OBJECTIVES:Limited evidence describes how geographic context and the built environment relate to non-fatal overdose. We examined demographic and spatial patterns of non-fatal overdoses in Palm Beach County, Florida, including differences between indoor and outdoor events and proximity to built environment features. METHODS:Emergency department encounters for suspected non-fatal overdoses were obtained from Florida's Overdose Data to Action surveillance system for 2024. Multivariable logistic regression examined factors associated with outdoor overdose and proximity to gas stations. Spatial analyses assessed proximity to gas stations and major roadways and identified geographic clustering. RESULTS:Among 1661 non-fatal overdose events, 39.6% occurred outdoors. Outdoor overdoses were more common among men, younger adults, uninsured individuals, and those identified as unstably housed, with housing status showing the strongest association. Overdoses involving stimulants and combined drug and alcohol use were also more likely to occur outdoors. In the gas-station proximity model, unstable housing was associated with more than fivefold higher odds of an overdose occurring within 0.25 miles of a gas station. Outdoor overdoses clustered in eastern PBC along major transportation corridors. Nearly 44% of outdoor overdoses occurred within 0.25 miles of a gas station and 33.6% within 0.25 miles of a major highway, proportions significantly higher than for indoor overdoses. CONCLUSIONS:Non-fatal overdoses in PBC show distinct spatial patterns by setting. Outdoor overdoses were concentrated near transportation corridors and gas stations and are more commonly observed among individuals experiencing housing instability. Spatial surveillance may inform targeted overdose intervention, outreach, and linkage to treatment.
Background Cannabis demand, a behavioural economic measure of cannabis relative reinforcing value (i.e., incentive salience), is robustly associated with cannabis involvement. Recreational cannabis legalization in Canada has shifted the availability and social acceptability of cannabis, potentially altering its reinforcing value. Though prior studies have examined legalization-related changes in cannabis use and misuse, none have examined changes in cannabis demand. Thus, we investigated intraindividual changes in cannabis demand over the six years following legalization, overall and moderated by pre-legalization cannabis use frequency, sex, and age, predicting an increase in reinforcing value in the post-legalization period. Method Community adults (n=1103) completed measures of cannabis demand in 14 assessment waves (median retention = 86.86%) from September 2018 to April 2025. Results Multilevel growth models indicated that, on average, all cannabis demand indices significantly decreased over time, contrary to hypotheses, and in contrast to cannabis consumption itself, which was relatively stable. Trajectories systematically differed based on pre-legalization cannabis use frequency and sex. Participants who were actively using cannabis pre-legalization exhibited declining cannabis demand over time, with steeper declines corresponding to more frequent pre-legalization cannabis use, whereas those not using cannabis pre-legalization exhibited stable or increasing cannabis demand. Males exhibited steeper decline in selected cannabis demand indices (intensity, Omax, breakpoint) relative to female participants. Conclusions These results reveal that Canadian recreational cannabis legalization was associated with overall declines in the reinforcing value of cannabis, even as actual cannabis use frequency remained relatively stable. These findings suggest that increased cannabis availability following legalization may have led to seemingly positive within-person shifts, albeit within a community sample.
Background Adverse-childhood-experiences (ACEs) are prevalent in substance-use-disorder (SUD) but show complex interplay with resilience, psychopathology and addictive-behaviour. The stress-diathesis model predicts that ACEs can induce psychopathologies and undermine resilience, leading to addictive-behaviour. However, previous research seldom investigated these variables using network analysis, and evidence remains limited to the Western population. We aimed to study the symptom-behaviour network for ACEs and resilience in the Chinese setting. Methods This cross-sectional study recruited 400 Chinese SUD patients, with 67% having comorbid psychiatric disorders, 61.5% having polysubstance use, and 63.3% having actively used substance within 30 days. We administered self-report scales to measure ACEs, resilience and psychological dependence. Clinician-rated scales measured substance-use-severity and psychopathologies. The regularized-partial-correlation-network with centrality indices examined the interplay of ACEs and resilience with psychopathologies and addictive-behaviour. The shortest-path-analysis outlined the graph-theoretic paths within the network, which linked ACEs (the independent variable) to substance-use-severity (the outcome variable) through intermediate variables. Results In the network, ACEs and resilience showed weak connections with psychopathology, psychological dependence and substance-use-severity. Moreover, anxiety and depressive symptoms, emotional and physical abuse showed high centrality. The graph-theoretic paths linking childhood abuse and substance-use-severity did not include psychopathological nodes but psychological dependence; whereas the paths linking childhood neglect and substance-use-severity included resilience and psychological dependence. Conclusions ACEs, in particular physical and emotional abuse, may be intervention targets for bringing changes to the symptom-behaviour network. Trauma-informed assessments and interventions should be considered. Longitudinal research is needed to verify causal mechanisms for the associations of ACEs with addictive-behaviour.
