The potential of non-psychedelic 5-HT2A agents in the treatment of substance use disorders: a narrative review of the clinical literature.

Introduction: Substance use disorders (SUDs) are a public health issue, with only some having FDA-approved indicated treatments and these having high attrition. Consequently, there has been interest in novel interventions (e.g.

Stability and Reliability of Repeated Plasma Pregnenolone Levels After Oral Pregnenolone Dosing in Individuals with Cocaine Use Disorder: Pilot Findings.

Substance use disorders (SUDs), including cocaine use disorder (CUD), have significant negative health risks and impose a substantial social burden, yet effective treatments are limited. Pregnenolone, a neuroactive steroid precursor, has been shown to reduce alcohol craving and normalize stress biology in individuals with CUD, but its clinical utility has been questioned due to limited data on bioavailability and the stability of blood levels in humans. Thus, this pilot study aimed to determine whether twice-daily oral pregnenolone (PREG) at 300 mg/day and 500 mg/day versus placebo in week two of PREG administration led to stable increased plasma pregnenolone levels in individuals with CUD.

Microglia-mediated neuroimmune suppression in PTSD is associated with anhedonia.

Dynamic brain immune function in individuals with posttraumatic stress disorder is rarely studied, despite evidence of peripheral immune dysfunction. Positron emission tomography brain imaging using the radiotracer [C]PBR28 was used to measure the 18-kDa translocator protein (TSPO), a microglial marker, at baseline and 3 h after administration of lipopolysaccharide (LPS), a potent immune activator. Data were acquired in 15 individuals with PTSD and 15 age-matched controls.

A review of the kappa opioid receptor system in opioid use.

The kappa opioid receptor (KOR) system is implicated in dysphoria and as an "anti-reward system" during withdrawal from opioids. However, no clear consensus has been made in the field, as mixed findings have been reported regarding the relationship between the KOR system and opioid use. This review summarizes the studies to date on the KOR system and opioids.

Substance use and spine density: a systematic review and meta-analysis of preclinical studies.

The elucidation of synaptic density changes provides valuable insights into the underlying brain mechanisms of substance use. In preclinical studies, synaptic density markers, like spine density, are altered by substances of abuse (e.g.

Cocaine self-administration behavior is associated with subcortical and cortical morphometry measures in individuals with cocaine use disorder.

Individual differences in gray-matter morphometry in the limbic system and frontal cortex have been linked to clinical features of cocaine use disorder (CUD). Self-administration paradigms can provide more direct measurements of the relationship between the regulation of cocaine use and gray-matter morphometry when compared to self-report assessments. Our goal was to investigate associations with self-administration behavior in subcortical and cortical brain regions.

Dysregulation of the endogenous cannabinoid system following opioid exposure.

Rates of opioid-related deaths and overdoses in the United States are at record-high levels. Thus, novel neurobiological targets for the treatment of OUD are greatly needed. Given the close interaction between the endogenous opioid system and the endocannabinoid system (ECS), targeting the ECS may have therapeutic potential in OUD.

"Dysregulated not deficit": A qualitative study on symptomatology of ADHD in young adults.

Objective: Attention-deficit/hyperactivity disorder (ADHD) is a common condition that often persists into adulthood, although data suggest that the current diagnostic criteria may not represent how the condition presents in adults. We aimed to use qualitative methods to better understand ADHD symptomatology in young adults, especially regarding attentional and emotional dysregulation.

Methods: Nine focus groups involving young adults (aged 18-35 years; N = 43; 84% female; 86% US and Canada) with diagnoses of ADHD were conducted.

Imaging the brain's immune response to alcohol with [C]PBR28 TSPO Positron Emission Tomography.

In humans, the negative effects of alcohol are linked to immune dysfunction in both the periphery and the brain. Yet acute effects of alcohol on the neuroimmune system and its relationships with peripheral immune function are not fully understood. To address this gap, immune response to an alcohol challenge was measured with positron emission tomography (PET) using the radiotracer [C]PBR28, which targets the 18-kDa translocator protein, a marker sensitive to immune challenges.

Discriminating cocaine use from other sympathomimetics using wearable electrocardiographic (ECG) sensors.

Background: Our group has established the feasibility of using on-body electrocardiographic (ECG) sensors to detect cocaine use in the human laboratory. The purpose of the current study was to test whether ECG sensors and features are capable of discriminating cocaine use from other non-cocaine sympathomimetics.

Methods: Eleven subjects with cocaine use disorder wore the Zephyr BioHarness™ 3 chest band under six experimental (drug and non-drug) conditions, including 1) laboratory, intravenous cocaine self-administration, 2) after a single oral dose of methylphenidate, 3) during aerobic exercise, 4) during tobacco use (N=7 who smoked tobacco), and 5) during routine activities of daily inpatient living (unit activity).

Changes in synaptic markers after administration of ketamine or psychedelics: a systematic scoping review.

Background: Ketamine and psychedelics have abuse liability. They can also induce "transformative experiences" where individuals experience enhanced states of awareness. This enhanced awareness can lead to changes in preexisting behavioral patterns which could be beneficial in the treatment of substance use disorders (SUDs).

Hypothalamic-pituitary-adrenal and autonomic response to psychological stress in abstinent alcohol use disorder individuals with and without depressive symptomatology.

Background: Stress and depression have each been associated with relapse risk. In clinical practice, chronic alcohol use is often accompanied by poor emotional and self-regulatory processes. Tonic and phasic changes in stress responsivity impact an individual's relapse risk to alcohol.

