CHEBI:30879

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:D062789


UMLS:C1456651


UMLS:C0242402


UMLS:C0701445

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X-waiver, a special credential required for clinicians to prescribe buprenorphine in the United States, will likely be repealed.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.


UMLS:C0701445


UMLS:C0001956

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.


UMLS:C4505254


CHEBI:30879


UMLS:C0939898


UMLS:C0596349

The paper discusses a multi-site randomized trial of an integrated care model for patients hospitalized with infections and opioid use disorder (OUD). The model combines the use of long-acting injectable buprenorphine (LAB) with infectious disease treatment. The study aims to test the effectiveness of this model, where infectious diseases and OUD are managed by infectious disease specialists and hospitalists using LAB. The primary outcome measure is the proportion of patients enrolled in effective medication treatment for OUD (MOUD) 12 weeks after randomization. Secondary outcomes include relapse to opioid use, adherence to infectious disease treatment, infection morbidity and mortality, and drug overdose.


UMLS:C0814470


UMLS:C0586873


UMLS:C0600620


UMLS:C0355800

The study analyzed the cost-effectiveness of extended-release naltrexone (XR-NTX) compared to buprenorphine-naloxone (BUP-NX) for preventing opioid relapse. The requirement for opioid detoxification before initiating XR-NTX resulted in lower initiation rates. However, the study found that the treatment site was a modifiable factor that could increase the likelihood of XR-NTX induction and decrease induction duration. By incorporating these factors, the incremental average 24-week total cost of XR-NTX treatment was reduced, making XR-NTX and BUP-NX of comparable economic value for patients seeking treatment for opioid use disorder at an inpatient detoxification facility.


UMLS:C2827983

Extended-release naltrexone (XR-NTX) induction

increases likelihood and decreases duration


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


CHEBI:30879

The study compared different methods of screening for alcohol and drug use in primary care clinics. The research found that electronic health record (EHR)-integrated screening was feasible to implement in all clinics. Screening at any visit, as opposed to only at annual examinations, was associated with higher screening rates for alcohol and drug use. Self-administered screening had a higher detection rate for moderate- to high-risk alcohol use compared to staff-administered screening. However, the detection of drug use was low across all clinics, as was clinician adoption of counseling.


UMLS:C2183194


UMLS:C2362543


UMLS:C1444711

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.


UMLS:C0337664


UMLS:C2188855


UMLS:C3160814


UMLS:C0355800

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.


UMLS:C1320105


UMLS:C1626306

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.


UMLS:C4324621

The study found that individuals with opioid use disorder (OUD) who were treated with extended-release naltrexone (XR-NTX, an opioid antagonist) smoked fewer cigarettes per day compared to those treated with buprenorphine (BUP-NX, a partial opioid agonist). This suggests that XR-NTX, in combination with other smoking cessation interventions, might be a better choice for OUD patients interested in reducing their tobacco use.


UMLS:C0355800


UMLS:C5451882


UMLS:C1144854

The study provides evidence that the implementation of a syringe services program (SSP) in Miami, Florida, led to a reduction in injection risk behaviors among people who inject drugs. The study found that men were more likely to reuse syringes, while those who reported injecting in public were less likely to do so. Hepatitis C virus (HCV)-positive clients showed a 62% reduction in sharing injection equipment, while those who reported public injection had a 62% increase in sharing injection equipment over time. Increasing syringe coverage was associated with a decrease in both sharing injection equipment and reusing syringes. The study suggests that improving syringe coverage among SSP clients may be an important factor in reducing behaviors that place individuals at risk for contracting HIV and HCV.


UMLS:C1144854


UMLS:C0562508

The study evaluated the effectiveness of initiating opioid use disorder (OUD) treatment in the emergency department (ED) and its impact on patient engagement in follow-up addiction care. The study found that young, white, male patients were most likely to receive ED-OUD care. Patients who received ED-OUD care were more likely to have subsequent treatment engagement. However, referrals were made less often for Black or Hispanic/Latinx patients. The initiation of treatment for OUD in the ED was associated with increased engagement in outpatient addiction care.


UMLS:C0562508


UMLS:C0237154

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.


