methadone / Generic mfg. - LARVOL DELTA

Tirzepatide reduces motivation for fentanyl in mice (Neuroscience 2026) - "Although medications for opioid use disorder are available, including methadone, buprenorphine, and naltrexone, many patients discontinue treatment or continue to experience craving and relapse...The effect of tirzepatide (0.01, 0.03, 0.1, and 0.3 mg/kg, i.p.) on the number of fentanyl vapor deliveries earned during these sessions was assessed under a fixed-ratio 1 (FR1) schedule of reinforcement and using a within-session behavioral economic demand procedure, in which response requirements increased hourly (FR1, 2, 4, 8, 16, 32) during a 6-hour session...Tirzepatide increased demand elasticity without affecting demand intensity, indicating reduced essential value and decreased motivation to work for fentanyl across sexes and dependence conditions. These findings identify dual GLP-1/GIP receptor agonists as a promising and readily repurposable pharmacological strategy for selectively reducing opioid motivation, supporting rapid clinical evaluation of tirzepatide for..."

Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders • Substance Abuse

Predictive Performance of Screening Methods for Neonatal Opioid Withdrawal Syndrome. (PubMed, Hosp Pediatr) - "Maternal self-disclosure demonstrated moderate agreement with maternal USS for perinatal opioid exposure. Although combining maternal self-disclosure with maternal USS provided the highest predictive ability for neonatal admission with NOWS, maternal self-disclosure alone remained a reliable predictor."

Journal

A CROSS-SECTIONAL STUDY OF LAXATIVE PRESCRIBING IN A TERTIARY REFERRAL CENTRE IN IRELAND (UEGW 2026) - "Surprisingly, 82% of patients taking scheduled methadone received no laxatives... The majority of inpatients in an acute tertiary referral hospital are prescribed laxatives. Sub-optimal prescribing practices were frequently encountered. This cross-sectional study identifies a clear need to improve laxative prescribing practices in this setting."

Observational data • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder

ESG 1 60, a Novel Dopamine D3 Receptor-Preferring Partial Agonist, Reduces Opioid Taking and Seeking Without Compromising Opioid Analgesia in Rodents (Neuroscience 2026) - "Although medications such as methadone, buprenorphine, and naloxone are available, their effectiveness in preventing relapse is limited, and long‑term agonist therapy carries significant abuse liability...In the present study, we evaluated whether cariprazine and ESG‑1‑60 similarly reduce opioid‑taking and opioid‑seeking behaviors...Together, these findings demonstrate that moderate D3‑preferring partial agonists reduce opioid‑taking and opioid‑seeking behaviors while preserving opioid analgesia. These compounds therefore represent promising candidates for the development of safer, non‑opioid pharmacotherapies for OUDs."

Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders • Substance Abuse

Developing the dopamine D3 receptor (D3R) antagonist, (R)-VK4-116, as a non-opioid medication for the treatment of opioid use disorder (Neuroscience 2026) - "Despite the availability of three approved medications for treating OUD (methadone, buprenorphine and naltrexone), all of which target opioid receptors, side effects, compliance and access remain challenges that confound recovery. A multi-kilogram scale GMP synthesis, formulation for maximized oral bioavailability, and toxicity studies were completed for the IND package, which recently received clearance from the FDA. A first-in-human clinical trial to assess the safety of (R)-VK4-116 in healthy individuals is planned for later this year."

First-in-human • Addiction (Opioid and Alcohol) • CNS Disorders • Cognitive Disorders • Substance Abuse

Striatal μ-opioid-dopamine D1 receptor heteromers drive dopaminergic hypersensitivity in a rodent model of restless legs syndrome (Neuroscience 2026) - "GABA release was assessed after systemic administration of the D1R agonist SKF81297 and the MOR agonist methadone...In transfected cells, co-expression of MORs, even in the absence of opioid ligands, impaired the ability of SKF81297 to promote D1R–Gs coupling, indicating a powerful antagonistic allosteric modulation of D1R function by MOR within the heteromer. Together, these findings suggest that the downregulation of striatal MORs is a driving factor behind BID-induced dopaminergic hypersensitivity in striosomal MOR–D1R neurons, highlighting a potential core pathogenic mechanism in RLS."

