Journal Of Addiction Medicine[JOURNAL]
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200 papers
A Narrative Review of the Metabolic Assessment of Patients on Methadone: An Alternative to Pharmacokinetically Blind Prescribing.
McCarthy JJ, Leamon MH
J Addict Med · 2026 May · PMID 42206660 · Publisher ↗
With the increase in fentanyl use, methadone remains one of the standards of care for opioid use disorder and may confer some advantages over buprenorphine. Yet the wide range of patient metabolism makes individual presc...
With the increase in fentanyl use, methadone remains one of the standards of care for opioid use disorder and may confer some advantages over buprenorphine. Yet the wide range of patient metabolism makes individual prescribing unpredictable. Induction and subsequent dose adjustments have historically been guided using a "start low and go slow" approach to minimize the risk of overdose, with individual metabolic differences unassessed. However, heroin's replacement by fentanyl in the illegal market has resulted in unprecedented levels of physical dependence necessitating higher doses and more rapid inductions. Methadone metabolism is unpredictable, largely due to phenotypic and genotypic variability of cytochrome P450 enzyme activity. Early research found a 17-fold variation in serum level for a given dose, corroborated recently by finding an equally wide range of individual metabolic speeds. Little work has been done documenting how this variability affects clinical response. Dosing practices have remained "pharmacokinetically blind" to a patient's capacity to metabolize a medication with a narrow therapeutic window and potentially serious consequences of underdosing or overdosing. Serum-based measures of methadone can provide objective information on individual metabolism. These tests include trough levels, peak levels, a methadone/metabolite ratio, and a peak/trough ratio. Genetic testing for variant alleles that alter metabolism (pharmacokinetics) or alter mu receptor activity (pharmacodynamics) can identify patients whose ability to metabolize methadone is either impaired or augmented. This review discusses the laboratory tools available to guide safe induction protocols and subsequent prescribing.
Utility of Methadone:Metabolite Ratio as Marker of Methadone Metabolism During Methadone Initiation in Pregnancy.
Boelig RC, Hand DJ, Belyakov A … +6 more , McCarthy JJ, Jain S, Soni V, Kaushal G, Zhan T, Kraft WK
J Addict Med · 2026 May · PMID 42206652 · Publisher ↗
OBJECTIVES: The methadone:metabolite ratio (MMR) is a laboratory value assessed pre-dose to discriminate between individuals who are rapid or slow metabolizers. It is a proposed alternative to peak:trough serum methadone...
OBJECTIVES: The methadone:metabolite ratio (MMR) is a laboratory value assessed pre-dose to discriminate between individuals who are rapid or slow metabolizers. It is a proposed alternative to peak:trough serum methadone ratios to assess the impact of individual genetics on methadone metabolism to guide dosing frequency of methadone in adults. Pregnancy represents a state of dynamic metabolism of many drugs, including methadone, but there is little study of the MMR in pregnancy. We aimed to (1) assess how well MMR assessed during methadone initiation in pregnancy correlates with the gold standard of assessing metabolism (peak:trough ratio which requires 2 blood draws), (2) describe MMR as assessed during initiation of methadone across gestation to see if it reflected altered metabolism in pregnancy, and (3) determine whether differences in MMR correlated with measures of therapeutic effect, which would suggest it is a potentially useful tool to guide dosing regimens of methadone in pregnancy. METHODS: This is a prospective study of pregnant patients with singleton gestation admitted for methadone initiation starting with a dose of 30 mg and increasing by 10 mg every 4 hours as needed based on withdrawal symptoms, with an increase in the daily dose the next day. Plasma samples of methadone and the metabolite EDDP were obtained pre-morning dose and 4 hours post-dose. MMR was evaluated both as a continuous variable and categorical: MMR<5: ultra-rapid metabolizer, MMR 5-11: extensive metabolizer, MMR 12-16: intermediate metabolizer, MMR≥16 ultra-slow metabolizer. Additional endpoints of Clinical Opioid Withdrawal Scale (COWS) and pupil dilation were assessed. Multivariable generalized estimating equations used for analyses. RESULTS: From March 2023 to May 2024 31 patients with 107 samples available were included. MMRtrough increased with methadone dose the prior 24 hours [0.01 (0.01, 0.02), P<0.001] and decreased with advancing trimester of admission [-2.95 (-5.00, -0.90), P=0.005 for second vs. first trimester and -2.78 (-4.98, -0.58), P=0.01 for third vs. first trimester]. A greater proportion of results reflected an ultra-rapid metabolizing state in the second and third trimester compared with the first (77% and 71% vs. 23%, P<0.001). MMR was highly correlated with log-corrected methadone peak:trough throughout gestation, regardless of trimester [B coefficient -3.36 (-5.65 to -1.06), P=0.004]. Regarding clinical effects-pupil dilation was significantly associated with methadone dose, with an expected pupilar constriction associated with increasing methadone dose [-0.55 (-0.75, -0.34) P<0.001]. There was significantly reduced pupillary constriction (relative larger post-dose diameter) identified in the third trimester versus first [adjusted mean difference 0.67 (0.20, 1.13)]. There was no significant association between MMR and pupillary change. MMR was associated with time needed to achieve a stable dose, with those who were extensive metabolizers requiring greater time to stable dose compared with ultra-rapid metabolizers [mean difference 3.37 (0.61-6.13) d, P=0.02]. CONCLUSIONS: Although MMR has historically been used to reflect genetic variants impacting methadone metabolism, in pregnancy it reflects the increased metabolism with advancing gestation and is associated with clinical/therapeutic effect. MMR may be a useful marker to guide methadone dosing protocols in pregnancy to optimize therapeutic effect.
