE phenotypes and validate risk assessments using survey methodology. Additional studies are needed to validate the revised OIE self-report measures with opioid-naive adolescents receiving opioids to treat acute pain.

Background:Encephalitis due to anti-N-methyl-D-aspartate receptor antibodies (ANMDARE) is the most frequent immune-mediated encephalitis. It is distinguished by the subacute onset of neuropsychiatric symptoms.Objective:To evaluate the characteristic neuropsychiatric symptoms and their outcome in patients diagnosed with ANMDARE.Methods:This was a prospective, longitudinal study in patients with a diagnostic suspicion of ANMDARE that presented to the National Institute of Neurology from March 2018 to February 2019. A comparative analysis of two groups (positive N-methyl-D-aspartate receptor [NMDAR] vs. negative NMDAR antibodies in cerebrospinal fluid [CSF]) was done on admission and at discharge. Neuropsychiatric systematic assessments included the Neuropsychiatric Inventory Questionnaire, the Bush Francis Catatonia Rating Scale, the Confusion Assessment Method Severity, the Montreal Cognitive Assessment, and the Overt Agitation Severity Scale.Results:24 individuals were analysed: 14 had positive NMDAR antibodies, and 10 had negative NMDAR antibodies in CSF. On admission, agitation/aggression, euphoria/exaltation, and disinhibition were more common in patients with positive antibodies. Excited catatonia and delirium were diagnosed more frequently in patients with positive antibodies. At discharge, there was an important decrease in neuropsychiatric symptoms, but substantial cognitive impairment remained. The mean hospitalisation length was 41.71 (SD 39.33) days for patients with definitive ANMDARE (p 0.259).Conclusions:Neuropsychiatric symptoms profile in ANMDARE was associated with the early onset of euphoria/exaltation and disinhibition, accompanied by marked psychomotor agitation. When ANMDARE was suspected, the presence of excited-type catatonia and delirium showed a tendency to predict definitive ANMDARE. At discharged, most patients recovered from catatonia, delirium, and psychosis, but marked cognitive symptoms, anxiety, and depression persisted at discharge.

Background Mania is a state of elated or irritable mood characterizing Bipolar Disorder type I (BD-I). Among the pharmacological treatments for the management of mania, mood stabilizers are regularly employed, with valproate being one of the most used because of its effectiveness. However, while the oral formulation is approved for acute mania, it is unclear whether the intravenous (IV) formulation could be a valid and safe alternative. Methods We performed a bibliographic research on PUBMED of all studies investigating the use of IV valproate as a treatment of acute mania in BD-I. A total of 13 studies met our inclusion criteria. Results Overall, the results suggest that IV valproate as a loading therapy is an efficacious, safe and well tolerated treatment for manic episodes, and it is comparable to the oral loading regimen. Interestingly, only a few patients experienced significant side effects due to the administration of the IV valproate. Limitations Few open label clinical trials have explored the effect of IV valproate in manic patients. Moreover, the original studies employed different clinical assessments and included manic patients taking other drugs, which made it impossible to determine whether the resolution of symptoms was due to valproate therapy alone. Additionally, serum valproate levels were not assessed by all studies. Conclusions IV valproate may represent a valid option for the management of acute mania, with comparable effects in terms of efficacy and safety to the oral valproate. However, larger and more homogeneous studies are warranted in order to collect more precise information on the beneficial effect of IV valproate.

For the first time, an ecstatic aura has been evoked through the electrical stimulation of the dorsal anterior insula during presurgical invasive intracerebral monitoring in a patient who did not suffer from an ecstatic form of epilepsy. This case provides more evidence that the anterior insula is the major generator of such a mystical-type experience even in individuals with no underlying brain network changes related to a preexisting ecstatic epilepsy. ANN NEUROL 2022;91:289-292.

This case report describes the ethical implications of paradoxical lucidity in persons with severe stage dementia. Paradoxical lucidity describes an episode of unexpected communication or connectedness in a person who is believed to be noncommunicative due to a progressive and pathological process that causes dementia. A caregiver who witnesses an event of paradoxical lucidity may experience it as ethically and emotionally transformative. We provide an ethical framework for addressing this event in clinical practice. The framework addresses clinician interactions with the patient, caregiver, and family to improve understanding of paradoxical lucidity and to enhance patient care, caregiver well-being, and decision-making. Participants for this case study consented to having the case published. Participant names are changed to protect confidentiality.

Experiences of childhood trauma (abuse and neglect) are disproportionately higher in those with opioid use disorder (OUD). Childhood trauma may affect the reinforcing and rewarding properties of opioid drugs and responses to pain, potentially via developmental changes to the endogenous opioid system. This has been supported by preclinical research, yet this has not been investigated in non-addicted humans. Physically healthy participants with either a history of severe childhood trauma or no previous history of childhood trauma attended two sessions where they received either an intramuscular active dose of morphine (0.15 mg/kg) or a very low dose control (0.01 mg/kg) in a randomised, double-blind crossover design. Sessions were held 1 week apart. Participants' physical pain threshold and tolerance were measured pre- and post-drug administration using the cold water pressor test, alongside acute subjective and behavioural responses over 2.5 h. The trauma group reported liking the effects of morphine, feeling more euphoric and wanting more of the drug over the session, as well as feeling less nauseous, dizzy, and dislike of the effects of morphine compared to the non-trauma comparison group. Morphine increased pain threshold and tolerance, yet this did not differ between the groups. Childhood trauma may therefore sensitise individuals to the pleasurable and motivational effects of opioids and reduce sensitivity to the negative effects, providing compelling evidence for individual differences in opioid reward sensitivity. This may explain the link between childhood trauma and vulnerability to OUD, with consequent implications on interventions for OUD, the prescribing of opioids, and reducing stigmas surrounding OUD.

BACKGROUND: Unhealthy substance use is a public health challenge. Much of the focus of interventions is upon narcotics, stimulants, hallucinogens, central nervous system depressants, and alcohol. However, inhalants are also commonly used in an unhealthy manner and are under-recognized. The purpose of this study is to describe incident emergency department visits for volatile substance use to induce euphoria (VSUIE) injuries in the U.S. METHODS: Data were obtained from the National Electronic Injury Surveillance System (NEISS) for the years 2015 to 2018. Descriptive frequencies, bivariate analyses using Rao-Scott Chi-Square, and multivariable logistic regression analyses were conducted to describe and examine the association between ED visits and VSUIE. RESULTS: The estimated (weighted) number of VSUIE ED visits during 2015–2018 was 13,130 (95% Confidence Interval, CI: 8,383–17876; Coefficient of variation, CV = 0.18) and accounted for 0.02% of all ED visits. Males were more likely than females (p < .0001), and young adults (ages ≥18 to ≤ 35 years) were more likely than older adults to have a VSUIE ED visit (p

Objectives: Nonpharmacological options to treat pain are in demand, in part to address the opioid crisis. One such option is acupuncture. Battlefield acupuncture (BFA) is an auricular needling protocol currently used to treat pain in the Veterans Health Administration. We aimed to identify the advantages and disadvantages of BFA from providers’ perspectives. Methods: We rely on an inductive qualitative approach to explore provider perceptions through thematic analysis of semistructured interviews with 43 BFA providers across the nation. Results: We identified the following themes. Disadvantages included: (1) clinical guidelines are insufficient; (2) patients often request multiple BFA visits from providers; (3) BFA can be uncomfortable; (4) BFA may not be an effective treatment option unless it can be provided “on demand”; and (5) BFA can promote euphoria, which can have deleterious consequences for patient self-care. Perceived advantages included: (1) BFA can simultaneously effectively control pain while reducing opioid use; (2) BFA may alleviate the pain that has been unsuccessfully treated by conventional methods; (3) BFA gives providers a treatment option to offer patients with substance use disorder; (4) BFA helps build a trusting patient-provider relationship; (5) BFA can create the opportunity for hope. Conclusions: Providers perceive BFA to have many benefits, both clinical and relational, including ways in which it may have utility in addressing the current opioid crisis. BFA is easy to deliver and has potential clinical and relational utility. Efforts to better understand effectiveness are warranted.

