Drug abuse, brain calcification and glutamate-induced neurodegeneration

Positive and negative reinforcing systems are part of the mechanism of drug dependence. Drugs with abuse potential may change the manner of response to negative emotional stimuli, activate positive emotional reactions and possess primary reinforcing properties. Catecholaminergic and peptidergic processes are of importance in these mechanisms. Current research needs to understand the types of adaptations that underlie the particularly long-lived aspects of addiction. Presently, glutamate is candidate to play a role in the enduring effects of drugs of abuse. For example, it participates in the chronic pathological changes of corticostriatal terminals produced by methamphetamine. At the synaptic level, a link between over-activation of glutamate receptors, [C(a2+)](i) increase and neuronal damage has been clearly established leading to neurodegeneration. Thus, neurodegeneration can start after an acute over-stimulation whose immediate effects depend on a diversity of calcium-activated mechanisms. If sufficient, the initial insult results in calcification and activation of a chronic on-going process with a progressive loss of neurons. At present, long-term effects of drug dependence underlie an excitotoxicity process linked to a polysynaptic pathway that dynamically regulates synaptic glutamate. Retaliatory mechanisms include energy capability of the neurons, inhibitory systems and cytoplasmic calcium precipitation as part of the neuron-glia interactions. This paper presents an integrated view of these molecular and cellular mechanisms to help understand their relationship and interdependence in a chronic pathological process that suggest new targets for therapeutic intervention.

Subtypes of adolescents with substance use disorders and psychiatric comorbidity using cluster and discriminant analysis of MMPI-A profiles

The main aim of this study was to replicate and extend previous results on subtypes of adolescents with substance use disorders (SUD), according to their Minnesota Multiphasic Personality Inventory for adolescents (MMPI-A) profiles. Sixty patients with SUD and psychiatric comorbidity (41.7% male, mean age = 15.9 years old) completed the MMPI-A, the Teen Addiction Severity Index (T-ASI), the Child Behaviour Checklist (CBCL), and were interviewed in order to determine DSMIV diagnoses and level of substance use. Mean MMPI-A personality profile showed moderate peaks in Psychopathic Deviate, Depression and Hysteria scales. Hierarchical cluster analysis revealed four profiles (acting-out, 35% of the sample; disorganized-conflictive, 15%; normative-impulsive, 15%; and deceptive-concealed, 35%). External correlates were found between cluster 1, CBCL externalizing symptoms at a clinical level and conduct disorders, and between cluster 2 and mixed CBCL internalized/externalized symptoms at a clinical level. Discriminant analysis showed that Depression, Psychopathic Deviate and Psychasthenia MMPI-A scales correctly classified 90% of the patients into the clusters obtained.

Video Gaming Disorder and Sport and Exercise in Emerging Adulthood: A Longitudinal Study.

Among the negative consequences of video gaming disorder, decreased participation in sport and exercise has received little attention. This study aimed to assess the longitudinal association between video gaming disorder and the level of sport and exercise in emerging adult men. A questionnaire was completed at baseline and 15-month follow-up by a representative national sample of 4,933 respondents. The seven items of the Game Addiction Scale were used to construct a latent variable representing video gaming disorder. Level of sport and exercise was also self-reported. Cross-lagged path modeling indicated a reciprocal causality between video gaming disorder and the level of sport and exercise, even after adjusting for a large set of confounders. These findings support the need for better promotion of sport and exercise among emerging adults in order to contribute to the prevention of video gaming disorder, and to raise the level of sport and exercise activity in addicted gamers.

Pathological video game use among young Swiss men: the use of monothetic and polythetic formats to distinguish between pathological, excessive and normal gaming

There is no agreement about the distinction between pathological, excessive and normal gaming. The present study compared two classifications for defining pathological gaming: the polythetic format (gamers who met at least half of the criteria) and monothetic format (gamers who met all criteria). Associations with mental, health and social issues were examined to assess differences between subgroups of gamers. A representative sample of 5,663 young Swiss men filled in a questionnaire as part of the ongoing Cohort Study on Substance Use Risk Factors (C-SURF). Game use was assessed with the Game Addiction Scale. Mental, social and physical factors (depression, anxiety, aggressiveness, physical and mental health, social and health consequences), gambling and substance use (illicit drug use, alcohol dependence and problematic cannabis use) were also assessed. The results indicated that monothetic gamers shared problems with polythetic gamers, but were even more inclined to mental health issues (depression, anxiety, and aggressiveness) and were more vulnerable to other dependencies like substance use, alcohol dependence or gambling. A second analysis using Latent Class Analysis confirmed the distinction between monothetic and polythetic gamers. These findings support the use of a monothetic format to diagnose pathological gaming and to differentiate it from excessive gaming.

