Background: Pain management physicians are increasingly focused on limiting prescription opioid abuse, yet existing tools for monitoring adherence have limited accuracy. Medication event monitoring system (MEMS) is an emerging technology for tracking medication usage in real-time but has not been tested in chronic pain patients on long-term opioid regimens.
Objective: We conducted a pilot clinical trial to investigate the utility of MEMS for monitoring opioid adherence and compared to traditional methods including self-report diaries, urine drug screen (UDS), and physicians' opinions.
Opioid misuse and opioid-involved overdose deaths are a massive public health problem involving the intertwined misuse of prescription opioids for pain management with the emergence of extremely potent fentanyl derivatives, sold as standalone products or adulterants in counterfeit prescription opioids or heroin. The incidence of repeated opioid overdose events indicates a problematic use pattern consistent with the development of the medical condition of opioid use disorder (). Prescription and illicit opioids reduce pain perception by activating µ-opioid receptors () localized to the central nervous system ().
View Article and Find Full Text PDFScience advisory boards and policy organizations have called for adolescent brain science to be incorporated into juvenile probation operations. To achieve this, Opportunity-Based Probation (OBP), a probation model that integrates knowledge of adolescent development and behavior change principles, was developed in collaboration with a local juvenile probation department. The current study compares outcomes (recidivism and probation violations) for youth in the OBP condition versus probation as usual.
View Article and Find Full Text PDFThe drug overdose crisis has spawned serious health consequences, including the increased incidence of substance use disorders (SUDs), conditions manifested by escalating medical and psychological impairments. While medication management is a key adjunct in SUD treatment, this crisis has crystallized the need to develop additional therapeutics to facilitate extended recovery from SUDs. The "hunger hormone" ghrelin acts by binding to the growth hormone secretagogue receptor 1α (GHS1αR) to control homeostatic and hedonic aspects of food intake and has been implicated in the mechanisms underlying SUDs.
View Article and Find Full Text PDFSignificant trauma histories and post-traumatic stress disorder (PTSD) are common in persons with substance use disorders (SUD) and often associate with increased SUD severity and poorer response to SUD treatment. As such, this sub-population has been associated with unique risk factors and treatment needs. Understanding the distinct etiological profile of persons with co-occurring SUD and PTSD is therefore crucial for advancing our knowledge of underlying mechanisms and the development of precision treatments.
View Article and Find Full Text PDFThe serotonin 5-HT receptor (5-HTR) and 5-HTR localize to the brain and share overlapping signal transduction facets that contribute to their roles in cognition, mood, learning, and memory. Achieving selective targeting of these receptors is challenged by the similarity in their 5-HT orthosteric binding pockets. A fragment-based discovery approach was employed to design and synthesize novel oleamide analogues as selective 5-HTR or dual 5-HTR/5-HTR positive allosteric modulators (PAMs).
View Article and Find Full Text PDFDrug overdose deaths involving cocaine have skyrocketed, an outcome attributable in part to the lack of FDA-approved medications for the treatment of cocaine use disorder (CUD), highlighting the need to identify new pharmacotherapeutic targets. Vulnerability to cocaine-associated environmental contexts and stimuli serves as a risk factor for relapse in CUD recovery, with individual differences evident in the motivational aspects of these cues. The medial prefrontal cortex (mPFC) provides top-down control of striatal circuitry to regulate the incentive-motivational properties of cocaine-associated stimuli.
View Article and Find Full Text PDFPhysicians are challenged in treating pain patients due to the lack of quantifiable, objective methods of measuring pain in the clinic; pain sensation is multifaceted and subjective to each individual. There is a critical need for point-of-care quantification of accessible biomarkers to provide objective analyses beyond the subjective pain scales currently employed in clinical care settings. In the present study, we employed an animal model to test the hypothesis that circulating regulators of the inflammatory response directly associate with an objective behavioral response to inflammatory pain.
