This Week in the ASAM Weekly

We may not often, in our daily work, consider the relationship between birth, opioids, and modern medicine but a study from the New England Journal of Medicine encourages us to. Formulated around the mother-baby dyad, the Eat, Sleep, Console approach to neonatal opioid withdrawal reduced hospital stays and pharmacologic treatment when compared to usual care (Finnegan tool) and did so during the height of pandemic disruptions.

We are learning how such disruptions put on hold some of our healthiest human interactions. A significant proportion of unexplained, excess opioid overdose deaths could have been derivatives of social isolation (PNAS Nexus). Building, or sometimes rebuilding, the protective effects of socialization into drug overdose prevention will take time and “a village” (American Journal of Psychiatry). One of the best things we did to save lives was transition to telehealth, so it’s reassuring to know the DEA has extended tele-healing until November 11, 2023, and beyond (Federal Register).

How “safe supply” initiatives fit into this is a challenging consideration. On the one hand, there’s harm reduction; on the other is a possible reduction of the patient-clinician relationship (Journal of Studies on Alcohol and Drugs). Adjacent to this are safe injection sites, which the US government will be funding a large-scale study of (AP News). Given the support provided and people involved, these aren’t just “sites," they’re safe spaces.

Don’t miss another important study about the close relationship between cannabis use disorder and schizophrenia (Psychological Medicine). They’ve been hanging out a lot lately.

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

Eat, Sleep, Console Approach or Usual Care for Neonatal Opioid Withdrawal

The New England Journal of Medicine

This multicenter randomized controlled trial was undertaken to evaluate the Eat, Sleep, Console Care Tool vs usual care for neonatal opioid withdrawal with the primary outcome being medically ready for hospital discharge. The Eat, Sleep, Console Care Tool relies on an assessment of withdrawal severity focused on an infant’s ability to eat, sleep, and be consoled, along with the use of nonpharmacologic interventions as first line of treatment. The Eat, Sleep, Console Care approach decreased the time until infants with opioid withdrawal were medically ready for discharge by a mean of 6.7 days, and the proportion of infants receiving pharmacologic treatment by 32.5%. Hence, this approach facilitates more judicious use of medication for these infants.

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Research and Science

Enumerating contributions of fentanyls and other factors to the unprecedented 2020 rise in opioid overdose deaths: model-based analysis 🔓

PNAS Nexus

Opioid overdose deaths (OOD) increased dramatically in 2020; to better understand what contributed to that increase, this study utilized the SOURCE (Simulation of Opioid Use, Response, Consequences, and Effects) model. Researchers estimated 18,276 excess OODs in 2020 relative to predicted based on prior trends, and among the excess OODs they attributed 42.6% (39.7-47.1%) to a rise in fentanyl supply, 6.9% (6.4-7.5%) to declines in methadone maintenance treatment, and 1.4% (1.2-1.5%) to a combination of the two. Unable to account for approximately 49% of the excess OODs, the authors note they could not consider factors such as social isolation or reduced access to harm reduction services in their model. Overall, fentanyl was the single greatest factor (43%) contributing to excess OODs, but multiple factors related to COVID accounted for the majority (up to 57%).

Alcohol Use Among Treatment-Seeking Individuals with Opioid Use Disorder

Journal of Studies on Alcohol and Drugs

Individuals in the United States with opioid use disorder (OUD) have high rates of co-occurring alcohol use disorder (AUD). Using baseline assessment data from a multisite, comparative effectiveness trial, this study examined the relationship between alcohol and opioid use in treatment-seeking individuals with an OUD. Controlling for age, gender, ethnicity, and years of education, the likelihood of same-day opioid use was significantly lower on days in which participants drank any alcohol as well as on days in which participants reported binge drinking. The prevalence of opioid use remained high on both alcohol and non-alcohol use days. Alcohol may be used to treat symptoms of opioid withdrawal and possibly play a secondary and substitutive role in individuals with OUD substance use patterns.