Therapeutic benefits of body percussion using the BAPNE method

Body percussion using to the BAPNE method is a means of cognitive stimulation with multiple applications. The aim of this research is to assess their full potential as a source of therapy. The methodology used is theoretical in nature and makes use of a wide bibliography to find evidence for its therapeutic effect. In essence, body percussion can be seen to lead to improvements in three areas. the Physical, as it stimulates awareness of the body, control of movement and muscular strength, coordination and balance; the Mental, as it improves concentration, memory and perception; and finally Socio-affective, as it helps to build egalitarian relationships and leads to a decrease in anxiety in social interactions. This means of therapy has several different uses and it is targeted at different groups. In the present investigation we categorise them into five main groups: individuals with neurodegenerative diseases like Alzheimer's or Parkinson's disease; individuals with learning disorders such as dyslexia or ADHD; patients affected by diseases of the spinal cord, cranial neuropathies and trauma (Neurorehabilitation); and for the treatment of addictive behavior (addiction); and depressive disorders or anxiety disorders.After thorough analysis, we have found scientific evidence that the therapeutic body percussion using the BAPNE method improves the quality of life of patients and it is an important factor in stabilizing the development of different diseases.In addition, evidence involving certain biological indicators (in control and experimental groups, and through a pre-test and post-test) show its effect on levels of stress and anxiety (reduction of cortisol), as well as improvement of social relations as a result of working as a group (increased levels of oxytocin), and improvements seen in self-esteem and in a variety of personal aspects through the Aspects of Identity questionnaire.

The cutting of cocaine and heroin: a critical review

The illicit drug cutting represents a complex problem that requires the sharing of knowledge from addiction studies, toxicology, criminology and criminalistics. Therefore, cutting is not well known by the forensic community. Thus, this review aims at deciphering the different aspects of cutting, by gathering information mainly from criminology and criminalistics. It tackles essentially specificities of cocaine and heroin cutting. The article presents the detected cutting agents (adulterants and diluents), their evolution in time and space and the analytical methodology implemented by forensic laboratories. Furthermore, it discusses when, in the history of the illicit drug, cutting may take place. Moreover, researches studying how much cutting occurs in the country of destination are analysed. Lastly, the reasons for cutting are addressed. According to the literature, adulterants are added during production of the illicit drug or at a relatively high level of its distribution chain (e.g. before the product arrives in the country of destination or just after its importation in the latter). Their addition seems hardly justified by the only desire to increase profits or to harm consumers' health. Instead, adulteration would be performed to enhance or to mimic the illicit drug effects or to facilitate administration of the drug. Nowadays, caffeine, diltiazem, hydroxyzine, levamisole, lidocaïne and phenacetin are frequently detected in cocaine specimens, while paracetamol and caffeine are almost exclusively identified in heroin specimens. This may reveal differences in the respective structures of production and/or distribution of cocaine and heroin. As the relevant information about cutting is spread across different scientific fields, a close collaboration should be set up to collect essential and unified data to improve knowledge and provide information for monitoring, control and harm reduction purposes. More research, on several areas of investigation, should be carried out to gather relevant information.

Smoking, Alcohol, Drug Use, Abuse and Dependence in Narcolepsy and Idiopathic Hypersomnia: A Case-Control Study.

