Network intervention analysis of ACT processes in cocaine use disorder.

Looking through the cracks: vulnerabilities and deprivation in the Brazilian open drug scenes.

Cocaine use disorder (CUD) remains a major public health concern, characterized by high relapse rates and the absence of approved pharmacological treatments. Glucagon-like peptide-1 receptor agonists (GLP-1RA), widely prescribed for metabolic disorders, modulate mesolimbic reward pathways and have been proposed as potential modulators of addictive behaviors. To describe clinical observations of GLP-1RA exposure in individuals with CUD identified through the French national vigilance system and to contextualize these findings through a structured narrative review of preclinical and clinical evidence. Cases involving GLP-1RA exposure in individuals with ongoing cocaine use were identified through the French national vigilance system and described. A structured literature search (MEDLINE, Embase, Google Scholar) identified original preclinical and clinical studies examining the effects of GLP-1 receptor activation on cocaine-related behavioral and neurobiological outcomes. Two cases involving patient-initiated off-label GLP-1RA use motivated by perceived anti-craving effects were identified through the vigilance system. The literature synthesis included 22 original publications (17 preclinical and 5 human studies). Across experimental models, GLP-1 receptor activation reduced cocaine self-administration, conditioned reward, and relapse-like behaviors. These effects were associated with the attenuation of mesolimbic dopamine signaling, including reduced cocaine-evoked dopamine release and modulation of dopamine transporter function. Human evidence remains limited and heterogeneous. GLP-1 receptor signaling represents a biologically plausible target in CUD. However, current clinical evidence remains preliminary. Patient-driven observations underscore the need for controlled clinical trials and continued vigilance monitoring.

Levamisole in opioid overdose patients: An evolving adulterant landscape.

Incidence of substance use disorders and comorbidities in the All of Us Research Program.

Anxiety sensitivity and substance use disorders: Associations across multiple drug classes and tests of a transdiagnostic mechanism.

Cocaine use disorder prevalence is around 2.2% for individuals age 12 and older, with higher rates reaching 6.2% in young adults ages 18-25. In 2021, around 23% of all US overdose deaths were related to cocaine. Cannabis use disorder is more prevalent than cocaine use disorder with prevalence reaching 14.7%. This study aims to evaluate the impact of cocaine and cannabis on clinical cardiovascular outcomes. Specifically, it investigates the incidence of new-onset cardiac arrhythmia between the cocaine and cannabis users, as well as the incidence of cardiac arrest events, major adverse cardiovascular events including myocardial infarction (MI) and stroke, and all-cause mortality. We did a retrospective cohort analysis using the TriNetX database of cocaine and cannabis user patients and created two cohorts: cocaine and cannabis. Propensity score matching was employed to reduce baseline disparities. The primary outcome was the incidence of new-onset cardiac arrhythmia. Secondary outcomes included cardiac arrest events, all-cause mortality, and occurrence of major adverse cardiovascular events (MI and stroke). After matching, 248 769 patients were included in each cohort (cocaine and cannabis users). New-onset cardiac arrhythmia occurred more frequently in the cocaine group (0.2%) compared with the cannabis group (0.15%) (HR: 1.067; 95% CI: 1.022-1.115, P < 0.035). Cocaine use was also associated with higher rates of the secondary outcomes: cardiac arrest (HR: 1.442; 95% CI: 1.346-1.545, P < 0.001), all-cause mortality (HR: 1.215; 95% CI: 1.187-1.243, P < 0.013), and major adverse cardiovascular events (HR: 1.147; 95% CI: 1.116-1.178, P < 0.001). Cocaine users experience significantly higher rates of new-onset cardiac arrhythmias, cardiac arrest, and major adverse cardiovascular events (MI and stroke) compared with cannabis users. These findings highlight the differing outcomes associated with substance use. Future research should aim to validate our findings through prospective, multicentre studies with standardized diagnostic methods as well as longer-term follow-up to more accurately define the outcomes.

