[11C]Fentanyl: Radiosynthesis and Preclinical PET Imaging for Its Pharmacokinetics.

Background Fentanyl is a potent synthetic opioid widely used for pain management and anesthesia, but the high prevalence of its misuse and its key contribution to overdose fatalities in the United States have made it a major drug of concern. Although fentanyl's onset, duration, and toxicity depend on its pharmacokinetics and specific tissue distribution, most studies have focused primarily on plasma concentrations, leaving its distribution in critical tissues largely unexplored (this knowledge gap limits our understanding of fentanyl's clinical effects, tissue accumulation, and the factors influencing its efficacy and safety). Here, we report the radiosynthesis of [ C]fentanyl for PET imaging and present a preliminary whole-body pharmacokinetic study in rodents.

Semaglutide or Tirzepatide and Optic Nerve and Visual Pathway Disorders in Type 2 Diabetes.

Importance: Semaglutide and tirzepatide, the new generation of glucagon-like peptide-1 receptor agonist used to treat type 2 diabetes and obesity, were recently reported to be associated with increased risk of nonarteritic anterior ischemic optic neuropathy (NAION). However, reported associations were inconsistent, and it remains unknown if semaglutide or tirzepatide is associated with other disorders of the optic nerve and visual pathways.

Objective: To examine associations of treatment with either semaglutide or tirzepatide with first-time diagnoses of optic nerve and visual pathway disorders in patients with type 2 diabetes.

Inhibition of iNOS reduced cerebral vasoconstriction from chronic cocaine and enhanced angiogenesis in the prefrontal cortex.

Cocaine is a highly addictive drug associated with neurovascular complications, such as transient ischemic attacks (TIAs) and strokes. Neuroimaging studies have documented marked decreases in cerebral blood flow (CBF) in the brain of cocaine abusers. Recently we showed astrocytes' involvement in cocaine-induced vasoconstriction and associated cortical ischemia in the mouse brain.

Development and Preclinical Evaluation of PET Radiotracers Targeting Adenosine A Receptors.

Several adenosine A receptor (AR) radiotracers for positron emission tomography (PET) have been developed to study their neuromodulatory functions and role in brain disorders. While two xanthine-based radiotracers ([C]-MPDX and [F]-CPFPX) have been used in humans, we aimed to improve the metabolic stability and specific binding. Guided by structure-activity relationship (SAR) studies, 10 derivatives were synthesized with binding affinities up to 0.

Associations of semaglutide with Alzheimer's disease-related dementias in patients with type 2 diabetes: A real-world target trial emulation study.

BackgroundAlmost half of the dementia cases are preventable. Semaglutide treats several medical conditions that are risk factors for dementia.ObjectiveWe aim to investigate if semaglutide is associated with a decreased risk of dementia.

Addictive-like Dimensions of Problematic Use of Social Media.

Compulsive use of social media, when it becomes problematic, shares behavioral similarities with substance use disorders. Moreover, preliminary imaging studies have reported structural and functional brain deficits that overlap with those seen in drug addiction, supporting an addictive dimensional component underlying problematic use of social media. Current evidence is consistent with the hypothesis that excessive or maladaptive reliance on social media can trigger or exacerbate symptoms of depression and anxiety, particularly among young people, further perpetuating its use and expanding its potential adverse effects.

Abnormal alterations in neurodevelopment in preterm children with very low birth weight during the adolescence.

Background: Preterm infants with very low birth weight are at high risk for long-term neurocognitive deficits. However, whether these neurocognitive deficits are improved or worsened in adolescence remains unclear.

Methods: We took advantage of the large sample from the Adolescent Brain Cognitive Development dataset to investigate alterations in brain structure, behavior, including cognitive function and mental health symptoms, and in puberty among preterm children with very low/normal birth weight (Pre_VLBW/Pre_NBW) and full-term children with normal birth weight (Con_NBW) from baseline to 2-year follow-up.

Brain asymmetry and its association with inattention and heritability during neurodevelopment.

The relationship between brain asymmetry and inattention, and their heritability is not well understood. Utilizing advanced neuroimaging, we examined brain asymmetry with data from the Adolescent Brain Cognitive Development (ABCD; n = 8943; 9-10 y) and the Human Connectome Project (HCP) cohorts (n = 1033; 5-100 y). Data-driven metrics from resting-state fMRI and morphometrics revealed reproducible and stable brain asymmetry patterns across the lifespan.

Neural basis for individual differences in the attention-enhancing effects of methylphenidate.

Stimulant drugs that boost dopamine, like methylphenidate (MP), enhance attention and are effective treatments for attention-deficit hyperactivity disorder (ADHD). Yet there is large individual variation in attentional capacity and response to MP. It is unclear whether this variation is driven by individual differences in relative density of dopamine receptor subtypes, magnitude of dopamine increases induced by MP, or both.

Prescription Stimulant Use, Misuse, and Use Disorder Among US Adults Aged 18 to 64 Years.

Importance: Stimulants are increasingly prescribed for US adults. Whether such prescribing is associated with misuse and prescription stimulant use disorder (PSUD) is less understood.

Objectives: To examine (1) sex- and age-specific trends in the number of persons dispensed stimulants and trends in dispensed prescription stimulants by prescriber specialty in 2019 through 2022; (2) prevalence of misuse and PSUD by use of prescription amphetamine-type stimulants (hereafter referred to as amphetamines) and methylphenidate; and (3) PSUD prevalence and sociodemographic and behavioral health correlates among persons using prescription stimulants with and without prescription stimulant misuse.

