In this episode recorded live at ASAM's 55th Annual Conference in Fort Worth, TX, host Dr. Nick Athanasiou sat down with Dr. Shannon Miller to discuss his work on PAM-7, and his path to addiction medicine.

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Risk of Incident Psychosis and Mania With Prescription Amphetamines

The American Journal of Psychiatry

This case-control study used electronic health records to examine the impact of dose levels of prescription amphetamines on the risk of incident psychosis and mania with prescription amphetamines. Among 1,374 case subjects and 2,748 control subjects, the odds of psychosis and mania were increased for individuals with past-month prescription amphetamine use compared with no use. A dose-response relationship was observed; high doses of amphetamines (>30 mg dextroamphetamine equivalents) were associated with 5.28-fold increased odds of psychosis or mania. Past-month methylphenidate use was not associated with increased odds of psychosis or mania compared with no use. Caution should be exercised when prescribing high doses of amphetamines, with regular screening for symptoms of psychosis or mania.

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Psilocybin desynchronizes the human brain 

Nature

To assess how human brain network changes relate to the subjective and lasting effects of psychedelics, this study tracked individual-specific brain changes with longitudinal precision functional mapping (roughly 18 magnetic resonance imaging visits per participant). Psilocybin massively disrupted functional connectivity (FC) in the cortex and subcortex, acutely causing more than threefold greater change than methylphenidate. These FC changes were driven by brain desynchronization across spatial scales (areal, global), which dissolved network distinctions by reducing correlations within and anticorrelations between networks. Persistent reduction of hippocampal-default mode network connectivity may represent a neuroanatomical and correlate of the proplasticity and therapeutic effects of psychedelics.

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Secondhand Nicotine Absorption From E-Cigarette Vapor vs Tobacco Smoke in Children 

JAMA Network Open

This cross-sectional study of 1,777 US children aged 3 to 11 years examined how children’s nicotine absorption, as indexed by serum cotinine level, differ among those exposed to (1) secondhand tobacco smoke only, (2) secondhand e-cigarette vapor only, or (3) neither. Compared with children exposed to secondhand smoke only, nicotine absorption was 83.6% lower in those exposed to secondhand vapor only and 96.7% lower in those exposed to neither. These findings suggest that children absorb much more nicotine from secondhand smoke than from secondhand vapor; switching from smoking to vaping indoors may substantially reduce children’s secondhand exposure to nicotine and other noxious substances, but both smoke and vapor increase children’s absorption vs no exposure.

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Benzodiazepine use in relation to long-term dementia risk and imaging markers of neurodegeneration: a population-based study 🔓

BMC Medicine

This study examined the relationship between benzodiazepine (BZD) use and dementia, using data from the population-based Rotterdam (Netherlands) study started in 1990. For 5,443 participants, BZD use during the 15 years from 1990 to 2005 was compared to dementia screens performed through 2020. Half of the participants had used BZD at some time during the 15-year baseline, and 13% developed dementia. Overall, there was no association between BZD use and dementia risk. However, the use of BZD as an anxiolytic in higher doses was associated with dementia risk (HR=1.3). The authors note that BZD with longer half-life are used as anxiolytics, whereas short half-life BZD are used as sedative-hypnotics. A reduction in hippocampal volume on MRI was also associated with BZD use. Overall, there was no association of BZD use with dementia risk, however, some associations were observed that deserve further study.

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Extended-release ketamine tablets for treatment-resistant depression: a randomized placebo-controlled phase 2 trial 

Nature Medicine

The safety and tolerability of racemic ketamine may be improved if given orally, as an extended-release tablet (R-107), compared with other routes of administration. In this phase 2 multicenter clinical trial, male and female adult patients with treatment-resistant major depression (TRD) and Montgomery–Asberg Depression Rating Scale (MADRS) scores ≥20 received open-label R-107 tablets 120 mg per day for 5 days and were assessed on day 8 (enrichment phase). On day 8, responders (MADRS scores ≤12 and reduction ≥50%) were randomized to receive double-blind R-107 doses of 30, 60, 120, or 180 mg, or placebo, twice weekly for 12 weeks. Nonresponders on day 8 exited the study. Tolerability was excellent, with no changes in blood pressure, minimal reports of sedation, and minimal dissociation. The most common adverse events were headache, dizziness, and anxiety. R-107 tablets were effective, safe, and well tolerated in patients with TRD, enriched for initial response to R-107 tablets.

