This Week in the ASAM Weekly

Dear readers,

As we approach the end of 2024, we'd like to thank our readers for making all of this possible. It is quite something to put out a publication 52 weeks a year and so this is the time of year when we slow things down a little for the ASAM Weekly editors and staff. 

Please enjoy the next several editions recapping the most-read research and most-read news publications from the ASAM Weekly 2024. In addition, you don't want to miss out on our newest holiday edition- a recap of ASAM Weekly Guest Editorials- coming out on January 7th.

Happy holidays and new year to all. See you in 2025.

Nicholas Athanasiou, MD, MBA, DFASAM
Editor in Chief

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

Association of semaglutide with risk of suicidal ideation in a real-world cohort

Nature Medicine

In this retrospective cohort study, the authors investigate associations between the glucagon-like peptide 1 receptor (GLP1R) semaglutide and suicidal ideation (SI). The authors examine SI in 4 cohorts: 1) patients with obesity and not history of SI, 2) patients with obesity and history of SI, 3) patients with type 2 Diabetes Mellitus (T2DM) and not history of SI and 4) patients with T2DM and history of SI. In all 4 groups, patients treated with semaglutide versus non-GLP1R anti-obesity or non-GLP1R anti-diabetes medication respectively had lower risk of SI at 6 months follow-up (Group 1: HR=0.27, Group 2: HR=0.44, Group 3: HR=0.36, Group 4: HR=0.51). In addition, in the T2DM patients, those treated with semaglutide also had lower risk of SI at 1, 2, and 3 years of follow-up. 

Effectiveness of Residential Treatment Services for Veterans with Substance Use Disorders A Propensity Score Matching Evaluation

Drug and Alcohol Dependence

This study evaluates the effectiveness of Veterans Affairs (VA) residential treatment for substance use disorders (SUD) compared with their outpatient programs. Researchers identified 6177 veterans who were screened and accepted for VA SUD residential treatment during the first half of 2019. Of these, 883 ended up receiving non-residential VA treatment and served as the comparison group. There were improvements in SUD symptoms throughout the year following treatment in the residential group that were significantly greater than in the comparison group (p<.001). There were also improvements in PTSD symptoms. However, improvements in depression and anxiety at 6 months were not sustained at 12 months. Finally, the authors found an impressive 66% reduction in mortality following VA residential treatment (p<.001). These results support the effectiveness of VA SUD residential treatment.

Prenatal Exposure to Cannabis Effects on Childhood Obesity and Cardiometabolic Health🔓

Current Obesity Reports

This study sought to consolidate information from 47 epidemiologic studies and 12 animal studies on the obesogenic and cardiometabolic effects of prenatal exposure to cannabis. Prenatal exposure to cannabis was consistently associated with small for gestational age and low birth weight. After birth, these offspring gain weight rapidly and have increased adiposity and higher glucose (fat mass percentage) in childhood. More preclinical and prospective studies are needed to deepen our understanding of whether these associations vary by sex, dose, timing, and composition of cannabis (e.g., ratio of delta-Δ9-tetrahydrocannabinol [Δ9-THC] to cannabidiol [CBD]). Addressing these gaps may help to solidify causality and identify intervention strategies.

Cannabidiol as a potential cessation therapeutic Effects on intravenous nicotine self-administration and withdrawal symptoms in mice🔓

Neuropharmacology

Some preliminary data have suggested that cannabidiol (CBD) may have some efficacy in treating nicotine dependence and may be potentially a new intervention for treatment. In a mouse model, the authors examine effects of orally dosed CBD on self-administration of low and moderate dose nicotine and withdrawal symptoms after nicotine cessation. The study showed a significant decrease in self-administration of nicotine at low or moderate dose (P<0.05). In addition, CBD pretreatment was associated with decrease in anxiety-like behavior, hyperalgesia behaviors, and somatic signs of withdrawal after nicotine cessation. Additional research will be needed to understand the mechanism of action and determine longer term efficacy. 