UMLS:C0237154


UMLS:C0401946


HP:0012531


UMLS:C5230801

Emergency department-initiated buprenorphine (EDIB)

The study investigates the effectiveness of emergency department-initiated buprenorphine (EDIB) in treating patients with opioid use disorder (OUD). The study found that 77.0% of patients attended their first referral appointment and 43.1% were retained in treatment after 30 days. The average time in treatment was 158 days. The majority of patients were male, white, and uninsured. Most patients reported no substance use other than opioids. The study concludes that EDIB programs are effective in promoting initial attendance for OUD treatment, but more work is needed to improve 30-day retention rates.


UMLS:C0162648

The COVID-19 pandemic has affected the delivery of treatment for substance use disorders (SUDs) in California, as observed by service providers. Initially, there was a slight decrease in patient admissions, but this was followed by an increase due to heightened mental health issues, alcohol use, and relapse. Clinics adapted by implementing flexible service delivery methods, such as curbside dosing and extended take-home medication, to facilitate social distancing. Telemedicine became a significant part of patient care, with many patients preferring telephone-based services over video-based ones. However, internet instability and technical difficulties limited the use of telemedicine. Despite the challenges, the health care systems quickly adjusted, potentially leading to long-term changes in SUD service delivery.


UMLS:C0162648


UMLS:C0772354

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.


UMLS:C4324621


UMLS:C0701445

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.


UMLS:C0701445


UMLS:C0700549

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


UMLS:C0556616


UNII:34969JX79R


UMLS:C0282233


MONDO:0005231

The study conducted a randomized clinical trial on individuals with Hepatitis C virus (HCV), Human Immunodeficiency Virus (HIV), and substance use to assess the effectiveness of care facilitation in advancing their movement along the HCV/HIV care continuum. The care facilitation group received motivation and strengths-based case management, while the control group received referral to HCV evaluation and assistance in making care appointments. The results showed that the care facilitation group completed a significantly higher number of steps along the HCV/HIV care continuum compared to the control group, particularly among men. However, there was no significant difference in achieving sustained virologic response (SVR) between the two groups.


UMLS:C0946431


UMLS:C4535971


UMLS:C0701445

The study investigates the retention rate in Opioid Agonist Therapy (OAT) among patients with Opioid Use Disorder (OUD), both with and without HIV. Data from the Veterans Aging Cohort Study was used, and it was found that 13.7% of 7,334 patients with OUD initiated OAT, with 27.8% retained after 12 months. The likelihood of initiation and retention did not vary with HIV status. Factors associated with improved retention included receiving buprenorphine (as opposed to methadone), receiving both buprenorphine and methadone at some point, or having a diagnosis of HCV. A history of homelessness was linked to lower retention. The predictors of retention varied between patients with and without HIV.


PUBCHEM.COMPOUND:643985


MONDO:0005231


UMLS:C0237154


UMLS:C4324621

patients with entity_1 are referred to entity_2

The study developed and validated a Markov model to estimate the impact of Addiction consult services (ACS) on 12-month mortality among hospitalized patients with opioid use disorder (OUD). The model was populated using Oregon Medicaid data and validated using international modeling standards. The results showed that 4% of patients were referred to an ACS, and 47% of those engaged in post-discharge OUD care. The risk of drug-related death at 12 months among patients in post-discharge OUD care was 3%, versus 6% not in care. The risk of non-drug related death was 7% among patients in post-discharge OUD treatment, versus 9% not in care.


UMLS:C5229475

patients referred to entity_1 engage in entity_2


UMLS:C3515061


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


MONDO:0002009


UMLS:C4324621


UMLS:C1140263

The Methadone Access Research Task Force, convened by the National Institute on Drug Abuse Center for Clinical Trials Network, has identified six areas of research to expand and create more equitable access to methadone treatment for opioid use disorder (OUD) in the US. These areas include access to methadone in general medical and outpatient settings, the impact of methadone treatment setting on patient outcomes, the impact of treatment structure on outcomes in patients receiving methadone, the comparative effectiveness of different medications to treat OUD, the optimal educational and support structure for provision of methadone by medical providers, and the benefits and harms of expanded methadone access. The task force also identified cross-cutting issues such as the impact of patient characteristics, treatment, and treatment system characteristics.


