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This Week in the ̽»¨ºÏ¼¯ Weekly

A non-profit out of Seattle is trying something remarkable — a low-dose induction of injectable buprenorphine that could automate around precipitated withdrawals in such a way that providers of MOUD should soon expect people with OUD to be asking about it (). This happens because what people read online moves much faster than what we read in peer-reviewed publications.  

Achieve Life Sciences will be applying for FDA approval of cytisinicline, potentially making it the first new smoking cessation drug to hit American markets in nearly twenty years (). But its market potential likely won’t be limited to tobacco; young adults have a heterogenous rapport with substance use these days and vaping nicotine continues to be the most common ().

Specialists from Pittsburgh have developed a multidisciplinary, clinical protocol for inpatient management of xylazine, and what the authors rightfully point out is that this collaborative model can be adapted for a changing drug supply (). This happens to be coming just in time as the end of the “tranq” era is turning into the dawn of the “dex” (aka medetomidine) era ().

These are just a few of the soon-to-be trending stories we’re covering this week, but if you’d rather read about something more traditionally certain, then there’s always death and taxes...and alcohol (). But even that comes with a modern twist wrapped in a spoiler alert: cannabis-infused libations ().

Thanks for reading,

Nicholas Athanasiou, MD, MBA, DFASAM
Editor in Chief

with Co-Editors: Brandon Aden, MD, MPH, FASAM; John A. Fromson, MD; Jack Woodside, MD

Lead Story 

Substance Use and Addiction Journal

Xylazine in the unregulated drug supply produces significant morbidity. This paper describes utilizing a multidisciplinary team to develop inpatient setting protocols to manage patients with xylazine exposure. Protocols developed include the use of scheduled clonidine or tizanidine to manage withdrawal with hold parameters. As there is no FDA-approved immunoassay screen, the authors recommend assuming xylazine exposure in areas with high prevalence and limited testing. The team also developed guidelines for cases in which surgical interventions would be considered, when to culture wounds, antibiotic usage, and consistent wound care based on size and clinical characteristics. In addition, they developed standardized discharge instructions, including referral to substance use disorder treatment, harm reduction, and education around xylazine test strip use.

Research and Science 

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JAMA Internal Medicine

This randomized clinical trial that included 248 adults examined the comparative effectiveness of initiating oral vs. extended-release injectable naltrexone on heavy drinking (defined as 5 or more drinks for men and 4 or more drinks for women). Among hospitalized patients with alcohol use disorder (AUD) there was not a statistically significant difference between groups in the 3-month change in percentage of heavy drinking days in the past 30 days (38.4–percentage point decrease in the oral naltrexone group vs. 46.4–percentage point decrease in the extended-release injectable naltrexone group). Hospitalization represents an opportunity to start AUD pharmacotherapy; given their similar effectiveness, choice of oral vs. extended-release injectable naltrexone should be directed by practical factors, such as patient preference and affordability. 

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JAMA Network Open

This study used the SAMHSA Treatment Episode Data Set to examine OUD treatment retention for pregnant individuals between 2015 and 2021. Across this time frame, about two-thirds (68%) of 29,071 treatment episodes included MOUD, with this figure increasing by 9% between 2015 and 2021. Episodes including MOUD had greater treatment retention at 6 months than those without MOUD (43% vs. 29%, aOR=1.86). States that expanded Medicaid had greater odds of treatment episodes including MOUD (72% vs. 48%). States with child maltreatment laws had lower odds of treatment episodes including MOUD (51% vs. 75%). Prior studies reveal fear that use of MOUD could result in loss of child custody. The authors conclude that treatment retention overall is low but improves with the inclusion of MOUD. 

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JAMA Network Open 

This randomized clinical trial of 770 adults with opioid-treated chronic low back pain (CLBP) assessed the comparative effectiveness of mindfulness-based therapy (MBT) and standard-of-care cognitive behavioral therapy (CBT) among adults with CLBP.  Although there were no differences between groups, both the MBT and CBT groups experienced improved pain, function, and health-related quality of life and reduced opioid dosage at 6 and 12 months. Results of the study suggest that both treatments have potential utility in treating adults with refractory CLBP and improving pain, function, and quality-of-life outcomes. 

Addictive Behaviors

In this study, researchers used a nationally representative sample of 12th graders to examine day-to-day alcohol, cannabis, and tobacco use patterns and within-person variability in young adults, and evaluate associations with stress, boredom, and loneliness. The authors identified 6 classes of substance use days: 1) nicotine vaping only (33.7%), 2) cannabis smoking (cannabis smoking + nicotine vaping) (23.5%), 3) alcohol only (17.2%), 4) cannabis vaping only (11.7%), 5) multiple combustibles (cannabis smoking + combustible tobacco) (7.3%), and 6) multimodal cannabis (cannabis smoking + vaping) (6.7%). Increased stress was associated with multimodal cannabis and multiple combustible days, while lower stress, boredom, and loneliness were associated with alcohol use only days.  

Learn More 

Annals of Internal Medicine

Psilocybin has been decriminalized in some states beginning in 2019 and in this study, researchers utilized 5 nationally representative data sets to examine trends in psilocybin use between 2014 and 2023. Prior to 2019, prevalence of psilocybin use was reasonably stable, but between 2019 and 2023 use increased across all age groups. Past-year use increased 44% in young adults (18-29) and 188% in older adults (≥30), with use of psilocybin being higher among those with mental health disorders and chronic pain. The authors suggest as more research is done and the regulatory status of psilocybin changes, increased surveillance is needed to understand populations using psilocybin, reasons for use, and clinical and public health impacts. 

Journal of Addiction Medicine

In this Letter to the Editor, the author notes the increasing use of phenobarbital (PHB) to treat alcohol and benzodiazepine withdrawal. PHB produces a potent and long-acting (days to weeks) induction of the cytochrome P450 enzymes that metabolize both buprenorphine and methadone. This could reduce blood levels of MOUD resulting in opioid withdrawal symptoms. As enzyme induction fades, MOUD effects would increase and could become too potent. Levels of other medications, eg, anticoagulants, could be disrupted in a similar fashion. The author suggests using long-acting benzodiazepines rather than PHB to treat alcohol and benzodiazepine withdrawal. 

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Clinical Toxicology

Loperamide is an opioid agonist available without prescription for treatment of diarrhea. At the therapeutic dose of 16 mg, it has limited central nervous system effects; however, it is increasingly used at high doses by patients with OUD. It also produces a non-opioid cardiotoxicity through inhibition of both sodium and potassium cardiac channels resulting in prolonged QRS and QT duration and ventricular tachycardia. Both loperamide and its metabolite produce cardiotoxicity and have long terminal half-lives (up to 39 and 89 hours respectively). A literature search resulted in 2 patients with 3 episodes of loperamide overdose. Both had long-term loperamide use up to 400 mg/day and QRS and QT prolongation with the second patient having ventricular tachycardia during 2 separate admissions. The authors advise that patients with loperamide overdose have continuous monitoring until the EKG returns to normal which may take several days. 

In the News 

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The Associated Press

The New England Journal of Medicine

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The Seattle Times

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USA Today

STAT

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CNET