The purpose of this study is to look at a standardized methadone-based enhanced recovery after surgery protocol following pediatric cardiac surgery. This study will consist of randomly assigning children to receive the methadone-based recovery procedures or to receive current standard of care recovery procedures. Randomly assigning means that there is a 50/50 chance, like a coin flip, of being assigned to either research group.

Start Date01 Oct 2025

Sponsor / Collaborator

University of Pittsburgh

NCT06877858

/ Not yet recruitingPhase 1IIT

A Dose-Finding Study of Methadone Loading Dose Initiation for Opioid Use Disorder with Fentanyl Use

The goal of this proposal is to develop a "loading dose" approach to starting methadone to treat fentanyl opioid use disorder (OUD). We aim to conduct an assessor-blinded dose-finding study of 24 participants with fentanyl OUD recruited to a research unit for monitored methadone dosing. Participants will be randomized to standard methadone initiation vs. one of three loading dose approaches. The primary goal is to identify the maximum tolerated methadone loading dose appropriate for future study.

Start Date01 Sep 2025

Sponsor / Collaborator

University of Pennsylvania

NCT06940570

/ Not yet recruitingPhase 3IIT

A Randomized Single Center Trial to Determine the Efficacy of Methadone as a First Line Agent in the Reduction and Treatment of Pain in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation

Mucositis is a normal side effect of stem cell transplant which happens as a result of chemotherapy being given prior to a new donor cell infusion (bone marrow transplant). The chemotherapy will kill cancer cells, but good cells, such as those in the mouth, are killed too. The mouth cells going away causes the areas in the mouth to be blistered, irritated, sore, and extremely painful. Pain medication (usually morphine or hydromorphone if allergic to morphine) are given when oral blisters are seen or felt by patient in patient's mouth. However, one pain medication given through a vein in the patient may or may not be effective and providers are often challenged with providing good pain control while waiting for the new donor cells to grow, which will then heal the mouth. This is a period of waiting that is 6-8 weeks.
The investigators know that methadone, a second pain medication, may decrease pain in a different way than morphine. This is because methadone works in a different way in the brain than morphine. By giving these pain medicines together, the hope of the study is to show decreased pain while waiting for new cells to grow.
The goal of this clinical trial is to hope to learn whether adding methadone (second pain medication) to the current pain medication which is morphine alone (all patients will receive this pain medication) will help reduce the pain experience of participant. Current treatment of morphine alone is sometimes not entirely effective and so any improvement of pain while waiting for new cells to grow is one of the goals of this study. If methadone is effective in decreasing pain, then patients may benefit in the future from using these two medications up front when getting a transplant.
Participant in this study between 6-18 years of age and is needing a stem cell transplant for a disease that can potentially be cured by transplantation.
Participant in this study is receiving chemotherapy and/or radiation conditioning that can cause mucositis. Participants are being asked to participate in this study because participants meet criteria to receive methadone that may or may not reduce pain experience versus just being given morphine alone, which is what all patients are given when the participants have mucositis.
The main goal of the study is to see if less opioid (pain medication) when methadone is added in comparison to participant who uses PCA only. The investigators also want to learn if patient's overall function is improved if given methadone. Another goal would be to see the number of TPN days the participant received and if the participant who was given methadone began to eat sooner. Other smaller goals include learning about side effects of methadone, and if the hospital stay is less for those who receive the study medication.
This medication will be given at Children's Medical Center of Dallas while participant is admitted for the stem cell transplant. There is no sponsor that is funding the study and this drug will be given free of charge in exchange for participation in the study

Start Date01 Aug 2025

Sponsor / Collaborator

The University of Texas Southwestern Medical Center

100 Clinical Results associated with Methadone Hydrochloride

100 Translational Medicine associated with Methadone Hydrochloride

100 Patents (Medical) associated with Methadone Hydrochloride

18,805

Literatures (Medical) associated with Methadone Hydrochloride

31 Dec 2025·VETERINARY QUARTERLY

Perioperative drug management in non-critical companion animals: a retrospective study at a Spanish veterinary teaching hospital (2018–2022)

Article

Author: Susperregui, Julen ; Altónaga, José R. ; López, Cristina ; de la Puente, Raúl ; Rodríguez, José M. ; Díez, Raquel ; Vázquez, Milena ; Romero, Beatriz ; Sahagún, Ana M.

There is little information in veterinary literature on the perioperative pharmacological management of small animal patients, despite the existence of common protocols and the importance of properly managing this period to reduce anaesthesia-related detrimental effects. This study aimed to analyse the current use of perioperative drugs in companion animals treated at the Veterinary Teaching Hospital of the University of León (HVULE) in Spain over a period of 5 years (2018-2022), describe the prescription patterns of these medicines, and identify the main variables associated with their prescription to explore possible strategies to promote their appropriateness. A total of 3438 cases were included in this study. The animals that most frequently underwent surgery were dogs (58.2%), females (57.0%), and adults (73.0%). The primary procedures performed were reproductive (56.6%) and traumatological (19.8%) surgeries. Regarding pharmacological treatments, more than half (62.3%) belonged to the ATCvet classification QN group (nervous system), and the most common compounds were isoflurane (13.5%), methadone (13.5%), and propofol (12.7%). Amoxicillin/clavulanic acid (3.7%) and marbofloxacin (2.8%) (categories C and B in the European Medicines Agency categorisation, respectively) were the most prescribed antibiotics. These findings provide detailed data to help veterinary policymakers improve drug use during surgical procedures.