Development and Validation of an Image-Based Deep Learning Tool for Identification of Xylazine-Associated Wounds.
Sompalle P, Sarker A, Love J … +5 more , Moon J, Spadaro A, Wightman R, Torgersen J, Perrone J
J Addict Med · 2026 May · PMID 42206647 · Publisher ↗
OBJECTIVES: Accurate identification of xylazine-associated wounds (XAWs) is critical to providing timely and optimal management; however, discerning the etiology of wounds by appearance alone poses a clinical challenge....
OBJECTIVES: Accurate identification of xylazine-associated wounds (XAWs) is critical to providing timely and optimal management; however, discerning the etiology of wounds by appearance alone poses a clinical challenge. This study sought to develop an accessible and accurate approach for XAW diagnosis using a deep learning tool applied to wound photographs. METHODS: Publicly accessible wound photographs were curated from academic publications, Reddit, and news media to develop, train, and test the deep learning tool. XAWs were defined by provided clinical confirmation or self-reported descriptions associated with each image. The data set included images of 114 xylazine-associated and 1710 nonxylazine wounds from 17 distinct pathologies. Four deep learning models (DenseNet121, EfficientNetB0, ResNet34, and SENet154) were trained on 1185 images (65%) and 163 for validation (9%) to predict xylazine exposure and tested using 476 unseen wound images (26%). RESULTS: All 4 deep learning models achieved consistent diagnostic performance on 476 unseen wound images (accuracy: 97.5%-98.5%; AUROC: 96.8%-99.7%; weighted F1 score: 97.2%-98.5%). High specificity, reaching 100.0%, was observed across the 4 models. Sensitivity ranged from 60.0% to 80.0% across the 4 models, with SENet154 demonstrating robust performance across all metrics. Qualitative assessment demonstrated accurate identification of XAWs with high-confidence exclusion of xylazine exposure in wounds attributed to trauma, surgery, pressure, or venous ulcers. CONCLUSIONS: This novel deep learning tool can enable accurate identification of XAW. With further validation, this tool may offer an accessible and automated approach to guide wound care, augment bedside clinical medicine assessments, and equip public health efforts to monitor xylazine's geographic distribution.
Association of Emergency Department Buprenorphine Initiation With Subsequent Pharmacotherapy and Outcomes Among Patients With Opioid Use Disorder.
Treitler P, Akincigil A, Peterson NA … +2 more , Williams AR, Crystal S
J Addict Med · 2026 May · PMID 42206614 · Full text
OBJECTIVES: To examine trends in emergency department (ED) buprenorphine initiation and evaluate its association with outcomes in the 180 days following discharge. METHODS: This observational cohort study used 2018-2022...
OBJECTIVES: To examine trends in emergency department (ED) buprenorphine initiation and evaluate its association with outcomes in the 180 days following discharge. METHODS: This observational cohort study used 2018-2022 New Jersey Medicaid claims data from patients presenting to EDs for opioid-related causes, excluding visits that resulted in inpatient admission. We used prescription and encounter data to identify patients with opioid use disorder (OUD) or opioid overdose who initiated buprenorphine in the ED and propensity score matching to compare outcomes of initiators and noninitiators. Outcomes measured during 180-day follow-up were the proportion of days covered (PDC) with medication for OUD (MOUD) and the number of drug overdoses, opioid overdoses, and all-cause ED/inpatient visits within 180 days. RESULTS: Buprenorphine was initiated in 978 of 24,732 (4.0%) opioid-related ED visits, with this proportion increasing from 0.8% in 2018 to 7.1% in 2022. Buprenorphine initiation was associated with greater MOUD PDC (β=0.10, 95% CI: 0.08-0.13) and fewer all-cause ED/inpatient visits (IRR=0.87, 95% CI: 0.77-0.98) during follow-up. We did not find a statistically significant association between ED buprenorphine initiation and postdischarge overdose; however, greater PDC in the 180-day follow-up period was associated with fewer drug overdoses (IRR=0.80, 95% CI: 0.68-0.94), opioid overdoses (IRR=0.78, 95% CI: 0.67-0.91), and all-cause ED/inpatient visits (IRR=0.89, 95% CI: 0.82-0.96). CONCLUSIONS: EDs play a central role in initiating patients on MOUD, but longer-term outcomes likely depend on multiple factors that may go beyond the scope of ED practice. Further efforts are needed to support MOUD retention and reduce the risk of adverse outcomes following opioid-related ED visits.
