Effects of medical cannabis use on physical and psychiatric symptoms across the day among older adults.

INTRODUCTION: Older adults are increasingly using medical cannabis (MC). It is unclear if therapeutic effects increase problematic use patterns. The current study addresses this issue by examining symptom trajectories across the day and using trajectories to predict problematic use. METHODS: One-hundred six older adults (age range 55-74) who endorsed medical conditions approved for treatment using MC were recruited online. Participants received six text messages/day to assess momentary symptoms for 15 days. RESULTS: Participants provided 5,156 momentary assessments across 1,106 use days. Symptom trajectories were examined across the day. There was a decline in all symptoms following use. Negative affect, pain, and nausea evinced momentary negative reinforcement associations with cannabis intoxication. Momentary negative reinforcement was associated with adverse cannabis outcomes. Declines in post-use trauma symptoms and momentary negative reinforcement effects for negative affect were both associated with cannabis use disorder symptoms. DISCUSSION: These data suggest that MC may be effective in reducing common symptom clusters. However, the negative reinforcing effect (i.e., the link between use and symptom relief at the event level) may complicate the therapeutic nature (i.e., symptom reduction). Identifying interventions to maximize benefits while minimizing costs may increase the efficacy and safety of MC in older adults.

Nicotine Vaping Expectancies: Organization and Activation in Memory Based on Vaping Use Patterns.

OBJECTIVE: The prevalence of smoking combustible cigarettes has decreased, but rates of nicotine vaping among adolescents and young adults have increased dramatically. Vaping is associated with acute health problems and exposes users to toxic metals with unknown long-term consequences. Research on factors influencing vaping is needed to inform the development of effective prevention and intervention methods. Nicotine vaping expectancies, or expected effects related to vaping, may be an important target as they can predict vaping behaviors. The purpose of this study was to examine nicotine expectancy activation patterns with corresponding nicotine vaping behaviors. METHOD: Using methods from alcohol expectancy research, we applied a memory model approach to identifying nicotine vaping expectancies and modeling organization and activation patterns concerning the frequency of nicotine vaping. We created a memory model-based nicotine expectancy measure based on information from 200 adolescents in 8th and 12th grades, and college students. Our expectancy measure was completed by a second sample of 862 college students. RESULTS: We mapped expectancies into network format using Individual Differences Scaling (INDSCAL) and we modeled likely paths of expectancy activation using Preference Mapping (PREFMAP). Nonusers primarily emphasized a positive-negative expectancy dimension and were more likely to activate expectancies of negative internal experiences about vaping. Students who vaped nicotine daily or almost daily primarily emphasized an external appearance-internal experience expectancy dimension and were more likely to activate expectancies of negative affect reduction and withdrawal relief. CONCLUSIONS: Our results identify specific targets for expectancy-based prevention and intervention methods that have the potential to be as effective as similar approaches to preventing and reducing alcohol use.

College Student Alcohol Use: Understanding the Role of Alcohol Expectancies, Social Anxiety, Social Connectedness, and Need to Belong.

ObjectiveCollege students consume more alcohol and engage in binge drinking more frequently than their non-college attending peers, and prevalence of alcohol-related consequences (e.g., drinking and driving; taking avoidable risks) has not decreased proportionally with decreases in consumption. Social anxiety and alcohol expectancies, or beliefs about the effects of alcohol, have been found to be significantly related to alcohol use and account for significant variance in alcohol use and related consequences. Few studies, however, have examined how other social variables such as need to belong and social connectedness may fit into existing models of increased and risky alcohol use. Methods: Students at a large state university (n = 1,278) completed an online survey measuring alcohol expectancies, need to belong, social anxiety, and social connectedness. Mean age of participants was 19.65 years, and 59.5% self-identified as female, 39.8% male, and 0.7% identified as transgender. Structural equation modeling supported hypothesized relationships between need to belong, social anxiety, social connectedness, alcohol expectancies, and alcohol use, a mean centered variable that included binge drinking, drinking frequency, and amount of consumption. Results: Positive alcohol expectancies related to tension reduction, sociability, and sexuality, were positively related to drinking, such that increased alcohol expectancies were associated with increased drinking. Alcohol expectancies mediated the relationship between need to belong and increased alcohol use, as well as social connectedness and increased alcohol use. Similarly, social anxiety also mediated these relationships. No direct relationships were found between need to belong or social connectedness and alcohol use, suggesting previous research exploring these relationships may have excluded control variables (e.g., biological sex, race/ethnicity) that better explain the impact of need to belong and social connectedness on alcohol use. Conclusion: Prevention and intervention efforts might be more effective in reducing alcohol use if social factors are more broadly targeted.

