Anxiolytic Research Articles

Anxiolytic-like Effects by trans-Ferulic Acid Possibly Occur through GABAergic Interaction Pathways.

Numerous previous studies reported that ferulic acid exerts anxiolytic activity. However, the mechanisms have yet to be elucidated. The current study aimed to investigate the anxiolytic effect of trans-ferulic acid (TFA), a stereoisomer of ferulic acid, and evaluated its underlying mechanism using in vivo and computational studies. For this, different experimental doses of TFA (25, 50, and 75 mg/kg) were administered orally to Swiss albino mice, and various behavioral methods of open field, hole board, swing box, and light-dark tests were carried out. Diazepam (DZP), a positive allosteric modulator of the GABAA receptor, was employed as a positive control at a dose of 2 mg/kg, and distilled water served as a vehicle. Additionally, molecular docking was performed to estimate the binding affinities of the TFA and DZP toward the GABAA receptor subunits of α2 and α3, which are associated with the anxiolytic effect; visualizations of the ligand-receptor interaction were carried out using various computational tools. Our findings indicate that TFA dose-dependently reduces the locomotor activity of the animals in comparison with the controls, calming their behaviors. In addition, TFA exerted the highest binding affinity (-5.8 kcal/mol) to the α2 subunit of the GABAA receptor by forming several hydrogen and hydrophobic bonds. Taken together, our findings suggest that TFA exerts a similar effect to DZP, and the compound exerts moderate anxiolytic activity through the GABAergic interaction pathway. We suggest further clinical studies to develop TFA as a reliable anxiolytic agent.

Pharmacological strategies to reduce perioperative anxiety in children – a narrative review

Preoperative anxiety is common among children, resulting in negative postoperative behavior and increased postoperative pain. This review focuses on the practical use, safety, and efficacy of pharmacological strategies to reduce perioperative anxiety in children. The PubMed® database was searched using MeSH terms: ((care, preoperative) AND (children) AND (anti-anxiety drugs); (medication, preanesthetic) AND (child, preschool). An in-dept assessment was performed after which 85 articles were retrieved. Benzodiazepines (midazolam, diazepam), zolpidem, melatonin, opioids (fentanyl, butorphanol), alpha-2-adrenergic receptor agonists (clonidine, dexmedetomidine), ketamine and antihistamines (hydroxyzine, promethazine) were reviewed. Their pharmacological properties, routes of administration, doses, efficacy and (dis)advantages are discussed in this review. Based upon the results of our review, some suggestions can be made. Oral midazolam, oral clonidine, intranasally dexmedetomidine and the combination of oral ketamine and midazolam are recommendable products. Some other products like oral diazepam, butorphanol, ketamine intranasal s-ketamine + midazolam and hydroxyzine can be considered because of their proper safety profile and benefits. Further research should focus on patient selection for specific pharmacological and non-pharmacological interventions to achieve a tailored approach. Standardized assessment of anxiety, clinical significancy and feasibility should be included in the objectives of these studies.

Effect of Fluoxetine and Escitalopram on Heart Rate Variability (HRV) and Serum Potassium Level in Patients of Depression and Anxiety Disorders

Background The present study was conducted to generate data regarding the effect of fluoxetine as an anti-depressant and escitalopram as an antianxiety agent on heart rate variability (HRV). There is a scarcity of data regarding the correlation between selective serotonin reuptake inhibitors (SSRIs) and serum potassium levels. Purpose To find out the effect of SSRIs on HRV, and whether it is either dependent or independent of serum potassium level. Materials and Methods In this prospective, open-label, observational study, 70 participants were enrolled and divided into two groups, the fluoxetine group ( n = 35) and the escitalopram group ( n = 35) suffering from depression and anxiety, respectively. Parameters, like HRV, serum potassium level, heart rate, respiratory rate, and blood pressure, were measured baseline and after the first, second, and third months of treatment. HRV was calculated by root mean square deviation of successive differences between adjacent RR intervals (RMSSD). ECG (electrocardiogram) was recorded by Physio Pac Digital Polygraph software. All values were expressed as mean ± SD, and statistical analysis was done by using the repeated measure analysis of variance (ANOVA) test with Greenhouse–Geisser correction, post hoc analysis with Bonferroni correction, and SPSS 20.0 software. Results Among a total of 70 participants, post hoc tests using the Bonferroni correction showed a statistically significant difference between the HRV of the pretreatment group and after the second, and third month of fluoxetine therapy ( p < 0.05). In the escitalopram group, the Bonferroni correction showed a significant difference between the HRV of the pretreatment and third-month value ( p < 0.05). Repeated measure ANOVA with Greenhouse–Geisser correction showed no statistical significance of serum potassium at different time points ( p > 0.05). There were also no significant changes in heart rate, respiratory rate, and blood pressure at different points of time in both groups. Pearson’s correlation coefficient test for a relationship between HRV and serum potassium was negative at different time points. Conclusion Fluoxetine significantly increased HRV from the pretreatment value to the second and third months of treatment, whereas in the escitalopram group of participants, the third-month value of HRV was increased compared to the first month. The effect of SSRIs on HRV was independent of serum potassium levels at different time points suggesting that the effect of SSRIs on HRV was independent of serum potassium level.