Cholinergic system adaptations are associated with cognitive function in people recently abstinent from smoking: a (-)-[F]flubatine PET study.

The cholinergic system is a critical mediator of cognition in animals. People who smoke cigarettes exhibit cognitive deficits, especially during quit attempts. Few studies jointly examine the cholinergic system and cognition in people while trying to quit smoking.

Neurotransmitter transporter occupancy following administration of centanafadine sustained-release tablets: A phase 1 study in healthy male adults.

Background: Centanafadine is an inhibitor of reuptake transporters for norepinephrine (NET), dopamine (DAT) and serotonin (SERT).

Aims: This phase 1, adaptive-design positron emission tomography study investigated the occupancy time course of NET, DAT, and SERT and the relationship to centanafadine plasma concentrations.

Methods: Healthy adult males received centanafadine sustained-release 400 mg/day for 4 days ( = 6) or 800 mg in a single day ( = 4).

The Potential of N-acetyl Cysteine in Behavioral Addictions and Related Compulsive and Impulsive Behaviors and Disorders: a Scoping Review.

Purpose Of Review: Behavioral addictions (also termed disorders due to addictive behaviors) contain impulsive and compulsive features and have been shown to involve glutamate dysregulation. N-acetylcysteine (NAC), a well-tolerated cysteine pro-drug and antioxidant, may reduce addictive behaviors by restoring glutamate homeostasis. The current review details and discusses the use of NAC in behavioral addictions and related impulsive and compulsive behaviors, including gambling disorder, problematic use of the internet, problematic video gaming, compulsive sexual behavior, problematic shopping/buying, problematic stealing, repetitive self-injurious behavior, and binge eating disorder.

The lived experiences of adults with attention-deficit/hyperactivity disorder: A rapid review of qualitative evidence.

Attention-deficit/hyperactivity disorder (ADHD) is a common condition that frequently persists into adulthood, although research and diagnostic criteria are focused on how the condition presents in children. We aimed to review qualitative research on lived experiences of adults with ADHD to characterize potential ADHD symptomatology in adulthood and provide perspectives on how needs might be better met. We searched three databases for qualitative studies on ADHD.

Helpful or Harmful? The Therapeutic Potential of Medications with Varying Degrees of Abuse Liability in the Treatment of Substance Use Disorders.

Purpose Of Review: This review summarizes recent clinical trial research on pharmacological treatments for substance use disorders, with a specific focus on agents with potential abuse liability.

Recent Findings: Pharmacological treatments for substance use disorders may include gabapentinoids, baclofen, modafinil, ketamine, cannabinoids, gamma-hydroxybutyrate, and psychedelics. Gabapentinoids may decrease negative subjective effects of withdrawal in alcohol and cannabis use disorders.

First Episode Psychosis and Pituitary Hyperplasia in a Patient With Untreated Hashimoto's Thyroiditis: A Case Report.

This case report describes a woman with no psychiatric history and previously diagnosed Hashimoto's thyroiditis who presented to the psychiatric emergency department with a first episode of psychosis. The initial workup for organic causes of psychosis revealed an astronomically high thyroid stimulating hormone (TSH) (> 1,000 μIU/mL) out of proportion to the patient's minimal physical symptoms of hypothyroidism. Additionally the patient's head imaging showed an enlarged pituitary, a rare, but reversible, presentation of chronically untreated primary hypothyroidism.

Multimodal neuroimaging of metabotropic glutamate 5 receptors and functional connectivity in alcohol use disorder.

Background: People recovering from alcohol use disorder (AUD) show altered resting brain connectivity. The metabotropic glutamate 5 (mGlu5) receptor is an important regulator of synaptic plasticity potentially linked with synchronized brain activity and a target of interest in treating AUD. The goal of this work was to assess potential relationships of brain connectivity at rest with mGlu5 receptor availability in people with AUD at two time points early in abstinence.

Imaging the effect of ketamine on synaptic density (SV2A) in the living brain.

The discovery of ketamine as a rapid and robust antidepressant marks the beginning of a new era in the treatment of psychiatric disorders. Ketamine is thought to produce rapid and sustained antidepressant effects through restoration of lost synaptic connections. We investigated this hypothesis in humans for the first time using positron emission tomography (PET) and [C]UCB-J-a radioligand that binds to the synaptic vesicle protein 2A (SV2A) and provides an index of axon terminal density.

Alcohol withdrawal symptoms predict corticostriatal dysfunction that is reversed by prazosin treatment in alcohol use disorder.

Chronic alcohol use increases risk of alcohol withdrawal symptoms (AW) and disrupts stress biology and resilient coping, thereby promoting excessive alcohol intake. Chronic alcohol intake and multiple alcohol detoxifications are known to impair brain medial prefrontal cortex (mPFC) and striatal functioning, regions involved in regulating stress, craving and alcohol intake. In two related studies, we examined whether AW predicts this functional brain pathology and whether Prazosin versus Placebo treatment may reverse these effects.

Lower prefrontal cortical synaptic vesicle binding in cocaine use disorder: An exploratory C-UCB-J positron emission tomography study in humans.

Preclinical studies have revealed robust and long-lasting alterations in dendritic spines in the brain following cocaine exposure. Such alterations are hypothesized to underlie enduring maladaptive behaviours observed in cocaine use disorder (CUD). The current study explored whether synaptic density is altered in CUD.