Oxytocin Reduces Noradrenergic-Induced Opioid-Like Withdrawal Symptoms in Individuals on Opioid Agonist Therapy.

Background: Intranasal administration of the neuropeptide oxytocin has been explored as a potential therapeutic agent for substance use disorder including opioid use disorder (OUD).

Methods: This phase 1, crossover, randomized, double-blind, placebo-controlled trial tested the safety, tolerability, and efficacy of intranasal oxytocin (80 IU) twice a day for 7 days in participants ( = 20) with OUD who were taking an opioid agonist therapy. In the laboratory, participants underwent opioid cue exposure paired with noradrenergic activation produced by yohimbine (32.

In the new era of psychedelic assisted therapy: A systematic review of study methodology in randomized controlled trials.

Recent years have seen a resurgence in randomized, placebo controlled trials (RCTs) utilizing non-classical psychedelics (e.g. 3,4-methyl enedioxy methamphetamine [MDMA]), and classical psychedelics (e.

Disruption of circadian rhythms promotes alcohol use: a systematic review.

This systematic review investigates the bidirectional relationship between alcohol consumption and disrupted circadian rhythms. The goal of this study was to identify (i) the types of circadian rhythm disruptors (i.e.

Treating posttraumatic stress disorder and alcohol use disorder comorbidity: Current pharmacological therapies and the future of MDMA-integrated psychotherapy.

Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) frequently co-occur in patients who have experienced trauma. This comorbidity leads to a vicious cycle where PTSD symptoms beget heavy drinking and vice versa. There are no FDA-approved medications to treat PTSD-AUD; therefore, individuals suffering from this comorbidity are treated with medication approved to treat the disorders separately or with off-label pharmacological interventions.

Evaluating the readability of online patient-facing resources for alcohol use disorder.

The goal of this study was to assess the readability of online resources pertaining to Alcohol Use Disorder (AUD) as perceived by patients seeking treatment. The National Institutes of Health (NIH) and American Medical Association (AMA) have recommended that medical resources should be written at a 6th-grade reading level. However, prior investigations in various medical fields have revealed that online materials often fail to adhere to these guidelines.

Mifepristone as a pharmacological intervention for stress-induced alcohol craving: A human laboratory study.

Preclinical and clinical work suggests that mifepristone may be a viable treatment for alcohol use disorder (AUD). This was a Phase 1/2, outpatient, cross-over, randomized, double-blind, placebo-controlled trial with non-treatment-seeking individuals with AUD (N = 32). We assessed safety, alcohol craving and consumption, after 1-week mifepristone 600 mg/day administration, in a human laboratory study comprised of a single oral yohimbine administration (32.

Mifepristone as a pharmacological intervention for stress-Induced alcohol craving: a translational crossover randomized trial.

Unlabelled: Preclinical and clinical work suggests that mifepristone (glucocorticoid receptor antagonist), may be a viable treatment for alcohol use disorder (AUD). The aim of this work was to translate our preclinical mifepristone study using yohimbine (α2 receptor antagonist) stress-induced reinstatement of alcohol-seeking to a clinical setting. This was a Phase 1/2, outpatient, cross-over, randomized, double-blind, placebo-controlled trial with non-treatment-seeking individuals with AUD ( =32).

COVID-19-Related Stressors and Clinical Mental Health Symptoms in a Northeast US Sample.

Unlabelled: Research has linked specific COVID-19-related stressors to the mental health burden, yet most previous studies have examined only a limited number of stressors and have paid little attention to their clinical significance. This study tested the hypothesis that individuals who reported greater COVID-19-related stressors would be more likely to have elevated levels of anxiety, posttraumatic stress symptoms, and serious psychological distress.

Methods: An online survey was administered to a convenience sample from 18 June to 19 July 2020, in US states that were most affected by COVID-19 infections and deaths at the time.

Development and use of a high-throughput screen to identify novel modulators of the corticotropin releasing factor binding protein.

Background: Stress responses are believed to involve corticotropin releasing factor (CRF), its two cognate receptors (CRF and CRF), and the CRF-binding protein (CRFBP). Whereas decades of research has focused on CRF, the role of CRF in the central nervous system (CNS) has not been thoroughly investigated. We have previously reported that CRF, interacting with a C terminal fragment of CRFBP, CRFBP(10kD), may have a role in the modulation of neuronal activity.

Yohimbine as a pharmacological probe for alcohol research: a systematic review of rodent and human studies.

Alcohol use disorder (AUD) is a significant public health concern, contributing to a myriad of social, psychological, and physiological issues. Despite substantial efforts within the alcohol research field, promising preclinical findings have failed to translate to clinical use, highlighting the necessity to develop safe and effective pharmacological probes with the ability to be used in preclinical and clinical research. Yohimbine, an α2 adrenergic receptor antagonist, is a well-validated pharmacological tool that has been widely employed in alcohol studies to evaluate noradrenergic activation.

The multitarget FAAH inhibitor/D3 partial agonist ARN15381 decreases nicotine self-administration in male rats.

