MESH:C051274

The study compared the effectiveness of extended-release naltrexone (XR-NTX) and sublingual buprenorphine-naloxone (BUP-NX) in treating opioid use disorder (OUD) among Black adults. The results showed no significant preference for either treatment. However, only 59.5% of those assigned to XR-NTX successfully started the medication compared to 91.6% for BUP-NX. No significant differences were found in treatment retention or relapse rates between the two groups. Despite a significant initiation hurdle with XR-NTX, both medications were similar in effectiveness once started, but dropout rates were high.


NCBIGene:12630

The study aimed to predict the occurrence of opioid use disorder (OUD) in 25-year-olds based on data collected when they were 16. The researchers used two measures: the transmissible liability index (TLI), which measures heritable risk, and the consumption frequency index (CFI), which documents substance use events. The study found that the TLI and CFI at 16 years of age could predict OUD at 25 years with 86% accuracy. These measures also mediated the association between parental substance use disorder and OUD in offspring, indicating their effectiveness in evaluating risk and prodrome.


CHEBI:35338

The study examined the presence of methamphetamine in toxicology tests among outpatients in Boston, Massachusetts over a 6-year period. The study found that the presence of methamphetamine, cocaine, and fentanyl in oral fluid samples increased over the study period, while the presence of 6-MAM, a metabolite of heroin, decreased. In 2019, 15.7% of samples had fentanyl present. Polysubstance use was common, with 44% of samples with methamphetamine also showing cocaine or benzoylecgonine, 25% showed fentanyl, and 3% showed 6-MAM presence.


MESH:D016578


PUBCHEM.COMPOUND:90477108


MESH:C523259


CHEBI:35338

The study found that 38% of emergency department patients with untreated opioid use disorder also used amphetamine-type stimulants. These patients were younger, more likely to be white, unemployed, have unstable housing, have a history of incarceration, be hepatitis C positive, and have reported drug injection in the month prior to the study. They were also less likely to have cocaine-positive urine tests and to seek treatment for substance use problems. The study suggests the need for improved screening, intervention, and referral protocols for these patients.


MONDO:0005231


NCBIGene:5173

The study aimed to determine if gene variants in the opioid gene system are associated with better or worse treatment response in opioid use disorder (OUD). The treatments evaluated were sublingual buprenorphine-naloxone (BUP-NX) and extended-release injection naltrexone (XR-NTX). Four opioid gene variants were evaluated: mu opioid receptor 118A>G, 68-bp repeat in prodynorphin, prodynorphin SNP rs910080, and kappa opioid receptor SNP rs6473797. The study found no significant effects of gene variant on receiving first dose or last dose, and no significant gene variant by treatment interactions. The researchers concluded that the outcome of OUD treatment with medications is likely a complex function of multiple factors, including environmental, psychosocial, and possibly genetic.


NCBIGene:767814


NCBIGene:284825


MONDO:0001225

The study analyzed the effectiveness of medications for opioid use disorder in young adults (18-25 years) compared to older adults (≥26 years). The trial used extended-release naltrexone or sublingual buprenorphine-naloxone for 6 months. The results showed that young adults had higher relapse rates (70.3%) compared to older adults (58.2%). The study suggests that young adults may have vulnerabilities that increase their risk for treatment dropout and medication nonadherence, indicating a need for specialized, developmentally informed interventions.


MESH:C095476


NCIT:C123400


NCBITaxon:3482

The paper discusses the growing interest in using cannabis and cannabinoids for treating opioid use disorder (OUD). However, the evidence supporting this treatment is currently weak and does not justify listing cannabis or cannabinoids as a treatment for OUD. The authors suggest that further research is needed to explore the potential therapeutic applications of cannabis and cannabinoids in treating OUD, and that this research should be conducted with the same rigor as for all pharmaceutical products. Until more research is available, policy makers and clinicians should not portray cannabis and cannabinoids as evidence-based treatments for OUD.


CHEBI:67201


MESH:C051274

The study found that extended-release naltrexone (XR-NTX) is as safe and effective as sublingual buprenorphine-naloxone (BUP-NX) for treating opioid use disorder (OUD). However, initiating XR-NTX treatment is more difficult due to the detoxification hurdle. Patient-identified barriers to initiating XR-NTX treatment include unfamiliarity with antagonist treatment and ambivalence. Once initiated, XR-NTX is perceived as an effective treatment for maintaining abstinence from opioids, with its once-monthly dosing and no physical dependence being appealing to patients.


MESH:C502494

The study aimed to understand participants' perceptions of their assigned treatment in a clinical trial examining the use of extended-release naltrexone versus usual treatment for substance use disorders. The study found that while participants generally had a positive experience, they also held or developed apprehensions and misperceptions about the study medication. Some participants felt a lack of control and uneasiness about their assigned treatment, while others perceived their treatment as ineffective or as a cure-all for substance use disorders. The findings highlight the need for better participant education about the nature of interventions and the potential of ongoing consent processes.


MESH:C502494


UBERON:0014689

The study investigates the use of transcranial magnetic stimulation (TMS) as a non-invasive treatment for chronic pain in opiate users. The researchers compared the effects of TMS on the dorsolateral prefrontal cortex (DLPFC) and the motor cortex (MC) in 22 individuals with chronic pain who were using prescription opiates. The results showed that MC stimulation significantly decreased pain interference more than DLPFC stimulation. Both sites had comparable effects on stress, pain, and discomfort, but MC stimulation had larger effects on pain interference and the urge to use opiates. This suggests that the MC may be a promising target for decreasing opiate dependence and pain interference among chronic pain patients.


UBERON:0014689


UBERON:0001384


UBERON:0035153


CHEBI:35482

The paper reviews the trends in opioid overdose rates in the United States from 1999 to 2018, attributing the rise of the overdose epidemic to the proliferation of opioid prescribing for chronic pain, changes in the heroin and illegally manufactured opioid synthetics markets, and social factors such as deindustrialization and concentrated poverty. The study also discusses how policies aimed at addressing the overdose epidemic may have reduced prescription opioid overdoses but increased overdoses involving illegal opioids. The paper suggests new research directions to understand the causes and solutions to this public health problem.


MESH:C029572


MESH:C502494

The study evaluated a hospital-wide Substance Use Disorder (SUD) initiative over 5 years, which included an inpatient addiction consult team, Bridge Clinic, recovery coaches, and office-based addiction treatment nurses. The initiative saw 7,036 unique patients, with alcohol use disorder being the most common (62%), followed by opioid use disorder (54%). Co-occurring medical and psychiatric illnesses were common, with 35% having hepatitis C, 59% depression, 66% anxiety, and 13% schizophrenia. The initiative effectively initiated SUD pharmacotherapy with naltrexone and buprenorphine, with medication treatment episodes being longer with buprenorphine.


MESH:C560330


MESH:C502494

The study conducted a secondary analysis of a randomized trial comparing extended-release naltrexone (XR-NTX) and sublingual buprenorphine-naloxone (BUP-NX) treatment for opioid use disorder. The analysis was based on urine testing data for non-study opioids from the last 22 weeks of the 24-week trial. The results suggested that XR-NTX appeared to be somewhat more effective than BUP-NX in reducing illicit opioid use in the per-protocol sample.


MESH:C051274


MESH:C002186

The study presents a drug repurposing strategy for opioid use disorders (OUD) and other substance use disorders (SUD). The strategy integrates computational prediction, clinical corroboration using electronic health records (EHRs) of over 72.9 million patients, and mechanisms of action analysis. The top-ranked repurposed candidate drugs, tramadol, olanzapine, mirtazapine, bupropion, and atomoxetine, were associated with increased odds of OUD remission. Genetic and functional analyses showed these five candidate drugs directly target multiple OUD-associated genes including BDNF, CYP2D6, OPRD1, OPRK1, OPRM1, HTR1B, POMC, SLC6A4 and OUD-associated pathways, including opioid signaling, G-protein activation, serotonin receptors, and GPCR signaling.


MESH:C580748


MESH:C116278


NCBIGene:12064


NCBIGene:1565


NCBIGene:18386


NCBIGene:18387


NCBIGene:4988


NCBIGene:3351


NCBIGene:18976


NCBIGene:15567


MESH:C502494

The study investigated the efficacy and safety of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day) in adults with moderate or severe methamphetamine use disorder. The results showed that the response rate was low but higher in the naltrexone-bupropion group than in the placebo group. Adverse events with naltrexone-bupropion included gastrointestinal disorders, tremor, malaise, hyperhidrosis, and anorexia.


MESH:C502494


MONDO:0001225

The study proposes a clinical decision support algorithm for the treatment of opioid use disorder (OUD) with buprenorphine in primary care. The algorithm is based on measures for universal screening and symptom tracking, developed through literature search and expert consensus. The Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) tool was chosen for universal screening. The OUD Symptom Checklist and the Patient Adherence Questionnaire for Opioid Use Disorder Treatment (PAQ-OUD) were created for symptom tracking and medication adherence respectively. The algorithm provides guidance for the first 12 weeks of buprenorphine treatment.


PUBCHEM.COMPOUND:145990900

Self-efficacy for HIV treatment adherence

The study evaluates the effectiveness of Patient Navigation (PN) and Contingency Management (CM) interventions in improving HIV care outcomes among people living with HIV who report substance use (PLWH-SU). The results show that the combined PN and CM intervention indirectly improved engagement in HIV care at 6 months by increasing self-efficacy for HIV treatment adherence. This increase in self-efficacy also led to increases in viral suppression at 6 and 12 months. No mediating effects were observed for PN alone.


MESH:C502495

The ED-INNOVATION study aims to increase access to medications for opioid use disorder (OUD) by comparing the effectiveness of two buprenorphine (BUP) formulations: sublingual (SL-BUP) and 7-day extended-release injectable (CAM2038, XR-BUP). The primary outcome is engagement in formal addiction treatment at 7 days, with secondary outcomes including self-reported opioid use, craving and satisfaction, health service utilization, overdose events, and engagement in formal addiction treatment at 30 days. An ancillary study will also be conducted to assess the safety of XR-BUP initiation in patients with minimal to no opioid withdrawal.


MESH:C000722768

7-day extended-release injectable buprenorphine (CAM2038, XR-BUP)


MESH:C560330

The study investigates the association between the use of methadone or buprenorphine during medically supervised opioid withdrawal and the failure of induction onto extended-release naltrexone (XR-NTX), a maintenance treatment for opioid use disorder. The results show that the use of either methadone or buprenorphine was significantly associated with a decreased likelihood of induction onto XR-NTX compared to non-opioid detoxification. However, after controlling for site as a random effect, the association lost statistical significance. The study concludes that the use of agonist medication during detoxification was associated with XR-NTX induction failure.


