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Novel Pharmacological Targets of Post-Traumatic Stress Disorders

LIFE-BASEL (2023)

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Article Biochemistry & Molecular Biology

The Effect of Combined Treatment of Psilocybin and Eugenol on Lipopolysaccharide-Induced Brain Inflammation in Mice

Timur Zanikov et al.

Summary: Inflammation is a biological defense mechanism that can cause brain inflammation. Disorders like depression and PTSD are often associated with increased inflammation. Recent studies have shown positive results of using psilocybin and eugenol for the treatment of depression and PTSD. This study aimed to test the effects of psilocybin alone or in combination with eugenol on cytokine levels in the brains of mice with induced inflammation.

MOLECULES (2023)

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Article Medicine, General & Internal

Study protocol of an open-label proof-of-concept trial examining the safety and clinical efficacy of psilocybin-assisted therapy for veterans with PTSD

Alan K. Davis et al.

Summary: This study aims to examine the safety and efficacy of two different doses of psilocybin combined with psychotherapy in the treatment of severe and treatment resistant post-traumatic stress disorder (PTSD) among US military veterans. The study will recruit 15 veterans with severe PTSD and administer one low dose (15 mg) and one moderate/high dose (25 mg) of psilocybin, along with preparatory and post-psilocybin therapy sessions. The primary outcomes include the type, severity, and frequency of adverse events and suicidal ideation/behavior, as well as the assessment of PTSD symptoms. The results will be disseminated through a peer-reviewed publication and other media.

BMJ OPEN (2023)

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Article Neurosciences

Dose-related effects of ketamine for antidepressant-resistant symptoms of posttraumatic stress disorder in veterans and active duty military: a double-blind, randomized, placebo-controlled multi-center clinical trial

Chadi G. Abdallah et al.

Summary: This study examined the efficacy of intravenous ketamine doses in reducing symptoms of posttraumatic stress disorder (PTSD). The results showed that ketamine did not have a dose-related effect on PTSD symptoms, but the standard dose had rapid antidepressant effects.

NEUROPSYCHOPHARMACOLOGY (2022)

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Article Neurosciences

Intranasal oxytocin administration impacts the acquisition and consolidation of trauma-associated memories: a double-blind randomized placebo-controlled experimental study in healthy women

Katharina Schultebraucks et al.

Summary: This study found that intranasal oxytocin significantly increased intrusive memories, and this effect was influenced by several biological and genetic factors, including salivary cortisol, heart rate variability, and polygenic risk for PTSD.

NEUROPSYCHOPHARMACOLOGY (2022)

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Article Pharmacology & Pharmacy

Response to intravenous racemic ketamine after switch from intranasal (S)-ketamine on symptoms of treatment-resistant depression and post-traumatic stress disorder in Veterans: A retrospective case series

Sean Bentley et al.

Summary: This study suggests that off-label IV racemic ketamine could be considered as a next step in patients who do not respond adequately to FDA-approved intranasal (S)-ketamine. Further research is needed to assess the effectiveness of IV racemic ketamine compared to intranasal (S)-ketamine.

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Article Neurosciences

Effects of cannabidiol on symptoms induced by the recall of traumatic events in patients with posttraumatic stress disorder

Livia Maria Bolsoni et al.

Summary: Studies suggest that CBD has anxiolytic properties and may attenuate symptoms induced by recall of traumatic events in individuals with PTSD. This double-blind trial found that CBD in a dosage of 300 mg significantly reduced cognitive impairment associated with trauma recall, with this effect lasting for a week after administration. However, CBD did not significantly affect anxiety, alertness, or discomfort induced by recall, and there were no differences in physiological measures between the CBD and placebo groups.

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Article Neurosciences

MiR-153 downregulation alleviates PTSD-like behaviors and reduces cell apoptosis by upregulating the Sigma-1 receptor in the hippocampus of rats exposed to single-prolonged stress

Yu-Lu Chen et al.