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Global status report on alcohol and health and treatment of substance use disorders

World Health Organization

This report utilizes data from the WHO member states to summarize alcohol consumption, its health consequences, and alcohol policies around the world. Overall, there was a decrease in alcohol consumption between 2010 and 2019, but alcohol-related deaths still accounted for 4.7% of all deaths in 2019. Despite the burden, there are still significant gaps in access to and types of treatment available worldwide, with the percentage of patients with substance use disorder receiving care ranging from 1% to 30% in countries that gather that data. The report makes several recommendations to address the concern, including a global advocacy campaign, increased training for health professionals at all levels, international knowledge transfers, and resource mobilization. 

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Community-Based Cluster-Randomized Trial to Reduce Opioid Overdose Deaths

The New England Journal of Medicine 

HEALing (Helping to End Addiction Long-term Initiative) Communities Study (HCS) investigators examined the potential of the community-engaged, data-driven Communities That HEAL (CTH) intervention to reduce the rate of opioid-related overdose deaths in highly affected communities. Intervention communities implemented hundreds of strategies to expand opioid overdose education and naloxone distribution, the use of medications for opioid use disorder, and safety measures for prescription opioid use, as well as communication campaigns to support these efforts. Although there were no significant between-group differences in the rate of opioid-related overdose deaths, the trial showed that the CTH community-engaged intervention, with its leveraging of community coalitions and a data-driven approach, can bring about meaningful progress in implementing evidence-based practices.

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Piloting a Hospital-Based Rapid Methadone Initiation Protocol for Fentanyl 

Journal of Addiction Medicine

The epidemic of fentanyl has led to increased opioid tolerance and made traditional dosing for methadone initiation insufficient. In this study, the authors examine an inpatient rapid titration of methadone initiation among patients with opioid use disorder (OUD). The protocol recommended dosing of 60 mg on day 1, 70 mg day 2, 80 mg day 3 and 100 mg day 4-7. After patients with significant underlying medical conditions, benzodiazepine or alcohol use and age >65 were excluded, 25 patients underwent the rapid initiation. No patients in the study experienced an adverse event and while additional research is needed, the study demonstrated the feasibility of rapid initiation of methadone for OUD in select patients in an inpatient setting. 

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Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population

Nature Communications

In this retrospective cohort study of patients receiving medication for treatment of obesity, the authors evaluated the association of semaglutide with incidence of and recurrence of alcohol use disorder (AUD). In the cohort patients received semaglutide or non-GLP1RA medications, including naltrexone and topiramate. In matched cohort analysis, patients who received semaglutide had much lower rates of incident AUD (HR=0.5) compared to those receiving non-GLP1RA medications and in sub-analysis comparing semaglutide to naltrexone/topiramate the also had lower incident AUD (HR=0.44). Among those with a history of AUD, semaglutide was also associated with lower recurrence of AUD (HR=0.44) overall and in sub-analysis (HR=0.25). These findings support potential benefit of semaglutide for AUD in a real-world population and need for randomized clinical trials.

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Innovation and adaptation: The rise of a fentanyl smoking culture in San Francisco

Plos One

This is a qualitative study describing the growing practice in the San Francisco area of smoking rather than injecting fentanyl. Fentanyl salts are stable up to 350°C making heating and inhalation more effective than for heroin. Some of the increase in smoking is driven by users’ difficulty finding accessible veins. There is also the perception that smoking presents less of a risk of overdose compared to injection. It is unclear if smoking is safer and overdose deaths continue to rise in San Francisco. Over time a brown residue accumulates that contains a high concentration of drug. The smoking equipment is often used for both methamphetamine and fentanyl so this residue contains an unknown mixture of the history of the drugs consumed. The residue is valued for potency but presents a new overdose risk due to the unknown amounts of drugs it contains.

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Rapid Initiation of Injection Naltrexone for Opioid Use Disorder

JAMA Network

Standard initiation procedures (SP) for extended-release (XR)-naltrexone can be a barrier to initiation for patients. In this stepped-wedge cluster-randomized trial, they compared SP initiation (3-5 days buprenorphine taper, 7-10 days opioid-free) to a rapid procedure (RP) initiation (1 day buprenorphine, 1 day opioid free, 3-4 days ascending dose of oral naltrexone). Patients in the RP group (62.7%) were more likely to receive the initial XR-naltrexone dose (OR 3.6, P<0.001) than the SP group (35.8%). There was not a statistically significant difference between the groups in rate of 2nd and 3rd doses. The study demonstrates that RP for initiation of XR-naltrexone is non-inferior to SP and may lead to shorter in-patient stay.

