Maria Lucia Oliveira Souza-Formigoni

A Randomized Controlled Trial of a Brief Intervention for Illicit Drugs Linked to the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) in clients recruited from primary health care settings in four countries

AIMS This study evaluated the effectiveness of a brief intervention (BI) for illicit drugs (cannabis, cocaine, amphetamine-type stimulants and opioids) linked to the World Health Organization (WHO) Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). The ASSIST screens for problem or risky use of 10 psychoactive substances, producing a score for each substance that falls into either a low-, moderate- or high-risk category. DESIGN Prospective, randomized controlled trial in which participants were either assigned to a 3-month waiting-list control condition or received brief motivational counselling lasting an average of 13.8 minutes for the drug receiving the highest ASSIST score. SETTING Primary health-care settings in four countries: Australia, Brazil, India and the United States. PARTICIPANTS A total of 731 males and females scoring within the moderate-risk range of the ASSIST for cannabis, cocaine, amphetamine-type stimulants or opioids. MEASUREMENTS ASSIST-specific substance involvement scores for cannabis, stimulants or opioids and ASSIST total illicit substance involvement score at baseline and 3 months post-randomization. FINDINGS Omnibus analyses indicated that those receiving the BI had significantly reduced scores for all measures, compared with control participants. Country-specific analyses showed that, with the exception of the site in the United States, BI participants had significantly lower ASSIST total illicit substance involvement scores at follow-up compared with the control participants. The sites in India and Brazil demonstrated a very strong brief intervention effect for cannabis scores (P < 0.005 for both sites), as did the sites in Australia (P < 0.005) and Brazil (P < 0.01) for stimulant scores and the Indian site for opioid scores (P < 0.01). CONCLUSIONS The Alcohol, Smoking and Substance Involvement Screening Test-linked brief intervention aimed at reducing illicit substance use and related risks is effective, at least in the short term, and the effect generalizes across countries.

Antiulcerogenic effects of two Maytenus species in laboratory animals.

Leaves of Maytenus species are commonly used in Brazil for the treatment of gastric ulcers, dyspepsias and other gastric problems. The present study evaluated the antiulcerogenic potential of a boiling water extract of equal parts of M. aquifolium and M. ilicifolia leaves against ulcer lesions induced by indomethacin and cold-restraint stress in rats. Ranitidine and cimetidine were used as reference drugs. The oral and intraperitoneal administration of the extract had a potent antiulcerogenic effect against both types of ulcers. The extract was shown to cause an increase in volume and pH of gastric juice of the animals with the pH effects comparable to those of cimetidine. The results tend to confirm the popular use of the plant.

Sensitization to ethanol's stimulant effect is associated with region-specific increases in brain D2 receptor binding

Abstract  Rationale: Stimulation of locomotor activity by low doses of ethanol (EtOH) and the potentiation of this response after repeated administration (sensitization) have been related to EtOH’s rewarding and addictive properties and to altered dopaminergic activity in brain. In mice, behavioral sensitization to EtOH occurs only in a subset of treated animals, and this provides an opportunity for distinguishing general drug effects from sensitization-specific brain effects. Objectives: In view of evidence suggesting a role for dopamine D2 receptors in EtOH preference and abuse liability, the present study addressed the hypothesis that D2 binding would be altered in specific brain regions in mice showing differential sensitization responses to chronic EtOH administration. Methods: Male albino Swiss mice received 2.4 g/kg EtOH i.p. daily for 21 days and were then separated into sensitized or non-sensitized subgroups on the basis of weekly locomotor activity tests. Results: Autoradiographic analyses of [3H]raclopride binding to D2 sites revealed significant increases in the anterior caudate-putamen of mice in the EtOH-sensitized group when compared with either saline controls (+40%, P<0.00009) or to mice in the EtOH non-sensitized group (+32%; P<0.0003). Smaller increases were seen in the ventrolateral caudate-putamen of sensitized animals (+18% vs control, P<0.02; and 12% vs non-sensitized mice, P<0.07). No differences were found in other brain regions, including the nucleus accumbens, olfactory bulb and substantia nigra. Conclusions: The observed increases in D2-receptor binding in circumscribed targets of nigrostriatal projections may reflect either a pre-existing condition in sensitization-prone animals or a selective vulnerability of D2 receptors to chronic EtOH in these animals. In either case, it may be a marker for differential susceptibility to EtOH sensitization.