Buprenorphine/Naloxone vs Methadone for the Treatment of Opioid Use Disorder

JAMA Network

This population-based retrospective cohort study assessed whether the use of buprenorphine/naloxone is associated with lower risk of treatment discontinuation and mortality compared with methadone. It included 30,891 individuals initiating treatment for the first time during the study period and found that the risk of treatment discontinuation was higher among recipients of buprenorphine/naloxone compared with methadone (88.8% vs 81.5% within 24 months), and the risk of mortality was low while in either form of treatment (0.08% vs 0.13%). 

Reduced drug use as an alternative valid outcome in individuals with stimulant use disorders Findings from 13 multisite randomized clinical trials

Addiction

This study assessed the validity of reduced stimulant use as an outcome measure in a pooled dataset of 13 randomized controlled trials of pharmacological interventions for stimulant use disorder. Participants were individuals seeking treatment for cocaine or methamphetamine use disorders (N = 2062) in a wide range of treatment facilities in the US. More participants reduced frequency of primary drug use than achieved abstinence. Reduced use was significantly associated with decreases in craving for the primary drug, drug seeking behaviors, and depression severity, as well as multiple measures of global improvement in psychosocial functioning and severity of drug-related problems, albeit less strongly so than abstinence. Moreover, reduced use was associated with sustained clinical benefit at follow-up, as confirmed by negative urine tests.

Medications For Opioid Use Disorder Increased Among Louisiana Medicaid Enrollees During Policy Reforms 2018-21

Health Affairs

This study analyzed trends in medications for opioid use disorder (MOUD) between enrollees treated in residential and nonresidential settings and across demographic subgroups and compared trends by MOUD type. MOUD use more than tripled from 2018 to 2021 among Louisiana Medicaid enrollees diagnosed with OUD. Most of the increase in MOUD was attributable to buprenorphine use. Methadone uptake also contributed to greater MOUD use but was almost exclusively used by enrollees treated in nonresidential settings, whereas naltrexone was consistently used more commonly in residential treatment. By 2021, differences persisted across demographic groups: MOUD use was highest among enrollees who were White, were older, had comorbidities, and lived in a metropolitan area.

Intranasal Naloxone for Opioid Overdose

JAMA Network

This paper reviews the use of intranasal naloxone for reversal of opioid overdose. Although intramuscular naloxone is more effective, intranasal naloxone significantly increases the odds of surviving opioid overdose (OR = 8.6, 95% CI, 3.9 – 13.3). Communities that trained more than 100 people/100,000 in the use of intranasal naloxone had a 46% reduction in opioid death rates. The CDC recommends naloxone be prescribed when opioid prescriptions exceed 50 morphine equivalents daily, or when opioids are coprescribed with benzodiazepines. Naloxone is also advised for settings where children could access opioids. There have been reports of fentanyl overdoses requiring more than 2 doses of naloxone. However, these cases may represent opioid overdoses involving other respiratory depressants not reversed by naloxone.

An update on the clinical pharmacology of kratom: uses, abuse potential, and future considerations 

Expert Review of Clinical Pharmacology

In this article, the authors discuss the pharmacokinetics, effects, and potential toxicity of kratom. Kratom contains 40 alkaloids, primarily mitragynine, and these alkaloids bind to opioid, serotonin, and adrenergic receptors. Anecdotally, kratom has been used to treat pain, opioid withdrawal symptoms, and psychiatric disorders including depression and anxiety. This article reviews the limited studies and evidence of kratom’s use for pain and opioid withdrawal. The authors also reviewed the potential toxicity of kratom, including opioid-like deaths, serotonin syndrome, cardiotoxicity, and liver injury; however, the picture is complicated as kratom is frequently used with other substances. Research is needed to better understand kratom’s potential therapeutic effects and toxicity and the role of each of its components. 

Disparities in Medication Use for Criminal Justice SystemReferred Opioid Use Disorder Treatment 🔓

JAMA Health Forum

This cross-sectional study examined whether disparities in medication for opioid use disorder (MOUD) treatment between individuals referred by the criminal justice system and other sources has decreased. Analyzing more than 3 million admissions to treatment centers for opioid use disorder between 2014 and 2021, researchers found that although the use of MOUD among people referred to treatment by the criminal justice system has increased, it remains far lower than for people referred by other sources. This disparity exists in most states and is closing slowly. Targeted efforts to increase MOUD use among individuals with opioid use disorder and criminal justice system involvement are needed to address the poor outcomes experienced by this population.