BACKGROUND:[¹ ¹C]PHNO is a positron emission tomography (PET) radioligand for dopamine D2/D3 receptors (D2R/D3R), while [¹ ¹C]P943 selectively targets 5-HT1B receptors. Although prior studies have shown differences in dopaminergic and serotonergic receptor availability in people with and without cocaine use disorder (CUD), these systems have been examined in isolation across separate studies and samples. METHODS:Ten non-treatment-seeking individuals with CUD (3 women; mean [SD] age, 40.6 [7.5] years) underwent PET imaging with [¹ ¹C]PHNO and [¹ ¹C]P943 following an average of 7 ± 3 days of abstinence under inpatient monitoring. Availability of D2R- and D3R-related receptors was measured with [¹ ¹C]PHNO binding potentials (BPND) in the putamen and substantia nigra/ventral tegmental area (SN/VTA), respectively. Exploratory linear regression analyses using both D2R- and D3R-related receptor availability as independent variables were applied to 5-HT1BBPND in the medial orbitofrontal cortex (mOFC) and dorsomedial prefrontal cortex (dmPFC), with secondary analyses examining the same dopaminergic-serotonergic associations in additional addiction-related prefrontal regions. RESULTS:D2R-related receptor availability was positively associated with 5-HT1BBPND in the dmPFC (p = 0.038) but not in the mOFC (p = 0.945). Conversely, D3R-related receptor availability was positively associated with 5-HT1BBPND in the mOFC (p = 0.043) but not in the dmPFC (p = 0.850). Analyses of secondary 5-HT1B regions revealed a positive association between D3R-related receptor availability and 5-HT1BBPND in the lateral OFC (lOFC) (p = 0.050). CONCLUSIONS:In individuals with CUD, D2R- and D3R-related measures were associated with 5-HT1B binding in distinct prefrontal regions. These findings provide preliminary in vivo evidence of cross-system dopaminergic-serotonergic relationships and may inform future development efforts toward targeted treatments for CUD.
Preclinical experiments have revealed much about opioid withdrawal, but have failed to discover novel treatments. The preclinical literature is dominated by experiments examining naloxone-precipitated withdrawal from morphine in male rats. These studies report a number of putative treatments for opioid withdrawal, none of which have become clinically approved. A major problem, supported by both human and animal research, is that antagonist-precipitated withdrawal is distinct from the spontaneous opioid withdrawal experienced by most opioid users. A second problem is the widespread focus in animal research on somatic symptoms (e.g., wet dog shakes). Although somatic symptoms can be disruptive, anxiety, anhedonia, and aches are the symptoms that cause distress and drive relapse. Somatic symptoms are also problematic because they are easily suppressed by treatments that produce sedative or motor effects. A potential solution to these problems is the use of voluntary home cage wheel running as a more general measure of opioid withdrawal. Wheel running provides a continuous and objective measure ideal for assessing changes in the magnitude and duration of spontaneous withdrawal over time. The decrease in wheel running caused by opioid withdrawal changes the definition of an effective treatment from suppressing behavior (somatic symptoms) to restoring behavior (wheel running), thereby avoiding confounds produced by sedative or motor effects. This review provides a detailed analysis of rodent experiments on opioid withdrawal, highlighting potential problems with external validity and describing wheel running experiments that align animal experiments with the clinical manifestation of opioid withdrawal to enhance the development of novel treatments.
OBJECTIVES:Methamphetamine use disorder (MUD) contributes to postpartum morbidity and mortality. Postpartum progesterone decline may destabilize γ-aminobutyric acid pathways, increasing craving and return to use. We assessed the feasibility and safety of micronized progesterone, generating efficacy estimates for preventing postpartum methamphetamine use. METHODS:We conducted a double-blind, randomized, placebo-controlled feasibility trial (November 2021-January 2024) at an academic center with a perinatal addiction clinic. Participants ≤ 12 weeks postpartum with ≥ 4 weeks of abstinence were randomized 1:1, stratified by opioid use disorder (OUD), to micronized progesterone 400mg (200mg twice daily) or identical placebo for 12 weeks. The primary outcome was feasibility, defined as achieving ≥ 80% of planned enrollment. Safety outcomes included adverse events (AEs) and serious adverse events (SAEs). Efficacy outcomes were return to methamphetamine use (weekly self-report and every two weeks urine toxicology) and methamphetamine craving. Analyses included intent-to-treat and per-protocol approaches, with loss to follow-up imputed as return to use. Craving trajectories were modeled using adjusted regression with interaction terms for medication for OUD (MOUD). RESULTS:Of 253 screened individuals, 43 were eligible and 34 were enrolled (91.8%; 18 progesterone, 16 placebo). Retention at 12 weeks was 88%. AE frequency was similar between groups (78% vs 81%; p > 0.05), and no maternal SAEs occurred. Four infant SAEs were deemed unrelated to treatment. Return to methamphetamine use did not differ between groups. Craving trajectories differed by MOUD type. CONCLUSIONS:Micronized progesterone was feasible and safe for postpartum individuals with MUD. MOUD-specific craving effects support evaluation in larger, multicenter efficacy trials. CLINICALTRIALS: GOV REGISTRATION NUMBER:NCT05128071 NCT REGISTRATION: Prevention of postpartum methamphetamine use with micronized progesterone trial https://clinicaltrials.gov/study/NCT05128071.
