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ASAM Weekly for June 20th, 2023

This Week in the ASAM Weekly

Not often do we lead with a study of a first-in-class pharmacotherapy, especially one that treats cannabis use disorder. Known as a signaling-specific inhibitor of the cannabinoid receptor type 1 (CB1-SSi), this new drug works by selectively targeting only a subset of intracellular processes resulting in a therapeutic that can reduce the use and subjective effects of cannabis while having minimal side effects and without precipitating withdrawal (Nature Medicine). The results of the phase 2a trial are promising. 

Although the burden of alcohol use is well-known globally, many of the studies linking alcohol consumption with various diseases have been conducted in Western populations. A study using data from the China Kadoorie Biobank has not only confirmed most of the known associations, but has also identified 33 additional alcohol-associated diseases in Chinese men not previously identified by the WHO (Nature Medicine). The additional genetic analysis adds an interesting consideration for causation. 

We also have several brief publications to consider. A perspective from the New England Journal of Medicine focuses our attention on the role of fentanyl test strips, the sphere of FDA authorization, and how both could innovate future harm-reduction strategies. A research letter from JAMA Health Forum demonstrates how New Jersey’s large-scale decarceration during the pandemic did not result in increased SUD-related acute care or overdose death. Also, an opinion piece from Yahoo Life critiques Kentucky’s plan to research ibogaine as a future treatment of opioid use disorder when not nearly enough is being spent to fund treatments already known to work today. 

Lastly, there is a must-read commentary from the Journal of Addiction Medicine. Overturning Roe v. Wade has created many harms in the delivery of healthcare with a disproportionate impact on individuals who use substances. Addiction specialists can help by asking, advocating, and informing. 

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 

Signaling-specific inhibition of the CB1 receptor for cannabis use disorder: phase 1 and phase 2a randomized trials ðŸ”“

Nature Medicine

Cannabis use disorder (CUD) is widespread, and there is no pharmacotherapy to facilitate its treatment. AEF0117, the first of a new pharmacological class, is a signaling-specific inhibitor of the cannabinoid receptor 1 (CB1-SSi). AEF0117 selectively inhibits a subset of intracellular effects resulting from Δ9-tetrahydrocannabinol (THC) binding without modifying behavior per se. In mice and non-human primates, AEF0117 decreased cannabinoid self-administration and THC-related behavioral impairment without producing significant adverse effects. In healthy human volunteers with CUD, AEF0117 was well tolerated and did not precipitate cannabis withdrawal. These data suggest that AEF0117 is a safe and potentially efficacious treatment for CUD.

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Research and Science

Identifying Biomarkers of Drug Use Recurrence using Wearable Device Technologies and Phone Applications

Drug and Alcohol Dependence

This study remotely monitored biomarkers on 77 participants in an OUD treatment program to identify patterns predictive of drug use recurrence (DUR). A phone app was installed that recorded a daily self-assessment questionnaire containing items such as stress, mood, craving, and others. Participants also wore a Garmin fitness tracker that recorded heart rate, blood oxygen saturation, and daily activity. A DUR was experienced by 44% of the participants. The Garmin stress score (derived from heart rate variability) was observed to be elevated during the month prior to a DUR. The character of the self-assessment questions was also different during periods of DUR. Finally, compliance with the questionnaire and wearing/syncing the Garmin device decreased during the week prior and the week of DUR. The authors conclude that this technology is potentially useful in predicting DUR.

Ventricular Arrhythmias Associated With Over-the-Counter and Recreational Opioids

Journal of the American College of Cardiology

This study explores links between ventricular arrhythmias with loperamide and mitragynine (kratom). Opioid agonists can have effects on cardiac ion channels. Methadone can cause QT prolongation, torsade de points, and sudden death. The study analyzed pharmacovigilance data and found over 1,000 cases of ventricular arrhythmia or sudden death for loperamide (and a similar number for methadone) as well as 46 cases for mitragynine. No association was found for buprenorphine, naltrexone, or diphenoxylate. The authors note that both loperamide and mitragynine are available OTC and are used (often in high doses) for their opioid effects. These data link these OTC opioid agonists with lethal arrhythmias.