Preclinical • CNS Disorders • Movement Disorders • Restless Legs Syndrome • Sleep Disorder

Allosteric modulation of µ-opioid receptor heteromers: Implications for opioid drug discovery (Neuroscience 2026) - "In this study, we evaluated the effects of D1R and Gal1R co-expression on the MOR-mediated G protein activation of diverse opioids, including R- and S-methadone, DFNZ, morphine, buprenorphine, fentanyl, DAMGO, and endomorphin-1. These results strongly support the therapeutic use of buprenorphine for the restlessness associated with RLS and OW, and encourage the clinical application of S-methadone and DFNZ. More generally, this study represents a proof of concept for leveraging the differential allosteric properties of distinct MOR heteromers to develop opioids with enhanced therapeutic profiles and reduced side effects."

Addiction (Opioid and Alcohol) • CNS Disorders • Movement Disorders • Restless Legs Syndrome • Sleep Disorder • GAL

Striatal dopamine D1 receptor function is modulated by µ-opioid receptors through receptor heteromerization (Neuroscience 2026) - "Furthermore, a NanoBiT assay demonstrated an allosteric mechanism within the heteromer whereby naloxone, but not methadone, counteracted SKF81297-induced Gs protein activation...We are leveraging molecular modeling and local TM peptide administration to further resolve the structural mechanics of this naloxone cross-antagonism. Ultimately, our findings identify MOR–D1R heteromers as a significant receptor population in the striatum and a novel therapeutic target for opioid use disorder and RLS."

Addiction (Opioid and Alcohol) • CNS Disorders • Movement Disorders • Restless Legs Syndrome • Sleep Disorder • Substance Abuse

Bilateral Ultrasound-Guided Transversus Thoracic Plane Block as Part of a Multimodal Analgesic Plan in Two Rabbits Undergoing Median Sternotomy. (PubMed, Vet Sci) - "Premedication included methadone, dexmedetomidine, and midazolam, with ketamine added for one rabbit. Anesthesia was maintained with isoflurane in oxygen and a ketamine infusion...These cases indicate that the TTP block is technically feasible in rabbits and can contribute to intraoperative analgesia during thoracic surgery. Further studies are needed to evaluate the optimal injectate volume and its distribution, as well as the safety and efficacy of the anesthetic dose."

Journal • Preclinical • Anesthesia • Pain

Racial and ethnic disparities in medication for opioid use disorder treatment among medicaid enrollees. (PubMed, Drug Alcohol Depend) - "Results highlight the critical need to identify and address ongoing barriers to MOUD, particularly for minoritized groups, and for further research to understand and address state-level variation in these disparities."

Journal • Reimbursement • US reimbursement • Addiction (Opioid and Alcohol) • Substance Abuse

Pharmacogenetic Evidence in Opioid-Related Toxicity and Death with an Appraisal of Emerging Multi-Omics Studies: A Systematic Review. (PubMed, Int J Mol Sci) - "The most coherent PGx findings concerned CYP2D6-dependent codeine and tramadol bioactivation, CYP2B6-dependent methadone disposition, and ABCB1-related tissue distribution. Downstream signatures may also reflect chronic exposure, terminal hypoxia, or postmortem change. Neither the descriptive evidence-map scores nor individual molecular markers provide validated estimates of forensic risk or establish cause of death independently."

Biomarker • Journal • Review • Addiction (Opioid and Alcohol) • ABCB1

De-implementation of inequitable methadone policy and treatment: lessons learned from COVID-19 to support a more just methadone treatment system in the United States. (PubMed, Front Public Health) - "We present the COVID-19 public health emergency as a naturalistic experiment in de-implementation, outline evidence from this period on how COVID-19 related flexibilities influenced treatment outcomes and patient experiences and present a de-implementation framework to contextualize these changes while imagining further expansion of de-implementation efforts to support sustained change. We highlight how patient advocacy can shape further de-implementation while noting current threats to progress."

