Anti-anxiety Effects Research Articles

Safety and Anti-Fatigue Activity of Ayurvedic Formulation <i>Sramahara Mahaakaasaya</i> - A Pre-Clinical Study

An experimental evaluation of anti-fatigue activity of Shramahara Mahaakashaaya (SM) and its applicability in sports medicine has been systematically evaluated. Aqueous, ethanolic and petroleum ether extracts of SM granules (200mg/kg) were studies for light-dark model test for assessment anti-anxiety effect, rota-rod test for assessment of the effect on muscle tone and muscle balance, weight loaded forced swimming test for assessment of anti-fatigue activity. The acute toxicity study of SM granules has also been evaluated as per the OECD 423. SM granules showed significant anti-fatigue activity in different experimental models and found safe up to 2000mg/kg body weight dose. The results provide an important basis for considering Shramahara Mahaakashaaya (SM) as an alternative medicine having anti-fatigue effects which can be further included in the sports medicine.

The research progress on the anxiolytic effect of plant-derived flavonoids by regulating neurotransmitters.

Phytopharmaceuticals have attracted a lot of attention due to their multicomponent and multiple targets. The natural phenolic chemicals known as flavonoids are found in a wide variety of plants, fruits, vegetables, and herbs. Recently, they have been found to have modulatory effects on anxiety disorders, with current research focusing on the modulation of neurotransmitters. There has not yet been a review of the various natural flavonoid monomer compounds and total plant flavonoids that have been found to have anxiolytic effects. The study on the anti-anxiety effects of plant-derived flavonoids on neurotransmitters was reviewed in this paper. We, therefore, anticipate that further study on the conformational interaction underlying flavonoids' anti-anxiety effects will offer a theoretical framework for the creation of pertinent treatments.

Agarwood essential oil inhalation exerts antianxiety and antidepressant effects via the regulation of Glu/GABA system homeostasis.

Depression and anxiety are common diseases that endanger the physical and mental health of individuals. Agarwood incense inhalation has been used as a traditional Chinese medicine for relaxation and to improve sleep for centuries. In a previous study by the authors it was demonstrated that agarwood essential oil (AEO) injection exerted anxiolytic and antidepressant effects. Therefore the present study further investigated the anxiolytic and antidepressant effects of AEO inhalation on anxiolytic mice induced by M-chlorophenylpiperazine and depressive mice induced by chronic unpredictable mild stress. The results demonstrated that AEO exerted a significant anxiolytic effect, whereby autonomous movements were inhibited during the light dark exploration test and open field test. Furthermore, the tail suspension test and the forced swimming test demonstrated that AEO also exerted an antidepressant effect, whereby the immobility times were decreased. Moreover, AEO was determined to increase the levels of 5-hydroxytryptamine, γ-aminobutyric acid (GABA) A receptor (GABAA) and glutamate (Glu) in anxiolytic mice and inhibit the levels of GABAA and Glu in depressive mice. Further investigations into how AEO affected the Glu/GABA system demonstrated that AEO markedly increased the protein expression levels of GABA transaminase (GABAT), glutamate metabotropic receptor 5 (GRM5), glutamate ionotropic receptor AMPA type subunit 1 (GluR1) and vesicular glutamate transporter 1 (VGluT1). Furthermore, AEO reduced the expression levels of GABAT, glutamate ionotropic receptor NMDA type subunit 2B and GRM5, and enhanced the expression levels of GluR1 and VGluT1. These results demonstrated that AEO potentially possesses antianxiety and antidepressant properties. The present study determined that the mechanism was related to the regulation of Glu/GABA neurotransmitter system homeostasis.

