Adverse Psychological and Therapeutic Effects of Kratom (Mitragyna speciosa) Use: A Systematic Review

@#Aims: This review aimed to comprehensively examine kratom’s therapeutic potential for treatment of mental health-related issues as well as any related benefits and risks. Design: Systematic review. Data sources: Google Scholar, Web of Science, PubMed, Scopus, PsycINFO, EMBASE, Cochrane Library, and Medline. Review methods: Three authors carried out electronic search of articles published between 1950 to September 2022 through major databases for a duration of three months (from July to September 2022). Each author independently screened the literature for inclusion and exclusion criteria, the findings were then compared, discrepancies between authors were resolved, and the final selection of articles were reviewed. Results: A total of 46 articles were included in this review. A total of three in vitro and animal studies and five cross-sectional online surveys reported the therapeutic potential of kratom in opioid replacement therapy. In addition, a total of two animal studies and three cross-sectional online surveys highlighted the role of kratom as a potential antidepressant and anxiolytic. Contrastingly, two animal studies, 11 studies in human subjects, and 16 case reports documented the risk of kratom dependence, cravings, tolerance, and kratom-related substance use disorder as the major safety concern of implementing kratom use as a therapeutic agent. Conclusion and impact: In the absence of human clinical trial, coupled with various considerable adverse events of kratom (not limited to psychological side effects), evidence to support kratom as potential therapeutic use remains inconclusive.

Anxiolytic and antidepressant effects of agarwood inhalation and its mechanism / 中国中药杂志

This study used m-chloropheniperazine(MCPP) and chronic unforeseeable mild stress(CUMS) to induce the rat models of anxiety and depression, respectively. The behaviors of rats were observed by the open field test(OFT), light-dark exploration test(LDE), tail suspension test(TST), and forced swimming test(FST), and the antidepressant and anxiolytic effects of agarwood essential oil(AEO), agarwood fragrant powder(AFP), and agarwood line incense(ALI) were explored. The enzyme-linked immunosorbent assay(ELISA) was used to determine the levels of 5-hydroxytryptamine(5-HT), glutamic acid(Glu), and γ-aminobutyric acid(GABA_A) in the hippocampal area. The Western blot assay was used to determine the protein expression levels of glutamate receptor 1(GluR1) and vesicular glutamate transporter type 1(VGluT1), exploring the anxiolytic and antidepressant mechanism of agarwood inhalation. The results showed that compared with the anxiety model group, the AEO, AFP, and ALI groups decreased the total distance(P<0.05), decreased the velocity of movements(P<0.05), prolonged the immobile time(P<0.05), and reduced the distance and velocity of the rat model of anxiety in the dark box(P<0.05). Compared with the depression model group, the AEO, AFP, and ALI groups increased the total distance and average velocity(P<0.05), reduced the immobile time(P<0.05), and reduced the forced swimming and tail suspension time(P<0.05). In terms of transmitter regulation, the AEO, AFP, and ALI groups decreased the level of Glu in the rat model of anxiety(P<0.05) and increased the levels of GABA_A and 5-HT(P<0.05), while the AEO, AFP, and ALI groups all increased the level of 5-HT in the rat model of depression(P<0.05) and decreased the levels of GABA_A and Glu(P<0.05). At the same time, the AEO, AFP, and ALI groups all increased the protein expression levels of GluR1 and VGluT1 in the hippocampus of the rat models of anxiety and depression(P<0.05). In conclusion, AEO, AFP, and ALI exert anxiolytic and antidepressant effects, and the mechanism might be related to the regulation of the neurotransmitter and the protein expression of GluR1 and VGluT1 in the hippocampus.

Jiawei Xiaoyao San in treatment of anxiety disorder and anxiety: A review / 中草药·英文版

Jiawei Xiaoyao San (JWXYS) has shown excellent clinical efficacy in anxiety disorder, but has not yet attracted widespread attention. The animal experiments, clinical trials and mechanism studies of JWXYS were reviewed in this article, which may provide a reference for developing new anxiolytic drugs based on this prescription. The literature was searched in PubMed and CNKI and the documents written in English or with English abstracts were selected. JWXYS could reduce the anxiety symptoms of patients alone and reduce the adverse reactions when it is used in combination with other drugs in the clinic. In preclinical studies, JWXYS also showed therapeutic effects in reducing anxiety-like behavior. The mechanisms may include improving the hypothalamic-pituitaryadrenal (HPA) axis and hormone disorders, increasing neurotransmitter content, neurogenesis, and regulating the synthesis of related enzymes. This article shows that JWXYS could effectively treat anxiety disorders by regulating the central nervous system. In the future, with the participation of more researchers, it is expected to develop innovative drugs for the treatment of anxiety disorders based on JWXYS.

