This Week in Addiction Medicine from ASAM

Lead: Smoking changes adaptive immunity with persistent effects

Lead Story
Smoking changes adaptive immunity with persistent effects
Nature
There is significant variability in immune response across the population, some of which is related to age, sex, and genetics, but this study examines other factors that may be related to immune response. Notably, the authors found that smoking affected both innate and adaptive immune response, and that the associations were consistent across number of years smoking and number of cigarettes. The effect on innate immune response was short-term, with immune response returning to levels comparable to non-smokers after quitting. The effect on adaptive immunity, however, was long-term and persisted even after quitting — the result of DNA methylation changes. These findings have clinical implications regarding risk of infection, cancer, and autoimmune disease in persons who smoke. 
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Lead: Overdose mortality incidence and supervised consumption services

Lead Story:
Overdose mortality incidence and supervised consumption services in Toronto, Canada: an ecological study and spatial analysis 
The Lancet Public Health
The objective of this study was to measure the effect of safe consumption sites (SCS) on overdose mortality. Between 2017 and 2019, nine SCS were implemented in Toronto, Canada. During this period there were 787 overdose deaths. In the 15 neighborhoods within 500 meters of an SCS, overdose deaths decreased by 67% (p=0.037) after SCS were implemented. There was no decrease in other neighborhoods. Researchers were surprised to observe some decrease in overdose deaths up to 5000m from SCS. They note that in addition to onsite overdose reversal, SCS also distribute naloxone and offer referrals to low-barrier MOUD. They speculate that these other services could explain the effects at greater distances. The authors conclude that SCS result in significant reductions in overdose deaths in surrounding neighborhoods.
 
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Lead: Safety of e-cigarettes and nicotine patches as stop-smoking aids in pregnancy

Lead Story:
Safety of e-cigarettes and nicotine patches as stop-smoking aids in pregnancy: Secondary analysis of the Pregnancy Trial of E-cigarettes and Patches (PREP) randomized controlled trial 
Addiction
It is not clear to what extent nicotine is responsible for adverse outcomes of smoking during pregnancy. This study examined outcomes of e-cigarette (EC) and nicotine replacement therapy (NRT) use in pregnancy. Pregnant smokers were randomly assigned to EC or NRT. ECs were more than twice as likely to be used regularly compared to NRT. Those abstaining from cigarettes had higher birth weights (3.3 Kg) than smokers (3.1 Kg), and the use of EC or NRT did not affect birth weight in abstainers. In the entire group (abstainers and smokers), use of EC and/or NRT was not associated with an increase in adverse events. Those using EC had less cough and phlegm than those using NRT. Other studies have confirmed the same, possibly resulting from antibacterial effects of additives to the EC liquid. The authors found no risks to pregnancy from EC or NRT use.
 
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Lead: Polysubstance mortality trends in White and Black Americans during the opioid epidemic

Polysubstance mortality trends in White and Black Americans during the opioid epidemic, 1999–2018 
BMC Public Health
The CDC characterizes the opioid epidemic in three waves: first, prescription opioids (1999-2010); second, heroin (2011-2013); and third, synthetic opioids (2013-present). The authors examine the epidemic, looking at trends in multiple substances involved in overdoses and differences by race. Psychostimulant and benzodiazepine involvement were more common among White persons, while cocaine-related deaths were higher among Black persons. Overdose deaths have increased faster among Black persons since 2013. Overall, overdose deaths frequently involve multiple substances and can’t simply be attributed to opioids. The authors give three policy implications for their findings: 1) polysubstance use should be considered the norm, 2) addressing racial disparities requires interventions across primary, secondary, and tertiary prevention, and 3) the importance of measures to address fentanyl specifically. 
 
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Lead: First Trimester Use of Buprenorphine or Methadone

Lead Story:
First Trimester Use of Buprenorphine or Methadone and the Risk of Congenital Malformations 🔓
JAMA Internal Medicine
In this cohort study of 9,514 pregnancies with first-trimester buprenorphine exposure and 3,846 with methadone exposure, the prevalence of congenital malformations overall and several malformation subtypes was lower among pregnant individuals treated with buprenorphine compared with methadone, except for gastrointestinal malformations. There was an 18% relative risk reduction for malformations overall, which translates to 1 less event per 100 patients treated with buprenorphine vs methadone.  When determining optimal treatment for pregnant individuals with opioid use disorder, considerations should include the relative risk reduction for malformations overall with buprenorphine vs methadone, as well as treatment access, previous success on a particular treatment, and the likelihood of retention in treatment.
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Lead: Trends in hallucinogen-associated emergency department visits

