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ASAM Weekly for December 12, 2023

Dec 13, 2023

This Week in the ASAM Weekly

It takes big data to tackle some of the biggest issues in addiction. Cannabis use rates have been rising in recent years and a new study leveraging data from the largest integrated health care system in the US (the VA) has found that cannabis use disorder (CUD) rates have more than doubled among veterans. Unfortunately, increases were disproportionately found among veterans with psychiatric disorders, especially those with the most severe diagnoses such as bipolar and psychotic spectrum disorders (American Journal of Psychiatry).

Similarly, cannabis use among pregnant women in North America has almost doubled, which means there is an urgent need to better understand the impact of prenatal cannabis exposure on early development. A comprehensive meta-analysis explored these nuances and found the only likely effect to be an increase in externalizing problems (e.g. aggression, hyperactivity), but the limitations of such reviews do encourage us to consider what we know from animal studies (Addiction).

Data from the National Violent Death Reporting System helped inform another study about the alcohol-firearm-suicide connection. It’s been shown that alcohol intoxication increases the risk of suicide by firearm across sex and age groups, but in this current study, middle-aged females had a significantly higher risk of using a firearm while intoxicated than their male counterparts (AJPM). This precedes data recently released from the National Center for Health Statistics which found that women had a higher increase in suicide rate than men last year (CDC).

As the study's authors (AJPM) acknowledge, it can be more difficult to solve the political inaction on gun violence than it is to reduce the impacts of alcohol. A meta-analysis re-confirms there are effective treatments for alcohol use disorder (AUD) that help reduce alcohol use (JAMA). The World Health Organization is encouraging better alcohol taxation to reduce public harm (WHO), and there is a case series reporting on the reduction of AUDIT scores in six patients after initiation of semaglutide therapy (The Journal of Clinical Psychiatry).

Now, don’t be surprised if one day there is a case report implicating a reduction in the alcohol-firearm-suicide-connection after semaglutide therapy. Just to be clear, there’s essentially no data on this, but even before there’s big data there is usually something small like a case report.

Thanks for reading,

Nicholas Athanasiou, MD, MBA, DFASAM
Editor in Chief

with Co-Editors: Brandon Aden, MD, MPH, FASAM, Debra R. Newman, PA-C, MSPAS, MPH, Jack Woodside, MD, John A. Fromson, MD

Lead

Relationship between alcohol use and firearm-involved suicide: Findings from the National Violent Death Reporting System, 2003-2020

American Journal of Preventive Medicine

This study evaluated the sex- and age group-specific relationship between alcohol intoxication and firearm-involved suicide. Among males of all ages and young and middle-aged females, alcohol intoxication was associated with increased risk of suicide by firearm, an extremely lethal method that accounts for a majority of suicides in the US. Interventions targeting excessive alcohol consumption may be effective in reducing suicide mortality rates.

Research and Science

Pharmacotherapy for Alcohol Use Disorder: A Systematic Review and Meta-Analysis

JAMA

This systematic review and meta-analysis considered the efficacy of nine medications for the treatment of alcohol use disorder (AUD). These included the FDA-approved medications acamprosate, disulfiram, and naltrexone, as well as six off-label medications: baclofen, gabapentin, varenicline, topiramate, prazosin, and ondansetron. Compared with placebo, numbers needed to treat to prevent one person from resuming drinking were 11 for acamprosate and 18 for oral naltrexone at a dose of 50 mg/day. Among the off-label medications, topiramate was shown to yield the greatest benefit.

Trends in Prevalence of Cannabis Use Disorder Among US Veterans With and Without Psychiatric Disorders Between 2005 and 2019

The American Journal of Psychiatry

Given the overlap between psychiatric disorders and cannabis use disorder (CUD) and that veterans are disproportionately affected by mental health disorders, such as PTSD, this study utilized Veterans Health Administration (VHA) records between 2005 and 2019 to examine trends in CUD in this population. Overall, the prevalence of CUD more than doubled among veterans, but the increase was much greater among those with comorbid psychiatric illness, particularly those with severe psychiatric illness including bipolar and psychotic disorders. In view of the potential impairment and harms of CUD and psychiatric illness, the authors suggest greater efforts for prevention of CUD in this population are needed.