Anxiolytic-like activity of Aloysia virgatavar. platyphylla leaves extract in mice / Actividad ansiolítica del extracto de hojas de Aloysia virgatavar. platyphylla en ratones

Background: Medicinal plants are part of traditional medicine and should be considered a therapeutic alternative for mental diseases. Several plants belonging to the Verbenaceae family have proved useful in treating general anxiety disorders, the most prevalent psychiatric disorders. Objective: This research aimed to verify the extract's safety, the effect on general behavior, and the effect on sleeping time, as well as to evaluate the anxiolytic-like effect of the methanol extract of Aloysia virgata var. platyphylla (Avp), in mice. Methodology: The toxicity test was done according to the OECD guide (mice groups n=5), and general behavior was observed during the assay. Sleeping time was assessed using the pentobarbital-induced hypnosis method (n=8). Male Swiss albino mice (n=6) were treated with 50 to 400 mg/kg of Avp extract and diazepam as a control. The anxiolytic-like effect was tested through the hole board and elevated plus-maze test. Results: The Avp extract has no side effects in tested doses, and no central nervous system depressant activity was noted. A. virgatavar. platyphyllaincreased exploration (number and time) in the hole board. In the elevated plus-maze, increased number and time into open arms were evidenced compared to the control group. Conclusion: With all these results, we concluded that the Avp extract is safe and has a potential anxiolytic-like activity in the animal model used

Antecedentes: Las plantas medicinales forman parte de la medicina tradicional y deben ser consideradas una alternativa terapéutica para las enfermedades mentales. Varias plantas pertenecientes a la familia Verbenaceae han demostrado su utilidad en el tratamiento de los trastornos de ansiedad, uno de los trastornos psiquiátricos más prevalentes. Objetivo: Esta investigación tuvo como objetivo verificar la seguridad del extracto, el efecto sobre el comportamiento general y el efecto sobre el tiempo de sueño, así como evaluar el efecto tipo ansiolítico del extracto metanólico de Aloysia virgata var. platyphylla(Avp), en ratones. Metodología: La prueba de toxicidad se realizó de acuerdo con la guía de la OCDE (grupos de ratones n=5), y se observó el comportamiento general durante el ensayo. El tiempo de sueño se evaluó mediante el método de hipnosis inducida por pentobarbital (n=8). Se trataron ratones albinos suizos macho (n=6) con 50 a 400 mg/kg de extracto de Avp y diazepam como control. El efecto ansiolítico se probó a través de la placa perforada y prueba del laberinto en cruz elevado. Resultados: El extracto de Avp no tiene efectos secundarios en las dosis probadas y no se observó actividad depresora del sistema nervioso central. A. virgata var. platyphylla aumentó la exploración (número y tiempo) en el tablero de agujeros. En el laberinto en cruz elevado, se evidenció un mayor número y tiempo en los brazos abiertos en comparación con el grupo de control. Conclusión: Con todos estos resultados, concluimos que el extracto de Avp es seguro y tiene una potencial actividad ansiolítica en el modelo animal utilizado

Avaliação do uso de psicofármacos por universitários / Evaluation of the use of psychopharmaceuticals by university students

