Biperiden reverses the increase in 50-kHz ultrasonic vocalizations but not the increase in locomotor activity induced by cocaine.

Cocaine use disorder (CUD) is a worldwide public health problem, associated with severe psychosocial and economic impacts. Currently, no FDA-approved treatment is available for CUD. However, an emerging body of evidence from clinical and preclinical studies suggests that biperiden, an M1 muscarinic receptor antagonist, presents potential therapeutic use for CUD. These studies have suggested that biperiden may reduce the reinforcing effects of cocaine. It is well established that rodents emit 50-kHz ultrasonic vocalizations (USV) in response to natural rewards and stimulant drugs, including cocaine. Nonetheless, the effects of biperiden on the cocaine-induced increase of 50-kHz USV remains unknown. Here, we hypothesized that biperiden could antagonize the acute effects of cocaine administration on rat 50-kHz USV. To test this hypothesis, adult male Wistar rats were divided into four experimental groups: saline, 5 mg/kg biperiden, 10 mg/kg cocaine, and biperiden/cocaine (5 and 10 mg/kg, i.p., respectively). USV and locomotor activity were recorded in baseline and test sessions. As expected, cocaine administration significantly increased the number of 50-kHz USV. Biperiden administration effectively antagonized the increase in 50-kHz USV induced by cocaine. Cocaine administration also increased the emission of trill and mixed 50 kHz USV subtypes and this effect was antagonized by biperiden. Additionally, we showed that biperiden did not affect the cocaine-induced increase in locomotor activity, although biperiden administration per se increased locomotor activity. In conclusion, our findings indicate that administering biperiden acutely reduces the positive affective effects of cocaine, as demonstrated by its ability to inhibit the increase in 50-kHz USV.

Mindfulness-based interventions in inpatient treatment for Substance Use Disorders: A systematic review.

Inpatient treatment for Substance Use Disorder (SUD), such as Therapeutic Communities and Residential Treatment has been used to test the effect of Mindfulness-Based Interventions (MBI) over different outcomes. Although there is evidence of the effectiveness of MBIs, little is known about the particularities that the place may have in the outcomes. The main objective of this Systematic Review was to evaluate the effectiveness of MBIs for SUDs performed in the inpatient context. PubMed, Web of Science and PsycInfo were used for the search. Quantitative and qualitative studies with no control, usual treatment or other active comparator intervention for SUDs inpatient treatment from 1980 to 2020 were included. From 21 selected studies, 18 were quantitative and 3 qualitative; 12 studies were RCT. Most samples were comprised with women. Based on characteristics of outcomes, we were able to divide them into: Substance Use and Associated Outcomes, Stress, Impulsivity e Evaluation of the MBI protocol. Results suggest that stress assessment is a determining factor for treatment success in these settings. Regarding substance use, although several outcomes have been assessed, the most remarkable results were craving reduction and improvement in treatment adherence. There is evidence that MBIs in inpatient settings benefited those who participated in the experimental groups on some outcomes, such as stress and substance use. Little is mentioned about the impact of the environment over the outcomes and short follow-ups were a relevant limitation of most of the studies. Future assessments must increase follow-up time and evaluate the relationship between the context and the MBI.

Sleep, psychiatric and socioeconomic factors associated with substance use in a large population sample: A cross-sectional study.

Multiple elements modulate drug use, including sleep, which is increasingly being considered as an important contributor to substance use and abuse. The present study aimed to evaluate the association between sleep, psychiatric and socioeconomic/demographic factors and substance use in a large-scale representative sample from the city of São Paulo, Brazil. Data from the 2007 São Paulo Epidemiological Sleep Study (EPISONO) database were used. In the EPISONO study, volunteers underwent a polysomnographic exam and completed a series of questionnaires to assess objective and subjective sleep quality and associated comorbidities. Drug use was assessed using the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). Linear (univariate and multivariate) and logistic regressions were performed to identify factors associated with the use of the 4 most commonly used substances in the sample (tobacco, alcohol, cannabis and cocaine/crack). Structural equation models were used to establish theoretical networks to explain the relationship between sleep, psychiatric and socioeconomic factors and use of these substances. The logistic regression results showed that psychiatric symptoms, lower income, and poorer subjective sleep were the main factors associated with tobacco consumption; gender and occupational status with alcohol intake; age and occupation with cannabis use; and education with cocaine/crack use. The structural equation models partially supported these findings and identified significant effects of psychiatric symptoms on tobacco consumption, both directly and mediated by sleep. Our results reinforce previous findings concerning factors associated with generally misused substances and suggest that sleep should be considered as an important element in future substance use disorder studies.

