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This Week in the ASAM Weekly

A fun part about doing a word search puzzle is that after you find a word, it seems to stand out from the rest of the letters on the page. The same can happen with scientific publications—some words or phrases just seem to jump off the page. Here are a few examples from this week.

Unwinding: The process in which states resumed Medicaid re-enrollment. Since April 2023, unwinding has led to the disenrollment of tens of millions of individuals, mostly because of paperwork issues. It's also associated with disruptions in buprenorphine therapy ().

Complexify: A transitive verb that also encapsulates the challenge of studying cannabis use, depression, and suicidality. Along with this word, you’ll find confounding, mediation, and moderation in an insightful discussion from the authors ().

Trainspotting: No one should expect to find the title of this academy award-nominated movie in a scientific paper—especially in one about how the orbito-frontal cortex is biased toward drug content during addiction but normalizes with treatment and recovery ().

Biased agonism: The ability to selectively trigger signal pathways at the cell receptor and a key mechanism for the future of pain treatment. For example, SBI-810 is a drug that can alleviate both acute and chronic pain in rodent models while avoiding the side effects usually seen with opioids ().

Contingency Management: A well-known word that’s worth finding over and over again because it’s the most effective evidence-based treatment for an illness that has no FDA-approved medication (). 

$700k: The estimated cost to businesses, governments, and households for each case of opioid use disorder, per year. Treatment for OUD can reduce these costs, sometimes by more than 40% (). 

So, give it a try. Find these words and more in this week’s publications. If you’re looking for something more than a word search, then how about trying an ASAM Weekly “Wordle”?

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Thanks for reading,

Nicholas Athanasiou, MD, MBA, DFASAM
Editor in Chief

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

Lead Story 

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JAMA Network Open

Among Medicaid-insured adults with buprenorphine use, this cross-sectional study examined if changes in buprenorphine dispensing were greater among those residing in states with the highest vs lowest decreases in Medicaid enrollment after “Medicaid unwinding” began in April 2023. Researchers used 2017-2023 data from a national prescription dispensing database that included 754,675 person-years from 569,069 patients. They found that patients in states with the highest decreases in Medicaid enrollment were more likely to decrease buprenorphine use, discontinue buprenorphine therapy, and use private insurance or cash to pay for buprenorphine prescriptions. The finding that Medicaid unwinding was associated with disruptions in buprenorphine therapy raises concerns about the potential for increased opioid-related morbidity and mortality.

Research and Science 

Cell

This study explores SBI-810, a neurotensin receptor 1 (NTSR1) modulator that favors β-arrestin-2 signaling. SBI-810 produces strong analgesic effects in rodent models of various pain types and requires NTSR1 and β-arrestin-2 for efficacy. Mechanistically, it suppresses excitatory signaling in spinal pain pathways, reduces sodium channel activity, and decreases neuronal excitability. Behaviorally, SBI-810 mitigates opioid-related side effects, such as reward, constipation, and withdrawal symptoms. These results suggest SBI-810 may offer a non-addictive alternative for treating acute and chronic pain, with potential to reduce reliance on opioids.

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Drug and Alcohol Dependence

This systematic review of articles concerning cannabis use and suicidality identified 25 articles that met inclusion criteria, and 12 of those met the criteria for pooling data in a meta-analysis. After adjusting for depression, researchers found the following: among adolescents, cannabis use was associated with suicidal ideation (OR=1.46) and suicide attempts (OR=2.17); among adults, cannabis use was associated with suicidal ideation (OR=1.78). However, 12 studies found no association between cannabis use and suicidality after controlling for depression. The authors conclude that cannabis use might be associated with suicidality independent of depression. Cannabis use is also associated with bipolar, borderline, and psychotic disorders which could play a role in the association with suicidality. The authors call for longitudinal studies that could reveal the sequence in which these events develop.

Drug and Alcohol Dependence

This study of patterns of stimulant use included 3,476 patients with OUD receiving outpatient OAT between 2013 and 2020. During this period, methamphetamine use increased from 2.0% to 17.7% of patients (p=0.002). Changes in cocaine use did not reach statistical significance. Use of stimulants daily increased from 0.4% to 3.8% of patients (p=0.009). Women were less likely than men to use methamphetamine (OR=0.67) and more likely to use crack cocaine (OR=1.47). Injection drug use was associated with any stimulant use (OR=7.95) and daily stimulant use (OR=4.55). In patients receiving OAT for OUD, stimulant use increased significantly between 2013 and 2020.

Brain

Maladaptive motivational salience attribution in persons with substance use disorder occurs where, within the normal environment, drug cues outcompete other reinforcers such as food or social relationships. In this study, using movies with drug use cues included in the normal story, researchers utilized functional MRI (fMRI) to watch the response in various brain networks to drug cues in persons with heroin use disorder (HUD) and health controls. Persons with HUD had a response to drug cues in the orbitofrontal cortex (OFC), with a subsequent reduction in that response after 15 weeks of inpatient treatment. The authors note that synchronized OFC response to drug cues could be a useful marker for cravings and in recovery. 

Learn More 

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Addiction Science and Clinical Practice

Cocaine and methamphetamine use disorders (CcUD/MtUD) have been increasing in prevalence, but there are currently no FDA-approved treatments. Repetitive transcranial magnetic stimulation (rTMS) has been approved for use in treatment of major depressive disorder and investigated for treatment of stimulant use disorder (StuD). In this study (STIMULUS), researchers will randomize patients with CcUD or MtUD to 30 sessions of rTMS to the left dorsolateral prefrontal cortex over 8 weeks with follow-up at 12 and 16 weeks. The goal is to assess feasibility of treatment and effects on self-reported substance use, cravings, mood, and sleep.

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Frontiers in Immunology

Subacute combined degeneration (SCD) of the spinal cord results from vitamin B12 deficiency (Vit B12-SCD). Nitrous oxide (N2O) inhibits an enzyme causing a functional vitamin B12 deficiency resulting in SCD (N2O-SCD) but with more severe signs and symptoms. In this study, the N2O-SCD group was more likely than the Vit B12-SCD group to have limb weakness (91% v 45%), have difficulty walking (74% v 35%), and be unable to walk (35% v 5%). The N2O-SCD group had confusion (26%), hallucinations (30%), and delusion (14%) that were not seen in the Vit B12-SCD group. Memory loss was more common in the N2O-SCD group (48% v 10%). MRIs show the spinal cord lesions in the N2O-SCD group were 4 times longer than in the Vit B12-SCD group. In addition to the effects on Vit B12, N2O has additional neurotoxicity due to neuroinflammation and NMDA receptor antagonism.

Journal of Gambling Studies

The Problem Gambling Severity Index (PGSI) is a screening tool to assess potential problems with gambling and includes low-, moderate-, and high-risk categories. While detection of those at higher risk is appropriate, there is significant variability among those in the moderate-risk category. In this study, researchers utilized prior PGSI survey data to identify 3 clusters among those in the moderate-risk category: 1) Possibly Episodic (PE), 2) Specific Problems (SP), and 3) Intermediate Cases (IC). The authors found there was significant variability in educational, financial, and employment status among these 3 groups. The authors suggest these categories provide beneficial information to further refine the moderate-risk category and potentially inform more targeted prevention strategies. 

In the News 

The New York Times

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Medscape

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MedPage Today

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Axios

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R Street Institute

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CNN Business