The Effect Of Yoga Exercise On Anxiety In Menopausal Women At Babakan Sari Sub-District, Bandung City

Introduction: Menopausal women experience various physical and psychological problems. One of the psychological problems that often arises is anxiety. Anxiety occurs because a decrease in estrogen causes a decrease in serotonin, a chemical that carries messages between nerve cells in the central nervous system, gut, blood, and humans. The impact of menopausal women's anxiety is a decrease in quality of life. One intervention that is easy and safe to do is yoga. Yoga exercise has movements that are relaxing so that it can be used to reduce anxiety. This study aims to determine the effectiveness of yoga exercises to reduce anxiety in menopausal women. Method: The research design used quasi-experimental with pretest and posttest. The population in this study were women aged > 45 years. Samples were taken using purposive sampling. The inclusion criteria were women>45 years who had experienced menopause. The exclusion criteria were menopausal women taking anti-anxiety drugs. The instrument is in the form of a Zung self-rating anxiety scale questionnaire sheet which consists of normal, mild anxiety, moderate anxiety, and severe anxiety. Results: It shows that in the pretest, the majority of respondents had mild anxiety 34 people (68%); in the posttest, the majority of respondents became normal, namely 32 people (64%). The results of the t-test showed p-value = 0.00, < a = 0.05, so yoga interventions are proven to reduce anxiety in menopausal women. Discussion: Yoga exercises are effective in reducing anxiety because yoga exercises provide relaxation for postmenopausal women, with interventions given every 3 times a week for 3 weeks, increasing the effectiveness of yoga in reducing anxiety. Every movement in yoga has a relaxing effect, which if done continuously can reduce body tension and anxiety. Intervening 9 times for three consecutive weeks has been proven to reduce anxiety, initially mild to most normal. So yoga is proven to reduce anxiety in menopausal women. Every movement in yoga has a relaxing effect, which if done continuously can reduce body tension and anxiety. So yoga is proven to reduce depression in menopausal women. Conclusion: Yoga exercises are effective in reducing anxiety in menopausal women. Suggestions for other researchers are yoga interventions on the anxiety of chronic disease patients.

Chemoselective chlorination of 1,5-benzodiazepin-2-one derivatives by activated DMSO

The chlorination of bioactive molecules involves the change of their physiological properties, which leads to an improvement in their pharmacokinetic and pharmacological properties. Therefore, it has been a privileged strategy for drugs design and development. Here, we report an efficient chlorination of 1,5-benzodiazepin-2-one with dimethyl sulfoxide activated by methane sulfonyl chloride. The structures of the target compounds were established based on extensive spectroscopic techniques, including 1H NMR, 13C NMR and confirmed by single crystal X-ray diffraction. Furthermore, the binding interactions of these active structures as potential anxiolytic agents were studied through molecular docking.

