探花合集

This Week in the 探花合集 Weekly

According to an article in , humans’ relationship with beer spans millennia, but we now may be discovering the health benefits of hops. Does this mean that low-to-moderate beer drinking could be good for you?

 What we do know is that the J-shaped curve of alcohol consumption and many health outcomes is not holding. There is yet another study using data from the UK Biobank, this time with Mendelian Randomization, which found a linear causal relationship between alcohol consumption and dementia (). 

Allodynia, a symptom of alcohol withdrawal, seems to be reversible in moderate alcohol consumption, but it may be more permanent in heavy-drinking animal models. Surprisingly, the difference may point us toward therapeutics that target the endocannabinoid system (). 

Gene expression studies can help us better understand the nature vs. nurture relationship with alcohol, and now a meta-analysis using multiple genetic datasets is opening the opportunity for repurposing drugs to treat AUD (). One thing we are certain about with nature vs. nurture is that our behaviors in youth have lasting effects. Data from Monitoring the Future indicate that individuals, especially women, who engaged in binge drinking as teens are more likely to exhibit high-risk use in midlife (). 

If all this seems eerily familiar, it is. The National Geographic article also made note of the scientific name for hops, Humulus lupulus, which happens to belong to the family .

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

Lead Story

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Alcohol Clinical and Experimental Research

Using data from the Monitoring the Future study, which enrolled cohorts of high school seniors annually starting in 1976, this analysis evaluated alcohol drinking patterns in adults 35-60 and potential association with their drinking patterns at age 18. Overall, the reported mean number of drinks at a time ranged from 1.7 to 1.4, and the mean maximum number of drinks ranged from 3.2 to 2.3. The reported number of drinks was generally lower at older ages. Those who reported binge drinking at 18 versus those who did not reported a significantly higher mean (2.3 vs. 1.3) and maximum (4.0 vs. 2.3) number of drinks as adults. Additionally, they were more likely to report binge drinking (39.5% vs 19.1%) and high-intensity drinking (10.5% vs 4.4%) as adults. Further, this association was even stronger in older age groups, suggesting adolescent binge drinking is a risk factor across the lifespan. 

Research and Science 

 馃敁&苍产蝉辫;

eClinical Medicine

This study used data from the UK Biobank to investigate the relationship between alcohol consumption and dementia risk. Current drinkers (n=313,958) consumed an average of 13.6 units/week alcohol (men averaged 20.2 units/week and women 9.5 units/week). During a mean follow-up of 13.2 years, 5,394 (1.7%) developed dementia. A positive linear causal relationship was identified between alcohol consumption and dementia among current drinkers. The J-shaped association found in conventional epidemiological analysis was not supported by non-linear MR analyses. Findings suggested that there was no safe level of alcohol consumption for dementia.

Pharmacotherapy

This study assessed the effect of opioid maintenance treatment (OMT) during the prenatal period on neurodevelopmental disorders (NDD) in the offspring. Medicaid data were analyzed for 416 mother-infant dyads with maternal OUD. The offspring were assessed for NDD through age 11 years. Overall, 40% had methadone exposure, 20% had buprenorphine exposure, and 40% had neither exposure and served as the “unexposed” comparison group. Methadone exposure was associated with a higher risk of NDD compared to buprenorphine (HR=2.1). No significant differences were found between the buprenorphine exposed group and the unexposed (no OMT) comparison group. Methadone exposure was associated with an even higher risk of NDD when compared to buprenorphine at higher doses (HR=3.5). These results suggest that for OMT during pregnancy, buprenorphine is associated with a lower risk of NDD than methadone.

