Impact of cannabidiol on brain glucose metabolism of C57Bl/6 male mice previously exposed to cocaine.

Despite evidence of the beneficial effects of cannabidiol (CBD) in animal models of cocaine use disorder (CUD), CBD neuronal mechanisms remain poorly understood. This study investigated the effects of CBD treatment on brain glucose metabolism, in a CUD animal model, using [18F]FDG positron emission tomography (PET). Male C57Bl/6 mice were injected with cocaine (20 mg/kg, i.p.) every other day for 9 days, followed by 8 days of CBD administration (30 mg/kg, i.p.). After 48 h, animals were challenged with cocaine. Control animals received saline/vehicle. [18F]FDG PET was performed at four time points: baseline, last day of sensitization, last day of withdrawal/CBD treatment, and challenge. Subsequently, the animals were euthanized and immunohistochemistry was performed on the hippocampus and amygdala to assess the CB1 receptors, neuronal nuclear protein, microglia (Iba1), and astrocytes (GFAP). Results showed that cocaine administration increased [18F]FDG uptake following sensitization. CBD treatment also increased [18F]FDG uptake in both saline and cocaine groups. However, animals that were sensitized and challenged with cocaine, and those receiving only an acute cocaine injection during the challenge phase, did not exhibit increased [18F]FDG uptake when treated with CBD. Furthermore, CBD induced modifications in the integrated density of NeuN, Iba, GFAP, and CB1R in the hippocampus and amygdala. This is the first study addressing the impact of CBD on brain glucose metabolism in a preclinical model of CUD using PET. Our findings suggest that CBD disrupts cocaine-induced changes in brain energy consumption and activity, which might be correlated with alterations in neuronal and glial function.

Prevalence of chronic pain in Brazil: A systematic review and meta-analysis.

OBJECTIVE: This review synthesized existing studies on the prevalence of chronic pain in Brazil and its associated factors to produce a recent estimation to guide public health politics. METHODS: A search was carried out in the Ovid Medline, Embase, Web of Science, and BVS Regional/Lilacs databases to identify population-based cross-sectional studies from 2005 to 2020, which reported the prevalence of benign chronic pain in Brazil (more than three months). The risk of bias was assessed using design, sample size determination, and random selection as essential issues. Pooled prevalence estimates were calculated for chronic pain in the general and elderly populations. The protocol was registered on Prospero (CRD42021249678). RESULTS: Of the 682 identified, 15 macheted the authors' inclusion criteria. Chronic pain prevalence in the general adult population ranged from 23.02% to 41.4% (pooled estimate 35.70%, 95% Cis 30.42 to 41.17) and was described as moderate to intense. It was associated with female sex, old age, lower education, intense professional activity, excessive alcohol consumption, smoking, central obesity, mood disorder, and sedentarism. The Southeastern and Southern regions presented a higher prevalence. The prevalence in the elderly population ranged from 29.3% to 76.2% (pooled estimate 47.32%, 95% Cis 33.73 to 61.11). In addition, this population visited doctors more frequently, had more sleep disorders, and was more dependent on daily living activities. Almost fifty percent of both populations with chronic pain reported pain-induced disability. CONCLUSION: Chronic Pain is highly prevalent in Brazil and associated with significant distress, disability, and poorly controlled.

Lifetime caffeine and adolescent nicotine exposure in mice: effects on anxiety-like behavior and reward.

Caffeine consumption occurs throughout life, while nicotine use typically begins during adolescence, the period when caffeine-nicotine epidemiological association begins in earnest. Despite that, few studies in animal models parallel the pattern of coexposure that occurs in humans. Therefore, the neurobehavioral consequences of the association between these drugs remain unclear. Here, we exposed Swiss mice to lifetime caffeine. Caffeine solutions of 0.1 g/L (CAF0.1), 0.3 g/L (CAF0.3), or water (CTRL) were used as the sole liquid source, being offered to progenitors until weaning and, after that, directly to the offspring until the last day of adolescent behavioral evaluation. The open field test was used to evaluate acute effects of nicotine, of lifetime caffeine and of their interaction on locomotion and anxiety-like behavior, while the conditioned place preference test was used to assess the impact of caffeine on nicotine (0.5 mg/Kg, i.p.) reward. Frontal cerebral cortex dopamine content, dopamine turnover, and norepinephrine levels, as well as hippocampal serotonin 1A receptor expression were assessed. CAF0.3 mice exhibited an increase in anxiety-like behavior when compared to CAF0.1 and CTRL ones, but nicotine coexposure mitigated the anxiogenic-like caffeine-induced effect. Distinctively, caffeine had no effect on locomotion and failed to interfere with both nicotine-induced hyperactivity and place preference. There were no significant effects on dopaminergic and serotonergic markers. In conclusion, although caffeine did not affect nicotine reward, considering the strong association between anxiety disorders and tobacco consumption, caffeine-induced anxiety-like behavior advises limiting its consumption during development, including adolescence, as caffeine could be a risk factor to nicotine use.

