Search Results (18)

Background and aim of this review: The ongoing opioid epidemic underscores the urgent need for innovative pharmacological and behavioral interventions to mitigate the impact of opioid use disorder (OUD). This review aims to explore theoretical overlaps between the neurobiological mechanisms underlying OUD development and the pharmacodynamic profile of methylphenidate (MPH). Particular attention is given to the potential shared molecular targets, safety considerations, and therapeutic implications of MPH use in this clinical context. Main finding: In the development of opioid dependence, the negative reinforcement of the dopaminergic transmission of the mesocorticolimbic pathway induced by the supraspinal action of opioid receptor agonists plays a major role. The induced state of hypodopaminergic and hyperadrenergic modulates the underlying disease process by affecting cognitive control, affective regulation, and motivational drive. MPH, acting as a dopamine reuptake inhibitor and modulator of vesicular monoamine transporter 2 (VMAT-2), increases extracellular dopamine availability and enhances dopaminergic signaling, suggesting potential utility in restoring dopaminergic tone in OUD. Additionally, MPH has shown efficacy in hypoactive delirium in patients with terminal cancer, improving both cognitive function and psychomotor drive. Conclusions and future perspectives: There appear to be converging neurobiological mechanisms between the action of MPH and the pathophysiology of OUD, particularly within the dopaminergic system. However, well-designed clinical trials are essential to identify the patient subgroups that may benefit from adjunctive MPH treatment, to evaluate its efficacy in this setting, and to assess the long-term safety and risk profile of stimulant use in individuals with OUD. Full article

Background/Objectives: Methadone maintenance treatment (MMT) is widely used in opioid use disorder (OUD). Its efficacy is influenced by its metabolism, primarily mediated by Cytochrome P450 (CYP450) enzymes in the liver. Genetic polymorphisms in CYP450 genes and other factors, such as age, sex, and concomitant treatments, contribute to interindividual variability in methadone response. This article addresses the relevance of pharmacokinetic biomarkers in methadone metabolism and its impact on treatment outcomes in European populations over the past 25 years. Methods: A systematic review was conducted using four databases (PsycINFO, PubMed, Scopus, and Web of Science) for studies published between 2000 and 2024 following the PRISMA 2020 guidelines (CRD42025641373 in PROSPERO). Two independent reviewers screened and assessed the study quality using NHLBI tools. Discrepancies were solved through consensus. Relevant data including sample size, genetic biomarkers, and key findings were extracted for each study. Data were synthesized and described in detail. Results: Fourteen studies on pharmacogenetic biomarkers influencing methadone metabolism in European populations were analyzed, encompassing a total of 3180 subjects. CYP2B6*6 was identified as a key variant associated with increased (S)-methadone plasma levels, potentially leading to cardiac complications, while the role of other pharmacokinetic genes, including ABCB1 and CYP2D6, was inconclusive. Conclusions: Genetic polymorphisms significantly influence methadone metabolism, with the CYP2B6*6 allele playing a key role in (S)-methadone metabolism and associated with cardiac risks. Pharmacogenetic studies integrating co-mediation—the principal cause of phenoconversion—as a potential variable alongside gender differences and encompassing adequate sample sizes could improve outcomes and establish the basis for personalized medicine of MMT. Full article

The opioid epidemic in the United States has significantly impacted pregnant women with opioid use disorder (OUD), leading to increased health and social complications. This study explores the feasibility of using machine learning algorithms with consumer-grade smartwatches to identify medication-taking gestures. The research specifically focuses on treatments for OUD, investigating methadone and buprenorphine taking gestures. Participants (n = 16, all female university students) simulated medication-taking gestures in a controlled lab environment over two weeks, with data collected via Ticwatch E and E3 smartwatches running custom ASPIRE software. The study employed a RegNet-style 1D ResNet model to analyze gesture data, achieving high performance in three classification scenarios: distinguishing between medication types, separating medication gestures from daily activities, and detecting any medication-taking gesture. The model’s overall F1 scores were 0.89, 0.88, and 0.96 for each scenario, respectively. These findings suggest that smartwatch-based gesture recognition could enhance real-time monitoring and adherence to medication regimens for OUD treatment. Limitations include the use of simulated gestures and a small, homogeneous participant pool, warranting further real-world validation. This approach has the potential to improve patient outcomes and management strategies. Full article