DEA

Alcohol consumption and risks of more than 200 diseases in Chinese men ðŸ”“

Nature Medicine

This study investigated the associations of alcohol consumption with 207 diseases in the 12-year China Kadoorie Biobank of >512,000 adults (41% men), including 168,050 genotyped for ALDH2-rs671 and ADH1B-rs1229984, with >1.1 million ICD-10 coded hospitalized events. At baseline, 33% of men drank alcohol regularly. Their alcohol intake was positively associated with 61 diseases, including 33 not defined by the World Health Organization as alcohol-related. Genotype-predicted mean alcohol intake was positively associated with established and new alcohol-associated diseases and with specific diseases such as liver cirrhosis, stroke, and gout, but not ischemic heart disease. Among women, 2% drank alcohol, resulting in low power to assess associations of self-reported alcohol intake with disease risks, but genetic findings in women suggested the excess male risks were not due to pleiotropic genotypic effects.

Spatiotemporal Analysis Exploring the Effect of Law Enforcement Drug Market Disruptions on Overdose, Indianapolis, Indiana, 2020–2021 ðŸ”“

American Journal of Public Health

Opioid overdoses continue to be of significant public health concern and in this study, the authors examine a potential relationship between law enforcement activities and local and temporal changes in overdoses. They found that seizures of opioids and stimulants were associated with increases in fatal and nonfatal overdoses. The authors hypothesize the seizures disrupted the drug supply, leading to periods of abstinence and persons with opioid use disorder seeking new supplies of unknown potency, thus increasing the risk of overdose. While the authors note additional research is needed, they do suggest that early notification of law enforcement drug seizures to agencies that provide prevention services and referral to care could decrease overdoses.

Learn More

Testing for Fentanyl — Urgent Need for Practice-Relevant and Public Health Research

The New England Journal of Medicine

In this perspective, fentanyl and its analogues are discussed as critical targets for harm-reduction efforts. Recognizing the potential for fentanyl test-strip use to reduce harm from fentanyl exposure, the CDC and SAMHSA issued a guidance document in April 2021 permitting their grantees to use federal funds for purchase. Emphasis is placed on more widespread integration of other methods to check for substances in illicit drugs, like those of other harm reduction services. Fentanyl test strips could also help steer interventions in the ED for those struggling with SUD. 

Hospital Use and Mortality Among Decarcerated Individuals With Substance Use Disorder After a Large-scale COVID-19 Emergency Prison Release Program ðŸ”“

JAMA Health Forum

In 2019, New Jersey enacted the Public Health Emergency Credit Act (PHECA) with the goal of reducing virus transmission among incarcerated persons. This study sought to examine whether during postrelease, persons with SUDs would tax the system. During the first 45 days after release, an SUD-related acute care visit (ACV) occurred in 526 releases (4.7%); overdose deaths occurred in 32 releases (0.3%). There was no evidence that postrelease rates of SUD-related ACVs or overdose death were higher for persons with SUD released after the PHECA than they were during earlier periods. New Jersey’s decarceration may offer a model for future policy reform.

The Fall of Roe v. Wade: The Addiction Specialist’s Role in Championing Reproductive Rights : Journal of Addiction Medicine

Journal of Addiction Medicine

Persons with SUD experience significant stigmatization in reproductive health and are less likely to use contraception, more likely to have unplanned pregnancies, and thus will experience higher burden from abortion access restrictions following the overturn of Roe v. Wade. Furthermore, they face significant barriers to prenatal care and punitive legal policies if forced to continue unwanted pregnancies. The authors urge addiction specialists to incorporate reproductive health into their care, screening patients for plans or desires to become pregnant and optimizing care and coordination with prenatal care providers. For patients who do not wish to become pregnant, providers must ensure contraceptive counseling and services are provided. Providers should also be familiar with abortion services resources to be able to guide patients to safe and legal abortion when requested.