Anti-inflammatory and analgesic effect of Forsythiaside B on complete Freund's adjuvant-induced inflammatory pain in mice

Chronic pain is frequently reported in clinical practice. Therefore, it is important to identify effective therapy to relieve pain. In this work, we selected Forsythoside B (FB), a phenylethanoid glycoside isolated from Forsythia suspensa (Thunb.) Vahl, to evaluate its effect in modulating inflammatory pain induced by complete Freund's adjuvant (CFA) and the involved mechanisms. We discovered that FB could attenuate inflammatory pain triggered by CFA injection and exert anti-anxiety effects. In detail, proinflammatory cytokines, consisting of IL-6 and TNF-α, were decreased after FB administration in the CFA-injected mice. Furthermore, the FB application ameliorated the activation of ionized calcium-binding adaptor molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP), the microglia and astrocytes markers respectively. Therefore, our findings indicate that FB could be a promising treatment for chronic inflammatory pain.

Anxiolytic-like effect of Suanzaoren–Wuweizi herb-pair and evidence for the involvement of the monoaminergic system in mice based on network pharmacology

BackgroundSuanzaoren-Wuweizi herb-pair (SWHP), composed of Zizyphi Spinosi Semen (Suanzaoren in Chinese) and Schisandrae Chinensis Fructus (Wuweizi in Chinese), is a traditional herbal formula that has been extensively used for the treatment of insomnia. The study aimed to explore the targets and signal pathways of Suanzaoren-Wuweizi (S-W) in the treatment of anxiety by network pharmacology, and to verify the pharmacodynamics and key targets of SWHP in mice.MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) as well as literature mining were used to obtain the main chemical ingredients of Suanzaoren and Wuweizi. The SwissTargetPrediction platform was used to predict drug-related targets. The GeneCards, TTD, DisGeNET and OMIM databases were used to obtain potential targets for the treatment of anxiety with the chemical components of S-W. Drug-disease intersection genes were selected, and a protein-protein interaction (PPI) network was constructed using STRING. The core targets of S-W in the treatment of anxiety were selected according to the topological parameters, and GO functional enrichment as well as KEGG pathways enrichment analyses were performed for potential targets. The relationship network of the “drug-active ingredient-disease-target-pathway” was constructed through Cytoscape 3.8.0. The pharmacodynamics of SWHP in the treatment of anxiety was evaluated by the elevated plus maze (EPM), the light/dark box test (LDB) and the open field test (OFT). The mechanisms were examined by measuring monoamine neurotransmitters in brain of mice.ResultsThe results showed that there were 13 active ingredients for the treatment of anxiety in the network. This includes sanjoinenine, swertisin, daucosterol, schizandrer B, wuweizisu C and gomisin-A. Additionally, there were 148 targets, such as AKT1, TNF, SLC6A4, SLC6A3, EGFR, ESR1, HSP90AA1, CCND1, and DRD2, mainly involved in neuroactive ligand-receptor interactions, the Serotonergic synapse pathway and the cAMP signaling pathway. After 1 week of treatment, SWHP (2 and 3 g/kg) induced a significant increase on the percentage of entries into and time spent on the open arms of the EPM. In the LDB test, SWHP exerted anxiolytic-like effect at 2 g/kg. In the open-field test, SWHP (2 g/kg) increased the number of central entries and time spent in central areas. The levels of brain monoamines (5-HT and DA) and their metabolites (5-HIAA, DOPAC) were decreased after SWHP treatment.ConclusionsThe anti-anxiety effect of SWHP may be mediated by regulating 5-HT, DA and other signaling pathways. These findings demonstrated that SWHP produced an anxiolytic-like effect and the mechanism of action involves the serotonergic and dopaminergic systems, although underlying mechanism remains to be further elucidated.

Preparation of β-lactoglobulin-derived tryptophan peptide and its effect on anxiety-like behaviors in Zebrafish.