UMLS:C1513884

National Institute on Drug Abuse Center for Clinical Trials Network


UMLS:C1521970


UMLS:C1960222


UMLS:C5191291

improves treatment outcome when combined with buprenorphine

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.


UMLS:C5191291

improves treatment outcome when combined with buprenorphine for opioid use disorder


UMLS:C0701445

used in treatment of co-occurring opioid use disorder


UMLS:C4505167

The study evaluated the effectiveness of the Prescription Drug Monitoring Program (PDMP)-based Narcotic Score (NS) metric in identifying risky opioid medication use. The NS metric was compared to the WHO Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST). The NS metric showed fair concurrent validity and was able to categorize participants into low-risk and moderate/high-risk groups. However, there were instances of false positives and negatives. The NS metric could be a useful initial universal prescription opioid-risk screener due to its low-burden, high accuracy, and broad availability.


UMLS:C0374142


UMLS:C0374142

WHO Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST)


UMLS:C0355800

The study compared the effectiveness of extended-release naltrexone (XR-NTX) and buprenorphine-naloxone (BUP-NX) in reducing drinking in patients with opioid use disorder (OUD). Both treatment groups showed a reduction in drinking from baseline to posttreatment, but no significant differences were observed between the groups. The hypothesis that XR-NTX would be superior to BUP-NX in reducing drinking was not supported.


UMLS:C1320105


UMLS:C2718080

The study explores the feasibility and acceptability of using mobile health (mHealth) platforms to electronically collect patient reported outcomes (PROs) from emergency department (ED) patients with non-medical opioid use. The study found that 78% of eligible patients consented to participate, and 95% of these completed registration in the mHealth platform. However, more than half of the participants were lost to follow-up after hospital discharge at 30 days. The study suggests that efforts to streamline communication and remove barriers to engagement are needed to improve the collection of PROs and pathways of care in ED patients with opioid use disorder (OUD).


UMLS:C1997897


UMLS:C0562508


UMLS:C4324621

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.


UMLS:C4324621


UMLS:C2138386

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.


UMLS:C2138386


UMLS:C0038586

showed smaller decline in visits during COVID-19

The study analyzed trends in emergency department (ED) visits for substance use disorders (SUDs) during the COVID-19 pandemic using a national emergency medicine registry. The study found that while overall ED visits declined during the early pandemic period, visits for SUDs showed smaller declines and even increased above baseline for opioid use disorder (OUD) since May 2020. This suggests the crucial role of EDs in providing care for people with SUDs and mental health conditions, particularly during the pandemic.


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.


UMLS:C0038586


UMLS:C4324621

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.


UMLS:C2186507

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.


UMLS:C0814544

Traditional healing and cultural identity


UMLS:C0814544


UMLS:C0701445

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.


PUBCHEM.COMPOUND:643985


UMLS:C0242402

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).


UMLS:C0242402


UMLS:C3871131

The study investigates the impact of interdisciplinary primary care (IPC) on health care utilization trends among veterans with addiction, social determinants of health, or other vulnerabilities. The study found that enrollment in an IPC clinic model was associated with overall reductions in emergency department (ED), inpatient, and behavioral health visits, and increases in primary care. The study also found that the IPC model of care reduces acute care and behavioral health service use, particularly for patients with historically high ED use.


UMLS:C3871131


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.


UMLS:C0440474

associated with better response to treatment


UMLS:C3840489


UMLS:C1320105


UMLS:C5556427


UMLS:C0242402

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).


CHEBI:30879

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.


UMLS:C0682884


MESH:D062789


UMLS:C0701445

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.


UMLS:C0031831


UMLS:C0401998


UMLS:C0242402

The study developed a prescription opioid registry across 10 diverse health systems in the US, tracking trends in prescribed opioids from 2012 to 2018. The registry includes data on prescription opioids, benzodiazepines, other select medications, opioid antagonists, clinical diagnoses, procedures, health services utilization, and health plan membership. The registry showed a decline in opioid fills from 0.718 per member-year in 2013 to 0.478 in 2018, and a decrease in morphine milligram equivalents (MMEs) per fill from 985 MMEs in 2012 to 758 MMEs in 2018. The registry will be used in future studies to address public health issues related to prescription opioid use.


