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Hongqing Zhao,1,2,* Yang Liu,1,2,* Na Cai,3 Xiaolin Liao,1,2 Lin Tang,2,4 Yuhong Wang1,2 1Science & Technology Innovation Center, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of China; 2Hunan Key Laboratory of Traditional Chinese Medicine Prevention & Treatment of Depressive Diseases, Changsha, Hunan, People’s Republic of China; 3Outpatient Department, the First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of China; 4Department of Pharmacy, the First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lin Tang; Yuhong Wang, Email tanglin0018@163.com; wangyh107@126.comAbstract: Over the past decade, the idea of targeting the endocannabinoid system to treat anxiety disorders has received increasing attention. Previous studies focused more on developing cannabinoid receptor agonists or supplementing exogenous cannabinoids, which are prone to various adverse effects due to their strong pharmacological activity and poor receptor selectivity, limiting their application in clinical research. Endocannabinoid hydrolase inhibitors are considered to be the most promising development strategies for the treatment of anxiety disorders. More recent efforts have emphasized that inhibition of two major endogenous cannabinoid hydrolases, monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), indirectly activates cannabinoid receptors by increasing endogenous cannabinoid levels in the synaptic gap, circumventing receptor desensitization resulting from direct enhancement of endogenous cannabinoid signaling. In this review, we comprehensively summarize the anxiolytic effects of MAGL and FAAH inhibitors and their potential pharmacological mechanisms, highlight reported novel inhibitors or natural products, and provide an outlook on future directions in this field.Keywords: endocannabinoid hydrolase inhibitors, endocannabinoid system, anxiety disorders, anxiolytic, MAGL, FAAH

Abstract Brassaiopsis palmata, an androgynous tree from Araliaceae family, has been widely found in the Asian subcontinent, and reported to have potentiality against skin infection, and many therapeutic properties still unidentified. Here, our current investigation aims to discover the innovative pharmacological potentials of the methanol extract of B. palmata leaves (MEBPL) through in‐vivo and in‐vitro approaches. Several secondary metabolites were revealed throughout the qualitative phytochemical screening of the plant extracts. MEBPL exhibited strong radical scavenging properties (IC50 178.13 µg/mL) through the 2, 2‐diphenyl‐1‐picryhydrazyl (DPPH) assay, and through the quantitative (phenolic and flavonoid) assays with a moderate (LD50 153.14 µg/mL) toxic effect. In anti‐inflammatory screening, MEBPL showed significant dose dependent inhibitory activity; and the peak inhibition were found 78.01 ± 1.22% and 82.46 ± 1.52% at 1000 µg/mL concentration on hypotonic‐induce RBC hemolysis & protein denaturation test respectively. Moreover, the plant extracts manifested moderate percentage of clot lysis (28.24 ± 2.50%) on the investigation of thrombolytic assay. The anti‐nociceptive activity of MEBPL was analyzed through acetic acid and formalin induce pain tests. Both 200 and 400 mg/kg dose of MEBPL exerted significant (p ˂ 0.001) dose depending depletion of acetic acid induced writhing and formalin stimulated licking test which indicated strong analgesic properties of plant extracts. In addition, the outcomes of anti‐depressant evaluation suggested that treatment with both 200 and 400 mg/kg doses showed potential dose depending activity on both FST and TST model. Furthermore, the plant extracts manifested dose dependent reduction of anxiety like behaviors in the rodent model. Particularly, mice administrated with 400 mg/kg dose of MEBPL significantly (p ˂ 0.05) enhanced the percentage of entries and time spent in the open arm in EPM, and also showed the highest amount of head dipping tendency in HBT. In contrast, the outcomes of this research suggest that B. palmata could be another source of antioxidant, cytotoxic, anti‐inflammatory, thrombolytic, anti‐nociceptive, anti‐depressant, and anxiolytic agents. Further research on the mechanisms underlying bioactivities is required.

IntroductionIn this study, we aimed to examine the effects of chotosan, a traditional Japanese botanical drug, and its active component, Uncaria hook, on anxiety-like behaviors induced by systemic inflammation in mice.MethodsTo induce systemic inflammation, the mice were treated with lipopolysaccharide (LPS), a bacterial endotoxin. Prior to LPS treatment, the mice were administered chotosan or Uncaria hook orally each day for 14 days. Anxiety-like behavior of the mice was evaluated using the light–dark test 24 h after LPS treatment.ResultsRepeated administration of chotosan prevented anxiety-like behavior in both normal and LPS-treated mice. Similarly, administration of Uncaria hook suppressed LPS-induced anxiety-like behavior in mice. Furthermore, treatment with tandospirone, a 5-HT1A receptor agonist, alleviated anxiety-like behavior in mice, whereas treatment with DOI, a 5-HT2A receptor agonist, enhanced anxiety-like behavior in mice. LPS treatment significantly increased serotonin (5-HT)2A receptor mRNA expression in the frontal cortex, whereas 5-HT1A receptor mRNA expression remained unchanged in the hippocampus. Notably, chotosan significantly suppressed the mRNA expression of 5-HT2A receptor.DiscussionThese findings indicate that chotosan exerts anxiolytic-like effects in the context of inflammation-induced anxiety, potentially mediated by the inhibition of 5-HT2A receptor hyperfunction in LPS-treated mice. Consequently, we postulate that chotosan may be effective in managing inflammation-induced anxiety-like behaviors.

IntroductionGuidelines for various psychiatric disorders recommend short-term use of benzodiazepine anxiolytic monotherapy in few cases. Contrarily, benzodiazepine anxiolytic polypharmacy (BAP) is not recommended in any case. However, BAP is often used in real world. Therefore, this study aimed to determine the association between BAP and concomitant use of psychotropic medications.MethodThis retrospective cross-sectional study used claims data from the Japan Medical Data Center. Medical information of health insurance subscribers treated with benzodiazepine anxiolytics in June 2019 was extracted. Prescription of two or more benzodiazepine anxiolytics was defined as BAP. Binary logistic regression analysis was performed to investigate the factors associated with BAP, using age group, sex, type of subscriber, and number of concomitant hypnotics, antidepressants, and antipsychotics (none, one, and two or more) as covariates.ResultThe eligible participants were 104,796 adults who were prescribed benzodiazepine anxiolytics. Among them, 12.6% were prescribed two or more drugs. Logistic regression analysis revealed that BAP was significantly associated with those who received hypnotic monotherapy (adjusted odds ratio [aOR]: 1.04, 95% confidence interval [CI]: 1.001–1.09, p=0.04), antidepressant monotherapy and polypharmacy (aOR: 1.57, 95% CI: 1.51–1.63, p

The original article was published in Veterinary Evidence Vol 9, Issue 1 (2024): https://doi.org/10.18849/ve.v9i1.679 In the original version of the article the contributions of one of the authors, Christopher Minami, were listed as "Investigation, Writing – Original draft". This has now been corrected to accurately reflect Minami's contributions, with the agreement of all the authors: Christopher Minami: Conceptualisation, Methodology, Investigation, Writing – Original draft. This error was in both the HTML and PDF versions. This has now been updated in both the HTML and PDF versions, and can be found in the author contributions section.