CHEBI:35482

The study examined the extent and correlates of problematic substance use among primary care patients. Data from 2000 adult primary care patients were analyzed. The prevalence of any past 3-month use was 53.9% for alcohol, 42.0% for tobacco, 24.2% for any illicit/Rx drug, and 5.3% for opioids. The prevalence of moderate/high-risk use was 45.1% for tobacco, 29.0% for any illicit/Rx drug, 14.2% for alcohol, and 9.1% for opioids. Male sex, white race, not being married, and having less education were associated with increased odds of moderate/high-risk use scores for each substance category. Older ages were associated with increased odds of moderate/high-risk opioid use.


MESH:C560330

The paper discusses the use of buprenorphine, a medication treatment for opioid use disorder (OUD), and its effectiveness in preventing overdose, increasing abstinence, and improving quality of life. The authors suggest that the X-waiver, a special credential required for clinicians to prescribe buprenorphine in the United States, will likely be repealed. They propose strategies for creating a new treatment system post-X-waiver, including educational outreach, systems strategies, and enhanced payments.


MONDO:0002046

The study analyzed data from the 2015-2017 National Surveys on Drug Use and Health to understand the comorbidity of substance use disorders (SUDs) and their relationship with the receipt of treatment. It was found that 7.9% of adults had at least one SUD in the past year. The most common comorbidity combination was alcohol and marijuana use disorder, which also had the lowest receipt of treatment. The odds of receiving treatment were higher for those with multiple SUDs. However, treatment prevalence was lower for those with higher family income and education, not employed full time, married, younger than 26 or older than 50, and Asian. Despite the reduction in the treatment gap among those with multiple SUDs, it remains large.


MONDO:0005689


CHEBI:30879


CHEBI:67201


HP:0012531

The study evaluated the psychometric properties of the Pain Frequency, Intensity, and Burden Scale (P-FIBS), a measure of pain, and its association with irritability and depression. The study found that pain was positively correlated with irritability and depression. Irritability accounted for 40.7%-65.5% of the effect of pain on depression. Higher irritability and depression were associated with poorer social functioning, quality of life, and productivity in work- and non-work-related activities. Pain was associated with non-work-related activity impairments even after controlling for irritability and depression.


HP:0012531


HP:0000737

accounts for a large proportion of the effect of pain on


HP:0031873

The study investigates the factors influencing opioid use disorder (OUD) treatment outcomes in young adults compared to older adults. The study found that young adults have higher relapse rates than older adults, with specific characteristics such as more smokers, more intravenous opioid use, and more cannabis use. However, no single factor was identified as a significant moderator of relapse. The study suggests that poorer treatment outcomes in young adults are likely due to multiple developmental vulnerabilities.


MESH:C502494

The study examined the outcomes of opioid use and the utilization of medications for opioid use disorder (MOUD) 36 weeks after treatment. The study involved two medications, Extended-Release Naltrexone (XR-NTX) and Buprenorphine-Naloxone (BUP-NX). The results showed that 53% of participants were receiving MOUD and 47% were not. Participants on medication had fewer opioid use days, fewer met relapse criteria, and reported less stimulant and sedative use. There was no difference in abstinence rates between those on or off MOUD. A greater proportion of participants on XR-NTX were abstinent from non-prescribed opioids compared to those on buprenorphine.


MESH:C502495


MESH:C502495

The study investigates the effectiveness of buprenorphine-naloxone (BUP) and methadone (MET) in reducing opioid use among adults with comorbid opioid use disorder (OUD) and mental disorders. The results showed that both BUP and MET significantly reduced opioid use, but BUP was associated with a lower likelihood of any opioid use among participants with mood disorders and those without mental disorders, and fewer days of opioid use among participants with other mental disorders.


MESH:C095476

The study compared the effectiveness of sublingual buprenorphine-naloxone and extended-release injection naltrexone in treating opioid use disorder. It was found that patients who were homeless had a lower relapse rate when treated with extended-release naltrexone compared to buprenorphine-naloxone. Conversely, patients who were not homeless had a higher relapse rate when treated with extended-release naltrexone compared to buprenorphine-naloxone. Other factors such as parole and probation status, medication preference, and presence of pain also influenced the effectiveness of the treatments.


MONDO:0001225

The study investigates the prevalence and treatment of opioid use disorder (OUD) among youth engaged in primary care. The study found that 0.7% of the 303,262 youth studied had a documented OUD diagnosis. The prevalence of OUD increased with age. About half of the youth with OUD had documented depression or anxiety and one third had co-occurring substance use disorders. The receipt of medication for OUD was lowest among youth aged 16-17 years old (14%) and highest among those aged 22-25 (39%). The study concluded that there is a low receipt of medication treatment, and high prevalence of other substance use disorders and mental health disorders, indicating an urgent need to increase medication treatment for OUD and to integrate treatment for other substance use and mental health disorders.


MESH:C560330

The study investigates the safety and effectiveness of high-dose buprenorphine induction for the treatment of opioid use disorder (OUD) in emergency departments (EDs). The data was collected from a single, urban, safety-net hospital in Oakland, California, for the year 2018. The results showed that high-dose buprenorphine induction was safe and well tolerated in patients with untreated OUD. No cases of respiratory depression or sedation were reported. All cases of precipitated withdrawal had no association with dose. Three serious adverse events unrelated to buprenorphine were identified. Nausea or vomiting was rare.


MESH:C560330


MESH:C091498

The study aimed to identify the predictors of naloxone ownership among people who inject drugs (PWID) in urban and rural Oregon. The study found that 61% of participants in the National HIV Behavioral Surveillance (NHBS) and 30% of participants in the Oregon HIV/Hepatitis and Opioid Prevention and Engagement Study (OR-HOPE) had naloxone. In the urban NHBS sample, naloxone ownership was associated with female gender, injecting goofballs (as opposed to heroin alone), housing stability, and overdose training. In the rural OR-HOPE sample, naloxone ownership was associated with drug of choice, frequency of injection, and race. The study concluded that naloxone ownership was insufficient and highly variable among the two samples of PWID in Oregon.


MONDO:0005109


MONDO:0002251


MESH:C029572


UNII:34969JX79R


CHEBI:35338


MONDO:0004985

The study examined the impact of psychiatric disorders on the treatment outcomes of patients with opioid use disorder (OUD). The patients were divided into four groups: bipolar disorder (BPD), major depressive disorder (MDD), anxiety disorder (AXD), and no comorbid mental disorder (NMD). The results showed that patients with mental disorders had worse substance use outcomes and poorer psychosocial functioning than the NMD group. Specifically, BPD patients reported more days using opioids and heroin, while MDD patients spent more time engaged with OUD pharmacotherapy. The findings suggest the need for mental health assessment and treatment in the context of pharmacotherapy for OUD patients.


MONDO:0004985


MESH:C560330

used in treatment of co-occurring opioid use disorder

The study conducted a secondary analysis of a large, multi-site randomized trial of buprenorphine maintenance with and without individual Opioid Drug Counseling (ODC) for the treatment of opioid use disorder. The results indicated that participants with posttraumatic stress disorder (PTSD) significantly benefited from the addition of ODC to their buprenorphine treatment. Specifically, 67% of those with PTSD had a successful opioid use disorder treatment outcome when they were assigned to receive both ODC and buprenorphine, compared to a 36% response rate among those who received buprenorphine alone.


MONDO:0001225

The paper reviews the impact of the opioid epidemic on women, highlighting the increased rates of use and overdose deaths in this group. It discusses the co-occurrence of psychiatric disorders, pain, and trauma among women with opioid use disorder. The paper emphasizes the importance of expanding medication treatment for perinatal opioid use disorder and addresses the need for innovative multi-systemic solutions to end the epidemic. It also identifies significant practice gaps in preventing rising death rates among women by opioid overdose, treating co-occurring psychiatric disorders and pain, and treating perinatal women with opioid use disorder and their infants.


MONDO:0001225


MONDO:0001225

The study investigates how craving influences the decisions of people with opioid use disorder to pursue drugs over other valuable and healthier alternatives. The research found that individuals with higher cravings had higher drug-related valuation. Furthermore, moments of increased craving led to a higher willingness to pay for items and foods closely related to their drug use, but not for non-drug-related but equally desirable options. This increase in value with craving was greater when the drug-related options were offered in higher quantities. The study suggests that craving narrows and focuses economic motivation towards the object of craving by selectively amplifying perceived value along a "drug relatedness" dimension.


MONDO:0005231

The study evaluated the cost of Hepatitis C (HCV) care facilitation for HIV/HCV co-infected individuals with substance use disorder. The average site start-up cost was $6320, primarily consisting of training. The mean weekly cost per participant was $20 for care facilitation visits and contacts, $360 for supervision and client outreach, and $70 for overhead. In sensitivity analyses applying a weekly caseload of 10 participants per care facilitator, the total mean weekly care facilitation cost from the healthcare sector perspective decreased to $110. No healthcare cost offsets were identified during the trial period, although future savings might result from successful HCV treatment.


MONDO:0002491


MONDO:0001225

The study explores the experiences and perspectives of patients with untreated opioid use disorder (OUD) who visited emergency departments (EDs) for treatment. The study found that these patients often felt stigmatized and minimized by ED staff. They also did not view the ED as a source of OUD treatment initiation. The study suggests that strategies to address stigma, acknowledge and treat pain, and provide ED staff training should be implemented to improve ED care for patients with OUD and enhance access to life-saving treatment.


HP:0031135

The paper reviews the relationship between substance use disorders (SUD) and trauma in American Indian and Alaska Native (AI/AN) individuals. The study found that rates of lifetime trauma exposure varied from 21 to 98% and were correlated with increased rates of SUDs. A dose response of traumatic events also increased the likelihood of an SUD among reservation-based AI populations. Factors from the Indigenist Stress Coping model, such as traditional healing and cultural identity, aided in recovery from SUD and trauma. However, rates of posttraumatic stress disorders (PTSD) are lower than might be expected, suggesting resilience.


MESH:C560330

The study compared the effectiveness of extended-release naltrexone (XR-NTX) and treatment as usual (TAU) with buprenorphine or methadone in patients with HIV and opioid use disorder (OUD). The primary outcome was viral suppression (HIV RNA ≤ 200 copies/ml) at 24 weeks. The results showed that the viral suppression was comparable for XR-NTX (52.7%) and TAU (49.2%). The secondary outcome was past 30-day use of opioids at 24 weeks, which was also comparable for XR-NTX and TAU. However, among those who initiated medication, XR-NTX resulted in fewer days of opioid use compared to TAU.


CHEBI:35482

The study aimed to identify opioid-related phenotypes in the emergency department (ED) for research and surveillance purposes. The researchers used a hybrid scheme that combined modified Delphi and conceptual mapping methods to achieve consensus around opioid-related phenotype topics. After three rounds of electronic meetings and questionnaires, 120 initial phenotype concepts were proposed, which were reduced to 73 after normalization. The highest combined importance and feasibility score was for opioid overdose. The final 12-cluster solution identified three key groups: opioid overdose, other opioid-specific phenotypes (opioid use disorder, opioid misuse, and opioid withdrawal), and opioid use-related phenotypes (homelessness, falls, infections, and suicidality).


