Acute or chronic effects of cannabinoids on spontaneous or pharmacologically induced yawning in rats

Abstract Yawning is a reflex or event that is not fully understood. It is controlled by many neurotransmitters and neuropeptides and can be induced pharmacologically by cholinergic or dopaminergic agonists. Amongst their many actions, cannabinoids acting on cannabinoid (CB 1 or CB 2 ) receptors can alter cholinergic and/or dopaminergic activity. This study examined the effects of D -THC. However, a high frequency of spontaneous yawning was observed 7 days after D 8 -THC discontinuation. These results suggest that cannabinoid agonists inhibited yawning induced by cholinergic or dopaminergic agonists. In addition, the increased frequency of spontaneous yawning following cessation of chronic administration of a cannabinoid agonist may be of importance as a withdrawal sign for these drugs.

FosB mRNA Expression in Peripheral Blood Lymphocytes in Drug Addicted Patients

FosB gene heterodimerizes with Jun family proteins to form activator protein 1 (AP-1) complexes that bind to AP-1 sites in responsive genes to regulate transcription in all cells. The genic expression of FosB seems to be modified after long time exposure to drugs of abuse and these changes may be involved in craving and addicted behavior. This study investigated the FosB mRNA expression in peripheral blood lymphocytes of drug addicted patients using real-time PCR approach. Thus, patients with crack-cocaine use disorder (CUD, n = 10), alcohol use disorder (AUD, n = 12), and healthy non-addicted subjects (CONT, n = 12) were assessed. FosB mRNA expression was reduced by 1.15-fold in CUD and 2.17-fold in AUD when compared to CONT. Hedge’s effect size gs over log FosB/Act was of 0.66 for CUD and of 0.30 for AUD when compared to controls. This study showed that FosB mRNA expression was detected in lymphocytes from peripheral blood for the first time, and it was less expressed in drug addicted patients. This molecular technique may constitute a potential peripheral marker for substance use disorder

Lack of Effects of Extended Sessions of Transcranial Direct Current Stimulation (tDCS) Over Dorsolateral Prefrontal Cortex on Craving and Relapses in Crack-Cocaine Users

Background: Non-invasive brain stimulation such as transcranial direct current stimulation (tDCS) has been investigated as additional therapeutic tool for drug use disorder. In a previous study, we showed that five sessions of tDCS applied bilaterally over the dorsolateral prefrontal cortex (dlPFC) reduced craving to the use of crack-cocaine in inpatients from a specialized clinic. In the present study, we examine if an extended number of sessions of the same intervention would reduce craving even further and affect also relapses to crack-cocaine use.Methods: A randomized, double-blind, sham-controlled, clinical trial with parallel arms was conducted (https://clinicaltrials.gov/ct2/show/NCT02091167). Crack-cocaine patients from two private and one public clinics for treatment of drug use disorder were randomly allocated to two groups: real tDCS (5 cm × 7 cm, 2 mA, for 20 min, cathodal over the left dlPFC and anodal over the right dlPFC, n = 19) and sham-tDCS (n = 16). Real or sham-tDCS was applied once a day, every other day, in a total of 10 sessions. Craving was monitored by a 5-item obsessive compulsive drinking scale once a week (one time before, three times during and once after brain stimulation) over about 5 weeks and relapse was monitored after their discharge from clinics for up to 60 days.Results: Craving scores progressively decreased over five measurements in both sham- and real tDCS groups. Corrected Hedges’ within-group (initial and final) effect sizes of craving scores were of 0.77 for the sham-tDCS and of 0.97 for the real tDCS group. The between-groups effect size was of 0.34, in favor of the real tDCS group over sham-tDCS group. Relapse rates were high and quite similar between groups in the 30- and 60-days follow-up after discharge from the hospital.Conclusion: Extended repetitive bilateral tDCS over the dlPFC had no add-on effects over regular treatment when considering craving and relapses to the crack-cocaine use in a sample of crack-cocaine patients with severe use disorder. Different tDCS montages targeting other cortical regions and perhaps additional extension of sessions need to be investigated to reach more efficiency in managing craving and relapses to crack-cocaine use

Would frontal midline theta indicate cognitive changes induced by non-invasive brain stimulation? A mini review