Abstract Background Conditions affecting the hypothalamic‐pituitary‐adrenal (HPA) axis are common in dogs. Testing the function of the HPA axis includes measurement of endogenous adrenocorticotropic hormone (eACTH) and performance of an adrenocorticotropic hormone (ACTH) stimulation test. Trazodone is commonly administered to dogs to decrease stress. In humans, trazodone significantly decreases plasma cortisol concentration via alpha‐1 adrenergic activity. Objectives Determine the influence of trazodone on eACTH and serum cortisol concentrations in healthy dogs. Animals Fourteen healthy, adult, companion dogs. Methods Prospective, randomized placebo‐controlled study. Trazodone (8‐10 mg/kg) or placebo was administered PO 1 hour before eACTH measurement and ACTH stimulation testing. After a ≥7‐day wash‐out period, dogs received the opposite treatment. Differences in eACTH, pre‐ and post‐ACTH stimulation cortisol concentrations, and delta (difference between pre‐ and post‐ACTH) cortisol concentrations were analyzed using a paired t or signed‐rank test with a P

Background and Aim: Despite the plethora of drugs currently available, neurodegenerative diseases are leading cause of morbidity and mortality globally. Hence, there is a need for the development of more alternatives that are safe, efficient, and effective. In Nigeria, the leaves of Cnidoscolus aconitifolius are used ethnomedicinally for the management of central nervous system related disorders such as convulsion and anxiety. In this study, we evaluated some neuropharmacological effects of the methanol leaf extract of C. aconitifolius (CAE) in mice. Methods: Different groups of mice (n = 5) were administered 100, 200 and 400 mg/kg of CAE and then evaluated for sedative-hypnotic, anxiolytic, antidepressant, anticonvulsant, and muscle relaxant properties using standard protocols. Results: The onset of sleep was significantly reduced (P < 0.001), and sleep duration was significantly (P < 0.01) prolonged at doses of 200 and 400 mg/kg. All doses of the extract significantly (P < 0.05) reduced the number of head dips in hole-board test. In elevated plus maze test, the dose of 400 mg/kg increased (P < 0.05) the number of open arm entries without altering the time spent in the open arms of the maze. At 400 mg/kg, there was a significant (P < 0.05) reduction in the duration of immobility in forced swimming test. Doses of 200 and 400 mg/kg of the extract reduced (P < 0.05) the duration of immobility in the tail suspension test. The extract did not exhibit any anticonvulsant effect either in chemically induced or electrically induced models, and there was no significant alteration in motor coordination in extract-treated mice. Conclusion: Our results showed that CAE possesses sedative-hypnotic and antidepressant properties but lack anticonvulsant, anxiolytic and muscle relaxant actions in mice.

PICO Question In dogs with anxious behaviours, is fluoxetine more effective than clomipramine in reducing anxiety-related behaviours? Clinical bottom line Category of research Treatment. Number and type of study designs reviewed Three controlled studies were critically appraised. Strength of evidence Moderate. Outcomes reported Administration of either fluoxetine or clomipramine to adult dogs reduces symptoms of fear and anxiety. Conclusion Both fluoxetine and clomipramine are effective in reducing acral lick dermatitis and tail chasing behaviours, but there is no evidence that one drug is more effective than the other. How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Background: Clinically significant psychoautonomous syndrome, along with other modifiable factors (obesity, dyslipidemia, low physical activity, smoking, arterial hypertension, etc.) increases the risk of development and progression of coronary artery disease (CAD). In particular, patients who have undergone coronary interventions and have a higher anxiety level are prone to the development of CAD complications. Aim: To characterize the basal parameters of clinically significant psychoautonomous syndrome and their changes over time under combination therapy, including anxiolytics, at various stages of rehabilitation of the patients after endovascular myocardial revascularization. Materials and methods: This open-label randomized controlled prospective study included 60 patients aged 45 to 75 years admitted to our in-patient department for rehabilitation treatment after coronary stent placement. The patients from the intervention group (n = 30), in addition to basic treatment for CAD, were administered anxiolytic therapy (alimemazine tartrate at daily dose of 12.5 to 25 mg i. m. at the early rehabilitation step and at 5 to 10 mg during their out-patient follow-up). The in-patient study period included 3 study visits (at admittance, i. e., Day 1, at Days 5 or 6, and at discharge at Day 10 to 14). Two further study visits were performed during the out-patient rehabilitation period at Days 30 and 60. At each visit, the emotional state, sleep quality, subjective signs of autonomous dysregulation, autonomous background and suprasegmental vegetative regulation, including temporal and spectral indicators of heart rate variability, were evaluated. Results: After endovascular myocardial revascularization (the in-patient study period, Day 1) patients of the intervention and control groups (n = 30 in both groups) demonstrated comparable moderate levels of state anxiety (median [Q1; Q3]: 42 [40; 46] and 42 [36; 43], respectively) and trait anxiety (45 [41; 48] and 42 [40; 46], associated with insomnia (PSQI score: 8 [6; 12] and 6 [3; 9]) and autonomous imbalance (SDNN: 73 [61; 89] and 70 [44; 95]) with a shift to sympathetic hyperactivity. Addition of an anxiolytic initiated the regression of psychoautonomous abnormalities already by the end of the early in-patient rehabilitation period) (Days 10 to 14), with a subsequent decrease in state anxiety to 36 [33; 39] and trait anxiety to 33 [32; 37] (p 0.001), regression of insomnia according to PSQI to 2 [2; 4] (p 0.001), and an improvement of autonomous balance (SDNN) to 113 [81; 132] (p 0.001) at days 45 to 60 of the outpatient follow-up. The only adverse event in the patients receiving the treatment for psychoautonomous dysfunction was increased sleepiness at daytime, which was registered in most of them at initiation of the therapy for 2 to 3 days and did not require any dose modification. There were no other clinically significant adverse events, including cardiovascular. Conclusion: Patients with an increased level of anxiety after endovascular myocardial revascularization are characterized by an autonomous imbalance with sympathetic hyperactivity. Addition of an anxiolytic to the basic treatment for CAD allows for a reduction of both components of the psychoautonomous syndrome, which may be an additional factor for successful patient rehabilitation and as a consequence for the prevention of CAD progression.

Due to the health benefits of polyphenols and dietary fiber in combating mental disorders, we hypothesized that a polyphenol- and dietary fiber-enriched soup (RJ6601) would improve mental wellness in a rat model of middle-aged women. To test this hypothesis, female Wistar rats aged 18 months (350–450 g) were orally administered RJ6601 at doses of 200 and 400 mg/kg BW for 28 days. The anxiolytic, antidepression, and memory-enhancing effects were assessed every 7 days throughout the study period. The neuron density and levels of activities of AChE, total MAO, MAO-A, MAO-B, MDA, SOD, CAT, GSH-Px, IL-1β, IL-6, and BDNF in the prefrontal cortex at the end of study were also investigated. Furthermore, the amounts of Lactobacillus spp. and Bifidobacterium spp. in their feces were also determined. The results revealed that the developed soup shows anxiolytic, antidepression, and memory-enhancing effects. An increased neuron density; reductions in AChE, total MAO, MAO-A, MAO-B, and MDA; and an elevation of serum BDNF, together with increased amounts of both bacterial species in feces, were also observed. Our results suggest that RJ6601 is a potential mental wellness promotion supplement that enhances BDNF levels, brain plasticity, neurotransmitter balance, and oxidative stress and inflammation status, along with improving microbiota.

Byttneria pilosa, a flowering plant from the Malvaceae family traditionally used to treat ailments such as boils and scabies, is here investigated for its potential health benefits. The study focused on evaluating its antioxidant and antidiabetic properties in vitro, as well as the in vivo anxiolytic and antidepressant activities of the methanol extract of B. pilosa leaf (MEBP). The study employed various assays to evaluate antioxidant activity, including 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, reducing power capacity, and quantification of the total phenolic and flavonoid contents of MEBP. Additionally, anxiolytic and antidepressant activities were evaluated through four tests: elevated plus-maze test (EPMT), light–dark box test (LDBT), forced swimming test (FST), and tail suspension test (TST). Antidiabetic effect was determined using α-amylase inhibition assay. Docking analysis was performed using BIOVIA and Schrödinger Maestro (v11.1), and the absorption, distribution, metabolism, and excretion/toxicity (ADME/T) properties of bioactive substances were investigated using a web-based technique. MEBP exhibited moderate antioxidant activity in DPPH radical scavenging and reducing power capacity assays, with a dose-dependent response. The total phenolic and flavonoid contents measured were 70 ± 1.53 mg and 22.33 ± 1.20 mg, respectively. MEBP demonstrated significant effects in α-amylase inhibition comparable to acarbose. In behavioral tests, MEBP dose-dependently altered time spent in open arms/light box and closed arms/dark box, indicating anxiolytic effects. Moreover, MEBP significantly reduced immobility duration in FST and TST, suggesting antidepressant properties. Molecular docking analysis revealed favorable interactions between beta-sitosterol and specific targets, suggesting the potential mediation of anxiolytic and antidiabetic effects. Overall, MEBP exhibits notable anxiolytic and antidepressant properties, along with moderate antioxidant and antidiabetic activities.