Minor tranquillizers for short-term treatment of newly onset symptoms of anxiety and distress: a systematic review with network meta-analysis of randomized trials

Unspecific symptoms of anxiety and distress are frequently encountered in patients in both general practice and acute psychiatric services. Minor tranquillizers may be a treatment option when non-pharmacological interventions are insufficient or unavailable. We conducted a systematic review with network meta-analysis of the evidence for short-term (1–4 weeks) pharmacological treatment of newly onset symptoms of anxiety and distress. We searched the PsycInfo, MEDLINE, EMBASE and Cochrane Library databases and extracted data following a predefined hierarchy of outcomes. We assessed risk of bias using the Cochrane Risk of Bias tool and the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation framework (GRADE). We included 34 randomized trials comprising a total of 7044 patients with adjustment disorders or anxiety spectrum disorders. The network meta-analysis showed that regarding the critical outcome symptoms of anxiety within 1–4 weeks benzodiazepines (SMD − 0.58, 95% CI − 0.77 to − 0.40), quetiapine (SMD − 0.51, 95% CI − 0.90 to − 0.13) and pregabalin (SMD − 0.58, 95% CI − 0.87 to − 0.28) all performed better than placebo with no statistically significant difference between the drugs. Data on other important outcomes were inconsistently reported. Adverse effects varied, but overall, it was uncertain whether adverse effects differed between interventions. The evidence regarding the risk of dependence was uncertain, but dependence may be a concern in susceptible individuals even with short-term treatment. Overall, the certainty of the evidence according to GRADE was rated as low to very low across outcomes. Despite the limitations in the evidence, the results of this review can inform treatment guidelines, supporting clinicians in the choice of minor tranquillizer in this prevalent and help-seeking, clinically heterogeneous population.

An Ethnobotanical and Phyto-Pharmacological Review on a Multifaceted Ornate Flowering Plant ‘Thunbergia erecta’

Abstract: Thunbergia erecta (Benth) T.Anderson (Meyenia erecta Benth) is an important therapeutic and medicinal plant belonging to the family Acanthaceae. Commonly called bush clock vine, king's mantel, potato bush, Nil Kantha, which is native to western Africa but commonly cultivated in India and other Asian countries. The species is commonly grown as an ornamental plant due to its bright flowers and is cultivated widely in the tropics. It is a decent source of alkaloids, flavonoids, tannins, phenolic acids, iridoids, and glucosides. Traditionally, it is used for treating bile disorders, insomnia, and depression, as a medicine given to children against worms and as an ingredient of headache poultice. The studies encompassed in this review have been designated using numerous databases, including Google Scholar, Pubmed, Wiley, Online Library, and Science Direct and covered the period from 1863 onwards. Several studies demonstrated the exploration of the pharmacological potential of various parts of plants for anthelminthic, anxiolytic, sedative, antimicrobial, antidiabetic, anticholinesterases and antiaging agents. The Thunbergia erecta plants possess potential pharmacological activity. The objective of the current review article is to put forward all relevant published information regarding ethnobotanical studies, traditional uses, phytochemistry and therapeutic potential, and other adequate background information on T. erecta that will contribute to establishing the validity of the plant for its commercial usage.

An analysis of the nutritional effects of Schisandra chinensis components based on mass spectrometry technology.

Schisandra chinensis (Turcz.) Baill. (S. chinensis) is a Traditional Chinese medicinal herb that can be used both for medicinal purposes and as a food ingredient due to its beneficial properties, and it is enriched with a wide of natural plant nutrients, including flavonoids, phenolic acids, anthocyanins, lignans, triterpenes, organic acids, and sugars. At present, there is lack of comprehensive study or systemic characterization of nutritional and active ingredients of S. chinensis using innovative mass spectrometry techniques. The comprehensive review was conducted by searching the PubMed databases for relevant literature of various mass spectrometry techniques employed in the analysis of nutritional components in S. chinensis, as well as their main nutritional effects. The literature search covered the past 5 years until March 15, 2023. The potential nutritional effects of S. chinensis are discussed, including its ability to enhance immunity, function as an antioxidant, anti-allergen, antidepressant, and anti-anxiety agent, as well as its ability to act as a sedative-hypnotic and improve memory, cognitive function, and metabolic imbalances. Meanwhile, the use of advanced mass spectrometry detection technologies have the potential to enable the discovery of new nutritional components of S. chinensis, and to verify the effects of different extraction methods on these components. The contents of anthocyanins, lignans, organic acids, and polysaccharides, the main nutritional components in S. chinensis, are also closely associated to its quality. This review will provide guidelines for an in-depth study on the nutritional value of S. chinensis and for the development of healthy food products with effective components.

Effect of Preoperative Antianxiety Medications on Blood Pressure and Blood Loss in Total Knee Arthroplasty: A Case-Control Study.

