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European Neuropsychopharmacology : the... Jul 2023The endocannabinoid system is a promising candidate for anxiolytic therapy, but translation to the clinic has been lagging. We meta-analyzed the evidence for... (Meta-Analysis)
Meta-Analysis Review
The endocannabinoid system is a promising candidate for anxiolytic therapy, but translation to the clinic has been lagging. We meta-analyzed the evidence for anxiety-reduction by compounds that facilitate endocannabinoid signaling in humans and animals. To identify areas of specific potential, effects of moderators were assessed. Literature was searched in Pubmed and Embase up to May 2021. A placebo/vehicle-control group was required and in human studies, randomization. We excluded studies that co-administered other substances. Risk of bias was assessed with SYRCLE's RoB tool and Cochrane RoB 2.0. We conducted three-level random effects meta-analyses and explored sources of heterogeneity using Bayesian regularized meta-regression (BRMA). The systematic review yielded 134 studies. We analyzed 120 studies (114 animal, 6 human) that investigated cannabidiol (CBD, 61), URB597 (39), PF-3845 (6) and AM404 (14). Pooled effects on conditioned and unconditioned anxiety in animals (with the exception of URB597 on unconditioned anxiety) and on experimentally induced anxiety in humans favored the investigational drugs over placebo/vehicle. Publication year was negatively associated with effects of CBD on unconditioned anxiety. Compared to approach avoidance tests, tests of repetitive-compulsive behavior were associated with larger effects of CBD and URB597, and the social interaction test with smaller effects of URB597. Larger effects of CBD on unconditioned anxiety were observed when anxiety pre-existed. Studies reported few side effects at therapeutic doses. The evidence quality was low with indications of publication bias. More clinical trials are needed to translate the overall positive results to clinical applications.
Topics: Animals; Humans; Anti-Anxiety Agents; Endocannabinoids; Bayes Theorem; Anxiety; Cannabidiol
PubMed: 37094409
DOI: 10.1016/j.euroneuro.2023.04.001 -
Behavioural Neurology 2023The current study was planned to assess the neuropharmacological benefits of the seed. These seeds have been conventionally used for the nutritional as well as...
The current study was planned to assess the neuropharmacological benefits of the seed. These seeds have been conventionally used for the nutritional as well as amelioration of various diseases. However, there was a need to provide a pharmacological basis for such use. Four central nervous system-related functions, that is, anxiety, depression, memory, and motor coordination, were evaluated, and the levels of brain biogenic amines were also assessed. Anxiety was evaluated through selected experimental models, such as light and dark apparatus, elevated plus maze, head dip, and open field test. The head dip test was mainly used to assess exploratory behavior. Depression was assessed by two animal models, that is, the forced swim test and tail suspension test. Memory and learning ability were assessed by the passive avoidance test, stationary rod apparatus, and Morris's water maze test. Motor skilled learning was assessed by stationary rod and rotarod apparatus. Reversed phase high-pressure liquid chromatography was used to determine biogenic amine levels. Results reveal that exhibited anxiolytic and antidepressant effects with memory improvement. There was a reduction in the weight of the animal following chronic administration. Furthermore, no remarkable effects were observed on motor coordination. Norepinephrine was found elevated, which may be linked to its antidepressant effects. These biological effects of may be due to the presence of secondary metabolites, such as cucurbitacin, beta-sitosterol, polyphenolic compounds, citrulline, kaempferol, arginine, -carotene, quercetin, and other antioxidants. The outcomes of the present study authenticate that the chronic use of seeds reduces the intensity of neurological problems like anxiety and depression.
Topics: Animals; Depression; Cucurbita; Anxiety; Antidepressive Agents; Anti-Anxiety Agents; Biogenic Amines; Behavior, Animal; Maze Learning
PubMed: 37006627
DOI: 10.1155/2023/7509937 -
Trends in Cancer Nov 2023Benzodiazepines (BZDs) are commonly prescribed for pancreatic cancer patients. To investigate the correlation between BZDs and survival outcomes a recent study by...
