Drug and Alcohol Dependence

This retrospective study compared outcomes for patients with stimulant use disorder enrolled in a smartphone-based contingency management program based on the amount of total incentives possible, either $75 (“low-value”) or $599 (“moderate-value”). The low-value program was based in New Jersey, funded through SAMHSA (which limited reimbursement to $75/patient at the time of implementation, which has since been increased), and rewarded completing drug testing, attending counseling visits, and completing CBT modules rather than abstinence over 16 weeks. The moderate-value program was funded by West Virginia’s Medicaid managed care organizations, lasted up to 26 weeks, and largely rewarded negative drug screening results, with additional rewards for counseling and CBT modules. Patients in the moderate-value program submitted significantly higher rates of negative substance tests (36%, with an average of 3.2 negative tests) compared to those in the low-value group (24.7%, with an average of 24.8 negative tests).

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Journal of the American Heart Association

This study included 1,309 patients treated for an acute myocardial infarct (MI) at a California health system between 2012 and 2022. A total of 194 patients (15%) were methamphetamine users. The Meth-MI group had less diabetes than the No-Meth-MI group (38% vs 51%, p=.001) but many more smokers (72% vs 28%, p<.001). Nonobstructive coronary disease (eg, vasospasm) was more common in the Meth-MI group (24% vs 11%, p<.001), which consequently had lower rates of revascularization, aspirin, and statin therapy. The Meth-MI group had double the mortality (HR, 2.1, p<.001), and methamphetamine use was the strongest predictor of mortality, greater than diabetes. The Meth-MI group was more likely to have a subsequent MI (42% vs 27%, p<.001). The risk of MI with methamphetamine use is 19% higher than the risk with cocaine use (this study excluded cocaine users). The authors believe presentations with methamphetamine use and angina, without MI, is even more common. 

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JAMA Network Open

This survey study used a 2-round Delphi process to develop expert consensus on best practices for hospital-based MOUD initiation for patients with OUD, with a goal to provide guidance on changing inpatient addiction treatment in response to increased synthetic opioids in the unregulated drug supply. A total of 42 expert clinicians participated; clinicians were considered a national expert if they had cared for at least 100 hospitalized patients with OUD in the last two years. There was consensus that buprenorphine and methadone initiation in the hospital setting were appropriate, with less support for hospital-based naltrexone initiation. Consensus was also reached to support rapid methadone initiation; high- and low-dose buprenorphine initiation; and provision of non-MOUD full agonist opioids for treatment of opioid withdrawal during methadone initiation, as a bridge to buprenorphine initiation, and for those declining MOUD.

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JAMA Network Open

This cohort study assessed 10,110 US veterans with homeless experience and opioid use disorder (OUD) residing in permanent supportive housing (PSH), in terms of what factors are associated with receipt of medications for opioid use disorder (MOUD).  Only 17% received MOUD within 12 months. Greater behavioral health engagement was associated with MOUD receipt, while older age, race minority status, and prior inpatient hospitalization were associated with lower odds. These results suggest that MOUD access in supportive housing should be expanding, which could require embedding addiction care into PSH teams, leveraging behavioral health touchpoints, and addressing persistent disparities.

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The Milbank Quarterly

Medicaid managed plan coverage for medications for alcohol use disorders (AUD) and opioid use disorder (OUD) varies across states but is generally lower in Republican-leaning states. Researchers conducted a national survey to evaluate if these differences in coverage were due to variation in state policy or variations in Medicaid managed plan alignment with state policy. Researchers found that while Republican-leaning states were generally a little less likely to require coverage of most or all medications for AUD and OUD and place limits on prior authorization, managed plans in Republican-leaning states were much less likely to follow state requirements. Given these findings, efforts to increase access to medications for AUD and OUD will need to address misalignment between managed care plans and state policy, and not just focus on making changes to state policy.