Methylphenidate promotes a frontoparietal-dominant brain state improving cognitive performance: a randomized trial.

Methylphenidate (MP) is a widely used stimulant medication for the treatment of attention deficit hyperactivity disorder that enhances brain dopamine signaling and improves attention. However, how dopamine stimulation alters brain state dynamics to support improved attention during task performance is still unclear. To address this, we employed a multimodal neuroimaging approach combining positron emission tomography, functional magnetic resonance imaging, and behavioral tasks, to discover associations between dopamine signaling, brain dynamics, and cognition.

Obesity is associated with progressive brain structural changes.

Objective: The aim of this study was to investigate the relationship between obesity (OB) progression and brain structural changes.

Methods: T1-weighted magnetic resonance images were acquired from 258 participants with overweight (OW) or OB and 74 participants with normal weight. Participants with OW or OB were divided into four groups according to BMI grades.

Single-dose psilocybin therapy for alcohol use disorder: Pharmacokinetics, feasibility, safety and efficacy in an open-label study.

Background: Psilocybin, a serotonin 2A receptor agonist with psychedelic properties, shows promise as a novel treatment for alcohol use disorder (AUD). While current studies involve two dosing sessions, the effects of a single dose have not been investigated.

Aims: To investigate the pharmacokinetics, feasibility, safety and efficacy of single-dose psilocybin therapy in AUD.

Prediction of alcohol intake patterns with olfactory and gustatory brain connectivity networks.

Craving in alcohol drinkers is often triggered by chemosensory cues, such as taste and smell, which are linked to brain network connectivity. This study aimed to investigate whether these brain connectivity patterns could predict alcohol intake in young adults. Resting-state fMRI data were obtained from the Human Connectome Project (HCP) Young Adult cohort, comprising 1003 participants.

Rest-Activity Rhythms, Their Modulators, and Brain-Clinical Correlates in Opioid Use Disorder.

Importance: Sleep and circadian disruptions are highly prevalent in opioid use disorder (OUD) and are a barrier to successful treatment and recovery; yet few objective data are available, especially for individuals in OUD treatment with opioid agonist therapy. If disruptions remain present despite OUD treatment, this information would yield potential new targets for adjunctive therapy.

Objective: To systematically investigate different aspects of rest-activity rhythms (RAR), including sleep, physical activity, circadian rhythmicity, and brain functional correlates in individuals with OUD.

Brain Function Outcomes of Recent and Lifetime Cannabis Use.

Importance: Cannabis use has increased globally, but its effects on brain function are not fully known, highlighting the need to better determine recent and long-term brain activation outcomes of cannabis use.

Objective: To examine the association of lifetime history of heavy cannabis use and recent cannabis use with brain activation across a range of brain functions in a large sample of young adults in the US.

Design, Setting, And Participants: This cross-sectional study used data (2017 release) from the Human Connectome Project (collected between August 2012 and 2015).

Prevalence of cannabis consumption methods among people with medically recommended and nonmedical cannabis use in the United States.

Aims: Some cannabis consumption methods (e.g. smoking, vaping, dabbing) are associated with more harms than others (e.

Sex disparities in outcome of medication-assisted therapy of opioid use disorder: Nationally representative outpatient clinic data.

Question: The opioid epidemic causes massive morbidity, and males have substantially greater overdose mortality rates than females. It is unclear whether there are sex-related disparities at different stages in the trajectory of opioid use disorders (OUD), from large samples in the community.

Goal: To determine sex disparities in non-medical opioid use (NMOU) at the end of treatment with medications for opioid use disorder (MOUD), using national data.

Does semaglutide reduce alcohol intake in Danish patients with alcohol use disorder and comorbid obesity? Trial protocol of a randomised, double-blinded, placebo-controlled clinical trial (the SEMALCO trial).

Introduction: Alcohol use disorder (AUD) is a massive burden for the individual, relatives and society. Despite this, the treatment gap is wide compared with other mental health disorders. Treatment options are sparse, with only three Food and Drug Administration (FDA)-approved pharmacotherapies.

The Limbic System in Co-Occurring Substance Use and Anxiety Disorders: A Narrative Review Using the RDoC Framework.

Substance use disorders (SUDs) and anxiety disorders (ADs) are highly comorbid, a co-occurrence linked to worse clinical outcomes than either condition alone. While the neurobiological mechanisms involved in SUDs and anxiety disorders are intensively studied separately, the mechanisms underlying their comorbidity remain an emerging area of interest. This narrative review explores the neurobiological processes underlying this comorbidity, using the Research Domain Criteria (RDoC) framework to map disruptions in positive valence, negative valence, and cognitive systems across the three stages of the addiction cycle: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation.

Evidence of cortical vascular impairments in early stage of Alzheimer's transgenic mice: Optical imaging.

Alzheimer's disease (AD), a neurodegenerative disorder with progressive cognitive decline, remains clinically challenging with limited understanding of etiology and interventions. Clinical studies have reported vascular defects prior to other pathological manifestations of AD, leading to the "Vascular Hypothesis" for the disorder. However, assessments of cerebral vasculature in AD rodent models have been constrained by limited spatiotemporal resolution or field of view of conventional imaging.