Introdução: depressão e ansiedade têm sido observadas entre universitários, sendo apontado como desencadeadores a sobrecarga de tarefas, cobranças pessoais e familiares entre outros fatores que podem resultar na necessidade de uso de psicofármacos. Objetivo: avaliar o uso de psicofármacos por universitários. Metodologia: estudo transversal, utilizando questionário contendo informações sociodemográficas, econômicas e sobre uso de psicofármacos. Foi realizada análise bivariada com teste qui-quadrado de Pearson para verificar associação entre as variáveis utilização de antidepressivos/ansiolíticos e sociodemográficas e econômicas. Resultados: dos 408 entrevistados, 22,3% afirmaram fazer uso de ansiolíticos/antidepressivos, tendo iniciado após o ingresso na universidade e em uso diário. A maioria relata ter alterado a dosagem sem consultar o médico, asseguraram conhecimento sobre os efeitos adversos do medicamento, sabe que a remoção do medicamento deve ser feita de maneira gradual, mas afirmam ter interrompido o tratamento sem consultar o médico. Permaneceram associadas a utilização de psicofármacos, no modelo final, ser do sexo feminino (p=0,013), idade maior que 29 anos (p=0,009) e possuir plano de saúde (p=0,020). Conclusão: verificou-se a necessidade de alertar a comunidade acadêmica e gestão sobre a necessidade de acolhimento dos universitários em sofrimento mental e propor ações que visem orientar sobre o uso racional dos psicofármacos.

Introduction: depression and anxiety have been observed among university students, with task overload, personal and family demands being pointed out as triggers, among other factors that result in the use of psychotropic drugs. Objective: to evaluate the use of psychopharmaceuticals by university students. Methodology: cross-sectional study, using a questionnaire containing sociodemographic, economic and psychotropic drug use information. A bivariate analysis was performed with Pearson's chi-square test to verify the association between the variables use of antidepressants/anxiolytics and sociodemographic and economic variables. Results: of the 408 respondents, 22.3% said they used anxiolytics/antidepressants, having started after entering university and in daily use. The majority report having changed the dosage without consulting the doctor, assured knowledge about the adverse effects of the medication, know that the removal of the medication must be done gradually, but claim to have stopped the treatment without consulting the doctor. The use of psychotropic drugs in the final model, being female (p=0.013), older than 29 years (p=0.009) and having a health plan (p=0.020) remained associated. Conclusion: there was a need to alert the academic and management community about the need to welcome university students in mental distress and propose actions that aim to guide the rational use of psychotropic drugs.

Anxiolytic and antidepressant effects of cannabidiol: a systematic review / Efeitos ansiolíticos e antidepressivos do canabidiol: uma revisão sistemática

Objetctive: Realize a systematic review on articles about cannabidiol (CBD) as an anxiolytic and antidepressant drug. Methodology: A systematic review in PubMed, Science Direct and PsycINFO databases taking into consideration articles published in English and Portuguese from 2008 to 2018 with animal experimentation. Results: Eleven articles with experimental studies on animals were included. All studies exhibited anxiolytic and antidepressant activities after CBD use. Conclusion: It was proven by several experiments the anxiolytic and antidepressant activity of CBD, however there is still a need of more preclinicals and clinicals studies to elucidate its mechanisms.

Objetivo: Realizar uma revisão sistemática de artigos sobre o canabidiol (CBD) como ansiolítico e antidepressivo. Metodos: Revisão sistemática nas bases de dados PubMed, Science Direct e PsycINFO considerando artigos publicados em inglês e português de 2008 a 2018 com experimentação animal. Resultados: Onze artigos com estudos experimentais em animais foram incluídos. Todos os estudos exibiram atividades ansiolíticas e antidepressivas após o uso de CBD. Conclusão: Foi comprovada por diversos experimentos a atividade ansiolítica e antidepressiva do CBD, porém ainda há necessidade de mais estudos pré-clínicos e clínicos para elucidar seus mecanismos.

Molecular modeling, synthesis, and evaluation of 1-(4-methoxybenzofuran-5-yl)-3-phenylpropane-1, 3-dione for its anxiolytic potentiality