To the best of our knowledge, neurophysiological markers indicating changes induced by non-invasive brain stimulation (NIBS) on cognitive performance, especially one of the most investigated under these procedures, working memory (WM), are little known. Here, we will briefly introduce frontal midline theta (FM-theta) oscillation (4–8 Hz) as a possible indicator for NIBS effects on WM processing. Electrophysiological recordings of FM-theta oscillation seem to originate in the medial frontal cortex and the anterior cingulate cortex, but they may be driven more subcortically. FM-theta has been acknowledged to occur during memory and emotion processing, and it has been related to WM and sustained attention. It mainly occurs in the frontal region during a delay period, in which specific information previously shown is no longer perceived and must be manipulated to allow a later (delayed) response and observed in posterior regions during information maintenance. Most NIBS studies investigating effects on cognitive performance have used n-back tasks that mix manipulation and maintenance processes. Thus, if considering FM-theta as a potential neurophysiological indicator for NIBS effects on different WM components, adequate cognitive tasks should be considered to better address the complexity of WM processing. Future research should also evaluate the potential use of FM-theta as an index of the therapeutic effects of NIBS intervention on neuropsychiatric disorders, especially those involving the ventral medial prefrontal cortex and cognitive dysfunctions

Evidence-based guidelines and secondary meta-analysis for the use of transcranial direct current stimulation in neurological and psychiatric disorders

Background: Transcranial direct current stimulation has shown promising clinical results, leading to increased demand for an evidence-based review on its clinical effects. Objective: We convened a team of transcranial direct current stimulation experts to conduct a systematic review of clinical trials with more than 1 session of stimulation testing: pain, Parkinson’s disease motor function and cognition, stroke motor function and language, epilepsy, major depressive disorder, obsessive compulsive disorder, Tourette syndrome, schizophrenia, and drug addiction. Methods: Experts were asked to conduct this systematic review according to the search methodology from PRISMA guidelines. Recommendations on efficacy were categorized into Levels A (definitely effective), B (probably effective), C (possibly effective), or no recommendation. We assessed risk of bias for all included studies to confirm whether results were driven by potentially biased studies. Results: Although most of the clinical trials have been designed as proof-of-concept trials, some of the indications analyzed in this review can be considered as definitely effective (Level A), such as depression, and probably effective (Level B), such as neuropathic pain, fibromyalgia, migraine, post-operative patient-controlled analgesia and pain, Parkinson’s disease (motor and cognition), stroke (motor), epilepsy, schizophrenia, and alcohol addiction. Assessment of bias showed that most of the studies had low risk of biases, and sensitivity analysis for bias did not change these results. Effect sizes vary from 0.01 to 0.70 and were significant in about 8 conditions, with the largest effect size being in postoperative acute pain and smaller in stroke motor recovery (nonsignificant when combined with robotic therapy). Conclusion: All recommendations listed here are based on current published PubMed-indexed data. Despite high levels of evidence in some conditions, it must be underscored that effect sizes and duration of effects are often limited; thus, real clinical impact needs to be further determined with different study designs

Acoes agudas e cronicas dos principios ativos da maconha sobre a memoria e o sistema colinergico central de ratos

BV UNIFESP: Teses e dissertaçõe

Tipologia de Lesch em alcoolistas no Brasil

OBJETIVOS: Alcoolismo é uma doença heterogênea, com apresentações clínicas, resultados terapêuticos e recaídas variáveis, indicando vulnerabilidades biológicas diferentes. A Tipologia de Lesch distingue quatro categorias de alcoolismo: Tipo I - graves sintomas de abstinência; Tipo II - álcool como solução para conflitos; Tipo III - álcool para "tratamento" de desordens psiquiátricas; Tipo IV - alterações neurológicas antes do uso de álcool. Este estudo verificou a aplicabilidade de uma classificação do tipo clínico de alcoolismo pela Tipologia de Lesch em um ambulatório público brasileiro de atendimento especializado de alta demanda. MÉTODO: Estudo seccional descritivo, que classificou pacientes do ambulatório de alcoolismo do Hospital Universitário da Universidade Federal do Espírito Santo de acordo com a Tipologia de Lesch. RESULTADOS: A diferenciação pela Tipologia de Lesch foi facilmente conduzida em um serviço ambulatorial público de alta demanda. De 170 pacientes, 21,2% foram classificados como Tipo I; 29,4%, Tipo II; 28,8%, Tipo III e 20,6%, Tipo IV. Embora os diferentes tipos de alcoolismo tenham diferentes apresentações clínicas, o padrão de ingestão alcoólica, idade da primeira ingestão e tempo de abstinência não diferiram entre os tipos de alcoolismo. CONCLUSÃO: A distinção do tipo clínico de alcoolismo de acordo com a Tipologia de Lesch foi considerada aplicável em um ambulatório público brasileiro de grande demanda, sendo os dados encontrados semelhantes aos relatados em estudos realizados em diferentes países. A aplicação dessa classificação poderá definir mudanças nas estratégias de enfrentamento individualizadas do alcoolismo, sendo, entretanto, necessários estudos de seguimento para avaliar os resultados terapêuticos das mesmas

