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This Week in the Ïã¸ÛÁùºÏ²Ê¿ª½±½á¹û¼Ç¼ Weekly

The field of addiction medicine has been working hard to raise awareness about the disease and its treatments. A new study from NIDA researchers is doing so because of unfortunate findings: overdose deaths rose significantly for pregnant and postpartum women across demographic groups and in areas with adequate health care access, underscoring how stigma and punitive policies are still discouraging treatment (). 

Such concerns raise some considerations for a recent review about monitoring substance use with nail trimmings and the potential to expand our understanding of prenatal exposure (). While promising, let’s hope it’s not used for punitive purposes or discourages treatment. The story of a 20-year-old new mom personalizes the tragedy of postpartum overdose, but also shows how hard it is to believe that technological marvels like Facebook are somehow not sophisticated enough to better manage drug trafficking on their sites ().

An important part of raising awareness is reducing stigma. Decriminalization policies can help “but not in isolation” and a new report from the Global Commission on Drug Policy encourages us to follow the evidence and fund the treatment (). Oregon’s experience has become a real-world lesson that decriminalization is not a one-size-fits-all approach and there can be pushback when not successful (). 

As much as we raise awareness, we may not always be accustomed to popularity. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) seem to be getting all the attention and are even impacting how much people ate at Thanksgiving (). There is also significant interest in the ability to reduce alcohol intake, but as a commentary from  advises us, the awareness around AUD is good but the attention is getting ahead of the evidence. 

Move over psychedelics, GLP-1RAs are the new “it” drugs.

Thanks for reading,

Nicholas Athanasiou, MD, MBA, DFÏã¸ÛÁùºÏ²Ê¿ª½±½á¹û¼Ç¼
Editor in Chief

with Co-Editors: Brandon Aden, MD, MPH, FÏã¸ÛÁùºÏ²Ê¿ª½±½á¹û¼Ç¼, Debra R. Newman, PA-C, MSPAS, MPH, Jack Woodside, MD, John A. Fromson, MD

Lead 

JAMA Psychiatry

This cross-sectional exploratory study examined knowledge gaps in overdose deaths among pregnant and postpartum persons from 2018-2021 as compared to nonpregnant overdose deaths and obstetrical deaths. Overdose deaths among pregnant and postpartum women consistently increased among those aged 10 to 44 years, and more than tripled among those aged 35 to 44 years, from 4.9 per 100,000 from January-June 2018 to 15.8 from July-December 2021. These deaths differed from nonpregnant overdose deaths and obstetrical deaths in sociodemographic characteristics and place of death. Among overdose deaths in total (pregnant and nonpregnant), nearly 75% occurred outside of health care settings. Clearly more work needs to be done to treat SUDs in this population. 

Research and Science

Nature Mental Health

Randomized control trials have demonstrated the efficacy of multiple sessions of repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex in reduction of anxiety symptoms and nicotine cravings and withdrawal. In this study, researchers assessed the association between nicotine withdrawal and anxiety state; and also if a single rTMS session would reduce withdrawal symptoms, was that mediated by reduction in anxiety. The study found a strong correlation between reported withdrawal symptoms and anxiety and that a single rTMS session did reduce acute cigarette cravings. However, the authors did not find that the reduction in cravings was mediated by reduction in anxiety and suggested additional research to elucidate the mechanism. 

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BMC Medicine

Metabolite signatures of long-term alcohol consumption are lacking. To better understand the molecular basis linking alcohol drinking and cardiovascular disease (CVD), this study investigated circulating metabolites associated with long-term alcohol consumption and examined whether these metabolites were associated with incident CVD. Sixty long-term alcohol consumption-associated metabolites were identified. The association analysis with incident CVD suggests a complex metabolic basis between alcohol consumption and CVD.

Drug and Alcohol Dependence

​​This literature review identified 35 studies concerning the use of nail clippings to assess exposure to four substances: alcohol (ethyl glucuronide), nicotine, opioids, and cannabis. The authors note that uptake of substances by hair is affected by hair texture and use of hair products and that nail samples avoid these confounders. Nail growth rates are such that fingernails reflect the past 3-5 months of exposure and toenails 8-16 months, which could span the entire gestation in pregnant individuals. For alcohol (EtG), fingernails were negative after 2 months of abstinence. For alcohol, nicotine and cannabis, higher concentrations were found in nails than hair. In some individuals with short nails it can be hard to collect sufficient sample for a full set of analyses. The authors conclude that nails are an acceptable matrix for assessment of exposures over an extended period of time.

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The Lancet

This editorial reviews the latest policy report from the Global Commission on Drug Policy, which emphasizes decriminalization as a precursor to ending HIV and viral hepatitis, and notes the importance of harm reduction approaches. Portugal’s approach to decriminalization is reviewed, and the reader is reminded that the recent increase in drug use in that country coincided with a reduction in services to treat those in need. Comprehensive strategies to support decriminalization should address other basic needs including housing, access to health care, and treatment of mental illness. This report suggests that health care professionals, not the justice system, be the first responders for those who use drugs.

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Cell

There is a need to better understand how opioids modulate cellular and neuronal plasticity within the central nervous system, such as analgesia, opioid tolerance, dependence, and withdrawal. This article reviews the molecular basis of opioid receptor signaling with a focus on the structures of opioid receptors bound to endogenous peptides or pharmacological agents. These insights unveil specific interactions that dictate ligand selectivity and likely their distinctive pharmacological profiles. Biochemical analysis further reveals molecular features governing opioid receptor signaling. Simultaneously, the synergy between computational biology and medicinal chemistry continues to expedite the discovery of novel chemotypes with the promise of yielding more efficacious and safer opioid compounds.

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Drug and Alcohol Dependence

This study used data from the state of Connecticut to identify accidental opioid deaths during 2017 and if the decedents had received treatment during the previous 6 months. The type of treatment was identified as MOUD with agonist medication (methadone or buprenorphine) or non-MOUD (short-term detoxification or longer-term rehabilitation). There were 915 accidental poisonings involving opioids in Connecticut in 2017. Of these, 69 had received methadone, 72 received buprenorphine, and 110 received non-MOUD treatment. The risk of death was lower for those with MOUD treatment compared to no treatment (RR 0.62, p<0.001). The risk of death was higher for those with non-MOUD treatment compared to no treatment (RR 1.77, p<0.001). The authors conclude that treatment with MOUD reduced the risk of fatal overdose and that non-MOUD treatment “might have produced worse outcomes than no treatment.”

Nature Medicine

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have already demonstrated significant treatment effects for diabetes and obesity and there is some early evidence of promise for alcohol use disorder (AUD) treatment. While animal models show GLP-1RAs reduce reward properties of alcohol and human research suggests a relationship between GLP-1 systems and alcohol, randomized control trials (RCTs) are still needed to demonstrate their efficacy and safety among those with AUD. Additionally, RCTs are needed to answer other questions about dosing, treatment duration, potential rebound effects, and safety in normal to low weight persons. The authors in this commentary advise caution about prescribing GLP-1RAs for treatment of AUD or other substance used disorders pending data from ongoing clinical RCTs. 

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