County-Level Uptake of Take-Home Methadone and Adverse Events Among Commercially Insured Individuals.
Wanga V, Cullen D, Kratchman J … +5 more , Adkins SH, Lerner B, Raina D, Pirard S, Gordon AS
J Addict Med · 2026 May · PMID 42184988 · Publisher ↗
OBJECTIVES: To maintain access to methadone treatment for opioid use disorder (OUD)-an ongoing public health issue in the United States-the Substance Abuse and Mental Health Services Administration (SAMHSA) implemented p...
OBJECTIVES: To maintain access to methadone treatment for opioid use disorder (OUD)-an ongoing public health issue in the United States-the Substance Abuse and Mental Health Services Administration (SAMHSA) implemented policy changes allowing states to expand take-home methadone doses during and after the COVID-19 pandemic. This study examined the association between county-level uptake of take-home methadone, under the policy changes, on adverse events (overdose rates, hospitalizations and emergency department [ED] visits) and methadone treatment continuity among adults with OUD. METHODS: Using difference-in-differences methodology, we analyzed administrative claims between January 2016 and April 2024 from commercially insured members of a large US health insurer, comparing outcomes between counties that had any uptake of take-home methadone and counties that had no uptake. RESULTS: Any county-level uptake of take-home methadone was not associated with a difference in rates of opioid and other drug overdoses, behavioral health (BH)-related or OUD-related ED visits or hospitalizations, or methadone continuity. CONCLUSIONS: Findings suggest that expanding access to take-home methadone may not increase public health risks, supporting implementation of policies that encourage take-home methadone dosing for eligible individuals with OUD.
Benzodiazepine Tapering: Evidence Limitations and Research Recommendations.
Kleykamp BA, Devoto A, Lindsay D … +15 more , Mazer-Amirshahi M, Brunner E, Chen CA, Klein T, Maust DT, Mecca M, Najera D, Ogbonna C, Rajneesh KF, Roll E, Sanders AE, Snodgrass B, VandenBerg A, Wright T, Boyle MP
J Addict Med · 2026 May · PMID 42160770 · Publisher ↗
INTRODUCTION: Current guidelines often recommend limiting benzodiazepine (BZD) use to 2-4 weeks. However, long-term use remains common, in part due to the challenges of tapering BZDs in the context of physical dependence...
INTRODUCTION: Current guidelines often recommend limiting benzodiazepine (BZD) use to 2-4 weeks. However, long-term use remains common, in part due to the challenges of tapering BZDs in the context of physical dependence and withdrawal risk. This publication aims to evaluate the current evidence on BZD tapering and outline key research recommendations. METHODS: In the process of developing the Joint Clinical Practice Guideline on Benzodiazepine Tapering, which included a systematic review (SR), we identified important research gaps in the literature on BZD tapering. We used the guideline development process, SR, other overlapping reviews, and feedback collected during guideline development to inform proposed research recommendations. RESULTS: Our review identified wide variability in tapering strategies and outcome measures, significant methodological limitations, and a lack of safety and patient-reported outcomes in the literature. Based on this knowledge, we propose research recommendations to address key gaps in the existing evidence base, including (1) comparative effectiveness and pragmatic trials; (2) adjunctive interventions; (3) adaptive approaches; (4) use of very long-acting agents for tapering; and (5) shared decision-making strategies. We also highlight 5 methodological recommendations, including the importance of collecting standardized data on patient-centered outcomes, safety, BZD use history, at-risk populations, and the use of consistent terminology. CONCLUSION: There is a critical need for rigorous, standardized, and patient-centered research on BZD tapering. Addressing the identified research gaps will improve the quality of evidence supporting clinical decision-making, thereby enhancing the safety and effectiveness of tapering strategies for diverse patient populations.
A Comparison of Neuropsychological Functioning Between Patients With Opioid Use Disorder Treated With Extended-Release Naltrexone or Buprenorphine-Naloxone.
Castillo F, Campbell ANC, Choo TH … +5 more , Pavlicova M, Rotrosen J, Selzer JA, Lee J, Nunes EV
J Addict Med · 2026 May · PMID 42150776 · Publisher ↗
BACKGROUND AND OBJECTIVES: People with opioid use disorder (OUD) who are in safety-sensitive occupations are often not allowed to work if taking methadone or buprenorphine due to concerns about cognitive impairment from...
