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ASAM Weekly for March 21, 2023

This Week in the ASAM Weekly

Informing the public is an important part of what we do. We educate caregivers about the harms of drug use in the home, proper storage of medications for OUD, and the use of naloxone in children because opioids were the most common substance contributing to fatal poisonings in children less than five (Pediatrics). Even Americans traveling to pharmacies in Mexico should be warned about medications contaminated with fentanyl and methamphetamines (NPR). 

Politicians pushing for harsher drug sentences seem to need more explanation about equitable harm-reduction approaches (NPR). A study in NYC shows that racial disparities in the naloxone care cascade are significant, particularly for Black women, and an informed approach that increases awareness and engagement with overdose prevention is needed (Harm Reduction Journal). 

DUI programs can help keep the public safe but can also help reduce re-arrests and mortality for drivers (JAMA Psychiatry). A meta-analysis found methadone use nearly doubled the risk for motor vehicle collisions, prompting the authors to suggest driving restrictions (Drug and Alcohol Dependence). The results do encourage us to properly educate patients about the risks and benefits but do not necessarily compel creating new barriers. 

Raising awareness about the harms of problematic substance use is an important part of what NIDA and NIAAA do. You can help them by submitting your thoughts (RFI) on the term preaddiction. 

Thanks for reading,

Nicholas Athanasiou, MD, MBA, DFASAM
Editor in Chief

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

 

Lead 

Characteristics of Fatal Poisonings Among Infants and Young Children in the United States 🔒

Pediatrics

Child death reviews present an opportunity to improve understanding of fatal poisonings. This study employed the National Fatality Review-Case Reporting System (NFR-CRS), a national standardized reporting tool, to describe the demographics of childhood deaths by poisoning, identify associated factors, and characterize those deaths attributable to opioids. Opioids were the most common substance (47.3%) contributing to death in young children, followed by OTC pain, cold, and allergy medications (14.8%). There was a substantial rise in these opioid-involved deaths over time, from 24.1% of the substances contributing to deaths in 2005 compared with 52.2% in 2018, illustrating the impact of the opioid epidemic on young children. Opportunities for naloxone education are paramount.

 
 

Research and Science

Early life adversity: Epigenetic regulation underlying drug addiction susceptibility 🔒

Molecular and Cellular Neuroscience

The authors review several studies examining the relationship between early life stressors and substance use exposures and substance use in adulthood in mice. Early life stressors have been found to be associated with changes in behavior, gene expression, and epigenome. In mouse models, they have also found sex-specific changes after early exposure in both behavior and gene expression levels, with many of these changes occurring in the amygdala and reward pathways. In mouse models, they also noted differences in response to substance exposures with cross-sensitization and differences in behavior response. As the effects are sex, brain-region, and exposure specific additional research is needed in this area. Notably, most research has historically been primarily in males. 

 

Racial/ethnic disparities in opioid overdose prevention: comparison of the naloxone care cascade in White, Latinx, and Black people who use opioids in New York City 🔒

Harm Reduction Journal

Overdose deaths in New York City (NYC) have increased disproportionately among Black and LatinX populations; even with well-funded efforts to distribute naloxone widely in NYC, there are disparities in coverage. This study examined disparities in the cascade of naloxone distribution for training, current and past 30-day possession, and presence of naloxone and another person to administer in the past 30 days. Black and LatinX individuals were less likely to have received naloxone training (aOR 0.40 and 0.54) than White participants. This difference was even more pronounced for Black women (aOR 0.27) and those over 51 (aOR 0.20). Black persons were also less likely to have daily past 30-day access (aOR 0.38) or presence of naloxone and another person to administer (aOR 0.44). There are still considerable gaps in naloxone protection, including risk of solitary drug use. 

 

Transcriptional control of nucleus accumbens neuronal excitability by retinoid X receptor alpha tunes sensitivity to drug rewards

Neuron

This study uses cell-type specific transcriptomics, electrophysiology, and behavior to single out retinoid X receptor alpha (RXRα), a putatively druggable transcription factor that governs larger gene networks to calibrate the physiology of nucleus accumbens (NAc) neurons and, in turn, individual sensitivity to substance use. NAc RXRα expression correlates with addiction-relevant behavioral and molecular features. RXRα transcriptionally controls neuronal excitability of NAc dopamine D1- and dopamine D2- medium spiny projection neurons (MSNs). Manipulating NAc RXRα levels modulates cocaine reward learning and reinforcing efficacy and systemic, pharmacological inhibition of RXRα weakens cocaine-related behaviors. This study demonstrates a key role for NAc RXRα in promoting drug addiction and paves the way for future studies of rexinoid signaling in psychiatric disease states.

Risk of motor vehicle collisions after methadone use: A systematic review and meta-analysis 🔒

Drug and Alcohol Dependence

This study examined the risk of motor vehicle collisions in patients receiving methadone maintenance therapy. The results from previous research have been inconsistent, but this is the first systematic review that also performed a meta-analysis on pooled data. A literature search found 19 potential articles of which 7 met inclusion criteria and represented 33,226,142 participants. Patients with methadone use had a higher risk of motor vehicle collisions (pooled RR=1.92, 95% confidence interval 1.25-2.95). The authors state “the results suggest that drivers exposed to methadone should have restrictions for driving.”Learn More

The risks of misclassifying addictive food substances as non-addictive 🔒

Addiction

The authors of this commentary recently published a discussion of how highly processed foods (HPFs) meet the criteria for addictive substances. This commentary responds to a suggestion that a concept of “para-addiction” be used for HPFs. They note that the tobacco industry used similar reasoning since tobacco is not highly intoxicating and rarely results in overdose. As a result, the term “habit forming” was used, obscuring the addictive nature of tobacco. HPFs result in a rate of preventable deaths similar to tobacco and alcohol. Using criteria for SUD, 14% of adults have addiction to HPFs, similar to rates for other SUDs. Treatments useful in addictions are used to treat obesity, such as bupropion/naltrexone and Overeaters Anonymous. Misclassifying HPFs as para-addictive leaves consumers ill-informed.

Association of an Alcohol Abstinence Program With Mortality in Individuals Arrested for Driving While Alcohol Impaired

JAMA Psychiatry

In the US, alcohol-impaired driving claimed 11,654 lives in 2020—a 14% increase over the previous year. Some jurisdictions are using 24/7 sobriety programs, which combine alcohol abstinence orders with frequent alcohol testing and swift, certain, and moderate sanctions for noncompliance to reduce alcohol consumption among those arrested or convicted for alcohol-involved offenses. This study, with instrumental variables analysis, was conducted to assess the association between 24/7 sobriety and time-to-mortality using individual-level data. The findings add a public health dimension to the growing evidence that 24/7 sobriety improves public safety by reducing rearrest. This is also the first evidence from individual-level data that such programs may also improve health outcomes.

Medical Complications of Injection Drug Use — Part II

NEJM Evidence

During the past two decades, the risk of death, as well as the prevalence of hospitalizations in the US, has increased substantially among people who inject drugs (PWID), in large part because of the opioid epidemic. Complications observed in PWID include viral infections; botulism; withdrawal symptoms that mimic infectious complications; and cardiovascular, vascular, hematologic, and pulmonary complications; in addition to depression and suicide. Strategies to mitigate risk of injection drug use (IDU) include overdose education and naloxone distribution, access to fentanyl test strips, a regulated safe supply of drugs, syringe service programs, safe consumption sites, and incorporating addiction treatment and harm reduction principles into clinical care settings.