BACKGROUND:People taking medications for opioid use disorder (MOUD) commonly experience chronic pain. Yoga interventions show promise for decreasing pain-related disability in other populations. More time spent in yoga practice may improve pain-related outcomes. METHODS:The Multiphase Optimization Strategy (MOST) provided the framework for developing an optimized yoga intervention package. In a 2x2x2x2 factorial experiment, we evaluated four candidate intervention components which, when added to a weekly yoga class, might increase yoga engagement. The primary outcome was minutes per week of yoga practice (classes and other yoga practice) over the 12-week intervention period. We sought to determine which combination of intervention components was associated with the most yoga practice for people with chronic pain taking buprenorphine or methadone as MOUD. RESULTS:We enrolled 192 adults. There was a significant main effect for Component "B" (having two private sessions with a yoga teachers; IRR = 1.10, 90%CI 1.02; 1.18), and a synergistic interaction between Components "B" and "D" (D was financial incentives for attending class; IRR = 1.11, 90%CI 1.02; 1.19). This combination of these two components (without other potential components) was associated with the second highest model-predicted mean minutes of yoga per week (157.1min; 90% CI = 120.1-194.0) which was only 4min less than the combination including all four components. CONCLUSIONS:We identified a combination of intervention components as the optimized intervention. A next step will be to test the effect of this optimized intervention on pain and substance use outcomes in a randomized controlled clinical trial.
BACKGROUND:Co-occurring substance use and mental health disorders (COD) are common, yet healthcare utilization patterns remain understudied. This study examined healthcare utilization patterns and sociodemographic and structural correlates among adults with COD in the All of Us Research Program (2019-2023). METHODS:Electronic health record data from the All of Us Research Program were analyzed for adults with COD. Healthcare utilization outcomes were assessed from 2019 to 2023 and categorized into counseling and therapy, medication/somatic services, telehealth services, and other supportive services. Multivariable logistic regression examined sociodemographic and structural correlates of healthcare utilization, including interaction effects between income, disability status, and insurance type. RESULTS:Among 11,238 participants, 32.9% received at least one documented substance use disorder- or mental health disorder-related healthcare service. Counseling and therapy accounted for the largest share of encounters, while telehealth utilization surged during the COVID-19 pandemic. Healthcare utilization increased with age (≥65 years: aOR=2.24, 95% CI:1.86-2.70) and was lower among female participants (aOR=0.72, 95% CI:0.67-0.79). Significant interaction effects indicated that the relationship between insurance coverage and healthcare utilization varied across income and disability subgroups. Participants with higher income combined with private or multiple insurance coverage demonstrated some of the highest odds of healthcare utilization. CONCLUSIONS:Healthcare utilization among adults with COD remained low and reflected persistent structural inequities across income, disability, and insurance subgroups. Findings highlight the importance of strengthening integrated healthcare services, improving equitable access to care, and sustaining telehealth infrastructure to support long-term engagement in care.
BACKGROUND:High-risk injecting behaviors often occur in the context of injecting partnerships, yet how interpersonal (dyadic) dynamics shape individual injecting practices remains poorly characterized. METHODS:Baseline cross-sectional data from 131 injecting partnerships (262 dyad-member observations) in San Francisco and Montreal were analyzed. Injecting-related interpersonal factors (trust, power imbalance, risk perception, intimacy, and cooperation) were measured using the validated 54-item Interpersonal Dynamics in Injecting Partnerships (IDIP) scale. Actor-Partner Interdependence Models (APIM), implemented via linear mixed-effects models, estimated the independent effects of each partner's IDIP scores on equipment sharing while accounting for dyadic interdependence. RESULTS:Overall, 74% reported recent equipment sharing. After covariate adjustment, actor-reported trust was positively associated with equipment sharing (β = 0.41, 95% CI: 0.17-0.65). Both actor (β = -0.50, 95% CI: -0.84 to -0.17) and partner (β = -0.51, 95% CI: -0.82 to -0.20) reports of power imbalance, and both actor (β = -0.28, 95% CI: -0.51 to -0.04) and partner (β = -0.23, 95% CI: -0.45 to -0.001) reports of risk perception, were associated with decreased sharing. In HCV-serodiscordant dyads, higher partner-reported trust was associated with lower sharing (interaction β = -0.56, 95% CI: -0.99 to -0.12); no other moderation effects were significant. CONCLUSIONS:Trust, power imbalance, and risk perception were associated with injecting equipment sharing, with a protective effect of partner trust most pronounced in HCV-serodiscordant dyads. Harm reduction strategies that leverage dyadic dynamics, including partner-based HCV testing and dyadic counseling, may strengthen HIV and HCV prevention, particularly when tailored to partnership composition.