31 Dec 2025·Human Vaccines & Immunotherapeutics

Immunogenicity persistence after four intramuscular triple-dose or standard-dose hepatitis B vaccine in patients receiving methadone maintenance treatment: A 1-year follow-up study in China

Article

Author: Liang, Xiaofeng ; Wang, Fuzhen ; Xue, Tongchuan ; Yao, Tian ; Men, Zhaoyue ; Mo, Xinyuan ; Liu, Yuan ; Feng, Yongliang ; Wang, Suping ; Gao, Linying ; Wang, Keke ; Yuan, Yuan ; Gao, Yizhuo

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov (NCT03962816).https://clinicaltrials.gov/ct2/show/NCT03962816.

01 Dec 2025·European Journal of Trauma and Emergency Surgery

Pre-injury narcotic drug use in isolated severe traumatic brain injury: effect on outcomes

Article

Author: Demetriades, Demetrios ; Jakob, Dominik Andreas ; Takahashi, Kyosuke ; Yamaguchi, Keishi ; Matsushima, Kazuhide ; Abe, Takeru

PURPOSE:

The aim of this study was to explore the association between pre-injury narcotic drug use (opioids, methadone, and/or oxycodone) and outcomes in isolated severe traumatic brain injury (TBI) patients.

METHODS:

ACS TQIP study included adult trauma patients (≥ 16 years) with complete drug and alcohol screening. Isolated severe TBI was defined as head trauma with AIS 3-5 and without significant extracranial trauma. Exact matching was used to compare patients with isolated pre-injury narcotic drug use to those with no illicit drug or alcohol use. Patients were matched 1:1 based on the following matching criteria: age, gender, mechanism of injury, Injury Severity Score, systolic blood pressure, head AIS, and comorbidities.

RESULTS:

Of 1,846,630 patients, 141,058 had isolated severe head injuries with complete drug and alcohol screenings. After exact matching, 1,560 patients in each group were analyzed. There were no significant differences in hospital mortality, craniectomy rates, complication rates, or length of hospital stay. Patients that tested positive for narcotics had lower rates of mechanical ventilation (16.5% vs. 25.3%, p < 0.01) and shorter ICU stays [3 (2-4) days vs. 3 (2-6) days; p < 0.01].

CONCLUSION:

Pre-injury narcotic drug use in isolated severe TBI is not associates with adverse outcomes. Further research is needed to understand the biochemical and physiological effects of narcotic drugs on TBI outcomes.

135

News (Medical) associated with Methadone Hydrochloride

13 Aug 2025

·ir.ensysce.com

Ensysce Biosciences Reports Second Quarter 2025 Financial Results and Latest Program Updates