PUBCHEM.COMPOUND:134664


UMLS:C3850135


UMLS:C0591830


UMLS:C4324621

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.


UMLS:C4324621


UMLS:C0360114

The study investigated the prevalence of polysubstance use in individuals undergoing treatment for opioid use disorder and its impact on treatment outcomes. The study found that pretreatment sedative use and cocaine use during the initial weeks of treatment were associated with an increased likelihood of opioid relapse. However, the effect of cocaine use was not significant when confounding by opioid use was considered. Sedative use during the initial weeks of treatment was also associated with increased opioid craving. No other significant relationships were found.


UMLS:C0282108


UMLS:C0360114


UMLS:C0701445

discontinuation after 91-180 days increases risk of

The study investigates the association between the duration of buprenorphine treatment and mortality rates among patients who discontinued the treatment. The study found that there is no specific treatment duration period that is associated with a reduced risk for all-cause mortality. However, patients who discontinued buprenorphine treatment after 91-180 days appear to be at a heightened risk for opioid overdose compared to patients who discontinue after more than 365 days of treatment.


UMLS:C0701445

no specific treatment duration reduces risk of


UMLS:C0242402

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.


UMLS:C0242402


UMLS:C0242402

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.


UMLS:C0701445

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.


UMLS:C0355800


UMLS:C0235196

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.


UMLS:C0038586


UMLS:C0556616


UMLS:C0013529

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).


UMLS:C2735026


UMLS:C2735026

prescribe more after Project ECHO training


UMLS:C0013529

Medication for opioid use disorder (MOUD)


UMLS:C4324621

The paper discusses a clinical trial designed to improve the identification and treatment of opioid use disorder (OUD) in primary care settings. The trial involves a shared decision-making (SDM) system that alerts primary care clinicians (PCCs) and patients to the risk of OUD and supports screening and treatment. The system provides guidance on OUD screening, diagnosis, treatment selection, and the use of buprenorphine for treatment. The primary outcome of the study is the percentage of high-risk patients receiving an OUD diagnosis within 30 days of their initial visit. Additional outcomes include the percentage of high-risk or diagnosed OUD patients receiving a naloxone prescription or a medication for OUD (MOUD) prescription, and the total days covered by a MOUD prescription within 90 days of an initial visit.


UMLS:C0700549


UMLS:C0127798

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.


UMLS:C0127798


UMLS:C0556616

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.


UMLS:C1197867

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.


UMLS:C1197867


UMLS:C5204562

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


PUBCHEM.COMPOUND:4688

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.


PUBCHEM.COMPOUND:5288826


PUBCHEM.COMPOUND:4688


UMLS:C0355800


UMLS:C0127798

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.


UMLS:C1829838

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.


UMLS:C1829838


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


UMLS:C0729169


UMLS:C0949270

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.


UMLS:C0162648

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.


UMLS:C0993671


UMLS:C4324621


UMLS:C0127798

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).


UMLS:C0127798


UMLS:C0242402

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


UMLS:C1098081


UMLS:C0457949

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.


UMLS:C0457949


UMLS:C1405033


UMLS:C5699812

The paper discusses the need for improved models of pain management, highlighting the limitations of opioids as frontline analgesics due to their undesirable effects such as abuse liability and respiratory depression. The authors suggest a paradigm shift in the pharmacotherapy of pain management, emphasizing the role of behavioral scientists in developing these new models. They critique the current models for their overreliance on simple reflex-based measures and suggest that new approaches should focus on the restoration of operant and other CNS-mediated behavior under painful conditions.


UMLS:C0394664

The study investigates the effects of acupuncture on chronic low back pain (cLBP). It was found that acupuncture can modulate the resting state functional connectivity (rsFC) of the periaqueductal gray (PAG) and ventral tegmental area (VTA) in patients with cLBP. The study also found that real acupuncture can increase VTA/PAG rsFC with the amygdala, and this increased rsFC was associated with decreased pain bothersomeness scores. The baseline PAG-amygdala rsFC could predict the four-week treatment response. The findings suggest that acupuncture may modulate key regions in the descending pain modulation and reward systems, and the amygdala may be a key node linking the two systems to produce antinociceptive effects.