BACKGROUND: Few studies have examined how Δ9-Tetrahydrocannabinol (THC), the main psychoactive component of cannabis, impacts brain reward circuitry in humans. In this study, we examined if an acute dose of THC altered resting state functional connectivity between the striatum and prefrontal cortex among healthy young adults with limited cannabis use. METHODS: Participants received THC (n=24) or placebo (n=22) in a double-blind, randomized, between-subject design. Participants completed self-report measures of euphoria and drug-liking throughout the visit. Approximately 120 minutes after drug administration, participants completed an 8-minute resting state functional MRI (rs-fMRI) scan. We utilized seed-based connectivity of the striatum (bilateral putamen, caudate, and NAcc seeds) to the frontal cortex. RESULTS: Individuals who received THC demonstrated greater rs-fMRI connectivity between the right NAcc and regions of the medial prefrontal cortex (mPFC) (p-values

Background Heroin dependence is a complex disease with multiple phenotypes. Classification of heroin users into more homogeneous subgroups on the basis of these phenotypes could help to identify the involved genetic factors and precise treatments. This study aimed to identify the association between genetic polymorphisms of DA synthesis and metabolism genes, including tyrosine hydroxylase (TH), DOPA decarboxylase (DDC), solute carrier family 6 member 3 (SLC6A3) and DA beta-hydroxylase (DBH), with six important phenotypes of heroin dependence. Methods A total of 801 heroin dependent patients were recruited and fourteen potential functional single nucleotide polymorphisms (SNPs) were genotyped by SNaPshot. Associations between SNPs with six phenotypes were mainly assessed by binary logistic regression. Generalized multifactor dimensionality reduction was used to analyze the gene-by-gene and gene-by-environment interactions. Results We found that DBH rs1611114 TT genotype had a protective effect on memory impairment after heroin dependence (P = 0.002, OR = 0.610). We also found that the income-rs12666409-rs129915-rs1611114 interaction yielded the highest testing balance accuracy and cross-validation consistency for memory change after heroin dependence. Conclusions Our results suggest that the memory change after heroin dependence was a result of a combination of genetics and environment. This finding could lead to a better understanding of heroin dependence and further improve personalized treatment.

Animal studies and anecdotal human reports suggest that cannabinoids have antinociceptive effects. Controlled human studies have produced mixed results. We sought to reduce existing variability by investigating the effects of intravenous delta-9-tetrahydrocannabinol (THC) in several pain paradigms within the same human subjects, addressing some of the limitations to the published literature. In this exploratory randomized, double-blind, placebo-controlled, cross-over study, healthy human subjects received 0.01 mg/kg or 0.03 mg/kg intravenous THC or placebo (ethanol vehicle) infused over 10 min on three test days, each separated by at least 72 h. Capsaicin (250 μg) was injected intradermally to induce chemical pain and hyperalgesia. Four other forms of acute pain were induced: mechanical (von Frey filament), hot and cold (thermode), and electrical (pulse generator). Pain ratings were obtained before drug administration, at peak drug effects, and 2 h after drug administration and included both objective and subjective measures. THC drug effects and vital signs were also collected during experimental sessions. Nonparametric analysis with repeated measures was performed. THC induced euphoria, perceptual and cognitive alterations, and tachycardia in a dose-related manner, but failed to have significant effects in experimentally induced acute chemical, mechanical, thermal, or electrical pain and capsaicin-induced hyperalgesia. In this exploratory controlled study, intravenous THC lacked significant antinociceptive properties in experimental models of acute pain and capsaicin-induced hyperalgesia in healthy human subjects. Continued study of THC and other cannabinoids through high-quality, controlled studies in both healthy volunteers and patients with pain conditions is warranted to inform the growing demand for the clinical application of cannabinoids in pain management.

Objective: The aims of this study were (1) to investigate the relationship between different neuropsychiatric symptoms (NPS) and the level of distress experienced by nurses caring for residents with young-onset dementia (YOD) and (2) to compare these findings with those for nurses caring for residents with late-onset dementia (LOD). Design/Setting: This is a retrospective study conducted in Dutch long-term care facilities. Data were used from the Behavior and Evolution of Young-ONset Dementia studies (BEYOND) Parts I and II and the WAAL Behavior in Dementia-II (Waalbed-II) study. Participants: A total of 382 nursing home residents with YOD and 261 nursing home residents with LOD were included. Measurements: The Neuropsychiatric Inventory, nursing home version, was used to assess nursing staff distress and the frequency (F) and severity (S) of NPS. Multilevel logistic regression analysis was used to investigate the relationships between nursing staff distress related to NPS and YOD and LOD care units, the F x S score per symptom, gender, dementia subtype, and dementia severity. Results: Nurses working in YOD care units rated sleep and nighttime behavior disorders, delusions, and agitation/aggression most often as highly distressing and euphoria most often as not distressing. Multivariate analyses indicated that the frequency and severity of NPS were significantly associated with staff distress in all symptoms, except for apathy. Comparison of the 2 groups of nurses demonstrated that the odds for distress related to sleep and nighttime behavior disorders were higher for nurses in YOD care units than for nurses in LOD units. For both the YOD and LOD nurses, irritability in male residents had higher impact than similar behavior in female residents. Conclusion: This study provides important insight into distress related to individual NPS and the interaction with residents' characteristics. All NPS result in distress. The frequency and severity of the behavior is an important predictor. Sleep and nighttime behavior disorders are more likely to result in distress in YOD nurses than in LOD nurses. The amount of distress related to NPS emphasizes the urgent need for adequate management of NPS and the support of professional caregivers. (C) 2017 AMDA - The Society for Post-Acute and Long-Term Care Medicine.