STUDY OBJECTIVES: Basic experiments support the impact of hypocretin on hyperarousal and motivated state required for increasing drug craving. Our aim was to assess the frequencies of smoking, alcohol and drug use, abuse and dependence in narcolepsy type 1 (NT1, hypocretin-deficient), narcolepsy type 2 (NT2), idiopathic hypersomnia (IH) (non-hypocretin-deficient conditions), in comparison to controls. We hypothesized that NT1 patients would be less vulnerable to drug abuse and addiction compared to other hypersomniac patients and controls from general population. METHODS: We performed a cross-sectional study in French reference centres for rare hypersomnia diseases and included 450 adult patients (median age 35 years; 41.3% men) with NT1 (n = 243), NT2 (n = 116), IH (n = 91), and 710 adult controls. All participants were evaluated for alcohol consumption, smoking habits, and substance (alcohol and illicit drug) abuse and dependence diagnosis during the past year using the Mini International Neuropsychiatric Interview. RESULTS: An increased proportion of both tobacco and heavy tobacco smokers was found in NT1 compared to controls and other hypersomniacs, despite adjustments for potential confounders. We reported an increased regular and frequent alcohol drinking habit in NT1 versus controls but not compared to other hypersomniacs in adjusted models. In contrast, heavy drinkers were significantly reduced in NT1 versus controls but not compared to other hypersomniacs. The proportion of patients with excessive drug use (codeine, cocaine, and cannabis), substance dependence, or abuse was low in all subgroups, without significant differences between either hypersomnia disorder categories or compared with controls. CONCLUSIONS: We first described a low frequency of illicit drug use, dependence, or abuse in patients with central hypersomnia, whether Hcrt-deficient or not, and whether drug-free or medicated, in the same range as in controls. Conversely, heavy drinkers were rare in NT1 compared to controls but not to other hypersomniacs, without any change in alcohol dependence or abuse frequency. Although disruption of hypocretin signaling in rodents reduces drug-seeking behaviors, our results do not support that hypocretin deficiency constitutes a protective factor against the development of drug addiction in humans.

Microstructural Brain Differences Predict Functional Hemodynamic Responses in a Reward Processing Task

Many aspects of human behavior are driven by rewards, yet different people are differentially sensitive to rewards and punishment. In this study, we showthat white matter microstructure inthe uncinate/inferiorfronto-occipitalfasciculus, defined byfractional anisotropy values derived from diffusion tensor magnetic resonance images, correlates with both short-term (indexed by the fMRI blood oxygenation level-dependent response to reward in the nucleus accumbens) and long-term (indexed by the trait measure sensitivity to punishment) reactivityto rewards.Moreover,traitmeasures of reward processingwere also correlatedwith reward-relatedfunctional activation in the nucleus accumbens. The white matter tract revealed by the correlational analysis connects the anterior temporal lobe with the medial and lateral orbitofrontal cortex and also supplies the ventral striatum. The pattern of strong correlations suggests an intimate relationship betweenwhitematter structure and reward-related behaviorthatmay also play a rolein a number of pathological conditions, such as addiction and pathological gambling.

Reward networks in the brain as captured by connectivity measures

An assortment of human behaviors is thought to be driven by rewards including reinforcement learning, novelty processing, learning, decision making, economic choice, incentive motivation, and addiction. In each case the ventral tegmental area/ventral striatum (nucleus accumbens) (VTAVS) system has been implicated as a key structure by functional imaging studies, mostly on the basis of standard, univariate analyses. Here we propose that standard functional magnetic resonance imaging analysis needs to be complemented by methods that take into account the differential connectivity of the VTAVS system in the different behavioral contexts in order to describe reward based processes more appropriately. We fi rst consider the wider network for reward processing as it emerged from animal experimentation. Subsequently, an example for a method to assess functional connectivity is given. Finally, we illustrate the usefulness of such analyses by examples regarding reward valuation, reward expectation and the role of reward in addiction.

The Problematic Internet Entertainment Use Scale for Adolescents: Prevalence of Problem Internet Use in Spanish High School Students

Many researchers and professionals have reported nonsubstance addiction to online entertainments in adolescents. However, very few scales have been designed to assess problem Internet use in this population, in spite of their high exposure and obvious vulnerability. The aim of this study was to review the currently available scales for assessing problematic Internet use and to validate a new scale of this kind for use, specifically in this age group, the Problematic Internet Entertainment Use Scale for Adolescents. The research was carried out in Spain in a gender-balanced sample of 1131 high school students aged between 12 and 18 years. Psychometric analyses showed the scale to be unidimensional, with excellent internal consistency (Cronbach"s alpha of 0.92), good construct validity, and positive associations with alternative measures of maladaptive Internet use. This selfadministered scale can rapidly measure the presence of symptoms of behavioral addiction to online videogames and social networking sites, as well as their degree of severity. The results estimate the prevalence of this problematic behavior in Spanish adolescents to be around 5 percent.