Prevalence of chronic pain in Brazil: A systematic review and meta-analysis

Abstract Objective This review synthesized existing studies on the prevalence of chronic pain in Brazil and its associated factors to produce a recent estimation to guide public health politics. Methods A search was carried out in the Ovid Medline, Embase, Web of Science, and BVS Regional/Lilacs databases to identify population-based cross-sectional studies from 2005 to 2020, which reported the prevalence of benign chronic pain in Brazil (more than three months). The risk of bias was assessed using design, sample size determination, and random selection as essential issues. Pooled prevalence estimates were calculated for chronic pain in the general and elderly populations. The protocol was registered on Prospero (CRD42021249678). Results Of the 682 identified, 15 macheted the authors' inclusion criteria. Chronic pain prevalence in the general adult population ranged from 23.02% to 41.4% (pooled estimate 35.70%, 95% Cis 30.42 to 41.17) and was described as moderate to intense. It was associated with female sex, old age, lower education, intense professional activity, excessive alcohol consumption, smoking, central obesity, mood disorder, and sedentarism. The Southeastern and Southern regions presented a higher prevalence. The prevalence in the elderly population ranged from 29.3% to 76.2% (pooled estimate 47.32%, 95% Cis 33.73 to 61.11). In addition, this population visited doctors more frequently, had more sleep disorders, and was more dependent on daily living activities. Almost fifty percent of both populations with chronic pain reported pain-induced disability. Conclusion Chronic Pain is highly prevalent in Brazil and associated with significant distress, disability, and poorly controlled.

Psychedelics and Mental Health: An Alternative Strategy to Treat Mental Impairments Triggered or Aggravated by COVID-19.

Despite the discovery of vaccines for COVID-19, one of the best security measures to contain the spread of the virus is social distancing and isolation. However, isolation might trigger negative mental outcomes, such as onset of a depressive and anxious condition, increased consumption of alcohol and drugs, relapse to substances of abuse, and even induce post-traumatic stress disorder. Interestingly, recent research with psychedelics suggests that when these substances are used in combination with psychotherapy, they may reduce these mental impairments. Nevertheless, scientists are still working to elucidate the possible mechanisms behind these phenomena.

Continuous pericapsular nerve group (PENG) block through an elastomeric infusion system, associated with the lateral cutaneous nerve block of the thigh for total hip arthroplasty.

Orthopaedic surgeries can lead to pain that is difficult to treat, sometimes requiring prolonged hospitalisation. Peripheral nerve blocks stand out as an efficient strategy within the context of multimodal analgesia. The hypothesis is that continuous pericapsular nerve group block, when combined with lateral femoral cutaneous nerve block, can provide excellent analgesic coverage for hip surgeries. Continuous infusion systems can prolong analgesia, minimising opioid consumption, adverse effects and providing faster recovery. We describe a case of efficient analgesia, in which a catheter was positioned between the iliopsoas muscle plane and the iliopubic eminence for total hip arthroplasty.

Ayahuasca, a psychedelic beverage, modulates neuroplasticity induced by ethanol in mice.

Alcohol use disorder needs more effective treatments because relapse rates remain high. Psychedelics, such as ayahuasca, have been used to treat substance use disorders. Our study aimed to evaluate the effects of ayahuasca on ethanol-induced behavioral sensitization (EIBS). Swiss mice received 2.2 g/kg ethanol or saline IP injections every other day across nine days (D1, D3, D5, D7, and D9), and locomotor activity was evaluated 10 min after each injection. Then, animals were treated daily with ayahuasca (corresponding to 1.76 mg/kg of N,N-dimethyltryptamine, DMT) or water by oral gavage for eight consecutive days. On the seventh day, mice were evaluated in the elevated plus maze. Then, mice were challenged with a single dose of ethanol to measure their locomotor activity. Dopamine receptors, serotonin receptors, dynorphin, and prodynorphin levels were quantified in the striatum and hippocampus by blot analysis. Repeated ethanol administration resulted in EIBS. However, those animals treated with ayahuasca had an attenuated EIBS. Moreover, ayahuasca reduced the anxiogenic response to ethanol withdrawal and prevented the ethanol-induced changes on 5-HT1a receptor and prodynorphin levels in the hippocampus and reduced ethanol effects in the dynorphin/prodynorphin ratio levels in the striatum. These results suggest a potential application of ayahuasca to modulate the neuroplastic changes induced by ethanol.