Objective: To compare the subjective effects of oxymorphone extended release (OM-ER ) versus oxycodone controlled release (OC-CR ).Design: Randomized, double-blind, crossover study.Setting: Inpatient unit.Subjects: Healthy, nondependent recreational opioid users.Interventions: Single intact oral tablets that were placebo or contained OM-ER (15 and 30 mg) or OC-CR (30 and 60 mg). Doses were representative of mid-range doses for chronic pain and were calculated using an established opioid conversion table.Main outcome measures: Visual Analog Scales, Subjective Drug Value (SDV), and Addiction Research Center Inventory (ARCI) measured positive, negative, and balance effects and pupillometry. Equianalgesic comparisons were between OM-ER 15 mg versus OC-CR 30 mg (low doses) and OM-ER 30 mg versus OC-CR 60 mg (high doses).Results: Thirty-five subjects received all five treatments. Positive subjective effects were lower for OM-ER 15 mg versus OC-CR 30 mg and for OM-ER 30 mg versus OC-CR 60 mg in ARCI Morphine Benzedrine Group (p ≤ 0.01 for both), Good Effects (p < 0.001 for both), Rush (p < 0.001 for both), and High VAS (p < 0.001 for both). Nausea was higher with OC-CR (p ≤ 0.02), and Bad Effects were higher for OC-CR 60 mg versus OM-ER 30 mg (p < 0.001). Balance effects were lower for OM-ER versus OC-CR (Drug Liking, p < 0.001; Overall Drug Liking, p ≤ 0.006; SDV, p ≤ 0.008), except for Take Drug Again (p < 0.001 for OC-CR 30 mg versus OM-ER 15 mg; p = 0.18 for high-dose group). Euphoric mood, nausea, somnolence, vomiting, and dizziness were more common with OC-CR than OM-ER.Limitations: Single-dose design; use of healthy, recreational opioid users.Conclusions: At equianalgesic doses, single oral intact OM-ER produced lower positive, negative, and balance subjective effects than OC-CR , indicating that analgesic potency may not necessarily be reflected in subjective/objective effects.

Background Examining how pharmaceuticals are used to induce pleasure presents a unique opportunity for analyzing not only how pleasure is assembled and experienced through distinct consumption practices but also how mundane medicines can become euphorigenic substances. Methods Drawing on qualitative research on the non-medical use of prescription drugs by young adults in the United States, this paper utilizes Actor–Network Theory (ANT) to examine how prescription medicines come to produce pleasure. Results Our research found an indeterminacy of experience as individuals were initiated into prescription drug pleasures. We also found that euphorigenic effects coalesce and are foregrounded through subsequent use, and that pleasure and other forms of gratification are made durable through repeated and deliberate pharmaceutical consumption. Conclusion Understanding how individuals are socialized into pharmaceutical pleasure, and how assemblages act to constitute the euphorigenic potential of pharmaceutical misuse, may allow for more context-appropriate intervention efforts. We suggest that the euphorigenic properties ascribed to prescription drugs are not inherent in their pharmaceutical formulations, but instead emerge through interactions within networks of heterogeneous actants.

Alcohol subjective experiences are multi-dimensional and demonstrate wide inter-individual variability. Recent efforts have sought to establish a clearer understanding of subjective alcohol responses by identifying core constructs derived from multiple measurement instruments. The aim of this study was to evaluate the temporal stability of this approach to conceptualizing alcohol subjective experiences across successive alcohol administrations in the same individuals. Healthy moderate alcohol drinkers (n = 104) completed six experimental sessions each, three with alcohol (0.8 g/kg), and three with a non-alcoholic control beverage. Participants reported subjective mood and drug effects using standardized questionnaires before and at repeated times after beverage consumption. We explored the underlying latent structure of subjective responses for all alcohol administrations using exploratory factor analysis and then tested measurement invariance over the three successive administrations using multi-group confirmatory factor analyses. Exploratory factor analyses on responses to alcohol across all administrations yielded four factors representing “Positive mood,” “Sedation,” “Stimulation/Euphoria,” and “Drug effects and Urges.” A confirmatory factor analysis on the separate administrations indicated acceptable configural and metric invariance and moderate scalar invariance. In this study, we demonstrate temporal stability of the underlying constructs of subjective alcohol responses derived from factor analysis. These findings strengthen the utility of this approach to conceptualizing subjective alcohol responses especially for use in prospective and longitudinal alcohol challenge studies relating subjective response to alcohol use disorder risk.

Children with autism spectrum disorder (ASD) have varied comorbidities. With regard to comorbidity, there has been increasing interest in bipolar disorder (BP) in children. However, the prevalence of BP with ASD has varied because of the methodological differences used. Therefore the adequate criteria for determining BP in children are still debated. The purpose of this study is to identify reliable prevalence of BP and to evaluate a variety of subclinical BP symptoms in children with ASD.This is a cross-sectional and case-control study. The participants were 110 referred children aged 6-15 years: 46 with ASD (the case group), 64 without ASD (the control group). We used the strict operational criteria for diagnosing BP, and assessed the presence of subclinical BP symptoms using a semi-structured diagnostic interview.None of the children were diagnosed with BP in the case group, although two children were diagnosed with BP in the control group. Based on the subclinical BP symptoms, the prevalence of elation/expansive mood and racing thoughts was significantly higher in the case group than in the control group: 26.1% versus 3.1% (p.001) and 32.6% versus 9.4% (p=0.002), respectively.Our finding indicates that school-aged ASD children frequently present subclinical BP symptoms. It is important to be aware of over-diagnosis of BP, even though the children present subclinical BP symptoms, and to provide -the children with effective treatments.

INTRODUCTION Endorphins, endocannabinoids, monoamines, and neurotrophins have all been implicated in the euphoric response to endurance running, known as a runner's high (RH). The epitranscriptional mechanisms regulating this effect have not been defined. Here, we investigate peripheral micro-ribonucleic acid (miRNA) changes unique to athletes experiencing postrun euphoria, yielding insights into gene networks that control an RH. METHODS A cohort study involving 25 collegiate runners (48% females, age = 20 ± 1 yr) examined salivary RNA levels before and after a long-distance run. Participants were divided into RH and nonrunner's high (NRH) groups based on surveys of four criteria (mood, lost sense of time, run quality, and euphoria). Physiological measures were also recorded (temperature, heart rate, blood pressure, pupillary dilatation, and salivary serotonin). Levels of miRNAs and their messenger RNA targets were compared across pre- and postrun samples from RH and NRH groups with two-way ANOVA. Representation of opioid, gamma-aminobutyic acid (GABA), endocannabinoid, neurotrophin, serotonergic, and dopaminergic pathways was assessed in DIANA miRPath. Pearson's correlation analyses examined relationships between miRNAs and RH indices. RESULTS RH participants (n = 13) demonstrated postrun mydriasis (P = 0.046) and hypothermia (P = 0.043) relative to NRH participants (n = 12) but had no difference in serotonin dynamics (P = 0.88). Six miRNAs (miR-194-5p, miR-4676-3p, miR-4254, miR-4425, miR-1273-3p, miR-6743-5p) exhibited significant effects (false discovery rate P value < 0.05) across pre- or postrun and RH/NRH groups. These miRNAs displayed target enrichment for opioid (P = 2.74E-06) and GABA (P = 0.00016) pathways. miR-1237-3p levels were related with lost sense of time (R = 0.40). Mitogen-activated protein kinase (MAPK11), an endocannabinoid target of miR-1273-3p, was nominally elevated in RH participants (false discovery rate P value = 0.11). CONCLUSIONS Unique dynamics in miRNA concentration occur in athletes with subjective/objective evidence of RH, targeting genes implicated endorphin, endocannabinoid, and GABAergic signaling.