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Journal of Addiction Medicine

Initiating weekly long-acting injectable buprenorphine (LAIB) without prior sublingual buprenorphine (“direct-to-inject” or DTI) may reduce buprenorphine initiation barriers. In this case series, outpatient DTI outcomes are described. Of the 23 patients with available data, 19 (83%) had no withdrawal symptoms pre-DTI. Of the 20 patients with documented post-DTI withdrawal symptoms, 3 (15%) had no withdrawal, 12 (60%) had mild, 4 (20%) had moderate, and one (5%) patient had severe withdrawal. Thirty days post-DTI, 14 (58%) patients were retained on any buprenorphine formulation, and 11 (46%) patients were retained at 90 days. The median post-DTI buprenorphine treatment days were 77 (range: 9–90).  The majority of patients had no pre-DTI withdrawal symptoms, no or mild withdrawal symptoms post-DTI, and were retained on buprenorphine at 30 days post-DTI, with nearly half retained at 90 days. DTI is a promising buprenorphine initiation strategy, but further research is warranted.

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Nature

This study identifies a novel µ-opioid receptor (MOR) agonist with supramaximal intrinsic efficacy and a unique pharmacological profile that produced effective analgesia in rodents with minimal adverse effects. N-desethyl-fluornitrazene (DFNZ) was derived from a class of synthetic benzimidazole opioids called nitazenes. DFNZ has impaired brain penetrance, a unique spatiotemporal MOR cellular signaling profile, and diminished efficacy at the MOR–galanin 1 receptor (GAL1) heteromer. DFNZ does not induce respiratory depression, tolerance, or MOR downregulation after repeated exposure. Compared with other MOR agonists, DFNZ has limited effects on dopamine neurotransmission in the nucleus accumbens and weaker reinforcing effects in the drug self-administration procedure. These results provide novel insights about MOR and nitazene pharmacology, have important implications for pain and addiction treatment, and challenge the prevailing dogma that high-efficacy MOR agonists cannot constitute safe and effective therapeutic agents.

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JAMA Network

This retrospective observational cohort study of 554 individuals examined rates of patient-directed discharge (PDD) among hospitalized patients with opioid use disorder who received methadone during the first 72 hours of hospitalization from July 2019 to June 2022. Higher doses of methadone were associated with a decreased rate of PDD. For each additional 10 mg of methadone received in the first 24 hours, there was a decrease in odds of PDD at 48 hours (adjusted OR 0.71). This study highlights the importance of adequate treatment of opioid withdrawal to reduce the risk of PDD.

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Journal of Addiction Medicine 

Participants (n=5250), part of Gallup’s random sample of US households, completed a web-based survey that explored their beliefs about addiction.  Asked if addiction is a health condition 77% of US adults agree, 16% disagree, and 6% don’t know. Men are more likely to disagree (20%) than women (15%). Those who have struggled with addiction but not in recovery were more likely to disagree (22%) than those in recovery (13%) or with no personal addiction experience (16%). Those with less education and income were more likely to disagree. Those who disagree that addiction is a health condition are less likely to believe it is treatable by doctors (OR=0.3), believe that medications are effective treatments (OR=0.4), or help friends or family with addiction (OR=0.5). 

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The American Journal on Addictions 

Researchers conducted a literature review of the neurocognitive effects of cannabis use and recovery from those effects. They found a range of neurocognitive effects including neuroreceptor adaptation, decrease in memory, processing speeds, and attention. Deficits increased with higher frequency and amount of use, but recovery can occur.  Receptor normalization can occur within weeks of abstinence while cognitive recovery can take months and years. Adolescent-onset users have more severe and persistent deficits, suggesting effects to neurodevelopment beyond reversible neuroadaptation. The authors suggest treatment for cannabis use disorder should focus on both the disorder and its neurocognitive effects. 

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Addiction

This study used a microsimulation model of methamphetamine use behavior among individuals with methamphetamine use disorder (MethUD) to assess the cost-effectiveness of contingency management (CM) for MethUD. Both 12-week and 24-week CM programs were modeled, using a maximum incentive of $750/patient, per SAMHSA guidelines. The model simulation was run for a cohort of 10,000 individuals with MethUD and looked at lifetime cost. Compared to no treatment, the model predicted an estimated net gain of 0.70 QALYs per person at a cost of $6850/QALY for a 12-week program, with an incremental cost-effectiveness ratio (ICER) of $9830/QALY. For a 24-week program, the benefit was 0.81 QALYs at a cost of $10,000, yielding an ICER of $12,312/QALY. This suggests that both durations of CM for MethUD are highly cost-effective, even at the maximum level of incentives.