The increasing number of canceled operations in patients undergoing total knee arthroplasty (TKA) due to high blood pressure readings has put a considerable burden on surgeons. In this study, we aim to assess the effect of giving antianxiety drugs preoperatively on maintaining blood pressure (BP) and blood loss for patients undergoing TKA surgery. This retrospective case-control study included patients who underwent total knee arthroplasty and divided them into two main groups: those who had taken a 3 mg bromazepam oral tablet at the night preoperatively and the control group. The blood pressure of patients was then measured preoperatively (baseline), in the morning of surgery, in the operating room before anesthesia, and during the surgery. The percentage of measured BP was calculated by dividing the measured BP by the baseline, then multiplying by 100. 301 patients were included in our study: 137 received bromazepam and 164 as a control group. The ratio of systolic BP (SBP) in the morning of surgery to the baseline (percentage of morning SBP) decreased significantly in the bromazepam group compared with the controls. The ratio of SBP, in the operating room before anesthesia (percentage of preanesthesia SBP) also decreased significantly in the bromazepam group. However, the percentage of SBP in the middle of surgery did not change significantly. In addition, there was a significant difference change from the baseline in diastolic BP and mean arterial BP between the two groups in the morning of surgery, inside the theatre, and in the middle of the operation. The bromazepam group also showed a significant decrease in blood loss. Preoperative oral antianxiety drugs (bromazepam) helps in controlling hemodynamic changes associated with anxiety, including maintaining BP in well-controlled hypertensive and healthy patients undergoing TKA, and it plays a role in decreasing the total blood loss.

Current Evidence of Cannabidiol's Potential as an Anxiolytic Agent

This article will summarize the current knowledge and scientific evidence regarding cannabidiol as a possible pharmacological tool for anxiety disorders. Although the use of this substance in medical practice is gaining momentum, gaps can still be found in the current knowledge regarding its molecular targets, drug-to-drug interactions, efficacy in different populations, adequate dosage, duration of treatment, and correct formulation. Moreover, current evidence is still preliminary, lacking robust, blinded, and placebo-controlled clinical trials in many areas of investigation. After reading this article, readers should have a thorough understanding of the current scientific evidence regarding the use of CBD as an anxiolytic drug. [ Psychiatr Ann . 2023;53(6):242–246.]

Internet addiction: issues and concerns

There is some addictive use of the internet which ultimately refers to a disorder. Internet addiction is characterized by excessive or poorly controlled preoccupations, urges or behaviors regarding computer use and internet access that led to impairment or distress. The diagnosis “Internet Gaming Disorder” (IGD) has been included in the fifth edition of Diagnostic and Statistical Manual of Mental Disorders. This proposed condition is limited to gaming and does not include problems with general use of the internet, online gambling, or use of social media or smartphones.Co morbidity found in this addictive behavior like depression and anxiety. Treatment options are limited, including Cognitive behavioral therapy, family therapy, couple therapy, antidepressant, anti-anxiety drugs and naltrexone. The mental health professionals, information technologists, young and students affairs professionals should be alert to this disorder. Internet addiction is a growing concern in today’s digital age. With the widespread availability and use of the internet, many people are finding it difficult to control their usage, leading to negative consequences in their daily lives. Some of the issues and concerns related to internet addiction include: Social isolation, Poor academic or work performance, Physical health problems, Sleep disturbances, Risks of Cyber bullying, financial problems, Behavioral and Relationship issues. It is important to seek help if you or someone you know is struggling with internet addiction. Management options may include psychotherapy, support groups, and behavior modification techniques to help individuals regain control of their internet use and improve their overall well-being and sometimes medication need when intractable behavioral issues persist. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 183-184