The disabling mental illness anxiety is gradually affecting the modern society in any age group worldwide. The searchfor novel bioactive entity from herbal origin for different disorders has become the center of attraction significantlyfrom the past few decades. Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter known tobe responsible for the anxiolytic activity of most of the potent anxiolytic agents. All the available data of pongamol1-(4-methoxybenzofuran-5-yl)-3-phenylpropane-1, 3-dione (MPD) were based on natural or semi-synthetic source.The synthetic routes were using easily available source and quick, cost-effective, and high yielding process. MPD hastraditionally been acquired from natural sources mainly from the extracts of fruits of Pongamia pinnata and Pongamiaglabra, where the yield value and the yield time are the main drawbacks. Keeping in view of the above aspects in thepresent research, it was approached to synthesize and evaluate the anxiolytic potential 1-(methoxybenzofuran-5yl)-3-phenylpropane-1, 3-dione on experimental animals and docking procedure after its synthesis. The study of MPDon the gross behavior of mice showed a significant Central Nervous System (CNS) depressant effect. Furthermore,its anxiolytic activity was confirmed by observing its reduced locomotion of mice using actophotometer and elevatedplus-maze apparatus. The highest docking score was observed to be −3.22 than the diazepam (−3.21) against GammaAmino Butyric Acid-A (GABAA). The present study provides a promising anxiolytic agent, MPD, which has itspotency due to the GABAA receptor binding and causing the mitigation of the symptoms of anxiety.

Evaluation Of Anti-Anxiety Effect Of Nifedipine Compared To Diazepam In Swiss Albino Mice Using Behavioural Models

Objective: The present study was undertaken to evaluate the acute and chronic anxiolytic effects of nifedipine in comparison to diazepam using in Swiss Albino mice using two behavioral models. Methods: 30 Swiss albino mice were divided into 5 groups with 6 mice in each group. The study was conducted in two phases to evaluate acute and chronic effects. The groups consisted of diazepam (1 mg/kg), 3 doses of nifedipine (2.6 mg/kg, 5.2 mg/kg and 10.4 mg/kg) and vehicle control. The Elevated Plus Maze (EPM) and Light and Dark box were used to evaluate the anti-anxiety effects. The number of entries and time spent in the open arm of the elevated plus-maze and in the light area of light and dark box model were noted and compared among the 5 groups. Observations were analyzed using ANOVA and post hoc Tukey's test. Results: Nifedipine (5.2 mg/kg and 10.4 mg/kg) significantly increased the number of entries and time spent in the open arm compared to vehicle control in the EPM test (p<0.001). Similarly, in the light and dark box test, nifedipine (5.2 mg/kg and 10.4 mg/kg) increased the number of entries and time spent in the light area compared to vehicle control (p<0.05). However, the low dose of nifedipine (2.6 mg/kg) did not exhibit significant findings. Conclusion: Two doses of nifedipine (5.2 mg/kg and 10.4 mg/kg) possess anti-anxiety effects both on acute and chronic administration in both elevated plus maze and light and dark box model.

Citrus limon (L.) Burm f. Essential Oil Has Anxiolytic and Sedative Properties by Modulating GABAA-Receptors

Abstract The high prevalence of anxiety disorders associated with pharmacotherapy side effects have motivated the search for new pharmacological agents. Species from Citrus genus, such as Citrus limon (sicilian lemon), have been used in folk medicine as a potential therapy to minimize emotional disorders. In order to searching for new effective treatments with fewer side effects, the present study evaluated the anxiolytic mechanism of action and the hypnotic-sedative activity from the Citrus limon fruit's peels essential oil (CLEO). Adults male Swiss mice were submitted to barbiturate-induced sleep test; elevated plus-maze (EPM) and light-dark box (LDB) (evaluation of the mechanism of action); rotarod; and catalepsy tests. CLEO oral treatment decreased latency and increased the sleep total time; moreover it induced in animals an increased the number of entries and percentage of time spent into open arms of the EPM; an increased the number of transitions and the percentage of time into light compartment in the LDB; which were only antagonized by flumazenil pretreatment, with no injury at motor function. Thus, results suggest that CLEO treatment induced an anxiolytic behavior suggestively modulated by the benzodiazepine binding site of the GABAA receptor or by an increase of GABAergic neurotransmission, without cause impairment in the motor coordination.

Anxiolytic Effect of Increased NREM Sleep after Acute Social Defeat Stress in Mice / 神经科学通报·英文版

Social defeat stress (SDS) plays a major role in the pathogenesis of psychiatric disorders like anxiety and depression. Sleep is generally considered to involve recovery of the brain from prior experience during wakefulness and is altered after acute SDS. However, the effect of acute SDS on sleep/wake behavior in mice varies between studies. In addition, whether sleep changes in response to stress contribute to anxiety is not well established. Here, we first investigated the effects of acute SDS on sleep/wake states in the active period in mice. Our results showed that total sleep time (time in rapid eye-movement [REM] and non-REM [NREM] sleep) increased in the active period after acute SDS. NREM sleep increased mainly during the first 3 h after SDS, while REM sleep increased at a later time. Then, we demonstrated that the increased NREM sleep had an anxiolytic benefit in acute SDS. Mice deprived of sleep for 1 h or 3 h after acute SDS remained in a highly anxious state, while in mice with ad libitum sleep the anxiety rapidly faded away. Altogether, our findings suggest an anxiolytic effect of NREM sleep, and indicate a potential therapeutic strategy for anxiety.