Initiates Critical Milestone, Launching Phase 3 Trial of PF614 to Advance Next-Generation Opioid Therapy Toward Regulatory Approval Receives $5.3 Million Installment from NIDA To Support Overdose Protection Program Accelerates PF614-MPAR-102 Study with Full Enrollment of Part 2 SAN DIEGO, CA / ACCESS Newswire / August 13, 2025 / Ensysce Biosciences, Inc. (NASDAQ:ENSC) ("Ensysce" or the "Company"), a clinical-stage pharmaceutical company developing innovative solutions for severe pain relief while reducing the potential for opioid abuse and overdose, today reported financial and operational results for the second quarter ended June 30, 2025. Dr. Lynn Kirkpatrick, Chief Executive Officer of Ensysce, commented, "Momentum continued in the second quarter as we forged ahead progressing, what we believe will be the next evolution in opioid therapeutics: safety features built in to help guard against both misuse and overdose. The initiation of our pivotal Phase 3 trial for PF614 marks a major achievement for Ensysce and a critical step toward achieving our clinical and commercial strategy. This study is designed to validate PF614's ability to deliver what we believe will be superior pain relief for post-surgical pain with built-in abuse deterrence, reinforcing our commitment to developing safer opioid therapies. As we advance to seeking regulatory approval, PF614 has the potential to reshape the opioid treatment landscape and create long-term value for both patients and shareholders." Dr. Kirkpatrick added, "Fully enrolling Part 2 of our PF614-MPAR-102 study marks another important step in progressing this product with built in overdose-protection. With continued financial support from NIDA and the FDA's Breakthrough Therapy designation, we are accelerating the development of what could be a game-changing solution for those in severe pain, one that not only has superior efficacy but is designed to prevent unintentional overdose." "With the significant advancements made to date, we believe Ensysce is well-positioned to disrupt the opioid analgesic market with our lead candidates, PF614 and PF614-MPAR. Our approach leverages innovative chemistry to create opioid therapies that maintain strong efficacy while incorporating built-in safeguards against abuse and overdose. As we progress through the second half of the year, we are executing on a clear path of clinical and regulatory milestones across our TAAP™, MPAR®, and overdose use disorder (OUD) programs. With the opioid crisis continuing to take a devastating toll, our mission remains focused on saving lives and transforming how patients with pain and addiction are treated," Dr. Kirkpatrick concluded. TAAPTM (Opioid Abuse Deterrent Program) Update The Company's lead product, PF614, is a Trypsin-Activated Abuse Protection (TAAPTM) extended-release oxycodone and a potential "next generation" analgesic to treat severe pain. PF614's TAAPTM chemical modification of oxycodone renders it inactive until it is swallowed and exposed to the body's own trypsin in the small intestine to activate or "switch on" to release oxycodone. The TAAPTM technology is designed to control release when administered orally, be highly resistant to tampering, and reduce abuse, with a goal of providing a safer opioid product for those suffering from severe pain who require opioid-strength analgesia. In July, Ensysce announced the initiation of its pivotal PF614-301 study evaluating PF614, to manage and moderate severe post-surgical pain after abdominoplasty. The study aims to demonstrate PF614's effectiveness in pain relief while minimizing the risk of abuse and supporting a safer transition to non-opioid outpatient care. Ensysce has engaged Rho, Inc., a clinical research organization with deep expertise in central nervous system (CNS) disorders and pain studies, to conduct the trial. The collaboration marks a major step toward redefining pain therapy with a safer class of opioids. MPAR® (Opioid Abuse Deterrent and Overdose Protection Program) Update PF614-MPAR is a combination product of the TAAPTM and MPAR® (Multi-Pill Abuse Resistance) technology to treat severe pain with the added benefit of oral overdose protection. PF614-MPAR combines prodrug PF614 with a trypsin inhibitor to reduce or "switch off" the release of the opioid in an overdose situation. Data from the initial clinical trial PF614-MPAR-101, demonstrating that the MPAR® technology worked as designed to provide the desired overdose protection to PF614-MPAR at a 25 mg dose, led to the FDA's Breakthrough Therapy designation in January 2024. During the second quarter of 2025, the Company completed enrollment for Part 2 of its PF614-MPAR-102 study, to examine how food affects its MPAR technology, and is awaiting final data. The study is continuing with the third part of the trial through end of year and the Company is continuing to complete non-clinical studies required to support its use for chronic pain. PF614-MPAR, which combines Ensysce's TAAP™ and MPAR® technologies, has received FDA Breakthrough Therapy designation for its potential to prevent overdose while maintaining pain relief. Supported by a multi-year grant from the National Institute on Drug Abuse (NIDA), the program is advancing toward a new class of opioids designed to reduce the risks of abuse and overdose, a major step toward transforming pain management. OUD Program Update In addition to its pain management pipeline, Ensysce is advancing innovative treatments for opioid use disorder, including novel compounds designed to reduce cravings and prevent relapse without compromising quality of life. Leveraging its proprietary TAAP™ and MPAR® technologies, the Company is developing what may be a safer methadone alternative. In 2024, Ensysce selected PF9001 as its lead OUD candidate, evaluating it for oral delivery, reduced cardiovascular risk, and built-in overdose protection. Supported by a multi-year HEAL (Helping to End Addiction Long-Term) grant from NIDA, the program is progressing toward non-clinical studies to support a future Investigational New Drug (IND) application. In a key milestone during the quarter, Ensysce also received a Notice of Allowance from the U.S. Patent and Trademark Office for a patent covering the composition and use of PF9001, further strengthening its intellectual property position in the OUD space. Q2 2025 