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Dialogues in Clinical Neuroscience Jun 2017Social anxiety is a form of anxiety characterized by continuous fear of one or more social or performance situations. Although multiple treatment modalities (cognitive... (Review)
Review
Social anxiety is a form of anxiety characterized by continuous fear of one or more social or performance situations. Although multiple treatment modalities (cognitive behavioral therapy, selective serotonin reuptake inhibitors/selective norepinephrine reuptake inhibitors, benzodiazepines) exist for social anxiety, they are effective for only 60% to 70% of patients. Thus, researchers have looked for other candidates for social anxiety treatment. Our review focuses on the peptide oxytocin as a potential therapeutic option for individuals with social anxiety. Animal research both in nonprimates and primates supports oxytocin's role in facilitation of prosocial behaviors and its anxiolytic effects. Human studies indicate significant associations between social anxiety and oxytocin receptor gene alleles, as well as social anxiety and oxytocin plasma levels. In addition, intranasal administration of oxytocin in humans has favorable effects on social anxiety symptomology. Other disorders, including autism, schizophrenia, and anorexia, have components of social anxiety in their pathophysiology. The therapeutic role of oxytocin for social dysfunction in these disorders is discussed.
Topics: Administration, Intranasal; Animals; Anti-Anxiety Agents; Fear; Humans; Oxytocin; Phobia, Social
PubMed: 28867943
DOI: 10.31887/DCNS.2017.19.2/cjones -
Neurotherapeutics : the Journal of the... Oct 2015Cannabidiol (CBD), a Cannabis sativa constituent, is a pharmacologically broad-spectrum drug that in recent years has drawn increasing interest as a treatment for a... (Review)
Review
Cannabidiol (CBD), a Cannabis sativa constituent, is a pharmacologically broad-spectrum drug that in recent years has drawn increasing interest as a treatment for a range of neuropsychiatric disorders. The purpose of the current review is to determine CBD's potential as a treatment for anxiety-related disorders, by assessing evidence from preclinical, human experimental, clinical, and epidemiological studies. We found that existing preclinical evidence strongly supports CBD as a treatment for generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder when administered acutely; however, few studies have investigated chronic CBD dosing. Likewise, evidence from human studies supports an anxiolytic role of CBD, but is currently limited to acute dosing, also with few studies in clinical populations. Overall, current evidence indicates CBD has considerable potential as a treatment for multiple anxiety disorders, with need for further study of chronic and therapeutic effects in relevant clinical populations.
Topics: Animals; Anti-Anxiety Agents; Anxiety Disorders; Cannabidiol; Humans
PubMed: 26341731
DOI: 10.1007/s13311-015-0387-1 -
International Journal of Molecular... Dec 2022Anxiety disorders are the most common mental diseases. Anxiety and the associated physical symptoms may disturb social and occupational life and increase the risk of... (Review)
Review
Anxiety disorders are the most common mental diseases. Anxiety and the associated physical symptoms may disturb social and occupational life and increase the risk of somatic diseases. The pathophysiology of anxiety development is complex and involves alterations in stress hormone production, neurosignaling pathways or free radical production. The various manifestations of anxiety, its complex pathophysiological background and the side effects of available treatments underlie the quest for constantly seeking therapies for these conditions. Melatonin, an indolamine produced in the pineal gland and released into the blood on a nightly basis, has been demonstrated to exert anxiolytic action in animal experiments and different clinical conditions. This hormone influences a number of physiological actions either via specific melatonin receptors or by receptor-independent pleiotropic effects. The underlying pathomechanism of melatonin's benefit in anxiety may reside in its sympatholytic action, interaction with the renin-angiotensin and glucocorticoid systems, modulation of interneuronal signaling and its extraordinary antioxidant and radical scavenging nature. Of importance, the concentration of this indolamine is significantly higher in cerebrospinal fluid than in the blood. Thus, ensuring sufficient melatonin production by reducing light pollution, which suppresses melatonin levels, may represent an endogenous neuroprotective and anxiolytic treatment. Since melatonin is freely available, economically undemanding and has limited side effects, it may be considered an additional or alternative treatment for various conditions associated with anxiety.
