Phase 1b/2a safety study of lemborexant as an adjunctive treatment for insomnia to buprenorphine-naloxone for opioid use disorder: A randomized controlled trial.

Background: Evidence supports the common incidence of sleep disturbance in opioid use disorder (OUD) as a potential marker of disrupted orexin system functioning. This study evaluated the initial safety and tolerability of a challenge dose of lemborexant, a dual orexin antagonist, as an adjunct to buprenorphine/naloxone.

Methods: Patients (18-65 years old) with OUD receiving sublingual buprenorphine/naloxone, with a Pittsburgh Sleep Quality Index total score of 6 or higher, were recruited from outpatient clinics.

Sex Affects Cognitive Outcomes in HIV-1 Tat Transgenic Mice: Role of CCR5.

People living with HIV (PLWH) experience HIV-associated neurocognitive disorders (HAND), even though combination antiretroviral therapy (cART) suppresses HIV replication. HIV-1 transactivator of transcription (HIV-1 Tat) contributes to the development of HAND through neuroinflammatory and neurotoxic mechanisms. C-C chemokine 5 receptor (CCR5) is important in immune cell targeting and is a co-receptor for HIV viral entry into CD4+ cells.

Discovery of 6α-Thiazolylcarboxamidonaltrexamine Derivative (NTZ) as a Potent and Central Nervous System Penetrant Opioid Receptor Modulator with Drug-like Properties for Potential Treatment of Opioid Use Disorder.

The development of highly potent and selective μ opioid receptor (MOR) modulators with favorable drug-like properties has always been a focus in the opioid domain. Our previous efforts led to the discovery of a lead compound designated as NAT, a potent centrally acting MOR modulator. However, the fact that NAT precipitated considerable withdrawal effects at higher doses largely impaired its further development.

Sex related differences in cognitive deficits: Disrupted Arc/Arg3.1 signaling in an HIV model.

Combined and highly active anti-retroviral therapies (cART) have transitioned HIV into a more chronic disease. Roughly half of people living with HIV (PLWH) still experience neurocognitive disorders, albeit less severely than in the pre-cART era. Sex-related effects on memory/cognition remain understudied, although the percentage of PLWH that are female has increased.

Novel voltage-dependent Cl channels in striatal medium spiny neurons are unrelated to ClC-1 or other known Ca-induced Cl channel/transporter types.

Intracellular chloride (Cl) homeostasis is a critical regulator of neuronal excitability. Voltage-dependent neuronal Cl channels remain the least understood in terms of their role as a source of Cl entry controlling excitability. We have shown recently that striatal medium spiny neurons (MSNs) express a functional Cl conducting ClC-1-like channel with properties similar but not identical to native ClC-1 channels (Yarotskyy, V.

Examining the effects of the HIV-1 protein Tat and morphine on antiretroviral accumulation and distribution within the brain.

Despite combination antiretroviral therapy effectively suppressing HIV within the periphery, neuro-acquired HIV (neuroHIV) remains a significant problem and approximately half of people living with HIV will experience HIV-associated neurocognitive disorders (HAND). Concurrent opioid use exacerbates neuroHIV by promoting neuroinflammation, neuronal injury and synaptodendritic culling, viral replication, and potentially altering antiretroviral concentrations within the brain. The present study examined the effects of HIV and morphine co-exposure on the accumulation and spatial distribution of antiretroviral drugs across multiple regions within the brain in an HIV-1 Tat transgenic mouse model by using infrared-matrix-assisted laser desorption electrospray ionization mass spectrometry imaging (IR-MALDESI MSI).

Relationship between central autonomic effective connectivity and heart rate variability: A Resting-state fMRI dynamic causal modeling study.

The central autonomic network (CAN) serves as a regulatory hub with top-down regulatory control and integration of bottom-up physiological feedback via the autonomic nervous system. Heart rate variability (HRV)-the time variance of the heart's beat-to-beat intervals-is an index of the CAN's affective and behavioral regulatory capacity. Although neural functional connectivities that are associated with HRV and CAN have been well studied, no published report to date has studied effective (directional) connectivities (EC) that are associated with HRV and CAN.

Profiling the sleep architecture of ageing adults using a seven-state continuous-time Markov model.

Sleep is a complex biological process regulated by networks of neurons and environmental factors. As one falls asleep, neurotransmitters from sleep-wake regulating neurones work in synergy to control the switching of different sleep states throughout the night. As sleep disorders or underlying neuropathology can manifest as irregular switching, analysing these patterns is crucial in sleep medicine and neuroscience.

Neuroimaging Biomarkers in Addiction.

As a neurobiological process, addiction involves pathological patterns of engagement with substances and a range of behaviors with a chronic and relapsing course. Neuroimaging technologies assess brain activity, structure, physiology, and metabolism at scales ranging from neurotransmitter receptors to large-scale brain networks, providing unique windows into the core neural processes implicated in substance use disorders. Identified aberrations in the neural substrates of reward and salience processing, response inhibition, interoception, and executive functions with neuroimaging can inform the development of pharmacological, neuromodulatory, and psychotherapeutic interventions to modulate the disordered neurobiology.