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Cannabis Laws and Utilization of Medications for the Treatment of Mental Health Disorders  🔓

JAMA Network Open

This cross-sectional study of 9,438,716 commercially insured patients examined if access to cannabis, via medical or recreational legalization, is associated with changes in the dispensing of prescription medications to treat mental health disorders. Researchers found statistically significant reductions in benzodiazepine dispensing after increases in both medical and recreational cannabis access. However, evidence suggests increases in other types of psychotropic dispensing. The study suggests that cannabis laws may be significantly associated with the population-level use of prescription drugs to treat mental health disorders, although the associations vary by drug class and state.

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Burden of Mental Disorders and Suicide Attributable to Childhood Maltreatment

JAMA Psychiatry

Studies have demonstrated that childhood maltreatment is strongly associated with mental health conditions, but this study uses a quasi-experimental design and meta-analysis to assess proportion of various mental health issues that are attributed to childhood maltreatment. The authors found that approximately 25% of mental health disorders (anxiety, depression, alcohol use disorder (AUD), substance use disorders (SUD), self-harm, and suicide) could be attributed to childhood mistreatment, accounting for approximately 1.8 million cases in Australia. Approximately 27% of AUD and 32% of SUD were attributed to childhood maltreatment. The findings strongly support the importance of efforts to prevent childhood maltreatment. 

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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. 

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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.

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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. 

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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.

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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.

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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.

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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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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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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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State-level racial and ethnic disparities in buprenorphine treatment duration in the United States 

The American Journal on Addictions

National trends reveal a concerning escalation in racial and ethnic disparities in buprenorphine treatment duration for opioid use disorder. This study examined such disparities at the state level. Analyzing 9,040,620 buprenorphine prescriptions dispensed between January 2011 and December 2020 from IQVIA Longitudinal Prescription data, the study revealed substantial statewide variations in racial and ethnic disparities. Specifically, 21 states showed longer treatment durations for White people across all episodes, and 8 states displayed similar trends among episodes lasting ≥180 days. Longer treatment durations for White people in both overall and long-term episodes were exhibited in 5 states, and 15 states showed no racial and ethnic disparities.

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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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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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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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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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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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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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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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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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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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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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Virtual reality-based Mindfulness-Oriented Recovery Enhancement (MORE-VR) as an adjunct to medications for opioid use disorder: a Phase 1 trial 🔓

Annals of Medicine

Mindfulness-Oriented Recovery Enhancement (MORE) uses mindfulness training to address dysregulation in brain reward systems. MORE has been shown to reduce drug cue reactivity and in an RCT reduced opioid misuse 45% at 9 months. Face-to-face MORE requires significant time of trained clinicians, and this study explored the feasibility of delivering MORE by virtual reality (VR). Treatment consisted of 8 weekly, one-hour MORE-VR sessions. Patients could choose the VR setting for their meditation (beach, forest, waterfall) and interact with virtual drugs and paraphernalia during session 5, which was devoted to examining and managing craving. Of 38 patients, 68% completed 4 or more sessions and 50% completed all sessions. Opioid use decreased significantly (p =.04), as well as craving (p<.001), and results showed a significant increase in positive affect (p<.001).

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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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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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Relationship between alcohol use and firearm-involved suicide: Findings from the National Violent Death Reporting System, 2003-2020

American Journal of Preventive Medicine

This study evaluated the sex- and age group-specific relationship between alcohol intoxication and firearm-involved suicide. Among males of all ages and young and middle-aged females, alcohol intoxication was associated with increased risk of suicide by firearm, an extremely lethal method that accounts for a majority of suicides in the US, compared to their non-intoxicated counterparts. Interventions targeting excessive alcohol consumption may be effective in reducing suicide mortality rates

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Pregnancy and Postpartum Drug Overdose Deaths in the US Before and During the COVID-19 Pandemic

JAMA Psychiatry

This cross-sectional exploratory study examined knowledge gaps in overdose deaths among pregnant and postpartum persons from 2018-2021 as compared to nonpregnant overdose deaths and obstetrical deaths. Overdose deaths among pregnant and postpartum women consistently increased among those aged 10 to 44 years, and more than tripled among those aged 35 to 44 years, from 4.9 per 100,000 from January-June 2018 to 15.8 from July-December 2021. These deaths differed from nonpregnant overdose deaths and obstetrical deaths in sociodemographic characteristics and place of death. Among overdose deaths in total (pregnant and nonpregnant), nearly 75% occurred outside of health care settings. Clearly more work needs to be done to treat SUDs in this population. 