RATIONALE: One risk factor for alcohol and substance misuse is hypomanic experiences, or periods of mood elevation. Young people who report hypomanic states are more likely to develop bipolar disorder (BP), and BP and other mood disorders increase the risk of addiction. We recently reported that young adults with a history of mood elevation experience less subjective effects from a low dose of alcohol, which may be predictive of future alcohol use. The finding with alcohol raised the question of whether this dampened response to a drug also applies to other drugs, such as amphetamine. OBJECTIVE: This study assessed responses of d-amphetamine in healthy young adults with varying experiences of mood elevation, as measured by the Mood Disorders Questionnaire (MDQ). METHODS: Healthy 18–19-year-olds (N = 30) with a range of MDQ scores participated in three 4-h laboratory sessions in which they received placebo, 10 mg, or 20 mg d-amphetamine. They completed mood questionnaires and cardiovascular measures. RESULTS: Individuals with higher MDQ scores reported less stimulation and euphoria after 10 mg, but not 20 mg, d-amphetamine, than individuals with lower scores. MDQ scores were not related to cardiovascular responses to the drug. CONCLUSIONS: A history of mood elevation experiences or hypomania states is related to dampened response to a low dose of a psychostimulant drug, extending previous findings with dampened response to alcohol. This phenotype for mood disorders of dampened responses to drugs may contribute to risk for subsequent drug use or misuse.

Suvorexant is a dual orexin receptor antagonist approved in the United States and Japan for the treatment of insomnia at a maximum dose of 20 mg. This randomized double-blind crossover study evaluated the abuse potential of suvorexant in 36 healthy recreational polydrug users with a history of sedative and psychedelic drug use. Single doses of suvorexant (40, 80, and 150 mg: 2-7.5 × maximum dose), zolpidem (15 and 30 mg: 1.5-3 × maximum dose), and placebo were administered, with a 10-day washout between treatments. Subjective and objective measures, including visual analog scales (VASs), Addiction Research Center Inventory, and cognitive/psychomotor tests, were evaluated for 24-hour postdose. Suvorexant had significantly greater peak effects on "drug liking" VAS (primary endpoint) than placebo. Although effects of suvorexant on abuse potential measures were generally similar to zolpidem, they remained constant across doses, whereas zolpidem often had greater effects at higher doses. Suvorexant (all doses) had significantly fewer effects than zolpidem 30 mg on secondary measures, such as "high" VAS, Bowdle VAS, and Addiction Research Center Inventory morphine-benzedrine group. The overall incidence of abuse-related adverse events, such as euphoric mood and hallucination, was numerically lower with suvorexant than zolpidem. In agreement with its classification as a schedule IV drug, suvorexant demonstrated abuse potential, compared with placebo. The abuse potential was similar to zolpidem using certain measures, but with a reduced incidence of abuse-related adverse events. Although this suggests that the overall abuse liability of suvorexant may be lower than zolpidem, the actual abuse rates will be assessed with the postmarketing experience.

Background The popularity of the Eurovision Song Contest (ESC) in Europe has been high for decades. We aimed to assess whether a country’s performance in the ESC is associated with life satisfaction and suicide mortality in European countries. Methods We analysed nationally representative Eurobarometer survey data on life satisfaction from 33 European countries (N = 162,773) and country-level standardised suicide mortality data for years 2009 to 2015. The associations of winning the Contest, performing terribly, and higher final ranking with life satisfaction and suicide rates were all assessed. Results Winning the ESC was not statistically significantly associated with increased life satisfaction or suicide rates, although every ten-place increase in final ranking was associated with an increase in life satisfaction (adjusted odds ratios [aOR] 1.04; 95% confidence interval [CI]: 1.02 to 1.05) and a decrease in suicide mortality rates (β = − 0.30; 95% CI: -0.59 to − 0.01). Terrible performance was associated with greater life satisfaction compared to not competing at all (aOR 1.13; 95%CI: 1.07 to 1.20). Conclusion The good news for participating countries is that just competing at the ESC is associated with higher life satisfaction among the population. As improved performance is linked to Ooh Aah Just a Little Bit of improved life satisfaction, further research into how such international competitions may impact public health is needed.

The medial orbitofrontal cortex has been linked to the experience of positive affect. Greater medial orbitofrontal cortex volume is associated with greater expression of positive affect and reduced medial orbital frontal cortex volume is associated with blunted positive affect. However, little is known about the experience of euphoria, or extreme joy, and how this state may relate to variability in medial orbitofrontal cortex structure. To test the hypothesis that variability in euphoric experience correlates with the volume of the medial orbitofrontal cortex, we measured individuals' (N = 31) level of self-reported euphoria in response to a highly anticipated first time skydive and measured orbitofrontal cortical volumes with structural magnetic resonance imaging. Skydiving elicited a large increase in self-reported euphoria. Participants' euphoric experience was predicted by the volume of their left medial orbitofrontal cortex such that, the greater the volume, the greater the euphoria. Further analyses indicated that the left medial orbitofrontal cortex and amygdalo-hippocampal complex independently explain variability in euphoric experience and that medial orbitofrontal cortex volume, in conjunction with other structures within the mOFC-centered corticolimbic circuit, can be used to predict individuals' euphoric experience.

Background: Qat (also known as Khat , Kat and Miraa ) is a green-leaved plant ( Catha edulis ). It is a shrub indigenous to Yemen and certain parts of eastern Africa. Chewing the leaves, which have sympathomimetic and euphoric effects, has been documented in many countries and increased with worldwide migration. The effect of long-term chewing Qat on the oral cavity is unknown. Objective: A systematic review was performed to identify any associations between Qat chewing and the occurrence of potentially malignant and malignant oral disorders. Methods: Medline and the Web of Science were searched for articles published before May 2014 without limits with regard to publication date and language. Results: From a total of 890 papers identified, 17 English papers reported potentially malignant or malignant oral disorders and Qat chewing. One additional paper in Arabic language was identified from reviewing the list of references of eligible papers. It was found that exposure to Qat may be associated with potentially malignant and malignant oral disorders, but methodological issues, such as inadequate study design, sample size, selection of study subjects, clinical evaluations of outcome and limited adjustment for confounders, limit the strength of the evidence base in this area. Conclusion: The association between Qat chewing and potentially malignant and malignant oral disorders remains debatable and requires further investigations.

Background The relationship between temperament and sexual orientation has been poorly characterized. We have used the Affective and Emotional Composite Temperament (AFECT) model to evaluate this association in a large population sample. Methods Data from 16,571 subjects between 21 and 45 years old (mean age=29.1±6.3 yrs, 69.4% females) was collected anonymously through Internet in Brazil. Results Regarding affective temperaments, male cyclothymics and dysphorics had the lowest percentage of people with heterosexual orientation and the highest percentages of people with bisexual and homosexual orientations. The opposite profile was observed in hyperthymic and euthymic types. Among females, the volatile, cyclothymic, apathetic, disinhibited and euphoric types were less often observed in people with “pure” heterosexual orientation and more often in people with bisexual orientation. In men only, homosexuality was more common among the depressive, cyclothymic and dyphorics temperaments. Emotional trait analysis showed that heterosexual subjects differed statistically from all other groups by having higher scores of coping and stability and lower scores of sensitivity and desire. Overall, the effect sizes were small to moderate, with the largest differences between “pure” heterosexuals and people with bisexual orientation, particularly in women. Subjects with heterosexual orientation who have had homosexual experience and those with homosexual orientation presented intermediate scores. Limitations Cross-sectional design, lack of potentially important covariates (e.g., maltreatment) and data collected by Internet only. Conclusion Externalized and unstable traits were associated mainly with bisexuality. The group of heterosexuals with homosexual fantasies or experiences offers a new approach for the study of sexual orientation.