Sustained fentanyl exposure inhibits neuronal activity in dissociated striatal neuronal-glial cocultures through actions independent of opioid receptors.

Besides having high potency and efficacy at the µ-opioid (MOR) and other opioid receptor types, fentanyl has some affinity for some adrenergic receptor types, which may underlie its unique pathophysiological differences from typical opioids. To better understand the unique actions of fentanyl, we assessed the extent to which fentanyl alters striatal medium spiny neuron (MSN) activity via opioid receptors or α-adrenoceptors in dopamine type 1 or type 2 receptor (D1 or D2)-expressing MSNs. In neuronal and mixed-glial cocultures from the striatum, acute fentanyl (100 nM) exposure decreased the frequency of spontaneous action potentials.

Post-traumatic stress disorder symptomatology is associated with insomnia among women engaged in opioid use disorder treatment with buprenorphine.

This study aimed to explore the association between the degree of PTSD symptomatology and severity of insomnia symptoms in a clinical sample of women receiving buprenorphine for OUD. PTSD symptomatology was assessed via the PCL-5, and insomnia symptoms were determined via the Insomnia Severity Index. Analyses indicated that more participants experiencing clinically significant PTSD symptomatology also reported insomnia symptoms than their counterparts.

Developmental differences in striatal recruitment by reward prospects as a function of attentional demand.

Adolescent risk-taking has been attributed to earlier-developing motivational neurocircuitry that is poorly controlled by immature executive-control neurocircuitry. Functional magnetic resonance imaging findings of increased ventral striatum (VS) recruitment by reward prospects in adolescents compared to adults support this theory. Other studies found blunted VS recruitment by reward-predictive cues in adolescents compared to adults.

Transparency and reproducibility in the Adolescent Brain Cognitive Development (ABCD) study.

Background: Transparency can build trust in the scientific process, but scientific findings can be undermined by poor and obscure data use and reporting practices. The purpose of this work is to report how data from the Adolescent Brain Cognitive Development (ABCD) Study has been used to date, and to provide practical recommendations on how to improve the transparency and reproducibility of findings.

Methods: Articles published from 2017 to 2023 that used ABCD Study data were reviewed using more than 30 data extraction items to gather information on data use practices.

Transparency and Reproducibility in the Adolescent Brain Cognitive Development (ABCD) Study.

Background: Transparency can build trust in the scientific process, but scientific findings can be undermined by poor and obscure data use and reporting practices. The purpose of this work is to report how data from the Adolescent Brain Cognitive Development (ABCD) Study has been used to date, and to provide practical recommendations on how to improve the transparency and reproducibility of findings.

Methods: Articles published from 2017 to 2023 that used ABCD Study data were reviewed using more than 30 data extraction items to gather information on data use practices.

Systematic Structure-Activity Relationship Study of Nalfurafine Analogues toward Development of Potentially Nonaddictive Pain Management Treatments.

Despite the availability of numerous pain medications, the current array of Food and Drug Administration-approved options falls short in adequately addressing pain states for numerous patients and consequently worsens the opioid crisis. Thus, it is imperative for basic research to develop novel and nonaddictive pain medications. Toward addressing this clinical goal, nalfurafine (NLF) was chosen as a lead and its structure-activity relationship (SAR) systematically studied through design, syntheses, and characterization of 24 analogues.

Blocking potential metabolic sites on NAT to improve its safety profile while retaining the pharmacological profile.

The number of opioid-related overdose deaths and individuals that have suffered from opioid use disorders have significantly increased over the last 30 years. FDA approved maintenance therapies to treat opioid use disorder may successfully curb drug craving and prevent relapse but harbor adverse effects that reduce patient compliance. This has created a need for new chemical entities with improved patient experience.

Utility of scores to predict alcohol use after liver transplant: Take them with a grain of salt.

The Sustained Alcohol use post-Liver Transplant (SALT) and the High-Risk Alcohol Relapse (HRAR) scores were developed to predict a return to alcohol use after a liver transplant (LT) for alcohol-associated liver disease. A retrospective analysis of deceased donor LT from October 2018 to April 2022 was performed. All patients underwent careful pre-LT psychosocial evaluation.

Low-dose buprenorphine initiation during pregnancy: a case report.

Buprenorphine is recommended for pregnant patients with opioid use disorder. Traditional buprenorphine initiation requires moderate withdrawal symptoms to prevent precipitating withdrawal. Low-dose buprenorphine initiation is newly emerging and does not require withdrawal prior to initiation.

HIV-1 Tat and morphine interactions dynamically shift striatal monoamine levels and exploratory behaviors over time.

Despite the advent of combination anti-retroviral therapy (cART), nearly half of people infected with HIV treated with cART still exhibit HIV-associated neurocognitive disorders (HAND). HAND can be worsened by co-morbid opioid use disorder. The basal ganglia are particularly vulnerable to HIV-1 and exhibit higher viral loads and more severe pathology, which can be exacerbated by co-exposure to opioids.