Financial Results Cash - Cash and cash equivalents were $2.2 million as of June 30, 2025, compared to $3.5 million as of December 31, 2024. During the quarter, the Company was awarded the second $5.3 million installment of a $15 million, three-year grant from the National Institute on Drug Abuse (NIDA)1. These funds are available for reimbursement of research and development expenses under the MPAR program through May 2026. Federal Grants - Funding under federal grants totaled $1.4 million for the second quarter of 2025, compared to $0.2 million in the same quarter of 2024. The $1.2 million difference is due to the timing of research activities eligible for funding, with increased clinical activities in 2025 for the PF614-MPAR-102 study under the MPAR grant which began in September 2024. Research & Development Expenses - R&D expenses were $1.9 million for the second quarter of 2025 compared to $0.9 million for the same period in 2024. The increase was primarily the result of external research and development costs related to PF614-MPAR, with increased pre-clinical and clinical activity in the 2025 period. General & Administrative Expenses - G&A expenses were constant at $1.2 million in the second quarter of both 2025 and 2024. Other Income (Expense) - Total other income (expense) was income of $16,998 for the second quarter of 2025 compared to expense of $12,351 in the same period of 2024. Net Income (Loss) - Net loss attributable to common stockholders for the second quarter of 2025 was $1.7 million compared to a net loss of $2.0 million for the second quarter of 2024. As a clinical-stage biotech company, the Company's continued research and development efforts toward regulatory approvals for its product candidates are expected to result in losses for the foreseeable future. ¹The research is supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number UO1DA059791. About Ensysce Biosciences Ensysce Biosciences is a clinical-stage company with a goal of disrupting the analgesic landscape by introducing a new class of highly novel opioids for the treatment of severe pain. Leveraging its Trypsin-Activated Abuse Protection (TAAP™) and Multi-Pill Abuse Resistance (MPAR®) platforms, the Company is developing unique, tamper-proof treatment options for pain that minimize the risk of both drug abuse and overdose. Ensysce's products are anticipated to provide safer options to treat patients suffering from severe pain and assist in preventing deaths caused by medication abuse. For more information, please visit www.ensysce.com. Definitions TAAP™: trypsin activated abuse protection - designed to protect against prescription drug abuse. MPAR®: multi-pill abuse resistance - designed to protect against abuse and accidental overdose. Forward-Looking Statements Statements contained in this press release that are not purely historical may be deemed to be forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995 and other federal securities laws. Without limiting the foregoing, the use of words such as "may," "intends," "can," "might," "will," "expect," "plan," "possible," "believe" and other similar expressions are intended to identify forward-looking statements. The product candidates discussed are in clinic and not approved and there can be no assurance that the clinical programs will be successful in demonstrating safety and/or efficacy, that Ensysce will not encounter problems or delays in clinical development, or that any product candidate will ever receive regulatory approval or be successfully commercialized. All forward-looking statements are based on estimates and assumptions by Ensysce's management that, although Ensysce believes to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that Ensysce expected. In addition, Ensysce's business is subject to additional risks and uncertainties, including among others, possible NASDAQ delisting, the initiation and conduct of preclinical studies and clinical trials; the timing and availability of data from preclinical studies and clinical trials; expectations for regulatory submissions and approvals; potential safety concerns related to, or efficacy of, Ensysce's product candidates; the availability or commercial potential of product candidates; continuation of government funding; the ability of Ensysce to fund its continued operations, including its planned clinical trials; the dilutive effect of stock issuances from our fundraising; and Ensysce's and its partners' ability to perform under their license, collaboration and manufacturing arrangements. These statements are also subject to a number of material risks and uncertainties that are described in Ensysce's most recent quarterly report on Form 10-Q and current reports on Form 8-K, available free of charge at the SEC's website at www.sec.gov. Any forward-looking statement speaks only as of the date on which it was made. Ensysce undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required under applicable law. Ensysce Biosciences Company Contact: Lynn Kirkpatrick, Ph.D.Chief Executive Officer(858) 263-4196 Ensysce Biosciences Investor Relations Contact: Shannon DevineMZ North AmericaMain: 203-741-8811ENSC@mzgroup.us Ensysce Biosciences, Inc.Condensed Consolidated Statements of Operations(Unaudited) 2025 2024 2025 2024 $ 1,371,438 $ 181,797 $ 2,691,210 $ 487,519 1,923,430 947,229 3,808,957 1,726,133 1,198,523 1,190,010 2,600,279 2,559,791 3,121,953 2,137,239 6,409,236 4,285,924 (1,750,515 ) (1,955,442 ) (3,718,026 ) (3,798,405 ) 16,998 (12,351 ) 38,936 (1,285,951 ) $ (1,733,517 ) $ (1,967,793 ) $ (3,679,090 ) $ (5,084,356 ) 166 - 166 (216 ) $ (1,733,351 ) $ (1,967,793 ) $ (3,678,924 ) $ (5,084,572 ) $ (0.79 ) $ (3.35 ) $ (2.04 ) $ (9.98 ) Ensysce Biosciences, Inc.Condensed Consolidated Statements of Cash Flows(Unaudited) Six Months Ended June 30, 2025 2024 $ (4,414,280 ) $ (5,718,294 ) 3,123,778 5,637,921 (1,290,502 ) (80,373 ) 3,502,077 1,123,604 $ 2,211,575 $ 1,043,231 Ensysce Biosciences, Inc.Condensed Consolidated Balance Sheets(Unaudited) June 30, December 31, 2025 2024 $ 2,211,575 $ 3,502,077 3,070,020 1,842,605 5,281,595 5,344,682 292,860 252,550 $ 5,574,455 $ 5,597,232 $ 1,042,832 $ 1,357,079 1,045,657 548,458 424,521 301,660 2,513,010 2,207,197 1,033 10,096 2,514,043 2,217,293 3,060,412 3,379,939 $ 5,574,455 $ 5,597,232 SOURCE: Ensysce Biosciences Released August 13, 2025