Previous pharmacological data have shown the possible existence of functional interactions between μ- (MOP), κ- (KOP), and δ-opioid receptors (DOP) in pain and mood disorders. We previously reported that MOP knockout (KO) mice exhibit a lower stress response compared with wildtype (WT) mice. Moreover, DOP agonists have been shown to exert antidepressant-like effects in numerous animal models. In the present study, the tail suspension test (TST) and forced swim test (FST) were used to examine the roles of MOP and DOP in behavioral despair. MOP-KO mice and WT mice were treated with KNT-127 (10 mg/kg), a selective DOP agonist. The results indicated a significant decrease in immobility time in the KNT-127 group compared with the saline group in all genotypes in both tests. In the saline groups, immobility time significantly decreased in MOP-KO mice compared with WT mice in both tests. In female MOP-KO mice, KNT-127 significantly decreased immobility time in the TST compared with WT mice. In male MOP-KO mice, however, no genotypic differences were found in the TST after either KNT-127 or saline treatment. Thus, at least in the FST and TST, the activation of DOP and absence of MOP had additive effects in reducing measures of behavioral despair, suggesting that effects on this behavior by DOP activation occur independently of MOP.

The lateral hypothalamus' orexinergic system has been associated with anxiety-related behaviors, and electroacupuncture (EA) modifies orexin neurons to control the anti-anxiety process. However, in a rat model of post-traumatic stress disorder (PTSD), the important role of LH orexin neurons (OXNs) in the anxiolytic effects induced by EA has not been explored. In this study, rats underwent modified single prolonged stress (MSPS) for seven days before developing EA. The rats were then subjected to elevated plus maze (EPM) and open field (OFT) tests, and western blot and c-Fos/orexin double labeling investigations were carried out to determine the functional activation of LH orexinergic neurons. Compared to MSPS model rats, it has been demonstrated that EA stimulation enhanced the amount of time spent in the central zone (TSCZ) in OFT and the amount of time spent in the open arm (TSOA) in EPM in MSPS model rats (P

Analyzing sleep electroencephalography (EEG) data can provide insights from application of basic principles of signal analysis (filtering, sampling, and spectral processing). This study investigated whether jasmine essential oil (JEO) intake differed in sleep EEG patterns from sedative drug intake. Adult male Swiss Albino (ICR) mice treated with distilled water, jasmine essential oil and lorazepam administration were assessed for sleep stages offline from the dorsal hippocampal brain activity. Two-way repeated measures ANOVA revealed that JEO reduced the wakening duration while increasing NREM sleep following 60 minutes of intake to the end of the 3-hour recording, in comparison to water gavage. Their pharmaco-EEG fingerprints after a single intake of jasmine oil and lorazepam showed a high power-level of delta and beta frequencies in the first 30 minutes of recording. A dramatic decrease in gamma2 power activity was observed only after lorazepam was administered. Slow wave activity within the hippocampus was a highlight of the scent relaxant as promoter of non-REM sleep.

Abstract Background Citrus maxima (Burm.) Merr. is traditionally used for its diverse pharmacological properties. Therefore, there remains a possibility that the seed extract may contain some bioactive compounds. The present study was carried out to evaluate the anxiolytic, analgesic, and anti-inflammatory effects of methanolic seed extract of Citrus maxima (MECM). Method The effect of MECM on the rodent central nervous system was evaluated using the hole-board and elevated plus-maze method. Analgesic effect was measured with the acetic acid-induced writhing and formalin-induced paw licking method. The anti-inflammatory effect was examined using a formalin and carrageenan-induced mice paw edema model. Results The MECM at doses of 200 mg/kg and 400 mg/kg significantly (p

Primary dermatological disorders which are frequently exacerbated by stress and whose course is affected by the psychological state of the patient are called psychophysiologic or psychosomatic diseases. Psychosocial stress plays a major role in the onset and/or aggravation of these skin diseases. A close relationship between the skin and the mind mediated via hormones and neurotransmitters and altered cutaneous permeability barrier homeostasis by psychological stress constitute the basic psychopathology. The common skin conditions precipitated/aggravated by stress include psoriasis, vitiligo, atopic dermatitis, acne vulgaris, alopecia areata, urticaria, lichen planus, prurigo, seborrheic dermatitis, and hyperhidrosis. These cutaneous diseases often have a chronic, unpredictable course with multiple remissions and relapses leading to significant psychiatric morbidity, and disease-related stress further acts as an aggravating factor for the cutaneous disease leading to a vicious cycle. Increased awareness about these psychophysiologic diseases among dermatologists has helped to incorporate psychotherapeutic treatment in the form of psychotropic drugs and nonpharmacological interventions in the management of these patients. A multidisciplinary approach consisting of dermatologists along with psychiatrists and psychologists in a liaison framework has proven useful for these patients.

Abstract Ortho-eugenol is a synthetic derivative from eugenol, the major compound of clove essential oil, which has demonstrated antidepressant and antinociceptive effects in pioneering studies. Additionally, its effects appear to be dependent on the noradrenergic and dopaminergic systems. Depression and anxiety disorders are known to share a great overlap in their pathophysiology, and many drugs are effective in the treatment of both diseases. Furthermore, high levels of anxiety are related to working memory deficits and increased oxidative stress. Thus, in this study we investigated the effects of acute treatment of ortho-eugenol, at 50, 75 and 100 mg/kg, on anxiety, working memory and oxidative stress in male Swiss mice. Our results show that the 100 mg/kg dose increased the number of head-dips and reduced the latency in the hole-board test. The 50 mg/kg dose reduced malondialdehyde levels in the prefrontal cortex and the number of Y-maze entries compared to the MK-801-induced hyperlocomotion group. All doses reduced nitrite levels in the hippocampus. It was also possible to assess a statistical correlation between the reduction of oxidative stress and hyperlocomotion after the administration of ortho-eugenol. However, acute treatment was not able to prevent working memory deficits. Therefore, the present study shows that ortho-eugenol has an anxiolytic and antioxidant effect, and was able to prevent substance-induced hyperlocomotion. Our results contribute to the elucidation of the pharmacological profile of ortho-eugenol, as well as to direct further studies that seek to investigate its possible clinical applications.

Absract: Drymaria cordata subsp. diandra (Sw.) J.A. Duke is one of the most important medicinal plants used by various tribes throughout India and the world. It is a traditional herbal medication that is used to treat peptic ulcers, female sterility, headaches, glomerulonephritis, sleeping problems, convulsions, and febrile illnesses in children as an ingredient in many local poly herbal formulations, as well as other major or minor ailments such as cold, headache, coryza, bronchitis, leprosy, tumors, and so on. The plant has been shown to contain a variety of secondary plant metabolites such as alkaloids, flavonoids, tannins, saponins, phenols, and terpenoids which have been proved to show Anti-bacterial, analgesic and anti-pyretic, anti-tussive, anxiolytic, anti-oxidant, anti-diabetic, sinusitis and cytotoxic activities. All the records associated with this plant was accrued from distinctive treatise including reference books, and databases like PubMed, Science Direct, Scopus, Web of Science, Google Scholar, Researchgate, Publons etc. The goal of this paper is to give an outline and critical analysis of the stated traditional uses, anatomy, phytochemistry, pharmacological actions, and toxicology studies of D. cordata, as well as to find the remaining holes and provide a base for further research. The review also tries to get people and academics interested in the wide range of medicinal qualities of the plant so that it can be used better in the future.