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JAMA Network Open

Drug concentration data for fentanyl, methamphetamine, cocaine, and heroin were measured in 921,931 urine specimens obtained from patients seeking SUD treatment throughout the US between 2013 and 2023. In 2023, compared to 2013, the concentration of fentanyl was 8.3 times higher, methamphetamine was 5.2 times higher, cocaine was 2.0 times higher, and heroin was lower by a factor of 0.4. These data demonstrate the significant increase in fentanyl use with an associated decrease in heroin use. The increased fentanyl concentrations pose a risk for precipitated withdrawal during initiation of buprenorphine treatment. There has also been a significant increase in methamphetamine use with a smaller increase in cocaine use. The concurrent use of stimulants is associated with poorer outcomes for treatment of OUD. This analysis of urine specimens provides rapid feedback on changes in drug use.

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Clinical Cardiology 

Inhalation of volatile substances is known to be associated with sudden death, likely resulting from ventricular arrhythmias. This study performed electrocardiography and echocardiography on 32 young adults with volatile substance addiction and compared the results with 30 healthy controls. The electrocardiogram showed a significantly increased corrected QT interval associated with volatile substance use (p=0.003). Volatile substance use was also associated with an increased P wave duration (p<0.001). Echocardiography showed no significant difference between the two groups. An increased QT interval is known to be associated with ventricular arrhythmias and sudden death, so these results are consistent with an increased risk of sudden cardiac death with use of volatile substances. The normal echocardiograms suggest the risk is electrical rather than structural.

Learn More 

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Pharmacological Research

Prior evidence has shown an association between alcohol use disorder (AUD) and neuropathic pain. To better understand that association, this study used rats to examine alcohol-related allodynia. Using the Marchigian Sardinia alcohol-preferring (msP) rats, researchers evaluated allodynia during alcohol exposure and found that allodynia was correlated with total alcohol intake in male rats only. During abstinence from alcohol, researchers found a significant increase in abstinence-related allodynia, which correlated with total alcohol intake in male and female rats. The authors found that a decrease in lumbar dorsal root ganglia (DRG) 2-arachidonoyglycerol (2-AG) was associated with development of mechanical allodynia. They suggest 2-AG metabolism is altered and may be a target for therapy for allodynia associated with AUD.

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Molecular Psychiatry

To improve understanding of neurobiological mechanisms associated with alcohol use disorder (AUD) in humans, this study compared gene expression data from deceased individuals with and without AUD across two addiction-relevant brain regions: the nucleus accumbens (NAc) and dorsolateral prefrontal cortex (DLPFC). Researchers identified 176 differentially expressed genes (DEGs; 12 in both regions, 78 in NAc only, 86 in DLPFC only) for AUD in the new dataset. After meta-analyzing with published data, the study identified 476 AUD DEGs (25 in both regions, 29 in NAc only, 422 in PFC only). Of these DEGs, 17 were significant when looked up in a genome-wide association study (GWAS) of problematic alcohol use or drinks per week. Researchers also identified 29 and 436 drug compounds that target DEGs from the meta-analysis in NAc and PFC, respectively. This study identified robust AUD-associated DEGs, contributing novel neurobiological insights into AUD and highlighting genes targeted by known drug compounds, generating opportunity for drug repurposing to treat AUD.

Substance Abuse and Mental Health Services Administration (SAMHSA)

On December 11, 2023, SAMHSA, in partnership with the FDA and NIDA, hosted a listening session to discuss the medical need around, emerging data on, and barriers to accessing higher doses of buprenorphine in the context of high potency synthetic opioid (HPSO) exposure. The meeting focused on gathering quantitative and qualitative data on the need for, effectiveness of, and safety of “high dose” buprenorphine (defined as > 24 mg of buprenorphine per day) in the treatment of opioid use disorders (OUD), to inform federal guidelines and policies. This document summarizes the recommendations and opinions of the participants and does not reflect an official position, policy, or set of recommendations from any federal or state agency. The meeting was structured around four panels: Setting the Context: The Current Landscape, Guidance, and Use of High Dose Buprenorphine; New and Original Data on the Use of High Dose Buprenorphine; Qualitative Data and Implementation Insights; and Identifying Barriers to Accessing High Dose Buprenorphine and Potential Solutions.

In The News 

National Geographic

The Wall Street Journal

WESA

KFF Health News

American Journal of Managed Care