CHEBI:35482


NCBIGene:5173

The study investigates the role of prodynorphin (PDYN) genetic markers in moderating the therapeutic response to buprenorphine/naloxone (Suboxone®; BUP) treatment for cocaine dependence. The results showed that the presence of certain PDYN variants (rs1022563 A-allele and rs1997794 A-allele) was associated with a better response to BUP treatment, as evidenced by fewer cocaine-positive urines. This was particularly true for the African American-ancestry subgroup with the rs1022563 A-allele. The findings suggest that PDYN variants may help identify patients who would respond best to treatment with XR-NTX plus buprenorphine for cocaine use disorder.


NCBIGene:329562

associated with better response to treatment


NCBIGene:100126324


MESH:C107567


CHEBI:35482

The study aimed to develop a standard set of outcomes for evaluating treatments for opioid use disorder (OUD), due to the lack of a gold standard and considerable heterogeneity in current outcome measures. The researchers used a four-round e-Delphi expert panel consensus study and plenary research group discussion to develop the Opioid Use Disorder Core Outcomes Set (OUD-COS). The panel reached consensus on five outcomes: two patient-reported (global impression of improvement and incident non-fatal overdose), one clinician-reported (illicit/non-medical drug toxicology), and two from administrative records (duration of treatment and fatal opioid poisoning).


MESH:D062789

The study analyzed alcohol use among patients who were dispensed opioid medications in community pharmacies in Indiana and Ohio. It was found that 18.1% reported weekly drinking and 6.8% reported daily drinking, with 9.6% reporting moderate/high risk drinking. Factors associated with increased likelihood of moderate/high risk alcohol use included being male, having higher pain interference, history of overdose, sedative use, and tobacco use. The study highlights the need for addressing the concomitant use of opioids and alcohol to improve patient safety.


MESH:C560330

The study analyzed the effects of buprenorphine dosage and therapeutic engagement on illicit opiate use in opioid use disorder treatment. Data from six buprenorphine efficacy and safety trials were used. The study found that higher doses of buprenorphine and greater engagement with providers and clinic staff were associated with reduced illicit opiate use. The study also found that the dosing protocol and the number of clinic visits were significant protective factors.


MONDO:0001225

The study aimed to understand the prevalence of mental disorders and nonnicotine substance use disorders among male and female primary care patients with opioid use disorder in the U.S. The data was collected from 2014-2016 from six health systems. The study found that females (53.2%) and males (46.8%) had a similar prevalence of opioid use disorder. However, comorbid mental disorders were more prevalent among females (86.4% vs. 74.3%), while comorbid other substance use disorders were more common among males (51.9% vs. 60.9%). These differences were also observed among those receiving medication treatment for opioid use disorder. The study concluded that there is a high rate of comorbid conditions among patients with opioid use disorder, indicating a need for integrated opioid use disorder treatment.


CHEBI:35482

The study aimed to identify and characterize subphenotypes of emergency department (ED) patients with opioid-related encounters. Using a latent class analysis on data from the National Emergency Department Sample (NEDS), five subphenotypes were identified: Chronic pain, Alcohol use, Depression and pain, Psychosis, liver disease, and polysubstance use, and Pregnancy. The greatest odds for hospitalization were found in the Depression and pain, and Psychosis, liver disease, and polysubstance use classes. The highest odds for in-hospital death were found in the Psychosis, liver disease, and polysubstance use class.


CHEBI:35482

The study investigates the long-term effects of opioid and benzodiazepine use during emergency department (ED) treatment for traumatic injury. The results show that while opioid use alone during the ED visit predicted a relatively lower likelihood of subsequent substance use and mental health diagnoses, the brief co-use of benzodiazepines was strongly associated with poorer outcomes. This suggests that even brief exposure to co-prescribed opioids and benzodiazepines during emergency traumatic injury care may lead to negative substance use and mental health consequences in the years following the event.


CHEBI:22720


MESH:C560330

The paper does not provide an abstract, but from the title, it can be inferred that the study is about the characteristics of patients who abstained from opioids after participating in a trial of Buprenorphine versus Injectable Naltrexone.


MESH:C502494


HP:0031589

The study investigated suicidality as a predictor of overdose in patients with substance use disorder (SUD). The research involved 2541 participants across eight multi-site clinical trials. Suicidality was assessed using the Concise Health Risk Tracking Self-Report (CHRT-SR) and overdose events were determined through various methods. The results showed that the likelihood of overdose increased as the CHRT-SR score increased. Additionally, participants with a history of heroin use were more likely to overdose.


MONDO:0002491


MESH:C029572


GO:0050959

Medication for opioid use disorder (MOUD)

The study investigates the impact of Project ECHO (Extension for Community Healthcare Outcomes) training on the prescription of buprenorphine, a medication for opioid use disorder (OUD), by primary care clinicians in Minnesota. The results show that clinicians who underwent ECHO training were more likely to obtain a DATA-waiver (required to prescribe buprenorphine) and prescribe buprenorphine to patients with OUD compared to those who did not participate in ECHO training. This suggests that Project ECHO training could be a useful tool for expanding access to medication for opioid use disorder (MOUD).


MESH:C112644

The study investigates the potential of methocinnamox (MCAM), a pseudoirreversible mu-opioid receptor antagonist, as a treatment for opioid abuse. The research was conducted on rhesus monkeys, who were given heroin, cocaine, or a choice between food and the mu-opioid receptor agonist remifentanil. The effects of MCAM were compared with those of naltrexone. Both MCAM and naltrexone decreased the monkeys' preference for heroin and remifentanil, increasing their choice of food. However, the effects of MCAM lasted for several days, and it did not affect the monkeys' heart rate, blood pressure, body temperature, or activity levels. MCAM also did not decrease the monkeys' response to cocaine or food. These findings suggest that MCAM could be a safe and effective alternative to current treatments for opioid abuse.


MESH:C112644


MESH:C029572

The study investigates the ability of Methocinnamox (MCAM), a novel μ-opioid receptor antagonist, to prevent and reverse the respiratory-depressant effects of heroin in Rhesus monkeys. The results show that MCAM can prevent and reverse respiratory depression caused by heroin for a longer duration than currently used opioid receptor antagonists, such as naloxone and naltrexone. This suggests that MCAM could be more effective in treating opioid overdose due to its sustained effects.


MESH:C091498


PUBCHEM.COMPOUND:44569239

Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)

The study developed and validated an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for quantifying ten key alkaloids in Kratom (Mitragyna speciosa), a plant used for self-treatment of pain and opioid addiction. The method was applied to various kratom products and extracts, with mitragynine, paynantheine, speciociliatine, and speciogynine found to be the major alkaloids. Minor alkaloids were also quantified, but mitraphylline was below the lower limit of quantification in all analyses.


MESH:C547644

The study compared the effects of mitragynine, an alkaloid constituent of Mitragyna speciosa (kratom), and morphine on operant responding for food delivery and response latency to a thermal stimulus in male and female Sprague-Dawley rats. Both drugs were found to decrease schedule-controlled responding and increase thermal antinociception. However, doses of the opioid antagonist naltrexone that antagonized morphine did not antagonize mitragynine. Furthermore, mitragynine did not alter the rate-decreasing or antinociceptive effects of morphine. The study concluded that the antinociceptive effects of mitragynine and morphine occur at doses larger than those that disrupt learned behavior and that the pharmacology of mitragynine includes a substantial non-opioid mechanism.


MESH:C523259


MESH:C547644


MESH:C112644

The study investigates the effects of methocinnamox (MCAM), a µ-opioid receptor antagonist, on the behavioral effects of µ-opioid receptor agonists in rats. The research found that MCAM attenuates the antinociceptive effects of morphine and fentanyl, but not spiradoline. It also blocked the effects of morphine on sensitivity to mechanical stimulation and gastrointestinal motility. The antagonist effects of MCAM were found to be long-lasting, persisting for 2 weeks or more. However, the duration of withdrawal precipitated by MCAM was not different from that precipitated by naloxone. This suggests that MCAM could be effective for treating opioid abuse and overdose without causing sustained withdrawal.


MESH:C075211

The study investigates the pharmacological profile of NFP, a MOR/KOR dual-selective opioid antagonist. The research shows that NFP significantly antagonizes the antinociceptive effects of morphine with lesser withdrawal effects than naloxone. In vitro and in vivo assays reveal that NFP can antagonize DAMGO-induced calcium flux and etorphine-induced MOR internalization. Unlike opioid agonists DAMGO and morphine, cells pretreated with NFP did not show apparent desensitization and down regulation of the MOR. Despite being a potential P-gp substrate, NFP can antagonize the antinociceptive effects of morphine, indicating potential central nervous system activity. This suggests that NFP could be used therapeutically in opioid use disorder treatment.


MESH:C075211


CHEBI:38958

The study evaluated selected indole-based kratom alkaloids for their binding and functional effects on opioid and adrenergic receptors, their in vivo antinociceptive effects, plasma protein binding, and metabolic stability. The major alkaloid in Mitragyna speciosa (kratom), mitragynine, showed higher affinity at opioid receptors than at adrenergic receptors, while corynantheidine showed the opposite. This polypharmacology of kratom alkaloids may support its use in treating opioid use disorder and withdrawal.


CHEBI:38958


CHEBI:76257


MESH:C055140

The paper reviews methods for evaluating potential medications to treat opioid use disorder (OUD). It suggests that drug self-administration procedures are the most direct method for assessing medication effectiveness, and that states of opioid dependence and withdrawal significantly influence both opioid reinforcement and the effects of potential medications. The paper reviews the effects of opioid medications and vaccines on opioid choice in nondependent and opioid-dependent subjects. It also discusses the future research focus on strategies for increasing the safety and/or effectiveness of opioid medications, such as G-protein-biased μ-opioid agonists, and the continued development of nonopioid medications, such as clonidine, that might serve as adjunctive agents to current opioid medications.


MONDO:0001225

The study investigates the effectiveness of treating Opioid Use Disorder (OUD) in pregnant women via telemedicine compared to in-person treatment. The trial included 98 women receiving perinatal OUD treatment either by telemedicine or in person. The outcomes measured were retention in treatment, urine drug screen results at delivery and 6 to 8 weeks post partum, and a neonatal abstinence syndrome (NAS) diagnosis. The results showed no significant differences between the telemedicine and in-person groups in terms of treatment retention and rates of NAS. This suggests that virtually integrated OUD care in obstetric practices can produce similar outcomes to in-person care.