Imepitoin is a low-affinity partial agonist for benzodiazepine binding sites of gamma-aminobutyric acid receptors with anxiolytic effects. It has been shown to reduce anxiety during noise-related events in dogs when given at 30 mg/kg PO BID, although this dose was associated with ataxia and increased appetite in some cases. The objective of this study was to assess its safety and efficacy for storm anxiety when started at 10 mg/kg PO BID and titrated to effect up to 30 mg/kg PO BID during storm season. Significant decreases in anxiety scores were seen in weekly surveys and storm logs (SLs) at 10, 20 and 30 mg/kg PO BID. Serious adverse events (AEs) were not reported in any subject. Ataxia was the most commonly reported non-serious AE (14/33), followed by increased hunger (13/33). The frequency of AEs was higher in the 20 mg/kg PO BID group than in the 10 mg/kg group PO BID. No clinically significant changes were seen in lab work pre- and post-study. In conclusion, Imepitoin given during storm season at doses ranging from 10 to 30 mg/kg PO BID reduced clinical signs of fear and anxiety during storms for the dogs in this study. These findings support the use of an individually titrated dose.

Two polyphenols–hyperoside (HYP) and protocatechuic acid (PCA) were reported to exert antidepressant activity in rodents after acute treatment. Our previous study also showed that this activity might have been influenced by the monoaminergic system and the upregulation of the brain-derived neurotropic factor (BDNF) level. A very long-term pharmacological therapy is required for the treatment of a patient with depression. The repetitive use of antidepressants is recognized to impact the brain structures responsible for regulating both emotional and cognitive behaviors. Thus, we investigated the antidepressant, anxiolytic, and procognitive effects of HYP and PCA in mice after acute and prolonged treatment (14 days). Both polyphenols induced an anxiogenic-like effect after acute treatment, whereas an anxiolytic effect occurred after repetitive administration. PCA and HYP showed procognitive effects when they were administered acutely and chronically, but it seems that their influence on long-term memory was stronger than on short-term memory. In addition, the preset study showed that the dose of 7.5 mg/kg of PCA and HYP was effective in counteracting the effects of co-administered scopolamine in the long-term memory impairment model induced by scopolamine. Our experiments revealed the compounds have no affinity for 5-HT1A and 5-HT2A receptors, whereas a significant increase in serum serotonin level after prolonged administration of PCA and HYP at a dose of 3.75 mg/kg was observed. Thus, it supports the involvement of the serotonergic system in the polyphenol mechanisms. These findings led us to hypothesize that the polyphenols isolated from Impatiens glandulifera can hold promise in treating mental disorders with cognitive dysfunction. Consequently, extended studies are necessary to delve into their pharmacological profile.

PICO question In hospitalised dogs or dogs confined postsurgery, does administration of trazodone reduce stress related behaviours compared to no treatment with trazodone? Clinical bottom line Category of research Treatment. Number and type of study designs reviewed Three papers were critically reviewed. One was a prospective, randomised, blinded observational study, another was a randomised, placebo-controlled clinical trial, and the last was a non-randomised prospective, open-label clinical trial. Strength of evidence Weak. Outcomes reported The administration of trazodone to hospitalised dogs reduced several observed stress related behaviours compared to a control group that was environmentally matched to the treatment group (Gilbert-Gregory et al., 2016). In dogs subjected to postsurgical confinement at home, trazodone administration was not more effective at reducing stress related behaviours compared with a placebo in one study (Gruen et al., 2017); however, it was effective when observed in a non-placebo controlled clinical trial (Gruen et al., 2014). Further investigation with a larger sample size would assist in strengthening the evidence of an association between trazodone administration and a reduction in the behavioural signs of stress in dogs. Conclusion The available evidence weakly supports the hypothesis that administration of trazodone is an effective treatment in reducing stress related behaviours in hospitalised dogs and dogs confined post-surgery, and further studies are required to confirm its efficacy. The quality of the evidence when hospitalised dogs was studied was moderate (Gilbert-Gregory et al., 2016), however in dogs studied that were confined postsurgery, the evidence is weaker (Gruen et al., 2014; Gruen et al., 2017). Different trazodone doses were evaluated in the studies and so further studies focusing on dose effects are required to determine appropriate dose rates. Further studies also need to be conducted to evaluate the appropriate length of time that trazodone should be given prior to a stressful event, as well as whether trazodone needs to be used in conjunction with other anxiolytic drugs to optimise efficacy. How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

The case of a 42-year-old female patient with pronounced itching and exanthema, mainly in the area of the trunk and lower limbs, is presented. Previously, the patient took antihistamines without effect, was treated for scabies, but the itching remained pronounced and led to rash and excoriations. From the anamnesis, it was found that the patient has a high level of stress. According to the Hospital Anxiety and Depression Scale, the anxiety of the patient reached 14 points, and depression 1 point. Functional (psychogenic) itching was suspected. Since the patient refused dermatologist consultation, therapy with the anxiolytic temgicoluril, topical antipruritic agents and nonpharmacological methods of treatment were recommended at the initial stage. The patient felt a significant relief of itching symptoms on the first day of anxiolytic usage, she withdrew topical antipruritic agents after 5 days of anxiolytic treatment, in 15 days she began to reduce the dose of temgicoluril, and at the end of the third week she stopped treatment with anxiolytic due to a significant positive effect. In three weeks, practically all elements of the rash, except for the largest wounds from scratching, disappeared. The peculiarity of the case is that functional itching was completely eliminated during anxiolytic therapy without other systemic medications, which emphasizes the importance of eliminating the component of stress and anxiety in the treatment of such patients.

AimWe aimed to develop a decision aid (DA) for individuals with anxiety disorders who consider tapering benzodiazepine (BZD) anxiolytics, and if tapering, tapering BZD anxiolytics with or without cognitive behavioral therapy (CBT) for anxiety. We also assessed its acceptability among stakeholders.MethodsFirst, we conducted a literature review regarding anxiety disorders to determine treatment options. We cited the results of the systematic review and meta-analysis, which we conducted previously, to describe the related outcomes of two options: tapering BZD anxiolytics with CBT and tapering BZD anxiolytics without CBT. Second, we developed a DA prototype in accordance with the International Patient Decision Aid Standards. We carried out a mixed methods survey to assess the acceptability among stakeholders including those with anxiety disorders and healthcare providers.ResultsOur DA provided information such as explanation of anxiety disorders, options of tapering or not tapering BZD anxiolytics (if tapering, the options of tapering BZD anxiolytics with or without CBT) for anxiety disorder, benefits and risks of each option, and a worksheet for value clarification. For patients (n = 21), the DA appeared to be acceptable language (86%), adequate information (81%), and well-balanced presentation (86%). The developed DA was also acceptable for healthcare providers (n = 10).ConclusionWe successfully created a DA for individuals with anxiety disorders who consider tapering BZD anxiolytics, which was acceptable for both patients and healthcare providers. Our DA was designed to assist patients and healthcare providers to involve decision-making about whether to taper BZD anxiolytics or not.

Psychiatric disorders are among the leading causes of global health burden, with depression and anxiety being the most disabling subtypes. The two common disorders, depression and anxiety, usually coexist and are pathologically polygenic with complicated etiologies. Current drug-based therapies include selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, and 5-hydroxytryptamine partial agonists. However, these modalities share common limitations, such as slow onset and low efficacy, which is why potential mechanistic insights for new drug targets are needed. In this review, we summarize recent advances in brain localization, pathology, and therapeutic mechanisms of the serotonergic system in depression and anxiety.

