A Retrospective Review of Supratherapeutic Modafinil Exposures

Modafinil is a non-amphetamine wakefulness-promoting agent used for the treatment of various sleep disorders characterized by excessive daytime sleepiness. There is little information in the medical literature with respect to supratherapeutic doses of this medication. We performed a retrospective review of the California Poison Control System database for all cases of single-substance ingestion of modafinil with follow-up to a known outcome for the time period 1998–2008. Data collected included age, gender, dose ingested, clinical effects, and medical outcome. There were a total of 87 patients, 53 (61%) of which were female. Patient ages ranged from 1.25 to 72 years with a mean of 30 years; 17 (20%) patients were aged 6 years or less. Thirty-three (38%) were intentional overdoses. Most commonly reported effects were tachycardia (n = 23), agitation (n = 14), anxiety (n = 11), headache (n = 8), hypertension (n = 6), dystonia/tremor (n = 6), and dizziness (n = 5). Forty-nine patients (56%) were managed at home, and 38 (44%) were managed in a healthcare setting. Therapies administered included activated charcoal (n = 8), benzodiazepines (n = 7), antihistamines (n = 2), intravenous fluids (n = 2), haloperidol (n = 2), and beta-blockers (n = 1). Effects were classified as none (n = 22), minor (n = 54), and moderate (n = 11). No major effects and no deaths occurred. Effects of modafinil overdose appear to be mild in most cases, with tachycardia and CNS symptoms predominating. Clinically significant effects requiring treatment occurred in a small number of patients

Reward-Related Dorsal Striatal Activity Differences between Former and Current Cocaine Dependent Individuals during an Interactive Competitive Game

Cocaine addiction is characterized by impulsivity, impaired social relationships, and abnormal mesocorticolimbic reward processing, but their interrelationships relative to stages of cocaine addiction are unclear. We assessed blood-oxygenation-level dependent (BOLD) signal in ventral and dorsal striatum during functional magnetic resonance imaging (fMRI) in current (CCD; n = 30) and former (FCD; n = 28) cocaine dependent subjects as well as healthy control (HC; n = 31) subjects while playing an interactive competitive Domino game involving risk-taking and reward/punishment processing. Out-of-scanner impulsivity-related measures were also collected. Although both FCD and CCD subjects scored significantly higher on impulsivity-related measures than did HC subjects, only FCD subjects had differences in striatal activation, specifically showing hypoactivation during their response to gains versus losses in right dorsal caudate, a brain region linked to habituation, cocaine craving and addiction maintenance. Right caudate activity in FCD subjects also correlated negatively with impulsivity-related measures of self-reported compulsivity and sensitivity to reward. These findings suggest that remitted cocaine dependence is associated with striatal dysfunction during social reward processing in a manner linked to compulsivity and reward sensitivity measures. Future research should investigate the extent to which such differences might reflect underlying vulnerabilities linked to cocaine-using propensities (e.g., relapses)

New Pharmacological Agents to Aid Smoking Cessation and Tobacco Harm Reduction: What has been Investigated and What is in the Pipeline?

A wide range of support is available to help smokers to quit and aid attempts at harm reduction, including three first-line smoking cessation medications: nicotine replacement therapy, varenicline and bupropion. Despite the efficacy of these, there is a continual need to diversify the range of medications so that the needs of tobacco users are met. This paper compares the first-line smoking cessation medications to: 1) two variants of these existing products: new galenic formulations of varenicline and novel nicotine delivery devices; and 2) twenty-four alternative products: cytisine (novel outside of central and eastern Europe), nortriptyline, other tricyclic antidepressants, electronic cigarettes, clonidine (an anxiolytic), other anxiolytics (e.g. buspirone), selective 5-hydroxytryptamine (5-HT) reuptake inhibitors, supplements (e.g. St John’s wort), silver acetate, nicobrevin, modafinil, venlafaxine, monoamine oxidase inhibitors (MAOI), opioid antagonist, nicotinic acetylcholine receptors (nAChR) antagonists, glucose tablets, selective cannabinoid type 1 receptor antagonists, nicotine vaccines, drugs that affect gamma-aminobutyric acid (GABA) transmission, drugs that affect N-methyl-D-aspartate receptors (NMDA), dopamine agonists (e.g. levodopa), pioglitazone (Actos; OMS405), noradrenaline reuptake inhibitors, and the weight management drug lorcaserin. Six criteria are used: relative efficacy, relative safety, relative cost, relative use (overall impact of effective medication use), relative scope (ability to serve new groups of patients), and relative ease of use (ESCUSE). Many of these products are in the early stages of clinical trials, however, cytisine looks most promising in having established efficacy and safety and being of low cost. Electronic cigarettes have become very popular, appear to be efficacious and are safer than smoking, but issues of continued dependence and possible harms need to be considered

Self-compassion and bedtime procrastination: an emotion regulation perspective

The current study extended previous research on self-compassion and health behaviours by examining the associations of self-compassion to bedtime procrastination, an important sleep-related behaviour. We hypothesized that lower negative affect and adaptive emotion regulation would explain the proposed links between self-compassion and less bedtime procrastination. Two cross-sectional online studies were conducted. Study 1 included 134 healthy individuals from the community (mean age 30.22, 77.4% female). Study 2 included 646 individuals from the community (mean age 30.74, 68.9% female) who were screened for the absence of clinical insomnia. Participants in both studies completed measures of self-compassion, positive and negative affect and bedtime procrastination. Participants in study 2 also completed a measure of cognitive reappraisal. Multiple mediation analysis in study 1 revealed the expected indirect effects of self-compassion on less bedtime procrastination through lower negative affect [b = − .09, 95% CI = (− .20, − .02), but not higher positive affect. Path analysis in study 2 replicated these findings and further demonstrated that cognitive reappraisal explained the lower negative affect linked to self-compassion [b = − .011; 95% CI = (− .025; − .003)]. The direct effect of self-compassion on less bedtime procrastination remained significant. Our novel findings provide preliminary evidence that self-compassionate people are less likely to engage in bedtime procrastination, due in part to their use of healthy emotion regulation strategies that downregulate negative mood

A new measure of longitudinal connectivity for stream networks

Habitat connectivity is a central factor in shaping aquatic biological communities, but few tools exist to describe and quantify this attribute at a network scale in riverine systems. Here, we develop a new index to quantify longitudinal connectivity of river networks based on the expected probability of an organism being able to move freely between two random points of the network. We apply this index to two fish life histories and evaluate the effects of the number, passability, and placement of barriers on river network connectivity through the use of simulated dendritic ecological networks. We then extend the index to a real world dendritic river system in Newfoundland, Canada. Our results indicate that connectivity in river systems, as represented by our index, is most impacted by the first few barriers added to the system. This is in contrast to terrestrial systems, which are more resilient to low levels of connectivity. The results show a curvilinear relationship between barrier passability and structural connectivity. This suggests that an incremental improvement in passability would result in a greater improvement to river network connectivity for more permeable barriers than for less permeable barriers. Our analysis of the index in simulated and real river networks also showed that barrier placement played an important role in connectivity. Not surprisingly, barriers located near the river mouth have the greatest impact on fish with diadromous life histories while those located near the center of the river network have the most impact on fish with potadromous life histories. The proposed index is conceptually simple and sufficiently flexible to deal with variations in river structure and biological communities. The index will enable researchers to account for connectivity in habitat studies and will also allow resource managers to characterize watersheds, assess cumulative impacts of multiple barriers and determine priorities for restoration