Summary: This study found that miR-153 alleviated PTSD-like behaviors in rats exposed to SPS by regulating the expression of sigma-1R in the hippocampus. It also reduced cell apoptosis and increased dendritic spine density. The mTOR signaling pathway might be involved in the regulation of sigma-1R in the hippocampus of SPS rats.

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Post-traumatic stress disorder: clinical and translational neuroscience from cells to circuits

Kerry J. Ressler et al.

Summary: Post-traumatic stress disorder (PTSD) is a psychiatric disorder characterized by maladaptive symptoms following exposure to severe trauma. The neurobiology of PTSD, including genetic factors and dysregulation of fear processes, has been extensively studied. Combining molecular-genetic approaches with a translational understanding of fear circuitry could lead to transformative advances in the diagnosis and treatment of PTSD.

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Review Psychiatry

Childhood Trauma, the HPA Axis and Psychiatric Illnesses: A Targeted Literature Synthesis

Felim Murphy et al.

Summary: Studies show that early life stress impacts developmental trajectories and can create vulnerability to psychological and psychiatric issues later in life. The mechanisms affecting the developing brain in children and the incorporation of adverse environmental stimuli into the adult brain are important areas of research focus.

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Review Psychiatry

The Multivariate Effect of Ketamine on PTSD: Systematic Review and Meta-Analysis

Rui Du et al.

Summary: This study analyzed the use of ketamine in the treatment of post-traumatic stress disorder (PTSD) and found that it had no significant effect on the incidence of PTSD among combatant soldiers on the battlefield and early PTSD patients, but it may improve the condition of chronic PTSD patients.

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Review Biochemistry & Molecular Biology

Oxytocin: An Old Hormone, a Novel Psychotropic Drug and its Possible Use in Treating Psychiatric Disorders

Donatella Marazziti et al.

Summary: Oxytocin plays an important role in neuropsychiatric disorders, and alterations in its expression and receptor isoforms may be associated with the occurrence of these disorders. Exogenous administration of oxytocin has shown to improve many neuropsychiatric clinical conditions.

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Article Neurosciences

MicroRNA-124 attenuates PTSD-like behaviors and reduces the level of inflammatory cytokines by downregulating the expression of TRAF6 in the hippocampus of rats following single-prolonged stress

Yao Chen et al.

Summary: In this study, the role of miR-124 in the progression of PTSD was investigated. The upregulation of miR-124 was found to alleviate PTSD-like behaviors and decrease the level of proinflammatory cytokines. This effect of miR-124 might be achieved through regulating the expression of its target gene TRAF6.

EXPERIMENTAL NEUROLOGY (2022)

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Review Pharmacology & Pharmacy

Diverse therapeutic developments for post-traumatic stress disorder (PTSD) indicate common mechanisms of memory modulation

Sanket B. Raut et al.

Summary: Post-traumatic stress disorder (PTSD) is a chronic debilitating condition in need of new treatment options. Early evidence suggests the beneficial effects of psychedelics in combination with psychotherapy for managing PTSD. Research into memory reconsolidation mechanisms has identified pharmacological targets to disrupt abnormally persistent memories. Novel therapeutic approaches like neuropeptide Y, oxytocin, etc., have also shown potential for PTSD treatment.

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Decreased Plasma Oxytocin Levels in Patients With PTSD

Claudia Carmassi et al.

Summary: This study found significantly lower plasma levels of oxytocin in outpatients with PTSD compared to healthy control subjects. While supporting the possible involvement of oxytocin in the pathophysiology of PTSD, further research is needed to better understand the relationship between oxytocin levels and traumatic events in PTSD patients.

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Suicide risk in people with post-traumatic stress disorder: A cohort study of 3.1 million people in Sweden

Verity Fox et al.

Summary: The study found that individuals with PTSD in the general population in Sweden had higher suicide rates regardless of sex, and if causal, 1.6% of general population suicides could be attributed to PTSD.

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Nina Marsh et al.

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Collin M. Reiff et al.