In Utero Exposure to Environmental Tobacco Smoke Increases Neuroinflammation in Offspring.

The embryonic stage is the most vulnerable period for congenital abnormalities. Due to its prolonged developmental course, the central nervous system (CNS) is susceptible to numerous genetic, epigenetic, and environmental influences. During embryo implantation, the CNS is more vulnerable to external influences such as environmental tobacco smoke (ETS), increasing the risk for delayed fetal growth, sudden infant death syndrome, and immune system abnormalities. This study aimed to evaluate the effects of in utero exposure to ETS on neuroinflammation in the offspring of pregnant mice challenged or not with lipopolysaccharide (LPS). After the confirmation of mating by the presence of the vaginal plug until offspring birth, pregnant C57BL/6 mice were exposed to either 3R4F cigarettes smoke (Kentucky University) or compressed air, twice a day (1h each), for 21 days. Enhanced glial cell and mixed cell cultures were prepared from 3-day-old mouse pups. After cell maturation, both cells were stimulated with LPS or saline. To inhibit microglia activation, minocycline was added to the mixed cell culture media 24 h before LPS challenge. To verify the influence of in utero exposure to ETS on the development of neuroinflammatory events in adulthood, a different set of 8-week-old animals was submitted to the Autoimmune Experimental Encephalomyelitis (EAE) model. The results indicate that cells from LPS-challenged pups exposed to ETS in utero presented high levels of proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNFα) and decreased cell viability. Such a proinflammatory environment could modulate fetal programming by an increase in microglia and astrocytes miRNA155. This scenario may lead to the more severe EAE observed in pups exposed to ETS in utero.

Efeito da suplementação de própolis verde no câncer de pâncreas: um relato de caso / Effect of green propolis supplementation on pancreas cancer: a case report

Introdução: O aumento da incidência de doenças crônicas não transmissíveis e a mortalidade associada a estas causas têm se destacado mundialmente. Entre essas doenças, destaca-se o câncer de pâncreas, que é caracterizado por tendência à evolução com metástase e baixa sobrevida. Relato de caso: As terapias oncológicas podem afetar a qualidade de vida e o estado nutricional dos pacientes e, por essa razão, a utilização de terapias alternativas e complementares, como o uso da própolis, podem auxiliar na melhoria da qualidade do tratamento, através da diminuição na proliferação de células neoplásicas e dos efeitos tóxicos da quimioterapia, devido às características epigenéticas, antitumorais, apoptóticas, antioxidantes e imunomodulatórias. Este relato de caso aborda o acompanhamento clínico e nutricional de um paciente idoso do sexo masculino, portador de câncer pancreático em tratamento quimioterápico, sob aconselhamento nutricional associado à suplementação de extrato hidroalcoólico de própolis verde. Conclusão: Observou-se com este relato de caso, a melhora da qualidade de vida e aumento da taxa de sobrevida do paciente de 12 meses para três anos e meio, além de estabilização da progressão tumoral. (AU)

Introduction: The increase in the incidence of chronic noncommunicable diseases has been highlighted in terms of worldwide mortality rates. Among these diseases, pancreatic cancer stands out, which is characterized by a tendency towards the evolution of metastasis and low survival. Weight loss is associated with increased basal energy expenditure, decreased energy consumption and malabsorption of nutrients. Case report: Oncological therapies can affect to quality of life and nutritional status of individuals, due to the toxic and immunosuppressive effects. For this reason, the use of alternative and complementary therapies, such as the use of propolis, can help to improve the quality of treatment, by decreasing the proliferation of neoplastic cells and the toxic effects of chemotherapy, due to the epigenetic, antitumor, apoptotic characteristics, antioxidants and immunomodulatory. This case report addresses the clinical and nutritional monitoring of an elderly male patient, with pancreatic cancer undergoing chemotherapy, under nutritional advice associated with the supplementation of hydroalcoholic extract of green propolis. Conclusion: There was an improvement in the quality of life and an increase in the patient’s survival rate from 12 months to three years, in addition to stabilization of tumor progression. (AU)

Fast Hollow Fiber Liquid-Phase Microextraction as a Greener Alternative for the Determination of N,N-Dimethyltryptamine and Harmala Alkaloids in Human Urine.