This study aimed to obtain three Trp-containing peptides from β-lactoglobulin and study their effects on anxiety-like behaviors in zebrafish. Three Trp-containing peptides were prepared from β-lactoglobulin by selective enzymatic hydrolysis and identified by UPLC-Q-TOF MS/MS. The anxiety-like behaviors of zebrafish were reduced after two weeks of administrated of β-lactoglobulin Trp peptides (LAWP), VAGTWY, VAGTW and G TW(concentration of 56 μg/mL or 500 μg/mL). As an index of serotonergic activity, we assessed the enhancing abilities of 5-HT synthesis. The treatment remarkably enhanced the 5-HT synthesis by upregulation of Trp concentration and Trp hydroxylase activation. In addition, this study further validated the anti-anxiety effects of whey protein hydrolysate with a high Trp index in animal and the experimental results were consistent with those reported in previous studies. Our results showed that β-lactoglobulin Trp peptides ingestion has a significant anti-anxiety effect as evidenced by the increasing Trp concentration, TPH activation and 5-HT level compared to the control group, with the VAGTW being the more effective.

Evaluation of anxiolytic effect of combination of tramadol with gabapentin and pregabalin in Wistar rats

Background: Anxiety is a widespread disorder that approximately 18% of the population experience at some stage in their lives. Pain is a common stimulus that induces anxiety in both animals and human beings. Combination of drugs with good anti-anxiety and analgesic effect can be used for the treatment of chronic pain induced anxiety, post-operative, and procedure-related pain-induced anxiety. Aims and Objectives: The study was conducted to evaluate the anxiolytic activity of combination of gabapentin with tramadol, pregabalin with tramadol compared to standard fluoxetine, in elevated plus maze (EPM) and light-dark arena (LDA) models of anxiety in Wistar albino rats. Materials and Methods: Twenty-four male or female albino Wistar rats from Central Animal House, MRMC, Kalaburagi, were utilized. Fluoxetine 10 mg/kg, gabapentin 30 mg/kg, tramadol 30 mg/kg, and pregabalin 30 mg/kg were used. Eddy’s hot plate method used for inducing anxiety. EPM and LDA models were used to study the effect of drugs in reducing the pain and anxiety. Results: The present study showed that the exposure to hot plate induces pain, creates anxiety, and reduces locomotor and explorative activity among the rats when exposed to hot plate. There was reduction in anxiety after drug administration, in fluoxetine and gabapentin with tramadol groups with >75% increase in entry into the light chamber or open arm at least once or more during the time period of 5 min when compared to hot plate post-exposure readings. Whereas in pregabalin and tramadol group, it was observed that 25% increase in entry of rats into open arm at least once during the time period of 5 min and 25% decrease in entry of rats into light chamber as compared to those rats after exposure to hot plate. Conclusion: Our study has demonstrated that tramadol, pregabalin, and gabapentin have got analgesic as well as anti-anxiety effects in rats when given in combination. All these experimental data, together with the previous experimental studies and the results reported in this work, suggest that combination of these drugs could be more effective in treating anxiety-related disorders such as chronic pain, pain-induced anxiety, post-operative, and procedure-related pain-induced anxiety with minimal side effects. Further dose ranging studies and models might be necessary to better understand the effects of these drugs in combination.

A Comparison of the Anti-Anxiety Effects of Oral Ketamine and Fluvoxamine in Children with Separation Anxiety Disorder Manifesting as School Refusal.

Children suffer from a high prevalence of anxiety problems that require prompt treatment. It has been demonstrated that ketamine offers rapid anti-anxiety effects. This study aimed to evaluate ketamine's anti-anxiety impact in the treatment of children with school-refusal separation anxiety disorder. In this open-labeled randomized clinical trial, 71 children (6-10 years) diagnosed with school refusal separation anxiety disorder were randomly assigned to two groups; a case group, who received ketamine at a weekly rising dose of 0.1 to 1 mg/kg; the control group treated with Fluvoxamine (25 mg/day), which could increase to 200 mg/day if necessary. The SCARED and CATS questionnaires were used to assess anxiety before treatment, at the 8th and 16th weeks of intervention. The data were analyzed using repeated-measures analysis of covariance. The mean anxiety scores in the eighth week (19.7 ± 16.1) were significantly lower in the ketamine group than before (31.5 ± 10.8). Until the sixteenth week (19.4 ± 14.6), there was no further decrease in scores in the ketamine group, in the fluvoxamine group, pre-treatment scores (36.3 ± 16.5) and eighth week (36.9 ± 16.6) were not significantly different, but scores decreased significantly in a sixteenth week (26.2 ± 12.5). In first eight weeks of treatment, ketamine was more successful than fluvoxamine at reducing anxiety disorder, considering the emergence of this disorder and the lack of major adverse effects of ketamine, it seems to be beneficial in early phases of treatment. Due to the quick onset of ketamine in future trials, their combination therapy is recommended during the initial weeks of treatment.

