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This Week in the ASAM Weekly

The ASAM Weekly showcases over 600 research and news publications every year. Sometimes, distilling the hundreds of outcomes, editorials, and news stories into smaller, more memorable messages can help keep track of the bigger picture. Here are just a few examples from this week. 

“One pill can kill.” This public health message is most often used to warn people about the dangers of fentanyl, but it also represents some of the most dynamic elements of the opioid crisis. Keep it in mind when you read about how and why drug deaths are plummeting among young Americans (). 

 “The market never lies.” This is a well-known investing principle that often rings true for addiction. People seem to be drinking less, and the most convincing evidence might be the falling stock value of major alcohol companies (). 

“State of mind” is an idiom that has become fundamental to understanding psychedelics across the domains of research, recreation, and even religion (). It also applies when comparing the therapeutic actions of antidepressants and psilocybin ().

“An ounce of prevention is worth a pound of cure.” This very American proverb gets straight to the point about addiction and Medicaid cuts. Unfortunately, too many politicians may have forgotten its meaning (). 

“Treat addiction. Save lives.” With the overwhelming evidence that OAT is life-saving (), “Treat addiction. Save lives,” becomes more than an effective slogan—it’s a clinical pearl.

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

Drug and Alcohol Dependence

People who experience a nonfatal opioid overdose are at increased risk of subsequent overdose, but a nonfatal overdose also provides a potential moment to intervene. In this cohort study, researchers used statewide data from Connecticut to assess differences in overdose outcomes in the year following a nonfatal overdose by treatment type received. Overall, 56% of patients received no treatment, while 35% received medication for opioid use disorder (MOUD) (25% buprenorphine and 11% methadone) and 21% received inpatient treatment (detox and/or extended inpatient). Both methadone (aHR=0.41) and buprenorphine (aHR=0.72) were associated with a decrease in subsequent overdose, whereas neither detox nor prolonged inpatient treatment were associated with decreased overdose. These findings further support the importance of MOUD and the need to increase access to treatment in this high-risk population.

Research and Science 

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Addiction Biology

This systematic review identified 20 studies, meeting specific inclusion criteria, concerning the efficacy of cannabidiol (CBD) for treatment of OUD. Two human randomized placebo-controlled trials and one open label trial found CBD reduced cue-induced craving in both patients receiving MOUD and those not on MOUD. Preclinical animal studies suggest CBD reduces opioids’ rewarding effects and reduces opioid withdrawal symptoms. However, these results in animal studies are mixed with some failing to show reduced withdrawal. In one animal study, CBD did not reduce morphine self-administration. The authors conclude that CBD has potential as a treatment for OUD; however, long-term follow-up studies are needed.

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Psychedelic Medicine

Using a randomized, waitlist-controlled design, this exploratory study examined the impact of psilocybin on clergy from various major religions with no prior psychedelic experience. Participants underwent 2 psilocybin sessions and were assessed over time. Results showed significant and lasting improvements in religious engagement, attitudes, leadership, mood, and behavior, with effects lasting up to 16 months. Most participants described the experience as spiritually profound and reported increased prayer, meditation, and appreciation for other faiths. While no serious adverse events occurred, nearly half found the experience psychologically challenging. The authors concluded that, in this population, psilocybin was safe and led to meaningful, enduring benefits, though further research is needed with more diverse samples and rigorous methods.

The American Journal of Psychiatry

This study compared the effects of psilocybin and SSRIs on brain activity related to emotional processing in patients with major depression. Using functional MRI, 2 groups were observed: one treated with psilocybin and placebo, and the other with escitalopram and a nonpsychoactive dose of psilocybin. Both groups received equal psychological support. Results showed that escitalopram reduced brain responses to emotional faces, particularly in the amygdala’s reaction to fear, while psilocybin caused little to no change or a slight increase in these responses. Despite significant symptom improvement in the psilocybin group, its impact on brain responsiveness to emotional stimuli was minor. These findings suggest that unlike SSRIs, which reduce emotional responsiveness, psilocybin may alleviate depression without dulling emotional processing.

Learn More 

Clinical Toxicology

Bromazolam (alprazolam with a bromine substituted for a chlorine) has appeared in the illicit drug supply. In 2023, San Francisco had a surge of bromazolam-related deaths with 44 deaths that year. In the last 6 months of 2023, an ED in Baltimore had 24 severe overdoses; 7 (29%) of these patients had bromazolam in their blood. Five reported they had taken an opioid, one reported using ecstasy, and one reported having taken an opioid plus cocaine. However, all had 3 or more substances detected, and xylazine was detected in 5 of the individuals. All 7 patients survived—4 were hospitalized and 3 discharged from the emergency department. The authors conclude that surveillance is important to detect substances in the drug supply not known to patients.

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Translational Psychiatry

Cocaine augments synaptic dopamine (DA) levels by inhibiting the dopamine transporter (DAT) that causes DA reuptake. Modafinil, used to treat narcolepsy, also inhibits the DAT but does not produce cocaine-like effects. Cocaine is described as a typical DAT inhibitor while modafinil is an atypical DAT inhibitor. Clinical studies have produced mixed results for modafinil as a treatment for cocaine use disorder (CUD). This study tested the effect of two modafinil analogues on cocaine self-administration in rats. RDS-03-094 acted like a typical DAT inhibitor and produced cocaine-like self-administration in rats. RDS-04-010 acted like an atypical DAT inhibitor and did not produce self-administration in rats. Pretreatment with RDS-04-010 inhibited cocaine self-administration in rats and shows promise as a treatment for CUD.

Journal of Addiction Medicine

In this commentary, the authors suggest the need for new outcomes evaluating opioid use disorder (OUD) treatment. Urine toxicology has been used as evidence of abstinence, but the authors provide scenarios in which toxicology can give a false picture of what is happening with patients and their use. The authors recognize urine toxicologies as a clinical tool but contend we need to move beyond them to evaluate OUD treatment. The authors propose using measures of physical, emotional, and social well-being, including overdose and health-related complications, and also patient-reported outcome measures (PROMs). The authors reason that PROMs that assess substance use, mental health, and quality of life are more patient-centered and tailor treatment to meet patient needs. 

The Lancet Gastroenterology and Hepatology

GLP-1 receptor agonists (GLP-1RA) have known potential benefits for diabetes and weight loss, but there is also early evidence for potential benefits in alcohol use disorder (AUD) and metabolic liver disease. The authors of this commentary discuss some of the preclinical evidence and early clinical trials of potential impact of GLP-1RA in decreasing alcohol consumption, cravings, and incidence of AUD. In addition, they discuss the beneficial impact on metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). As alcohol is the leading cause of liver disease, cirrhosis, and indication for liver transplant, the authors note the potential role for GLP-1RA in addressing alcohol-associated liver disease (ALD) and support clinical trials in patients with ALD and AUD.

In the News 

The Boston Globe

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NJ Spotlight News

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Newsweek

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National Public Radio (NPR)

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Dallas Morning News

Financial Times

The New York Times 123