BACKGROUND AND OBJECTIVES: People with opioid use disorder (OUD) who are in safety-sensitive occupations are often not allowed to work if taking methadone or buprenorphine due to concerns about cognitive impairment from opioid agonist effects. Naltrexone, an antagonist which lacks opioid agonist effects, has fewer restrictions. However, comparisons of neurocognitive effects across treatments are limited. METHODS: This post hoc analysis examined observed Trailmaking Test (TMT) difference scores and Stroop Color-Word accuracy and interference scores at 4, 8, 16, and 24 weeks after treatment initiation with either extended-release injection naltrexone (XR-NTX) (N=283) or sublingual buprenorphine-naloxone (BUP-NX) (N=287) in a randomized, nonblinded, trial of patients with OUD. Scores were compared between medication groups across time points with linear mixed-effects regression. RESULTS: There were no significant effects of medication group or time for either the TMT or the Stroop tests. TMT difference scores at baseline were 48.40±24.12 (XR-NTX) and 48.26±25.45 seconds (BUP-NX), with model-estimated means (SE) across post-initiation time points: XR-NTX: 37.53 (1.62); BUP-NX: 37.80 (1.51); difference: -0.26 (1.59), P=0.87; 95% CI [-3.38, 2.86]. Stroop Color-Word accuracy and interference scores at baseline were 49.65 (XR-NTX) versus 50.88 (BUP-NX) and 51.11 (XR-NTX) versus 51.68 (BUP-NX), respectively. Model estimated means (SE) across post-initiation timepoints were: accuracy: XR-NTX: 56.54 (0.90); BUP-NX: 56.22 (0.75); difference: 0.33 (0.73), P=0.65; 95% CI [-1.1, 1.76]; interference: XR-NTX: 54.15 (0.76); BUP-NX: 54.67 (0.73); difference: -0.52 (0.62), P=0.41; 95% CI [-1.74, 0.70]. CONCLUSIONS: Neurocognitive performance did not significantly differ between patients with OUD treated with XR-NTX or BUP-NX. These results suggest that absolute restrictions on buprenorphine use in safety-sensitive occupations may be unwarranted. Individual cognitive assessments may still be appropriate based on specific job demands.
Kratom Use and Associations With Mental Health in the United States.
McCabe SE, Bogan RC, Dickinson K … +3 more , McCabe VV, Menke NB, Schepis TS
J Addict Med · 2026 May · PMID 42127205 · Full text
OBJECTIVES: To assess the US lifetime and past-year prevalence of kratom Mitragyna speciosa use and its associations with mental health and DSM-5 substance use disorder (SUD). METHODS: This study examined cross-sectional...
OBJECTIVES: To assess the US lifetime and past-year prevalence of kratom Mitragyna speciosa use and its associations with mental health and DSM-5 substance use disorder (SUD). METHODS: This study examined cross-sectional survey data collected from 169,408 non-institutionalized individuals aged 12 and older in US households between 2021 and 2024. Measures included kratom use, nonmedical use of cannabis, prescription drugs (opioids, sedatives/tranquilizers, stimulants), other drugs, mental health indicators (serious psychological distress, DSM-5 major depression, suicidal ideation), and DSM-5 SUD. RESULTS: Between 2021 and 2024, lifetime and past-year kratom use were highest among adults aged 21 to 34, 3.40% (95% CI: 3.17-3.65) and 1.01% (95% CI: 0.91-1.13), respectively. Among people who reported prior-to-past-year kratom use, most reported past-year cannabis (65.7%; 95% CI: 60.4-70.3) and had a past-year SUD (52.8%; 95% CI: 50.1-55.4), whereas an estimated 37.8% (95% CI: 37.2-47.3) experienced serious psychological distress. Similar results were observed for those who reported past-year kratom use. Multivariate logistic regression analysis revealed prior-to-past-year and past-year kratom use was associated with increased adjusted odds of past-year SUD (AOR: 4.36; 95% CI: 3.89-4.88 and AOR: 4.81; 95% CI: 3.99-5.80, respectively). Similar results were found for other substance use, DSM-5 major depression, and suicidal ideation. CONCLUSIONS: Over 5 million people in the United States used kratom in their lifetime, with the highest use at ages 21-34 years. Kratom use is increasing and strongly associated among individuals who use cannabis, have a DSM-5 SUD, and experience serious psychological distress. These findings reinforce a profile of individuals who use kratom, many with behavioral health symptoms, and need evidence-based treatment warranting consideration in clinical and policy efforts.
Response to Correspondence on "Precipitated Withdrawal Following Emergency Department-initiated Buprenorphine: A Retrospective Study.
Wilkerson RG, Gingold DB
J Addict Med · 2026 May · PMID 42117382 · Publisher ↗
Abstract loading — click title to view on PubMed.
Does 6.7% Reflect Reality? Response to "Precipitated Withdrawal Following Emergency Department-initiated Buprenorphine: A Retrospective Study".
Marrone E, Esposito E
J Addict Med · 2026 May · PMID 42117379 · Publisher ↗
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Development and Testing of a Peer Recovery Support Services Intervention for Retention on Medications for Opioid Use Disorder.