Percepciones y experiencias de usuarios de benzodiazepinas en la atención primaria de salud en Cuba / Perceptions and experiences of benzodiazepine users in primary health care in Cuba

Resumen A pesar de que son ampliamente conocidos los perfiles de utilización de las benzodiazepinas (BZD) y los riesgos asociados, este conocimiento no ha conducido a visibles transformaciones que mejoren la seguridad de los tratamientos y la salud de los pacientes. Por tanto, es necesaria una mejor compresión del contexto de su utilización, con el fin de implementar acciones educativas eficaces, tomar decisiones clínicas pertinentes y perfeccionar su regulación en los servicios de salud. Este artículo se propone caracterizar el perfil de utilización de benzodiazepinas en un área de salud de Santiago de Cuba y analizar el contexto de consumo a partir de los sentidos construidos por usuarios crónicos. Se realiza un estudio de caso, que describe el perfil de consumo a partir de las recetas dispensadas en la Farmacia Principal Municipal, y se realizan entrevistas a profundidad a los usuarios crónicos. El contenido de las entrevistas fue realizado temáticamente. Los resultados revelan los siguientes temas: poca concientización sobre el beneficio-riesgo del tratamiento, sufrimiento con la dependencia y tolerancia, autonomía en el tratamiento y limitada credibilidad en las terapias alternativas. La proporción de adultos mayores que reciben las BZD es mayor que la identificada en otros estudios. Se concluye que los usuarios perciben aspectos negativos del uso, pero están presos en la dependencia. Se evidencia la importancia de estudiar estrategias para el tratamiento del insomnio y la ansiedad en la atención primaria de salud, así como valorizar las políticas de implementación de terapias naturales y otros abordajes para contribuir al uso racional de las BZD.

Abstract The profiles for the use of benzodiazepines and associated risks are well known. However, this knowledge has not led to visible transformations that improve the safety of treatments and the health of patients. It is therefore necessary to better understand the context of use of these medications in order to implement effective educational actions, make relevant clinical decisions and improve their regulation in health services, especially in primary care. To characterize the profile of use of benzodiazepines in a health area of Santiago de Cuba and to analyze the context of consumption from the senses built by chronic users. Methods: A case study was carried out on the consumption patterns and interviews with chronic users was performed. The content of the interviews was thematically analyzed. The themes revealed were: little awareness of the benefit-risk of treatment; suffering with dependence and tolerance; autonomy in treatment; and limited credibility in alternative therapies. The proportion of older adults receiving benzodiazepines is greater than that identified in other studies. The users perceive negative aspects of use, but they are tied to the dependence. It is evident the importance of studying strategies for the treatment of insomnia and anxiety in primary health care, as well as valuing the policies of implementation of natural therapies and other approaches to contribute to the rational use of benzodiazepines.

Evaluation of anxiolytic properties of BacoMind extract of plant Bacopa monnieri Linn. in comparison with diazepam in rodent model