MESH:C112644

The study investigates the effects of Methocinnamox (MCAM), a mu opioid receptor antagonist, on fentanyl self-administration in rhesus monkeys. The results show that both acute and repeated MCAM administration decreased fentanyl self-administration, with the effects lasting up to two weeks after a single large dose and more than two months with repeated administration. MCAM did not alter cocaine self-administration. The study suggests that MCAM's long-lasting effects are due to pharmacodynamic factors (i.e., pseudoirreversible binding to mu opioid receptors) rather than pharmacokinetic factors. These findings suggest that MCAM could be a potential treatment for opioid use disorder (OUD).


MESH:C502494


CHEBI:35482

The study focuses on the mu opioid receptors (MOR-1), which are responsible for the biological effects of opioids like morphine, oxycodone, and fentanyl. The gene OPRM1, which undergoes extensive alternative splicing, generates these receptors. One type of splice variant is the truncated variant with six transmembrane domains (6TM) that mediate the analgesic action of novel opioid drugs such as 3'-iodobenzoylnaltrexamide (IBNtxA). The researchers synthesized two arylazido analogs of IBNtxA that allow photolabeling of mouse mu opioid receptors (mMOR-1) in transfected cell lines and mMOR-1 protein complexes in mouse brain. These analogs efficiently radio-photolabeled mMOR-1 in cell lines and MOR-1 protein complexes, providing useful tools for further investigation of ligand-protein contacts and signaling complexes.


NCBIGene:4988


MESH:C106664


MESH:C071618


HP:0007021

The study found that chronic low back pain (cLBP) is associated with disruptions in the mesocortical and mesolimbic circuits of the reward system, which may contribute to pain sensitization and the chronic nature of cLBP. Resting-state functional connectivity (rsFC) between the ventral tegmental area (VTA) and the rostral anterior cingulate cortex (rACC), medial prefrontal cortex (mPFC), and hippocampus/parahippocampus was found to be reduced in cLBP patients compared to pain-free controls. Increased back pain intensity was associated with increased mesocortical and mesolimbic connectivity. The study suggests that mesolimbic dysconnectivity may mediate the association between mechanical pain sensitivity and cLBP severity.


MESH:C548959

The study synthesized and evaluated (-)-N-Phenethyl analogs of optically pure N-norhydromorphone. One compound, N-p-chloro-phenethynorhydromorphone, showed nanomolar binding affinity at MOR (mu-opioid receptor) and DOR (delta-opioid receptor). It acted as a potent partial agonist at MOR and a full potent agonist at DOR. Bifunctional opioids that interact with MOR and DOR have been reported to have fewer side-effects than MOR agonists. The compound did not depress respiration in mice or squirrel monkeys under normal air conditions, but did depress respiration in squirrel monkeys under conditions of hypercapnia (using air mixed with 5% CO2).


MESH:C548959


MESH:C548959

causes in squirrel monkeys under certain conditions


PUBCHEM.COMPOUND:53710962

The study investigates the analgesic effects of real acupuncture and video-guided acupuncture imagery treatment (VGAIT) by examining their impact on brain regional connectivity. The study found that real acupuncture decreased regional homogeneity (ReHo) and functional connectivity (FC) in sensorimotor areas, while VGAIT increased ReHo in basal ganglia (BG) and FC between the BG subcortical network and default mode network. These changes were associated with changes in pain threshold. The study also found that individual variability in response to acupuncture and VGAIT was associated with ReHo and gray matter volume (GMV) in BG and the anterior insula, respectively.


PUBCHEM.COMPOUND:53710962


MESH:C547644

The study investigates the safety and pharmacokinetic properties of mitragynine, a psychoactive alkaloid derived from the leaves of Mitragyna speciosa (kratom), in beagle dogs. The study found that mitragynine has a large volume of distribution and high clearance following intravenous administration. After oral dosing, peak plasma concentrations were observed within 0.5 hours. The active metabolite of mitragynine, 7-hydroxymitragynine, was also observed in orally dosed dogs. The absolute oral bioavailability of mitragynine was 69.6%. Administration of mitragynine was well tolerated, with mild sedation and anxiolytic effects observed.


MESH:C109363


CHEBI:87230

The study compares the pharmacological properties of Nalfurafine, a kappa opioid receptor (KOR) agonist, and its 3-dehydroxy analogue, compound 42B. Both Nalfurafine and 42B act as full KOR agonists and partial μ opioid receptor (MOR) agonists, but 42B has lower potency for both receptors and lower KOR/MOR selectivity. Molecular modeling revealed that the higher KOR potency of Nalfurafine is due to a water-mediated hydrogen-bond formation. In mice, both compounds produced antinociceptive and antiscratch effects without causing conditioned place aversion (CPA). However, 42B caused motor incoordination and hypolocomotion, unlike Nalfurafine. The study suggests caution in correlating in vitro biochemical data with in vivo behavior effects.


CHEBI:87230


MESH:C475429


MESH:C000627326

The study focuses on the use of natural products salvinorin A, mitragynine, and collybolide as potential next-generation analgesics. These substances are potent selective agonists of opioid receptors, which are traditionally targeted by opiates for pain management. However, traditional opiates often have significant side effects. The natural products mentioned are nonmorphinan and have shown promising results in terms of affinity, selectivity, analgesic actions, and other opioid-receptor-related behavioral effects.


MESH:C426964


MESH:D053610


MESH:C523259


PR:000007134

The study focuses on soluble epoxide hydrolase (sEH), an enzyme that degrades epoxy-fatty acids (EpFAs), which are important lipid signaling molecules. sEH is a potential therapeutic target for neuropathic pain. The researchers aimed to improve the physical properties and potency of sEH inhibitors, specifically those carrying a 1,3-disubstituted urea, which has been reported to have the highest affinity for sEH. The team identified two structural modifications that significantly improved the potency and physical properties of these sEH inhibitors, which could facilitate their clinical use.


CHEBI:188147


PR:000007134


MESH:D064148

The study investigates the effects of a novel antagonist, D24M, of the mu-/delta-opioid receptor (MOR/DOR) heterodimer in male rats. High doses of D24M did not disrupt home cage wheel running, a method used to assess spontaneous opioid withdrawal. Repeated administration of increasing doses of morphine over 5 days resulted in depressed wheel running and induced antinociceptive tolerance. D24M had no effect on morphine tolerance but tended to prolong morphine antinociception in non-tolerant rats. Spontaneous morphine withdrawal was evident as a decrease in body weight, a reduction in wheel running, and changes in sleep patterns. D24M had no effect on morphine withdrawal.


MESH:D064148


MESH:C016005

The study investigates the effect of different C-terminal variants on mu agonist-induced G protein coupling, β-arrestin2 recruitment, and signaling bias. It was found that mu agonists produced significant differences in G protein activation and β-arrestin2 recruitment among various C-terminal variants, leading to biased signaling at various levels. Particularly, MOR-1O, an exon 7-associated variant, showed greater β-arrestin2 bias for most mu agonists than MOR-1, an exon 4-associated variant. This suggests that a single mu agonist can induce differential signaling through multiple 7TM splice variants, which is important for understanding the complex mu opioid actions in vivo where all the 7TM splice variants co-exist.


MESH:C016005


CHEBI:35480

The paper discusses the use of home cage wheel running as a tool for assessing pain in laboratory animals. This method is beneficial as it provides an objective measure of pain's magnitude and duration, and it is a clinically relevant way to screen new drugs. Unlike traditional pain-evoked tests, the restoration of home cage wheel running evaluates treatments for both their ability to reduce pain and the absence of disruptive side effects. The paper argues that this method is effective and clinically relevant for screening potential new analgesics.


MESH:C040902

The paper presents a methodology for the synthesis of 6α/β-3-dehydroxynaltrexamines and 6α/β- N-methyl-3-dehydroxynaltrexamines. A stereoselective route is provided for each target compound and a novel one-pot method for the synthesis of 6 α/β-3-N-methyl-3-dehydroxynaltrexamines is also explored. These results enable the preparation of key epoxymorphinan intermediates to facilitate future selective opioid ligand discovery and development.


MESH:D009022


MESH:C029844

The paper discusses the limitations of naloxone, the only FDA-approved medication for preventing and treating opioid overdose, and explores alternative approaches. These include intranasal nalmefene, methocinnamox, covalent naloxone nanoparticles, serotonin (5-HT)1A receptor agonists, fentanyl-binding cyclodextrin scaffolds, detoxifying biomimetic "nanosponge" decoy receptors, and antibody-based strategies. These new approaches could also be used to treat opioid use disorder.


CHEBI:35941


MESH:C434444


MESH:C112124

Detoxifying Biomimetic 'Nanosponge' Decoy Receptors


MESH:D000906


CHEBI:46931

Carfentanyl amide-based opioid derivatives

The study focuses on a series of carfentanyl amide-based opioid derivatives targeting the mu opioid receptor (μOR) and the delta opioid receptor (δOR) heteromer for pain management therapy. A lead compound, MP135, was identified that shows high G-protein activity at μ-δ heteromers compared to the homomeric δOR or μOR and low β-arrestin2 recruitment activity. MP135 has a distinct signaling profile compared to the previously identified agonist, CYM51010. MP135 could potentially be developed as an antinociceptive agent similar to morphine in rodents, but it still maintains side effects such as respiratory depression and reward behavior, suggesting that further optimization is needed.


CHEBI:46931


PUBCHEM.COMPOUND:3025067


PUBCHEM.COMPOUND:3025067

could be developed as an antinociceptive agent similar to


MESH:D014612

The study focuses on the development of therapeutic and prophylactic vaccines to combat the effects of fentanyl use disorders and toxicity. The vaccines, made from novel fentanyl-based haptens conjugated to carrier proteins, were tested on mice and rats. The results showed that the vaccines reduced the effects of fentanyl and its analogues, including opioid-induced behavior and toxicity. The vaccines did not interfere with the effects of commonly used anesthetics or other opioids like methadone, naloxone, oxycodone, or heroin.


MESH:D014612


MESH:C493100

The study investigates the effects of the glucagon-like peptide-1 receptor (GLP-1R) agonist, exendin-4 (Ex-4), on heroin-seeking behavior in rats. The results show that treatment with Ex-4 reduces both cue-induced seeking and drug-induced reinstatement of heroin seeking. Additionally, Ex-4 treatment was associated with increased Orexin 1 receptor (OX1) mRNA expression in the nucleus accumbens shell.


MESH:C493100

increases mRNA expression in nucleus accumbens shell


MESH:C493100


MESH:C000611464

The study reveals that 7-Hydroxymitragynine (7-HMG), a metabolite of the kratom alkaloid mitragynine, is converted into mitragynine pseudoindoxyl in human plasma. This new metabolite is more potent than either mitragynine or 7-HMG. The conversion of 7-HMG to mitragynine pseudoindoxyl is more prevalent in human plasma than in the plasma of other tested species (mouse, rat, dog, and cynomolgus monkey). This suggests that mitragynine pseudoindoxyl may significantly contribute to the pharmacology of kratom in humans.