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The BMJ

This study investigated whether initiation of glucagon-like peptide-1 (GLP-1) receptor agonists is associated with both reduced risks of incident alcohol, cannabis, cocaine, nicotine, opioid, and other substance use disorders (SUDs) in people with no history of SUDs (protocol 1) and with reduced risk of SUD-related adverse clinical outcomes among people with a pre-existing SUDs (protocol 2).  Researchers found that use of GLP-1 receptor agonists was consistently associated with reduced risks of developing various incident SUDs, suggesting a broad preventive effect across multiple substance types. Use was also associated with reduced risks of adverse clinical outcomes in people with pre-existing SUDs. These observational data suggest a potential role for GLP-1 receptor agonists in both the prevention and treatment of various SUDs, warranting further evaluation.

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Addiction

This repeated cross-sectional study based on annual surveys tested whether the total consumption model and its extension, the theory of collectivity, apply to adolescent cannabis use in Sweden. Frequency of cannabis use was measured by a question on how many occasions the respondent has used hashish or marijuana. The seven response alternatives ranged from 0 to 50 times or more. Increases in mean frequency use were associated with a higher prevalence of high-frequency users.  Adolescent cannabis use in Sweden appears to conform to key predictions of the total consumption model and its extension, the theory of collectivity.

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JAMA Psychiatry

This meta-analysis of 55 rigorous studies on spirituality and harmful or hazardous drug use (alcohol, tobacco, marijuana, or illicit drugs) examined the association between spiritual exposures and related drug use outcomes.  It documented a significant protective association of 13% related to both prevention and recovery. The risk reduction, which extended across all 4 drug categories, reached 18% for individuals with greater than weekly religious service attendance.  These results have implications for clinicians and communities regarding future strategies to address harmful or hazardous alcohol or other drug use.

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JAMA Network

This multicenter randomized study examined if 7-day extended-release injectable buprenorphine compared with sublingual buprenorphine to improve treatment engagement at 7 days.  It included 1,994 adult patients presenting to the emergency department with untreated opioid use disorder and a Clinical Opiate Withdrawal Scale (COWS) score of 4 or higher.  In treatment at 7 days, 40.5% were in the extended-release group and 38.5% were in the sublingual buprenorphine group, demonstrating no significant difference between groups. The study concluded that a 7-day extended-release injectable preparation of buprenorphine does not improve treatment engagement.

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Drug and Alcohol Dependence

Gabapentin prescriptions have increased due to off-label use, including managing withdrawal/comorbidities in substance use disorder (SUD) treatment, despite gaps in evidence bases and corresponding increases in nonmedical use. This retrospective, serial cross-sectional study sought to identify trends in gabapentin use with and without a prescription in SUD treatment settings.  Researchers found that gabapentin prescribing significantly increased in SUD treatment settings despite a lack of strong evidence bases for its utility. While rates of gabapentin use outside a prescription were nearly double that for prescribed use, this appears to be decreasing over time. Polysubstance use and potential gaps in multimorbidity care may contribute to the use of gabapentin without a prescription.

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Cancer

This study analyzed data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to look for an association between alcohol intake and colorectal cancer (CRC) or colorectal adenoma. Participants' lifetime pattern of alcohol intake was determined from a dietary history recorded as part of the PLCO trial. Current drinkers with a lifetime average of over 14 drinks per week had a higher CRC risk than those with under 1 drink per week (HR 1.25, p = .003) and an even higher risk of rectal cancer (HR 1.95). There was no consistent association between alcohol intake and colorectal adenoma risk, however results suggested that former drinkers may have a reduced risk of adenoma. They discussed potential mechanisms such as acetaldehyde, a known carcinogen and product of alcohol metabolism, and effects of alcohol on gut microbiome. They conclude that heavy alcohol intake increases CRC risk and that alcohol cessation may lower adenoma risk.