Background: Anxiety is a state characterized by somatic, emotional, cognitive, and behavioral components, associated with significant disability. The pharmacotherapy for anxiety remains limited for achievable safety and tolerability of the medicines. Benzodiazepines use associated with side effects like psychomotor impairment and addiction liability. Due to the ADRs associated with antianxiety drugs, the drug trials have focused on screening herbal medicines that are reportedly used in the treatment of anxiety and which have minimal side effects.Methods: The anxiolytic activity was examined by using the elevated plus maze (EPM) and open field test (OFT), forty Albino wistar strain rats of both sex of weighing 120 to 200 g were divided into four groups of ten rats each.. Group 1 received vehicle (normal saline); group 2 received diazepam (1 mg/kg); groups 3 and 4 received BacoMind�, 30 and 60 mg/kg oral, respectively.Results: Rats treated with diazepam (1 mg/kg, p.o.) showed significant (p<0.001) increase in the percentage of open arms entries and time spent whereas, in closed arm the number of entries and time spent were significantly (p<0.05) decreased. Intraperitonial administration of BacoMind� extract of plant Bacopa monnieri Linn. exhibited significant (p<0.05) increase in the number of open arm entries and time spent with significant (p<0.05) reduction in number of entries and time spent in the closed arm as compared to group 1. BacoMind� treated rats also produced significant increase in the number of rearings (p<0.05), assisted rearings and number of squares crossed (p<0.01).Conclusions: BacoMind� extract of plant Bacopa monnieri Linn possess significant anxiolytic activity in the rats. It can be a promising anxiolytic agent.

Effects Of Oral Lorazepam Versus Oral Alprazolam On The Postoperative Cognitive Function

Objectives: To compare the effect of oral Lorazepam 1 mg or oral alprazolam 0.5 mg given at night before surgery on cognitive function in patients undergoing elective general surgery receiving general anaesthesia. Methodology: In a prospective double-blind manner 128 patients aged 30 to 50 years belonging to ASA I and II scheduled for elective surgery under general anaesthesia were randomly divided into two equal groups. Group A (n=64) received oral lorazepam 1 mg and Group B (n=64) received oral alprazolam 0.5 mg). Cognitive function were assessed by 1. Rey’s Auditory Verbal Learning test, (RAVLT) test to assess the ability to form new verbal memory, 2. Trail Making Test (TMT) part A to assess psychomotor ability and 3. Digit Span Test to assess short term verbal memory. These were assessed thrice: 1) during preoperative assessment, 2) 30 minutes before induction and 3) 30 minutes after reversal of general anaesthesia, Results: Oral alprazolam affected cognitive processing speed more than oral lorazepam and the association was statistically significant (P-value <0.05) in one of the three tests performed. Other two tests showed statistically insignificant results. Conclusion: Lorazepam might be a better anxiolytic premedicant than alprazolam.

Starvation-induced Changes in Memory Sensitization, Habituation and Psychosomatic Responses

Starvation is a global challenge. Nutritional status of an organism may influence its psychosocial behavior and other nervous system processes like motor responses and its ability to learn and memorize. This study determined the impact of starvation-induced stress on memory sensitization, habituation and psychosomatic responses in an experimental animal design. 25 wistar rats were randomly sampled and grouped into 1-control, 2-feed after 6 hours deprivation, 3-feed after12 hours deprivation, 4-feed after 18 hours deprivation and 5-feed after 24 hours deprivation. Behavioral tests carried out included the multiple maze tests and elevated plus maze test. Grip strength test was performed to determine neuromuscular response and endurance in all groups. Biochemical investigation of brain stress markers was done on the last day of the study. There was a significant (P≤0.05) enhancement in memory processes and anxiolytic behavior after 6 hours feed deprivation. An increase in antioxidants after 6 hours feed deprivation was suspected to be a compensatory response. A progressive decrease in memory facilitation, anxiolytic behavior and muscular strength was reported after 12, 18 and 24 hours feed deprivation. The increase in habituation and decrease in psychosomatic response was observed and appreciated as the duration of feed deprivation was increased. This study provided evidence about a possible link between memory processes and stress-related alterations in calcium, magnesium and nitric oxide. Starvation may impairlearning, memory and motor responses, but this tendency is dependent on the extent of feed deprivation and nutrient depletion.

Neuropharmacological evaluation of methanolic extract of Costus speciosus Linn. rhizome in Swiss albino mice

Objective: To evaluate the neuropharmacological properties of Costus speciosus (C. speciosus) rhizome using different experimental mouse models. Methods: The anxiolytic effect was investigated by hole-board test, elevated plus maze and light/dark test, while central nervous system (CNS) depressant effect was evaluated by thiopental sodium-induced sleep test. Finally, antidepressant effect was evaluated by forced swimming test and tail suspension test. Results: In both elevated plus maze and hole board test, 400 mg/kg C. speciosus showed more significant CNS depressant effect than 1 mg/kg diazepam. Both 200 mg/kg and 400 mg/kg C. speciosus extract produced a significant dose-dependent decrease in onset of sleep. In forced swimming test, C. speciosus rhizome showed a decrease in duration of immobility in a dose-dependent manner. Imipramine (10 mg/kg) and C. speciosus extract at 400 mg/kg dose exhibited a significant reduction in duration of immobility in tail suspension test which provided additional evidence of antidepressant effect of C. speciosus rhizome. Conclusions: Our study indicates that C. speciosus rhizome possesses CNS depressant, anxiolytic and antidepressant-like activities. Further studies are warranted determine the exact phytoconstituents and mechanism of action responsible for the neuropharmacological effect.