Wenzel KR, Carrano J, Bormel A … +3 more , Olaiya O, Pattanaik S, Fishman M
J Addict Med · 2026 May · PMID 42109228 · Full text
OBJECTIVES: This study investigated the acceptability and preliminary efficacy of a peer recovery support services (PRSS) intervention focused on enhancing retention on medication for opioid use disorder (MOUD) through a...
OBJECTIVES: This study investigated the acceptability and preliminary efficacy of a peer recovery support services (PRSS) intervention focused on enhancing retention on medication for opioid use disorder (MOUD) through a pilot RCT. METHODS: Individuals on MOUD who were newly living in a recovery residence or a long-term residential program (ie, ASAM level 3.1) were randomized to either MOUD-focused PRSS or usual care only for 24 weeks (168 d). Negative binomial and logistic regression analyses using data from 40 adults (n=20 in PRSS and n=20 in TAU) tested for group differences on the primary outcome of cumulative days of MOUD adherence and secondary outcomes of other MOUD retention metrics, opioid use and return to regular use, and intervention acceptability assessed with an investigator-created satisfaction survey. RESULTS: Results revealed no group differences on primary or secondary outcomes, with those in PRSS reporting M=126 days of MOUD adherence compared with M=127 days in TAU. Overall satisfaction levels averaged 6.71 out of a possible 7. CONCLUSIONS: The results of this study did not support our hypothesis that PRSS would enhance MOUD adherence; however, this is likely due to a ceiling effect. Participants from both groups had higher-than-expected MOUD adherence (∼75% of days). Participants who received the PRSS intervention rated it very highly, and notably, were not opposed to the integration of MOUD into PRSS. These results suggest that the PRSS intervention was acceptable and feasible, but that it should be further developed and tested for patients who face more barriers to MOUD retention.
Contingency Management for Stimulant-Opioid Co-Use: A Systematic Review and Meta-Analysis.
Jegede OO, Oliva HNP, Prudente TP … +3 more , Rash CJ, Muvvala SB, Angarita GA
J Addict Med · 2026 May · PMID 42109226 · Publisher ↗
OBJECTIVE: We conducted a meta-analysis (PROSPERO CRD420251000204) examining treatment outcomes associated with contingency management for individuals with stimulant-opioid co-use. METHODS: We searched Cochrane Library,...
OBJECTIVE: We conducted a meta-analysis (PROSPERO CRD420251000204) examining treatment outcomes associated with contingency management for individuals with stimulant-opioid co-use. METHODS: We searched Cochrane Library, Embase, PubMed, PsycINFO, and Web of Science through March 2026. Randomized controlled trials evaluating contingency management among individuals with past-year stimulant-opioid co-use were eligible. Outcomes included the longest duration of continuous, simultaneous abstinence from stimulants and opioids during treatment, the percentage of combined stimulant-opioid-negative urine toxicology samples, and treatment retention. Data were extracted following PRISMA guidelines, and random-effects meta-analyses were performed. RESULTS: Twenty-six trials (N=2356) were included. Across studies, cocaine was the stimulant of interest and heroin the primary opioid; fentanyl exposure was not reported in any trial. Contingency management significantly increased the longest duration of continuous abstinence from concurrent stimulant and opioid use compared with control conditions (mean difference=1.42 wk, 95% CI: 0.77-2.08; I²=50%). Participants receiving contingency management were more likely to submit combined stimulant-opioid-negative urine samples (odds ratio=2.46, 95% CI: 1.96-3.10; I2=0%). Overall treatment retention did not differ between groups, though subgroup analyses suggested improved retention among participants not receiving medication for opioid use disorder. CONCLUSIONS: Contingency management improves abstinence outcomes among individuals with stimulant-opioid co-use across treatment settings. The absence of fentanyl-specific data highlights an urgent need for research addressing treatment strategies in the context of the evolving synthetic opioid epidemic.
Prolonged Fentanyl Detection on Urine Drug Testing: A Case for Revising Interpretation Frameworks in the Setting of Chronic Use.
Plaza N, Hernandez T, Vais S
J Addict Med · 2026 May · PMID 42109223 · Publisher ↗
Urine drug testing (UDT) plays a central role in monitoring substance use during pregnancy and the postpartum period, with results carrying significant legal and social consequences, including family separation. We prese...