Cocaine Use Disorder (CUD) poses a major public health challenge, with no Food and Drug Administration-approved pharmacotherapies currently available. A deeper understanding of Morphometric Similarity Network (MSN) alterations and their associations with neurotransmitter systems in CUD may facilitate the development of targeted therapeutic strategies. We aimed to investigate the aberrant MSN patterns and their relationships with neurotransmitter distributions in CUD. This case-control study enrolled 70 patients with CUD and 57 age- and sex-matched healthy controls (HCs). Individual-level MSNs were constructed for each participant, and regional morphometric similarity (MS) strength was computed. Group differences in MSN connectivity and regional MS strength were compared between the CUD and HC groups. The JuSpace toolbox was employed to assess spatial correlations between regional MS alterations and specific neurotransmitter maps. Network-based statistic analysis revealed disrupted MSN connectivity in patients with CUD, primarily involving the prefrontal cortex, striatum, thalamus, frontoparietal control network, and insula. Regional MS strength abnormalities demonstrated significant spatial correlations with the neurotransmitter density distributions of the serotonergic, dopaminergic, glutamatergic, GA-BAergic, and cholinergic systems. These spatial correlations were further associated with CUD severity and weekly cocaine dose. These findings provide novel insights into the neuropathological mechanisms of CUD from the perspectives of gray matter morphometric covariance patterns and neurotransmitter systems. The consistency with existing findings further supports the clinical translational value of the neurotransmitter targets we have identified. Our findings revealed co-altered patterns of gray matter morphometric covariance and neurotransmitter interactions in CUD, providing novel insights into the neuropathological mechanisms of CUD and identifying potential therapeutic targets.

Stimulant use disorder (StUD), including cocaine and methamphetamine use disorders, remains a major unmet clinical need with no approved pharmacotherapies. Despite strong mechanistic rationale, dopamine transporter (DAT)-directed strategies have largely failed to translate into consistent clinical benefit. This review evaluates the contemporary pharmacotherapy landscape for StUD, focusing on phase II/III clinical trials and systematic reviews published from January 2020- April 2026. Evidence was identified through PubMed/MEDLINE and ClinicalTrials.gov and synthesized narratively due to study heterogeneity. Therapeutic approaches are organized by mechanistic class, including DAT-targeting agents, non-DAT strategies (multi-monoaminergic, glutamatergic, serotonergic, and neuroimmune), and combination pharmacotherapy. Across studies, monotherapies generally demonstrate limited or inconsistent efficacy, although mirtazapine has shown the most consistent positive findings. Combination pharmacotherapy approaches, particularly naltrexone-bupropion, have generated some of the most encouraging clinical results to date. The role of DAT is reappraised within emerging biological frameworks and a systems-level model of addiction. Current evidence supports a reappraisal of DAT as one component of a broader neurobiology of stimulant addiction. Future therapeutic development may benefit from moving beyond DAT-centric strategies toward integrated, multi-target approaches. Combination pharmacotherapy represents a promising direction for investigation, although available evidence remains heterogeneous and requires substantial clinical validation.

The effects of repetitive transcranial magnetic stimulation on sleep in individuals with substance use disorders: A systematic review.

Intravenous self-administration (SA) in rodents is widely regarded as the standard approach for studying the neurobiological mechanisms of drug addiction. However, its use in mice is limited by the frequent complications of intravenous catheterization, including catheter failure or occlusion. To overcome these challenges, we developed and validated a noninvasive vapor approach for cocaine SA in mice. In this study, mice were trained to self-administer cocaine vapor under fixed-ratio schedules (FR1 and FR3) and exposure to cocaine SA in both short-access (1 hour/day) and long-access (3 hours/day) sessions. Our findings show that the vaporized cocaine SA model induces robust behavioral and physiological effects consistent with cocaine use disorder. Our results demonstrated increased operant responding under higher reinforcement schedules, and the escalation of vaporized cocaine intake during extended access sessions (3 hours/day) emulates features of compulsive drug use in humans. Our findings show that the vaporized cocaine SA model offers a translational model to advance preclinical research and develop effective treatments. This vapor-based approach circumvents the need for catheterization, reduces animal stress, and is suitable for longitudinal studies and compatible for use with various modern neurogenetic techniques that require a tether for imaging free-moving, behaving animals (e.g., optogenetics and brain imaging).

Systematic Review and Meta-Analysis: Prevalence, Correlates, and Impact of Cannabis Use and Cannabis Use Disorder in Early-Onset Psychosis.