View Article and Find Full Text PDFThe nucleus accumbens shell (NAcSh) and its afferent and efferent neuronal projections control key aspects of motivation for cocaine. A recently described regulator of γ-aminobutyric acid (GABA) projections from the dorsal raphe nucleus (DRN) to the NAcSh (DRN → NAcSh) is the neuropeptide neuromedin U (NMU). Here, we find that systemic administration of NMU decreases breakpoint for cocaine on a progressive ratio schedule of reinforcement in male rats.
View Article and Find Full Text PDFThe anorexigenic effect of serotonergic compounds has largely been attributed to activation of serotonin 2C receptors (Htr2cs). Using mouse genetic models in which Htr2c can be selectively deleted or restored (in Htr2c-null mice), we investigate the role of Htr2c in forebrain Sim1 neurons. Unexpectedly, we find that Htr2c acts in these neurons to promote food intake and counteract the anorectic effect of serotonergic appetite suppressants.
View Article and Find Full Text PDFPreclinical studies show serotonin (5-HT) 5-HT receptor (5-HTR) agonists reduce cocaine-seeking and cocaine intake. This study examined safety of the 5-HTR agonist lorcaserin administered with cocaine in participants with cocaine use disorder (CocUD). Secondarily, subjective response to cocaine and choice of cocaine vs.
View Article and Find Full Text PDFJuveniles referred for adjudicative competence evaluations make up a subset of youth involved in the juvenile justice system. Among those referred for adjudicative competence evaluations, a significant number involve youth with current or past charges for sexual offenses. This study examines the profiles of youth with sexual offense charges who have been referred for competence evaluations at a state psychiatric hospital for children and adolescents.
View Article and Find Full Text PDFThe concept of 'impulse control' has its roots in early psychiatry and today has progressed into a well-described, although poorly understood, multidimensional endophenotype underlying many neuropsychiatric disorders (e.g., attention deficit hyperactivity disorder, schizophrenia, substance use disorders).
View Article and Find Full Text PDF5-HT receptors expressed throughout the human body are targets for established therapeutics and various drugs in development. Their diversity of structure and function reflects the important role 5-HT receptors play in physiologic and pathophysiological processes. The present review offers a framework for the official receptor nomenclature and a detailed understanding of each of the 14 5-HT receptor subtypes, their roles in the systems of the body, and, where appropriate, the (potential) utility of therapeutics targeting these receptors.
View Article and Find Full Text PDFNeuropsychopharmacology
January 2021
This article provides a comprehensive review of juvenile adjudicative competence (AC) literature published between 2010 and 2019. Publications included in this article are peer-reviewed and disseminate original research or provide new commentary on forensic evaluation, policy, or theory. The review is organized in the following sequence: (i) factors associated with juvenile AC, (ii) evaluating juvenile AC (assessment tools and techniques, quality of evaluations, evaluation recommendations), (iii) remediation (remediation recommendations), (iv) systemic issues (inconsistency in statutes and court processes, defense attorneys' concerns about AC, age-related issues, developmental immaturity), and (v) special topics (special populations, international research).
View Article and Find Full Text PDFRelapse during abstinence in cocaine use disorder (CUD) is often hastened by high impulsivity (predisposition toward rapid unplanned reactions to stimuli without regard to negative consequences) and high cue reactivity (e.g., attentional bias towards drug reward stimuli).
View Article and Find Full Text PDFTargeting the serotonin (5-HT) 5-HT receptor (5-HTR) allosteric site to potentiate endogenous 5-HT tone may provide novel therapeutics to alleviate the impact of costly, chronic diseases such as obesity and substance use disorders. Expanding upon our recently described 5-HTR-positive allosteric modulators (PAMs) based on the 4-alkylpiperidine-2-carboxamide scaffold, we optimized the undecyl moiety at the 4-position with variations of cyclohexyl- or phenyl-containing fragments to reduce rotatable bonds and lipophilicity. Compound (CTW0415) was discovered as a 5-HTR PAM with improved pharmacokinetics and reduced off-target interactions relative to our previous series of molecules.
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