Urine drug testing (UDT) plays a central role in monitoring substance use during pregnancy and the postpartum period, with results carrying significant legal and social consequences, including family separation. We present 2 cases of individuals with opioid use disorder who continued testing positive for fentanyl on UDS for 170 and 210 days, respectively, after their last reported use. Both cases involved a fentanyl cutoff threshold of 0.5 ng/mL. In case 1, a 33-year-old male remained intermittently positive for 170 days, with fentanyl levels ranging from 0-7.1 ng/mL. In case 2, a 33-year-old female remained intermittently positive for 210 days, with fentanyl levels ranging from 0-1.9 ng/mL. Both individuals maintained low but detectable fentanyl concentrations throughout this extended period. These prolonged positive results delayed child custody reunification for both families. Despite mounting evidence of prolonged fentanyl detection, many agencies continue to rely on outdated guidelines suggesting fentanyl persists for only 1-3 days after last use. Without national standards for fentanyl detection window cutoffs, individuals maintaining abstinence continue to be suspected of recent use based solely on positive UDT results. We urge clinicians and child welfare professionals to consider these extended detection windows when interpreting positive fentanyl tests and to avoid misattributing persistently low positive results to recent drug use. These findings underscore the urgent need to revise decision-making frameworks to prevent harm to families and ensure appropriate clinical and legal outcomes.
The Economic Impact of Medetomidine on Critical Care Utilization: A Longitudinal Analysis of Intensive Care Unit Charges for Opioid Withdrawal Across the Adulterated Era.
Hilton R, Chakravorty S, Ghbrial M … +7 more , Rose J, Cherney A, Randolph F, Jaffe R, Weinstein LC, Durney P, London KS
J Addict Med · 2026 May · PMID 42109221 · Publisher ↗
OBJECTIVES: To quantify the impact of the adulterated fentanyl supply, through the eras of xylazine and medetomidine predominance, on critical care charges associated with treatment of opioid withdrawal. METHODS: A longi...
OBJECTIVES: To quantify the impact of the adulterated fentanyl supply, through the eras of xylazine and medetomidine predominance, on critical care charges associated with treatment of opioid withdrawal. METHODS: A longitudinal retrospective analysis was conducted at 2 intensive care units (ICUs) in Philadelphia, PA, USA, from April 1, 2017, to September 30, 2025. Primary outcomes included median per quarter and per patient charges and median quarterly ICU admissions with a primary or secondary ICD-10 diagnosis of opioid withdrawal (F11.23) from Q2 2017 to Q3 2025. These dates were correlated with quarterly drug supply adulterant prevalence reports by the Philadelphia Department of Public Health (PDPH). Secondary outcomes included ICU length of stay. RESULTS: Median quarterly ICU charges for F11.23 increased from $1,383,688 (1,138,614-1,602,562), during the period when the drug supply only included fentanyl (BX), to $2,883,659 (2,625,205-3,466,314) during the period of xylazine dominance (XE), to $17,168,020 (11,302,464-19,963,551) (H=23.50, P <0.001) in the period following the emergence of medetomidine (ME). Increasing cost was driven primarily by an increase in patient admissions (median 62 admissions XE per quarter vs. 261 ME), rather than median charge per patient for (XE $28,336 vs. ME $44,525, P =0.167). CONCLUSIONS: The adulteration of synthetic opioids with medetomidine was associated with a dramatic increase in ICU admissions and charges related to opioid withdrawal diagnoses. These changes represent a substantial public health challenge that may require systematic changes to health system resource allocation and withdrawal protocols.
The Scientific Debate on Khat Addiction: Evidence Across Humans, Animals, and Policy Domains.
Lim SYM, Alshagga M
J Addict Med · 2026 May · PMID 42091099 · Publisher ↗
Khat's addictive status is highly contested, shaped by conflicting evidence, varied epidemiology, and politically charged regulation. Although its psychoactive alkaloids, cathinone and cathine, are controlled in several...
Khat's addictive status is highly contested, shaped by conflicting evidence, varied epidemiology, and politically charged regulation. Although its psychoactive alkaloids, cathinone and cathine, are controlled in several jurisdictions, khat itself remains ambiguously regulated, as shown by the UK's 2014 move to classify it as a Class C drug, a decision driven as much by sociopolitical narratives as pharmacology. WHO assessments describe khat as capable of producing mild to moderate psychological dependence, with harms linked more to patterns of use and structural vulnerabilities than alkaloid exposure alone. Human studies show widely differing dependence rates due to cultural factors and inconsistent diagnostic tools, and recent adolescent research warns against equating prevalence with addiction without validated measures. Limited preclinical work finds khat extract can induce conditioned place preference and relapse-like behavior, though weaker than classic stimulants. Evidence-based treatments remain underdeveloped. Progress requires standardized assessments, expanded neurobehavioral studies, and community-grounded interventions.
Methadone and Torsades de Pointes: A Case Series.
Cheng A, Kalayilparampil B, Stamatis SE … +3 more , Shrestha S, Tetrault JM, Cohen SM
J Addict Med · 2026 May · PMID 42091098 · Publisher ↗
This case series reports on three patients undergoing methadone treatment for opioid use disorder (OUD) who developed significant QT prolongation and Torsades de Pointes (TdP). We compare patient-specific risk factors co...