MESH:C547644

is more prevalent in compared to other species' plasma


MESH:C502494

The study compared the effects of mitragynine and 7-hydroxymitragynine on µ-opioid receptor (MOR) efficacy and their effects in rats. The results showed that mitragynine has a low affinity for MOR and acts as an antagonist, while 7-hydroxymitragynine has a higher affinity and acts as a partial agonist. In rats, mitragynine showed a complex pharmacology including MOR agonism, while 7-hydroxymitragynine showed higher MOR potency and efficacy. The study also found that naltrexone antagonized all effects of morphine and 7-hydroxymitragynine, but only antagonized the discriminative stimulus effects of mitragynine.


MESH:C112644

The study investigates the effects of Methocinnamox (MCAM), a long-lasting opioid receptor antagonist, on fentanyl-induced ventilatory depression in male Sprague-Dawley rats. The results show that MCAM, like naloxone, can reverse the ventilatory-depressant effects of fentanyl in a dose-related manner. However, unlike naloxone, MCAM's effects last up to 3 days and at least 2 weeks after intravenous and subcutaneous administration, respectively. MCAM also attenuated the antinociceptive effects of fentanyl, with antagonism lasting up to 5 days and more than 2 weeks after intravenous and subcutaneous administration, respectively. This suggests that MCAM could be a potential treatment for opioid overdose, including fentanyl overdose.


MESH:C091498


PUBCHEM.COMPOUND:90477108


MESH:C519918

The study discusses the development of EC5026, an orally active analgesic that acts on the cytochrome P450 branch of the arachidonate cascade to stabilize epoxides of polyunsaturated fatty acids (EpFA). EC5026 inhibits the soluble epoxide hydrolase (sEH) at picomolar concentrations, which increases EpFA in vivo and confers beneficial effects. This mechanism shifts endoplasmic reticulum stress from promoting cellular senescence and inflammation toward cell survival and homeostasis. EC5026 has passed human Phase 1a trials with no drug-related adverse events.


MESH:C519918


MESH:C519918

Epoxides of polyunsaturated fatty acids (EpFA)


PR:000007134


GO:0030968


MESH:D003988

The study investigates the modulation and selectivity mechanisms of seven mixed-action kappa opioid receptor (KOR)/mu opioid receptor (MOR) bitopic modulators. The findings suggest that the 'message' moiety of these modulators shares the same binding mode with the orthostic site of KOR and MOR, while the 'address' moiety binds with different subdomains of the allosteric site of KOR and MOR. This binding may lead to distinguishable allosteric modulations to the binding affinity and/or efficacy of the 'message' moiety. The 3-hydroxy group on the phenolic moiety of the modulators was found to induce selectivity to the KOR over the MOR.


MESH:D003988


CHEBI:61355


MESH:C547644

The study developed a method to quantify 11 alkaloids found in kratom, a plant used for pain management and reduction of opioid withdrawal symptoms. The method was used to analyze samples from lyophilized kratom tea (LKT) and a commercial product, OPMS liquid shot, in rats. Of the 11 alkaloids, only mitragynine, 7-hydroxymitragynine, speciociliatine, and corynantheidine showed systemic exposure 8 hours postdose. The dose-normalized systemic exposure of these four alkaloids was higher following the administration of the commercial OPMS liquid.


MESH:C109363


PUBCHEM.COMPOUND:44151929


CHEBI:76257


CHEBI:61355

The study investigates the role of the 3-hydroxy group in a series of epoxymorphinan derivatives and their binding affinity and selectivity profiles toward opioid receptors (ORs). The 3-hydroxy group was found to be crucial for the binding affinity of these derivatives for all three ORs. Compounds carrying the 3-hydroxy group had similar selectivity profiles for the kappa opioid receptor over the mu opioid receptor as their corresponding 3-dehydroxy derivatives. The 3-hydroxy group of these epoxymorphinan derivatives was important for maintaining their potency on the ORs with various effects.


MESH:C117440

The study isolated ten indole and oxindole alkaloids from the leaves of Malaysian Mitragyna speciosa (Kratom). The chemical structures of these compounds were established using 1D and 2D NMR and HRMS data analysis. The spatial configuration of one of these alkaloids, mitragynine oxindole B, was confirmed by single-crystal X-ray diffraction. The alkaloids were quantified in the M. speciosa leaf specimens collected from different locations in the northern region of Peninsular Malaysia using UPLC-MS/MS. The oxindole alkaloids and the indole alkaloid were assessed for binding affinity at opioid receptors. Corynoxine showed high binding affinity to μ-opioid receptors and was 1.8-fold more potent than morphine in rats subjected to a nociceptive hot plate assay.


MESH:C117440


NCBITaxon:10114

The study aimed to translate a drug-vs-food choice procedure from monkeys to rats and develop a surgical method for sustained intravenous catheter patency for long-term drug-choice studies. The surgical protocol resulted in a median intravenous jugular catheter patency in male and female rats of 126 days. Drug-vs-food choice was established with opioids (fentanyl and heroin), psychostimulants (cocaine, methamphetamine, and amphetamine), and an opioid/psychostimulant mixture (fentanyl + methamphetamine). The average time from catheter implantation to stable choice behavior across all drugs was 27 sessions. Choice behavior stabilized more quickly for cocaine and fentanyl than for other drugs. Manipulations of both environmental variables and pharmacological variables significantly shifted opioid-vs-food choice consistent with previous monkey studies. The concordance of behavioral results between rats and monkeys using the present drug-vs-food choice procedure supports its utility to improve our basic understanding of the expression and mechanisms of substance use disorders towards to development of more effective therapeutics.


NCBITaxon:10114

Psychostimulants (cocaine, methamphetamine, and amphetamine)


NCBITaxon:10114

Opioid/psychostimulant mixture (fentanyl + methamphetamine)


MONDO:0002491


MESH:C040902

The study explores the application of a nitrogen-walk approach in developing new opioid ligands that contain an azaindole moiety at the C6-position of the epoxymorphinan skeleton. The in vitro results showed that introducing a nitrogen atom around the indole moiety not only maintained excellent binding affinity but also led to a significant functional switch at the mu opioid receptor (MOR). These novel MOR ligands have high binding affinity and low efficacy, which could be beneficial in designing low efficacy MOR ligands for opioid use disorder therapeutics.


CHEBI:50893


MESH:C482460

The study investigates the neuropathic pain caused by Stavudine (D4T), a highly active antiviral therapy (HAART) used to treat HIV. The research was conducted on male and female C57BL/6 J mice, which were injected with D4T and tested for mechanical allodynia and thermal hyperalgesia. The results showed that D4T produced dose- and time-dependent mechanical allodynia and thermal hyperalgesia. The smallest effective D4T dose was 17.8 mg/kg, which produced mechanical allodynia but not thermal hyperalgesia. Larger D4T doses produced both symptoms lasting 92 days. Morphine was found to alleviate both symptoms in D4T-treated mice, while Naltrexone increased the ED50 value of morphine.


MESH:C482460


MESH:C523259


MESH:C487760

The study introduces RM1490, a medium efficacy µ opioid receptor (MOR) agonist, as a potential therapeutic for opioid use disorder (OUD). RM1490, derived from a nonmorphinan scaffold, exhibits approximately half the intrinsic MOR efficacy of buprenorphine, a current OUD pharmacotherapy. In preclinical assays, RM1490 showed a behavioral profile consistent with reduced reward, dependence, and precipitated withdrawal liabilities. It was also more effective than buprenorphine at reversing the respiratory depressant effects of fentanyl and did not suppress respiration when combined with diazepam.


MESH:C560330


MESH:C502494


MESH:C487760


MESH:C487760

does not suppress respiration when combined


MESH:C091498

The study focuses on the development of quick- and long-acting naloxone delivery systems to counteract opioid effects. Naloxone-loaded poly(lactide-co-glycolide) (PLGA) microparticles were prepared using an emulsification solvent extraction approach. The naloxone encapsulation efficiency was found to be between 70-85%. The in vitro naloxone release duration ranged from 4 to 35 days. The study also found that naloxone released from the three selected formulations could inhibit DAMGO-induced β-arrestin 2 recruitment, indicating the proposed naloxone delivery system is adequate for opioid reversal during the naloxone release duration.


MESH:C091498


MESH:C438305


PUBCHEM.COMPOUND:88145

The study investigates the efficacy of the Oxy(Gly)4-sKLH vaccine in treating opioid use disorders. The vaccine, which targets oxycodone, has shown pre-clinical proof of efficacy, selectivity, and safety. The study found that repeated immunizations were necessary to maintain the antibody response, but exposure to free oxycodone did not boost oxycodone-specific antibody levels. The vaccine achieved sustained antibody titers over five months, indicating potential for long-lasting protection. The vaccine prevented oxycodone-induced antinociception but did not interfere with methadone-induced antinociception or fentanyl distribution to the brain. The vaccine also extended oxycodone's half-life and reduced its reinforcing efficacy without showing signs of toxicity.


PUBCHEM.COMPOUND:88145


CHEBI:76257

The study investigates the effects of minor indole and oxindole alkaloids from kratom on opioid receptors. The alkaloids corynantheidine, corynoxine, corynoxine B, mitraciliatine, and isopaynantheine were studied for their receptor affinity, G-protein activity, and βarrestin-2 signaling at mouse and human opioid receptors. Corynantheidine and mitraciliatine were identified as partial agonists of the mu opioid receptor (MOR), while corynoxine was a full MOR agonist. Isopaynantheine was identified as a kappa opioid receptor (KOR) agonist. Corynantheidine, corynoxine, and mitraciliatine showed MOR-dependent antinociception in mice, but mitraciliatine and corynoxine caused less respiratory depression and hyperlocomotion than morphine when administered supraspinally. Isopaynantheine was identified as the first kratom-derived KOR agonist in vivo.


MESH:C578008


MESH:C121999


CHEBI:76257


MESH:C117440


MESH:D064148

The study investigates the role of the mu-delta opioid receptor heterodimer (MDOR) in pain regulation. The researchers used a MDOR-selective antagonist, D24M, in mice models and found that it enhanced the pain-relieving effects of the opioid oxymorphone by 54.7% to 628%. This enhancement was not observed with other opioids like morphine or buprenorphine, suggesting a specific interaction with the MDOR. The study also found that the kinases Src and CaMKII, which were repressed by oxymorphone, were restored by D24M. The use of small molecule inhibitors confirmed the role of Src and CaMKII in D24M-enhanced pain relief. The findings suggest that MDOR acts as a negative feedback brake on opioid-induced analgesia and that antagonism of MDOR could improve clinical opioid therapy.