Delivery of a Prevention Program in Large College Classes: Effectiveness of the Expectancy Challenge Alcohol Literacy Curriculum.

Background: Despite modest reductions in alcohol use among college students, drinking-related harms continue to be prevalent. Group-delivered programs have had little impact on drinking except for experiential expectancy challenge interventions that are impractical because they rely on alcohol administration. Expectancy Challenge Alcohol Literacy Curriculum (ECALC), however, offers a non-experiential alternative suitable for widespread implementation for universal, selective, or indicated prevention. Objectives: ECALC has been effective with mandated students, fraternity members, and small classes of 30 or fewer first-year college students. Larger universities, however, typically have classes with 100 students or more, and ECALC has not yet been tested with groups of this size. To fill this gap, we conducted a group randomized trial in which five class sections with over 100 college students received either ECALC or an attention-matched control presentation and completed follow-up at four weeks. Results: ECALC was associated with significant changes on six subscales of the Comprehensive Effects of Alcohol Scale (CEOA), post-intervention expectancies predicted drinking at four-week follow-up, and there were significant expectancy differences between groups. Compared to the control group, students who received ECALC demonstrated significant expectancy changes and reported less alcohol use at follow-up. Conclusions: Findings suggest ECALC is an effective, single session group-delivered intervention program that can be successfully implemented in large classes.

Activin A directly impairs human cardiomyocyte contractile function indicating a potential role in heart failure development.

Activin A has been linked to cardiac dysfunction in aging and disease, with elevated circulating levels found in patients with hypertension, atherosclerosis, and heart failure. Here, we investigated whether Activin A directly impairs cardiomyocyte (CM) contractile function and kinetics utilizing cell, tissue, and animal models. Hydrodynamic gene delivery-mediated overexpression of Activin A in wild-type mice was sufficient to impair cardiac function, and resulted in increased cardiac stress markers (N-terminal pro-atrial natriuretic peptide) and cardiac atrophy. In human-induced pluripotent stem cell-derived (hiPSC) CMs, Activin A caused increased phosphorylation of SMAD2/3 and significantly upregulated SERPINE1 and FSTL3 (markers of SMAD2/3 activation and activin signaling, respectively). Activin A signaling in hiPSC-CMs resulted in impaired contractility, prolonged relaxation kinetics, and spontaneous beating in a dose-dependent manner. To identify the cardiac cellular source of Activin A, inflammatory cytokines were applied to human cardiac fibroblasts. Interleukin -1ß induced a strong upregulation of Activin A. Mechanistically, we observed that Activin A-treated hiPSC-CMs exhibited impaired diastolic calcium handling with reduced expression of calcium regulatory genes (SERCA2, RYR2, CACNB2). Importantly, when Activin A was inhibited with an anti-Activin A antibody, maladaptive calcium handling and CM contractile dysfunction were abrogated. Therefore, inflammatory cytokines may play a key role by acting on cardiac fibroblasts, causing local upregulation of Activin A that directly acts on CMs to impair contractility. These findings demonstrate that Activin A acts directly on CMs, which may contribute to the cardiac dysfunction seen in aging populations and in patients with heart failure.

Effective prevention programming for reducing alcohol-related harms experienced by first year college students: Evaluation of the expectancy challenge alcohol literacy curriculum (ECALC).

Prevention programs may have contributed to modest declines in alcohol use among college students in recent years, but negative consequences continue to be pervasive. First year college students (FYCS) are particularly vulnerable, and there is clearly a need for more effective methods to reduce risk. Meta-analyses focused on expectancy challenge (EC) have found this approach to be effective, but "experiential" EC that includes a drinking exercise is not suitable for most FYCS, many of whom are underage. A non-experiential alternative, the Expectancy Challenge Alcohol Literacy Curriculum (ECALC), is practical for widespread implementation. ECALC has been effective with mandated students and members of fraternities, and in the present study, we focused on evaluating effects with FYCS. In a group randomized trial, 48 class sections of a course designed for FYCS received either ECALC or an attention-matched control presentation. ECALC was associated with significant changes on six expectancy subscales of the Comprehensive Effects of Alcohol Scale (CEOA). Structural equation modeling was used to examine the mediated effects of the intervention on alcohol-related harms via alcohol expectancies. There were significant indirect effects from condition to alcohol use (IND = -0.04, p <.001) and alcohol harms (IND = -0.07, p <.001). This model accounted for 54% of the variance in alcohol use and 46% of the variance in alcohol-related harms. These findings suggest ECALC is an effective, single session group-delivered program that can be incorporated into classroom curricula.

