Inter-individual divergence in thresholds for detecting opioid effects: Within-subject human laboratory evidence of a testable behavioral phenotype.

Variations in inter-individual response to opioid medications has not been well-investigated in prospective, empirical designs or in persons who have no learned experience with opioids or current pain conditions. These analyses categorized response to opioids during rigorous human laboratory experimental conditions. Healthy individuals (N = 75) with little to no prior opioid exposure completed a 5-day residential study wherein they received triple-blinded doses of placebo or oral hydromorphone (2mg, 4mg, 8mg).

A within-subject, double-blind, placebo-controlled randomized evaluation of the combined effects of cannabidiol and hydromorphone in a human laboratory pain model.

Preclinical and epidemiological evidence supports that cannabinoids may have opioid-sparing properties and could be one strategy to decrease opioid use and associated harms like overdose and extramedical use. The objective of this within subjects, double-blind, double-dummy, randomized human laboratory trial was to examine whether cannabidiol (CBD) increases opioid analgesic effects and whether there are corresponding increases in other opioid mediated effects. Healthy participants (N = 31) attended 5 outpatient sessions where they received the following drug conditions: (1) placebo + placebo, (2) 4 mg hydromorphone + placebo, (3) 4 mg hydromorphone + 50 mg CBD, (4) 4 mg hydromorphone + 100 mg CBD, and (5) 4 mg hydromorphone + 200 mg CBD.

Case Series: Magnitude and duration of fentanyl and xylazine detection in the urine of persons with opioid use disorder.

Background/objectives: The pharmacology of fentanyl and xylazine is not characterized in persons regularly exposed to illicit fentanyl. This case series presents individual-level urine pharmacokinetics of fentanyl, norfentanyl, and xylazine in persons with opioid use disorder (OUD).

Methods: Participants (N = 11) provided urine samples (n = 95) for quantitative analysis.

Treating Opioid Use Disorder and Opioid Withdrawal in the Context of Fentanyl.

The opioid crisis, driven by illicitly manufactured fentanyl, presents significant challenges in treating opioid use disorder (OUD) and opioid withdrawal syndrome. Fentanyl is uniquely lethal due to its rapid onset and respiratory depressant effects, driving the surge in overdose deaths. This review examines the limitations of traditional diagnostic criteria like those of the , Fifth Edition, Text Revision (DSM-5-TR) and explores the potential of dimensional models such as the Hierarchical Taxonomy of Psychopathology (HiTOP) for a more nuanced understanding of OUD.

Application of Causal Forest Model to Examine Treatment Effect Heterogeneity in Substance Use Disorder Psychosocial Treatments.

Objectives: Heterogeneity of treatment effect (HTE) is a concern in substance use disorder (SUD) treatments but has not been rigorously examined. This exploratory study applied a causal forest approach to examine HTE in psychosocial SUD treatments, considering multiple covariates simultaneously.

Methods: Data from 12 randomized controlled trials of nine psychosocial treatments were obtained from the National Institute on Drug Abuse Clinical Trials Network.

Predictors of participant compliance with ecological momentary assessment among individuals with chronic pain who are using cannabis and opioids.

Background: Cannabis may be an alternative or adjunct to opioid therapy for chronic pain. However, there are limited data on patterns of opioid medication and medical cannabis use. The current study investigated the feasibility of using Ecological Momentary Assessment (EMA) to assess patterns of prescription opioids and medical cannabis among individuals experiencing chronic pain.

Examining the Severity and Progression of Illicitly Manufactured Fentanyl Withdrawal: A Quasi-experimental Comparison.

Objective: Illicitly manufactured fentanyl has largely replaced heroin throughout the United States. Characteristics of fentanyl-specific withdrawal are not well understood compared to traditional opioid withdrawal. This study examines opioid withdrawal severity among 2 cohorts of study participants who underwent identical morphine stabilization procedures before and after fentanyl was introduced to the local drug market.

Exposure to Bupropion-SR vs. Placebo is associated with reductions in smoking among persons receiving methadone with no stated interest in smoking cessation.

Smoking is prevalent among individuals receiving methadone treatment. Reducing smoking among this population is needed as smoking is a leading cause of morbidity and preventable death. Smoking cessation interventions for persons receiving medication for opioid use disorder have yielded small changes in abstinence.

Kratom (Mitragyna speciosa) use for self-management of pain: Insights from cross-sectional and ecological momentary assessment data.

Kratom (Mitragyna speciosa) is increasingly used in the US for self-management of pain, despite limited research on its efficacy and safety. To better understand how and why people use kratom for pain self-management, we analyzed baseline survey data (N = 395) and 15-day ecological momentary assessment (EMA) data (N = 357) from kratom consumers across the US. Although we recruited participants based on their kratom use, not on whether they used it for pain management, nearly half (49.

Fentanyl, Heroin, Methamphetamine, and Cocaine Analyte Concentrations in Urine Drug Testing Specimens.

Importance: The US is experiencing a protracted drug overdose crisis primarily associated with exposure to illicitly manufactured fentanyl (IMF), methamphetamine, and cocaine. Overdose risk and treatment responses may be directly affected by absolute drug exposure concentrations and drug use prevalence.

Objective: To quantify changes in absolute drug exposure concentrations from 2013 to 2023.

Trajectories of craving in the course of pharmacotherapy trials for methamphetamine use disorder.

Aims: The aim of this study was to measure trajectories of craving for methamphetamine during the course of pharmacotherapy trials for methamphetamine use disorder.