This case series reports on three patients undergoing methadone treatment for opioid use disorder (OUD) who developed significant QT prolongation and Torsades de Pointes (TdP). We compare patient-specific risk factors contributing to QT prolongation, including methadone dose. During their hospitalization and outpatient care, we review the use of various management strategies, including methadone dose reduction, transition to buprenorphine, and cardiac therapies such as antiarrhythmics and implantable cardioverter-defibrillators (ICDs) to reduce cardiac risk. Lastly, we examine post-hospitalization outcomes and follow-up. By reporting these cases, we aim to highlight treatment strategies that balance the risk of dysrhythmia with the risk of destabilizing OUD treatment. Patient consent was obtained for the development of the case series.
From Management to Maintenance: A Pilot Ambulatory Gabapentin Bridge Protocol for Treatment of Low-risk Alcohol Withdrawal Syndrome.
Sharma SR, Takayoshi K, Hardenstine R … +1 more , Suzuki J
J Addict Med · 2026 May · PMID 42091090 · Publisher ↗
OBJECTIVE: Ambulatory management of mild to moderate alcohol withdrawal syndrome (AWS) remains underutilized despite evidence supporting its safety and effectiveness. We developed and tested a fixed-dose gabapentin taper...
OBJECTIVE: Ambulatory management of mild to moderate alcohol withdrawal syndrome (AWS) remains underutilized despite evidence supporting its safety and effectiveness. We developed and tested a fixed-dose gabapentin taper protocol for AWS, designed to standardize patient selection, monitoring during treatment, and also allow for transition to maintenance pharmacotherapy for alcohol use disorder (AUD). METHODS: Retrospective case series of the first 10 consecutive patients treated with a 6-day fixed-dose gabapentin taper (1800 mg tapered to 300 mg) at a hospital-based bridge clinic. Eligibility required low risk for complicated withdrawal per validated screening criteria. Follow-up included telemedicine visits on days 2-3 and in-person or virtual assessment at day 7 and 1 month. RESULTS: No patients experienced progression to complicated AWS, and none required emergency department visits or inpatient escalation. All patients either successfully completed the taper or opted to remain on a maintenance dose of gabapentin before the conclusion of the taper. Nine of 10 patients (90%) reported abstinence through day 7. At 1-month follow-up, 7 patients (70%) remained abstinent, 9 (90%) were retained in treatment, and all 10 (100%) had transitioned to medication for alcohol use disorder (MAUD) maintenance pharmacotherapy. CONCLUSIONS: A standardized gabapentin taper with telemedicine follow-up demonstrated early safety signals, high short-term abstinence, and successful transition to maintenance treatment for patients with AWS who were deemed low risk for progression to complicated withdrawal. Prospective, randomized trials comparing fixed-dose gabapentin tapers with symptom-triggered benzodiazepine or phenobarbital regimens are needed across diverse ambulatory settings to confirm these preliminary findings.
Maternal Opioid-related Diagnosis in Pregnancy and Risk of Adverse Perinatal Outcomes.
Prewitt KC, Ryan KS, Garg B … +6 more , Hayer S, Hagen OL, Sullivan EL, Caughey AB, Benson AE, Lo JO
J Addict Med · 2025 Dec · PMID 42090577 · Full text
OBJECTIVES: To examine the associations between opioid-related diagnoses in pregnancy and maternal and neonatal outcomes in a large, diverse population-based cohort. METHODS: This is a retrospective cohort study of Calif...
OBJECTIVES: To examine the associations between opioid-related diagnoses in pregnancy and maternal and neonatal outcomes in a large, diverse population-based cohort. METHODS: This is a retrospective cohort study of California linked hospital discharge-vital statistics data from 2008 to 2020. We included singleton pregnancies with gestational age of 23-42 weeks. Data analysis was completed on May 17, 2025. Opioid-related diagnosis, maternal morbidity, and neonatal outcomes were identified using ICD-9 and ICD-10 codes from hospital discharge data. χ 2 and multivariable Poisson regression models with robust variance estimator were utilized for statistical analyses. RESULTS: A total of 5,546,744 pregnancies met the inclusion criteria, and 13,749 (0.25%) had an opioid-related diagnosis. The prevalence of an opioid-related diagnosis increased from 0.14% in 2008 to 0.33% in 2020 ( P < 0.001) in pregnant individuals. Individuals with opioid-related diagnoses were associated with a higher risk of hypertensive disease (aRR = 1.23; 95% CI: 1.18-1.29), severe maternal morbidity (SMM; aRR = 1.84, 95% CI: 1.68-2.01), nontransfusion SMM (aRR = 2.16; 95% 1.87-2.49) and blood transfusion (aRR = 1.77; 95% 1.60-1.96). Neonates of individuals with an opioid-related diagnosis had higher risk of infant death (aRR = 1.72, 95% CI: 1.44-2.05), preterm birth <37 weeks (aRR = 1.71; 95% CI: 1.64-1.77), NICU admission (aRR = 2.80, 95% CI: 2.74-2.86), respiratory distress syndrome (aRR = 2.40, 95% CI: 2.28-2.53), and neonatal abstinence syndrome (aRR = 70.18, 95% CI: 64.34-76.56). CONCLUSIONS: Over the past decade, rates of an opioid-related diagnosis in pregnant individuals have more than doubled. In this large, diverse, population-based cohort study, a prenatal opioid-related diagnosis was associated with a significantly increased risk of maternal and neonatal morbidity.