Benzodiazepines (BZDs) are commonly prescribed for pancreatic cancer patients. To investigate the correlation between BZDs and survival outcomes a recent study by Cornwell et al. found that lorazepam (LOR) correlates with poor survival. The mechanistic study shows that LOR increases interleukin 6 (IL6) expression in cancer-associated fibroblasts via GPR68.
Topics: Humans; Anti-Anxiety Agents; Benzodiazepines; Lorazepam; Anxiety; Pancreatic Neoplasms; Receptors, G-Protein-Coupled
PubMed: 37778962
DOI: 10.1016/j.trecan.2023.09.005 -
Prague Medical Report 2020Buspirone (BUS) belongs to the azapirone chemical class. The aim of this literature review is to evaluate the clinical epidemiological profile, pathological mechanisms,... (Review)
Review
Buspirone (BUS) belongs to the azapirone chemical class. The aim of this literature review is to evaluate the clinical epidemiological profile, pathological mechanisms, and management of BUS-associated movement disorders (MD). Relevant reports in six databases were identified and assessed by two reviewers without language restriction. A total of 25 reports containing 65 cases were assessed. The MD associated with BUS were: dyskinesia in 14 cases, 10 of akathisia, 8 of myoclonus, 6 of Parkinsonism, and 6 of dystonia. The cases not clearly defined were 7 tension, 14 incoordination, and the undefined number of dyskinesia, tics, and Parkinsonism. The mean age was 45.23 years (range: 15-74). The male was the predominant sex in 60.86% and the most common BUS-indication was anxiety disorder. The mean BUS-dose was 42.16 mg (range: 5-100). The time from the beginning of BUS administration to the MD onset was one month or less in 76%. The time from BUS withdrawal to complete recovery was within one month in 87.5%. The most common management was BUS withdrawal. In 16 patients the follow-up was reported: 14 had a full recovery, but in two (1 dyskinesia + 1 dystonia) the symptoms continued after the BUS withdrawal. MD associated with BUS were scarcely reported in the literature. Moreover, in the majority of cases, no clear description of the clinical profile, neurological examination, or the time data of the movement disorder onset and recovery were given.
Topics: Adolescent; Adult; Aged; Anti-Anxiety Agents; Buspirone; Humans; Male; Middle Aged; Movement Disorders; Young Adult
PubMed: 32191616
DOI: 10.14712/23362936.2020.1 -
Irish Journal of Psychological Medicine Mar 2020Sexual side effects have rarely been reported secondary to treatment with Pregabalin, a structural analogue of the inhibitory neurotransmitter gamma amino butyric acid...
INTRODUCTION
Sexual side effects have rarely been reported secondary to treatment with Pregabalin, a structural analogue of the inhibitory neurotransmitter gamma amino butyric acid (GABA).
METHOD
We present the case of AB, a 27-year-old single man with a diagnosis of recurrent depressive disorder who was prescribed pregabalin to alleviate the significant anxiety symptoms he was experiencing.
RESULTS
A significant amelioration in anxiety symptoms was attained; however, he developed the adverse effects of acute sexual disinhibition and increased libido. These adverse effects were temporally related to treatment with pregabalin and reduced with dose reduction of this agent.
CONCLUSIONS
To date, limited published data are available relating such a reaction to pregabalin. A greater clinical recognition of this association between pregabalin and sexual disinhibition, would allow clinicians to intervene at an earlier stage of this adverse effect and potentially as in this case, management may only require dose reduction rather than treatment discontinuation.