Substance use self-stigma is a barrier to treatment and can negatively impact individuals’ well-being and treatment engagement. Given the mixed findings in previous research and the limited specific investigation into the concept of self-stigma within the context of opioid misuse, examining factors associated with self-stigma in the context of opioid use disorder (OUD) is warranted. The current study examines the influence of individual-level factors (race, sex, urban/rural status, support group attendance) on self-stigma and willingness to disclose opioid use. Data for this study were from a larger study of OUD-related stigma among adults in Pennsylvania, U.S. The current study included participants who indicated a personal past or current history with OUD were included (n = 84). Exploratory factor analysis and multiple indicators, multiple causes (MIMIC) model were used to explore the associations between demographic factors (i.e., sex, age, race/ethnicity, urban/rural status), attendance at mutual support groups, and self-stigma factors. Results indicated that sex and attendance at mutual support groups significantly predicted levels of self-stigma. Women and individuals with no previous experience attending mutual support groups endorsed lower levels of self-stigma. Additionally, attendance at mutual support groups predicted willingness to self-disclose past and present opioid use. Individuals who reported no history of attending mutual support groups demonstrated less willingness to disclose past and present OUD use compared to participants who were support group attendees. The current research findings enhance the understanding of OUD-related self-stigma by examining its relationship with individual-level factors, disclosure, and attendance to mutual support groups. The results offer insights into the influence of sex and support group attendance on self-stigma and disclosure. These findings have significant clinical implications for developing future interventions and promoting health policy changes. Full article

Background: Substance use disorders present a tremendous challenge within contemporary healthcare systems. Specifically, in the domain of opioid use disorders (OUDs), several foundational elements are crucial for the efficacious management of afflicted individuals. Regrettably, the premature discontinuation of inpatient opioid withdrawal treatment is a prevalent phenomenon. This study aims to elucidate the prevalence of the premature termination of inpatient opioid withdrawal treatment among patients with comorbid ADHD. Methods: We conducted a comprehensive assessment of all participants currently undergoing inpatient opioid withdrawal treatment. Our assessment protocol included the administration of the ADHD Self-Report Scale (ADHD-SR) and the Wender Utah Rating Scale (WURS-k). Additionally, participants who met the thresholds on one or both questionnaires underwent further evaluation using the Diagnostic Interview for ADHD in Adults (DIVA-2.0). Results: The prevalence of individuals diagnosed with ADHD within the studied cohort was determined to be 29.3%. Among the subset of participants identified as ADHD-positive, a notable 54.5% prematurely ceased therapy. In contrast, among those identified as ADHD-negative, the premature discontinuation rate was substantially lower at 28.3%. Conclusions: In summary, the impact of ADHD as a comorbid condition on the efficacy of inpatient opioid withdrawal treatment has been underscored. By identifying comorbid ADHD early in the treatment process, tailored therapeutic approaches may help to maximize the effectiveness of interventions and may improve patient outcomes. This underscores the importance of proactive screening for ADHD as a psychiatric comorbidity in optimizing the management of individuals undergoing inpatient opioid withdrawal treatment. Full article

The escalating rates of morbidity and mortality associated with opioid use disorder (OUD) have spurred a critical need for improved treatment outcomes. This study aimed to investigate the impact of prolonged exposure to Fentanyl, a potent opioid, on behavior, biochemical markers, oxidative stress, and the composition of the gut microbiome. Additionally, we sought to explore the therapeutic potential of Anacyclus pyrethrum in mitigating the adverse effects of Fentanyl withdrawal. The study unveiled that chronic Fentanyl administration induced a withdrawal syndrome characterized by elevated cortisol levels (12.09 mg/mL, compared to 6.3 mg/mL for the control group). This was accompanied by heightened anxiety, indicated by a reduction in time spent and entries made into the open arm in the Elevated Plus Maze Test, as well as depressive-like behaviors, manifested through increased immobility time in the Forced Swim Test. Additionally, Fentanyl exposure correlated with decreased gut microbiome density and diversity, coupled with heightened oxidative stress levels, evidenced by elevated malondialdehyde (MDA) and reduced levels of catalase (CAT) and superoxide dismutase (SOD). However, both post- and co-administration of A. pyrethrum exhibited substantial improvements in these adverse effects, effectively alleviating symptoms associated with OUD withdrawal syndrome and eliciting positive influences on gut microbiota. In conclusion, this research underscores the therapeutic potential of A. pyrethrum in managing Fentanyl withdrawal symptoms. The findings indicate promising effects in alleviating behavioral impairments, reducing stress, restoring gut microbiota, and mitigating oxidative stress, offering valuable insights for addressing the challenges of OUD treatment. Full article