Ayahuasca tea is an entheogen hallucinogenic beverage used for shamanic and spiritual purposes, prepared by the decoction of different Amazonian plants containing N,N-dimethyltryptamine (DMT) and harmala alkaloids. Since the therapeutic potential of this tea has been broadly studied in recent years, mainly for the treatment of psychiatric disorders, the determination of the ayahuasca tea components in human and animal matrices is of utmost importance. In order to avoid the use of large amounts of toxic solvents, typically employed in traditional sample preparation methods, hollow fiber liquid-phase microextraction (HF-LPME) presents a greener and time-saving alternative. The present study aims to fully develop and apply an HF-LPME method for the determination of DMT, harmine (HRM), harmaline (HRL), and tetrahydroharmine (THH) in human urine samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Fractional factorial and Box-Behnken designs were used to identify and optimize significant method variables. Once optimized, validation has shown a limit of detection (LoD) of 1.0 ng/ml for DMT and 2.0 ng/ml for the harmala alkaloid. The limit of quantification (LoQ) was of 5.0 ng/ml for all analytes. The method has shown to be linear over a concentration range of 5-200 ng/ml (r 2 ≥ 0.99). Intra/inter-day precision and accuracy met the acceptance criteria at the three quality control (QC) levels studied (15.0, 90.0, and 170.0 ng/ml, n = 6, each). Matrix effect evaluation showed predominant ion enhancement and recovery values were above 80%. Dilution factors of 10- and 20-fold have shown acceptable values of accuracy. Selectivity studies showed no interferences. Analysis of eight authentic samples collected from four subjects proved method feasibility. A simple, time-saving and green alternative for the analysis of DMT and harmala alkaloids in human urine samples was developed, optimized using design of experiments, fully validated and applied to authentic samples.

Ayahuasca no tratamento da farmacodependência à cocaína: possíveis intervenções terapêuticas? / Ayahuasca in the treatment of cocaine addiction: possible therapeutic interventions?

Alucinógenos (ALU) são substâncias psicoativas que não induzem o indivíduo à dependência, possuem perfil de segurança de uso mais alto quando comparado a outras drogas e baixa capacidade de causar tolerância ao uso. Estudos recentes propõem o uso de ALU como tratamento a algumas doenças e transtornos relacionados ao sistema nervoso central, como a depressão, ansiedade e dependência. Dentre os ALU, a ayahuasca (AYA), cujo princípio ativo é a dimetiltriptamina (DMT), é uma bebida psicoativa amplamente utilizada pelas populações indígenas em rituais religiosos. Existem evidências de que pode ser eficaz no tratamento de dependência relacionada ao álcool e nicotina. No entanto, para a cocaína, a segunda droga ilícita mais utilizada no Brasil e na Europa, não existem muitos estudos. O objetivo deste trabalho foi avaliar o potencial da AYA em prevenir a expressão da sensibilização comportamental (SC) induzida pela cocaína e as repercussões neuroquímicas do tratamento em camundongos C57Bl/6. Para tanto, foi avaliada a influência da administração aguda de AYA (1,76; 3,0; 17,6; 30,0 mg/kg de DMT v.o.) na atividade locomotora dos animais em campo aberto (CA). Como não houve diferença estatística na distância percorrida durante a análise, as duas menores doses (1,76 e 3,0 mg/kg de DMT v.o.) foram escolhidas como doses iniciais para a realização do protocolo de prevenção à expressão da SC induzida pela cocaína. Inicialmente, os animais foram habituados no CA durante 3 dias consecutivos após a administração de solução salina 0,9% i.p. No 4o dia experimental, os animais receberam, durante 10 dias alternados, cocaína 10 mg/kg ou salina 0,9% i.p. e foram submetidos diretamente à avaliação da atividade locomotora no CA por 30 minutos. Vinte e quatro horas depois, receberam, durante 8 dias consecutivos, água ou AYA (1,76 ou 3,0 mg/kg de DMT v.o.) e após 30 minutos da administração, foram colocados no CA por 30 minutos para análise da atividade locomotora. No dia seguinte, os camundongos foram desafiados com uma administração de salina. E, no último dia experimental, foi realizado um desafio com cocaína, sempre colocando o animal no CA por 30 minutos. Nessas doses, a AYA não foi eficaz em prevenir a expressão da SC induzida pela cocaína. Dessa forma, avaliamos doses superiores de AYA (15, 30 e 45 mg/kg de DMT v.o.), as quais foram capazes de prevenir a expressão da SC à cocaína. Assim, o protocolo experimental foi novamente realizado com a menor dose (15 mg/kg de DMT v.o.), ao término do protocolo experimental, os animais foram eutanasiados e tiveram seu córtex pré-frontal, estriado e hipocampo dissecados para análise por immunoblotting dos receptores serotoninérgicos 5-HT1A e 5-HT2A. No entanto, não foram não observadas diferenças significativas ao comparar o nível proteico dos receptores nos grupos experimentais. Dessa forma, esses resultados sugerem que a AYA pode ser uma boa estratégia terapêutica para a dependência em cocaína, abrindo caminho para novos estudos