Cross-lagged analyses between gastrointestinal symptoms, psychological distress, and disability in emerging adults.

The gut-brain connection refers to communication between the brain and gastrointestinal (GI) system. Disorders of gut-brain interaction (DGBI) are characterized by GI symptoms that accompany distress and disability. Epidemiological research has suggested DGBI rates in emerging adults are increasing. This study investigated the relationship between GI health, distress, and disability in emerging adults across time. Emerging adults were recruited. A repeated-measure design with a 1-month time lag was used to collect data via an online survey (N = 861) across five academic semesters (Spring 2019 to Summer 2020). Measurement equivalence across time was established and a cross-lagged panel model (CLPM) was specified. Distress at Time 1 predicted GI symptoms at Time 2 (ß = .206, SE = .084, p < .05). GI symptoms at Time 1 predicted disability at Time 2 (ß = .117, SE = .039, p < .01). Higher disability at Time 1 predicted distress at Time 2 (ß = .092, SE = .027, p < .01). The cross-lagged design offers stronger causal inferences than cross-sectional studies used to study the effects of GI symptoms. Findings provide initial evidence of a directional pathway between brain and gut rather than a bidirectional network. Findings highlight the importance of psychogastroenterology.

Examining the Role of Anxiety and Depression in Dietary Choices among College Students.

This study examines the role of anxiety and depression symptoms in predicting dietary choices in emerging adults while accounting for sex differences in these relationships. Participants were 225 English speaking undergraduates enrolled in a university in southeastern United States. Participants were recruited through an online research recruitment application utilized by the university. Participants volunteered for a two-phased anonymous survey monitoring the effects of eating habits and gastrointestinal health in young adults. As part of this effort, participants completed self-reporting measures related to anxiety and depression, as well as an automated, self-administered 24-h diet recall. Multigroup path analysis was used to test primary hypotheses. Overall, a decrease in total caloric intake and an increase in sugar consumption were found as self-reported symptoms of anxiety and depression increased. In addition, there were sex differences in the relationship between depression and food choices. Men consumed more saturated fat as well as less fruits and vegetables as self-reported symptoms of depression increased. Results suggest symptoms of depression are a greater risk factor for poor nutrition in male college students than females. The findings provide another justification to screen for psychological distress in student health services given the implications on behavioral lifestyle and health.

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure.

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.

Organization and activation of alcohol expectancies across empirically derived profiles of college student drinkers.

Alcohol expectancies have been linked to the development of alcohol pathology. Research has shown college drinkers can be classified into unique drinking profiles that vary by use and related problems. The current study examines paths of alcohol expectancy activation as a function of drinking profile. College student drinkers (n = 1,226; 60.77% female) completed assessments of alcohol involvement and alcohol expectancies. Latent profile analysis (LPA) was used to classify drinking profiles. Multidimensional scaling (MDS) techniques were then applied to examine differences in the likely activation of alcohol expectancies as a function of drinking profile. LPA identified 6 classes of college student drinkers: light drinkers with minor problems, moderate drinkers with mild problems, moderate drinkers with severe problems, heavy drinkers with mild problems, heavy drinkers with severe problems, and heavy drinkers with physical dependence. MDS was used to develop a hypothetical memory network of alcohol expectancies. Preference mapping was then used to plot paths of expectancy activation through the hypothetical memory network for each drinking profile. Light drinkers showed expectancy activation along a prosocial-antisocial dimension. As use patterns became increasingly pathological, paths of activation shifted toward arousal-sedation. The shift in activation paths from prosocial-antisocial to arousal-sedation was driven more by alcohol-related pathology than by consumption. This suggests that individuals high in arousal-sedation expectancies may be at an increased risk for more severe alcohol pathology. Further, individuals high in arousal-sedation expectancies may benefit most from programs that restructure expectancy pathways away from arousal-sedation. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Reducing alcohol use in mandated college students: A comparison of a Brief Motivational Intervention (BMI) and the Expectancy Challenge Alcohol Literacy Curriculum (ECALC).