(369) Sexual Satisfaction After Wearable Device Use For Erectile Dysfunction

Abstract Introduction Erectile dysfunction (ED) is the inability to achieve and maintain an erection firm enough for sexual performance. ED devices such as pumps and constriction devices and prescription oral phosphodiesterase inhibitors are commonly known ED treatments. Objective Our aim was to evaluate an alternative therapy for ED for the approximately 80 percent of men who currently do not use any form of the aforementioned ED treatment options. Eddie by Giddy™ is a device that allows patients to use a novel constriction device to enhance the normal physiology of an erection to treat ED. Medical comorbidities such as anxiety, ADHD, obesity, hypertension, diabetes and depression, as well as medications such as antidepressants, anti anxiety medications, opioids and cardiac medications can impact erectile function. Our goal was to specifically evaluate the efficacy of the device in the general patient populations. Methods Our research team surveyed 60 male participants (59 who completed the study), 26 to 81 years of age, about their erectile performance over a 12 week period of time, during which participants utilized the Eddie by Giddy device. Participants completed an intake assessment, medical history, and reported on their sexual behavior and erectile performance as they used the device over the 12 weeks, during which patients rated their experience with the device, self-esteem, quality of life changes, the impact on their relationships, frequency of erections, duration of erections and the quality of erections. Results Participants showed improvement in all but one question in the survey over the 12 week period, with a particularly higher improvement between weeks 4 and 8, and sustained that improved sexual function and erection quantity and quality through week 12. Of the participants who concluded the study, 95 percent reported having overall positive results from using the Eddie by Giddy device. With respect to the survey questions, participants on average showed a 63 percent improvement in number of times attempting to receive oral sex, a 53 percent improvement in ability to maintain an erection during masturbation, a 52 percent improvement in confidence to perform sexually, and a 47 percent improvement in satisfaction of erections when attempting sexual intercourse. Conclusions Attitudes of participants with ED using Eddie® showed strong, significant improvement in erectile function, quality of life, hopefulness for future sex life and overall self-esteem in all categories of patients. Eddie by Giddy use over 12 weeks was shown to improve satisfaction among male participants of sexual health and mental health without the need for oral medication. Disclosure Yes, this is sponsored by industry/sponsor: Giddy, Inc Clarification Industry funding only - investigator initiated and executed study Any of the authors act as a consultant, employee or shareholder of an industry for: Giddy, Inc.

The potential of lemon balm (Melissa officinalis L.) essential oil as an anti-anxiety agent – is the citronellal the activity carrier?

Ethnopharmacological relevanceAmong the fewest drugs discovered are those belonging to the class of anxiolytics. Although some drug targets for anxiety disorders are established, it is hard to modify and selectively choose the active principle for those targets. Thus, the ethnomedical approach to treating anxiety disorders remains one of the most prevalent ways for (self)managing the symptoms. Melissa officinalis L. (lemon balm) has been extensively used as an ethnomedicinal remedy for the treatment of different psyche-related symptoms, especially dose related to restlessness. Aim of the studyThis work aimed to evaluate the anxiolytic activity, in several in vivo models, of the essential oil extracted from Melissa officinalis (MO) and its main constituent citronellal, a widespread plant utilized for managing anxiety. Materials and methodsIn the present study several animal models were used to assess MO anxiolytic potential in mice. The effect of the MO essential oil applied in doses ranging from 12.5 to 100 mg/kg was estimated in light/dark, hole board, and marble burying tests. In parallel doses of citronellal corresponding to the ones in the MO essential oil were applied to animals to determine if this is the activity carrier. ResultsThe results indicate that the MO essential oil exerts anxiolytic potential in all three experimental settings by significantly altering the traced parameters. The effects of citronellal are somewhat inconclusive and should not be interpreted only as anxiolytic but rather as a combination of anti-anxiety and motor-inhibiting effects. ConclusionsIn conclusion, we could say that the results of the present study provide a base for future mechanistic studies that would evaluate the activity of M. officinalis essential oil on various neurotransmitter systems involved in the generation, propagation, and maintenance of anxiety.

Intralipid as a matrix additive for evaluating hyperlipidemic postmortem blood.