Effects of biperiden (cholinergic muscarinic m1/m4 receptor antagonist) on ethanol conditioned place preference in mice.

BACKGROUND: Previous studies suggest that muscarinic cholinergic receptors might act upon the dopamine release in the mesolimbic system and alter drug-reinforcing values related to drug craving. AIMS: We examined the effects of systemic biperiden administration, a muscarinic cholinergic (M1/M4) receptor antagonist, on ethanol (dose of 2 g/Kg) conditioned place preference (CPP), neuronal activation, dopamine and its metabolites levels in the nucleus accumbens. METHODS: Thirty minutes before the ethanol-induced CPP test, mice received saline or biperiden at doses of 1.0, 5.0, or 10.0 mg/kg. The time spent in each compartment was recorded for 15 min. After the CPP protocol, animals were euthanized, and we investigated the activation of the nucleus accumbens by immunohistochemistry for Fos. We also quantified dopamine, homovanillic acid (HVA), and dihydroxyphenylacetic acid (DOPAC) levels in the nucleus accumbens by high-performance liquid chromatography (HPLC). Additionally, the rotarod was employed to evaluate the effects of biperiden on motor coordination. RESULTS: Biperiden at different doses (1.0, 5.0, and 10.0 mg/kg) blocked the expression of ethanol-induced CPP. These biperiden doses increased the number of Fos-positive cells and the dopamine turnover in the nucleus accumbens. None of the doses affected the motor coordination evaluated by the rotarod. CONCLUSIONS: Our results show that biperiden can modulate the effect of alcohol reward, and its mechanism of action may involve a change in dopamine and cholinergic mesolimbic neurotransmission.

Could PCSO-524® be a potential adjuvant treatment to sleep therapy in the management of depression?

Sleep is essential in neural system homeostasis due to its regulation of the immunological system and inflammatory cytokines. Poor sleep quality can induce a pro-inflammatory state and aggravate depressive symptoms. Depression has been linked with high levels of peripheral and central pro-inflammatory markers. In this context, we highlight a possible role for PCSO-524®, a nutritional supplement extracted from the New Zealand green lipped mussel that has already been shown to have anti-inflammatory effects, as an adjuvant treatment for depression alongside sleep therapy. Although there are not as yet any studies on its use in treating depression, it has been demonstrated to be a promising treatment in another condition that has been linked with inflammation, attention deficit/hyperactivity disorder, and in some other neurodegenerative disorders. Therefore, PCSO-524®, associated with good sleep quality, could be an option to reinforce depression management.

OMEGA-3 Interventions in Alcohol Dependence and Related Outcomes: A Systematic Review and Propositions.

BACKGROUND: Pharmacological treatment for alcohol dependence has only three approved drugs: disulfiram, naltrexone and acamprosate. The effects of these drugs are, however, limited, presenting several side effects and a modestly higher efficacy compared to placebo. The administration of omega-3 might bring new perspectives to relapse prevention. METHODS: This systematic review aimed to analyze the available literature, compiling the studies that used omega-3 to prevent relapse in alcohol dependents. RESULTS: The databases used were PubMed and Web of Science. We identified 2,231 studies and only five articles addressed the administration of omega-3 and alcoholism. Preclinical studies evaluating the effects of PUFAs related to chronic alcohol administration showed improvements in behavioral, cellular and molecular levels. The clinical trial yielded inconclusive results. CONCLUSION: Despite the reduced number of studies, omega-3 interventions seem to be promising for controlling issues related to alcohol dependence.

Effects of Sulpiride on True and False Memories of Thematically Related Pictures and Associated Words in Healthy Volunteers.

Episodic memory, working memory, emotional memory, and attention are subject to dopaminergic modulation. However, the potential role of dopamine on the generation of false memories is unknown. This study defined the role of the dopamine D2 receptor on true and false recognition memories. Twenty-four young, healthy volunteers ingested a single dose of placebo or 400 mg oral sulpiride, a dopamine D2-receptor antagonist, just before starting the recognition memory task in a randomized, double-blind, and placebo-controlled trial. The sulpiride group presented more false recognitions during visual and verbal processing than the placebo group, although both groups had the same indices of true memory. These findings demonstrate that dopamine D2 receptors blockade in healthy volunteers can specifically increase the rate of false recognitions. The findings fit well the two-process view of causes of false memories, the activation/monitoring failures model.

Omega-3 Levels and Nicotine Dependence: A Cross-Sectional Study and Clinical Trial.

