The ASAM Weekly for March 11th, 2025

This Week in the ASAM Weekly

Dear Reader,

• Last week, the ASAM Weekly published a guest editorial about ASAM’s clinical guideline on benzodiazepine tapering.

• The week before, we made a call for applications to become an ASAM Weekly Co-Editor (apply here). 

• This week, we’re going back to fundamentals by showcasing publications on the opioid crisis.

Let’s start with a Research Letter from JAMA Network Open. It’s not long enough to burst any bubbles (yet), but it presents a striking conclusion nonetheless: national reductions in overdose deaths may have just been a detour from the pandemic’s acceleration, not a change in trajectory from 2019.

This means our vigilance can’t let up if we want to close the gap and treat addiction. We’ll still need to protect telehealth rules that move us forward and support “low-barrier prescribing” (Health Affairs). We’ll also need to build more equitable care cascades that improve initiation and retention, and save lives (Drug and Alcohol Dependence). We’ll even need to build better consensus and agreement around outcomes if we want to improve quality of care and quality of life (International Journal of Mental Health and Addiction). Yes, we can do this.

But we’ll also need to be bold. A study in Addiction shows that we should be dosing buprenorphine beyond 24 mg. The authors go so far as to critique outdated guidance from the FDA and even ASAM (circa 2020). But a little self-reflection isn’t a bad thing; we could use some to expand our advocacy to protect people with addiction from unfair Medicaid work requirements (Health Affairs).

If you’ve read this far, you might know where this is going. Treating addiction is not to be taken lightly, so if you receive an email asking what you did last week (NPR), consider this:

• Treated addiction.

• Saved lives.

• Read the ASAM Weekly.

Thank you for what you do and see you next week,

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 

The association between buprenorphine doses above 16 milligrams and treatment retention in a multi-payer national sample in the United States, 2014 to 2021

Addiction

Buprenorphine labeling identifies 16 mg as the “target dose,” supported by prior evidence that higher doses (≥16 mg) were associated with increased retention in treatment. Studies comparing doses above 16 mg to 16 mg, particularly in the era of fentanyl, have been very limited. The authors conducted a cohort study to look at retention for those receiving 24, 32, and 40 mg compared to 16 mg. Overall, higher doses were associated with increased retention, as follows: 1) 24 mg was more effective than 16 mg at 1 (aOR=1.52) and 18 months (aOR=1.17), 2) 32 mg was more effective than 24 mg at 6 (aOR=1.06), 12 (aOR=1.09), and 18 months (aOR=1.12), and 3) 40 mg was more effective than 24 mg at 12 (aOR=1.10) and 18 months (aOR=1.18). The authors suggest updates to label language and recommendations are prudent, while also supporting more research on long-term treatment with these higher doses.

Research and Science

The OPTIMUS International Consensus Guidance for Monitoring User-Reported Outcomes of Opioid Maintenance Treatment: a Delphi Study 🔓

International Journal of Mental Health and Addiction

Evaluation of treatment for opioid use disorder (OUD) is not consistent, with a lack of consensus on which outcomes are important and a large variation in the outcomes reported in current scientific literature. The authors conducted a Delphi study, including providers, researchers, and people with lived experience from 29 countries, to develop guidance for outcomes. The authors focused on service user-reported and public health-centered outcomes to develop a list of core questions and optional questions to assess the following 6 domains: 1) treatment, 2) physical health, 3) substance use, 4) mental health, 5) social functioning, and 6) quality of life. The guidance can provide consensus outcomes to evaluate program treatment impacts and policies. 

Assessing inequities in buprenorphine treatment across the care cascade

Drug and Alcohol Dependence

This observational cohort study of new opioid use disorder (OUD) treatment episodes between 1/1/15 and 12/31/21 identified buprenorphine treatment gaps across the care cascade by race, ethnicity, age, sex, and key clinical characteristics. Researchers found inequity in 6-month buprenorphine retention by race, reflecting a gap at initiation; inequity in 6-month buprenorphine retention by sex, reflecting one-month treatment gaps; and inequity in 6-month buprenorphine retention by age, reflecting treatment gaps across the cascade. Past buprenorphine use increases probability of initiation but not retention, and co-occurring substance use disorders are associated with low initiation probability.