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2022 National Survey on Drug Use and Health (NSDUH) 

SAMHSA 

Key findings include that in 2022, 70.3 million people aged 12 or older (or 24.9%) used illicit drugs in the past year. Marijuana was the most used illicit drug, with 22.0% of people aged 12 or older (or 61.9 million people) using it in the past year. In 2022, 48.7 million people aged 12 or older (or 17.3%) had a substance use disorder (SUD) in the past year, including 29.5 million who had an alcohol use disorder (AUD), 27.2 million who had a drug use disorder (DUD), and 8.0 million people who had both an AUD and a DUD. Almost 1 in 4 adults aged 18 or older had any mental illness (AMI) in the past year (59.3 million or 23.1%) and among adolescents aged 12 to 17 in 2022, 19.5% (or 4.8 million people) had a past year major depressive episode (MDE).

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Neural circuit selective for fast but not slow dopamine increases in drug reward🔓

Nature Communications

The authors note that rapid delivery to the brain when drugs are injected or smoked results in more severe substance use disorders. They used functional MRI and PET scans to monitor dopamine increases while subjects (n=20) received methylphenidate either orally or intravenously. Intravenous methylphenidate caused a more rapid increase in dopamine than oral. Activity in the medial prefrontal cortex decreased in both groups but was more pronounced with intravenous methylphenidate. However, only intravenous methylphenidate produced increased activity in the dorsal anterior cingulate cortex and insula that was reflected in the subjective rating of “high.”  This brain region was activated only by intravenous methylphenidate and the associated rapid increase in dopamine.

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Public health approaches to gambling: a global review of legislative trends 

The Lancet Public Health

Authors of this article systematically reviewed legislation of jurisdictions that introduced major gambling legislation change (i.e., restricting or extending gambling provision) between Jan 1, 2018, and Dec 31, 2021. More than 80% of countries worldwide now legally permit gambling. Harmful gambling was recognized as a health and wellbeing issue in most of the analyzed jurisdictions, but near-exclusive focus was given to individual-level harms rather than to wider social and economic harms or harms to others. Most of the proposed prevention measures focused on individual responsibility. Gambling policies worldwide are changing, but addressing gambling as a public health issue has not yet translated into comprehensive policy action across jurisdictions.

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Clinical Practice Guideline on the Management of Stimulant Use Disorder 

American Society of Addiction Medicine and American Academy of Addiction Psychiatry

Overdose deaths involving stimulant drugs – including cocaine, methamphetamine, amphetamine, and prescription stimulants – have been rising precipitously over the past decade. In 2021, over fifty percent of overdose deaths in the US involved stimulant drugs. Beyond the mortality risk, stimulant use disorders (StUD) can also lead to long term health problems including infectious diseases, cardiac, pulmonary, psychiatric, dental, nutritional, skin, and cognitive issues.  The Clinical Practice Guideline on the Management of Stimulant Use Disorder, developed by the American Society of Addiction Medicine (ASAM) and the American Academy of Addiction Psychiatry (AAAP), provides information on evidence-based strategies and standards of care for the prevention and treatment of stimulant use disorders (StUD), stimulant intoxication, and stimulant withdrawal.

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Chronic pain, cannabis legalisation, and cannabis use disorder among patients in the US Veterans Health Administration system, 2005 to 2019: a repeated, cross-sectional study

The Lancet Psychiatry

The prevalence of cannabis use disorder (CUD) in patients with chronic pain is increasing. This study considered the impact of both recreational (RCL) and medical cannabis laws (MCL) on the diagnosis of CUD using a VA population with chronic pain. Results demonstrate that MCL led to a 0.135% increase in the prevalence of CUD. Enacting RCL led to a 0.188% increase in its prevalence. The authors emphasize the importance of these findings and their public health implications, with a focus on clinician monitoring and patient education.