In this randomized trial, 121 mandated college students (33% female, 74% Caucasian, M age = 19.42 years) received either a Brief Motivational Intervention (BMI) with personalized normative feedback (PNF) or the Expectancy Challenge Alcohol Literacy Curriculum (ECALC) to compare effectiveness in reducing alcohol use and associated harms. All participants received either BMI content (n = 63) or ECALC (n = 58). ECALC was delivered as a web-based program with clinician assistance. Measures of alcohol use and harms were completed at baseline and 4 weeks postintervention. ECALC produced significant reductions on all 4 positive expectancy subscales of the Comprehensive Effects of Alcohol Scale (CEOA). Both programs were associated with significant reductions on all alcohol use variables and harms, and expectancies significantly mediated the intervention to outcome relationship in the ECALC condition. There were no significant gender differences. Two one-sided equivalence test indicated superior effects for ECALC compared to BMI on four alcohol use variables (mean blood alcohol concentration, peak blood alcohol concentration, peak drinks per sitting, and drinking days per month), and noninferior to BMI in reducing others (mean drinks per sitting, mean drinks per week, & binge drinking). Superior effects of ECALC versus BMI are based on a short-term follow-up, and longevity of ECALC effects have yet to be established. ECALC has previously been found to be effective as a group-delivered program for male fraternity members, and these findings provide preliminary support for effectiveness for both males and females when delivered individually using a web-based clinician-assisted format. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Within- and between-person associations from mood to alcohol consequences: The mediating role of enhancement and coping drinking motives.

Between-subjects literature has established that trait-like negative mood predicts coping motives, which predict alcohol-related problems and that trait-like positive mood predicts mood enhancement motives, which then predict alcohol consumption. However, there is considerable within-person variation in drinking motives, and the relationship between mood, motives, and alcohol outcomes must be more closely examined at a daily level. The current study used ecological momentary assessment (EMA) to measure mood, motives, alcohol use, and alcohol consequences in 101 college drinkers over a 15-day period. At the between-subjects level, positive mood predicted enhancement motives, which in turn predicted alcohol consumption and consequences. Negative mood predicted coping motives, which were associated with only alcohol-related consequences. At the within-subjects level, daily anxious and depressed mood were associated with endorsing coping motives, but coping motives were not associated with alcohol consumption or problems. Positive mood was associated with enhancement motives, which was associated with both daily alcohol consumption and problems. These results corroborate previous findings that enhancement motives are most predictive of outcomes in the college population and highlight the importance of considering within-subject variance in drinking motives. The relationships between mood, motives, and alcohol outcomes differ when examined as between-subjects versus within-subject constructs. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Tension reduction and affect regulation: An examination of mood indices on drinking and non-drinking days among university student drinkers.

Several theories posit problematic alcohol use develops through mechanisms of positive and negative reinforcement. However, the literature on these mechanisms remains inconsistent. This may be due to a number of issues including a failure to disaggregate negative mood or a failure to account for mood functioning (i.e., stability in mood). Alternatively, there may be differences in typical postdrinking/evening mood on drinking and nondrinking days, however, this has yet to be fully explored. We examined multiple indices of distinct mood states prior to and after typical drinking onset times on drinking and nondrinking days using ecological momentary assessment. College student drinkers (n = 102) carried personal data devices for 15 days. They reported on mood and alcohol use several times per day. Tonic positive mood was higher on drinking days than nondrinking days prior to typical drinking initiation. After typical drinking times, positive mood was higher on drinking days than nondrinking days. Similarly, negative moods (anxiety, stress, anger, and stress instability) indicated a pattern of lower levels relative to both predrinking mood on drinking days, and matched mood time-points on nondrinking days; though, not all of these differences were statistically different. Results suggest positive and negative reinforcing mechanisms may be at play-though the negative reinforcement effects may manifest through subjectively "better" mood on drinking versus nondrinking days. (PsycINFO Database Record

Serum Natriuretic Peptides as Differential Biomarkers Allowing for the Distinction between Physiologic and Pathologic Left Ventricular Hypertrophy.

Given the proven utility of natriuretic peptides as serum biomarkers of cardiovascular maladaptation and dysfunction in humans and the high cross-species sequence conservation of atrial natriuretic peptides, natriuretic peptides have the potential to serve as translational biomarkers for the identification of cardiotoxic compounds during multiple phases of drug development. This work evaluated and compared the response of N-terminal proatrial natriuretic peptide (NT-proANP) and N-terminal probrain natriuretic peptide (NT-proBNP) in rats during exercise-induced and drug-induced increases in cardiac mass after chronic swimming or daily oral dosing with a peroxisome proliferator-activated receptor γ agonist. Male Sprague-Dawley rats aged 8 to 10 weeks were assigned to control, active control, swimming, or drug-induced cardiac hypertrophy groups. While the relative heart weights from both the swimming and drug-induced cardiac hypertrophy groups were increased 15% after 28 days of dosing, the serum NT-proANP and NT-proBNP values were only increased in association with cardiac hypertrophy caused by compound administration. Serum natriuretic peptide concentrations did not change in response to adaptive physiologic cardiac hypertrophy induced by a 28-day swimming protocol. These data support the use of natriuretic peptides as fluid biomarkers for the distinction between physiological and drug-induced cardiac hypertrophy.