UMLS:C0394664


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

does not depress under normal air conditions


MESH:C548959

causes in squirrel monkeys under certain conditions


UMLS:C0394664

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


UMLS:C3489631

Video-guided acupuncture imagery treatment (VGAIT)

The study investigates the effects of video-guided acupuncture imagery treatment (VGAIT) on patients with chronic low back pain (cLBP). The results showed that VGAIT, real acupuncture, and sham acupuncture all significantly reduced pain severity. VGAIT produced similar effects to real acupuncture and greater pain relief compared to sham acupuncture, although the difference was not statistically significant. The study suggests that VGAIT could be a promising method for pain management.


PUBCHEM.COMPOUND:4688

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.


PUBCHEM.COMPOUND:4688


MESH:C109363

observed in after oral dosing of Mitragynine


MESH:C109363


UMLS:C2194043

The study investigates the effects of methocinnamox (MCAM), a mu opioid receptor antagonist, on opioid abuse and overdose. The research was conducted on rhesus monkeys and it was found that MCAM did not impair memory or decrease the consumption of sucrose pellets. It was also found that MCAM blocked the behavioral suppressant effects of morphine for at least 7 days. The study also tested the effects of the muscarinic receptor antagonist scopolamine and the N-methyl-D-aspartate antagonist phencyclidine, both of which decreased delayed matching-to-sample accuracy and the number of trials completed. The results suggest that MCAM could be useful in treating opioid abuse and overdose without adverse effects on memory.


UMLS:C0360123


MESH:C109363

The study investigates the potential rewarding properties of mitragynine and 7-hydroxymitragynine, primary alkaloids in kratom, and morphine in male and female rats. The compounds were tested in an intracranial self-stimulation (ICSS) procedure, which evaluates the rewarding/aversive and sedative effects of drugs. The results showed that a high dose of 7-hydroxymitragynine increased the brain reward thresholds, while an intermediate dose of morphine decreased the reward thresholds. There were no significant sex differences in the effects of these compounds on the reward thresholds and response latencies. The findings suggest that mitragynine and 7-hydroxymitragynine do not have abuse potential.


PUBCHEM.COMPOUND:5288826


UMLS:C1654703

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.


UMLS:C1654703


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


UMLS:C0376196


UMLS:C0014628

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


UMLS:C0014628


UMLS:C0279226

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.


UMLS:C0279226


UMLS:C3853055

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.


UMLS:C3853055


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.


UMLS:C0360445


UMLS:C0700549

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.


UMLS:C4325236


PUBCHEM.COMPOUND:54677971


UMLS:C1449885


CHEBI:35941


MESH:C434444


UMLS:C0682781

Detoxifying Biomimetic 'Nanosponge' Decoy Receptors


UMLS:C0281176


UMLS:C0682781


UMLS:C3713932

The paper discusses a project aimed at creating a novel chemical entity (NCE) named Kindolor, designed to alleviate chronic pain and reduce opiate use. Kindolor is a non-opiate, non-addictive molecule that targets three aspects of the peripheral sensory system involved in chronic pain. Initial preclinical studies have shown Kindolor's effectiveness in reducing or eliminating chronic pain in five animal models. The project's goal is to complete preclinical studies of Kindolor, gain investigational new drug (IND) approval, and proceed to clinical Phase Ia, 1b safety studies, and a Phase 2a efficacy study.


UMLS:C3713932


UMLS:C3653393

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.


UMLS:C3653393


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.


UMLS:C0885285

is more prevalent in compared to other species' plasma


UMLS:C0355800

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.


UMLS:C0127798

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.


UMLS:C0700549


UMLS:C1714006


UMLS:C0733482

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.


UMLS:C0733482


UMLS:C0733482

Epoxides of polyunsaturated fatty acids (EpFA)


UMLS:C0014628


UMLS:C3178870


UMLS:C3653440

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.


UMLS:C3653440


CHEBI:61355


PUBCHEM.COMPOUND:4688

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


UMLS:C0729169


UMLS:C0547016


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.