Problematic Internet use in British adolescents: An exploration of the addictive symptomatology

Research into online addictions has increased substantially over the last decade, particularly amongst youth. This study adapted the Problematic Internet Entertainment Use Scale for Adolescents [PIEUSA] for use with a British population. The adapted scale was used to (i) validate the instrument for English-speaking adolescent samples, (ii) estimate the prevalence of adolescent online problem users and describe their profile, and (iii) assess the accuracy of the scale"s classification of symptomatology. A survey was administered to 1097 adolescents aged between 11 and 18 years. The results indicated that (i) reliability of the adapted scale was excellent; factor validity showed unidimensionality, and construct validity was adequate. The findings also indicated that (ii) prevalence of online problem users was 5.2% and that they were more likely to younger males that engaged in online gaming for more than two hours most days. The majority of online problem users displayed negative addictive symptoms, especially"loss of control" and"conflict". The adapted scale showed (iii) very good sensitivity, specificity, and classification accuracy, and was able to clearly differentiate between problem and non-problem users. The results suggest certain differences between adolescent and adult online problem users based in the predominance of slightly different psychological components.

Prevalence of Problematic Mobile Phone Use in British Adolescents

The problematic use of mobile phones among adolescents has not been widely studied. There are very few instruments for assessing potential technological addiction to mobile phones, or for categorizing different types of users or uses. The most widely used scale is the Mobile Phone Problem Use Scale (MPPUS), which is used to study adult populations, and has been applied in various forms in international contexts. The aims of this study were to adapt the Spanish version of this scale (MPPUSA) to British adolescents, and then to estimate the prevalence of possible problematic users. A questionnaire was administered to a sample of 1,529 secondary school pupils aged between 11 and 18 years, with 1,026 completed questionnaires being collected. The analysis showed that the factor and construct validity and reliability were comparable to those obtained in previous studies. The prevalence of problematic users among the students was 10%, and the typical problematic user tended to be an adolescent between 11 and 14 years old, studying in a public school, who considered themselves to be an expert user of this technology, who made extensive use of his/her mobile phone, and who attributed the same problem of use among their peers. These users presented notable scores in all the symptoms covered by the scale used to assess problematic use. In conclusion, the adaptation of the MPPUSA as a screening scale for British adolescents presents good sensitivity and specificity for detecting the main addictive symptoms proposed in this validated version.

Gambling in Spain: update on experience, research and policy

AIMS: To describe the current situation of gambling in Spain, sketching its history and discussing the regulations and legislation currently in force within the framework of the European Union (EU), and to review the epidemiology of gambling in Spain, the self-help groups and professional treatments available, and their potential effectiveness. METHODS: A systematic computerized search was performed in three databases (EMBASE, PubMed and PsychINFO, including articles and chapters) and the reference lists from previous reviews to obtain some of the most relevant studies published up to now on the topic of pathologic gambling in Spain. RESULTS: Similar to other EU countries, Spain has a high prevalence of pathologic gambling, focused on specific culturally bounded types of gambling. Expenditure in online gaming has risen significantly in the last few years, prompting the Spanish government to draft new legislation to regulate gaming. CONCLUSIONS: The gaming industry is expected to be one of the fastest growing sectors in Spain in the coming years owing to the rise of new technologies and the development of online gaming

Estudo químico e atividade antibacteriana do caule de Aristolochia esperanzae kuntze (Aristolochiaceae)

From the ethanolic extract of the stem of A. esperanzae ethyl and methyl fatty acid esters, fatty acids, aristolochic I and II acids, and β-cubebin were isolated. In addiction asarinin, populifolic and 2-oxo-populifolic acids, aristolactams AIa and AII, and sitosterol 3-O-β-D-glucopyranoside were also isolated and firstly described in the species. Asarinin and β-cubebin showed antibacterial activity against Bacillus cereus and aristolochic acid I against Staphylococcus aureus and Listeria monocitogenes.