MESH:D064148


PUBCHEM.COMPOUND:53710962

The study investigated the effects of real and imagined acupuncture on the functional connectivity of the periaqueductal gray (PAG) and ventral tegmental area (VTA), key regions in the descending pain modulatory system and dopaminergic reward system. Real acupuncture decreased PAG-precuneus functional connectivity and increased VTA-amygdala/hippocampus functional connectivity. Changes in heat pain threshold were associated with these changes in functional connectivity. Imagined acupuncture, or video-guided acupuncture imagery treatment (VGAIT), also produced changes in functional connectivity in these areas, but through different pathways. These findings suggest that both real and imagined acupuncture can modulate pain and reward networks, potentially offering new methods for pain management.


PUBCHEM.COMPOUND:53710962


MESH:C523259

The study investigates the effects of morphine and naloxone on rats with hindpaw inflammation. The inflammation caused a decrease in wheel running and body weight. Morphine administration resulted in an increase in body weight and a gradual restoration of wheel running, particularly during the dark phase of the circadian cycle. However, morphine did not protect against opioid withdrawal. Naloxone administration depressed wheel running for about 4 hours and caused an increase in wet dog shakes, a symptom of opioid withdrawal. The effects of naloxone were no longer evident 6 hours after administration. The study supports the use of home cage wheel running as a method to assess changes in well-being due to pain, analgesia, and opioid withdrawal.


CHEBI:35482

The study evaluated the effectiveness of cognitive behavioral therapy (CBT) for chronic pain management and shared decision-making for prescription opioid dose reduction in pregnant women misusing opioids. The 8-week clinical trial involved 20 pregnant women aged 18 to 45 years who were misusing opioids but did not meet DSM-IV criteria for an opioid use disorder or other substance use disorder. The results showed significant reductions in average prescription opioid morphine equivalent dose, prescription opioid misuse, worst pain ratings, and pain interference in general activity and at work.


MESH:C523259


CHEBI:82760

The study investigates the activity of kratom alkaloids at serotonin receptors. The alkaloids paynantheine and speciogynine showed high affinity for 5-HT1ARs and 5-HT2BRs, unlike mitragynine. These alkaloids produced antinociceptive properties in rats through an opioid receptor-independent mechanism. The effects of paynantheine, speciogynine, and mitragynine were blocked by a selective 5-HT1AR antagonist. The in vivo 5-HT1AR agonistic effects may be due to the metabolites 9-O-desmethylspeciogynine and 9-O-desmethylpaynantheine, not the parent compounds. These metabolites did not activate 5-HT2BR, suggesting a low risk of causing valvulopathy. The 5-HT1AR agonism by kratom alkaloids may contribute to the mood-enhancing effects associated with kratom use.


CHEBI:46703


CHEBI:82760


MESH:C426083


MESH:C434786


MESH:C560330

The study investigates the impact of two medications for opioid use disorder (OUD), methadone and buprenorphine, on the risk of neonatal abstinence syndrome (NAS) in infants born to women with OUD. The findings suggest that infants exposed to methadone have a higher risk of NAS compared to those exposed to buprenorphine. Furthermore, buprenorphine-exposed infants showed a decreased risk for NAS compared to unexposed infants, although these associations were not statistically significant. The study suggests that buprenorphine may be a better option for treating OUD in pregnant women due to its potential to reduce the risk of NAS in newborns.


MONDO:0021698

The study developed patient-reported outcome measures for individuals receiving treatment for alcohol use disorder (AUD) and/or substance use disorder. The study found that past 30-day alcohol and/or opioid use at admission were correlated with worse self-reported physical and mental health, sleep, and quality of life, and greater negative affect and craving. Previous history of treatment and/or withdrawal management were associated with worse self-reported physical and mental health, quality of life, and increased craving. Physical and mental health improved across timepoints and was most pronounced when comparing persons receiving treatment for opioid use disorder versus AUD.


MONDO:0021698


MONDO:0002491


NCBIGene:4988

The study focuses on the mu opioid receptor gene, OPRM1, which is responsible for the action of opioid analgesics like morphine, fentanyl, and heroin. The OPRM1 gene undergoes extensive alternative splicing, creating multiple splice variants or isoforms. These variants are categorized into three major types based on the receptor structure. The study suggests that these OPRM1 splice variants play a significant role in mediating the distinct actions of various mu opioids. The OPRM1 variants can be targeted for the development of novel opioid analgesics that are potent against multiple types of pain, but devoid of many side-effects associated with traditional opiates.


NCBIGene:4988


CHEBI:35482


MESH:C520803

The study investigates the antinociceptive effects of Mitragynine (MTG), a major alkaloid in Kratom, and its active metabolite, 7-hydroxymitragynine (7HMG), in male and female C57BL/6 mice. The results show that 7HMG, despite having a higher affinity and efficacy at µ-opioid receptors than MTG, has a negligible role in the antinociceptive effects of MTG. This is due to the marked difference in the maximum brain concentration of 7HMG achieved when administered alone versus as a metabolite of MTG. The study also found that 7HMG was 2.8-fold more potent than MTG in producing antinociception when administered alone.


MESH:C000631585

has higher affinity and efficacy than MTG


MESH:C520803

achieves lower maximum concentration when metabolized into 7HMG


MESH:C000631585

is 2.8-fold more potent than MTG when administered alone


PR:000001612

The paper reviews strategies for developing safer opioid analgesics. The focus is on the μ opioid receptor, which is targeted by most clinically used analgesics. Activation of this receptor can lead to adverse effects such as respiratory depression, addiction, and abuse liability. The paper discusses various approaches to separate analgesic actions from adverse effects, including biased agonism, opioids targeting multiple receptors, allosteric modulators, heteromers, and splice variants of the μ receptor. The paper also highlights upcoming targets of interest for the development of safer analgesics.


PR:000001612


CHEBI:35480


CHEBI:48406


MESH:C406450

Nociceptin opioid peptide receptor (NOP)

The study aimed to determine the effectiveness of the nociceptin opioid peptide receptor (NOP) agonist Ro 64-6198 in producing antinociception and attenuating opioid self-administration in rats. The results showed that Ro 64-6198 produced dose- and time-dependent intracranial self-stimulation (ICSS) depression, which was blocked by the selective NOP antagonist SB612111 but not by naltrexone. However, Ro 64-6198 failed to block acid-induced depression of ICSS and did not attenuate heroin-vs-food choice. Therefore, the study concluded that Ro 64-6198 may not be useful as a stand-alone medication for either acute pain or opioid use disorder.


MESH:C406450


MESH:C527017

The study focuses on the development of peripherally acting μ opioid receptor antagonists (PAMORAs) for the treatment of opioid-induced constipation (OIC). A naltrexamine derivative, NAP, was previously identified as a potent and selective MOR antagonist. In this study, four compounds (2, 5, 17, and 19) were introduced with a highly polar aromatic moiety to decrease CNS MPO scores and reduce passive BBB permeability. Among these, compound 19 significantly improved GI tract motility by 75% during morphine-induced constipation, showing promise as an oral treatment for OIC.


MESH:C547644

The study investigates the pharmacology of kratom, focusing on its primary alkaloid, mitragynine, and its metabolite, 7-hydroxymitragynine. The research suggests that kratom and mitragynine have low efficacy agonist activity at the mu-opioid receptor, and can antagonize the effects of high efficacy mu-opioid agonists. The metabolite 7-hydroxymitragynine may have minimal involvement in the overall behavioral profile of mitragynine and kratom, but at high doses, it shares many of the same abuse- and dependence-related behavioral effects associated with traditional opioid agonists. The low efficacy of kratom and mitragynine at mu-opioid receptors supports their potential as safe medications for opioid use disorder.


MESH:C109363


MESH:C547644


MESH:C516146

The study investigates the safety and toxicology of the Oxy(Gly)4-sKLH Conjugate Vaccine, a potential treatment for opioid use disorders (OUD). The vaccine was tested on Sprague Dawley rats, with no observed toxicological findings related to the vaccine. The vaccine was well tolerated, induced high antibody titers, and did not produce undesired side effects, even at low doses.


MESH:C516146


MESH:C108985

The study investigates the activity of alkaloids from the tropical plant Mitragyna speciosa, or kratom, at serotonin G protein-coupled receptors (5-HT GPCRs). The alkaloids speciogynine and paynantheine, prevalent in kratom leaves, bind to serotonin 5-HT1ARs and 5-HT2BRs with affinities less than or equal to 100 nM. Their 9-O-desmethyl metabolites are efficacious agonists at 5-HT1ARs. The study also evaluates the potency and efficacy of kratom alkaloids to modulate the activity of unique G alpha subtypes linked to 5-HTRs. The 5-HT2BR is a crucial target for drug safety profiling as its activation can lead to cardiac valvulopathy. The study also tests kratom alkaloids with an appreciable 5-HT2BR affinity for their potential mitogenic activity in HEK cells.


CHEBI:22315


PR:000001167


CHEBI:22315

tested for potential mitogenic activity in


NCIT:C13239

The study investigates the use of multivalent vaccines as a strategy against polydrug use in opioid use disorders. The vaccines target fentanyl, carfentanil, oxycodone, heroin, and their analogs or metabolites. The vaccines are made up of haptens, small molecules that mimic the structure of the targeted drug, conjugated to carrier proteins like detoxified diphtheria toxin (CRM) or keyhole limpet hemocyanin (KLH). The study found that the quadrivalent vaccine increased fentanyl-, carfentanil-, oxycodone-, and heroin-specific IgG titers in immunized mice and prevented the distribution of these drugs to the brain. The individual efficacy of monovalent vaccine was preserved in a multivalent formulation without interference.


NCIT:C13239


CHEBI:23818

The study investigates the interaction between the opioid fentanyl and the 5-HT2A receptor agonist DOM in rhesus monkeys. The results show that DOM does not enhance the reinforcing effects of fentanyl, whether given as a pretreatment or in combination with fentanyl. However, DOM did reduce the choice of fentanyl at doses that also reduced trials completed, suggesting that the effects of DOM might be due to generalized rate-decreasing effects. The study concludes that combining a 5-HT2A receptor agonist with an opioid to treat pain would not increase potential for abuse.


PUBCHEM.COMPOUND:90477108


CHEBI:23818


MESH:D014612

The study investigates the use of monovalent and bivalent vaccination strategies to protect against the effects of carfentanil, fentanyl, and their mixtures. The vaccines were found to elicit polyclonal antibody responses that were effective in protecting against the pharmacological actions of these substances. A lead vaccine was identified that was protective against carfentanil-induced antinociception, respiratory depression, and bradycardia. Efficacy against both carfentanil and fentanyl was achieved through bivalent vaccination strategies that combined the lead anti-carfentanil and anti-fentanyl vaccines.