Evaluation of antianxiety effect of Nigella sativa Linn. seed oil in mice

Evaluation of antianxiety effect of Nigella sativa Linn. seed oil in mice

Evaluation of anti-anxiety effects of the hydromethanolic extract of Boerhaavia diffusa L. roots in mice exposed to unpredictable chronic mild stress

Evaluation of anti-anxiety effects of the hydromethanolic extract of Boerhaavia diffusa L. roots in mice exposed to unpredictable chronic mild stress

Analgesic and anti-anxiety activity of two Ayurvedic formulations (Rasnadi ksheerapaka and Sahacharadi taila) on experimental rat models

Background: Rasnadi ksheerapaka and Sahacharadi taila are known to be effective in shula and vatavyadhi and used very frequently in conditions involving pain. Aims and objective: To evaluate the analgesic and anti-anxiety activity of Rasnadi ksheerapaka and Sahacharadi taila matrabasti in Charles Foster Albino rats. Materials and method: For evaluation of analgesic study tail flick response in tail flick test and paw licking response in Eddy’s hot plate test was performed. Anti-anxiety study was conducted with elevated plus maze and open field maze. Result and conclusion: After both the experiments it is effectively proven that both test drugs Rasnadi ksheera paka and Sahacharadi taila have analgesics effects but they failed to exhibit anti-anxiety effect in rats.

Astrocytic SIRT6 is a potential anti-depression and anti-anxiety target

Sirtuin 6 (SIRT6) is a nuclear silencing information regulator that is widely expressed in brain. Inhibition of SIRT6 in the brain induced antidepressant effects in rodents. However, SIRT6 knockout in neurons induced developmental retardation and cognitive impairments. In this study, a mouse strain of astrocyte conditional knockout SIRT6 (AKO) was constructed. Unlike whole brain SIRT6 knockout mice, AKO mice did not show growth retardation. We showed that SIRT6 knockout in astrocytes did not impair the learning and memory ability of mice. Chronic unpredictable mild stress (CUMS) was used to evaluate the anti-depression and anti-anxiety effects in mice. In tail suspension test and forced swimming test, AKO mice did not show depression like phenotype induced by CUMS. In addition, knockout of SIRT6 in astrocytes alleviated the high anxiety level induced by CUMS in light and dark box test, open field test and elevated cross maze test. Three box social test showed that the deletion of SIRT6 in astrocytes changed the social preference of mice. Re-expression of SIRT6 in astrocytes mediated by adeno-associated virus reversed the social preference of AKO mice, but the re-expression also eliminated the anti-depression and anti-anxiety effects in AKO mice. Deletion of SIRT6 in astrocytes change the purine metabolic homeostasis of medial prefrontal cortex in mice. The results of transcriptomics and metabolomics analysis showed that the deletion of SIRT6 would change the purine metabolic pathway of cultured astrocytes and increase the contents of inosine and the second messenger cyclic adenosine monophosphate in astrocytes. In conclusion, knockout of SIRT6 in astrocytes induced anti-depression and anti-anxiety effects in mice without impairing the development and cognitive ability of mice.