Psychedelics (PSY) are psychoactive substances that do not induce the individual to addiction, have a higher use safety profile when compared to other drugs and low ability to cause tolerance to use. Recent studies propose the use of PSY as a treatment for some diseases and disorders related to the central nervous system, such as depression, anxiety and addiction. Among the PSY, ayahuasca (AYA), whose active component is dimethyltryptamine (DMT), is a psychoactive drink widely used by indigenous populations in religious rituals. There is evidence that it may be effective in treating alcohol and nicotine addiction. However, for cocaine, the second most widely used illicit drug in Brazil and Europe, there are not many studies. The aim of this study was to evaluate the potential of AYA in preventing cocaine-induced behavioral sensitization (BS) expression and the neurochemical repercussions of this treatment in C57Bl/6 mice. Thus, we evaluated the influence of acute administration of AYA (1.76; 3.0; 17.6; 30.0 mg/kg of DMT, orally) on the locomotor activity of animals in the open field (OF). As there was no statistical difference in the distance travelled during the analysis, the two lowest doses (1.76 and 3.0 mg/kg of DMT, orally) were chosen as initial doses to perform the cocaine-induced expression prevention protocol. First, animals were habituated to OF for 3 consecutive days following administration of saline 0.9% i.p. On the fourth experimental day, the animals received for 10 alternate days cocaine 10 mg/kg or saline 0,9% i.p. and were directly submitted to the evaluation of locomotor activity in OF for 30 minutes. Twenty-four hours later they received, for 8 consecutive days, water or AYA (1.76 or 3.0 mg/kg of DMT, orally), and 30 minutes after administration, they were placed in the OF for 30 minutes for analysis of locomotor activity. The next day, the mice were challenged with saline administration. On the last experimental day, a cocaine challenge was performed, always placing the animal in the OF for 30 minutes. At these doses, AYA was not effective in preventing cocaine-induced expression of BS. Thus, we evaluated higher doses of AYA (15, 30 and 45 mg/kg of DMT, orally), which were able to prevent the expression of cocaine-induced BS. Thus, the experimental protocol was again performed with the lowest dose (15 mg/kg of DMT, orally). At the end of the experimental protocol, the animals were euthanized and their prefrontal cortex, striatum and hippocampus were dissected for serotonergic receptor 5-HT1A and 5-HT2A by immunoblotting. However, no significant differences were observed when comparing receptor protein level in the experimental groups. Thus, these results suggest that AYA may be a good therapeutic strategy for cocaine addiction, paving the way for further studies

Comparative Study of Genotoxicity Induced by Six Different PBDEs.

Indiscriminate use of synthetic substances has led to environmental contamination and increasing human and animal exposure to harmful chemicals. Polybrominated flame retardants (PBDEs), which serve as non-covalent additives that enhance the safety of a variety of commercial and consumer goods, are an important class among potentially damaging synthetic substances. Its use is very common in developing countries, including Brazil. In theory, 209 different PBDE congeners exist, and many are currently being used during the manufacture of several products. Unfortunately, PBDEs are easily released from the original products, promptly reaching the environment. Knowledge about the toxicological power of these substances is still limited, which has prevented environmental and regulatory authorities from conducting adequate risk assessments. This research addresses the genotoxic and mutagenic potential of PBDEs. The effects of HepG2 cells and Salmonella typhimurium exposure to six main representatives of PBDEs, namely tetrabromodiphenyl ether (BDE-47), pentabromodiphenyl ether (BDE-99 and BDE-100), hexabromodiphenyl ether (BDE-153 and BDE-154) and decabromodiphenyl ether (BDE-209), were evaluated. The comet assay revealed that all the assessed BDEs exerted genotoxic effects but induced no micronuclei formation in HepG2 cells. These BDEs had no significant mutagenic effects on the Salmonella typhimurium strains TA98 and TA100. Taken together, the results of the genomic instability assays showed that PBDEs can represent a risk to the health of directly and indirectly exposed population, because the assessed BDEs induce genotoxic effects in the HepG2 cell line.