Postmortem whole blood samples can differ greatly in quality where hyperlipemia is a frequent variable that can influence the results of analytical methods. The aim of this study was to investigate the influence of lipemia on postmortem analysis as well as demonstrate the usage of Intralipid in comparison to pooled postmortem lipids as matrix additives for meaningful evaluation and validation of hyperlipidemic postmortem samples. Hyperlipidemic blood samples were simulated by adding different concentrations of Intralipid or pooled authentic postmortem lipids to bovine whole blood. The hyperlipidemic blood samples were spiked with 14 benzodiazepines and five sedative and antianxiety drugs (alprazolam, clonazepam, 7-aminoclonazepam, diazepam, flunitrazepam, 7-aminoflunitrazepam, hydroxyzine, lorazepam, midazolam, nitrazepam, 7-aminonitrazepam, nordazepam, oxazepam, propiomazine, dihydropropiomazine, temazepam, triazolam, zolpidem and zopiclone). Samples were prepared with liquid-liquid extraction followed by ultra-high performance liquid chromatography-mass spectrometry. The effects of lipemia on the recovery of analytes and internal standards (ISs) were evaluated to determine the effect of, and any differences between, the two additives. Lipemia was found to cause major interference when quantifying the analytes. For most analytes, the ISs could compensate for analyte losses. However, the most hydrophilic analytes (7-amino metabolites), together with the most lipophilic analytes (propiomazine and dihydropropiomazine), were greatly affected by lipemia (<50% recovery), and the IS could not compensate for analyte losses. In general, lower analyte recoveries were observed for samples with Intralipid as a lipemic additive in comparison to those containing pooled postmortem lipids. Both Intralipid and pooled postmortem lipids showed marked effects on the analytical results. Intralipid gave a good indication of the effects of lipemia and could be a useful tool for making a meaningful evaluation of hyperlipidemic postmortem samples during the method development and validation.

Effects of the aroma of lemone verbena (Aloysia citriodora Paláu) essential oil on anxiety and the hemodynamic profile before cesarean section: A randomized clinical trial.

Aromatherapy is a noninvasive method used for alleviating anxiety. Lemon verbena (Aloysia citriodora Paláu, LV) has been frequently used in traditional medicine as an anxiolytic agent due to its pharmacological ingredients. This randomized controlled trial aimed to assess the effects of inhaling essential oil of LV on the level of anxiety and subsequent hemodynamic changes before cesarean section. The recent study was a randomized single-blind trial. Participants (n = 84) were randomly divided into two groups: LV essential oil (group A) and placebo (group B). The intervention group underwent aromatherapy using three drops of LV essential oil at a distance of 10 cm for 30 min. The placebo group received aromatherapy in a similar fashion. The State-Trait Anxiety Inventory of Spielberger questionnaire was administered before and 5 min after aroma inhalation. Vital signs were recorded before and after aromatherapy. Likewise, pain severity was assessed using the Numeric Rating Scale and vital signs were recorded. Data were analyzed using t-test, χ 2, and the Kolmogrov-Smirnov test through SPSS21 software. Anxiety level was significantly attenuated in group A after aromatherapy. Heart rate, respiratory rate, and blood pressure decreased after inhalation; but no significant variation of pain scores was observed after inhalation in both groups. We concluded that LV decreased preoperative anxiety in this recent study, therefore, aromatherapy with LV essential oil as a preemptive adjuvant to relieve anxiety before cesarean section is recommended by us; although more studies are required to endorse the results.

Preclinical evaluation of ZL006-05, a new antistroke drug with fast-onset antidepressant and anxiolytic effects

BackgroundPoststroke depression and anxiety, independent predictor of poor functional outcomes, are common in the acute phase of stroke. Up to now, there is no fast-onset antidepressive and anxiolytic agents suitable...

COVID-19-Related Shifts in Polysubstance Use

Background: Big Events, such as economic crises and natural disasters, affect drug use patterns (e.g. Friedman & Rossi, 2015). The COVID-19 pandemic is a Big Event that led to lockdowns, travel restrictions, protocols on businesses, and rules for social engagements across the globe. Studies primarily in Europe and Oceania show that the pandemic impacted the type and amount of substances used (e.g. Winstock et al., 2020). Objectives: This study examines the impact of COVID-19 on substance use using a sample of 257 individuals across 36 states, who engage in polysubstance use. Results: The sample was recruited via DanceSafe, Inc.’s social media to complete an online survey (April–October 2020) about drug use during the pandemic. The mostly White, heterosexual sample used an average of seven different substances in the past 12 months. Slightly less than half reported increasing use since the onset of the COVID-19 pandemic, with young adults and lesbian, gay, bisexual, pansexual, or queer (LGBPQ) identifying individuals significantly more likely to do so. Relative to other substances, benzodiazepine use increased, and 3,4- methylenedioxymethamphetamine (MDMA) and psychedelic use decreased, while alcohol use stayed the same. Conclusions: The COVID-19 pandemic disproportionately affected those who are young adults, LGBPQ, and use drugs. Their unique needs during the pandemic warrant attention. The swap from leisure (e.g. MDMA) to anti-anxiety (e.g. Xanax) drugs is not surprising. Yet, the rise in novel benzodiazepines (Laing et al., 2021) is a point of concern that suggests drug checking and educational efforts can best reduce potential risks.