Stand-Alone Personalized Normative Feedback for College Student Drinkers: A Meta-Analytic Review, 2004 to 2014.

BACKGROUND: Norms clarification has been identified as an effective component of college student drinking interventions, prompting research on norms clarification as a single-component intervention known as Personalized Normative Feedback (PNF). Previous reviews have examined PNF in combination with other components but not as a stand-alone intervention. OBJECTIVES: To investigate the degree to which computer-delivered stand-alone personalized normative feedback interventions reduce alcohol consumption and alcohol-related harms among college students and to compare gender-neutral and gender-specific PNF. DATA SOURCES: Electronic databases were searched systematically through November 2014. Reference lists were reviewed manually and forward and backward searches were conducted. SELECTION CRITERIA: Outcome studies that compared computer-delivered, stand-alone PNF intervention with an assessment only, attention-matched, or active treatment control and reported alcohol use and harms among college students. METHODS: Between-group effect sizes were calculated as the standardized mean difference in change scores between treatment and control groups divided by pooled standard deviation. Within-group effect sizes were calculated as the raw mean difference between baseline and follow-up divided by pooled within-groups standard deviation. RESULTS: Eight studies (13 interventions) with a total of 2,050 participants were included. Compared to control participants, students who received gender-neutral (dbetween = 0.291, 95% CI [0.159, 0.423]) and gender-specific PNF (dbetween = 0.284, 95% CI [0.117, 0.451]) reported greater reductions in drinking from baseline to follow-up. Students who received gender-neutral PNF reported 3.027 (95% CI [2.171, 3.882]) fewer drinks per week at first follow-up and gender-specific PNF reported 3.089 (95% CI [0.992, 5.186]) fewer drinks. Intervention effects were small for harms (dbetween = 0.157, 95% CI [0.037, 0.278]). CONCLUSIONS: Computer-delivered PNF is an effective stand-alone approach for reducing college student drinking and has a small impact on alcohol-related harms. Effects are small but clinically relevant when considered from a public health perspective. Additional research is needed to examine computer-delivered, stand-alone PNF as a population-level prevention program.

Development and Initial Evaluation of a Web-Based Program to Increase Parental Awareness and Monitoring of Underage Alcohol Use: A Brief Report.

The development of a web-based parent-focused intervention to improve parental awareness and monitoring of adolescent alcohol use was preliminarily evaluated. Upon completion of baseline assessment, sixty-seven parents were randomly assigned to the experimental web-based parent-focused intervention or an assessment only control condition. Participants who completed the experimental program, relative to control participants, significantly improved knowledge of problems related to underage drinking (p < .01) while improvements in overall monitoring of their children approached significance (p = .08). Improvements in monitoring by experimental participants, relative to controls, were pronounced in phone monitoring (p < .01) and indirect monitoring (p = .05). Participants in this study improved their communication about alcohol from pre- to post-intervention regardless of intervention. There were no statistical between group differences found regarding underage drinking attitudes. This pilot evaluation demonstrates that this program warrants further examination in controlled trials with greater power. Study implications are discussed in light of results.

Differential analysis of transient increases of serum cTnI in response to handling in rats.

Serum cardiac troponins are the key biomarkers of myocardial necrosis in humans and in preclinical species. The use of ultrasensitive assays for serum cardiac troponin I (cTnI) as a biomarker in safety studies is hampered by interindividual differences. In this study, we investigated the effect of handling procedures on serum cTnI and explored modeling and simulation approaches to mitigate the impact of these interindividual differences. Femoral-catheterized male Crl:WI(Han) rats (n = 16/group) were left undisturbed in their cages with no handling; subjected to 5 min of isoflurane/O2 anesthesia (A); or placed into a rodent restrainer followed by simulated tail vein injection (RR). Serum cTnI concentrations were assessed over a 24-h period using an ultrasensitive assay, and the study was repeated for confirmation. The mean serum cTnI concentration pre-procedure was 4.2 pg/mL, and remained stable throughout the duration of the study in the rats submitted to the A procedure. Serum cTnI concentrations increased transiently after the RR procedure with a median time to maximum concentration (T max), of 1 and 2 h and a mean maximum value concentration (C max), of 53.0 and 7.2 pg/mL in the initial and repeat studies, respectively. A population pharmacodynamic model identified interindividual, procedure- and study-specific effects on serum cTnI concentrations in rats. It is concluded that a modeling and simulation approach more appropriately describes and statistically analyzes the data obtained with this ultrasensitive assays.