Design, Setting And Participants: Craving trajectories were identified using Group-Based Trajectory Modeling. The association of craving trajectories with drug use trajectories was examined using a dual trajectory model.

Association of prenatal substance exposure and the development of the amygdala, hippocampus, and parahippocampus.

Context: Prenatal substance exposure (PSE) can lead to various harmful outcomes for the developing fetus and is linked to many emotional, behavioral, and cognitive difficulties later in life. Therefore, examination of the relationship between the development of associated brain structures and PSE is important for the development of more specific or new preventative methods.

Objectives: Our study's primary objective was to examine the relationship between the physical development of the amygdala, hippocampus, and parahippocampus following prenatal alcohol, tobacco, and prescription opioid exposure.

Availability and Opportunities for Expansion of Buprenorphine for the Treatment of Opioid Use Disorder.

There is an urgent need to expand access to treatment for persons with opioid use disorder (OUD). As neurologists may frequently encounter patients with chronic pain who have developed OUD, they are in a position to serve as advocates for treatment. Buprenorphine is the most scalable medication for OUD in the United States, yet expansion has plateaued in recent years despite growing treatment needs.

Pain and withdrawal are common among patients receiving medications for opioid use disorder and associated with pain catastrophizing, negative affect, and poor sleep.

Substantial percentages of persons receiving medications for opioid use disorder (MOUD) continue to experience clinically significant levels of pain and opioid withdrawal, which may pose barriers to reducing opioid use. Continued pain, in particular, may increase the risk for psychiatric problems and poorer treatment retention, especially with a lack of adequate care for pain. The goals of these analyses were to characterize the prevalence of, and patient-level variables associated with, pain and opioid withdrawal, as well as utilization of related coping strategies and treatments.

Harm Reduction for Opioid Use Disorder: Strategies and Outcome Metrics.

Tweet: The authors discuss harm reduction strategies and associated outcome metrics in relation to the ongoing opioid crisis.

Virtual focus groups among individuals with use disorders: assessing feasibility and acceptability in an underserved clinical population.

Objective: There are substantial barriers to conducting research among individuals with stigmatized and complicated health conditions like substance use disorders. These barriers slow progress when developing, refining, and assessing interventions to better treat underserved populations. Virtual focus groups are an innovative method for collecting data from individuals via a discreet and accessible platform which can inform novel as well as existing treatment approaches.

The IMPOWR Network Divided or Single Exposure Study (DOSE) Protocol: A Randomized Controlled Comparison of Once Versus Split Dosing of Methadone for the Treatment of Comorbid Chronic Pain and Opioid Use Disorder.

Background: The Divided or Single Exposure (DOSE) trial is a double-blind, placebo-controlled examination of once versus split dosing of methadone for comorbid pain and opioid use disorder (OUD) among persons receiving methadone for OUD treatment.

Methods: This multisite trial consists of a 12-week active intervention phase and 6-month follow-up period. Persons receiving methadone who endorse clinically-significant chronic pain are randomized into once-daily dosing or split dosing that is managed remotely via an electronic pillbox.

Establishing a research agenda for the study and assessment of opioid withdrawal.

The opioid crisis is an international public health concern. Treatments for opioid use disorder centre largely on the management of opioid withdrawal, an aversive collection of signs and symptoms that contribute to opioid use disorder. Whereas in the past 50 years more than 90 medications have been developed for depression, only five medications have been developed for opioid use disorder during this period.

Effects of kratom on driving: Results from a cross-sectional survey, ecological momentary assessment, and pilot simulated driving Study.

Objectives: Despite widespread kratom use, there is a lack of knowledge regarding its effects on driving. We evaluated the self-reported driving behaviors of kratom consumers and assessed their simulated-driving performance after self-administering kratom products.

Methods: We present results from: 1) a remote, national study of US adults who regularly use kratom, and 2) an in-person substudy from which we re-recruited participants.

Intersectional Risk and the Significant Gap in Care for Persons With Co-occurring Chronic Pain and Opioid Withdrawal.

Objectives: Persons with chronic pain and women tend to enter treatment for opioid use disorder with greater opioid withdrawal severity than persons without chronic pain and men, respectively. This study examined characteristics of facilities with opioid withdrawal treatment, including gender-based services, as a function of whether they reported having a tailored pain management program.

Methods: The National Survey of Substance Abuse Treatment Services 2020 was used to examine 3942 facilities with opioid withdrawal treatment in the United States.

Suvorexant alters dynamics of the sleep-electroencephalography-power spectrum and depressive-symptom trajectories during inpatient opioid withdrawal.

Study Objectives: Opioid withdrawal is an aversive experience that often exacerbates depressive symptoms and poor sleep. The aims of the present study were to examine the effects of suvorexant on oscillatory sleep-electroencephalography (EEG) band power during medically managed opioid withdrawal, and to examine their association with withdrawal severity and depressive symptoms.

Methods: Participants with opioid use disorder (N = 38: age-range:21-63, 87% male, 45% white) underwent an 11-day buprenorphine taper, in which they were randomly assigned to suvorexant (20 mg [n = 14] or 40 mg [n = 12]), or placebo [n = 12], while ambulatory sleep-EEG data was collected.

Ecological Momentary Assessment of Self-Reported Kratom Use, Effects, and Motivations Among US Adults.

Importance: Kratom products, which are sold legally in most of the US, contain alkaloids with opioidergic, adrenergic, and serotonergic activity. Millions of people use kratom to relieve pain, improve mood, or self-manage substance use disorders (SUDs). Kratom use has primarily been examined via surveys, in which recall biases among satisfied users may lead to minimization of transient negative outcomes.