Financial StatementBreakthrough TherapyPhase 3

31 Jul 2025

·www.einpresswire.com

FDA is requiring opioid pain medicine manufacturers to update prescribing information regarding long-term use

Using its authority under Section 505(o)(3) of the Federal Food, Drug, and Cosmetic Act, FDA required extended-release/long-acting (ER/LA) opioid analgesic (OA) new drug application holders to conduct epidemiologic studies to 1) quantify the serious risks of misuse, abuse, addiction, and fatal and non-fatal overdose in patients using OAs long term and 2) assess potential risk factors for these outcomes. The studies were conducted using prespecified protocols and statistical analysis plans that were reviewed by FDA and discussed in a public scientific workshop. Studies conducted under postmarket requirements (PMRs) 3033-1 and 3033-2 were large, multisite investigations that included patients enrolled in various health insurance plans and health systems across the United States. These studies were, by design, restricted to the relatively small proportion of patients receiving OAs who go on to use them long term and therefore do not inform quantitative questions of risk related to shorter-term use of OAs. PMR 3033-1 was a prospective, observational cohort study that estimated the risks of addiction, abuse, and misuse in adult patients initiating long-term use of Schedule II OAs. Patients were recruited and data were collected from 2017 through 2021. Study participants had been enrolled in selected health insurance plans or health systems for at least one year, and either 1) filled multiple ER/LA OA prescriptions during a 90-day period (“ER/LA cohort”); or 2) filled any Schedule II OA prescriptions covering at least 70 of 90 days (“long-term opioid therapy [LtOT] cohort”). Patients who received any of the qualifying opioid analgesics (i.e., ER/LA OAs or Schedule II OAs, depending on the study cohort) in the previous six months were excluded; however, patients were not excluded for use of other prescription OA therapy. In addition, patients with an existing diagnosis of a terminal illness or opioid use disorder (OUD) in the previous 12 months, receiving methadone or buprenorphine for the treatment of OUD, or receiving hospice care were excluded. Continued OA use was not required during follow-up. After meeting the study eligibility criteria, patients were required to be free of at least one outcome at baseline and to have completed a minimum number of follow-up assessments (at least two of the three-, six-, nine-, and 12-month assessments for misuse and abuse; the 12-month assessment for OUD) to be included in one or more analyses. This resulted in 978 and 1,244 patients being included in one or more analyses for the ER/LA and LtOT cohorts, respectively. Opioid misuse was defined as the intentional use of a drug for a therapeutic purpose inappropriately outside labeling directions or in a way other than prescribed or directed by a health care professional. Opioid abuse was defined as the intentional use of a drug for a nontherapeutic purpose, repeatedly or sporadically, or for the purpose of achieving a positive psychological or physical effect. Misuse and abuse were measured using the Prescription Opioid Misuse and Abuse Questionnaire, a self-reported questionnaire validated for use in this population, which asks about symptoms in the past three months. Over 12 months, across the two cohorts, approximately 22% of included patients newly met criteria for prescription opioid misuse and approximately 9% of included patients newly met criteria for prescription opioid abuse, based on information reported at three-, six-, nine-, and 12-month assessments ( Table 1 ). Addiction was defined in this study as moderate-to-severe OUD, as assessed using a validated, semi-structured interview tool, the Psychiatric Research Interview for Substance and Mental Disorders, DSM-5, Opioid Version (PRISM-5-Op), which asks about symptoms in the past 12 months. OUD was based on a count of symptoms reported in the interview and defined in two ways: 1) using standard DSM-5 criteria, and 2) using modified criteria in which most DSM-5 symptoms were counted toward an OUD designation only when the patient indicated a non-pain reason for opioid use associated with that symptom, and the “persistent desire or attempts to quit or cut down on opioid use” criterion was counted only if multiple unsuccessful attempts were made. Over 12 months, across the two cohorts, the percentage of included patients who newly met criteria for moderate-to-severe OUD was approximately 3-6% using the standard DSM-5 criteria and approximately 1-2% using the modified DSM-5 criteria, based on information reported at the 12-month assessment ( Table 1 ). Several factors (e.g., potential volunteer bias, predominance of managed care and integrated healthcare systems) may have limited the generalizability and interpretability of findings. PMR 3033-2 was a retrospective, observational cohort study that estimated the risk of opioid-involved overdose or opioid overdose-related death (together, abbreviated as OOD) in adult patients with new long-term use of Schedule II OAs between 2006 and 2016 (n=220,249). The study included patients enrolled in either one of two commercial insurance programs, one managed care program, or one Medicaid program for at least nine months. New long-term use was defined as having Schedule II OA prescriptions 1 covering at least a 70-days’ supply over the three months before cohort entry and none during the preceding six months. Patients were excluded if they had an opioid-involved overdose in the nine months prior to cohort entry. The outcome was the first OOD event during the follow-up period, as measured using a validated medical-code-based algorithm with linkage to the National Death Index database. The cumulative incidence of OOD increased