The current study sought to determine the anxiolytic, antidepressant, and anti-inflammatory properties of distilled water-soluble extract of beehive (WSE-BH). Gas chromatography–mass spectrometry (GC-MS) studies were used to characterize the chemical compositions obtained from beehives extracted in water and methanol (also fractions). The GC-MS analysis identified 19 compounds in WSE-BH, including high total phenol and flavonoid contents, compared with the methanol extract (21 compounds), ethyl acetate fraction (9 compounds), and CCl4 fraction (27 compounds). The oral administration of WSE-BH (50 and 150 mg/kg) showed significant anxiolytic activities assessed by time spent in (30.80% and 39.47%, respectively) and entry into (47.49% and 55.93%, respectively) the open arms of the elevated plus-maze (EPM). Only the 150 mg/kg dose resulted in a significant effect on the number of head-dipping events in the hole-board test (HBT) (40.2 ± 2.33; p

Crateva adansonii (CA) is traditionally used in the treatment of epilepsy and memory loss. This work aims to evaluate the antidepressant and anxiolytic activities of the dichloromethane/methanol extract of CA trunk bark in a chronic unpredictable stress-induced depression (UCMS) model in mice. After exposure of mice to UCMS for 42 days, anhedonia was assessed using the sucrose preference test, antidepressant effects by the forced swim and caudal suspension tests, anxiolytic effects by the light/dark compartment (LDB) and open arena (OF) tests. Oxidative stress parameters Malondialdehyde (MDA), Superoxide Dismutase (SOD), Catalase (CAT), and Reduced Glutathione (GSH) were assessed. The results showed that multiple administrations of C. adansonii extract (150 and 300 mg/kg, resulted in a significant increase from 38.5% to 64.9% (p

Duabanga grandiflora (DC.) Walp. is an ethnomedicinally significant plant used to treat various illnesses, but there is little scientific evidence to support its use. This study explored the pharmacological activities of methanol extract of D. grandiflora stem barks (MEDG) through in vivo approaches in Swiss albino mice and a computer-aided molecular approach. The forced swimming test (FST), tail suspension test (TST), elevated plus maze (EPM), and hole board test (HBT) were used to determine anti-depressant and anxiolytic activity in experimental mice. In addition, anti-diarrheal studies were performed using castor oil-induced diarrhea, castor oil-induced enter pooling, and the charcoal-induced gastrointestinal motility test. MEDG showed substantial depletions in the immobility times in both FST and TST after treatment with the MEDG extract, whereas moderate anxiolytic activity was manifested at a higher dose (400 mg/kg) compared with the control. Correspondingly, MEDG extract revealed a significant reduction in wet feces and decreased the small intestinal transit of charcoal meal in castor oil-induced diarrhea and charcoal-induced gastrointestinal motility test. In the computer-aided molecular approaches, vanillin displayed a promising binding score for both anxiolytic and anti-diarrheal activities, while duabanganal C showed a promising score for the anti-depressant activity. The present experimental findings along with a computer-aided model conclude that MEDG could be a possible Phyto therapeutic agent with potential anti-depressant, anxiolytic and anti-diarrheal activity.

Schinus lentiscifolius (Anacardiaceae) is widely used in folk medicine for treating gastrointestinal and emotional complaints but there are no scientific studies that support these uses. This work aims at evaluating the antispasmodic and central effects of S. lentiscifolius as well as the flavonoids presence in the tincture (SchT) and the composition of the essential oil (SchO). SchT inhibited the concentration-response curves (CRC) of carbachol and calcium in a non-competitive way in isolated rat intestine, bladder and uterus. SchT also non-competitively inhibited the CRC of histamine in guinea-pig intestine and the CRCs of serotonin and oxytocin in rat uterus. Isoquercetin and rutin were identified in SchT. The behavioral effects of SchT, SchO and infusion of S. lentiscifolius leaves (SchW) were tested in mice. These extracts showed an anxiolytic-like effect in the novelty-suppressed feeding test, which was reversed by flumazenil except in SchO-treated mice. Only SchO reduced the spontaneous locomotor function in the open field test. Also, SchT and SchW decreased immobility time in both, the tail suspension (TST) and forced swimming tests, while SchO produced the same effect in the TST. d-limonene and α-santalol were the main components found in SchO. The results demonstrated that extracts obtained from S. lentiscifolius leaves were effective as intestinal, urinary and uterine antispasmodics. SchT and SchW exhibited anxiolytic and antidepressant properties without sedation, whereas SchO showed also sedative properties. Therefore, the present study gives preclinical support to the traditional use of this plant for gastrointestinal and depressive or emotional symptoms.

The common daisy (Bellis perennis) belongs to the family Asteraceae and, in recent years, some new research has been published on the bioactive compounds and biological activities of its extracts. In 2014, the knowledge was partially summarized, but several new studies have been published in the last nine years. In addition, the substances were tabularly consolidated to give a comprehensive overview of over 310 individual components, compound classes, and bioactivities, as well as their accurate plant organ origin. The latest results have shown that the plant has antioxidative, antimicrobial, anticancerogenic, wound healing, antidepressive, anxiolytic, nephroprotective, and insulin mimetic effects, as well as an effect on lipid metabolism. Some studies in the field of homeopathy were also listed. Ideally, a biological effect and one or several compound(s) can be correlated. However, the compounds of the extracts used have often been qualified and quantified, but it remains unclear which of these substances have an activity. The works often stick at the level of the crude extract or a fraction, but not at a single purified and tested compound and, consequently, they are hampered by a missing comprehensive bioactivity workflow. This review provides a critical overview and gaps and offers a basis for further research in this area.

Mental and neurological disorders are conditions that affect thoughts, emotions, behavior, and relationships. Malpighia mexicana A. Juss. is a plant used in Mexican traditional medicine for the treatment of such disorders. This work aimed to investigate the antidepressant, anxiolytic, sedative, hypnotic, and anticonvulsant effects of the acetonic extract (MmAE) of M. mexicana and its fractions (F3, F4-10, F14) using the forced swimming test (FST), elevated plus maze (EPM), open field test (OFT), pentobarbital-induced sleep test (PBTt), and pentylenetetrazol-induced seizure test (PTZt). MmAE, F3, F4-10, F14, and vehicle were administrated orally 24, 18, and 1 h prior to the evaluations. Imipramine (15 mg/kg, p.o.) was administrated 1 h prior to the evaluations as a positive control for the FST, while diazepam (1 mg/kg, p.o.) was administrated 1 h prior to the evaluations as a positive control for the EPM, OFT, PBTt, and PTZt. MmAE had an anxiolytic effect; MmAE and F3, F4-10, and F14 showed an antidepressant effect, sedative effect, hypnotic effect, and anticonvulsant effect. Using HPLC, we identified the compounds quercetin 3-O-rutinoside (1), kaempferol 3-O-glucoside (2), luteolin 7-O-glucoside (3), quercetin (4), and kaempferol (5) in MmAE and compounds (1), (2), and (3) in F14. Using GC-MS, we identified α-tocopherol, phytol, and β-amyrin in F3; β-tocopherol, phytol, β-sitosterol, and β-amyrin in F4-10; and α- tocopherol, phytol, β-sitosterol, and β-amyrin in F4-10. The neuropharmacological effects found in this work may be due to the presence of vitamins, phytosterols, terpenes, and flavonoids. This research requires further study to clarify the mechanisms of action of the identified compounds.

The investigation of monoterpenes as natural products has gained significant attention in the search for new pharmacological agents due to their ability to exhibit a wide range in biological activities, including antifungal, antibacterial, antioxidant, anticancer, antispasmodic, hypotensive, and vasodilating properties. In vitro and in vivo studies reveal their antidepressant, anxiolytic, and memory-enhancing effects in experimental dementia and Parkinson’s disease. Chemical modification of natural substances by conjugation with various synthetic components is a modern method of obtaining new biologically active compounds. The discovery of new potential drugs among monoterpene derivatives is a progressive avenue within experimental pharmacology, offering a promising approach for the therapy of diverse pathological conditions. Biologically active substances such as monoterpenes, for example, borneol, camphor, geraniol, pinene, and thymol, are used to synthesize compounds with analgesic, anti-inflammatory, anticonvulsive, antidepressant, anti-Alzheimer’s, antiparkinsonian, antiviral and antibacterial (antituberculosis) properties. Myrtenal is a perspective monoterpenoid with therapeutic potential in various fields of medicine. Its chemical modifications often lead to new or more pronounced biological effects. As an example, the conjugation of myrtenal with the established pharmacophore adamantane enables the augmentation of several of its pivotal properties. Myrtenal–adamantane derivatives exhibited a variety of beneficial characteristics, such as antimicrobial, antifungal, antiviral, anticancer, anxiolytic, and neuroprotective properties, which are worth examining in more detail and at length.

