This Week in the ASAM Weekly

Drug use and overdose rates are a concern for the public’s health. A new report from the CDC looks at how overdose rates during the pandemic varied across different industries and work settings while highlighting significant health equity issues in the US (National Vital Statistics Report). It’s hard not to think about “deaths of despair” when reading this, but then an article from TIME reminds us that “deaths of despair” might be too narrow a view because there is more to "despair-ism" than originally conceptualized.

Data from Monitoring the Future found that young adults report using marijuana and hallucinogens at or near historically high levels while middle-aged adults report record levels of binge drinking (NIDA News). Maybe Generation X is responding to the difficulties of being sandwiched between two hippie generations.

Cannabis is now the most commonly used illegal (federal) drug in pregnancy, which means that perinatal research needs to close the knowledge gap quickly -- both for maternal and paternal use -- so we can better guide clinicians, develop policy, and inform the public (JAMA). A review on nitrous oxide toxicity reminds us that use of a cheap and easily accessible substance should be included on our differentials, especially when seeing youth and young adults with unusual gait (CMAJ).

More globally, Bashar al-Assad’s regime in Syria is looking to spread addiction and turmoil to global enemies by dealing a new amphetamine-type stimulant called captagon (The Messenger).

Evidently, drug use and overdose rates are a concern for geopolitical foes too.

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

Marijuana and hallucinogen use, binge drinking reached historic highs among adults 35 to 50 🔓

NIDA News

According to data from the Monitoring the Future (MTF) study, use of marijuana and hallucinogens reached their highest levels ever for people 35-50 years of age in 2022. Binge drinking among this age group also reached peak levels. For those 19-30 years of age, marijuana and vaping reached their highest levels since reporting MTF data. Past year use of other substances including sedatives, cigarettes, and non-prescribed opioids, however, revealed a 10-year decline for both age groups. According to NIDA director Dr. Nora Volkow, “Understanding these trends is a first step, and it is crucial that research continues to illuminate how substance use and related health impacts may change over time.”

Research and Science

Drug Overdose Mortality by Usual Occupation and Industry: 46 U.S. States and New York City, 2020 🔓

National Vital Statistics Reports

This report describes deaths from drug overdoses in 2020 in US residents in 46 states and New York City by usual occupation and industry. Workers in the construction and extraction occupation group and construction industry group had the highest drug overdose death rates. The highest group-level drug overdose proportionate mortality ratios (PMRs) were observed in decedents in the construction and extraction occupation group and the construction industry group. Differences in drug overdose PMRs by usual occupation and industry group were observed within each sex, within each race and Hispanic origin group, by drug type, and by drug overdose intent. Among individual occupations and industries, the highest drug overdose PMRs were observed in decedents who worked as fishers and related fishing occupations and in fishing, hunting, and trapping industries.

Risks of returning to opioid use at treatment entry and early in opioid use disorder treatment: role of non-opioid substances

Drug and Alcohol Dependence

This study asks if the outcome of MOUD treatment is affected by the use of other substances. Data from 3 previously published MOUD clinical trials was combined and analyzed for return to opioid use by week 12 of treatment. Use of other substances (cannabis, cocaine, alcohol, amphetamine, benzodiazepine) prior to treatment was not associated with outcome at week 12. However, use during the first 4 weeks of treatment was associated with increased risk of recurrence at week 12: for cocaine use (OR 1.4, p=0.0002) and amphetamine use (OR 1.7, p=0.0003). An interesting finding was that patients who received MOUD treatment with XR naltrexone and used cocaine during the first 4 weeks of treatment had a reduced risk of recurrence (OR 0.7, p<0.0001).

Diagnosis and management of toxicity associated with the recreational use of nitrous oxide 🔓

Canadian Medical Association Journal

While inhalant use typically peaks around 13-14 years old, nitrous oxide use peaks early adulthood and is the most common inhalant use in adults. Its relatively low cost, easy access, and perceived safety likely contribute to its frequent use. Chronic use can lead to vitamin B12 deficiency, causing myelopathy, peripheral sensorimotor neuropathy, and/or encephalopathy, and should be considered as a diagnosis in people -- particularly young people -- presenting with these symptoms. Diagnostic testing can include low vitamin B12 levels, MRI abnormalities, and abnormal nerve conduction studies. Improvement in symptoms can occur with discontinuation of use and vitamin B12 supplements.

An Engineered Human-Antibody Fragment with Fentanyl Pan-Specificity That Reverses Carfentanil-Induced Respiratory Depression

ACS Chemical Neuroscience

The opioid overdose crisis primarily driven by potent synthetic opioids resulted in more than 500,000 deaths in the US over the last 20 years. Though naloxone, a short-acting medication, remains the primary treatment option for temporarily reversing opioid overdose effects, alternative countermeasures are needed. Monoclonal antibodies present a versatile therapeutic opportunity that can be tailored to synthetic opioids and help prevent post-treatment renarcotization. The monoclonal antibody described in this study displays high affinity to carfentanil, fentanyl, and other analogs and reversed carfentanil-induced respiratory depression. Additionally, X-ray crystal structures with carfentanil and fentanyl bound provided structural insight into key drug:antibody interactions.

Learn More

Low-dose Initiation of Buprenorphine in Hospitalized Patients on Full Agonist Opioid Therapy: A Retrospective Observational Study

Journal of Addiction Medicine

In this retrospective study, researchers evaluated the low-dose initiation of buprenorphine in 76 hospitalized patients on full agonist opioids. Patients were started on <0.5 mg of buprenorphine and titrated to a minimum of 4 mg daily. Of the 76 patients, 54 (76%) completed the initiation and 2 (3%) had precipitated withdrawal. The average morphine milligram equivalents decreased from 1,000 mg pre-initiation to 37.5 mg after reaching target dose. The study demonstrated that low-dose initiation of buprenorphine can be a safe option for inpatients on full opioid agonists who cannot tolerate an opioid-free period and should be considered in this population.

Misclassification of overdose events in the X:BOT study 🔓

The Lancet

The X:BOT study compared the safety and efficacy of buprenorphine and naltrexone for treatment of OUD. A letter to the editor from another group of researchers reanalyzed the X:BOT data. A different search strategy of diagnoses identified 6 additional overdose events not included in the original study. Five were in the naltrexone group and one in the buprenorphine group resulting in an increased risk of overdose with naltrexone (HR 2.4, p=0.03). In an accompanying letter, the X:BOT authors acknowledge the additional overdoses but state the difference was not statistically significant in their analysis. In addition, some of the overdoses were in patients who failed induction on naltrexone and others occurred after study medications had been discontinued. The Lancet put the matter to the original reviewers of X:BOT who agreed these letters should be published but did not warrant not a retraction or correction of the original paper.

Cannabis Use and Perinatal Health Research 🔓

JAMA

Cannabis is now the most commonly used federally illegal drug in pregnancy, with a prevalence of use as high as 25% in northern California. In this viewpoint, the authors report on the significant knowledge gap that exists regarding prenatal cannabis use and perinatal outcomes. The unknown effects of synthetic cannabinoids in this population also deserve consideration. As evidence amasses regarding these concerns, clinicians are required to help assuage any adverse consequences related to these populations.

In The News