This Week in the ASAM Weekly

This week we showcase publications from leading journals across the scientific fields. In a way, this mirrors the diversity of specialists in clinical settings and beyond who collaborate to treat addiction.

A study from JAMA Network Open is a first to evaluate increased naloxone requirements and clinical outcomes from nitazene overdose: a class of novel potent opioids that have found their way into the illicit drug supply. The title of a publication from ACS Central Science may be technical and targeting fields related to chemistry, but the findings imply that a new way to synthesize methylphenidate may lead to future treatments in cocaine use disorders and more.

A Cochrane Review of over 300 RCT’s has found that the most effective interventions for smoking are e-cigarettes, varenicline, and cytisine (CDSR). It’s unfortunate then that two of these three interventions are either underregulated or unapproved for smoking cessation in the US. Substance use in pregnancy is a known risk factor for intellectual disability (ID) but a study of national registry data found that having either mothers or fathers with SUDs diagnosed before childbirth is also a significant and modifiable risk factor (eClinicalMedicine).

More news about alcohol’s unhealthy effects on the heart comes from a national database study in South Korea. Chronic heavy drinkers have a significantly lower risk of new onset a-fib if they abstain, but little improvement was found if they reduced drinking (EJPC). In the US, addiction plus suicide make up deaths of despair but the diseases themselves are a risk for atherosclerotic cardiovascular disease (BMJ Open).

Together these publications also showcase how addiction is not just a disease of the brain but an illness that affects the whole body, person, society, and more.

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

Naloxone Use in Novel Potent Opioid and Fentanyl Overdoses in Emergency Department Patients 🔓

JAMA Network Open

In this cohort study of 537 patients, all patients with novel potent opioid (NPO) overdose presented with opioid overdose symptoms and received multiple doses of naloxone. Compared with fentanyl overdose, patients with NPO overdose had a higher number of naloxone doses administered in-hospital; metonitazene overdose was associated with cardiac arrest and more naloxone doses overall. These findings suggest that NPOs may have a higher potency than fentanyl due to the observed naloxone administration in the clinical setting of overdose.

Research and Science

Pharmacological and electronic cigarette interventions for smoking cessation in adults: component network meta‐analyses 🔓

Cochrane Database of Systematic Reviews

This Cochrane review examined the evidence for multiple pharmacotherapies utilized worldwide, including electronic cigarettes (e-cig), for sustained smoking cessation. It included 319 articles, discussing predominantly randomized controlled trials from Europe, the US, or Canada (248). The evidence for Varenicline (OR 2.33), Cytosine (OR 2.21), e-cig (OR 2.37), and nicotine replacement (NRT) (patch + fast acting) (OR 1.93) shows high efficacy. Other therapies were still effective, but with lower efficacy; these included NRT patch alone, fast acting NRT alone, and Bupropion. In the context of limited resources, this review of the data regarding effectiveness of these interventions can help guide therapy. Additional research is needed to evaluate behavioral interventions and the combined behavioral/pharmacological interventions.

Contact reduces substance use stigma through bad character attributions, especially for U.S. health care professionals

Psychology of Addictive Behaviors

This study of substance use stigma surveyed 7600 people including 788 health care professionals. Participants were given a vignette of a person with substance use disorder and stigma was measured. Participants were asked if they attributed SUD to personal characteristics (such as bad character) or biological factors (such as genetics or chemical imbalance). They were also asked if they had had personal contact with someone similar to the individual portrayed in the vignette. Although education about the biological nature of SUD is often expected to reduce stigma, this study found stigma most strongly associated with attributions of bad character. Having personal contact with someone with an SUD mitigated this effect. The authors suggest that such personal contact be used to reduce stigma towards SUD.

Association between diseases of despair and atherosclerotic cardiovascular disease among insured adults in the USA: a retrospective cohort study from 2017 to 2021 🔓

BMJ Open

An insurance database of over 5 million people was used to examine the relationship between diseases of despair (DoD: alcohol-related disorders, substance-related disorders, suicidality) and ASCVD (atherosclerotic cardiovascular disease: cardiac, cerebral, or peripheral vascular). After adjustment for medical risk factors, DoD were associated with an increased risk of ASCVD (HR 1.42). Association with ASCVD existed for each diagnosis: substance-related disorders (HR 1.5), alcohol-related disorders (HR 1.33), and suicidality (HR 1.3). The combination of substance-related disorders and suicidality had the strongest association (HR 2.01). The authors suggest that treatment for these DoD include screening for ASCVD.

Changes in alcohol consumption habits and risk of atrial fibrillation: a nationwide population-based study 🔓

European Journal of Preventive Cardiology

This retrospective observational study investigated whether reducing or abstaining from alcohol would lower the risk of atrial fibrillation (AF) in those who drink heavily. While reducing consumption did not result in lower incident AF, when compared to sustained heavy drinkers, the absolute abstinence group showed a 62% lower incidence of AF. The benefit of abstinence was also noted in those individuals without such medical conditions as CAD, hypertension, stroke, and diabetes. These results support alcohol abstinence over reduction to reduce the incidence of AF.

Learn More

The Tungsten-Promoted Synthesis of Piperidyl-Modified erythro-Methylphenidate Derivatives 🔓

ACS Central Science

Due to its efficacy as a dopamine receptor agonist, methylphenidate (MPH) is of interest as a potential therapeutic for cocaine addiction. While numerous derivatives of MPH have been investigated for their potential medicinal value, functionalization of the piperidine ring has not been explored. This study describes a methodology capable of accessing piperidine-functionalized mesyl erythro methylphenidate analogues with high degrees of regioselectivity, stereoselectivity, and functional group tolerance. This method was utilized to develop a library of piperidyl-containing drug analogues. All identities of the newly reported compounds are supported by comprehensive 2D NMR and HRMS data or crystallographic data.

Endocannabinoid release at ventral hippocampal-amygdala synapses regulates stress-induced behavioral adaptation 🔓

Cell Reports

The ventral hippocampus (vHPC) – basolateral amygdala (BLA) is known to play a role in adaptations that occur after exposure to stress, which increases the risk of developing psychiatric disorders. In this study, they examine the role and mechanism of the endocannabinoid system (eCB), specifically cannabinoid receptor type 1 (CB1R) and 2-arachidonoylgycerol (2-AG) in that process. They demonstrated that impairment in 2-AG CB1R signaling could increase the stress-related response and risk of neuropsychiatric disorders. Interventions that enhance this signaling could potentially be targets for treatment of stress-related disorders in the future.

Parental substance use disorder and risk of intellectual disability in offspring in Sweden: a national register study 🔓

eClinicalMedicine

This study explored the link between parental substance use and risk of intellectual disability (ID) in a cohort of children born between 1978 and 2002. The timing of parental SUD diagnosis (first diagnosis before pregnancy, during pregnancy, or after birth) in relation to risk of ID in offspring was also investigated. Regardless of the timing of diagnosis, parental SUD corresponded to increased odds of all forms of ID in children. Of infants born with parental SUD diagnoses before birth, 3% had ID compared to 1.2% in those with no parental SUD diagnoses. Of note, parents with SUD diagnosed prior to birth had higher rates of psychiatric comorbidities. Parental alcohol use disorder during pregnancy was associated with the greatest risk increase for ID.

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