Background While mood elevation and euphoria are the most commonly described phenotypic descriptors of hypo/mania, irritability and anger may dominate. This study was designed to pursue possible determinants of such differing states. Methods Patients with bipolar I or II disorder were assigned to an ‘irritable/snappy’ or ‘euphoric/happy’ sub-set on the basis of their dominant hypo/manic symptoms. Group differences were examined across clinical, personality, lifestyle and illness impact measures. Results The two sub-sets did not differ on age of depression onset, family history of mood disorders, or depression severity and impairment. The snappy sub-set reported higher levels of irritability in depressed phases and were more likely to have a comorbid anxiety disorder. Their hypo/manic episodes were shorter and they were more likely to be hospitalized at such times. On a temperament measure they scored as more irritable and self-focussed and as less cooperative and effective – indicative of higher levels of disordered personality functioning. Limitations Some comparison analyses were undertaken on a reduced sample size, giving rise to power issues. Our bipolar I and II diagnoses deviated to some extent from DSM-5 criteria in not imposing duration criteria for hypo/manic episodes. Conclusions Findings support a spectrum model for the bipolar disorders linking temperament to bipolar symptomatic state and which may have treatment implications.

Those who are not addicted to ecstasy, but who use it persistently over time, could be viewed as having a "passionate attachment" to a highly valued activity. To evaluate the associations of obsessive and harmonious passion with psychological and behavioral aspects of ecstasy consumption, we recruited a community sample of ecstasy users to complete a modified version of the Passion Scale (Vallerand et al. 2003) and other questionnaires assessing their substance use history, self-efficacy to refuse ecstasy, and use of ecstasy to cope with worries and problems. Both Obsessive and Harmonious passion scores were negatively correlated with self-efficacy to refuse ecstasy and positively correlated with using ecstasy to cope with worries and problems. The findings also provided partial support for our hypotheses that scores on the Obsessive Passion subscale would be associated with number of times participants had used ecstasy, the frequency of use, and the typical number of pills consumed. Participants agreed more strongly with statements indicative of Harmonious Passion to consume ecstasy, but Harmonious subscale scores were not associated with several measures of consumption. As a supplemental measure, the modified questionnaire could provide a more comprehensive picture of the psychology of one's ecstasy use.

Long-term or excessive application of morphine leads to tolerance and addiction, which hindered its conventional applications as a drug. Although tremendous progress has been made on the mechanisms of morphine, crucial evidence elaborating the neurobiological basis of tolerance and dependence is still lacking. To further explore the physiological adaptions during morphine's application, a systematic screening of small molecules in blood has been carried out. The plasma of morphine dependent rats was collected at different time points with or without naloxone treatment, and was analyzed by gas chromatography-mass spectrometry (GC-MS). Partial least squares discriminate analysis (PLS-DA) and the Student's t Tests with the false discovery rate (FDR) correction were conducted on the normalized data for the distinction of groups and the identification of the most contributed metabolites. Clear separation is observed between different treatments, and 29 out of 41 metabolites changes significantly compared with the corresponding controls. The concentration of threonine, glycine, serine, beta-d-glucose and oxalic acid are consistently changed in all morphine treated groups compared with controls. Through this experiment we find characteristic metabolites in different dependent states and discuss the possible compensation effects. The interpretation of these metabolites would throw light on the biological effects of morphine and reveal the possibilities to become marker of morphine addiction.

The aim of this study was to develop two culture-specific scales to measure the level of felt stigma, and level of concealment of Turkish adult people with epilepsy (PWE). For this purpose, a 10-item felt-stigma scale and a 17-item disclosure of epilepsy scale were developed and then applied to 200 adult PWE. After item and factor analyses of the stigma scale, the 10 items with a one-factor solution explained 45.6% of the variance with a 0.86 internal consistency value. Higher scores represent higher felt stigma. The concealment of epilepsy scale has 17 items loaded on one factor, which explained 45.1% of the variance. Cronbach's alpha coefficient was found to be 0.92. The higher the score, the higher the concealment of illness by the participant. For convergent validity, the relationship between stigma and disclosure scales was examined, and a positive significant relation (r=0.64, p

OBJECTIVE: Supra therapeutic doses of methylphenidate (MPH) activate mu opioid receptors, which are linked to euphoria. This study assessed whether naltrexone, a mixed mu opioid antagonist, may attenuate the euphoric effects of stimulants, thereby minimizing their abuse potential in subjects with Attention Deficit Hyperactivity Disorder (ADHD). METHODS: We conducted a six-week, double-blind, placebo-controlled, randomized clinical trial of naltrexone in adults with DSM-IV ADHD receiving open treatment with a long acting formulation of MPH (January 2013 to June 2015). Spheroidal Oral Drug Absorption System (SODAS)–MPH was administered BID and titrated to ~1 mg/kg/day over three weeks and continued for three additional weeks depending on response and adverse effects. Subjects were adults with ADHD preselected for having experienced euphoria with an oral test dose of 60 mg of immediate release (IR) MPH. The primary outcome measure was Question 2 (liking) on the Drug Rating Questionnaire (DRQ-S) after additional oral test doses of 60 mg of IR-MPH at the 3(rd) and 6(th) week of treatment with SODAS-MPH. Thirty-seven subjects who experienced stimulant-induced (mild) euphoria on a baseline visit were started in the open trial of SODAS-MPH and randomized to 50 mg naltrexone or placebo. RESULTS: Thirty-one subjects completed through Week 3, twenty-five through Week 6. Naltrexone significantly diminished the euphoric effect of IR-MPH during the heightened risk titration phase (primary outcome; first three weeks) (χ(2)=5.07, p=0.02) but not the maintenance phase (Weeks 4 to 6) (χ(2)=0.22, p=0.64) of SODAS-MPH treatment. CONCLUSION: Preclinical findings are extended to humans showing that naltrexone may mitigate stimulant-associated euphoria. These findings extend to humans preclinical findings showing that naltrexone may mitigate stimulant-associated euphoria. Our findings provide support for further studies combining opioid receptor antagonists with stimulants to reduce abuse potential. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT01673594

Willingness to lay down one’s life for a group of non-kin, well documented in thehistorical and ethnographic records, represents an evolutionary puzzle. Here wepresent a novel explanation for the willingness to fight and die for a group, combining evolutionary theorizing with empirical evidence from real-world human groups. Building on research in social psychology, we develop a mathematical model showing how conditioning cooperation on previous shared experience can allow extreme (i.e., life-threatening) pro-social behavior to evolve. The model generates a series of predictions that we then test empirically in a range of special sample populations (including military veterans, college fraternity/sorority members, football fans, martial arts practitioners, and twins). Our results show that sharing painful experiences produces “identity fusion” – a visceral sense of oneness – more so even than bonds of kinship, in turn motivating extreme pro-group behavior, including willingness to fight and die for the group. These findings have theoretical and practical relevance. Theoretically, our results speak to the origins of human cooperation, as we offer an explanation of extremely costly actions left unexplained by existing models.Practically, our account of how shared dysphoric experiences produce identity fusion, which produces a willingness to fight and die for a non-kin group, helps us better understand such pressing social issues as suicide terrorism, holy wars, sectarian violence, gang-related violence, and other forms of intergroup conflict.

