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The ASAM Weekly for December 3rd, 2024

This Week in the ASAM Weekly

Tis the season to read about alcohol. The New York Times, for example, has several articles on the topic, starting with high-intensity drinking. It’s a pattern more concerning than binge drinking and seems to have tracked with generational increases in alcohol intake among those who are currently middle-aged (The New York Times). Unfortunately, for too many, what happened in college did not stay in college.

This coincides with sharp increases in alcohol-related deaths, which have more than doubled from 1999 to 2022 (The New York Times). According to a study from the American Journal of Medicine - which did not include deaths related to accidents – several groups experienced notable increases, including women and Midwesterners. Along with these findings, the authors also discuss concerns about the overlapping risks from alcohol use, cardiomyopathy, and obesity. 

These co-morbidities are partly why there is great interest in the use of GLP-1s to treat alcohol use disorder. Unfortunately, a systematic review finds there is still not enough research to make a definitive determination, but the promise is there (eClinicalMedicine). 

As important as it is that we are talking about alcohol consumption, how we are talking about it may be more important. Many of the articles this week rely on quantifying consumption: British units, American drinks, binge drinking, heavy drinking, BAC, etc. So when The New York Times also publishes an article about how exercise could help with a hangover but only quantifies the amount as “you overdid it,” are we (unintentionally) normalizing behavior because we haven’t normalized a way to monitor it? 

Sure, it’s complicated, but what if The New York Times also wrote an article about gifting personal breathalyzers this holiday season? Tracking BAC would surely seem pretty normal at that point. 

Thanks for reading,

Nicholas Athanasiou, MD, MBA, DFASAM
Editor in Chief

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

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Lead Story

Xylazine Pharmacokinetics in Patients Testing Positive for Fentanyl and Xylazine ðŸ”“

Clinical Chemistry

This study of xylazine pharmacokinetics used plasma samples from 28 patients who had urine screens positive for xylazine and fentanyl. The patients were being treated for skin lesions, most commonly, then shortness of breath or opioid overdose. At least two subsequent plasma samples were analyzed for xylazine and xylazine metabolites by LC-MS/MS. The median terminal half-life for xylazine in plasma was 12 hours (range 6-21 hours). Animal studies show xylazine to be extensively metabolized, with little unchanged xylazine eliminated in urine. The two most abundant metabolites were oxo-x and sulfone-x, which did not have a window of detection longer than xylazine. Researchers had no information as to the timing or route of xylazine ingestion or if additional xylazine was consumed during the study period. These factors could affect the accuracy of the results.

Research and Science 

Emergency Department Visits Involving Hallucinogen Use and Risk of Schizophrenia Spectrum Disorder 

JAMA Psychiatry

This cohort study of 9,244,292 individuals assessed whether those who have emergency department (ED) visits involving hallucinogen use have an increased risk of incident schizophrenia spectrum disorder. Individuals with no history of psychosis who had an ED visit involving hallucinogen use had an increased risk of schizophrenia spectrum disorder when compared with members of the general population of the same age and sex and after further adjustment for comorbid mental and substance use disorders. Thus, individuals who require emergency care for hallucinogen use may have an increased risk of developing a schizophrenia spectrum disorder.

New Clinical and Public Health Challenges: Increasing Trends in United States Alcohol Related Mortality

The American Journal of Medicine

Utilizing the CDC's Wide-ranging Online Data for Epidemiologic Research (WONDER), this study evaluated mortality trends due to alcohol between 1999 and 2020. Over the study period, the alcohol-related death mortality rate doubled from 10.7 to 21.6 per 100,000, with the largest increase among those aged 25-34 (3.8-fold increase). There was a statistically significant increase in both men and women, but the increase was greater among women, from 4.8 to 12.0 per 100,000. The Midwest region saw the greatest increase in mortality rates from 8.9 to 22.5 per 100,000. The authors suggest these data can be used to target public health interventions to combat rising alcohol-related mortality.

Opioids and Dementia in the Danish Population ðŸ”“ 

JAMA Network Open

This study from Denmark used a nationwide cohort of 1,872,854 individuals, of which 5.0% developed dementia. The National Prescription Register was used to quantify an individual's opioid use for chronic, noncancer pain (excluding those with a diagnosis of opioid addiction). Opioid use was expressed as total standardized doses (TSDs) where 1 TSD = 30 oral morphine equivalents. For those with <90 TSDs, there was no increased risk of dementia. Above 90 TSDs, the incidence risk ratios for dementia (diagnosed at 60-69 years) ranged from 1.29 for 91-200 TSDs up to 1.59 for >500 TSDs. Smaller risk ratios were found for dementia diagnosed in older decades, and no association with opioids was seen for dementia diagnosed at ages over 90 years. This was likely due to the increasing influence of other dementia risk factors with advancing age. The authors concluded that opioid use above 90 TSDs was associated with an increased risk of dementia.

Learn More 

Neuroimaging biomarkers of addiction 

Nature Mental Health

This analysis provides an overview of neuroimaging modalities in addiction medicine, potential neuroimaging biomarkers, and their physiologic and clinical relevance. Identified aberrations in the neural substrates of reward and salience processing, response inhibition, interoception, and executive functions with neuroimaging can inform the development of pharmacological, neuromodulatory, and psychotherapeutic interventions to modulate the disordered neurobiology. Closed- or open-loop interventions can integrate these biomarkers with neuromodulation in real time or offline to personalize stimulation parameters and deliver precise intervention. Future directions and challenges in bringing these putative biomarkers from the bench to the bedside are also discussed.

Association between glucagon-like peptide-1 receptor agonists use and change in alcohol consumption: a systematic review ðŸ”“

eClinicalMedicine

Preclinical and animal models have provided evidence that glucagon-like peptide-1 receptor agonists (GLP-1 RA) may reduce alcohol intake and high-risk alcohol intake behavior. In this systematic review, researchers examined GLP-1 RA interaction with alcohol intake in persons who drink excessive alcohol across 6 studies, including 2 randomized controlled trials. Overall, the impact on alcohol consumption across the studies was heterogeneous, with some support for GLP-1 RAs decreasing alcohol intake, but the authors conclude additional and more robust research is needed. 

ASAM Criteria Strategy Steering Committee
Call for Applications!

The ASAM Criteria Strategy Steering Committee is seeking experts in addiction medicine, particularly in adolescent treatment and training of treatment professionals. Knowledge in health disparities across the addiction medicine field is preferred. Click the link below to learn more and apply.

Application Deadline:
December 6, 2024