Association between cannabis use disorder and schizophrenia stronger in young males than in females 🔓

Psychological Medicine

In this Danish register-based cohort study of close to 7,000,000 individuals, sex differences between cannabis use disorder (CUD) and schizophrenia were investigated. For males, the overall adjusted hazard ratio (HR) for CUD on schizophrenia among 16–20-year-olds was twice that of females. A consistent increase in population attributable risk fraction (PARFs) for males vs females of CUD in schizophrenia from 1972-2021 was also observed. Under the assumption of causality, some 15% of recent cases of schizophrenia among males would have been prevented in the absence of CUD. These findings highlight the importance of early detection and treatment.

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“No Excuses Anymore”: Substance Use Screening and Treatment for Justice-involved Youth

Journal of Addiction Medicine

This study concerned provision of substance use screening and treatment for youth in the criminal justice system. Semistructured interviews were conducted with 14 medical and behavioral health providers from 11 institutions. Several themes were identified. All team members should have substance use training. Screening for and treatment of substance use needs to be automatic. Other needs identified include resources, such as staffing and funding, and provisions to continue substance care after detention. Barriers include staff beliefs about substance use, such as distrust of MOUD, and youth ambivalence, believing substance use is normal with few consequences. The authors conclude there is a critical need for improved substance use care for justice-involved youth.

Drug Overdose Prevention: An Exercise in Optimism 🔓

The American Journal of Psychiatry

This editorial starts by discussing a recent study of factors associated with overdose in people receiving MOUD. Three risk factors for overdose were failure to initiate MOUD (particularly for naltrexone), early discontinuation, and benzodiazepine use. The authors note that elimination of the X waiver has improved access to MOUD, but addressing the overdose rate will also require improving initiation and retention rates. Barriers to initiation include criminalization of drug use, stigma, pessimism about recovery, and fear of a continued yearning to get high. The most common reasons for discontinuing MOUD are ineffectiveness in stopping opioid use and leaving a person unable to get high. Reducing overdose deaths will involve addressing such factors.

‘Safe Supply’ initiatives: Are they a recipe for harm through reduced healthcare input and supply induced toxicity and overdose?

Journal of Studies on Alcohol and Drugs

In this perspective, the authors discuss initiatives to provide people who use drugs with access to ‘safe supply’ medications as a harm reduction. While deregulatory changes to naloxone have had significant impact on negative outcomes for opioid use disorder, the authors note such an approach for ‘safer supply’ should not be considered in the same way. Motivations to decrease barriers to access are understandable, but ‘safer supply’ medications do have potential bad outcomes, both among people who use drugs and others who may intentionally or unintentionally access these medications. Further, if the need to see a provider for evaluation and to receive the medication were eliminated in efforts to reduce barriers, we lose opportunities for engagement in the healthcare system and potential for other interventions including treatments.

Structure-based discovery of conformationally selective inhibitors of the serotonin transporter

Cell

The serotonin transporter (SERT) removes synaptic serotonin and is the target of anti-depressant drugs. SERT adopts three conformations: outward-open, occluded, and inward-open. All known inhibitors target the outward-open state except ibogaine, which has unusual anti-depressant and substance-withdrawal effects and stabilizes the inward-open conformation. Unfortunately, ibogaine’s promiscuity and cardiotoxicity limit the understanding of inward-open state ligands. This study docked over 200 million small molecules against the inward-open state of the SERT. Two potent (low nanomolar) inhibitors stabilized an outward-closed state of the SERT with little activity against common off-targets. In mouse behavioral assays, both compounds had anxiolytic- and anti-depressant-like activity, with potencies up to 200-fold better than fluoxetine (Prozac), and one substantially reversed morphine withdrawal effects.

In The News

Temporary Extension of COVID-19 Telemedicine Flexibilities for Prescription of Controlled Medications

Federal Register