Considering unintentional exposure when testing for cocaine use via oral fluid testing.

Chronic cocaine exposure modulates decision-making in mice in a sex-dependent manner.

Chronic cocaine use is associated with neuroinflammation and cognitive dysfunction, but the underlying mechanisms remain unclear. We previously identified oral enrichment of Streptococcus parasanguinis (SP) and other species in individuals with cocaine use disorder (CUD), and here demonstrate that cocaine selectively enhanced SP growth in vitro . To investigate causality, antibiotic-pretreated wild-type C57BL/6 mice received chronic oral inoculation of SP, S. salivarius , Neisseria flavescens , or vehicle. SP-treated mice exhibited spatial memory impairment, increased brain IL-1β, and non-region-specific microglial activation, without detectable bacterial translocation into the brain. While amyloid-associated signaling changes were observed across all bacterial treatment groups, only SP induced cognitive deficits and neuroinflammation. Untargeted metabolomics identified distinct SP-associated oral-to-brain metabolite signatures, including cysteine S-sulfate (CSS) and altered histamine-associated metabolites. CSS and histamine induced neuroinflammatory and amyloid-associated responses in vitro . Together, these findings identify a cocaine-associated oral pathobiont that promotes neuroinflammation and neurodegeneration, suggesting a novel oral microbiome-brain axis in CUD.

To investigate whether participation in a multicomponent physical exercise program is associated with longitudinal changes in craving, cognition, and self-esteem among inpatients with crack cocaine use disorder. This prospective, naturalistic, non-randomized longitudinal study included 37 inpatients with crack cocaine use disorder classified into an exercise group (EG, n = 21) or non-exercise group (NEG, n = 16) based on participation in the institutional exercise program. Assessments were conducted at baseline, week 5, and week 10. Outcomes included global cognition (MMSE), executive function (TMT-A/B), self-esteem (RSE), and craving (CCQ-Brief). Longitudinal data were analyzed using repeated-measures models. No significant group-by-time interactions were observed for cognition or self-esteem, although both groups improved over time. In the primary analysis, a significant group-by-time interaction was observed for craving (p = 0.034), with greater reductions in the exercise group, particularly during the first five weeks. However, this interaction was attenuated after adjustment for age and duration of crack cocaine use. Participation in multicomponent exercise was associated with greater reductions in craving in the primary analysis, although this finding was attenuated after adjustment for baseline group differences. Improvements in cognition and self-esteem were observed in both groups, suggesting shared effects of structured care and abstinence. These findings support further investigation of exercise as a complementary strategy in substance use disorder treatment.

To evaluate the association between substance use disorders (SUDs), cardiovascular disease (CVD), and all-cause mortality in patients with type 2 diabetes mellitus (T2DM). Using the TriNetX Research Network, we performed a retrospective cohort analysis of adults aged ≥ 18 years diagnosed with T2DM between January 2016 and December 2022. Patients diagnosed with cannabis-, opioid-, or cocaine-related disorders within 1 year prior to their T2DM diagnosis were identified. Propensity score matching (PSM) was utilized to balance demographics, comorbidities, and medication use between the SUD and non-SUD cohorts. After PSM, each group included 69 419 individuals. Over a 3-year follow-up period, the SUD cohort exhibited significantly elevated risks of acute myocardial infarction (HR 1.994; 95% CI 1.766-2.253), atrial fibrillation (HR 1.455; 95% CI 1.300-1.630), heart failure (HR 1.837; 95% CI 1.693-1.994), stroke (HR 1.524; 95% CI 1.354-1.715), and all-cause mortality (HR 1.420; 95% CI 1.359-1.483). Subgroup analyses demonstrated consistent risk elevations across all substance types, with the highest relative mortality risk observed in patients with opioid-related disorders. All associations were statistically significant (p < 0.001). Co-occurring SUDs are strongly associated with increased risk of cardiovascular morbidity and all-cause mortality in T2DM patients. However, these associations should be interpreted cautiously due to potential residual confounding despite propensity score matching. These findings underscore the urgent need for integrated risk assessment alongside tailored preventive and therapeutic strategies in this high-risk population.