Introduction/Objective. Somatosensory evoked potentials are a neurophysiological tool for testing the effects of drugs in humans and animals. The aim of this study was to estimate the way that bromazepam and ibuprofen had on tooth pulp-evoked potentials (TPEPs) after non-painful stimuli, as well as to detect possible differences in this activity. Methods. Sixty young healthy subjects were included in the study. They were arranged into three groups: ibuprofen, bromazepam, and placebo. To record TPEPs response, dental pulp were electrically stimulated through intact enamel with non-painful stimuli. For stimulation and registration we used Xltek Protektor 32 system, software EPWorks, version 5.0 (Natus Medical Incorporated, Oakville, ON, Canada). The experiment consisted of two testing sessions. Five recordings were performed in each session. The first test session was before, and the second was 45 minutes after administration of a single dose of the ibuprofen (400 mg), bromazepam (1.5 mg) or placebo. Results. The results of the present study exhibit that both ibuprofen and bromazepam significantly increased all the latencies; ibuprofen decreased amplitudes of all the waves except the first one (p < 0.05), and bromazepam decreased amplitudes of all the waves except the first one (p < 0.05); placebo did not modified TPEPs waves (p > 0.05). Additionally, there were no significant differences in influence on TPEPs between bromazepam and ibuprofen (p > 0.05). Conclusion. Our study showed that both bromazepam and ibuprofen had the same influence on TPEPs after non-painful stimuli. That indicates that anxiolytic dose of bromazepam affects neurotransmission in the same manner as non-opioid analgesics ibuprofen.

Anxiolytics and hypnotics are widely used drugs. First-line psychiatric indications for benzodiazepines (BZD) are alcohol/sedative-hypnotic withdrawal and catatonia, while panic disorder, general anxiety disorder, social anxiety disorder and insomnia are indications after failing of first/second-line treatments, and its use is recommended only for a short time. The spread of the SARS-CoV-2 virus influenced regular daily living, psychological, social, and economic stability. The COVID-19 pandemic has a multifactorial effect on people's mental health and has directly and indirectly influenced changing trends in the prescription, use and misuse of anxiolytics and hypnotics during the pandemic. This article will show use of anxiolytics and hypnotics in inpatients with SARS-CoV-2 infection with or without delirium, will present recommendation for BZD utilization in the infected individuals and will review interactions between BZD and antiviral drugs. Moreover, it will summarize available data on the frequency and reasons for use and abuse of BZD in the general population during the pandemic.

Buspirone is commonly used to treat generalized anxiety disorder and demonstrates a limited side-effect profile compared to other anxiolytics. Buspirone is considered generally safe, and neuropsychiatric adverse reactions are uncommon. There are rare clinical case reports that suggest buspirone-induced psychosis. We present a case of buspirone worsening psychosis for a patient psychiatrically hospitalized for an episode of decompensated schizoaffective disorder. The patient had a primary diagnosis of schizoaffective disorder and was treated with antipsychotics during this hospitalization, but his symptoms worsened when buspirone was administered on two separate occasions. During the first trial of buspirone, the patient exhibited traits of increased aggression, odd behaviors, and paranoia. The buspirone was discontinued after the patient admitted to hiding his pills to later consume through nasal ingestion. The second trial resulted in repeated exacerbated symptoms of paranoia related to food and substantially decreased oral intake. Considering its complex mechanism of action, buspirone is suggested to derive its neuropharmacological effects through 5-HT1A receptors. However, the drug also has been found to mediate dopamine neurotransmission. Buspirone acts as an antagonist at presynaptic dopamine D2, D3, and D4 receptors. Yet, contrary to expected outcomes, it was unable to produce antipsychotic effects and instead resulted in a substantial increase in dopaminergic metabolites. The route of administration may also play a role in the enhancement of the buspirone’s effects, particularly considering that after first-pass metabolism, buspirone has approximately 4% oral bioavailability. Intranasal administration of buspirone leads to faster drug absorption by direct transport from the nasal mucosa to the brain and increased bioavailability.

Bijia Song, Junchao Zhu Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of ChinaCorrespondence: Junchao ZhuDepartment of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of ChinaEmail zhujunchao1@hotmail.comAbstract: Perioperative sleep disturbances are commonly observed before, during, and after surgery and can be caused by several factors, such as preoperative negative moods, general anesthetics, surgery trauma, and pain. Over the past decade, the fast-acting antidepressant effects of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine represent one of the most attractive discoveries in the field of psychiatry, such as antidepressant and anxiolytic effects. It is also widely used as a short-acting anesthetic and analgesic. Recent research has revealed new possible applications for ketamine, such as for perioperative sleep disorders and circadian rhythm disorders. Here, we summarize the risk factors for perioperative sleep disturbances, outcomes of perioperative sleep disturbances, and mechanism of action of ketamine in improving perioperative sleep quality.Keywords: perioperative sleep disturbances, ketamine, antidepressant, anxiolytic, anti-inflammation

Diabetes mellitus is a chronic metabolic complaint with numerous short- and long-term complications that harm a person’s physical and psychological health. Plumeria obtusa L. is a traditional medicine used in the treatment of diabetes to reduce complications related to behavior. Plumeria is a genus with antipsychotic activities. The objective of this study was to examine the effects of a methanolic extract of Plumeria obtusa L. in the attenuation of diabetes, on symptoms of Alzheimer disease, and on other associated behavioral aspects. A single dose of alloxan was administered to an experimental group of rats to induce development of diabetes (150 mg/kg, intraperitoneal) and the rats were then administered selected doses of methanolic extract of Plumeria obtusa L. (Po.Cr) or glibenclamide (0.6 mg/kg) for 45 consecutive days. Behavioral effects were evaluated using three validated assays of anxiety-related behavior: the open field test, the light and dark test, and the elevated plus maze. Anti-depressant effects of Plumeria obtusa L. were evaluated using the forced swim test (FST) and memory and learning were assessed using the Morris water maze (MWM) task. Po.Cr was also evaluated for phytochemicals using total phenolic content (TPC), total flavonoid content (TFC), and high-performance liquid chromatography assays, and antioxidant capability was assessed through assays of DPPH radical scavenging, total oxidation capacity, and total reducing capacity. In the alloxan-induced model of diabetes, the administration of Po.Cr and glibenclamide for 45 days produced a marked decrease (p < 0.001) in hyperglycemia compared to control animals. Po.Cr treatment also resulted in improvement in indicators, such as body weight and lipid profile (p < 0.05), as well as restoration of normal levels of alanine transaminase (ALT) (p < 0.001), a biomarker of liver function. Diabetic rats presented more Alzheimer-like symptoms, with greater impairment of memory and learning, and increased anxiety and depression compared to non-diabetic normal rats, whereas treated diabetic rats showed significant improvements in memory and behavioral outcomes. These results demonstrate that Po.Cr reversed alloxan-induced hyperglycemia and ameliorated Alzheimer-related behavioral changes, which supports additional study and assessment of conventional use of the plant to treat diabetes and associated behavioral complications.

Ganoderma lucidum is known as lingzhi mushroom, which is said to have medicinal properties by the local residents. This research was focused to assess the antidepressant, anxiolytic, and sedative activities of the mentioned mushroom extracts by means of in vivo and in silico approaches. The antidepressant, anxiolytic, and sedative properties of the methanol extracts of G. lucidum (MEGL) were assessed using the forced swim test hole board, open field test, elevated plus maze, hole cross test, and thiopental sodium-induced sleeping time. The extracts revealed significant antidepressant, anxiolytic, and sedative activities in a dose-dependent manner. Rutin and quercetin were found to be the most effective enzyme inhibitors in the molecular docking study. According to the findings of in vivo and molecular docking study, it could be forecast that, the extract could have substantial antidepressant, anxiolytic, and sedative characteristics and deep molecular strategies on this extracts might create a target for the development of novel therapeutics. Further investigations are needed to appraise the molecular mechanisms implicated and isolate the bioactive components.