BRAZILIAN JOURNAL OF PSYCHIATRY (2021)

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The Molecular Biology of Susceptibility to Post-Traumatic Stress Disorder: Highlights of Epigenetics and Epigenomics

Ghazi I. Al Jowf et al.

Summary: Exposure to trauma is a major risk factor for mental and physical health, with individuals showing varying susceptibility to developing mental illness after exposure. Epigenetic changes are suggested to play a role in the relationship between traumatic stress exposure and vulnerability to developing PTSD.

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Oxytocin in Schizophrenia: Pathophysiology and Implications for Future Treatment

Kah Kheng Goh et al.

Summary: Schizophrenia is characterized by abnormal behavior, and dysregulation of oxytocin may play a role in its expression. Studies have shown potential clinical benefits of oxytocin in improving the psychopathology of patients with schizophrenia. Oxytocin has the potential to be a therapeutic agent for schizophrenia and may have implications for future treatment.

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Kasper B. Hansen et al.

Summary: This study summarizes the physiological effects of L-glutamate and the importance of ionotropic glutamate receptors in brain function. Research on iGluRs has advanced rapidly, particularly in areas such as receptor structure, function, pharmacology, and roles in neurophysiology.

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MicroRNAs as biomarker and novel therapeutic target for posttraumatic stress disorder in Veterans

Sudhiranjan Gupta et al.

Summary: Posttraumatic stress disorder (PTSD) is a common psychiatric disorder characterized by a complex biological underpinning that is not fully understood. Circulatory microRNAs (miRNAs) and exosomes have shown to play important roles in PTSD research. Researchers suggest that miRNAs may be used as circulatory biomarker detection in Veterans with PTSD.

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Article Clinical Neurology

Effects of intranasal oxytocin on threat- and reward-related functional connectivity in men and women with and without childhood abuse-related PTSD

Lauren M. Sippel et al.

Summary: The study found that intranasal oxytocin modulates threat salience among childhood trauma-exposed individuals, and these effects vary as a function of gender and hemisphere.

PSYCHIATRY RESEARCH-NEUROIMAGING (2021)

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Oxytocin, Neural Plasticity, and Social Behavior

Robert C. Froemke et al.

Annual Review of Neuroscience (2021)

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Dysregulation of miR-15a-5p, miR-497a-5p and miR-511-5p Is Associated with Modulation of BDNF and FKBP5 in Brain Areas of PTSD-Related Susceptible and Resilient Mice

Oriana Maria Maurel et al.

Summary: Our study found that the expression of miRNAs in different brain areas is associated with susceptibility/resilience to PTSD. Changes in specific miRNAs may influence the transcription levels of FKBP5 and BDNF, and show a linear correlation with stress-induced behavioral phenotypes.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Psychiatry

Low-dose clonidine in veterans with Posttraumatic stress disorder

Gregory A. Burek et al.

Summary: This retrospective study evaluated the clinical records of veterans with PTSD treated with clonidine. After treatment with low-dose clonidine, 72% of patients experienced improvement, with 49% scoring "much improved" or "very much improved". Adverse effects were reported by 18 out of 79 subjects, suggesting minimal side effects with clonidine use in PTSD treatment.

JOURNAL OF PSYCHIATRIC RESEARCH (2021)

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Article Biochemistry & Molecular Biology

MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study

Jennifer M. Mitchell et al.

Summary: The results demonstrate that MDMA-assisted therapy is safe and effective in treating severe post-traumatic stress disorder. Compared with placebo, MDMA significantly reduces CAPS-5 scores and improves functional impairment.

NATURE MEDICINE (2021)

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Review Biochemistry & Molecular Biology

The Role of HPA Axis and Allopregnanolone on the Neurobiology of Major Depressive Disorders and PTSD

Felipe Borges Almeida et al.

Summary: This article discusses the role of the HPA axis under stressful conditions and the importance of allopregnanolone in promoting negative feedback mechanisms to restore homeostasis. Chronic, repeated exposure to stress may lead to dysfunction, contributing to the pathogenesis of major depressive disorder and post-traumatic stress disorder (PTSD).