CHEBI:38958

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:C427739


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


NCBITaxon:10114

Psychostimulants (cocaine, methamphetamine, and amphetamine)


NCBITaxon:10114

Opioid/psychostimulant mixture (fentanyl + methamphetamine)


UMLS:C0038586


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


PUBCHEM.COMPOUND:33039

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.


PUBCHEM.COMPOUND:33039


PUBCHEM.COMPOUND:5288826


UMLS:C0073408

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.


UMLS:C0701445


UMLS:C0355800


UMLS:C0073408


UMLS:C0073408

does not suppress respiration when combined


UMLS:C0394162

The study evaluated the safety and effects of deep brain stimulation (DBS) on a patient with severe, treatment refractory opioid and benzodiazepine use disorders. DBS electrodes were implanted within the Nucleus Accumbens/Ventral anterior internal capsule (NAc/VC) of the patient. The treatment was found to be safe, with no serious adverse events noted. The patient remained abstinent and engaged in comprehensive treatment at the 12-week endpoint. Substance cravings decreased post-DBS implantation, most substantially in benzodiazepine craving. An improvement trend in frontal/executive function was observed. FDG PET showed an increase in glucose metabolism in the dorsolateral prefrontal and medial premotor cortices at the 12-week endpoint compared to post-surgery/pre-DBS titration. Heart Rate Variability (HRV) improved following the final titration.


UMLS:C0394162


UMLS:C0700549

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.


UMLS:C0700549


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


UMLS:C0729169

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:C117440


MESH:C578008


UMLS:C0443408


UMLS:C0729169


UMLS:C0279226

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.


UMLS:C0279226


UMLS:C0282275


UMLS:C0394664

decreases functional connectivity with Precuneus

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


PUBCHEM.COMPOUND:5288826

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.


PUBCHEM.COMPOUND:5288826


UMLS:C4273841

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.


UMLS:C4273841


UMLS:C0242402


UMLS:C0086079

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


UMLS:C0086079


MESH:C426083


MESH:C434786


PUBCHEM.COMPOUND:643985

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.


UMLS:C0001956

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.


UMLS:C0001956


UMLS:C0038586


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


UMLS:C0242402

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


UMLS:C0243071


UMLS:C1120432

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.


UMLS:C1120432


UMLS:C0245498

Intracranial self-stimulation (ICSS) depression caused by Ro 64-6198


UMLS:C0355800


UMLS:C0457949

has increased anatomical connectivity in

The study investigates the role of the thalamo-sensorimotor circuit in chronic low back pain (cLBP) using diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging. The results showed increased anatomical connectivity of the left thalamo-motor pathway and altered resting-state functional connectivity (rsFC) of bilateral thalamo-motor/somatosensory pathways in patients with cLBP compared to healthy controls. A significant correlation was also found between pain intensity during the MRI scan and rsFC of the right thalamo-somatosensory pathway in cLBP patients.


UMLS:C0457949

has altered resting-state functional connectivity in


UMLS:C0518087

correlates with resting-state functional connectivity in


UMLS:C2917250

Peripherally acting μ opioid receptor antagonists (PAMORAs)

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.


UMLS:C3159526


MESH:C527017


PUBCHEM.COMPOUND:5288826


UMLS:C4400675

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.


PUBCHEM.COMPOUND:4688


UMLS:C4400675


MESH:C109363


UMLS:C4055422

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.


UMLS:C4055422


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


UMLS:C4318638


UMLS:C0301360

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.


UMLS:C1714006


UMLS:C0301360


PUBCHEM.COMPOUND:62156

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:62156


MESH:D014612


UMLS:C1714006

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


UMLS:C0038586

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.


UMLS:C0001956


UMLS:C0162701


UMLS:C1171301


UMLS:C0013819


MONDO:0005296


UMLS:C0038586

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.


UNII:5E7U48495E


PUBCHEM.COMPOUND:23727689

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.