Buprenorphine is a safe and effective medication to treat opioid use disorder (OUD) in pregnant patients and is intended to be continued throughout pregnancy, delivery, and at least the one-year postpartum period. However, delivery often involves the need for acute pain management with opioid medications, such as after a cesarean section. For patients receiving buprenorphine, the provision of prescription opioids may negatively impact OUD treatment outcomes; however, not optimally managing acute pain may also impede OUD treatment benefit. Evidence is needed to disentangle the impacts of opioid prescription provision and methods of pain management in the immediate postpartum period on OUD treatment trajectories, ultimately to inform clinical guidelines tailored to the unique needs of pregnant and postpartum people receiving buprenorphine. Accordingly, this study took an initial step towards this goal to conduct a secondary analysis of a retrospective cohort of pregnant patients taking buprenorphine for OUD at the time of delivery (n = 142) to determine whether receipt of an opioid prescription at birth hospitalization discharge was associated with the time of buprenorphine discontinuation within the 12 months following delivery. Among the sample, 26% (n = 37) were prescribed an opioid at the time of birth hospitalization discharge. The number of weeks post-delivery until buprenorphine discontinuation occurred was shorter amongst patients who were prescribed an opioid (median 11 weeks) compared to patients who were not prescribed an opioid (median 39 weeks; p < 0.001 by Mann–Whitney U test). However, a Cox regression model reported that receipt of an opioid prescription following delivery did not significantly increase the hazard ratio for buprenorphine discontinuation. In other words, OUD patients not prescribed an opioid at birth hospitalization discharge continued their buprenorphine for a longer median duration after delivery compared to their counterparts who received prescription opioids; yet, this finding did not reach statistical significance when taking into account additional clinical variables. The findings indicate how further research is warranted to inform evidence-based post-delivery pain practices for postpartum OUD treatment patients. Full article

Objective: Many persons with opioid use disorders (OUDs) have HIV disease and experience clinically significant stress after they enroll in abstinence-based treatment and undergo medically assisted withdrawal. We examined whether opioid withdrawal affects virologic control, inflammatory markers, cognition, and mood in persons with an OUD and HIV, and explored whether measures of withdrawal stress, such as activation of the HPA axis, contribute to alterations in immune function, cognition, and mood. Method and participants: Study participants were 53 persons with HIV who were admitted for OUD treatment at the City Addiction Hospital in Saint Petersburg, Russian Federation. Participants were examined at admission, at the anticipated peak of withdrawal 3 to 7 days after the last day of a clonidine-based withdrawal process lasting 7 to 14 days, and 3 to 4 weeks after completing withdrawal. At these times, participants received medical exams and were evaluated for symptoms of withdrawal, as well as cognition and mood. Viral load, plasma cortisol, DHEA sulfate ester (DHEA-S), interleukin-6 (IL-6), and soluble CD14 (sCD14) were determined. Multivariable models examined the relationships between markers of HPA activation and the other parameters over time. Results: HPA activation as indexed by cortisol/DHEA-S ratio increased during withdrawal, as did markers of immune activation, IL-6 and sCD14. There were no significant associations between viral load and indicators of HPA activation. In longitudinal analyses, higher cortisol/DHEA sulfate was related to worse cognition overall, and more mood disturbance. Increase in IL-6 was associated with worse cognitive performance on a learning task. There were no significant associations with sCD14. Conclusions: Worsening of cognition and measures of mood disturbance during withdrawal were associated with activation of the HPA axis and some measures of inflammation. Whether repeated episodes of opioid withdrawal have a cumulative impact on long-term HIV outcomes and neurocognition is a topic for further investigation. Full article