steadily throughout the five-year follow up period, resulting in a five-year cumulative incidence ranging from approximately 1.5% to approximately 4% ( Table 2 ). Over the entire study period (5-11 years, depending on study site), approximately 17% of first OOD events were fatal. There are a number of considerations when interpreting the findings from PMR 3033-2. OOD events may not have involved the prescribed OAs; rather, they could have occurred after a patient discontinued prescribed OA use and could have involved illicit opioids like heroin or fentanyl. Since the outcome for this study included only the first OOD event, a patient could have experienced subsequent events, including fatal overdose, that would not have been included in the OOD incidence estimates. Additionally, the intentionality of the OOD event (i.e., suicide vs. accidental) could not be adequately confirmed. Several factors could have contributed to bias. There was substantial attrition over the first five years of follow-up, and although this study used an incidence measure designed to account for loss to follow-up, if those who left the cohort (e.g., due to insurance disenrollment) systematically had a different risk of OOD than those remaining in the study, incidence estimates could have been biased. In addition, limiting the cohort to patients with no recent documented opioid-involved overdose likely selected patients at lower risk of OOD during follow-up. Finally, opioid overdoses that were reversed by a bystander or that otherwise did not result in either a medical claim or death were not captured. Both studies collected patient- and drug-related characteristics at baseline and conducted exploratory analyses of potential risk factors for misuse, abuse, addiction, and overdose. Many factors were associated with one or more outcomes, with one of the strongest and most consistent risk factors being a personal history of a substance use disorder. 2 In addition, higher OA dose during the three months before cohort entry was a strong and consistent risk factor for OOD. Neither study was designed to assess associations between changes in OA dose or discontinuation of opioids and adverse opioid-related outcomes. 1 Hydrocodone fixed combinations were reclassified from Schedule III to Schedule II in October 2014. Products containing hydrocodone were treated as a Schedule II opioid throughout PMR 3033-2. 2 A notable proportion of patients starting long-term OA therapy in these studies had a personal history of SUD, whether in the past year (in PMR 3033-1, 6.5% to 8% had a past-year non-opioid, non-nicotine substance use disorder, based on interview measures; in PMR 3033-2, approximately 4-6% each had OUD, alcohol use disorder, or another substance use disorder, based on diagnostic codes). PMR 3033-1 also assessed SUDs prior to the past year (29% to 34.1% had a prior-to-past-year non-opioid, non-nicotine substance use disorder, based on interview measures). Table 1. Incidence of Prescription Opioid Misuse, Prescription Opioid Abuse, and OUD in Prospective PMR 3033-1 Prescription Opioid Misuse Prescription Opioid Abuse Moderate-to-Severe OUD Pain-Adjusted DSM-5-OUD 1 DSM-5-OUD 2 ER/LA cohort 3 N 804 911 850 850 12-month incidence proportion (%, 95% CI) 22.8 (21.6, 24.0) 9.4 (7.7, 11.6) 1.4 (0.9, 2.3) 5.8 (4.5, 7.3) LtOT cohort 4 N 1,003 1,151 1,102 1,102 12-month incidence proportion (%, 95% CI) 21.6 (18.3, 25.5) 8.6 (7.4, 10.0) 1.6 (0.9, 2.9) 3.4 (2.5, 3.1) Source: Adapted from Final Study Report for Prospective PMR 3033-1. 1 Moderate-to-severe pain-adjusted DSM-5-OUD was defined as having four or more pain-adjusted DSM-5 criteria for OUD related to prescription opioid use or two or more DSM-5 criteria related to heroin use, as measured by the PRISM-5-Op. 2 Moderate-to-severe DSM-5 OUD was defined as having four or more standard DSM-5 criteria for OUD related to prescription opioid use or two or more DSM-5 criteria related to heroin use, as measured by the PRISM-5-Op. 3 Includes patients who initiated an ER/LA OA that included at least 28 days’ supply of an ER/LA OA within a 60-day window followed by a subsequent ER/LA OA prescription within a 7-day period, all within a 90-day period prior to the patient’s baseline interview. Patients could not have used an ER/LA OA in the 6 months before the initial 28 days’ supply of an ER/LA OA, but patients on IR/SA OAs during the same 6 months were still eligible for this cohort. 4 Includes patients who initiated either an ER/LA OA or a Schedule II IR/SA OA for at least 70 of the past 90 days. Patients could not have used an ER/LA OA or a Schedule II IR/SA OA in the 6 months before the initial ER/LA OA or Schedule II IR/SA OA prescription contributing to at least 70 days of use, but other prescription OA therapy would not exclude them (e.g., tramadol use). Abbreviations: CI, confidence interval; DSM-5, Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; ER/LA, extended-release/long-acting; LtOT, long-term opioid therapy; N, number; OA, opioid analgesic; OUD, opioid use disorder; PMR, postmarketing requirement; PRISM-5-Op, Psychiatric Research Interview for Substance and Mental Disorders, DMS-5, Opioid Version Table 2. Cumulative Incidence of OOD in PMR 3033-2 HealthCore KPNW Optum VUMC N 81,782 12,009 54,515 71,932 5-year cumulative incidence (%, 95% CI) 1 1.5 (1.4, 1.6) 1.4 (1.2, 1.7) 1.5 (1.3, 1.8) 4.1 (3.9, 4.3) Source: Adapted from the Final Study Report for PMR 3033-2. 1 Five-year cumulative incidence is the complement of the Kaplan-Meier OOD-free survival preceding 5 years measured in percent (%) scale Abbreviations: CI, confidence interval; KPNW, Kaiser Permanente Northwest; N, number; OOD, opioid-involved overdose or opioid overdose-related death; PMR, postmarketing requirement; VUMC, Vanderbilt University Medical Center (Medicaid) Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.