BACKGROUND: High oxidative stress, which is caused by smoking, can alter omega-3 fatty acid concentrations. Since omega-3 fatty acids play a role in dopaminergic neurotransmission related to dependence, it is important to understand their effects on nicotine dependence. METHODS: This research comprised 2 studies. The first one consisted of a cross-sectional evaluation, in which the levels of the most important omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were compared between smokers and non-smokers in a sample of 171 individuals; of them, 120 were smokers and 51 were non-smokers. The other study was a clinical, double-blind, randomized, placebo controlled, in which 63 smokers received daily treatment with capsules of fish oil (a source of omega-3/3 g/day) or mineral oil (used as placebo, also 3 g/day), taken 3 times a day for 90 days. Each fish oil capsules contained approximately 210.99 mg EPA and 129.84 mg of DHA. The outcome was evaluated by means of psychometric and biological measures as well as self-reports of tobacco use. The evaluations were carried out at the beginning of treatment and once a month thereafter (total of 4 times). OUTCOMES: The omega-3 fatty acid lipid profile showed that smokers present lower concentrations of DHA. After treatment, the omega-3 group showed a significant reduction in their levels of dependence. INTERPRETATION: Smokers showed lower peripheral levels of omega-3, and treatment with the most important omega-3 fatty acids brought about a reduction in nicotine dependence.

Possible adverse reactions to herbal products: a study with individuals who resort to popular medicine in the city of Diadema, SP, Brazil.

The present study aimed to investigate the occurrence of adverse reactions (ADRs) related to herbal products (HPs), which are purchased over-the-counter for self-treatment, reported by 100 users. Samples of the HPs related to those ADRs were purchased for their pharmacobotanical identification. The ADRs reported were evaluated based on specialized literature and were analyzed according to causality into probable (PR), possible (PO), unrelated (UR) or unclassifiable (UC); according to expectance into unexpected adverse reaction (UNEX) and expected adverse reaction (EX); seriousness into serious adverse event or reaction (S) and non-serious (NS); and severity into mild (MI), moderate (MO) and severe (SE). Among 100 interviews, five complaints of ADRs were reported in relation to HPs: Senna alexandrina, with a report of cramps (PR; MI; EX; NS); Camellia sinensis, associated with tachycardia (PO; MI; EX; NS); Bauhinia sp., a strong allergic reaction that led to hospitalization (UC; MO; UNEX; S); Picrasma crenata, with several symptoms and hospitalization (UR; MO; UNEX; S); and 21-herb tea, related to an allergic reaction (UC; MI; EX; NS). The strategies used in this study allowed us to carry out an analysis of ADRs attributed to HPs. This analysis could serve as a model in the study of similar cases.

Informal Trade of Psychoactive Herbal Products in the City of Diadema, SP, Brazil: Quality and Potential Risks.

The present study aimed to assess the quality and risks involved in the consumption of psychoactive herbal products (PHs) that are available through informal commerce in the city of Diadema, SP, Brazil. Methods of ethnography were used to conduct the fieldwork during which four dealers were selected to record the collection, handling, packaging, types of PHs marketed, and their therapeutic purposes. In addition, lots of the PHs selected were purchased from the dealers and analyzed using microbiology and pharmacognosy techniques. 217 PHs were recorded and categorized into two main groups: stimulants (67%) and depressants (27%) of the central nervous system; sixteen of them were selected, and their 52 lots were acquired. The deficiencies observed in handling and packaging these lots by dealers were confirmed by microbiological analysis; 80.8% of them presented risk according to the indicators defined by the Brazilian Pharmacopoeia. The pharmacognostic analysis confirmed the authenticity of only 9 to 16 PHs analyzed. In addition, descriptions of contraindications, adverse reactions, and drug interactions were found in the literature for the PHs. The results of this study allow the observation of the priorities for the sanitary adequacy of the popular trade of herbs.

Formulas used by Tibetan doctors at Men-Tsee-Khang in India for the treatment of neuropsychiatric disorders and their correlation with pharmacological data.

The aim of the present study was to identify formulas used at Men-Tsee-Khang (Tibetan Medical and Astrological Institute), India, for the treatment of neuropsychiatric disorders and to compare the Tibetan usage of particular ingredients with pharmacological data from the scientific database. Using ethnographic methods, five doctors were selected and interviewed. A correlation was observed between central nervous system disorders and rLung, one of the three humors in Tibetan medicine, which imbalance is the source of mental disorders, and ten multi-ingredient formulas used to treat the imbalance of this particular humor were identified. These formulas utilize 61 ingredients; among them were 48 plant species. Each formula treats several symptoms related to rLung imbalance, so the plants may have therapeutic uses distinct from those of the formulas in which they are included. Myristica fragrans, nutmeg, is contained in 100% of the formulas, and its seeds exhibit stimulant and depressant actions affecting the central nervous system. Preclinical and clinical data from the scientific literature indicate that all of the formulas include ingredients with neuropsychiatric action and corroborate the therapeutic use of 75.6% of the plants. These findings indicate a level of congruence between the therapeutic uses of particular plant species in Tibetan and Western medicines.