Long-acting buprenorphine formulations have been recently marketed for the Opioid Agonist Treatment (OAT) of opioid use disorder (OUD) associated with medical, social, and psychological support. Their duration of action ranges from one week up to 6 months. The non-medical use of opioids is increasing with a parallel rise in lethal overdoses. Methadone and buprenorphine are the standard treatment for opioid dependence. Methadone Maintenance Treatment (MMT) is widely recognized as one of the most effective ways of reducing the risks of overdose, crime, and transmission of HIV (Human Immunodeficiency Virus) in people who use opioids; however, its effectiveness has been hindered by low rates of uptake and retention in treatment. Furthermore, both methadone and buprenorphine are widely diverted and misused. Thus, a crucial aspect of treating OUD is facilitating patients’ access to treatment while minimizing substance-related harm and improving quality of life. The newly developed long-acting buprenorphine formulations represent a significant change in the paradigm of OUD treatment, allowing an approach individualized to patients’ needs. Strengths of this individualized approach are improved adherence (lack of peaks and troughs in blood concentrations) and a reduced stigma since the patient doesn’t need to attend their clinic daily or nearly daily, thus facilitating social and occupational integrations as the quality of life. However, less frequent attendance at the clinic should not affect the patient–physician relationship. Therefore, teleconsulting or digital therapeutic services should be developed in parallel. In addition, diversion and intravenous misuse of buprenorphine are unlikely due to the characteristics of these formulations. These features make this approach of interest for treating OUD in particular settings, such as subjects staying or when released from prison or those receiving long-term residential treatment for OUD in the therapeutic communities. The long-lasting formulations of buprenorphine can positively impact the OUD treatment and suggest future medical and logistic developments to maximize their personalized management and impact. Full article

Community pharmacists have become increasingly exposed to opioid use disorders in recent decades. However, both pharmacist training and traditional practice environments have not been adequate to prepare the pharmacist for both the patient care needs and regulatory barriers of patients experiencing opioid use disorders (OUD). As a result, there is a need to increase pharmacists’ awareness of both the overall patient experience as they navigate their OUD and the role of the community pharmacy as a touchpoint within that experience. To this end, a Community-Centered Patient Journey in Drug Addiction Treatment journey map was developed with expert insights, clinical experience, and in-depth interviews (conducted in spring of 2021) with 16 participants enrolled in licensed opioid treatment programs in Tennessee. Patients, policymakers, clinicians, and academic researchers were involved in the map development. Lived experiences of key informants were captured via in-depth interviews. A consensus decision-making approach was used throughout the patient journey map development process. The final patient journey map illustrates a non-linear pathway, describes the central role of the patient’s community, and emphasizes three major “pain points” within the system (access, adherence, and affordability). Future research should investigate the impact of such a journey map on pharmacy personnel’s knowledge, attitudes, and behaviors. Full article

In the wake of COVID-19, morbidity and mortality due to Opioid Use Disorder (OUD) is beginning to emerge as a second wave of deaths of despair. Medication assisted treatment (MAT) for opioid use disorder MAT delivered by Emergency Medicine (EM) providers can decrease mortality due to OUD; however, there are numerous cited barriers to MAT delivery. We examined the impact of MAT training on these barriers among EM residents in an urban, tertiary care facility with a large EM residency. Training included the scripted and standardized content from the Provider Clinical Support System curriculum. Residents completed pre- and post-training surveys on knowledge, barriers, and biases surrounding OUD. We performed Wilcoxon matched-pairs signed-ranks test to detect statistical differences. Of 74 residents, 49 (66%) completed the pre-training survey, and 34 (69%) of these completed the follow-up survey. Residents reported improved preparedness to treat aspects of OUD across all areas queried, reported decreased perception of barriers to providing MAT, and increased comfort prescribing naloxone, counseling patients, prescribing buprenorphine, and treating opioid withdrawal. A didactic training on MAT was associated with residents reporting improved comfort providing buprenorphine and naloxone. As the wake of morbidity and mortality from both COVID and OUD continue to increase, programs should offer dedicated training on MAT. Full article