Poor inhibitory control and sensitivity to drug reward are two significant risk factors for drug abuse. Although the two have been largely viewed as separate and independent risk factors, there is new evidence to suggest that they may be related at both the behavioral and neural level. This study examined associations between behavioral and neural correlates of inhibitory control and sensitivity to the subjective rewarding effects of amphetamine in humans. Healthy volunteers (n=63) first completed the stop signal task, a behavioral measure of inhibitory control. Then they participated in four sessions in which they received amphetamine (20 mg) and placebo in alternating order, providing self-report measures of euphoria and arousal at regular intervals. Finally, a subset of participants (n=38) underwent an fMRI scan to assess neural correlates of inhibitory control. In the first phase of the study, participants with longer stop signal reaction time (SSRT) reported greater amphetamine-induced euphoria and stimulation than those with shorter SSRT. In the second phase, fMRI of response inhibition showed the expected activation in right prefrontal regions. Further, individuals who exhibited less activation in the right middle frontal gyrus during the inhibition task reported more euphoria during the amphetamine sessions. This study is the first to show associations between poor inhibitory control and amphetamine reward sensitivity at both behavioral and neural levels in humans. These findings extend our understanding of risk for drug abuse in individuals with poor inhibitory control and suggest novel targets for prevention efforts.

Background: Acute stress may trigger vascular events. We aimed to investigate whether important football competitions involving the French football team increased the occurrence of stroke. Methods: We retrospectively retrieved data of fatal and nonfatal stroke during 4 World Football Cups (1986, 1998, 2002, and 2006) and 4 European Championships (1992, 1996, 2000, and 2004), based on data from the population-based Stroke Registry of Dijon, France. One period of exposure was analyzed: the period of competition extended to 15 days before and after the competitions. The number of strokes was compared between exposed and unexposed corresponding periods of preceding and following years using Poisson regression. Results: A total of 175 strokes were observed during the exposed periods compared with 192 and 217 strokes in the unexposed preceding and following periods. Multivariate regression analyses showed an overall 30% significant decrease in stroke numbers between periods of competition and unexposed periods of following year (risk ratio (RR) 5 1.3; 95% confidence interval [CI] 5 1.0-1.6; P 5.029) but not with that of preceding year (RR 5 1.1; 95% CI 5 .9-1.3; P 5.367). This was mostly explained by a 40% decrease in stroke numbers during European Championships, compared with the unexposed following periods (RR 5 1.4; 95% CI 5 1.0-1.9; P 5.044) in stratified analyses by football competitions. Conclusions: Watching European football competitions had a positive impact in the city of Dijon with a decrease of stroke numbers. European championship is possibly associated with higher television audience and long-lasting euphoria although other factors may be involved. Further studies using nationwide data are recommended to vali

UR-144 [(1-pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone] is a synthetic cannabinoid, which has been detected in many 'legal highs', seized from the global drug market since the beginning of 2012. It has gained popularity as a 'legal' alternative to classic cannabis in countries where it was not controlled. Despite the widespread distribution of this substance, the data on its effects on the human body are scarce. Therefore, this paper describes the results of analysis and observed effects in 39 cases in which UR-144 was determined in blood. Symptoms were noted from the blood sampling forms filled out by the representative doctor. The determined concentrations of UR-144 were in the range of trace amounts (LOD-0.15ng/mL; LOQ-0.5ng/mL) up to 17ng/mL. The most common observed effects included slurred speech, dilated pupils, sluggish and abnormal pupillary reaction, cheerful behaviour, poor coordination, and staggering. Less frequently observed were: verbosity, narrow pupils, loss of consciousness, pale or reddened facial skin, blackout, euphoria, agitation, hallucinations, hindered communication, shaking hands, seizures, convulsions, somnolence, delayed movements, redness of the conjunctiva, and tachycardia. The discussed cases show the effects observed after UR-144 use. This study can assist in the recognition of possible effects caused by this substance.

Tropicamide is a mydriatic drug used as eye-drops for diagnostic or therapeutic purposes. From 2013, a diverted use by intravenous route has been suspected in Eastern Europe in opioids users. To date, no signal of misuse has been identified in France. The aims of this study were to investigate any early signals of a diverted use of tropicamide eye drops and to collect information regarding motives for the misuse and tropicamide-induced effects.Information was obtained at three levels: (1) at regional level (Midi-Pyrénées area), from reimbursement data and pharmacists' reports on suspicious requests; (2) at national level: from reimbursement data and prescriptions suggesting possible abuse from the OSIAP (Ordonnances Suspectes, Indicateur d'Abus Possible) survey; and (3) at international level: from VigiBaseIn France, in 2014-2015, 17 (0.91%, 95% CI [0.53-1.46%]) falsified prescriptions involving tropicamide were identified in the OSIAP survey (compared with 0%, 95% CI [0-0.19%] for beta-blockers). Moreover, 37 other suspicious prescriptions were presented in 2015 (notified in 2016). In Midi-Pyrénées, seven patients aged 35-49 were reimbursed for 19-45 vials of 10 ml, in a year. Since September 2014, the regional Addictovigilance Centre has received 91 notifications of suspicious requests to obtain tropicamide. In VigiBaseThese results represent the first early warnings of a tropicamide diverted use in France. Tropicamide abusers would seek euphoria or hallucinations. The high doses involved in intravenous administration could lead to serious complications.

Dopamine replacement therapy in PD has been associated with both behavioral addictions and dopamine addiction.To investigate potential association between l-dopa induced neuropsychiatric fluctuations and addictions in PD.A cohort of 102 patients with PD suffering from motor complications of l-dopa treatment was prospectively analyzed. We evaluated dopamine addiction, behavioral addictions, and neuropsychiatric fluctuations using the Ardouin scale of behavior in PD.Patients with (n = 51) or without (n = 51) neuropsychiatric fluctuations did not differ in age, disease duration, medication, or UPDRS III motor score during on and off drug condition. Patients with neuropsychiatric fluctuations had a higher HY stage in off-drug condition. A multivariate model showed that dopamine addiction (odds ratio: 8.9; P = 0.02) and behavioral addictions (odds ratio: 3.76; P = 0.033) were more frequent in the presence of neuropsychiatric fluctuations. Behavioral addictions and dopamine addiction were more frequent in the presence than in the absence of on-drug euphoria (46% vs. 13.9%; P 0.001 and 27% vs 6.2 %; P = 0.003), while conversely, no association emerged between dopamine or behavioral addictions and presence of off-drug dysphoria. Patients with neuropsychiatric fluctuations had a poorer quality of life and a more frequent history of anxiety disorder.The psychostimulant effects of dopamine treatment during on-drug euphoria, rather than avoidance of off-drug dysphoria, appear to drive both behavioral addictions and abuse of medication. © 2017 International Parkinson and Movement Disorder Society.