Topics: Animals; Melatonin; Anti-Anxiety Agents; Antioxidants; Free Radicals; Anxiety
PubMed: 36555831
DOI: 10.3390/ijms232416187 -
Pharmacology & Therapeutics Dec 2019Current medication for anxiety disorders is suboptimal in terms of efficiency and tolerability, highlighting the need for improved drug treatments. In this review an... (Review)
Review
Current medication for anxiety disorders is suboptimal in terms of efficiency and tolerability, highlighting the need for improved drug treatments. In this review an overview of drugs being studied in different phases of clinical trials for their potential in the treatment of fear-, anxiety- and trauma-related disorders is presented. One strategy followed in drug development is refining and improving compounds interacting with existing anxiolytic drug targets, such as serotonergic and prototypical GABAergic benzodiazepines. A more innovative approach involves the search for compounds with novel mechanisms of anxiolytic action using the growing knowledge base concerning the relevant neurocircuitries and neurobiological mechanisms underlying pathological fear and anxiety. The target systems evaluated in clinical trials include glutamate, endocannabinoid and neuropeptide systems, as well as ion channels and targets derived from phytochemicals. Examples of promising novel candidates currently in clinical development for generalised anxiety disorder, social anxiety disorder, panic disorder, obsessive compulsive disorder or post-traumatic stress disorder include ketamine, riluzole, xenon with one common pharmacological action of modulation of glutamatergic neurotransmission, as well as the neurosteroid aloradine. Finally, compounds such as D-cycloserine, MDMA, L-DOPA and cannabinoids have shown efficacy in enhancing fear-extinction learning in humans. They are thus investigated in clinical trials as an augmentative strategy for speeding up and enhancing the long-term effectiveness of exposure-based psychotherapy, which could render chronic anxiolytic drug treatment dispensable for many patients. These efforts are indicative of a rekindled interest and renewed optimism in the anxiety drug discovery field, after decades of relative stagnation.
Topics: Animals; Anti-Anxiety Agents; Anxiety Disorders; Humans; Molecular Targeted Therapy
PubMed: 31470029
DOI: 10.1016/j.pharmthera.2019.107402 -
British Journal of Clinical Pharmacology Feb 2014The benzodiazepines (BZDs) are anxiolytics, hypnotics, anticonvulsants, muscle-relaxants and induce anaesthesia. Adverse effects comprise sedation subjectively and... (Review)
Review
The benzodiazepines (BZDs) are anxiolytics, hypnotics, anticonvulsants, muscle-relaxants and induce anaesthesia. Adverse effects comprise sedation subjectively and cognitive and psychomotor impairment objectively. Complex skills such as driving can be compromised. Paradoxical excitement can have forensic implications. Long term use beyond the licensed durations is common but both efficacy and adverse effects associated with this have been poorly documented. Withdrawal and dependence have excited particular concern, and even polemic. Perhaps a third of long term (beyond 6 months) users experience symptoms and signs on attempting to withdraw - anxiety, insomnia, muscle spasms and tension and perceptual hypersensitivity. Uncommonly, fits or a psychosis may supervene. The patterns following withdrawal vary widely. The usual method of withdrawal is slow tapering but it may not obviate the problems completely. BZDs are also drugs of abuse either on their own or in conjunction with opioids and stimulants. Claims have been made that the use of BZDs is associated with increased mortality. This is a concern in view of the widespread usage of these drugs, particularly in the elderly. All of these factors impinge on the risk : benefit ratio and the severity of the indications. Harm reduction should focus on choice of alternative treatments both psychological and pharmacological. Guidelines emphasise that BZDs are not drugs of first choice and should only be used short term. Schedules are available to educate about methods of withdrawal in current users, emphasising the slow rate of taper. General principles of harm minimization in the addiction field are appropriate to BZD abuse.