Factors Associated With Telehealth Buprenorphine Initiation.
Yazdanfard S, Thornton D, Tatar M … +4 more , Prasad S, Adepoju OE, Rinker D, Varisco T
J Addict Med · 2026 May · PMID 42065256 · Publisher ↗
OBJECTIVE: Telehealth expanded buprenorphine access for opioid use disorder (OUD) after COVID-19 federal flexibilities permitted telehealth initiation. Limited evidence exists comparing telehealth and in-person buprenorp...
OBJECTIVE: Telehealth expanded buprenorphine access for opioid use disorder (OUD) after COVID-19 federal flexibilities permitted telehealth initiation. Limited evidence exists comparing telehealth and in-person buprenorphine initiation. This study examines correlates of telehealth versus in-person buprenorphine initiation among adults with OUD. METHODS: We conducted a retrospective, cross-sectional analysis using the Integrated Humana Medical and Pharmacy dataset, including commercial, Medicaid, Medicare Advantage (MAPD), and Medicare Part D prescription drug plans (PDP). Adults with newly diagnosed OUD who initiated buprenorphine between March 17, 2020, and December 31, 2023, with no prior use in the preceding 180 days, were included. Correlates of telehealth initiation were identified using the Least Absolute Shrinkage and Selection Operator-penalized logistic regression. RESULTS: Among 4034 patients, 748 (18.5%) initiated treatment via telehealth and 3286 (81.5%) in-person visits. Telehealth initiation was most common among patients aged 24-35 (25.0%) and least common among those aged 65+ (12.2%). Adjusted analyses found younger age (aOR: 1.54, 95% CI: 1.07-2.21 for ages 24-35 vs. 65+), prior telehealth use (aOR: 1.92, 1.55-2.37), cannabis use disorder (aOR: 1.38, 1.08-1.76), sedative use disorder (aOR: 1.63, 1.22-2.16), psychiatric/behavioral provider type (aOR: 2.38, 1.87-3.04), and zero comorbidities (aOR: 1.76, 1.33-2.34) as positively associated with telehealth initiation. Suburban (aOR: 0.73, 0.58-0.91) and urban (aOR: 0.77, 0.62-0.96) patients were less likely to initiate via telehealth compared with rural patients. CONCLUSIONS: Approximately 1 in 5 patients initiated buprenorphine via telehealth, with significant variation by age, geography, prior telehealth experience, comorbidity burden, and provider speciality. These findings underscore the need for postpandemic policies that preserve telehealth access although maintaining robust in-person treatment options to address diverse patient needs.
Methadone Diversion and Overdose: What Does the Evidence Say? A Narrative Review.
Miller M, Krawczyk N
J Addict Med · 2026 Apr · PMID 42008827 · Publisher ↗
OBJECTIVES: Policy reforms are being considered to increase methadone treatment (MT) access for opioid use disorder in the United States. Proponents of more structured MT reference risks of diversion, including non-presc...
OBJECTIVES: Policy reforms are being considered to increase methadone treatment (MT) access for opioid use disorder in the United States. Proponents of more structured MT reference risks of diversion, including non-prescribed use or redistribution of methadone, and overdose as arguments for limiting access to specialty settings. However, the scientific evidence behind these claims has not been thoroughly reviewed. METHODS: We conducted a narrative review of studies on methadone diversion, diverted methadone-involved overdoses, and how these compare in countries with specialty-care-only policies (methadone dispensed only through regulated treatment programs) versus general physician-prescribing policies (physicians prescribe methadone in office-based settings). A narrative approach was chosen, given substantial heterogeneity in study designs, diversion definitions, outcome measures, and data sources. We synthesize and discuss findings from international papers published before October 2025. RESULTS: We identified 29 articles studying methadone diversion or diverted methadone-involved overdoses in 7 countries. Lifetime methadone diversion occurrence varied between 6% and 68%, and using diverted methadone occurrence varied between 22% and 88%. Diverting methadone was most often done to help sick friends/partners. Common reasons for using diverted methadone were preventing withdrawal and avoiding opioid use. Three studies found no association between self-reported diverted methadone use and increased individual-level risk of overdose. CONCLUSIONS: The link between specialty-care-only policies and lower diversion and overdose risk is not supported by the reviewed literature. Policymakers should weigh diversion risks against benefits of lives saved through expanded MT access. Further research is needed to better understand the circumstances related to diverted methadone and inform policy-making that appropriately mitigates risks.
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