Anxiolytic Effect of Chanmu Anshen Granule and Its Bioactive Mechanism / 中国实验方剂学杂志

Objective:To assess the anxiolytic effect of Chaimu Anshen granules (CMASG) and investigate its bioactive mechanism. Method:ICR mice were randomly divided into normal group, diazepam group(0.002 g·kg-1),Jieyu Anshen granules group(0.001 4 g·kg-1), high, medium, and low-dose (0.001 98,0.000 99,0.000 495 g·kg-1)Chaimu Anshen granule groups, with 20 mice in each group. To detect the anxiolytic effect of CMASG, mice were intragastrically administered for 4 weeks in the morning, and light-dark box transition test and open field test were performed once the other day. After the behavior tests, blood samples were collected. Six mice of each group were perfused with formalin through heart, and then the brains were fixed for immunohistochemistry test. Hippocampus of the other mice in each group were collected and stored in liquid nitrogen. The content of γ-aminobutyric acid(GABA)and glutamic acid(Glu)in hippocampus and blood samples were detected by enzyme-linked immunosorbent assay (ELISA), and the ratio of GABA/Glu was calculated. The expression of GABAα1 receptor was evaluated by the immunohistochemistry method. To test the hypnosis effect of CMASG, mice were administered intragastrically for 7 days. The sub-threshold dose of pentobarbital sodium in the sleep experiment was tested. Result:Compared with normal group, the light-dark box transitions test demonstrated that low-dose and medium-dose CMASG groups significantly prolonged the duration in light box(PPPPPPPPPPα1 receptor protein in hippocampus showed that the medium-dose CMASG significantly increased the expression of GABAα1 protein. The sub-threshold dose of pentobarbital sodium on sleep experiments confirmed that the medium-dose CMASG significantly increased the rate of sleep in mice. Conclusion:CMASG showed an anxiolytic effect, and its bioactive mechanism was related with the increase of GABA content, and the decrease of Glu content in hippocampus. Furthermore, it increased the expression of GABAα1 protein in hippocampus. The changes in content of GABA and Glu in peripheral blood were positively correlated with the changes in hippocampal tissues, which provided reference for clinical diagnosis. CMASG also exhibited an effect in improvement of sleep.

Neuropharmacological evaluation of methanolic extract of Costus speciosus Linn. rhizome in Swiss albino mice

To evaluate the neuropharmacological properties of Costus speciosus (C. speciosus) rhizome using different experimental mouse models. Methods: The anxiolytic effect was investigated by hole-board test, elevated plus maze and light/dark test, while central nervous system (CNS) depressant effect was evaluated by thiopental sodium-induced sleep test. Finally, antidepressant effect was evaluated by forced swimming test and tail suspension test. Results: In both elevated plus maze and hole board test, 400 mg/kg C. speciosus showed more significant CNS depressant effect than 1 mg/kg diazepam. Both 200 mg/kg and 400 mg/kg C. speciosus extract produced a significant dose-dependent decrease in onset of sleep. In forced swimming test, C. speciosus rhizome showed a decrease in duration of immobility in a dose-dependent manner. Imipramine (10 mg/kg) and C. speciosus extract at 400 mg/kg dose exhibited a significant reduction in duration of immobility in tail suspension test which provided additional evidence of antidepressant effect of C. speciosus rhizome. Conclusions: Our study indicates that C. speciosus rhizome possesses CNS depressant, anxiolytic and antidepressant-like activities. Further studies are warranted determine the exact phytoconstituents and mechanism of action responsible for the neuropharmacological effect.