A new module in the drug development process: preclinical multi-center randomized controlled trial of R-ketamine on alcohol relapse 🔓

Neuropsychopharmacology

This multi-center preclinical randomized controlled trial (preRCT) used the alcohol deprivation effect (ADE) model to assess the impact of ketamine and R-ketamine on alcohol relapse across three European research centers. Ketamine (20 mg/kg) significantly reduced relapse, while R-ketamine showed efficacy only in females. A higher dose of R-ketamine (40 mg/kg) was also effective in males. These sex-dependent effects were linked to plasma R-ketamine levels, which were two-fold higher in female compared to male rats. Notably, R-ketamine demonstrated a lasting reduction in alcohol consumption without adverse effects. In conclusion, this preRCT demonstrates R-ketamine’s effectiveness in reducing alcohol relapse and supports translation to a clinical RCT that accounts for sex-dependent effects.

Buprenorphine-Naloxone versus Buprenorphine for Opioid Use Disorder During Pregnancy: A Systematic Review and Meta-Analysis

Drug and Alcohol Dependence

This systematic review and meta-analysis compared buprenorphine-naloxone (Bup-Nx) with buprenorphine monoproduct (Bup) for treatment of OUD during pregnancy. Five studies totaling 9,348 mother-infant dyads met inclusion criteria. Researchers found that Bup-Nx was associated with a lower incidence of neonatal abstinence syndrome than Bup (RR 0.77, p<0.01). Bup-Nx was also associated with a lower incidence of small for gestational age than Bup (RR 0.85, p=0.03). There was no significant difference between Bup-Nx and Bup for APGAR<7, birth weight, preterm delivery, congenital malformations, or illicit drug use. The fact that these studies were not randomized increases the risk of bias and resulted in a low confidence of evidence score for the neonatal abstinence and small for gestational age results.

Learn More

The Impact of Frequency of Cannabis Use on Hypertensive Disorders During Pregnancy 🔓

Journal of Addiction Medicine

This study included 587,486 participants from the nine states that collect frequency of cannabis use during pregnancy data. Of the total participants, 3.8% reported any cannabis use during pregnancy, and of those, 23% reported minimal use (≤1 time/month), 24% moderate use (2-4 times/month), and 53% frequent use (up to daily use). Frequent use was associated with the following maternal characteristics: White race, younger age, no high school diploma, Medicaid insurance, depression, enrolled in WIC, cigarette smoking, and state of residence. Hypertension during pregnancy was less likely in the minimal use group than those with no use (aOR 0.34). However, those with frequent cannabis use were 3.1 times more likely to be diagnosed with hypertension during pregnancy than those with minimal use (18% vs 6.7%).

US Youth Exposed to Parental Substance Use Disorder in the Home: A Comparison of DSM-IV and DSM-5 Criteria 🔓 

Journal of Addiction Medicine

Children and adolescents under 18 years of age exposed to parental substance use disorder (SUD) are at high risk for poor outcomes, including substance use, psychopathology, and child welfare involvement. With the changing SUD criteria from DSM-IV to DSM-5, revised estimates of youth exposed to parental SUD in the home are needed to provide more recent estimates and investigate whether the change from DSM-IV to DSM-5 may change estimated SUD exposure. Using nationally representative data from the 2020 National Survey on Drug Use and Health, the authors found that the change from DSM-IV to DSM-5 criteria resulted in a large increase in youth exposed to parental SUD. The health needs of these youth will require large-scale planning to limit poor outcomes in the roughly 17 million exposed youth; family-based interventions may help limit harm to all members of the family.

Recent Drug Overdose Mortality Decline Compared With Pre–COVID-19 Trend 🔓

JAMA Network Open

In the year preceding June 2024, there was a 14.5% decrease in annual drug overdose mortality in the US. However, during the years 2020-2023, most states had higher than expected mortality compared to pre-2020 data. Nine mostly Western states had rapidly increasing mortality during this period (the states being California, Colorado, Oregon, Washington, Alaska, Oklahoma, Texas, Wyoming, and Alabama). This could be due to the increase in synthetic opioids in these 9 states. The authors conclude that the recent decline in overdose mortality may be the waning of the exacerbation during the COVID-19 pandemic and resumption of pre-pandemic trends. They expect overdose mortality in Western states may increase in the next few years.

In The News

Cannabis addiction is rising in America. Reddit is here to help. 🔓

SFGate

Imposing Medicaid Work Requirements Could Cause Many Adults With Substance Use Disorders To Lose Access To Treatment 🔓

Health Affairs

Concerns rise over impact of Senate Bill 204 on opioid treatment centers in West Virginia 🔓

WCHS Charleston

Violence, Overdose Threaten Pregnant Women’s Lives 🔓

Medscape

Prescribing Buprenorphine By Telehealth: Lessons From San Francisco Amidst A Changing Regulatory Landscape 🔓

Health Affairs 

'A blitz attack': VA mental health experts liken Elon Musk's emails to warfare 🔓

National Public Radio