Does an Energy Drink Modify the Effects of Alcohol in a Maximal Effort Test

BACKGROUND There are popular reports on the combined use of alcohol and energy drinks (such as Red Bull and similar beverages, which contain caffeine, taurine, carbohydrates, etc.) to reduce the depressant effects of alcohol on central nervous system, but no controlled studies have been performed. The main purpose of this study was to verify the effects of alcohol, and alcohol combined with energy drink, on the performance of volunteers in a maximal effort test (cycle ergometer) and also on physiological indicators (oxygen uptake, ventilatory threshold, respiratory exchange rate, heart rate, and blood pressure), biochemical variables (glucose, lactate, insulin, cortisol, ACTH, dopamine, noradrenaline, and adrenaline), and blood alcohol levels. METHODS Fourteen healthy subjects completed a double-blind protocol made up of four sessions: control (water), alcohol (1.0 g/kg), energy drink (3.57 ml/kg Red Bull), and alcohol + energy drink, each 1 week apart. The effort test began 60 min after drug or control ingestion, and the dependent variables were measured until 60 min after the test. RESULTS Heart rate at the ventilatory threshold was higher in the alcohol and alcohol + energy drink sessions in comparison with control and energy drink sessions. Although in comparison to the control session, the peak oxygen uptake was 5.0% smaller after alcohol ingestion, 1.4% smaller after energy drink, and 2.7% smaller after the combined ingestion, no significant differences were detected. Lactate levels (30 min after drug ingestion, 30 and 60 min after the effort test) and noradrenaline levels (30 min after the effort test) were higher in the alcohol and alcohol + energy drink sessions compared with the control session. CONCLUSIONS The performance in the maximal effort test observed after alcohol + energy drink ingestion was similar to that observed after alcohol only. No significant differences between alcohol and alcohol + energy drink were detected in the physiological and biochemical parameters analyzed. Our findings suggest that energy drinks, at least in the tested doses, did not improve performance or reduce alterations induced by acute alcohol ingestion.

Locomotor Sensitization to Ethanol Impairs NMDA Receptor-Dependent Synaptic Plasticity in the Nucleus Accumbens and Increases Ethanol Self-Administration

Although alcoholism is a worldwide problem resulting in millions of deaths, only a small percentage of alcohol users become addicted. The specific neural substrates responsible for individual differences in vulnerability to alcohol addiction are not known. In this study, we used rodent models to study behavioral and synaptic correlates related to individual differences in the development of ethanol locomotor sensitization, a form of drug-dependent behavioral plasticity associated with addiction vulnerability. Male Swiss Webster mice were treated daily with saline or 1.8 g/kg ethanol for 21 d. Locomotor activity tests were performed once a week for 15 min immediately after saline or ethanol injections. After at least 11 d of withdrawal, cohorts of saline- or ethanol-treated mice were used to characterize the relationships between locomotor sensitization, ethanol drinking, and glutamatergic synaptic transmission in the nucleus accumbens. Ethanol-treated mice that expressed locomotor sensitization to ethanol drank significantly more ethanol than saline-treated subjects and ethanol-treated animals resilient to this form of behavioral plasticity. Moreover, ethanol-sensitized mice also had reduced accumbal NMDA receptor function and expression, as well as deficits in NMDA receptor-dependent long-term depression in the nucleus accumbens core after a protracted withdrawal. These findings suggest that disruption of accumbal core NMDA receptor-dependent plasticity may represent a synaptic correlate associated with ethanol-induced locomotor sensitization and increased propensity to consume ethanol.