During 2020, Kentucky saw the third highest increase in overdose deaths in the U.S. Employment issues, inadequate housing, transportation problems, and childcare needs present barriers to accessing treatment in rural areas. These barriers and others (e.g., technology) arose during the pandemic negatively affecting individuals in recovery and service providers as they adjusted services to provide primarily telehealth and remote services. This study examines the impact of COVID-19 in its early stages on an opioid use disorder (OUD) support services program in a nonprofit located in rural eastern Kentucky, part of the central Appalachia region. A qualitative design was applied, employing semi-structured interviews in early fall 2020. Participants were associated with one OUD support services program, including service recipients, program coordinators, and business vendors. Guided by the Social Determinants of Health framework, two-cycle coding–descriptive coding and pattern coding–was utilized. Codes were sorted into three patterns: changes to daily life; financial impacts; and service access and provision. Overall, early stages of COVID-19 brought increased stress for individuals in recovery, as they were taking on more responsibility and navigating a changing environment. Coordinators were under pressure to provide services in a safe, timely manner. Vendors vocalized their struggles and successes related to finances. These findings can help organizations make realistic adjustments and policymakers set reasonable expectations and consider additional financial support. Full article

Opioid use disorders (OUDs) are increasingly common among minoritized populations, who have historically experienced limited access to healthcare, a situation that may have worsened during the COVID-19 pandemic. Using a structured keyword search in Pubmed, we reviewed the literature to synthesize the evidence on changes in racial/ethnic disparities in OUD-related outcomes in urban areas during the COVID-19 pandemic in the US. Nine articles were included in the final analysis. Six found increases in OUD-related outcomes during the pandemic, with four showing a widening of disparities. Results also point to the worsening of opioid outcomes among Black and Latinx individuals related to shelter-in-place or stay-at-home orders. Studies examining the use of telehealth and access to OUD treatment showed that minoritized groups have benefited from telehealth programs. The limited number of studies in a small number of jurisdictions indicate a gap in research examining the intersection between COVID-19 and OUD-related outcomes with a focus on disparities. More research is needed to understand the impact of the COVID-19 pandemic and related policies on OUD outcomes among racial/ethnic minoritized groups, including examining the impact of service disruptions on vulnerable groups with OUD. Full article

The number of drug overdose deaths involving opioids continues to rise in the United States. Many patients with opioid use disorder (OUD) that seek treatment still experience relapse. Perseverant opioid seeking behaviors represent a major challenge to treating OUD and additional therapeutic development will require insight into opioid-induced neurobiological adaptations. In this study, we explored the regulation of a novel class of RNAs, circular RNAs (circRNAs), by the addictive opioid heroin in the rat orbitofrontal cortex (OFC), a brain region that mediates behavioral responses to rewarding stimuli. Microarray analysis identified 76 OFC circRNAs significantly regulated in male rats after heroin self-administration. We evaluated the specificity of these findings by measuring heroin-associated circRNA expression in female rats after heroin self-administration and in rats that self-administered sucrose. We identify circGrin2b, circUbe2cp, circAnks1a, circAdcy5 and circSlc24A2 as heroin-responsive circRNAs in the OFC. Linear mRNA levels of heroin-associated circRNAs were unchanged except for Grin2b and Adcy5. An integrated bioinformatics analysis of regulated circRNAs identified microRNAs predicted to bind heroin-associated circRNAs and downstream targets of circRNA: microRNA sponging. Thus, heroin regulates the expression of OFC RNA splice variants that circularize and may impact cellular processes that contribute to the neurobiological adaptations that arise from chronic heroin exposure. Full article

Background: The majority of women who are pregnant with opioid use disorder (OUD) also smoke tobacco but are rarely offered tobacco cessation counseling. While the effects of exposure to opioids and nicotine in utero are well-understood separately, understanding the impact of the combined exposure to these substances on neonatal outcomes is lacking. Methods: A scoping review was conducted using PubMed and Scopus databases for studies addressing the combined exposure to opioids and nicotine during pregnancy published between 1 January 1980 and 9 July 2019. A total of 29 papers met the eligibility criteria for inclusion, with nine being identified as clinical trials (three from the MOTHER study) and two as secondary data analysis of clinical trial data. Results: Neonatal outcomes for infants who had a combined exposure to opioids and nicotine in utero indicated a reduction in birth weight and birth length. Findings in infants exposed to both nicotine and opioids were mixed with regard to the duration of neonatal abstinence syndrome (NAS), the likelihood of treatment for NAS, doses of medicine used to treat NAS, and NAS scores when compared with infants who had opioid exposure without nicotine. Conclusions: The combined exposure to nicotine and opioids during pregnancy may lead to a reduction in neonatal birth weight and birth length and more severe NAS signs, compared with opioid use alone, but more research is necessary to identify the minimum dosage and length of nicotine exposure to accurately predict these outcomes. Full article