Topics: Adult; Anti-Anxiety Agents; Depressive Disorder; Humans; Libido; Pregabalin
PubMed: 32223791
DOI: 10.1017/ipm.2017.5 -
Protein and Peptide Letters 2020The current pharmacological strategies for the management of anxiety disorders and depression, serious conditions which are gaining greater prevalence worldwide, depend... (Review)
Review
The current pharmacological strategies for the management of anxiety disorders and depression, serious conditions which are gaining greater prevalence worldwide, depend on only two therapeutic classes of mood-stabilizing drugs: Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs). Although first line agents with proven efficacy, their clinical success in the management of anxiety disorders and depression is still considered highly complex due to the multifaceted nature of such conditions. Several studies have shown a possible therapeutic target could be found in the form of the Angiotensin-Converting Enzyme [ACE] type 2 (ACE2), Angiotensin [Ang]-(1-7) and Mas receptor pathway of the Renin- Angiotensin System (RAS), which as will be discussed, has been described to exhibit promising therapeutic properties for the management of anxiety disorders and depression. In this article, the literature to describe recent findings related to the role of the RAS in anxiety and depression disorders was briefly revised. The literature used covers a time range from 1988 to 2019 and were acquired from the National Center for Biotechnology Information's (NCBI) PubMed search engine. The results demonstrated in this review are promising and encourage the development of new research for the treatment of anxiety and depression disorders focusing on the RAS. In conclusion, the ACE2/Ang-(1-7)/Mas pathway may exhibit anxiolytic and anti-depressive effects through many possible biochemical mechanisms both centrally and peripherally, and result in highly promising mental health benefits which justifies further investigation into this system as a possible new therapeutic target in the management of neuropsychiatric disorders, including any as of yet undescribed risk-benefit analysis compared to currently-implemented pharmacological strategies.
Topics: Angiotensin I; Angiotensin-Converting Enzyme 2; Animals; Anti-Anxiety Agents; Antidepressive Agents; Anxiety Disorders; Depression; Humans; Peptide Fragments; Receptors, G-Protein-Coupled; Renin-Angiotensin System; Signal Transduction
PubMed: 31868143
DOI: 10.2174/0929866527666191223143230 -
The American Journal of Psychiatry Jun 2020
Topics: Anti-Anxiety Agents; Anxiety Disorders; Benzodiazepines; Humans; Risk Assessment; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors
PubMed: 32475138
DOI: 10.1176/appi.ajp.2020.20040376 -
Phytotherapy Research : PTR May 2023Anxiety disorders are prevalent conditions in the world population, whose standard approaches include pharmacotherapy, psychotherapy, and combinations of these... (Review)
Review
Anxiety disorders are prevalent conditions in the world population, whose standard approaches include pharmacotherapy, psychotherapy, and combinations of these interventions. Different classes of psychopharmaceuticals are recommended as the first line of drugs to treat these disorders, which can have several adverse effects, treatment resistance, dependence, and drug-drug interactions making it necessary to search for new therapeutic agents. In particular, diazepam (DZP), a prototype drug from the group of benzodiazepines, has been commonly used and evaluated for its efficacy and safety in different anxiety disorders in clinical trials. DZP is also the most widely used reference standard in in vivo pharmacological assays of natural compounds. However, translating the results obtained in different rodent species and physiological anxiety tests instead of psychopathological animal models that can be of clinical application remains challenging. A systematic review of scientific articles published between 2010 and 2020 that included in vivo pre-clinical tests to define the anxiolytic, sedative and/or hypnotic effect of flower extracts is proposed. PRISMA and Rayyan were used for the selection of studies using four databases (Pubmed, Scopus, Web of Science, and QInsight), using the keywords: "Animals," "Anxiolytic," "Diazepam," "Elevated Plus Maze," "Flower Extracts," "Insomnia," "In vivo," "Mice," "Open Field Test," "Pre clinical" and "Sedative." The characteristics of anxiety studies in animal models, other studies related to locomotor activity, and the hypnotic effect of the extracts were compiled. Twenty-four articles were included, 21 of them performed the animal model of anxiety-like behavior of the elevated plus maze, seven the open field test, and six the light-dark box test. The locomotor activity was evaluated in 10 studies after the administration of the extracts to the animals to define their sedative effect, where only one defined that the extract (Matricaria chamomilla) had a sedative effect. The plants declared with this type of activity were Achyranthes aspera, Alcea aucheri, Brassica nigra, Cananga odorata, Carthamus tinctorius, Chrysanthemum indicum, Citrus aurantium, Couroupita guianensis, Echium amoenum, Erythrina berteroana, Gardenia jasminoides, Hibiscus tilliaceus, Lavandula officinalis, Lawsonia inermis, Matricaria chamomilla, Melia azedarach, Nerium oleander, Passiflora incarnata, Plumeria rubra, Salix aegyptiaca, Syzygium aromaticum, Tagetes erecta, Tilia americana. Although this review showed that some flower extracts have an anxiolytic effect as effective as diazepam, their therapeutic utility in anxiety disorders remains to be extensively demonstrated. Hence, more reliable and predictive behavioral tests and appropriate strategies for the experimental designs are needed to obtain more conclusive evidence with clinical significance.