Background: Anxiety is one of the psychiatric disorders that disturbs routine life including moods and motivation. Excessive anxiety causes mental illnesses or anxiety disorders, which are commonly treated by synthetic medicines. Recently, there is a substantial increase in the studies of phytochemicals as alternatives to first-line conventional anxiolytic drugs. Yet there is insufficient information about the mechanisms of how these bioactive constitutes from plants manage anxiety disorders. This systematic review aims to answer the following research questions: (1) Which plant extracts and phytochemicals have anxiolytic effect? what is the mechanism of action? (2) Have human trials been conducted to confirm their anxiolytic effect? (3) If not, which plants/phytochemicals are recommended for further human trials? Methodology: To define and summarize such information, this systematic review consolidated in vitro, preclinical, and clinical studies that examine the anti-anxiety activity of plant extracts via oral administration, conducted through three scientific databases including PubMed, Scopus, and Google Scholar following the PRISMA protocol. Results and conclusion: Similar to synthetic drugs, most bioactive phytochemical compounds modulate anxiolytic activity through six main neurotransmitter pathways including acetylcholine (ACh), γ-aminobutyric acid (GABA), glutamate, serotonin (5-HT), dopamine (DA), and norepinephrine (NE). These bioactive compounds mainly belong to phenolics, alkaloids, and terpenoids, and they demonstrated effective therapeutic benefits against anxiety symptoms. Four plants, including Aloysia polystachya, Lavandula angustifolia, Matricaria chamomilla L. and Humulus lupulus, have been evaluated in human trials. However, studies on majority plants were performed using animal models, and among them, Tanacetum parthenium L. Schultz-Bip (Asreraceae), demethoxysudachitin, Albizzia julibrissin, Nelumbo nucifera Gaertn. leaves, Zizyphi spinosi semen seed extract, obovatol, Mangifera indica stem barks, Nectandra grandiflora Ness and Lavandula angustifolia, Bupleurum yinchowense roots, Citrus aurantium L. and Foeniculum vulgare exhibited the most significant anxiolytic effect at dosage of 30 mg/kg/day or lower. Further human trials are recommended to validate the efficacy and safety of these plants/plant extracts/phytochemicals in managing psychiatric disorders.

Introduction: Gabapentin and pregabalin were earlier used as antiepileptics. These have been also found to have analgesic, anticonvulsant and anxiolytic effects. Aim: To compare the pre-emptive use of pregabalin and gabapentin on their opioid sparing effects among patients undergoing laparoscopic cholecystectomy. Materials and Methods: This randomised controlled, single-blind study was conducted in Department of Anaesthesiology at Mahatma Gandhi Medical College and M.Y Hospital Indore, Madhya Pradesh, India, from August 2020 to August 2021. The study included 90 patients of American Society of Anaesthesiologists (ASA) physical status class I/II, undergoing elective laparoscopic cholecystectomy. Patients were allocated randomly into three groups, 30 patients each. Group P receiving tablet oral pregabalin 150 mg, group G receiving oral gabapentin 600 mg and group C receiving tablet multivitamin (control group), before induction of anaethesia. Intraoperative requirement of opioids, sedation score, Visual Analogue Scale (VAS) score, and postoperatively analgesia requirement in the form of opioid were noted. Association between two non parametric variables was done using Pearson Chi-square test. Comparison of means between three groups was done using One-way Analysis of Variance (ANOVA) followed by Post-hoc Turkey test. Statistical Package for Social Sciences (SPSS) version 20.0 software was used. Results: The mean age in group P, C and G was 39.73±13.55, 38.67±13.33 and 41.03±5.62 (p-value=0.726). The mean intraoperative requirement of opioid in pregabalin group was 100 μg, in gabapentin group was 100 μg when compared to control group 150 μg. Postoperative requirement of analgesic was later in pregabalin group (7.23±0.64 hours) compared to gabapentin group (5.78±0.49 hours) and control group (4.37±0.47 hours). Conclusion: Pregabalin and gabapentin have opioid-sparing effect intraoperatively and postoperatively and can be used pre-emptively as an attractive choice.

Argemone ochroleuca Sweet (Papaveraceae) is used in folk medicine as a sedative and hypnotic agent. This study aimed to evaluate the anxiolytic-like, sedative, antidepressant-like, and anticonvulsant activities of a dichloromethane extract of A. ochroleuca stems (AOE), chemically standardized using gas chromatography–mass spectrometry (GC–MS), and its active compound dihydrosanguinarine (DHS). The anxiolytic-like, sedative, antidepressant-like, and anticonvulsant activities of the AOE (0.1–50 mg/kg p.o.) and DHS (0.1–10 mg/kg p.o.) were evaluated using murine models. A possible mechanism for the neurological actions induced by the AOE or DHS was assessed using inhibitors of neurotransmission pathways and molecular docking. Effective dose 50 (ED50) values were calculated by a linear regression analysis. The AOE showed anxiolytic-like activity in the cylinder exploratory test (ED50 = 33 mg/kg), and antidepressant-like effects in the forced swimming test (ED50 = 3 mg/kg) and the tail suspension test (ED50 = 23 mg/kg), whereas DHS showed anxiolytic-like activity (ED50 = 2 mg/kg) in the hole board test. The AOE (1–50 mg/kg) showed no locomotive affectations or sedation in mice. A docking study revealed the affinity of DHS for α2-adrenoreceptors and GABAA receptors. The anxiolytic-like and anticonvulsant effects of the AOE are due to GABAergic participation, whereas the antidepressant-like effects of the AOE are due to the noradrenergic system. The noradrenergic and GABAergic systems are involved in the anxiolytic-like actions of DHS.

In folklore medicine, Conocarpus lancifolius is used to treat various illnesses. The main objective of this study was a comprehensive investigation of Conocarpus lancifolius leaf aqueous extract (CLAE) for its antioxidant, cardioprotective, anxiolytic, antidepressant and memory-enhancing capabilities by using different in vitro, in vivo and in silico models. The in vitro experimentation revealed that CLAE consumed an ample amount of total phenolics (67.70 ± 0.15 µg GAE/mg) and flavonoids (47.54 ± 0.45 µg QE/mg) with stronger antiradical effects through DPPH (IC50 = 16.66 ± 0.42 µg/mL), TAC (77.33 ± 0.41 µg AAE/mg) and TRP (79.11 ± 0.67 µg GAE/mg) assays. The extract also displayed suitable acetylcholinesterase (AChE) inhibitory (IC50 = 110.13 ± 1.71 µg/mL) activity through a modified Ellman’s method. The toxicology examination presented no mortality or any signs of clinical toxicity in both single-dose and repeated-dose tests. In line with the cardioprotective study, the pretreatment of CLAE was found to be effective in relieving the isoproterenol (ISO)-induced myocardial injury in rats by normalizing the heart weight index, serum cardiac biomarkers, lipid profile and various histopathological variations. In the noise-stress-induced model for behavior attributes, the results demonstrated that CLAE has the tendency to increase the time spent in the central zone and elevated open arms in the open field and elevated plus maze tests (examined for anxiety assessment), reduced periods of immobility in the forced swimming test (for depression) and improved recognition and working memory in the novel object recognition and Morris water maze tests, respectively. Moreover, the LC-ESI-MS/MS profiling predicted 53 phytocompounds in CLAE. The drug-likeness and ADMET analysis exhibited that the majority of the identified compounds have reasonable physicochemical and pharmacokinetic profiles. The co-expression of molecular docking and network analysis indicated that top-ranked CLAE phytoconstituents act efficiently against the key proteins and target multiple signaling pathways to exert its cardiovascular-protectant, anxiolytic, antidepressant and memory-enhancing activity. Hence, this artifact illustrates that the observed biological properties of CLAE elucidate its significance as a sustainable source of bioactive phytochemicals, which appears to be advantageous for pursuing further studies for the development of new therapeutic agents of desired interest.