Journal • Review • Hepatology • Infectious Disease • Novel Coronavirus Disease • Substance Abuse

Scleroderma, Stasis, and Sarcina: A Rare Gastric Infection in Systemic Sclerosis (ACG 2026) - "Case Description/ A 70-year-old woman with systemic sclerosis complicated by esophageal aperistalsis, and chronic use of methadone and trazodone presented with progressive dysphagia and reflux...She was treated with amoxicillin-clavulanate, high-dose proton pump inhibitor, and prucalopride as a prokinetic agent...Although ciprofloxacin plus metronidazole is the most commonly reported regimen, no formal treatment guidelines exist. In vitro susceptibility data suggest efficacy of penicillins, fluoroquinolones, macrolides, and tetracyclines. Our use of amoxicillin-clavulanate to avoid QT prolongation risk represents a novel therapeutic approach. This case highlights the importance of evaluating for underlying causes of delayed gastric emptying when S. ventriculi is detected, the variable clinical spectrum of this organism, and the role of individualized antibiotic selection when standard regimens are contraindicated."

Gastrointestinal Disorder • Immunology • Infectious Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis

Ulcerative Colitis Patients With Opiate Use Disorder Have Higher Healthcare Utilization and Higher Mortality: A Propensity-Matched Multicenter Analysis (ACG 2026) - "Cases were UC patients with OUD (identified by ICD-10 codes for OUD, methadone use or buprenorphine/naloxone use, n=38,997), and controls were UC patients without OUD (n=383,178), matched 1:1 by age and gender via propensity score matching (total n=77,994). Cohort demographics and selection are outlined in Figure 1. UC patients with OUD demonstrated higher rates of food insecurity (RR 4.81, 95% CI [4.00, 5.80]) and housing instability (RR 7.26, 95% CI [5.61, 9.38]). They were more likely to use TCAs, SNRIs, acetaminophen, NSAIDs, and gabapentin (Fig."

Clinical • HEOR • Addiction (Opioid and Alcohol) • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Substance Abuse • Ulcerative Colitis

A Treatment Gap With Consequences: Underutilization of Medications for Opioid Use Disorder and Associated Mortality in Chronic Gastrointestinal Disease (ACG 2026) - "The primary outcome was initiation of MOUD (buprenorphine, methadone, or naltrexone) within 90 days of OUD diagnosis. After matching, 11,522 pairs were analyzed. Patients with GI-OUD were less likely to initiate MOUD within 90 days than matched patients with OUD alone (8.6% vs 9.8%; RR 0.88, 95% CI 0.81â0.95; p=0.002). Among GI-OUD patients, MOUD receipt was associated with lower all-cause mortality (2.9% vs 4.1%; RR 0.71, 95% CI 0.53â0.95) and reduced mortality risk (HR 0.66, 95% CI 0.49â0.89; p=0.019)."

Addiction (Opioid and Alcohol) • CNS Disorders • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Inflammation • Inflammatory Bowel Disease • Mental Retardation • Pancreatitis • Substance Abuse

Diagnosis and Treatment Gaps in Opioid-Induced Constipation: A National Real-World Analysis Using the Epic Cosmos EHR Network (ACG 2026) - "Adults â¥18 years with chronic opioid exposure (â¥3 prescription orders spanning â¥90 days; hydrocodone, oxycodone, morphine, fentanyl, tramadol, or methadone) were included...During 12 months of follow-up, we assessed formal OIC diagnosis (K59.03), laxative prescriptions, PAMORA prescriptions (methylnaltrexone, naloxegol, naldemedine), and constipation-related ED visits or hospitalizations (K59.0x, K56.41)... Among chronic opioid users, 40.73% received laxatives, while only 8.81% had a formal OIC diagnosis, representing a >4-fold gap between treatment and documented coding. PAMORA prescribing was 13.97%, exceeding formal diagnosis rates and suggesting targeted therapy may occur despite absent structured OIC coding. Constipation-related complications increased with age (18â44: 0.48%; â¥85: 1.37%), whereas PAMORA prescribing was lowest in patients â¥85 years (11.57%) despite higher complication burden."