Trends in hallucinogen-associated emergency department visits and hospitalizations in California, USA, from 2016 to 2022 🔓
Addiction
There has been growing interest in recent years around hallucinogens as potential therapeutics, and use among young adults has increased significantly. With limited data, the mounting perception is that hallucinogens are safe. In this context, the authors examined emergency department (ED) visits and hospitalizations due to hallucinogens versus alcohol and cannabis in California between 2016 and 2022. Hallucinogen-associated ED visits increased by 54% (2260 visits to 3476 visits), while alcohol-associated visits decreased by 20% and cannabis-associated visits increased by 15%. Additionally, hallucinogen-associated hospital admissions increased by 55% (2556 to 3965) with no significant changes in alcohol- and cannabis-associated hospitalizations. Additional research is needed to assess hallucinogen-associated potential harms. 
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Lead: Adolescent Residential Addiction Treatment In The US

Lead Story:
Adolescent Residential Addiction Treatment In The US: Uneven Access, Waitlists, And High Costs
Health Affairs
Residential treatment facilities are one treatment option for adolescents with substance use disorders, yet little is known about their accessibility or cost. This study identified 160 residential addiction treatment facilities that treated adolescents with opioid use disorder as of December 2022. Eighty-seven facilities (54.4 percent) had a bed immediately available. Among sites with a waitlist, the mean wait time for a bed was 28.4 days. Of facilities providing cost information, the mean cost of treatment per day was $878. Daily costs among for-profit facilities were triple those of nonprofit facilities. Half of facilities required up-front payment by self-pay patients. The mean up-front cost was $28,731. The authors were unable to identify any facilities for adolescents in ten states or Washington, D.C. Access to adolescent residential addiction treatment centers in the United States is limited and costly.
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Lead: Benzodiazepine Discontinuation and Mortality

Lead Story:
Benzodiazepine Discontinuation and Mortality Among Patients Receiving Long-Term Benzodiazepine Therapy 
JAMA Network Open
In this comparative effectiveness study among 353,576 patients receiving stable long-term treatment with benzodiazepines, discontinuation was associated with small absolute increases in mortality and other potential harms, including nonfatal overdose, suicide attempt, suicidal ideation, and emergency department visits. These results suggest benzodiazepine discontinuation among patients prescribed for stable long-term treatment may be associated with unanticipated harms, and that efforts to promote discontinuation should carefully consider the potential risks of discontinuation relative to continuation.
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ASAM Weekly Top 10 Peer reviewed Scientific Publications of 2023

Top Publication of 2023:
ASAM Clinical Considerations: Buprenorphine Treatment of Opioid Use Disorder for Individuals Using High-potency Synthetic Opioids 🔓
Journal of Addiction Medicine
This clinical considerations document is based on a narrative literature review and expert consensus and addresses considerations for changes to the clinical practice of treatment of opioid use disorder (OUD) with buprenorphine for individuals using high-potency synthetic opioids (HPSOs). Broadly, it suggests that individualized strategies for buprenorphine initiation may be needed. The experience of opioid withdrawal negatively impacts the success of buprenorphine treatment, and attention to withdrawal management before and during buprenorphine initiation should be proactively addressed. Buprenorphine dose and dosing frequency should be individualized based on patients’ treatment needs, the possibility of novel components in the drug supply should be considered during OUD treatment, and all forms of opioid agonist treatment should be offered and considered for patients.
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Lead: Examining the benefit of a higher maintenance dose of extended-release buprenorphine

Lead Story:
Examining the benefit of a higher maintenance dose of extended-release buprenorphine in opioid-injecting participants treated for opioid use disorder 
Harm Reduction Journal 
This is a secondary analysis of a randomized, double-blind study comparing 100 mg and 300 mg maintenance doses of extended-release buprenorphine (BUP-XR). All patients (n=311) received 2 monthly induction doses of 300 mg BUP-XR followed by 4 monthly maintenance doses of either 100 mg or 300 mg BUP-XR. For patients who had not been using opioids by injection, there was no difference in weekly abstinence or treatment retention comparing the two maintenance doses. However, for patients with a history of injecting opioids, the 300 mg maintenance dose resulted in significantly higher percentages of weeks abstinent as well as improved treatment retention. The authors speculated that opioid injecting patients may have had higher levels of tolerance that required a higher maintenance dose.
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