PUBCHEM.COMPOUND:23727689


PR:000008476


UMLS:C1721242

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


UMLS:C0355800


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


UMLS:C1320105

The study investigates a new long-acting oral formulation of buprenorphine/naloxone developed by Lyndra Therapeutics. The formulation was tested on rhesus monkeys for its efficacy in reducing fentanyl self-administration. The results showed that the formulation significantly decreased the rate of fentanyl intake for up to 8 days. The time to reach maximal buprenorphine levels ranged between 56 and 68 hours for all doses. The maximal buprenorphine level following 168 mg was significantly greater than those observed for 56 mg and 112 mg. The study concludes that this formulation could provide a new opportunity to treat opioid use disorders.


UMLS:C0378073

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).


UMLS:C0061355


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.


UNII:5E7U48495E


UMLS:C4544496

Transcutaneous cervical vagus nerve stimulation (tcVNS)

The study investigates the effects of transcutaneous cervical vagus nerve stimulation (tcVNS) on patients with Opioid Use Disorder (OUD) undergoing acute opioid withdrawal. The results showed that tcVNS significantly reduced subjective opioid withdrawal, pain, distress, and heart rate in patients compared to sham stimulation. However, there was no significant difference in craving between the two groups. The findings suggest that tcVNS could be a potential non-pharmacologic treatment for OUD.


UMLS:C4544496


UMLS:C0355800

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.


UMLS:C0355800

undergoes polymorphic transition/crystallization at larger sizes


PUBCHEM.COMPOUND:4688

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.


PUBCHEM.COMPOUND:4688


MESH:C109363


PUBCHEM.COMPOUND:4688

produces antinociceptive synergism when combined


UMLS:C0355800

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.


UMLS:C0355800


UMLS:C0032494


UMLS:C3653393

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.


UMLS:C3853055


UMLS:C3850135


PUBCHEM.COMPOUND:85875

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


UMLS:C1714006


UMLS:C0430759

The study investigates the mechanisms of weight-bearing and non-weight-bearing pain in knee osteoarthritis (OA). The research used data from a cohort of older adults with or at risk of knee OA and evaluated quantitative sensory testing (QST) measures. The results showed that each standard deviation unit decrease in patellar pressure pain threshold (PPT) was associated with greater odds of both weight-bearing and non-weight-bearing pain. Wrist PPT was associated with greater odds of weight-bearing pain but only with pain during sitting/lying. Mechanical temporal summation (TS) was significantly associated with greater odds of pain with walking and stairs. Conditioned pain modulation (CPM) was not associated with any pain outcomes. The findings challenge the hypothesis that non-weight-bearing pain may reflect greater pain sensitization and/or inefficient CPM than weight-bearing pain in knee OA.


UMLS:C0430759


UMLS:C2146437


UMLS:C0234110


UMLS:C2032522


UMLS:C1305855

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.


UMLS:C1305855


PR:000009758


UMLS:C1305855

High-sensitivity C-reactive protein (hsCRP)


NCBIGene:1401

High-sensitivity C-reactive protein (hsCRP)


UMLS:C4039932

Urologic chronic pelvic pain syndrome (UCPPS)

The study investigates the relationship between pelvic floor muscle tenderness (PFT) and urologic chronic pelvic pain syndrome (UCPPS) symptom severity. The study involved 562 UCCPS participants and 69 controls, with diagnoses including interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome. The results showed that 81% of UCPPS participants had PFT, and those with higher PFT scores had more severe disease burden, worse quality of life, and more widespread distribution of nonpelvic pain. The findings suggest that widespread PFT may be a phenotypic predictor in UCPPS.


UMLS:C4039932


UMLS:C3850080

The HEALing Communities Study (HCS) aims to reduce opioid overdose deaths through the Communities That HEAL (CTH) intervention, a community-engaged, data-driven planning process. The CTH protocol provides a common structure for the community-engaged intervention and allows for tailored approaches that meet the unique needs or sociocultural context of each community. The study will show how community engagement can support the implementation of evidence-based practices for addressing the opioid crisis in highly impacted communities.


UMLS:C0039786

Communities That HEAL (CTH) intervention


UMLS:C3850080

The HEALing Communities Study (HCS), launched in May 2019, aims to reduce opioid overdose deaths by 40% in three years. This is to be achieved by enhancing and integrating the delivery of multiple evidence-based practices across health care, justice, and community settings. The study is being conducted amidst the opioid epidemic and the COVID-19 pandemic in the United States.