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Xylazine Adulteration of the Heroin–Fentanyl Drug Supply

Annals of Internal Medicine

Since 2016, xylazine has appeared in the illicitly manufactured fentanyl supply and has increased in prevalence, due to its low cost, easy availability, and presumed synergistic psychoactive effect. It remains unclear whether a distinct xylazine withdrawal syndrome occurs. Xylazine may alter the findings and management of patients with fentanyl overdose and withdrawal. Inadequately treated opioid (and possibly xylazine) withdrawal contributes to the increase in self-directed discharges from treatment settings. Initiation of buprenorphine and perhaps methadone may be compounded by the concomitant use of xylazine. The presence of extensive wounds in people who use xylazine prevents them from accessing resources, including medically managed withdrawal treatment, leading to a cycle of continued and escalating use.

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The Lancet Psychiatry Commission on youth mental health🔓

The Lancet Psychiatry

Mental ill health, which has been the leading health and social issue impacting the lives and futures of young people for decades, has entered a dangerous phase. Accumulating research evidence indicates that in many countries, the mental health of emerging adults has been declining steadily over the past two decades, with a major surge of mental ill health driven by the COVID-19 pandemic, the measures taken to contain it, and its aftermath. This alarming trend signals a warning that global megatrends (major, long-lasting societal changes such as environmental, social, economic, political, or technological changes) and changes in many societies around the world in the past two decades have harmed the mental health of young people and increased mental ill health among them.

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Heterogeneous neuroimaging findings across substance use disorders localize to a common brain network 

Nature Mental Health

This study used network mapping approaches and a functional connectome from a large cohort of healthy participants (n = 1,000) to test whether neuroimaging abnormalities across substance use disorders map to a common brain network. Starting with coordinates of regional brain atrophy from 45 studies, researchers found that 91% of the neuroimaging findings mapped to a common brain network specific to substance use disorders compared to atrophy associated with normal aging and neurodegenerative disease. Coordinates of functional MRI abnormalities from 99 studies mapped to a similar brain network. Neuroimaging abnormalities across substance use disorders map to a common brain network that is similar across imaging modalities, substances, and lesion locations that cause remission from substance use disorders.

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The association between temperature and alcohol- and substance-related disorder hospital visits in New York State 

Communications Medicine

Using New York State hospital data, this study investigated the link between daily temperature and hospital visits as a result of substance use from 1995-2014. An increase in temperature 0-6 days prior to seeking hospital care was associated with an increase in rates in care. Increase in visits was highest when opioids were involved, and lowest for sedatives. The 25-44 age group was primarily affected, and males made up the highest proportion of cases. These results indicate that the rise in SUD hospital visits is linked to continued rising temperatures related to climate change; healthcare and social interventions could potentially mitigate these harms.

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US tobacco companies selectively disseminated hyper-palatable foods into the US food system: Empirical evidence and current implications

Addiction

Hyper-palatable foods (HPF) contain fat and sodium, fat and simple sugars, and carbohydrate and sodium at specific thresholds to induce hyperpalatability, creating an artificially rewarding experience. This study compared tobacco companies who owned food companies to food companies not owned by tobacco companies, with regard to hyperpalatability between 1988 and 2001. Upon review of industry documents, this study found that tobacco companies “selectively disseminated” HPF into the US market. Tobacco-owned foods were 29% more likely to be classified as fat and sodium HPF and 80% more likely to be classified as carbohydrate and sodium HPF than foods that were not tobacco-owned. As late as 2018, market saturation of fat and sodium HPF was close to 60% and carbohydrate and sodium HPF was almost 20% regardless of tobacco ownership. Further research should consider the links between industries to appreciate potential impact on public health.

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America's Opioid Ecosystem: How Leveraging System Interactions Can Help Curb Addiction, Overdose, and Other Harms 

RAND Corporation

This ebook highlights that although opioids play an outsized role in US drug problems, they also play a critically important role in medicine. Thus, they deserve special attention. Illegally manufactured opioids are involved in a majority of US drug overdoses. Efforts to address problems related to opioids are insufficient and sometimes contradictory.  Components of the opioid ecosystem include substance use disorder treatment, harm reduction, medical care, the criminal legal system, illegal supply and supply control, first responders, the child welfare system, income support and homeless services, employment, and education. Leveraging the interactions of the opioid ecosystem can reduce addiction, overdose, suffering, and other harms.

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