Clinical ResultPhase 2

28 Jul 2025

·www.prnewswire.com

Standard drug screening fails to identify some children who have been exposed to substances in unsafe home environments

New findings at ADLM 2025 could remedy this CHICAGO, July 28, 2025 /PRNewswire/ -- According to research presented today at ADLM 2025 (formerly the AACC Annual Scientific Meeting & Clinical Lab Expo), standard drug screening misses low concentrations of targeted substances in around 5% of urine samples taken from patients under age 18, suggesting that children with drugs in their systems are sometimes released from healthcare settings into unsafe home environments. The study highlights an adjustment that clinical labs can make to improve the accuracy of results and to help ensure that substance-exposed children and their families get appropriate support. Researchers have long known that standard urine drug screening (UDS) — which is typically done using a technique known as immunoassay — can sometimes trigger false positives, or erroneous results that indicate the presence of a drug when there isn't one. It's the reason a second confirmatory test with mass spectrometry is typically used to verify results for patients who test positive on immunoassay. However, the opposite issue, where UDS indicates an absence of drugs in patients who have actually taken them (false negatives), has not been well studied. This mistake is more likely to occur in samples taken from infants and young children whose kidneys are still developing or who have incidental exposure to a low level of drugs, resulting in a low drug concentration in their urine that may not reach the cutoff used in standard UDS. One approach for minimizing this possibility is to use mass spectrometry on all pediatric patients, skipping the initial immunoassay. "To our knowledge, St. Louis Children's is the only hospital in the U.S. to adopt this 'direct-to-mass-spectrometry' approach," said Dr. Yanchun Lin, one of the study's authors and a clinical chemistry fellow at Washington University in Saint Louis, Missouri. "So we really want to urge laboratorians to reconsider the approach they adopt for pediatric UDS testing." The researchers used two strategies to compare immunoassay results with mass spectrometry for detecting substances in common drug tests, including amphetamine/methamphetamine, cocaine/benzoylecgonine (the main metabolite of cocaine), THC, opiates, fentanyl, benzodiazepines, and methadone. In the first approach, they studied 125 urine samples over a 5-month period from pediatric patients with weakly positive results on mass spectrometry to check how many of them were missed by immunoassay (forward approach). For the second strategy, they assessed 115 urine samples that tested negative on immunoassay to assess if mass spectrometry could detect any drugs (reverse approach). Among the 125 samples that tested positive on mass spectrometry, 112 (approximately 90%) contained compounds not detected by immunoassay, most commonly methamphetamine and benzoylecgonine. Thirty-eight (33%) of the 115 samples found negative on routine UDS tested positive for at least one substance when re-examined by mass spectrometry. Moreover, mass spectrometry identified substances in six samples (5%) that were targeted but missed by immunoassay. In addition, the researchers identified 32 pediatric urine samples that contained prescription medications not picked up by immunoassay, including lorazepam, ketamine, bupropion, methylphenidate, clonidine, quetiapine, venlafaxine, and naloxone. They also found five samples containing fentanyl, which wasn't on the UDS menu at some study centers from which samples were taken. Taken together, the results indicate that UDS may miss low drug concentrations in approximately 1 in 20 pediatric urine samples. This finding held true using both the forward and reverse schemes, spanning multiple clinical environments and analytic platforms. Using a direct-to-mass spectrometry approach would significantly lessen the risk of false-negative drug screens and largely eliminate false-positive findings as well, the authors conclude. That said, making this change isn't without challenges for labs. "It's actually pretty labor intense," Lin said, "and it's much harder to maintain the assay" using the direct-to-mass spectrometry approach. "You need highly trained personnel and dedicated full-time employees," she added. But labs that can make the shift will benefit from more accurate results that could translate to better care. "If it's possible, it should definitely be adopted, especially for pediatric patients," Lin said. Session information ADLM 2025 registration is free for members of the media. Reporters can register online here: Abstract A-349: False-negative immunoassay drug screens uncovered with a direct to mass spectrometry approach in a pediatric population will be presented during: Student poster competition Monday, July 28 9:30 a.m. – 4 p.m. Room S405 Scientific poster session Tuesday, July 29 9:30 a.m. – 5 p.m. (presenting authors in attendance from 1:30 – 2:30 p.m.) Poster Hall on the Expo show floor Both sessions will take place at McCormick Place, Chicago. About ADLM 2025 ADLM 2025 (formerly the AACC Annual Scientific Meeting & Clinical Lab Expo) offers 5 days packed with opportunities to learn about exciting science from July 27-31 in Chicago. Plenary sessions will explore urgent problems related to clinical artificial intelligence (AI) integration, fake medical news, and the pervasiveness of plastics, as well as tapping into the promise of genomics and microbiome medicine for personalized healthcare. At the ADLM 2025 Clinical Lab Expo, more than 800 exhibitors will fill the show floor of the McCormick Place Convention Center in Chicago, with displays of the latest diagnostic technology, including but not limited to AI, point-of-care, and automation. About the Association for Diagnostics & Laboratory Medicine (ADLM) Dedicated to achieving better health for all through laboratory medicine, ADLM (formerly AACC) unites more than 70,000 clinical laboratory professionals, physicians, research scientists, and business leaders from 110 countries around the world. Our community is at the forefront of laboratory medicine's diverse subdisciplines, including clinical chemistry, molecular diagnostics, mass spectrometry, clinical microbiology, and data science, and is comprised of individuals holding the spectrum of lab-related professional degrees, certifications, and credentials. Since 1948, ADLM has championed the advancement of laboratory medicine by fostering scientific collaboration, knowledge sharing, and the development of innovative solutions that enhance health outcomes. For more information, visit . Christine DeLong ADLM Director, Editorial and Media Relations (p) 202.835.8722 [email protected] Bill Malone ADLM Senior Director, Strategic Communications (p) 202.835.8756 [email protected] SOURCE Association for Diagnostics & Laboratory Medicine (ADLM) WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultClinical Study