Background Although substance use continues to increase among people living with HIV (PLWH), it is often overlooked among older PLWH and may explain poor engagement in care and the increase in overdose deaths, particularly among Black PLWH. The purpose of this study was to assess the relationship between stimulant and opioid use and visit and medication non-adherence among African American older adults with HIV. Methods An online survey was completed among 52 older PLWH in Ohio, who identified as Black, living with HIV, and 50 years of age and older. Past three-month use of cocaine, amphetamines, and opioids were self-reported. Visit non-adherence was defined as missing at least one clinic visit in the past 12-months and medication non-adherence was defined as missing all medications for ≥4 days in the past 3-months, both self-reported. Inverse probability weighting was used to adjust for confounding and odds ratios (OR) and 95% confidence intervals (CI) were calculated. Results The study sample was predominately male (94%). Cocaine use was the most prevalent substance reported (56.0%), followed by amphetamine (54.0%) and opioid use (52.0%). Visit non-adherence was associated with amphetamine (OR: 20.42; 95% CI: 2.35, 177.35), cocaine (OR: 21.81; 95% CI: 2.54, 186.99), and opioid use (OR: 11.93; 95% CI: 3.74, 38.05). There were no statistically significant associations between substance use and medication non-adherence. Conclusions Stimulant and opioid use impedes optimal engagement in HIV care among older Black PLWH.

Cocaine use disorder (CUD) is a major public health crisis. The specific genes mediating CUD remain largely unknown. We conducted a genome-wide association study (GWAS) using outbred N/NIH Heterogeneous Stock (HS; n = 836, female = 415, male = 421) rats. We examined CUD-related phenotypes including acquisition of self-administration, escalation of intake, and compulsive-like responding. These traits were phenotypically correlated and exhibited modest SNP heritability (h2 = 0.07 – 0.16). We identified six genome-wide significant associations (>-log10(p)=5.58; α = 0.05 by permutation). One locus on chromosome 19 was associated with variable time between cocaine infusions (post infusion interval) and contains several carboxylesterase genes that are orthologous to the human CES1 gene. Notably, carboxylesterases metabolize cocaine. Three non-synonymous coding variants in Ces1c and Ces1d were in perfect linkage disequilibrium with this locus. The other five loci contained promising coding and expression variants, including Trak2, a gene previously associated with CUD in human GWAS and Slc10a7, Plcl1, and Satb2 which have been associated with alcohol and tobacco use disorder. This is the largest genetic study of cocaine self-administration ever conducted in rats. Our results replicate previous loci associated with CUD in humans and provide several novel biological insights including the potential of pharmacological strategies targeting carboxylesterases.

Cocaine use is occasionally associated with development of acute leukoencephalopathy but only rarely do the magnetic resonance imaging (MRI) features resemble Baló concentric sclerosis, a demyelinating disorder traditionally considered within the multiple sclerosis spectrum. Here, we report 2 patients with history of cocaine use living in the same geographic area who were referred for acute multifocal leukoencephalopathy with a Baló-like pattern.Patient 1, a 31-year-old woman originally from the Philippines with chronic cocaine use history, presented with 1 week of rapidly worsening nonfluent aphasia, neglect, severe right hemiparesis, and numbness on the same side. Two months later, patient 2, a 25-year-old man originally from Morocco with chronic cocaine use history, presented with acute left leg weakness, confusion, and neglect. In both patients, brain MRI revealed multiple T2-hyperintense rounded lesions in the white matter, characterized by a concentric target-like appearance and gadolinium-enhanced incomplete ring pattern. In patient 1, a stereotactic biopsy confirmed a demyelinating inflammatory process with microcystic degeneration, increased cellularity, and macrophage/CD4+ lymphocyte infiltration. Both patients were treated with high-dose IV corticosteroid, resulting in significant clinical and radiologic improvement sustained at 1-year follow-up. Although corticosteroids yield promising outcomes, long-term prognosis hinges on sustained treatment adherence and abstinence from cocaine.The temporal and geographic proximity of these cases, occurring within 2 months in the same Italian province (covering an area of approximately 70 miles), raises the possibility of a shared toxic exposure which might explain the unique pathology and provide clues to the immune mechanisms that drive Baló-like demyelination.