This Week in Addiction Medicine from ASAM

Associations of cannabis use, use frequency, and cannabis use disorder with violent behavior among young adults in the United States International Journal of Drug Policy An association between cannabis use and violent behavior has previously been reported, so the authors used the 2015-2019 National Survey on Drug Use and Health to better explore this association. In adjusted models, the authors found an increased prevalence of violent behavior among males reporting daily cannabis use with and without cannabis use disorder (CUD) versus no cannabis use. However, there was no increase among males reporting non-daily cannabis use with or without CUD. Researchers found an increase in violent behavior among females reporting non-daily use with or without CUD and daily use with or without CUD. While additional research is needed to better understand this relationship and the sex differences, these findings support the importance of early screening and treatment for CUD. Read this issue of the ASAM Weekly Subscribe to the ASAM Weekly Visit ASAM

Lead Story Biomarkers of metal exposure in adolescent e-cigarette users: correlations with vaping frequency and flavouring Tobacco Control Various metals have been identified in e-cigarettes and, as their use among youth has increased in the last decade, this is of public health concern. In this study, researchers utilized a national sample of youth who use e-cigarettes and associated between lead, cadmium, and uranium levels and use patterns. Youth who reported intermittent or frequent use had higher levels of lead than occasional users, and frequent users also had higher levels of uranium. In addition, when evaluating by flavor types, sweet flavor e-cigarette use was associated with higher uranium levels than menthol/mint flavors. Given the potential deleterious health effects of these metals, particularly in youth, these findings support the need for regulations and public health interventions to target youth populations and minimize e-cigarette use. Read this issue of the ASAM Weekly Subscribe to the ASAM Weekly Visit ASAM

Association of regular opioid use with incident dementia and neuroimaging markers of brain health in chronic pain patients: analysis of UK Biobank The American Journal of Geriatric Psychiatry In this cohort study, researchers examine the association between regular opioid use in patients with chronic pain and development of dementia over 15 years of follow-up. Regular opioid use versus non-opioid analgesic use in this population was associated with increased risk of incident dementia (HR=1.18 CL,1.08-1.30). In addition, there appeared a dose-dependent response with those receiving more prescriptions being more likely to develop dementia: 1-5 prescriptions OR=1.21, 6-20 prescriptions OR=1.27, and >20 prescriptions OR=1.43. Finally, in brain imaging, those with regular opioid use exhibited lower total gray matter and higher white matter hyperintensities. While additional research may be needed to support causality, the authors suggest these findings support caution in regular use of opioids for chronic pain. Read this issue of the ASAM Weekly Subscribe to the ASAM Weekly Visit ASAM

Preventing deaths after prison release The Lancet Formerly incarcerated people have exceptionally poor health profiles and are at increased risk of preventable mortality when compared to their general population peers. This accompanying editorial discusses a study by Borschmann et al published in the same issue of The Lancet. Using administrative data from the multi-national Mortality After Release from Incarceration Consortium (MARIC) study, the authors examined mortality outcomes for 1,471,526 people released from incarceration in eight countries. 75,427 deaths were recorded. The markedly elevated rate of death in the first week post-release underscores an urgent need for investment in evidence-based, coordinated transitional healthcare, including treatment for mental illness and substance use disorders to prevent post-release deaths due to suicide and overdose. Temporal variations in rates and causes of death highlight the need for routine monitoring of post-release mortality. Read this issue of the ASAM Weekly Subscribe to the ASAM Weekly Visit ASAM

Lead Story: Telling the story of the opioid crisis: A narrative analysis of the TV series Dopesick PLOS One Dopesick (2021) is the first TV series whose plot deals exclusively with the opioid crisis in the United States. The current study uses narrative analysis and framing theory to explore this series, discussing its portrayal of the people and themes involved in the opioid crisis. This analysis found that although Dopesick attempts to portray multiple dimensions of the opioid crisis, its narrative oversimplifies the story in attributing the cause of the problem almost exclusively to Purdue Pharma and its director Richard Sackler, while downplaying other factors that contributed to the opioid crisis. Thus, the narrative in this TV series tends to offer simple explanations to a complex problem for which simple solutions are likely to be inadequate. Read this issue of the ASAM Weekly Subscribe to the ASAM Weekly Visit ASAM

Lead Story: Impact of jail-based methadone or buprenorphine treatment on non-fatal opioid overdose after incarceration Drug and Alcohol Dependence The authors studied the effect of receiving MOUD during incarceration in New York City jails on non-fatal overdose events during the year after discharge. Data were analyzed for patients with OUD incarcerated between 2011-2017 who either received MOUD during the 3 days before release (n=8660) or did not receive MOUD just prior to release (n=10,163). After controlling for covariates, those receiving MOUD had a significant reduction in non-fatal overdoses during the 14 days after release (adjusted HR: 0.49; 95% CI = 0.33-0.74). However, there was no reduction in non-fatal overdoses during the remainder of the 1 year after release. The authors speculate that this lack of benefit beyond 14 days may be due to failure to transition to outpatient MOUD after release. They conclude that MOUD in jail could be lifesaving and that it is important to ensure MOUD continues after release. Read this issue of the ASAM Weekly Subscribe to the ASAM Weekly Visit ASAM

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. Read this issue of the ASAM Weekly Subscribe to the ASAM Weekly Visit ASAM

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. Read this issue of the ASAM Weekly Subscribe to the ASAM Weekly Visit ASAM

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. Read this issue of the ASAM Weekly Subscribe to the ASAM Weekly Visit ASAM

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. Read this issue of the ASAM Weekly Subscribe to the ASAM Weekly Visit ASAM

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. Read this issue of the ASAM Weekly Subscribe to the ASAM Weekly Visit ASAM

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. Read this issue of the ASAM Weekly Subscribe to the ASAM Weekly Visit ASAM

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. Read this issue of the ASAM Weekly Subscribe to the ASAM Weekly Visit ASAM

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. Read this issue of the ASAM Weekly Subscribe to the ASAM Weekly Visit ASAM

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. Read this issue of the ASAM Weekly Subscribe to the ASAM Weekly Visit ASAM

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. Read this issue of the ASAM Weekly Subscribe to the ASAM Weekly Visit ASAM

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. Read this issue of the ASAM Weekly Subscribe to the ASAM Weekly Visit ASAM

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. Read this issue of the ASAM Weekly Subscribe to the ASAM Weekly Visit ASAM

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. Read this issue of the ASAM Weekly Subscribe to the ASAM Weekly Visit ASAM

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. Read this issue of the ASAM Weekly Subscribe to the ASAM Weekly Visit ASAM