PUBCHEM.COMPOUND:90477108

The study investigates the efficacy of vaccines targeting fentanyl and its analogues, alfentanil, sufentanil, and acetylfentanyl, in the context of opioid use disorders (OUD) and overdose. The lead conjugate vaccine (F1-CRM) and a series of novel vaccines were tested in rats. The results showed that while no vaccine provided significant protection against alfentanil, the lead formulations were effective in reducing the pharmacological effects induced by fentanyl, sufentanil, and acetylfentanyl. Vaccination with F1-CRM also reduced drug levels in the brain of rats challenged with lethal doses of fentanyl.


PUBCHEM.COMPOUND:5302132


MONDO:0002494

The paper reviews the use of technologies to objectively measure sleep outcomes in randomized-controlled trials (RCTs) conducted in persons with substance use disorders (SUDs). The most common SUD was alcohol use disorder. The most common technology used to assess sleep was polysomnography, followed by actigraphy, ambulatory polysomnography or components of polysomnography (e.g., electroencephalography), and at-home sleep apnea testing. The most common sleep outcome reported was total sleep time. The study suggests that polysomnography or ambulatory devices that directly measure brain activity are critical to advance medications through the regulatory process for the indication of improving sleep duration, continuity, and/or sleep onset latency outcomes.


MONDO:0002046


MONDO:0005296


MONDO:0002494

The paper is a systematic review of randomized-controlled trials (RCTs) that have studied patient-reported sleep outcomes in individuals with substance use disorders (SUDs). The review found that sleep disturbances are a common issue in people recovering from SUDs. The most commonly used measures for assessing sleep quality in these trials were the Pittsburgh Sleep Quality Index, the Insomnia Severity Index, and sleep diaries. The authors suggest that the field of addiction medicine could benefit from a more streamlined approach to assessing patient-reported sleep in RCTs.


UNII:5E7U48495E

The study investigates the acute effects of the glucagon-like peptide-1 (GLP-1) analog, liraglutide, on heroin-seeking behavior in rats. The findings suggest that a single subcutaneous dose of 0.3-mg/kg liraglutide effectively prevents drug-seeking behavior triggered by drug-associated cues, stress (induced by yohimbine), and the drug itself. The study also confirmed that the reduction in drug-seeking behavior is not due to a locomotor impairment, as liraglutide did not significantly alter performance in a rotarod test. Therefore, acute use of GLP-1 analogs may serve as a new and effective nonopioid bridge to treatment.


PR:000008476

The study investigated the effects of suvorexant, a dual-orexin receptor antagonist, on sleep and withdrawal symptoms during a buprenorphine/naloxone taper in individuals with opioid use disorder. The results showed that participants who received suvorexant had increased total sleep time during the taper and decreased opioid withdrawal symptoms post-taper. There was no evidence of abuse potential. The findings suggest that suvorexant could be a promising treatment for sleep disturbances and opioid withdrawal in individuals undergoing a buprenorphine/naloxone taper.


MESH:D000077182

The study focuses on the challenges of scaling up the manufacturing of PLGA microparticles from benchtop-scale formulation to larger clinical scale batches. The researchers examined the in vitro and in vivo performance of a long-acting naltrexone formulation, noting that minor changes in the initial formulation and processing parameters can significantly affect the performance of the microparticles. The study found that while there were slight differences in the in vitro release profiles and particle morphologies, the in vivo pharmacokinetics were similar, suggesting that scale-up production with the same drug release kinetics can be achieved by controlling the formulation and processing parameters.


MESH:D001592


MESH:C502494


PR:000001612

The study investigates the effects of age and sex on opioid signaling in the ventrolateral periaqueductal gray (vlPAG) in rats with chronic inflammatory pain. The results show that adult male rats have the highest μ-opioid receptor (MOR) binding potential and G-protein activation efficiency compared to aged males and females. No significant impact of age or sex on MOR phosphorylation state was observed. However, DAMGO-induced cAMP inhibition was highest in adult males compared to aged males and females. The study also found that adult rats exhibited lower levels of vlPAG RGS4 and RGS9-2 mRNA expression compared to aged rats. These findings suggest potential mechanisms for the decreased potency of opioids in the aged population.


MESH:C438305


NCBIGene:5999


NCBIGene:19739


PUBCHEM.COMPOUND:44151929

The study investigates the metabolism of Speciociliatine, an alkaloid found in Kratom (Mitragyna speciosa), which is used for pain relief, opioid dependence, mood enhancement, and energy boosting. Speciociliatine is a partial µ-opioid agonist with a higher binding affinity than mitragynine. The metabolism of Speciociliatine was studied in human and preclinical species (mouse, rat, dog, and cynomolgus monkey) liver microsomes and hepatocytes. It was found that Speciociliatine metabolizes rapidly in monkey, rat, and mouse hepatocytes, while slower metabolism was observed in human and dog hepatocytes. The metabolism of Speciociliatine was predominantly mediated by CYP3A4 with minor contributions by CYP2D6.


PUBCHEM.COMPOUND:44151929


NCBIGene:2740

Glucagon-like peptide-1 receptor (GLP-1R)

The study investigates the effects of the glucagon-like peptide-1 receptor (GLP-1R) agonist, liraglutide, on fentanyl seeking behavior in rats. The results show that acute treatment with liraglutide can reduce both cue-induced and drug-induced fentanyl seeking in rats. This suggests that GLP-1, a known satiety signal, may serve as an effective non-opioid alternative for the treatment of Opioid Use Disorder (OUD).


UNII:5E7U48495E


UniProtKB:P13508


UNII:5E7U48495E

has similar efficacy in reducing fentanyl seeking


UNII:5E7U48495E

The study investigates the use of the glucagon-like peptide-1 receptor agonist (GLP-1RA), liraglutide, in reducing heroin seeking behavior in rats. The results show that a titration regimen of liraglutide effectively reduces both cue-induced and drug-induced reinstatement of heroin seeking, especially in rats with a history of high drug-taking. This treatment regimen had no effect on either circulating glucose or insulin. Therefore, GLP-1RAs appear to be strong candidates for non-opioid prevention of relapse to opioids.


MESH:C502494

The study investigates the effect of particle size on the solid-state properties of naltrexone in PLGA microparticles. It was found that as the particle size increases, the crystallinity of naltrexone also increases, with additional polymorphic forms more readily noted at larger particle sizes. During dissolution, a polymorphic transition and/or crystallization occurs at larger size fractions. The study emphasizes the importance of controlling manufacturing parameters during microparticle formation, specifically solvent extraction and particle size control.


MESH:C547644

The study investigates the effects of the primary kratom alkaloid mitragynine and its metabolite 7-hydroxymitragynine, which are proposed to act through µ-opioid receptors (MORs) and adrenergic-α 2 receptors (Aα 2Rs). The research found that mitragynine displayed binding affinity at both receptors, while 7-hydroxymitragynine only displayed MOR binding affinity. The study suggests that mitragynine and 7-hydroxymitragynine may produce antinociceptive synergism with Aα 2R and MOR agonists. Additionally, when combined with Aα 2R agonists, mitragynine could also produce hypothermic synergism.


MESH:C547644


MESH:C109363


MESH:C547644

produces antinociceptive synergism when combined


MESH:C502494

The study used a new characterization method called surface analysis of (semisolvent) vapor impact (SAVI) to analyze the release of naltrexone from Poly(lactide-co-glycolide) (PLGA) microparticles. The SAVI method was applied to both internally manufactured naltrexone-loaded microparticles and a commercial formulation, Vivitrol. The results indicated that the release of naltrexone was primarily controlled by the formation of self-crystallized portions of naltrexone within the PLGA structure and the degradation of PLGA chains. The presence of higher amounts of naltrexone crystals resulted in prolonged release compared to lower amounts of crystals.


MESH:C502494


MESH:C489708


MESH:D001060

The study designed and synthesized four sets of diastereomeric C9-alkenyl 5-phenylmorphans to examine their effect on opioid receptors. The study found that the length of the C9-alkenyl chain and stereochemistry of these compounds influenced their activity. Three MOR antagonists were found to be as or more potent than naltrexone and did not have MOR, KOR, or DOR agonist activity. Several potent MOR full agonists were also identified. Some partial agonists were found to cause less respiratory depression than morphine. Molecular modeling was used to explore the effect of stereochemistry and the length of the C9-alkenyl chain.


MESH:D009022


CHEBI:35482


CHEBI:72588


MESH:C477015

The study investigates the effects of 2,5-dimethoxy-4-methylamphetamine (DOM) and 2-piperazin-1-yl-quinoline (quipazine), both serotonin 2A subtype (5-HT2A) receptor agonists, on the reinforcing effects of fentanyl in rhesus monkeys. The results showed that neither DOM nor quipazine significantly altered fentanyl choice, suggesting that 5-HT2A receptor agonists do not enhance the reinforcing effects of opioids and will not likely enhance abuse potential.


MESH:C108948


PUBCHEM.COMPOUND:90477108


NCIT:C138901

The study found that in people with hand osteoarthritis (OA), a higher body mass index (BMI) is associated with greater pain severity in the hands, feet, and knees/hips. This association is partially mediated by the systemic inflammatory biomarkers leptin and high-sensitivity C-reactive protein (hsCRP). The effects of BMI on hand pain and total body joint count were found to be partially mediated by leptin and hsCRP respectively. The mediating role of leptin was found to be larger for pain in the hands than in the lower extremities.


NCIT:C138901


PR:000009758


NCIT:C138901

High-sensitivity C-reactive protein (hsCRP)


NCBIGene:1401

High-sensitivity C-reactive protein (hsCRP)


MESH:C091498

The study found that the receipt of naloxone rescue kits among people with HIV (PWH) on chronic opioid therapy (COT) was uncommon. A history of overdose was associated with receiving naloxone, but having a clinician who reported providing overdose prevention care was not. The study suggests that clinicians prescribing COT to PWH should improve overdose prevention care, including naloxone co-prescribing.


NCIT:C41362


CHEBI:35482

The study explores community-based perspectives on efforts to change opioid prescribing practices to reduce opioid overprescribing, and ultimately reduce prescription opioid use disorder, overdoses and fatalities. The study identified three major themes: acknowledging progress, emergent challenges, and opportunities for change. The opportunities for change included culture change around pain expectations, awareness of safe disposal, additional provider education, and increased coverage and acceptability of non-opioid treatments.


CHEBI:35482

Medications for opioid use disorder (MOUD)

The HEALing Communities Study (HCS) aims to develop and test an intervention, Communities That HEAL (CTH), to support communities in implementing evidence-based practices (EBPs) to reduce opioid-involved overdose deaths. The CTH intervention is being implemented in 67 communities across four states. The community coalitions must select at least five strategies, including overdose education and naloxone distribution, access to medications for opioid use disorder (MOUD), linkage to MOUD, retention in MOUD, and safer opioid prescribing/dispensing. The selection process is facilitated by decision aid tools and focuses on feasibility, appropriateness within the community context, and potential impact on reducing opioid-involved overdose deaths.