Hypericum perforatum L. (St. John's wort) is a medicinal plant that has been intensivly studied by clinicians, pharmacologists, and chemists. It has resulted in the publication of both original articles and a number of, reviews devoted to the general spectrum of the biological activity of its extracts and the separate chemical components of this species. Unlike many other known medicinal plants, the pharmacological study of which is accompanied by the establishment of new (or rediscovered) structures of chemical compounds, the dynamics of the present study of H. perforatum is mostly associated with a detailed study of the mechanisms of its therapeutic effect and less with the search for new components.The aim of this work is to review and analyze the data on the biological activity of extracts and individual components of Hypericum perforatum L. (Hypericaceae), or St. John's wort, published in the scientific literature over the past 10 years.Materials and methods. To collect and analyze the information, such electronic databases as PubMed, Scopus, Web of Science, Google Scholar, and other available resources have been used. The following keywords and word combinations were used for search in the databases for 2010-2020: “Hypericum perforatum”, “St. John's wort”, “the biological activity of St. John's wort”, “hypericin”, “hyperforin”.Results. The review provides information on antidepressant, neuroprotective, nootropic, anxiolytic activity, antibacterial, cytotoxic, anti-inflammatory properties, analgesic, hypoglycaemic effects, and other types of activity of H. perforatum extracts, as well as individual compounds (hypericin, hyperforin, amentoflavone, and others), isolated from this species. It is well known that the secondary metabolites of St. John's wort are naphthodianthrons, flavonoids and other phenolic compounds, several classes of lipophilic substances including phloroglucinol derivatives and terpenoids. Apart from extracts and their fractions, the biological activity of photoreactive naphthodianthrone hypericin and hyperforin (a phloroglucinol derivative) has been studied in detail.This review provides an analysis of published data from 2010 to 2020 on the biological activity of St. John's wort. At the present time H. perforatum is primarily well-known for its antidepressant-like properties, which are confirmed by numerous pharmacological studies and clinical trials. Still there is no consensus on the effective treatment of severe or even moderate depression with St. John's wort. This review also provides information on the neuroprotective, nootropic, antiepileptic, anxiolytic, antimicrobial, antiviral, antiprotozoal, antitumor, cytotoxic, analgesic, anti-inflammatory and other effects of H. perforatum extracts, as well as its individual compounds.Conclusion. Despite the popularity of H. perforatum as a plant with an antidepressant-like activity, intensive research work continues to be carried out to elucidate the molecular mechanisms of the actions of extracts and individual compounds in disorders of the nervous system. Studying its antibacterial, antiviral, and cytotoxic activity may also open up some great prospects, along with determining the possibility of using St. John's wort in metabolic disorders, genitourinary disorders, and other fields of medicine.

Hochuekkito (HET) is a Kampo medicine used to treat postoperative and post-illness general malaise and decreased motivation. HET is known to regulate immunity and modulate inflammation. However, the precise mechanism and effects of HET on inflammation-induced central nervous system disorders remain unclear. This study aimed to assess the effect of HET on inflammation-induced anxiety-like behavior and the mechanism underlying anxiety-like behavior induced by lipopolysaccharide (LPS). Institute of Cancer Research mice were treated with LPS (300 μg/kg, intraperitoneally), a bacterial endotoxin, to induce systemic inflammation. The mice were administered HET (1.0 g/kg, orally) once a day for 2 weeks before LPS treatment. The light-dark box test and the hole-board test were performed 24 h after the LPS injection to evaluate the effects of HET on anxiety-like behaviors. Serum samples were obtained at 2, 5, and 24 h after LPS injection, and interleukin-6 (IL-6) levels in serum were measured. Human and mouse macrophage cells (THP-1 and RAW264.7 cells, respectively) were used to investigate the effect of HET on LPS-induced IL-6 secretion. The repeated administration of HET prevented anxiety-like behavior and decreased serum IL-6 levels in LPS-treated mice. HET significantly suppressed LPS-induced IL-6 secretion in RAW264.7 and THP-1 cells. Similarly, glycyrrhizin, one of the chemical constituents of HET, suppressed LPS-induced anxiety-like behaviors. Our study revealed that HET ameliorated LPS-induced anxiety-like behavior and inhibited IL-6 release in vivo and in vitro. Therefore, we postulate that HET may be useful against inflammation-induced anxiety-like behavior.

Grewia asiatica Linn. is a well-known plant for its nutritional and therapeutic attributes. It has been mentioned in ancient Indian literature as Rasayana due to its stimulant and tonic effects. Thus, present investigation was carried out to evaluate the antiepileptic and anxiolytic action of G. asiatica Linn. leaves using animal models. Methanol extract at dose levels of 100 and 200 mg/kg was capable of providing protection against both pentylenetetrazole and maximal electroshock induced seizures in mice. Extract also showed significant anxiolytic activity in elevated plus maze, light/dark box and mirror chamber mice models at same dose levels. Results of this study indicated that the methanol extract of leaves of G. asiatica plant possess significant antiepileptic and anxiolytic effect.

Introduction Generalized anxiety disorder (GAD) is associated with reduced attention, inhibition, decrease of processing speed. The impact of a new peptide antagonist of central cholecystokinin-1 receptors (GB-115) on cognitive processes in patients with GAD is reported. Objectives To research the cognitive effects of GB-115 in patients with GAD. Methods 25 patients with GAD in ICD-10 (mean age 35,76±8,55 years) treated with GB-115 in clinically relevant dose (6 mg/d) were enrolled to the study. The evaluation of cognitive functions was conducted at background, Day 3, Day 7, Day 14 and Day 21. The laboratory test toolkit included reaction time test, Shulte-Platonov tables, attention tests (using hardware and software complex “NeuroSoft-PsychoTest”). Statistical significance was ascertained by Wilcoxon signed-rank test. Results Speed of reaction time increased on the Day 7 (418,17±61,49 msec, p≤0,01), the Day 14 (422,25±70,69 msec, p≤0,01) and the Day 21 of treatment (406,5±52,79 msec, p≤0,01) in comparison with background (449,19±64,91). Attention parameters improved on the Day 3 (305,95±45,31 msec, p≤0,05) and the Day 21 of treatment (300,14±47,74 msec, p≤0,05) in comparison with the background (316,41±42,35 msec). Decrease of time in performance of tables of Shulte-Platonov was also observed on the Day 7 (59,40±13,71 sec, p≤0,01), the Day 14 (57,88±12,82 sec, p≤0,01) and the Day 21 (53,40±13,19 sec, p≤0,01) in comparison with the background (68,84±16,78 sec). Conclusions GB-115 revealed cognitive effects such as an increase of processing speed and improvement of different aspects of attention (attentional resource allocation, attention span and switching) after the Day 7 of treatment. Disclosure No significant relationships.

Introduction Personalized approach in drug therapy is an essential line of modern psychiatry. Experimental and clinical studies of anxiolytics have shown differences in drug effects in dependence on genetically determined reactions to stress and personal features. Objectives To evaluate of the therapeutic effects and effectiveness of bromodihydrochlorophenylbenzodiazepine and fabomotizole in dependence on individually-typological features of patients with anxiety disorders. Methods 45 patients (mean age 33,3±9,7 years) with generalized anxiety disorder (n=22) and panic disorders with agoraphobia (n=23) participated in this open-label study. 13 patients treated with typical anxiolytics bromodihydrochlorophenylbenzodiazepine at dose 2 mg daily and 32 patients treated with atypical fabomotizole at dose 30 mg daily. The duration of treatment was 14 days. Minnesota Multiphasic Personality Inventory, Psychiatric Symptoms Severity Evaluation Questionnaire and CGI-E were administered. Results Asthenic features (high pessimism, anxiety, individualism) were revealed in 26 patients and stenic features (high impulsivity, rigidity and optimism) were revealed in 19 patients. Patients with asthenic features had tranquilo-activating effect of bromodihydrochlorophenylbenzodiazepine, whereas patients with stenic features had tranquilo-sedative effect. The tranquilo-activating effect of fabomotizole was revealed in patients with stenic features. High efficacy of bromodihydrochlorophenylbenzodiazepine was observed in patients with asthenic personality traits (χ 2 = 7,8), whereas in fabomotizole-in patients with stenic individual typological features (χ 2 = 9,1). Conclusions Patients with stenic and asthenic features had differences in therapeutic effects and the effectiveness of anxiolytics. Personality features determine the sensitivity of patients with anxiety disorders to psychotropic drugs. Disclosure No significant relationships.