Psychometric properties of the sixth version of the Addiction Severity Index (ASI-6) in Brazil

BACKGROUND There are few research tools in Brazil to assess more broadly the alcohol and other drug related problems. OBJECTIVE To test the psychometric properties of ASI in its sixth version (ASI-6). METHODS A multicenter cross-sectional study was conducted in four Brazilian state capitals. Four research centers interviewed 150 adult inpatients or outpatients, and one research center interviewed 140 patients. A total of 740 substance abusers were selected. Training and supervision of interviewers were performed to assure the quality of dada collected. RESULTS Most areas of the ASI showed good reliability between the instrument and the interviewers, with no statistically significant differences between the ASI-6 Summary Scores for Recent Functioning (SS-Rs) of both interviews. Cronbachs alpha for ASI-6 subscales ranged from 0.64 to 0.95. Correlations between the ASI-6 Alcohol and Drug scores and the concurrent instrument (ASSIST) were high (0.72 and 0.89, respectively). There was a significant negative correlation between the scores in psychiatric, medical and drug areas and the scores of WHOQOL. CONCLUSION Analysis of the psychometric properties of ASI-6 both in outpatients and inpatients in Brazil indicate a good reliability and validity of this instrument for the Brazilian culture. The development of this instrument in Brazil is an important advancement, which will certainly have implications for the prevention, clinical research, and social rehabilitation fields.INTRODUCAO: Existem poucos instrumentos de pesquisa no Brasil que avaliam de forma mais ampla os problemas relacionados ao alcool e a outras drogas. OBJETIVO: Testar as propriedades psicometricas da ASI, em sua sexta versao (ASI-6). METODOS: Um estudo transversal e multicentrico foi conduzido em quatro capitais de estados brasileiros. Quatro centros de pesquisa entrevistaram 150 pacientes adultos internados ou em tratamento ambulatorial. Foram selecionados um total de 740 abusadores de substâncias. A qualidade dos dados coletados foi assegurada pelo treinamento e supervisao aos entrevistadores. RESULTADOS: A maioria das areas da ASI mostraram boa confiabilidade entre o instrumento e os entrevistadores, sem diferencas estatisticamente significativas entre os Escores Sumarios de Funcionamento Recente da ASI-6. O alfa de Cronbach para as subescalas da ASI-6 variou de 0,64 a 0,95. Correlacoes entre os escores da area Alcool e Drogas da ASI-6 e o instrumento concorrente (ASSIST) foram altas (0,72 e 0,89, respectivamente). Existiu uma correlacao negativa estatisticamente significativa entre os escores nas areas psiquiatrica, medica e drogas, e os escores da WHOQOL. CONCLUSAO: A analise das propriedades psicometricas da ASI-6 tanto em sujeitos internados quanto em tratamento ambulatorial no Brasil apontam para uma boa confiabilidade e validade deste instrumento para a cultura brasileira.

Can energy drinks reduce the depressor effect of ethanol? An experimental study in mice

Although the popularization of the combined use of alcoholic beverages and energy drinks (ED) containing caffeine, taurine and other substances has increased, there are no controlled experimental studies on the effects of ED alone or combined with ethanol. This work aimed at evaluating the effects of different doses of ED combined or not with ethanol, on the locomotor activity of Swiss mice. The administration of 3.57, 10.71 or 17.86 ml/kg of ED alone increased the locomotor activity of the animals in relation to a control group. Low doses of ethanol (0.5, 1.0 and 1.5 g/kg) alone or in combination with 10.71 ml/kg of ED did not affect their locomotor activity. However, the reduction of activity observed after 2.5 g/kg of ethanol was antagonized by 10.71 ml/kg of ED. Further studies on the mechanisms of this interaction are still needed.

Resistance to ethanol sensitization is associated with increased NMDA receptor binding in specific brain areas.