Objective Methylphenidate activates μ-opioid receptors, which are linked to euphoria. μ-Opioid antagonists, such as naltrexone, may attenuate the euphoric effects of stimulants, thereby minimizing their abuse potential. This study assessed whether the combination of naltrexone with methylphenidate is well-tolerated while preserving the clinical benefits of stimulants in subjects with attention-deficit/hyperactivity disorder (ADHD). Methods We conducted a 6-week, double-blind, placebo-controlled, randomized clinical trial of naltrexone in adults with DSM-IV ADHD receiving open treatment with a long-acting formulation of methylphenidate from January 2013 to July 2015. Spheroidal Oral Drug Absorption System (SODAS) methylphenidate was administered twice daily, was titrated to approximately 1 mg/kg/d over 3 weeks, and was continued for 3 additional weeks depending on response and adverse effects. Subjects were adults with ADHD preselected for having experienced euphoria with a test dose of immediate-release methylphenidate. The primary outcome measure was the Adult ADHD Investigator Symptom Report Scale (AISRS). Results Thirty-seven subjects who experienced stimulant-induced (mild) euphoria at a baseline visit were started in the open trial of SODAS methylphenidate and randomly assigned to naltrexone 50 mg or placebo. Thirty-one subjects completed the study through week 3, and 25 completed through week 6. Throughout 6 weeks of blinded naltrexone and open methylphenidate treatment, the coadministration of naltrexone with methylphenidate did not interfere with the clinical effectiveness of methylphenidate for ADHD symptoms. Additionally, the combination of naltrexone and methylphenidate did not produce an increase in adverse events compared with methylphenidate alone. Conclusions Our findings provide support for the concept of combining opioid receptor antagonists with stimulants to provide an effective stimulant formulation with less abuse potential. Trial registration ClinicalTrials.gov identifier: NCT01673594​.

Background Salvia divinorum (Salvia) is an increasingly popular recreational drug amongst adolescents and young adults. Its primary active ingredient, Salvinorin A (SA)—a highly selective agonist at the κ opiate receptor—is believed to be one of the most potent naturally occurring hallucinogens. However, there is little experimental data on the effects of SA in humans. Methods In a 3-day, double-blind, randomized, crossover, counterbalanced study, the behavioral, subjective, cognitive, psychophysiological, and endocrine effects of 0 mg, 8 mg, and 12 mg of inhaled SA were characterized in 10 healthy individuals who had previously used Salvia. Results SA produced psychotomimetic effects and perceptual alterations, including dissociative and somaesthetic effects, increased plasma cortisol and prolactin, and reduced resting electroencephalogram spectral power. The SA administration was associated with a rapid increase of its levels in the blood. SA did not produce euphoria, cognitive deficits, or changes in vital signs. The effects were transient and not dose-related. SA administration was very well-tolerated without acute or delayed adverse effects. Conclusions SA produced a wide range of transient effects in healthy subjects. The perceptual altering effects and lack of euphoric effects would explain its intermittent use pattern. Such a profile would also suggest a low addictive potential similar to other hallucinogens and consistent with κ opiate receptor agonism. Further work is warranted to carefully characterize a full spectrum of its effects in humans, to elucidate the underlying mechanisms involved, and to explore the basis for individual variability in its effects.

Background Levodopa therapy in Parkinson9s disease (PD) is associated with non-motor complications resulting from sensitisation of the ventral striatum system. Recent studies showed an improvement in non-motor complications in PD patients with subthalamic stimulation. We hypothesised that ventral striatum desensitisation might contribute to this improvement. Methods Psychostimulant effects of levodopa were prospectively assessed in 36 PD patients with an acute levodopa challenge, before and 1 year after chronic subthalamic stimulation, using the Addiction Research Centre Inventory euphoria subscale. Postoperative evaluation was performed with the same dose of levodopa used in the preoperative assessment and after switching off stimulation. Preoperative and postoperative non-motor fluctuations in everyday life were investigated with the Ardouin Scale. Furthermore, in order to artificially reproduce non-motor fluctuations, a levodopa challenge keeping subthalamic stimulation on was performed to assess depression, anxiety and motivation before and after surgery under the different medication conditions. Results After 1 year of chronic subthalamic stimulation with 60.3% reduction in dopaminergic medication, the acute psychostimulant effects of levodopa were significantly reduced compared with preoperatively, as measured by the euphoria subscale (7.22±4.75 vs 4.75±5.68; p=0.0110). On chronic subthalamic stimulation and with markedly reduced dopaminergic medication, non-motor fluctuations were significantly improved. While off medication/on stimulation scores of depression and anxiety were improved, in the on medication/on stimulation condition the motivation score worsened. Conclusions Acute psychostimulant effects of levodopa (off stimulation) were significantly reduced 1 year after surgery. These findings are likely due to desensitisation of the ventral striatum, allowed by the reduction of dopaminergic treatment, and the replacement of pulsatile treatment with continuous subthalamic stimulation.

Most studies of the reinforcing effects of stimulants have focused on the drugs' capacity to induce positive mood (i.e., euphoria). However, recent findings suggest drugs may also alter emotional reactivity to external stimuli, and that this may occur independently of direct effects on mood.We aimed to examine effects of D: -amphetamine, a prototypic stimulant, on self-reported and psychophysiological reactivity to emotional stimuli as well as overall subjective mood. We predicted that amphetamine would enhance reactivity to pleasant stimuli, particularly, stimuli with social content and that these effects would be independent of the drug's direct effects on mood.Over three sessions, 36 healthy normal adults received placebo, D: -amphetamine 10 and 20 mg under counterbalanced double-blind conditions. At each session, emotional reactivity to standardized positive, neutral, and negative pictures with and without social content was measured in self-reports and facial muscles sensitive to emotional state. Drug effects on cardiovascular variables and subjective mood were also measured.Amphetamine produced euphoria, feelings of drug effect, and increased blood pressure. Most notably, amphetamine enhanced self-reported positive reactions to all pictures and psychophysiological reactions to positive pictures. These effects were not significantly related to drug-induced mood changes. Contrary to our hypothesis, effects of amphetamine on emotional reactivity were not moderated by social content.This study demonstrates a previously unexamined and potentially reinforcing effect of stimulant drugs in humans, distinct from more typically measured euphorigenic effects, and suggests new areas of research in stimulant abuse risk and adaptations occurring during drug dependence.

Post-error slowing has long been considered a sign of healthy error detection and an important component of cognitive function. However, the neuropharmacological processes underlying post-error slowing are poorly understood.This study investigated the effect of the dopamine agonist d-amphetamine on post-error slowing and secondarily, the potential mediator of drug-induced euphoria and potential moderators of personality and baseline task performance.Healthy male and female participants (N = 110) completed four study sessions, at which d-amphetamine (placebo 5, 10, 20 mg) was administered under double-blind, counter-balanced conditions. At each session, participants completed subjective drug effect assessments and a working memory task (N-back) to measure post-error slowing. They completed the Multidimensional Personality Questionnaire (MPQ) during screening.Amphetamine (20 mg) reduced post-error slowing, consistent with a dampened behavioral reactivity to errors. This was not related to drug-induced euphoria. Although higher scores on MPQ constraint were related to less post-error slowing under placebo conditions, neither personality nor baseline cognitive performance moderated the effects of amphetamine on post-error slowing.The finding that amphetamine reduced post-error slowing supports the idea that dopamine plays a role in error stimulus processing. The finding is discussed in relation to an existing literature on the mechanisms and function of behavioral and electrophysiological indices of error sensitivity.

An emotional experience can last for only a couple of seconds up to several hours or even longer. In the present study, we examine to which extent covert intrapersonal actions (cognitions both related and unrelated to the emotion-eliciting stimulus) as well as overt interpersonal actions (social sharing) account for this variability in emotion duration. Participants were asked to report the duration of their anger, sadness, joy, and gratitude episodes on a daily basis during five days. Furthermore, information was collected with regard to their cognitions during the episodes and their social sharing behavior. Discrete-time survival analyses revealed that for three of the four emotions under study, stimulus-related cognitions with the same valence as the emotion lead to a prolongation of the episode; in contrast, both stimulus-related and stimulus-unrelated cognitions with a valence opposite to the emotion lead to a shortening. Finally, for the four emotions under study, social sharing was associated with a prolongation. The findings are discussed in terms of a possible process basis underlying the time dynamics of negative as well as positive emotions.