Divergent modulation of pain and anxiety by GABAergic neurons in the ventrolateral periaqueductal gray and dorsal raphe

The ventrolateral periaqueductal gray (vlPAG) collaborates with the dorsal raphe (DR) in pain regulation and emotional response. However, the roles of vlPAG and DR γ-aminobutyric acid (GABA)-ergic neurons in regulating nociception and anxiety are contradictory and poorly understood. Here, we observed that pharmacogenetic co-activation of vlPAG and DR GABAergic (vlPAG-DRGABA+) neurons enhanced sensitivity to mechanical stimulation and promoted anxiety-like behavior in naïve mice. Simultaneous inhibition of vlPAG-DRGABA+ neurons showed adaptive anti-nociception and anti-anxiety effects on mice with inflammatory pain. Notably, vlPAGGABA+ and DRGABA+ neurons exhibited opposing effects on the sensitivity to mechanical stimulation in both naïve state and inflammatory pain. In contrast to the role of vlPAGGABA+ neurons in pain processing, chemogenetic inhibition and chronic ablation of DRGABA+ neurons remarkably promoted nociception while selectively activating DRGABA+ neurons ameliorated inflammatory pain. Additionally, utilizing optogenetic technology, we observed that the pronociceptive effect arising from DRGABA+ neuronal inhibition was reversed by the systemic administration of morphine. Our results collectively provide new insights into the modulation of pain and anxiety by specific midbrain GABAergic subpopulations, which may provide a basis for cell type-targeted or subregion-targeted therapies for pain management.

Investigating the Avocado (Persea americana) fruit's anti-anxiety potentials in rat models

Background and aimAnxiety has an effect on the common regular living of a human as it causes fatigue and restlessness. In the current study, an effort was undertaken to investigate the anti-anxiety behavior of male albino by the treatment of Avocado Powder and Juice in vivo. MethodsAvocado Powder 10 % (AP1) and 15 % (AP2) substituted from the diet and Avocado Juice 100 mL/kg (AJ1) and150ml/kg body weight (AJ2) rat over control rats. ResultsThe oral intake of Avocado powder and Juice caused a significant decrease in the body weight gain, daily feed intake, and feed efficiency ratio (FER) in all experimental groups tested as compared to control. Also, the activity of the antioxidant enzymes like SOD, GST, GPX, and Catalase is not much influenced by the intake of avocado fruit. This significant result has confirmed the effectiveness of this fruit for the treatment of anxiety. The anti-anxiety effect of the avocado fruit was tested by exploring the behavioral changes tests in experimental rats. All the experiments conducted showed that the intake of dose AP2 and AJ2 has significantly decreased the number of head dips and cage crossing and increased the time spent in light side in light–dark transition box test, and increased time spent in open arm in elevated plus maze test. ConclusionsThis result proved that the avocado fruit as powder then as juice have an anxiolytic effects and will be a better alternative for people with an anxiety disorder.

MOLECULAR MECHANISMS DEFINING APPLICATION OF GLYCINE AND ZINC COMBINATIONIN CORRECTION OF STRESS AND ANXIETY MAIN MANIFESTATIONS

The aim of the work was to carry out a systematic analysis of the molecular mechanisms that determine the possibility of a combined use of amino acid glycine and zinc compounds for the treatment of patients with manifestations of stress and anxiety.Materials and methods. Information retrieval (Scopus, PubMed) and library (eLibrary) databases were used as research tools. In some cases, the ResearchGate application was applied for a semantic search. The analysis and generalization of references was carried out on the research topic, covering the period from 2000 to the present time.Results. It has been shown that amino acid glycine, along with gamma-aminobutyric acid (GABA), is a key neurotransmitter that regulates physiological inhibition processes in the central nervous system (CNS) by increasing transmembrane conductance in specific pentameric ligand-gated ion channels. The introduction of zinc ions can potentiate the opening of these receptors by increasing their affinity for glycine, resulting in an inhibitory processes increase in CNS neurons. The replenishment of the glycine and zinc combined deficiency is an important element in the correction of a post-stress dysfunction of the central nervous system. A balanced intake of zinc and glycine is essential for most people who experience daily effects of multiple stresses and anxiety. This combination is especially useful for the people experiencing a state of chronic psycho-emotional stress and maladaptation, including those who have a difficulty in falling asleep.Conclusion. A balanced maintenance of the zinc and glycine concentration in the body of a healthy person leads to the development of a stable anti-anxiety effect, which is accompanied by the normalization of the sleep-wake rhythm, which makes it possible to have a good rest without any loss of working efficiency after waking up.