Drinking and driving: a decrease in executive frontal functions in young drivers with high blood alcohol concentration

This study correlated the executive frontal functions with blood alcohol concentration (BAC) in night drivers in a Brazilian city. of 592 drivers randomly recruited between December 17, 2005 and May 5, 2006, during nighttime hours on main streets or avenues with intense vehicle traffic in Vitoria, Brazil, 444 had the BAC determined by a portable digital breath alcohol analyzer and 389 were submitted to a frontal function examination by a frontal assessment battery (FAB). A high percentage (24.4%) of drivers presented alcohol in their blood. Most of these drivers were male (82%), and nearly half (43.7%) were young adults (aged between 20 and 30 years). the results showed an inverse relationship between the BAC and FAB total scores, with a higher BAC corresponding to a smaller FAB total score, delineating a progressive decrease in frontal function with increasing concentrations of alcohol. the most intriguing result was that alcohol-induced impairment on frontal executive function was particularly important in young adults, and more specifically in the motor programming subset of FAB, an executive function highly involved in driving skills. Considering the worldwide evidence of the high-risk involvement of youth in automobile crashes, the effects of alcohol in young adults need to be more thoroughly examined by cognitive studies, and more direct preventive solutions need to be taken focusing on this age range. (C) 2009 Elsevier Inc. All rights reserved.Univ Fed Espirito Santo, Hlth Sci Ctr, Dept Physiol Sci, Lab Neuropsychopharmacol, BR-29042755 Vitoria, ES, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Psiquiatria, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Psiquiatria, São Paulo, BrazilWeb of Scienc

A Randomized Placebo-Controlled Trial of Targeted Prefrontal Cortex Modulation with Bilateral tDCS in Patients with Crack-Cocaine Dependence

Background: Transcranial direct current stimulation over the dorsolateral prefrontal cortex has been shown to be clinically useful in the treatment of drug addiction. Methods: We conducted a double-blind randomized clinical trial aiming to assess the effects of bilateral dorsolateral prefrontal cortex transcranial direct current stimulation (left cathodal/right anodal) on crack-cocaine addiction. We defined craving as the primary outcome, and other clinical measurements, including depressive and anxiety symtoms, and quality of life, as secondary outcomes. Seventeen male crack-cocaine users (mean age 30.4±9.8 SD) were randomized to receive 5 sessions of active transcranial direct current stimulation (2 mA, 35cm2, for 20 minutes), every other day, and 19 males (mean age 30.3±8.4 SD) to receive sham-transcranial direct current stimulation (placebo) as control group. Results: Craving scores were significantly reduced in the transcranial direct current stimulation group after treatment when compared with sham-transcranial direct current stimulation (P=.028) and baseline values (P=.003), and decreased linearly over 4 weeks (before, during, and after treatment) in the transcranial direct current stimulation group only (P=.047). Changes of anxiety scores towards increase in the sham-transcranial direct current stimulation and decrease in the transcranial direct current stimulation group (P=.03), and of the overall perception of quality of life (P=.031) and of health (P=.048) towards decrease in the sham-transcranial direct current stimulation group and increase in the transcranial direct current stimulation group differed significantly between groups. Conclusions: Repetitive bilateral transcranial direct current stimulation over the dorsolateral prefrontal cortex reduced craving for crack-cocaine use, decreased anxiety, and improved quality of life. We hypothesize that transcranial direct current stimulation effects may be associated with increased prefrontal processing and regulation of craving behavior