Pharmacokinetics of intranasal amiloride in healthy volunteers.

Anxiety and panic disorders are the most common mental illnesses in the United States and lack effective treatment options. Acid-sending ion channels (ASICs) in the brain were shown to be associated with fear conditioning and anxiety responses and therefore are potential targets for treating panic disorder. Amiloride is an inhibitor of the ASICs in the brain and was shown to reduce panic symptoms in preclinical animal models. An intranasal formulation of amiloride will be highly beneficial to treat acute panic attacks due to advantages such as the rapid onset of action and patient compliance. The aim of this single-center, open-label trial was to evaluate the basic pharmacokinetics (PKs) and safety of amiloride after intranasal administration in healthy human volunteers at three doses (0.2, 0.4, and 0.6 mg). Amiloride was detected in plasma within 10 min of intranasal administration and showed a biphasic PK profile with an initial peak within 10 min of administration followed by a second peak between 4 and 8 h of administration. The biphasic PKs indicate an initial rapid absorption via the nasal pathway and later slower absorption by non-nasal pathways. Intranasal amiloride exhibited a dose-proportional increase in the area under the curve and did not exhibit any systemic toxicity. These data indicate that intranasal amiloride is rapidly absorbed and safe at the doses evaluated and can be further considered for clinical development as a portable, rapid, noninvasive, and nonaddictive anxiolytic agent to treat acute panic attacks.

The role of psychological factors in functional gastrointestinal disorders: a systematic review and meta-analysis.

To systematically reevaluate the role of psychological factors in functional gastrointestinal disorders (FGIDs) and thus provide a scientific basis for the psychological treatment of FGIDs. A literature search was conducted using the PubMed, Embase, Web of Science, and Cochrane Library databases from January 2018 to August 2022 for researches on psychological factors affecting patients with functional gastrointestinal disorders. Meta-analysis was carried out with Stata17.0 after the screening, extraction, and evaluation of article quality. The search included 22 articles with 2430 patients in the FGIDs group and 12,397 patients in the healthy controls. Meta-analysis showed anxiety [(pooled SMD = 0.74, 95%CI: 0.62 ~ 0.86, p < 0.000) (pooled OR = 3.14, 95%CI: 2.47 ~ 4.00, p < 0.000)], depression [(pooled SMD = 0.79, 95%CI: 0.63 ~ 0.95, p < 0.000) (pooled OR = 3.09, 95%CI: 2.12 ~ 4.52, p < 0.000)], mental disorders (pooled MD = -5.53, 95%CI: -7.12 ~ -3.95, p < 0.05), somatization (pooled SMD = 0.92, 95%CI: 0.61 ~ 1.23, p < 0.000), and sleep disorders (pooled SMD = 0.69, 95%CI: 0.04 ~ 1.34, p < 0.05) are risk factors for functional gastrointestinal disorders. There is a significant association between psychological factors and FGIDs. Interventions such as anti-anxiety drugs, antidepressants, and behavioral therapy are of great clinical significance in reducing FGIDs risk and improving prognosis.

Design, Synthesis, and Study of the Anxiolytic Activity of New Pyrrolo[1,2-&lt;i&gt;a&lt;/i&gt;]pyrazine-Containing TSPO Ligands

A new group of 1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamides, in which substituents at the amide nitrogen atom are alkyl, benzyl or alkoxyphenylalkyl groups, amino acid residues or their derivatives, has been obtained in this work. The synthesized compounds have high theoretical affinities for the 18 kDa translocator protein (TSPO) and a favorable profile of ADMET characteristics, which makes them promising for drug development. Anxiolytic activity was detected for eight compounds at doses of 0.1–5.0 mg/kg when administered intraperitoneally under conditions of emotional stress in the open field test in Balb/c mice and in the elevated plus maze test in ICR mice. N-Benzhydryl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide was selected as a lead compound for further development as a potential anxiolytic agent, which showed the presence of anti-anxiety activity in a wide range of doses in both tests used.