Hydroethanolic extract of Tropaeolum majus promotes anxiolytic effects on rats

Abstract Tropaeolum majus L., Tropaeolaceae, popularly known in Brazil as 'capuchinha' is widely used due its anti-inflammatory, antiseptic, anti-hypertensive and anti-depressive properties. However, scientific investigations about its effects on the central nervous system are still scarce. This study investigated the central pharmacological actions of the prolonged treatment with a hydroethanolic extract of T. majus in male Wistar rats in the elevated plus maze and hole-board behavioral models. For this, rats were daily treated with distillated water (negative control); diazepam (1 mg/kg) or hydroethanolic extract of T. majus (75, 150 and 300 mg/kg), for 29 days (by gavage) and were submitted to elevated plus maze and hole-board. Animals treated with all hydroethanolic extract of T. majus or diazepam doses increased the percentage of entries in open arms when compared to control group. However, only treatment with diazepam increased the length of time spent in the open arms of the elevated plus maze. No differences between all groups were observed regardless rearing, grooming, stretched-attend postures and defecation rates. In the HB test, in opposite to diazepam, treatment with hydroethanolic extract of T. majus did not interfere in the exploratory activity of rats. The hydroethanolic extract of T. majus promotes anxiolytic-like effects when orally administered in rats.

Evaluation of anxiolytic activity of aqueous extract of Nerium oleander flowers in albino rats

Background: Anxiety has become a very important area of research interest in psychopharmacology as it affects one-eighth of the population worldwide. Benzodiazepines are still the most commonly used drugs for anxiety despite a number of side effects.There is a need for newer antianxiety drugs with increased safety and efficacy, hence this study was undertaken to evaluate the anxiolytic activity of Nerium oleander flowers.Methods: Aqueous extract of Nerium oleander flowers (NA) was prepared using soxhalet apparatus. A total of 24 Albino rats aged 8-10 weeks of either sex weighing about 100-150g were obtained and divided into 4 groups of 6 rats each. Group I: Normal saline 10mL/kg. Group II: Diazepam 2mg/kg Group III: NA at a dose of 200 mg/kg Group IV: NA at a dose of 400mg/kg. The anxiolytic activity of Aqueous extract of NA was tested by elevated plus maze and digital actophotometer models. Data was analysed using one way ANOVA followed by Posthoc Tukey’s test.Results: In EPM model, the NA at 200, 400mg/kg doses showed that the number of entries and time spent in the open arms were increased significantly as compared to the control animals. (p<0.001). In Actophoptometer model, two different doses of NA (200 and 400mg/kg) showed a dose-dependent decrease in the locomotor activity, when compared to the control animals (p<0.001).Conclusions: Both the doses of aqueous extract of Nerium oleander flowers (200mg and 400mg/kg) possess anxiolytic activity and could be used as a new approach to treat anxiety.

A study on anxiolytic activity and locomotor behavior of Curcuma amada rhizomes using Wistar albino rats

Background: Global burden of disease statistics indicate that 4 of 10 most important causes of disease worldwide are psychiatric in origin. Anxiety affects 1/8th of total population of the world and is a very important area of research interest in psychopharmacology. Medicinal plants and plant products are the oldest tried health-care products. Their importance is growing not only in developing countries but in many developed countries. Curcuma amada Roxb. (CA) commonly known as Mango Ginger is a rhizomatous aromatic herb which is used in this country for culinary purposes and also to treat various diseases. The rhizomes of Curcuma amada was screened for anxiolytic activity and locomotor behavior in Wistar albino rats.Methods: Wistar albino rats were divided into three groups as control (Distilled water with 0.1% CMC), standard (Diazepam - 1mg/kg) and test - Ethanolic Extract of Curcuma amada Rhizome (EECAR-250 mg/kg). They were administered drugs orally for a period of 10 days, and screened for anxiolytic activity using Light dark arena model and Actophotometer for assessing the locomotor behavior on the 10th day. The number of crossings and time spent in light arena for anxiolytic activity, and the number of movements in Actophotometer was noted. Data was analyzed by one way ANOVA followed by Tukey Kramer multiple comparison test using GraphPad InStat software.Results: Curcuma amada (250mg/kg) showed increased time spent in light arena and decreased locomotor behavior which was statistically significant.Conclusions: Curcuma amada possesses significant anxiolytic with CNS depressant activity.