Although numerous studies have assessed subjective effects of nitrous oxide, few studies have analyzed for sex differences. Since sex differences have been reported in subjective effects of several drugs such as opioids, nicotine and alcohol, we sought to determine if sex modulates the subjective effects of the inhalant, nitrous oxide, in healthy volunteers.Thirty-eight females and seventy-two males from nine studies that were conducted in our laboratory were included in this retrospective analysis. All experimental studies utilized randomized, placebo-controlled, repeated measures designs in which subjects inhaled 30% nitrous oxide in oxygen and 100% oxygen (placebo). Dependent measures in this analysis were subjective effects measured at baseline and 15 min into the inhalation period.Nitrous oxide produced a number of subjective effects, including those that could be considered abuse liability-related ("elated," "having pleasant thoughts," drug liking), but sex did not modulate these effects.Females and males showed similar subjective responses to 30% nitrous oxide. Future prospective studies might assess other concentrations, other measures (choice, analgesic response), and other inhaled general anesthetics to more comprehensively characterize the role of sex in response to inhalants.

Objective: Gamma-hydroxybutyrate (GHB) is an endogenous GHB-/GABA-B receptor agonist and a narcolepsy treatment. However, GHB is also abused for its prohedonic effects. On a neuronal level, it was shown that GHB increases regional cerebral blood flow in limbic areas such as the right anterior insula (rAI) and the anterior cingulate cortex (ACC). We aimed to further explore the association between the subjective and neuronal signatures of GHB. Method: We assessed subjective effects and resting-state functional connectivity (rsFC) of an rAI- and an ACC-seed in 19 healthy male subjects after GHB (35mg/kg p.o.) using a placebo-controlled, double-blind, randomized, cross-over functional magnet resonance imaging design. Results: GHB increased subjective ratings for euphoria (p&nbsp

Objective. The side effects of opioids have been widely investigated, but it is unknown whether the subjective effects of mu agonists and mixed action opioids produce similar symptom profiles. This study examined the structure and predictive validity of somatic and cognitive/affective side-effect profiles of morphine and pentazocine using the Somatic Side Effects Questionnaire and the Cognitive and Affective Side Effects Questionnaire. Design. The subjects were 122 female and 90 male healthy volunteers that received an intravenous bolus administration of either 0.08 mg/kg of morphine or 0.5 mg/kg pentazocine. Pre- and post-drug experimental pain testing was also performed. Exploratory and confirmatory factor analysis resulted in similar factor structures for both drugs. Results. The most frequently reported side effects across both drugs involved feeling relaxed, sedation, and feeling in control. At equianalgesic doses, pentazocine had greater aversive side effects than morphine, whereas morphine was more associated with feelings of control and euphoria. For both drugs, females reported greater frequency of negative side effects than males. Using cluster analysis, we identified similar symptom profiles for each drug. These drug-related side-effect profiles were linked with analgesic responses. Specifically, groups that had a more positive side-effect profile experienced the greatest analgesic effect based on changes in ischemic pain sensitivity. Conclusions. These findings have implications for decisions regarding opioid management of acute, chronic, and malignant pain conditions.

Although volatile substance inhalation is prevalent in many contexts and presents a serious threat to public health, this pernicious form of substance misuse remains poorly understood. The question of why people seek and misuse inhalants may be addressed by examining phenomenological accounts of inhalant intoxication, yet few investigations of inhalant intoxication experiences are reported in the literature. This investigation employed a structured interview to assess inhalant intoxication experiences of 267 low-, moderate-, and high-frequency inhalant users. Low-frequency inhalant users reported predominately hedonic experiences during inhalant intoxication, whereas high-frequency users reported a mixture of hedonic and aversive experiences. Aversive experiences such as depressed mood, suicidal ideation, and chest pain were commonly reported by high-frequency users but were relatively rare among low-frequency users. High-frequency users also experienced significantly more euphoria, talkativeness, and grandiosity during inhalant intoxication than low-frequency users. Hedonic and aversive experiences during episodes of inhalant intoxication are relatively common among high-frequency adolescent inhalant users.

In the effort to develop medications to combat addiction, researchers have developed models that attempt to describe the neurobiological process of cocaine dependence. It has not, however, yet been determined which of these models, if any, best fits the behaviors and experiences of patients. This project retrospectively evaluated changes in patients' experiences with cocaine over time in order to clarify the model that best fits clinical observations. In 2005 and 2007, 100 treatment-seeking, long-term cocaine users were recruited from an urban university-based treatment center in Philadelphia, PA, United States. Each participant was administered the "Cocaine History Questionnaire" which asked them to describe the initiation and escalation of their cocaine usage, changing reward perceptions, and effects of intoxication at certain points in their drug use careers. This data was then analyzed using repeated measures, examining the within subject differences in reported information over the time points. We found evidence that while the amount of drug used increases, self-reported euphoria decreases while negative symptoms associated with cocaine use also increase. The data provide preliminary evidence for the hedonic dysregulation model of addiction. Limitations and implications of the study are discussed in the conclusion.

Background Although DSM-IV and the literature on pediatric bipolarity recognize mania and mixed phases neither recognizes states of “mixed hypomania.” There has been preliminary presentation of the latter phenomenon in the adult bipolar literature. The authors herein describe this phenomenon in a consecutive clinical series of bipolar children and adolescents. Methods This exploratory study involved 47 consecutive bipolar patients between the ages of 7 and 17 years presenting to an outpatient clinic. They were evaluated using a structured instrument designed to ascertain the presence of major depressive episodes (MDE), hypomania, mania, psychotic disorders, behavioral disorders such as oppositional defiant disorder and conduct disorder and substance use disorders. We defined mixed hypomania as MDE and hypomania coexisting over at least 2 weeks. Results Of 47 patients, 9 girls (42.9%) and 9 boys (34.6%) were bipolar II mixed. This paper focuses on them. The mean ages of the bipolar II girls and boys were 14.3 (1.9) years and 12.0 (3.4) years, respectively ( p t = 2.45, df = 17). This mixed subgroup tended to experience rising mood in the evening, often with spikes of euphoria; a history of late afternoon to evening increased talkativeness or pressured speech was common. Some patients exhibited flight of ideas. Psychomotor acceleration, heightened level of energy, and increased goal directed activity between 1900 and 0300 were frequently reported. Retrospectively obtained circadian information revealed, in most cases an age inappropriate phase delay of sleep onset: After falling asleep in the early hours of the morning the patients awoke feeling depressed, lethargic and as if they could sleep throughout much of the day. Limitation Cross-sectional, exploratory study based on a relatively small sample size and in need of replication in other clinical settings. Conclusion Mixed hypomania was a common phenomenon in pediatric bipolar II patients. It is apt to go unrecognized in cross-sectional assessments done in the morning or in the early or mid-afternoon. Those with this proposed phenotype would appear “depressed” at these times. Alternatively, what we have proposed can also be described as severe diurnal variation between depression and hypomania in the evening. Further study is required combining 24-hour clinical observation and state of the art technologically derived data.