This Week in Addiction Medicine from ASAM

Lead: Epigenome-wide association study on methamphetamine dependence

Lead Story:
Epigenome-wide association study on methamphetamine dependence
Addiction Biology
The authors of this study postulate that some of the biologic changes resulting from methamphetamine use may be associated with epigenetic changes from DNA methylation. Such associations have been seen in schizophrenia, mood disorder, obsessive-compulsive disorder, and Parkinson’s disease. Subjects with methamphetamine dependence (n=24) as well as age and sex matched controls had an epigenome-wide analysis of DNA methylation and identification of sites where methylation differed between subjects with methamphetamine dependence and controls. Thirteen regions with differential methylation were found. Of particular interest was hypomethylation of the CNOT1 and PUM1 genes leading to alterations in mRNA metabolism similar to those seen in bipolar disorder and schizophrenia. These changes relate to symptoms in common such as psychosis. The authors conclude that symptoms seen in methamphetamine dependency may result from genetic changes similar to those in other psychiatric disorders.
 
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Lead: Disposable E-Cigarette Use and Subsequent Use Patterns in Adolescents and Young Adults

Disposable E-Cigarette Use and Subsequent Use Patterns in Adolescents and Young Adults 
Pediatrics
Utilizing sequential surveys in adolescents and young adults, the study evaluated the association between disposable e-cigarette (E-cig) use versus non-disposable E-cig and subsequent E-cig use. Those reporting the use of disposable e-cigs at baseline reported greater number of use days in past 30-days. In the follow-up survey, while controlling for demographics and baseline e-cig use patterns, disposable e-cig use was associated with continued e-cig use (OR=1.92) and greater number of times used daily (IRR=1.29). The authors note that disposable E-cigs are generally inexpensive, relatively easy to hide, and sold in various flavors (not regulated compared to non-disposable forms) and thus recommend comprehensive policies to regulate all forms of nicotine products.
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Lead: Adolescent Δ8-THC and Marijuana Use in the US

Lead Story:
Adolescent Δ8-THC and Marijuana Use in the US 🔓
JAMA 
D8-THC is synthesized from legal hemp plants (with low D9-THC) and has intoxicating effects similar to D9-THC. D8-THC is available in smoking, vaping, and edible products and is marketed as federally legal. To investigate the extent of D8-THC use by adolescents, data were extracted from the 2023 Monitoring the Future study in which a random selection of 12th grade students were asked about D8-THC use (n=2186). Prevalence of D8-THC use over the past 12 months was 11.4%, and for marijuana use was 30.4%. D8-THC use was lower in western states (5%) than southern states (14.4%), states where D8-THC was regulated (5.7% v. 14.4%), and states where marijuana was legal (8.0% v. 14.0%). The authors conclude that D8-THC use among adolescents is significant and deserves further attention.
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Lead: Association of Cannabis Use With Cardiovascular Outcomes Among US Adults

Lead Story:
Association of Cannabis Use With Cardiovascular Outcomes Among US Adults 
Journal of the American Heart Association
Cannabis use has increased in the US and perceived harmfulness has decreased, but there is evidence to suggest that cannabis use may increase risk of cardiovascular disease. In this study, the authors utilized the Brief Risk Factor Surveillance System survey to assess association between cannabis use and cardiovascular disease. In a multivariate analysis, they found an association between daily cannabis use and myocardial infarction (MI) (aOR=1.25) and stroke (aOR=1.42). Among adults who had never smoked cigarettes, the association was even greater for MI (aOR=1.49) and stroke (aOR=2.16). While additional research is needed, these findings suggest cannabis may be a risk for cardiovascular disease, independent of cigarette use.
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Lead: Racial and Ethnic Disparities in Geographic Availability of Buprenorphine

Lead Story:
Racial and Ethnic Disparities in Geographic Availability of Buprenorphine
Journal of Addiction Medicine
To identify whether buprenorphine availability equitably meets the needs of diverse populations, this study examined the differential geographic availability of buprenorphine in areas with greater concentrations of racial and ethnic minority groups. There were 45% to 55% fewer prescribers in urban areas and 62% to 79% fewer prescribers in rural areas as minority composition increased. Differences in dispensed buprenorphine per capita were similar but larger in magnitude. Achieving more equitable buprenorphine access requires not only increasing the number of buprenorphine-prescribing clinicians; in urban areas with higher racial and ethnic minority group populations, it also requires efforts to promote greater buprenorphine prescribing among already prescribing clinicians.
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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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