The effectiveness of treatments for cocaine dependence in schizophrenic patients: a systematic review.

OBJECTIVES: To evaluate and compare the effectiveness of available treatments for cocaine dependence in schizophrenic patients. METHOD: We searched articles published between May 2002 and June 2012 in the following databases: Scopus, Pubmed and Web of Knowledge. The key words utilised were "schizophrenia", "dementia praecox", "schizophrenic disorder", "cocaine related disorder", "cocaine abuse", "cocaine addiction", "cocaine dependence", "treatment", "therapeutic", and "drug therapy". SELECTION OF STUDIES AND DATA EXTRACTION: Original articles in English, Portuguese and Spanish were selected. Controlled, double-blind and open-label studies involving only human subjects were included in this review. DATA SYNTHESIS: We found studies on typical and atypical antipsychotics and one monoamine transporter antagonist. There were few indications of the effectiveness of atypical antipsychotic medications for the treatment of cocaine dependence in patients with schizophrenia. CONCLUSIONS: We suggest that further studies be conducted with atypical antipsychotic medicationsand greater methodological strictness, including using a placebo group in the studies, so that health professionals can determine the real effectiveness of this class of medication for the treatment of cocaine dependence in schizophrenic patients.

Influence of blood viscosity to cerebral blood flow in older humans compared to young subjects.

OBJECTIVE: Since blood viscosity (BV) is one of the most important factors determining blood flow, this study aimed to investigate the possible correlation between increased blood viscosity and reduction of regional cerebral blood flow (rCBF) in healthy ageing. METHODS: Male subjects were distributed in two groups: "young", aged 20-30 (27 volunteers), or "elderly", aged 60-70 (50 volunteers). Whole blood viscosity was obtained with a Wells-Brookfield Cone/Plate Viscometer. Cerebral blood flow was analysed by means of single photon emission computed tomography (SPECT). RESULTS: The mean BV values were 3.28±0.43 mPa in the group of young volunteers and 4.33±0.73 mPa in the group of elderly volunteers (t=-6.9, p<0.0001). The elderly had a lower blood flow than the young in the following regions: bilateral parietal; temporal-parietal and temporal of the left hemisphere. Pearson's correlation between BV and rCBF showed a good inverse correlation when the BV was above 3.95±0.83 mPa. CONCLUSIONS: Our results point to a close relationship between the two parameters analysed, BV and rCBF. The impairment in rCBF observed in the elderly volunteers might be due to an increase in BV, among other factors. SIGNIFICANCE: These findings suggest interesting possibilities for the treatment/prevention of brain ageing.

The effects of polyunsaturated fatty acids in alcohol dependence treatment--a double-blind, placebo-controlled pilot study.

BACKGROUND: The lipid fraction of cell membranes consists of polyunsaturated fatty acids (PUFAS), and chronic alcohol use alters it, modifying its permeability, what might contribute for the dysfunctional metabolism observed in the central nervous system of alcohol dependent patients. Therefore, the supplementation of PUFAS can be an important adjuvant in alcoholism treatment. METHODS: This was a placebo controlled, double blind, randomized study where, 80 alcohol dependent patients, according to DSM-IV, were allocated in four groups with 20 patient each: 'PUFAS', 'Naltrexone', 'Naltrexone + PUFAS' and 'Placebo'. Those substances were administered for 90 days and scales were applied to assess patients craving (OCDS) and alcohol dependence severity (SADD) at baseline and after 90 days. PUFAS serum levels were assessed before and after treatment by high performance liquid chromatography assay. RESULTS: Forty-three patients completed the trial. There was a significant improvement over time on drinking days, SADD and OCDS scores in all groups (p < 0.001). The drinking days comparison between groups did not show statistical significant difference. The same effect was observed for compulsion (OCDS) and severity of dependence scale (SADD). The serum levels of PUFAS increased in all the supplemented groups after treatment, although not significantly. CONCLUSIONS: The oral supplementation of 2 g PUFAS for 3 months did not significantly differ from placebo in reducing the amount of alcohol ingestion, or OCDS and SADD scores in a group of alcohol dependent patient. TRIAL REGISTRATION: NCT01211769.