Topics: Mice; Animals; Anti-Anxiety Agents; Hypnotics and Sedatives; Research Design; Plant Extracts; Anxiety; Diazepam; Oils, Volatile; Maze Learning; Flowers; Behavior, Animal
PubMed: 37039741
DOI: 10.1002/ptr.7830 -
Biomedicine & Pharmacotherapy =... Nov 2020Parkinson's disease (PD) is a progressive neurodegenerative disease which affects millions of population worldwide. It is characterized by motor symptoms such as... (Review)
Review
Parkinson's disease (PD) is a progressive neurodegenerative disease which affects millions of population worldwide. It is characterized by motor symptoms such as excessive tremor, bradykinesia, rigidity, postural instability and non-motor symptoms include neuropsychiatric complications like anxiety, depression, insomnia and cognitive impairment, orthostatic hypotension, sexual dysfunction and gastrointestinal complications. Treatment of anxiety in PD poses extensive challenge to global healthcare which makes it urgent to develop innovative treatment for the better management of the disease. The gold standard treatment by Levodopa provides symptomatic relief and its effect on neuropsychiatric complications like anxiety is elusive. Presence of anxiety worsens the condition and challenges therapeutic management of the PD. The in-depth analysis and understanding the molecular mechanism and pathophysiological pathways associated with the onset of anxiety in PD is essential. The disturbances in serotonergic, adrenergic and GABAergic neurons and hypothalamic pituitary adrenal axis play a significant role in the pathophysiology of anxiety. The drugs like Selective Serotonin Reuptake Inhibitors, tricyclic antidepressants and benzodiazepines are useful in the management of anxiety but due to severe side effects and progression of the disease it results in the failure of treatment. The present review imparts an insight in the management of anxiety in PD by understanding molecular mechanism and application of alternative treatment options which can enlighten the perception of researchers towards better therapeutic management of the disease.
Topics: Animals; Anti-Anxiety Agents; Antiparkinson Agents; Anxiety; Disease Progression; Humans; Levodopa; Parkinson Disease
PubMed: 33152935
DOI: 10.1016/j.biopha.2020.110776 -
Molecules (Basel, Switzerland) May 2022Chrysin (5,7-dihydroxyflavone) is a flavonoid isolated from plants, such as , , and . This natural molecule exerts diverse pharmacological effects, which includes... (Review)
Review
Chrysin (5,7-dihydroxyflavone) is a flavonoid isolated from plants, such as , , and . This natural molecule exerts diverse pharmacological effects, which includes antioxidant, anti-inflammatory, anti-cancer, neuroprotective, and anti-apoptotic effects. Additionally, in brain structures, such as the hippocampus, prefrontal cortex, raphe nucleus, and striatum, involved in the physiopathology of anxiety and depression disorders, several neuropharmacological activities, including the activation of neurotransmitter systems (GABAergic, serotonergic, dopaminergic, and noradrenergic), neurotrophic factors, such as brain-derived neurotrophic factor and the nerve growth factor, and some signaling pathways are affected. The results showed that the anxiolytic and antidepressant-like effects of chrysin occurs through its interaction with specific neurotransmitter systems, principally the GABAergic and the serotonergic, and activation of other neurotrophic factors. However, it is not possible to discard the antioxidant and anti-inflammatory activities of chrysin while producing its anxiolytic- and antidepressant-like effects. Although these results have been obtained principally from pre-clinical research, they consistently demonstrate the potential therapeutic use of flavonoid chrysin as an anxiolytic and antidepressant agent. Therefore, this flavonoid could be considered as a promising novel therapy for anxiety and depression disorders.
Topics: Anti-Anxiety Agents; Antidepressive Agents; Antioxidants; Flavonoids; Passiflora
PubMed: 35684488
DOI: 10.3390/molecules27113551