100 Deals associated with Methadone Hydrochloride

External Link

KEGG	Wiki	ATC	Drug Bank
D02102	Methadone Hydrochloride	N07BC02	DB00333

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Indication	Country/Location	Organization	Date
Cancer Pain	Japan	Shionogi & Co., Ltd.	01 Mar 2013
Opioid-Related Disorders	China	Central Pharmaceutical JSC No. 3	01 Jan 1997
Opioid abuse	United States	Hikma Pharmaceuticals USA, Inc.	14 Mar 1973
psychological symptoms behavior compulsive behavior addiction	United States	Hikma Pharmaceuticals USA, Inc.	14 Mar 1973
psychological symptoms behavior compulsive behavior addiction	United States	SpecGx LLC	14 Mar 1973
Opium Dependence	United States	Mylan Institutional LLC	13 Aug 1947
Pain	United States	Mylan Institutional LLC	13 Aug 1947

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetic Neuropathies	Phase 2	-	Methapharm, Inc.	01 Jan 2012

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT06110546 (IMPACTOR, CTgov)	Phase 4	-	2	Methadone group (Methadone Group)	hsfrbyavxa = kxbqfjxeok cteoiuceex (yqewrnvdbv, jnbcdtjdoy - piymrzdtgr) View more	-	01 Aug 2025
				Usual care (Non-Methadone Group)	zrzauukvbn(vxxoagtktt) = bqlwvczcec fccimzqfci (xoourklgmz, ngtvgdbqmt - dcdirdyujp) View more
NCT05445856 (EudraCT ID 2022-002496-11, Pubmed \| BJA Open)	Phase 4	-	120	Methadone	hyfldnxxrn(ptzvhezdxf) = srfxhumyfc tabrqlyhbx (ugmwteyvcy, 10 - 50)	Positive	01 Jun 2025
				Fentanyl	hyfldnxxrn(ptzvhezdxf) = clcrwyatgf tabrqlyhbx (ugmwteyvcy, 29 - 80)
NCT04214834 (CTgov)	Phase 3	Neonatal Abstinence Syndrome	189	methadone+morphine (Rapid Wean)	epxpixgjvc(uivhylobjp) = osgoeruzln fpwkwxnmde (fwbjdmikhy, 6.3) View more	-	13 Mar 2025
				methadone+morphine (Slow Wean)	epxpixgjvc(uivhylobjp) = tmyqxepeue fpwkwxnmde (fwbjdmikhy, 6.1) View more
NCT05425420 (MTH02, CTgov)	Phase 1/2	Pain, Postoperative	22	Methadone	oimnqjbvda(bicepscktb) = wsknqsszyk earvsrakwe (fyfsswfqib, 1.42) View more	-	10 Feb 2025
NCT05244226 (CTgov)	Phase 2	Sleep Apnea, Obstructive \| Tonsillitis \| Pain, Procedural	66	Hydromorphone+Fentanyl	cxhhjneipu(zedgsnlhvb) = nqwqvoljti irzazzojmk (uvfezpkuil, viriryaurw - napbssuvuc) View more	-	17 Oct 2024
NCT03033732 (Pubmed \| HIV Med)	Phase 4	Opioid abuse	272	Methadone	wbruuxofom(acauyjfkjh) = uqrwgczwus fpapmdpjvd (bzgwzvxwph ) View more	Positive	01 Jul 2024
				Buprenorphine/naloxone	wbruuxofom(acauyjfkjh) = eaueqsjlfq fpapmdpjvd (bzgwzvxwph ) View more
NCT03033732 (Pubmed \| Can J Psychiatry) Manual	Phase 4	Opioid abuse	268	methadone or buprenorphine/naloxone	-	Negative	01 Mar 2024
				Methadone Maintenance Therapy (MMT)	whvwhhzark(thakyhufmn) = ekpxsgouch pjgmajcnxc (nubyjbpujt ) View more
NCT02252432 (CTgov)	Phase 4	Pain, Postoperative	13	methadone+Ketamine (Ketamine)	fprlbfvezd(oglsqfugid) = dujqlzdxcr zccagilero (ueyqxmkdpz, 20) View more	-	29 Feb 2024
				methadone+ketamine (Methadone)	fprlbfvezd(oglsqfugid) = fyhzadfdig zccagilero (ueyqxmkdpz, 16) View more
WSC2023	Not Applicable	-	-	Opioid medications	diywqaxjgn(cbgbpuceym) = aiquwokiks plwyuiulwf (jlestoqyte )	-	23 Oct 2023
EUCTR2018-004351-20-DK \| NCT03908060 (Pubmed)	Phase 4	-	-	Methadone 0.2 mg/kg	cagxjjsgnz(abdtdaxlro) = iviscrfwho axoynfxtmx (ptknglacxb )	-	01 Sep 2023
				Morphine 0.2 mg/kg	cagxjjsgnz(abdtdaxlro) = mbozohuexu axoynfxtmx (ptknglacxb )

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