Co-administration of N-methyl-D-aspartate (NMDA) receptor antagonists is known to block the development of behavioral sensitization to ethanol and other psychostimulants. Since ethanol sensitization in mice does not occur uniformly in all treated animals, the present study examined the possibility that NMDA receptor binding would be selectively altered in mice susceptible to ethanol sensitization. Mice received 2.4 g/kg ethanol or saline i.p. daily for 21 days and were sacrificed 24 h later. No differences in [3H]dizocilpine ([3H](+)MK-801) binding were found between sensitized and vehicle-treated mice in any of the brain regions analyzed. However, ethanol-treated mice that did not develop sensitization showed significantly higher binding in the nucleus accumbens core (+32% and +40% compared to controls and ethanol-sensitized mice, respectively; P<0.04) and the prefrontal cortex (+15% and +22%; P<0.02). In a separate experiment, sensitization resistant mice challenged with 0.25 mg/kg (+)MK 801 showed significantly less motor activation than saline-treated or ethanol-sensitized mice. These results point to a clear association between elevated NMDA receptor binding in specific brain regions and resistance to ethanol sensitization.

Does the increase in locomotion induced by ethanol indicate its stimulant or anxiolytic properties

The responses of mice to low doses of acutely and chronically administered ethanol (2.0 g/kg) and diazepam (2.0 mg/kg) were observed in activity cages, the open field and the elevated plus-maze. After prolonged administration, ethanol significantly increased locomotion in the activity cages and the plus-maze. In the open field, an increase was only observed in the tests performed after 7 and 14 days of treatment. Ethanol increased the open-arm time in the plus-maze in all the tests, including after acute administration, suggesting an anxiolytic effect. Diazepam induced an anxiolytic effect after 14 days of daily injections but had no stimulant effect on locomotion. Moreover, after prolonged administration sensitization to the anxiolytic, but not to the stimulant effect, was observed. In short, the present papers data support the hypothesis that the stimulant and anxiolytic effects of ethanol are probably being mediated by distinct mechanisms. Furthermore, these data support the hypothesis that drugs that lead to abusive use, such as ethanol, may act both as positive and negative reinforcement.

Nucleus accumbens dopamine D 1 receptors regulate the expression of ethanol-induced behavioural sensitization

Repeated ethanol administration may induce behavioural sensitization, defined as a progressive potentiation of locomotor stimulant effects. This process is associated with neuroadaptations in the mesolimbic pathway and the nucleus accumbens. The aim of the present study was to analyse dopamine D₁ receptor (D₁R) participation in locomotor response to an agonist and an antagonist of the D₁R in mice with different levels of sensitization to ethanol. In three separate experiments, mice received administrations of 2.2 g/kg ethanol or saline every other day for 10 d. According to their locomotor response on the last day, ethanol-treated animals were classified into two groups: sensitized or non-sensitized. After the treatment, mice were challenged with 4 or 8 mg/kg SKF-38393 (i.p.), a D₁R agonist (expt 1); or with 0.01 or 0.1 mg/kg SCH-23390 (i.p.), a D₁R antagonist, followed by 2.2 g/kg ethanol (i.p.) administration (expt 2). In expt 3, mice were challenged with intra-accumbens (intra-NAc) SKF-38393 (1 μg/side, in 0.2 μl), and with intra-NAc SCH-23390 (3 μg/side, in 0.2 μl) followed by 2.2 g/kg ethanol (i.p.). Although the i.p. administration of SKF-38393 did not affect the locomotion of mice, the intra-NAc administration of SKF-38393 significantly increased the locomotor activity in sensitized mice, suggesting that sensitized mice present functionally hyperresponsive D₁Rs in the NAc. Both i.p. and intra-NAc administration of SCH-23390 blocked the expression of ethanol sensitization, suggesting that the activation of NAc D₁Rs seems to be essential for the expression of ethanol sensitization.