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Biochemistry & Molecular Biology

Ketamine for post-traumatic stress disorders and it's possible therapeutic mechanism

Muhammad Asim et al.

Summary: Ketamine shows rapid and persistent efficacy against PTSD, possibly by modulating glutamate receptors and activating downstream BDNF and mTOR signaling pathways to enhance synaptic plasticity.

NEUROCHEMISTRY INTERNATIONAL (2021)

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A. Taylor Kelley et al.

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Monica A. Garcia et al.

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Protagonist Role of Opioidergic System on Post -Traumatic Stress Disorder and Associated Pain

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Buprenorphine: prospective novel therapy for depression and PTSD

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Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases-A Systematic Review and Meta-Analysis of Clinical Trials

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Longitudinal analyses of the DNA methylome in deployed military servicemen identify susceptibility loci for post-traumatic stress disorder

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Review Clinical Neurology

A Psychobiological Rationale for Oxytocin in the Treatment of Posttraumatic Stress Disorder

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A Study of the Protective Function of Acute Morphine Administration on Subsequent Posttraumatic Stress Disorder

Richard A. Bryant et al.

BIOLOGICAL PSYCHIATRY (2009)

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Preliminary Evidence for the Effects of Morphine on Posttraumatic Stress Disorder Symptoms in One- to Four-Year-Olds With Burns

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JOURNAL OF BURN CARE & RESEARCH (2009)

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Lower CSF oxytocin concentrations in women with a history of childhood abuse

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MOLECULAR PSYCHIATRY (2009)

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Development of the PTSD-alcohol expectancy questionnaire

Sonya B. Norman et al.

ADDICTIVE BEHAVIORS (2008)

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Divalproex in the treatment of posttraumatic stress disorder - A randomized, double-blind, placebo-controlled trial in a veteran population

Lori L. Davis et al.

JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY (2008)

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Amygdala intercalated neurons are required for expression of fear extinction

Ekaterina Likhtik et al.

NATURE (2008)

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High-affinity CRF1 receptor antagonist NBI-34041:: Preclinical and clinical data suggest safety and efficacy in attenuating elevated stress response

Marcus Ising et al.

NEUROPSYCHOPHARMACOLOGY (2007)

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A placebo-controlled trial of bupropion SR in the treatment of chronic posttraumatic stress disorder

Mary E. Becker et al.

JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY (2007)

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Open-label trial of escitalopram in the treatment of posttraumatic stress disorder

Sophie Robert et al.

JOURNAL OF CLINICAL PSYCHIATRY (2006)

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Historical approaches to post-combat disorders

E Jones

PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES (2006)

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SSRIs versus non-SSRIs in post-traumatic stress disorder - An update with recommendations

GM Asnis et al.

DRUGS (2004)

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Comparison of nefazodone and sertraline for the treatment of posttraumatic stress disorder

AL McRae et al.

DEPRESSION AND ANXIETY (2004)

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Systemic oxytocin treatment modulates glucocorticoid and mineralocorticoid receptor mRNA in the rat hippocampus

M Petersson et al.

NEUROSCIENCE LETTERS (2003)

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Early historical literature for post-traumatic symptomatology

P Birmes et al.

STRESS AND HEALTH (2003)

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Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin:: A placebo-controlled study

MA Raskind et al.

AMERICAN JOURNAL OF PSYCHIATRY (2003)

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Beyond the role of glutamate as a neurotransmitter

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NATURE REVIEWS NEUROSCIENCE (2002)

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Prazosin reduces nightmares in combat veterans with posttraumatic stress disorder

MA Raskind et al.

JOURNAL OF CLINICAL PSYCHIATRY (2002)

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Relationship between acute morphine and the course of PTSD in children with burns

G Saxe et al.

JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY (2001)

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Meta-analysis of risk factors for posttraumatic stress disorder in trauma-exposed adults

CR Brewin et al.

JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY (2000)

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