EVALUATION OF CNS DEPRESSANT AND BEHAVIORAL ACTIVITY OF AN ETHANOL EXTRACT OF ZIZIPHUS JUJUBA (BER) IN MOUSE MODEL

Objective: Ziziphus jujuba, known as Ber (Hindi), is an indigenous herb found in India. Z. jujuba has been used to treat various diseases such as respiratory system diseases (asthma, cough, and laryngitis), gastrointestinal problems (constipation, colitis, and liver diseases), as well as cardiovascular and genitourinary system diseases. Seeds and fruit have been also reported to have central nervous system (CNS) depressant effect. Hence, in this study, neuropharmacological effects of leaves are studied which are not reported previously. Z. jujuba extract’s potential to depress the CNS and affect behavior was examined in this study, along with the phytochemicals that may be responsible for these effects. Methods: 400 mg/kg of the extract was administered intraperitoneally. As a benchmark, diazepam (2 mg/kg body weight i.p.) was used. ANOVA and Dunnett’s tests were used to evaluate the data. The results were all presented as Mean (SEM) values. p>0.05 was regarded as meaningful. Result: The outcome of the study demonstrated that ethanol extract of Z. jujuba (400 mg/kg i.p.) reduced locomotion, caused muscle relaxation, and had anti-anxiety effects. Conclusions: Ethanols extract of Z. jujuba leaves exhibits CNS depressant action and significant anxiolytic activity comparable to diazepam.

First Anti-Inflammatory Peptide AnmTX Sco 9a-1 from the Swimming Sea Anemone Stomphia coccinea.

A novel peptide AnmTX Sco 9a-1 with the β-hairpin fold was isolated from the swimming sea anemone Stomphia coccinea (Actinostolidae family). The peptide consists of 28 amino acid residues, including modified hydroxyproline residue, and its measured molecular mass is 2960 Da. The peptide was not toxic on mice; however, it stimulated their exploratory motivation and active search behavior, and demonstrated an anti-anxiety effect. AnmTX Sco 9a-1 at doses of 0.1 and 1 mg/kg reduced the volume of edema during 24 h better than the nonsteroidal anti-inflammatory drug, Diclofenac, at dose of 1 mg/kg in a model of acute local λ-carrageenan-induced inflammation. ELISA analysis of the animal's blood showed that peptide at a dose of 1 mg/kg reduced the content of tumor necrosis factor-α (TNF-α), a pro-inflammatory mediator responsible in the edema development, up to the level of TNF-α in the intact group. Besides, AnmTX Sco 9a-1 demonstrated a significant analgesic effect on acute pain sensitivity in the carrageenan-induced thermal hyperalgesia model at doses of 0.1 and 1 mg/kg. Activity of AnmTX Sco 9a-1 was shown not to be associated with modulation of nociceptive ASIC channels.

Overcoming Anxiety Disorder by Probiotic Lactiplantibacillus plantarum LZU-J-TSL6 through Regulating Intestinal Homeostasis.

Lactiplantibacillus plantarum LZU-J-TSL6 with high γ-aminobutyric acid (GABA) production (3.838 g/L) was screened and isolated from the Chinese fermented food snack "Jiangshui". The improvement effect on anxiety disorder was explored using mice as animal models. In vitro results revealed that LZU-J-TSL6 had the potential to colonize the intestine (p < 0.01) and the anxiety-like behavior of the mice after seven days' gavage with LZU-J-TSL6 was significantly improved (p < 0.01) when compared to the model group. LZU-J-TSL6 was able to effectively increase the GABA content in the mice hippocampus (p < 0.0001) and restore some markers related to anxiety such as brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), and 5-hydroxytryptamine (5-HT). Simultaneously, it had a certain repair effect on Nissl bodies and colon tissue in mice hippocampus. In addition, LZU-J-TSL6 increased the relative abundance of beneficial bacteria Bacteroides and Muribaculum, thereby regulating the imbalance of intestinal microbiota caused by anxiety disorder. It also affects the nerve pathway and intestinal mucosal barrier by increasing the content of glutamine and γ-aminobutyric acid and other related metabolites, thereby improving anxiety. Therefore, the GABA-producing Lactobacillus plantus LZU-J-TSL6 can be used as a probiotic to exert an indirect or direct anti-anxiety effect by maintaining the balance of the intestinal environment, producing related metabolites that affect nerve pathways and repair the intestinal mucosal barrier. It can be used as an adjuvant treatment to improve anxiety disorders.