Tobacco use disorder is a worldwide health problem for which available medications show limited efficacy. Nicotine is the psychoactive component of tobacco responsible for its addictive liability. Similar to other addictive drugs, nicotine enhances mesolimbic dopamine transmission.

The Amygdala Noradrenergic System Is Compromised With Alcohol Use Disorder.

Background: Alcohol use disorder (AUD) is a leading preventable cause of death. The central amygdala (CeA) is a hub for stress and AUD, while dysfunction of the noradrenaline stress system is implicated in AUD relapse.

Methods: Here, we investigated whether alcohol (ethanol) dependence and protracted withdrawal alter noradrenergic regulation of the amygdala in rodents and humans.

Corticotropin Releasing Factor Binding Protein as a Novel Target to Restore Brain Homeostasis: Lessons Learned From Alcohol Use Disorder Research.

Stress is well-known to contribute to the development of many psychiatric illnesses including alcohol and substance use disorder (AUD and SUD). The deleterious effects of stress have also been implicated in the acceleration of biological age, and age-related neurodegenerative disease. The physio-pathology of stress is regulated by the corticotropin-releasing factor (CRF) system, the upstream component of the hypothalamic-pituitary-adrenal (HPA) axis.

An inpatient human laboratory study assessing the safety and tolerability, pharmacokinetics, and biobehavioral effect of GET 73 when co-administered with alcohol in individuals with alcohol use disorder.

Rationale: Previous work suggests that GET 73, a novel compound with putative activity on the metabotropic glutamate receptor subtype 5 (mGluR5), may represent a novel pharmacological treatment for alcohol use disorder (AUD).

Objective: In this study, we investigated the safety, tolerability, pharmacokinetics, and biobehavioral effects of GET 73, when co-administered with alcohol, in individuals with alcohol dependence (AD).

Methods: This was an inpatient, cross-over, randomized, double-blind, placebo-controlled, human laboratory study with non-treatment-seeking, alcohol-dependent individuals.

Alcohol-related changes in behaviors and characteristics from the baseline to the randomization session for treatment and non-treatment seeking participants with alcohol use disorder.

Background: Participants who are enrolled in randomized controlled trials (RCTs) may be more motivated to change their behaviors after being enrolled in a study and that motivation may vary by treatment status.

Objectives: The objectives of this secondary analysis were to investigate if changes in alcohol-related behaviors/characteristics from the baseline to the randomization session differed overall and to assess those differences between non-treatment and treatment seeking individuals with alcohol use disorder (AUD).

Methods: Our sample included participants from eight RCTs conducted at Brown University ( = 281, 34% female).

Neuroendocrine Response to Exogenous Ghrelin Administration, Combined With Alcohol, in Heavy-Drinking Individuals: Findings From a Randomized, Double-Blind, Placebo-Controlled Human Laboratory Study.

Background: Accumulating evidence has established a role for the orexigenic hormone ghrelin in alcohol-seeking behaviors. Accordingly, the ghrelin system may represent a potential pharmacotherapeutic target for alcohol use disorder. Ghrelin modulates several neuroendocrine pathways, such as appetitive, metabolic, and stress-related hormones, which are particularly relevant in the context of alcohol use.

Randomized controlled trials for alcohol use disorder during the COVID-19 pandemic.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) altered the logistics of ongoing randomized controlled trials (RCTs). The need to reduce in-person research and clinical activities, however, presented an additional level of complexity in order to continue conducting RCTs that focused on the development of medications for Alcohol Use Disorder (AUD). The visits required a systematic objective evaluation from the physician and mental health professional and clinical staff, as many of the safety and efficacy assessments are self-reported.

Andrographis paniculata and Its Main Bioactive Ingredient Andrographolide Decrease Alcohol Drinking and Seeking in Rats Through Activation of Nuclear PPARγ Pathway.

Background And Aims: Andrographis paniculata is an annual herbaceous plant which belongs to the Acanthaceae family. Extracts from this plant have shown hepatoprotective, anti-inflammatory and antidiabetic properties, at least in part, through activation of the nuclear receptor Peroxisome Proliferator-Activated Receptor-gamma (PPAR γ). Recent evidence has demonstrated that activation of PPARγ reduces alcohol drinking and seeking in Marchigian Sardinian (msP) alcohol-preferring rats.

Differences in Sociodemographic and Alcohol-Related Clinical Characteristics Between Treatment Seekers and Nontreatment Seekers and Their Role in Predicting Outcomes in the COMBINE Study for Alcohol Use Disorder.

Background: One of the challenges in early-stage clinical research aimed at developing novel treatments for alcohol use disorder (AUD) is that the enrolled participants are heavy drinkers, but do not seek treatment for AUD.

Aims: To compare nontreatment seekers with alcohol dependence (AD) from 4 human laboratory studies conducted at Brown University (N = 240; 65.4% male) to treatment seekers with AD from the multisite COMBINE study (N = 1,383; 69.