Clinical • Real-world • Real-world evidence • Constipation • Gastroenterology • Gastrointestinal Disorder

Incidental Pancreatic Metastatic Melanoma Discovered During Evaluation for Pulmonary Embolism (ACG 2026) - "Case Description/ A 61 year old male with medical history of deep vein thrombosis (DVT) on apixaban and substance use disorder on methadone presented with pleuritic chest pain. Figure: Figure 1. Endoscopic ultrasound showing pancreatic tail lesion."

Metastases • Cardiovascular • Melanoma • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pulmonary Embolism • Respiratory Diseases • Solid Tumor • Venous Thromboembolism

OMICS: Oral Methadone in Cardiac Surgery (clinicaltrials.gov) - P4 | N=100 | Active, not recruiting | Sponsor: Mayo Clinic | Recruiting ➔ Active, not recruiting

Enrollment closed • Anesthesia • Cardiovascular • Pain

A Study of Ulonivirine (MK-8507) and Methadone in Healthy Volunteers (MK-8507-019) (clinicaltrials.gov) - P1 | N=14 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open

Investigating hierarchical control among functional networks disrupted by opioid use disorder using effective connectivity. (PubMed, Imaging Neurosci (Camb)) - "Task-fMRI data were collected from healthy controls (HC; n = 22) and OUD participants on methadone maintenance treatment (OUD; n = 25), during a heroin cue reactivity (CR) and monetary incentive delay (MID) task...EC patterns were unable to form distinct clusters that corresponded to clinical groups; instead, clusters separated by task. Little evidence was found that disrupted VMN-mediated reward drove dysregulated whole-brain function in OUD."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Cognitive Disorders • Psychiatry • Substance Abuse

In silico modeling of methadone-related ion current effects to predict QT interval prolongation. (PubMed, J Pharmacokinet Pharmacodyn) - "Evaluation of individual ion currents toward QTc interval modulation suggested that IKr and IK1 have a similar impact on methadone-related QTc interval prolongation. This study highlights the potential contribution of multiple ion currents to methadone's proarrhythmic effects and advances the understanding of ion current interplay underlying methadone-induced arrhythmia."

Journal • Cardiovascular

From compliance to participation in US methadone maintenance treatment: Realizing the promise of person-centered services for people who use opioids. (PubMed, Int J Drug Policy) - "We review examples in Canada, Australia, and the US to illustrate both the promise and challenges to institutionalizing participation of people who use drugs. Strategies to integrate participation by people who use opioids into individual healthcare, organization, and policies decisions are reviewed."

Compliance • Journal • Substance Abuse

Opioid use and perioperative pain management practices in dogs and cats in Latvia: A national survey highlighting regional disparities and generational differences. (PubMed, Vet World) - "Butorphanol and buprenorphine were the most widely available opioids, whereas fentanyl and methadone availability was significantly associated with higher surgical caseloads (p < 0.01). The findings demonstrate broad adoption of evidence-based multimodal analgesia while identifying important regional inequalities in opioid availability and persistent underuse of standardized pain assessment tools. These results highlight priorities for continuing professional education, wider implementation of validated pain assessment methods, and improved access to essential analgesics to promote consistent, evidence-based pain management in veterinary practice."

Journal • Pain

When Buprenorphine Was Not Enough: Methadone Treatment of Tianeptine Use Disorder. (PubMed, J Addict Med) - "Patients with tianeptine use disorder, and with use disorders resulting from regular use of substances characterized as nonopioid but with µ-opioid receptor agonist effects, may follow a similar clinical course to patients with OUD. This case highlights an emerging treatment gap for use disorders involving substances with clinically relevant µ-opioid receptor agonist effects that do not fall within the OUD-based OTP treatment framework."

Journal • CNS Disorders • Depression • Endocrine Disorders • Major Depressive Disorder • Mood Disorders • Psychiatry • Substance Abuse

Trends in Buprenorphine and Methadone Dispensing Among Medicare Advantage and Commercial Enrollees, 2019-2024. (PubMed, AJPM Focus) - "The decline in commercial buprenorphine dispensing after 2022 warrants further investigation. Tailored efforts may be needed to close payer-related treatment gaps and support broader medications for opioid use disorder access."

Journal • Medicare • Reimbursement • US reimbursement • Addiction (Opioid and Alcohol) • Infectious Disease • Novel Coronavirus Disease • Substance Abuse