Birth, cognitive and behavioral effects of intrauterine cannabis exposure in infants and children: A systematic review and meta-analysis

Addiction

This systematic review considered the effects of intrauterine cannabis exposure on birth and a variety of outcomes (physical, psychological, developmental, and behavioral) through early childhood. Among exposed infants, there was an increased risk of preterm delivery, low birth weight, and need for NICU admission, as compared to infants with no exposure. There was no evidence to support impacts on cognitive or behavioral outcomes, with the possible exception of attention and externalizing problems, such as aggression and hyperactivity and no increased risk of birth defects or death. This review indirectly established that a considerable number of pregnant women who use cannabis are using multiple substances.

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Investigation of monoclonal antibody CSX-1004 for fentanyl overdose 🔓

Nature Communications

Fentanyl and fentanyl analogs (F/FAs) are the leading cause of death in the ongoing opioid overdose epidemic due to various factors, including its potency and rapid onset. While naloxone is the standard of care for opioid overdose reversal, the window for administration is much shorter with F/FAs and multiple doses are frequently needed. Therefore, there is a need for alternative interventions to address overdoses from F/Fas. This study evaluated CSX-1004, a human IgG1λ monoclonal antibody in animal models. In a mouse model, CSX-1004 diminished the effects of F/FAs and in non-human primate models it provided protection against respiratory depression for > 7 days. While additional studies are needed, this study does provide evidence for CSX-1004 as a prevention strategy against F/Fas overdose.

Associations between parental smoking and teenage alcohol and drug use in the Growing Up in Ireland cohort study: a longitudinal observational study

The Lancet

This study from Ireland included 6039 teenagers to examine the relationship between alcohol or drug use at age 17-18 years and smoking status of their parents when they were age 9. At age 9, 31% had a primary parent who smoked. At age 17-18, 85% used alcohol and 35% used other drugs. Having a primary parent who smoked as a child was associated with an increased risk of substance use as a teenager. For alcohol the odds ratio was 1.88 and for other drugs the odds ratio was 1.70. The authors call for interventions to reduce parental smoking.

Cross-species epigenetic regulation of nucleus accumbens KCNN3 transcripts by excessive ethanol drinking 🔓

Translational Psychiatry

This cross-species study found genetic and epigenetic adaptations in the KCNN3 gene by excessive alcohol consumption representing a complex mechanism through the use of alternative promoters that likely impact the intrinsic excitability of nucleus accumbens core (NAcC) medium spiny neurons (MSNs) and, ultimately, ethanol-seeking behaviors. The authors propose a model in which methylated region in exon 1 (MR-ex1) functions as a regulatory region to modulate the expression of the alternative transcripts SK3_ex1B and SK3_ex4. These findings provide the first evidence that hypermethylation of the MR-ex1 region of KCNN3 by heavy alcohol drinking as a key cross-species mechanism that may be important for the maintenance of excessive drinking and the development of alcohol use disorder.

Significant Decrease in Alcohol Use Disorder Symptoms Secondary to Semaglutide Therapy for Weight Loss: A Case Series

The Journal of Clinical Psychiatry

This study assessed the effect of semaglutide (a GLP-1 agonist) on alcohol consumption. A retrospective chart review of 79 patients at a weight loss clinic identified 6 with a positive AUDIT score (³8). The average follow-up interval was 5.3 months (range 1 – 9 months). At follow-up all 6 patients had a negative AUDIT score. The mean AUDIT score decreased with semaglutide therapy (14.0 to 4.5, p<0.001). The authors note that animal studies have shown promise for semaglutide in alcohol use disorder (AUD), but this is the first study to report results in humans. There are multiple randomized controlled trials of semaglutide in AUD underway and the authors suggest waiting for these results before adopting this treatment.