Pharmacological Aspects and Biological Effects of Cannabigerol and Its Synthetic Derivatives.

Cannabigerol (CBG) is a cannabinoid from the plant Cannabis sativa that lacks psychotomimetic effects. Its precursor is the acidic form, cannabigerolic acid (CBGA), which is, in turn, a biosynthetic precursor of the compounds cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). CBGA decarboxylation leads to the formation of neutral cannabinoid CBG, through a chemical reaction catalyzed by heat. On the basis of the growing interest in CBG and with the aim of highlighting scientific information on this phytocannabinoid, we focused the content of this article on its pharmacokinetic and pharmacodynamic characteristics and on its principal pharmacological effects. CBG is metabolized in the liver by the enzyme CYP2J2 to produce hydroxyl and di-oxygenated products. CBG is considered a partial agonist at the CB1 receptor (R) and CB2R, as well as a regulator of endocannabinoid signaling. Potential pharmacological targets for CBG include transient receptor potential (TRP) channels, cyclooxygenase (COX-1 and COX-2) enzymes, cannabinoid, 5-HT1A, and alpha-2 receptors. Pre-clinical findings show that CBG reduces intraocular pressure, possesses antioxidant, anti-inflammatory, and anti-tumoral activities, and has anti-anxiety, neuroprotective, dermatological, and appetite-stimulating effects. Several findings suggest that research on CBG deserves to be deepened, as it could be used, alone or in association, for novel therapeutic approaches for several disorders.

A Comparative Evaluation of the Anxiolytic Effect of Oral Midazolam and a Homeopathic Remedy in Children During Dental Treatment.

Background Midazolam is recommended by many health standards. However, there is no compelling evidence that midazolam has anti-anxiety effects in children. Homeopathy can be one of the mainstays for effective child management while reducing negative side effects. The aim of the study was to evaluate the anxiolytic efficacy of midazolam (oral) and homeopathic remedies in children during dental treatments. Methodology The current ex-vivo study was conducted in the department of Pedodontics and Preventive Dentistry department of a private dental institution. A total of 48 children aged four to 14 years were selected based on the inclusion and exclusion criteria. The participants were evenly and randomly divided into groups A and B using the lottery method. Group A: 20 minutes previous to the treatment, a right blend of an equal volume of 0.5mg/kg injectable solution of midazolam hydrochloride. Group B: Received Aconite napellus (homeopathic remedy). Results During anxiety, the hypothalamic pituitary adrenal axis gets activated which causes a release of body fluids including salivary cortisol levels. Salivary amylase also responds quickly during stress and anxiety by increasing its levels. Midazolam is used in Dentistry to reduce anxiety as it is able to reduce salivary cortisol and amylase levels.Aconite napellus being homeopathic remedy is useful in Dentistry to reduce salivary cortisol and amylase levels which is observed in the present study. There was a decrease in salivary cortisol and amylase concentrations following midazolam (8.51 ± 6.7) (41.48 ± 23.8) and Aconite napellus (homeopathic remedy) (7.53 ± 5.2) (37.08± 22.8) administration, as well as a decrease in heart rate, systolic and diastolic blood pressure. Furthermore, all of the differences were statistically significant (p<0.05). Conclusion In children with behavioral difficulties, homeopathic remedy was marginally more successful than oral midazolam in lowering anxiety during dental treatment.