Feedback-based alcohol interventions for mandated students: an effectiveness study of three modalities.

UNLABELLED: The present study used a randomized clinical trial design to examine the effectiveness of personalized alcohol feedback delivered individually, in a group and via computer on alcohol use and related negative consequences in a sample of 173 college students referred for alcohol-related violations. Findings revealed statistically significant reductions in alcohol use and related harms for the individually delivered intervention, with significant reductions in alcohol-related harms for the electronically delivered intervention. No statistically significant results were found for the group-delivered intervention or between groups, and a main effect of time was noted for all outcome variables. This study adds to the literature by being the first randomized clinical trial to include analyses of an empirically supported individually delivered personalized alcohol feedback intervention with more cost-effective group-delivered and electronically delivered feedback formats within a single research design, by expanding the range of participant drinking habits reported at baseline to include all drinking levels and not solely those classified as 'heavy drinking' and by providing anonymity pre-intervention and post-intervention given the potential demand characteristics to underreport illegal and/or illicit behaviours in this vulnerable population. KEY PRACTITIONER MESSAGE: Personalized alcohol feedback delivered in a one-on-one, face-to-face format serves to decrease both alcohol use and harms in mandated college students. The use of web-delivered personalized alcohol feedback may be clinically useful when working with a mandated student population to reduce alcohol-related harms. Personalized alcohol feedback delivered in a group setting may not be indicated for use with a mandated student population as it does not demonstrate decreases in either alcohol use or harms, possibly because of the normalization of deviant behaviour.

Residual effects of cannabis use on neurocognitive performance after prolonged abstinence: a meta-analysis.

Cannabis is the most widely used illicit drug in the U.S., and the number of illicit and licit users is rising. Lasting neurocognitive changes or deficits as a result of use are frequently noted despite a lack of clarity in the scientific literature. In an effort to resolve inconsistencies in the evidence of lasting residual effects of cannabis use, we conducted two meta-analyses. First, we updated a previous meta-analysis on broad nonacute cognitive effects of cannabis use through inclusion of newer studies. In a second meta-analysis, we focused on evidence for lasting residual effects by including only studies that tested users after at least 25 days of abstinence. In the first meta-analysis, 33 studies met inclusion criteria. Results indicated a small negative effect for global neurocognitive performance as well for most cognitive domains assessed. Unfortunately, methodological limitations of these studies prevented the exclusion of withdrawal symptoms as an explanation for observed effects. In the second meta-analysis, 13 of the original 33 studies met inclusion criteria. Results indicated no significant effect of cannabis use on global neurocognitive performance or any effect on the eight assessed domains. Overall, these meta-analyses demonstrate that any negative residual effects on neurocognitive performance attributable to either cannabis residue or withdrawal symptoms are limited to the first 25 days of abstinence. Furthermore, there was no evidence for enduring negative effects of cannabis use.

Myocardial mononuclear cell infiltrates are not associated with increased serum cardiac troponin I in cynomolgus monkeys.

Myocardial mononuclear cell infiltrate is a spontaneous cardiac finding commonly identified in laboratory cynomolgus monkeys. The infiltrates are predominantly composed of macrophages with lesser lymphocytes and are not typically associated with histologically detectable cardiomyocyte degeneration. These infiltrates are of concern because they confound interpretation of test article-related histopathology findings in nonclinical safety toxicology studies. The interpretation of safety studies would be simplified by a biomarker that could identify myocardial infiltrates prior to animal placement on study. We hypothesized that monkeys with myocardial mononuclear cell infiltrates could be identified before necropsy using an ultrasensitive immunoassay for cardiac troponin I (cTnI). Serum cTnI concentrations in monkeys with myocardial infiltrates were not higher than those in monkeys without infiltrates at any of the sampling times before and on the day of necropsy. Increased serum cTnI levels are not suitable for screening monkeys with myocardial mononuclear cell infiltrates before placement in the study.