Topics: Aged; Anti-Anxiety Agents; Benzodiazepines; Harm Reduction; Humans; Hypnotics and Sedatives; Practice Guidelines as Topic; Practice Patterns, Physicians'; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors
PubMed: 22882333
DOI: 10.1111/j.1365-2125.2012.04418.x -
TheScientificWorldJournal 2020Herbal medicines containing species have been widely used to treat anxiety since ancient times. The species L. is included in many Pharmacopoeias, and it is the most... (Review)
Review
Herbal medicines containing species have been widely used to treat anxiety since ancient times. The species L. is included in many Pharmacopoeias, and it is the most used species in food, cosmetic, and pharmaceutical industries. However, there are around 600 species of the genus and probably other species that can be used safely. Thus, this article was based on a search into the uses of the main species of the genus with anxiolytic activity and its main secondary metabolites and some pharmacological studies, patents, and registered products containing Furthermore, the Brazilian Regulatory Health Agency Datavisa, Medicines and Healthcare Products Regulatory Agency of the United Kingdom, and the European Medicines Agency websites were consulted. The results showed that species have health benefits but clinical trials are still scarce. The complexity of extracts creates challenges for the development of herbal medicines. is the most studied species of the genus and the most used in natural anxiolytic herbal medicine formulations. However, there are hundreds of species potentially useful for medicinal and nutraceutical purposes that are still little explored.
Topics: Anti-Anxiety Agents; Brazil; Humans; Passiflora; Patents as Topic; Plant Extracts; Plants, Medicinal
PubMed: 32765195
DOI: 10.1155/2020/6598434 -
Ugeskrift For Laeger Jan 2020
Topics: Anti-Anxiety Agents; Benzodiazepines; Depression; Depressive Disorder; Humans
PubMed: 31928618
DOI: No ID Found -
Molecules (Basel, Switzerland) Apr 2022Aromas have a powerful influence in our everyday life and are known to exhibit an array of pharmacological properties, including anxiolytic, anti-stress, relaxing, and... (Review)
Review
Aromas have a powerful influence in our everyday life and are known to exhibit an array of pharmacological properties, including anxiolytic, anti-stress, relaxing, and sedative effects. Numerous animal and human studies support the use of aromas and their constituents to reduce anxiety-related symptoms and/or behaviours. Although the exact mechanism of how these aromas exert their anxiolytic effects is not fully understood, the GABAergic system is thought to be primarily involved. The fragrance emitted from a number of plant essential oils has shown promise in recent studies in modulating GABAergic neurotransmission, with GABA receptors being the primary therapeutic target. This review will explore the anxiolytic and sedative properties of aromas found in common beverages, such as coffee, tea, and whisky as well aromas found in food, spices, volatile organic compounds, and popular botanicals and their constituents. In doing so, this review will focus on these aromas and their influence on the GABAergic system and provide greater insight into viable anxiety treatment options.
Topics: Animals; Anti-Anxiety Agents; Anxiety; Hypnotics and Sedatives; Odorants; Oils, Volatile; Plant Oils; Receptors, GABA-A
PubMed: 35458615
DOI: 10.3390/molecules27082414 -
Nature Nov 2015At least 120 non-olfactory G-protein-coupled receptors in the human genome are 'orphans' for which endogenous ligands are unknown, and many have no selective ligands,...
At least 120 non-olfactory G-protein-coupled receptors in the human genome are 'orphans' for which endogenous ligands are unknown, and many have no selective ligands, hindering the determination of their biological functions and clinical relevance. Among these is GPR68, a proton receptor that lacks small molecule modulators for probing its biology. Using yeast-based screens against GPR68, here we identify the benzodiazepine drug lorazepam as a non-selective GPR68 positive allosteric modulator. More than 3,000 GPR68 homology models were refined to recognize lorazepam in a putative allosteric site. Docking 3.1 million molecules predicted new GPR68 modulators, many of which were confirmed in functional assays. One potent GPR68 modulator, ogerin, suppressed recall in fear conditioning in wild-type but not in GPR68-knockout mice. The same approach led to the discovery of allosteric agonists and negative allosteric modulators for GPR65. Combining physical and structure-based screening may be broadly useful for ligand discovery for understudied and orphan GPCRs.
Topics: Allosteric Regulation; Allosteric Site; Animals; Anti-Anxiety Agents; Benzyl Alcohols; Conditioning, Classical; Drug Discovery; Fear; Female; HEK293 Cells; Humans; Ligands; Lorazepam; Male; Memory; Mice; Mice, Knockout; Models, Molecular; Receptors, G-Protein-Coupled; Signal Transduction; Triazines
PubMed: 26550826
DOI: 10.1038/nature15699 -
Journal of Pain and Symptom Management May 2014
Review
Topics: Anti-Anxiety Agents; Benzodiazepines; Hospice Care; Humans; Palliative Care
PubMed: 24681184
DOI: 10.1016/j.jpainsymman.2014.03.001