MONDO:0001225

The study estimates the prevalence of opioid use disorder (OUD) in Kentucky in 2018 and 2019 using a multi-sample capture-recapture analysis. Four statewide datasets were used: Registry of Vital Statistics, Emergency Medical Services (EMS), Kentucky's Prescription Drug Monitoring Program (PDMP), and Kentucky Medicaid. The estimated statewide OUD prevalence was 5.5% and 5.9% for 2018 and 2019, respectively, with a range of 1.3% to 17.7% across Kentucky counties. The highest OUD rates were found in Appalachian counties (eastern area) of the state. The study reveals a larger proportion of Kentucky residents have OUD than previously estimated.


MONDO:0001225


CHEBI:30879

The study investigates the impact of prenatal substance exposure (alcohol, opioids) on infant self-regulation and emotional reactivity. The study involved 100 mother-child dyads and used the Still Face Paradigm (SFP) to assess infant stress reactivity and self-regulation. Infants were grouped based on their prenatal exposure: unexposed controls, alcohol-exposed, opioid-exposed, and both MOUD and alcohol exposed. The results showed that the group exposed to both MOUD and alcohol had significantly lower self-regulation at baseline compared to controls. Higher self-regulation was associated with lower negative affect in the MOUD+Alcohol group but not other groups. This suggests that self-regulation skills are particularly important for emotional modulation in infants with prenatal polysubstance exposure.


CHEBI:35482


MESH:C085585


GO:0140729


MONDO:0005566

Neonatal opioid withdrawal syndrome (NOWS)

The study found that infants with neonatal opioid withdrawal syndrome (NOWS) had higher healthcare utilization in their first year of life, especially those with severe NOWS. The severity of NOWS was associated with an increase in composite one-year utilization. In a subset of full-term infants, having a NOWS diagnosis was associated with higher odds of a 30-day and one-year rehospitalization.


MONDO:0005566


CHEBI:35482

The study investigates the effects of prenatal opioid exposure on the development of brain networks in infants. Using resting-state functional connectivity MRI (rsfMRI), the researchers found that opioid-exposed infants had differences in the distribution of betweenness centrality and connection length, with unique connections in the opioid-exposed group being more often inter-network connections. The opioid-exposed group also had smaller network volumes, particularly in the primary visual network, but similar network strength as controls. The network topologies were different between groups, especially in visual and executive control networks. These findings may explain the developmental and visual problems associated with prenatal opioid exposure.


CHEBI:35482

Neonatal opioid withdrawal syndrome (NOWS)

The study evaluated the severity of neonatal opioid withdrawal syndrome (NOWS) in infants exposed prenatally to medications for opioid use disorder (MOUD) and serotonin reuptake inhibitors (SRI). The study found that infants in the MOUD + SRI group were more likely to require pharmacologic treatment for NOWS and had a longer hospitalization compared to the MOUD group. The use of SRIs among pregnant women on MOUD might be associated with more severe NOWS, suggesting a potential drug-drug interaction between maternal SRIs and opioid medications that inhibit the reuptake of serotonin.


CHEBI:35941


CHEBI:35482

The paper discusses the combined effects of maternal opioid use during pregnancy and a history of childhood adversity (CA) on the neurodevelopment of the offspring. The study emphasizes that these factors often co-occur and may interact to influence brain development in utero. The paper suggests that these factors could have cumulative effects on offspring neurodevelopment, but more research is needed to understand the specific mechanisms involved.


NCBIGene:406916

The study found that the expression of certain extracellular microRNAs (miRNAs) in the umbilical cord plasma of infants exposed to opioids prenatally can predict the severity of neonatal opioid withdrawal syndrome (NOWS). Specifically, the miRNAs miR-128-3p, miR-30c-5p, and miR-421 predicted the need for pharmacologic treatment and prolonged hospitalization. The predictive validity improved when miRNAs let-7d-5p, miR-584-5p were added to the model for pharmacologic treatment and miRNAs let-7b-5p, miR-10-5p were added to the model for prolonged hospitalization.


NCBIGene:407031


NCBIGene:693122


NCBIGene:406886


NCBIGene:693169


NCBIGene:406884


NCBIGene:406902


CHEBI:35482

Medication for opioid use disorder (MOUD)

The study investigates the effects of prenatal opioid/other drug exposure (PODE) and the benefits of medication for opioid use disorder (MOUD) on neonatal brain functional organization. The study found that PODE neonates showed alterations in reward-related frontal-sensory connectivity. However, MOUD was associated with a significant reduction of PODE-related alterations in key regions of endogenous opioid pathways including limbic and frontal connections. Despite this, significant residual effects in limbic and subcortical circuitry were observed. The study concludes that MOUD confers significant normalization effects on functional connectivity of regions associated with socioemotional development and reward processing, highlighting the importance of MOUD intervention for better neurodevelopmental outcomes.


CHEBI:35482

Functional connectivity of regions associated with socioemotional development and reward processing


CHEBI:35482

The study investigates the neural effects of prenatal opioid exposure on infants. Using MRI scans and machine-learning methods, the researchers constructed edge-centric functional networks to identify neural features distinguishing opioid-exposed infants from unexposed controls. The results showed that prenatal opioid exposure primarily affects inter-network dynamic functional connections, particularly with the visual, subcortical, and default mode networks. These findings may explain the higher rates of visual and emotional problems observed in infants exposed to opioids in utero.


CHEBI:35482

exposure results in smaller brain measurements

The study investigated the impact of in utero opioid exposure on fetal brain development. It was found that opioid-exposed fetuses had smaller measurements in seven areas of the brain, including cerebral frontooccipital diameter, bone biparietal diameter, brain biparietal diameter, corpus callosum length, vermis height, anteroposterior pons measurement, and transverse cerebellar diameter. Additionally, the frontoocccipital index was larger in opioid-exposed fetuses. There were no significant differences in fetal motion, cervical length, and deepest vertical pocket of amniotic fluid between the groups. However, opioid-exposed fetuses showed higher frequencies of breech position and increased amniotic fluid volume.


CHEBI:35482


MONDO:0004375

The paper discusses the challenges of managing pain in patients with end-stage kidney disease (ESKD). Pain is a common symptom in ESKD patients and negatively affects their quality of life, dialysis adherence, healthcare utilization, and mortality. The limited availability of effective and safe non-opiate analgesics has resulted in the overuse of opioids. The authors propose a framework for pain assessment and treatment using nonpharmacological and pharmacological approaches to optimize pain management and opioid use. They also recommend system-level changes to improve care coordination and pain management in ESKD patients.


CHEBI:35482

should be minimized due to increased adverse events

The paper reviews pain management strategies for patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD). It emphasizes the use of physical activity and nonpharmacologic therapies, along with pharmacological therapies like nonopioid analgesics (acetaminophen, topical analgesics, gabapentinoids, serotonin-norepinephrine reuptake inhibitors, and TCA). NSAIDs can be used for short durations with careful monitoring. Opioid use should be minimized and reserved for patients who have failed other therapies due to their association with increased adverse events. Safer opioids for kidney disease include oxycodone, hydromorphone, fentanyl, methadone, and buprenorphine, with buprenorphine being a promising option due to its partial agonism at the mu opioid receptor.


MESH:C560330

The paper discusses the prevalence of chronic pain in adults undergoing maintenance haemodialysis (HD) for kidney failure. It is reported that 50-80% of these patients experience pain, with half of them experiencing moderate-to-severe chronic pain. The paper also discusses the use of opioid analgesics in managing this pain, noting that they are prescribed more frequently for patients receiving HD than for the general population with chronic pain. However, the effectiveness of opioids in managing pain in these patients is not well established. The paper also discusses the potential use of buprenorphine as an analgesic option for these patients due to its unique pharmacological properties.


MONDO:0005300

The paper discusses the prevalence of moderate to severe pain in patients with chronic kidney disease (CKD), maintenance dialysis, and kidney transplant. It highlights the impact of comorbid depression and anxiety, which can lead to maladaptive coping responses such as pain catastrophizing and illness-related post-traumatic stress disorder. These conditions, if untreated, can lead to increased perception of pain, worsened disability, decreased quality of life, social withdrawal, and increased morbidity and mortality. The paper also discusses the potential of nonpharmacologic treatments for pain, which target coping mechanisms as well as comorbid anxiety and depression. The paper calls for more research into these treatments in the context of CKD and end-stage kidney disease.


MONDO:0002050


MONDO:0005146


MONDO:0005133

The study investigates the incidence of persistent pelvic pain following hysterectomy in women with chronic pelvic pain. It was found that 11.9% of the participants reported persistent pelvic pain 6 months after the surgery. Factors such as endometriosis and uterine fibroids were associated with a higher incidence of persistent pain. However, the surgical route, pelvic adhesions, uterine weight, and adenomyosis were not related to the risk of persistent pain. The study also found that higher preoperative centralized pain scores were more common in women with persistent pelvic pain. Every 1-point increase in centralized pain before hysterectomy was associated with a 27% increase in the odds of persistent pelvic pain 6 months after surgery.


MONDO:0001664


NCIT:C96210


CHEBI:59163

The Acute to Chronic Pain Signatures (A2CPS) Program is a multi-site observational study that aims to identify biomarkers and biosignatures that can predict an individual's susceptibility or resilience to developing chronic pain after surgery. The study focuses on patients undergoing knee arthroplasty and thoracic surgery. Biomarkers are evaluated before and up to three months after surgery to predict patient outcomes six months post-surgery. The data from this study will be available for further research into the transition from acute to chronic postsurgical pain.


GO:0032501


MESH:C560330

The study compared the long-term criminal justice outcomes among opioid-dependent individuals who were randomized to receive either buprenorphine/naloxone or methadone. The study found no significant difference in the proportion of arrests or incarcerations between the two groups. However, continued treatment with either buprenorphine or methadone was associated with a reduction in arrests relative to no treatment. Factors such as cocaine use, injection drug use, Hispanic ethnicity, and younger age were associated with a higher likelihood of arrest.


MESH:C091498


MESH:D016578


MONDO:0001225

The study investigates the opioid crisis in rural northern New England, focusing on eleven counties in Massachusetts, New Hampshire, and Vermont from 2014 to 2018. The research characterizes the epidemiology, policy, and resource environment for opioid use disorder (OUD) and its consequences. The study found that Vermont's comprehensive drug treatment and harm reduction policies were associated with the lowest fatal overdose rates. Franklin County, Massachusetts had good access to naloxone, drug treatment, and SSPs, but high overdose and HIV rates. New Hampshire had high proportions of uninsured community members, the highest overdose rates, no HCV surveillance data, and no local access to SSPs, placing PWID in rural New Hampshire at elevated risk.


MONDO:0001225