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JAMA Network Open

This study examined the availability of medications for alcohol use disorder (MAUD) in SUD treatment facilities (SUDTF) from 2017 to 2023.  Data was obtained from SAMSA’s Mental Health and Addiction Treatment Tracking Repository. The percentage of counties with a SUDTF offering MAUD increased from 34% in 2017 to 50% in 2021. This increase leveled out between 2021 and 2023 perhaps related to the pandemic. Counties with a MAUD-offering facility were more likely to be metropolitan (57% vs 25%, p<.001) with substantially more population (mean 220,100 vs 26,650, p<.001), and fewer uninsured residents (8.5% vs 10.7, p<.001).  They call for policies supporting MAUD-offering facilities, particularly in underserved counties.

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JAMA Network Open

This study completed a national web-based survey of 1552 adults in the United States in April 2025 to assess perceptions of opioid overdose deaths and opinions of people who use opioids. Those who responded to the survey primarily identified as female (60.5%) and aged 30-44 (33.7%). Political views varied, with 28.9% conservatives, 39.6% moderates, and 31.5% liberals. Most respondents viewed opioid overdose deaths as serious (88.2%). Respondents felt that people who use opioids (81%) and pharmaceutical companies (72.7%) were most responsible for reducing overdose deaths, with more liberals identifying pharmaceutical companies as responsible while moderates and conservatives more often identified individuals as responsible. 38.3% of respondents reported they were unwilling to have a person with OUD as a neighbor and 58.4% were unwilling to have a person with OUD marry into their family, with higher percentages of conservatives than liberals endorsing these beliefs.

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Science

In the United States overdose deaths (ODDs) from synthetic opioids peaked in mid-2023 and then began a sharp decline decreasing by over one third by the end of 2024. One possible explanation is a decrease in fentanyl supply. The purity of fentanyl powder rose in 2022, cresting at 25% in early 2023, but by the end of 2024 purity had fallen to 11%. From 2019 to 2024 the rate of ODDs correlated with the purity of fentanyl in both powder and pills. Drug seizures also peaked in early 2023 and then decreased by 37% in 2024. Analysis of Reddit posts by drug users found increased mentions of “drought” in 2023 that remained high at the end of 2024. All these indicators suggest a reduction in fentanyl supply beginning in 2023. In 2023 China took aggressive action against suppliers of synthetic opioid precursor chemicals, likely a result of meetings between Presidents Biden and Xi. This suggests international cooperation can help reduce ODDs. 

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JAMA Network Open

This is a survey study of 396 buprenorphine-prescribing clinicians in the US to determine if they faced problems initiating buprenorphine among patients using fentanyl, and whether their practice had changed as a result. Participants were selected from a stratified random sample of X-waivered clinicians registered with the DEA who had prescribed buprenorphine in 2022, with representation across all regions nationally. 72.8% of participants reported difficulty with buprenorphine initiation (either precipitated and/or prolonged withdrawal). Clinicians with waivers to treat larger numbers of patients, those reporting fentanyl use by their patients, and those in outpatient settings were more likely to report challenges with buprenorphine initiation. 67.3% of participants reported they had modified their standard buprenorphine treatment protocols for patients using fentanyl.

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American Journal of Preventive Medicine

Information on morbidity-related productivity losses attributable to substance use disorder is limited. This study estimates morbidity-related productivity losses attributable to substance use disorder among U.S. adults aged ≥18 years in 2023. It found that total morbidity-related productivity losses attributable to substance use disorder in the U.S. are substantial, amounting to $92.65 billion in 2023. Inability to work cost accounted for $45.25 billion, followed by absenteeism cost of $25.65 billion, presenteeism cost of $12.06 billion, and cost of household productivity loss of $9.68 billion. Given that these estimates depend on the prevalence of substance use disorder and the amount of lost productive time, evidence-based prevention efforts and policies addressing them can help reduce these losses.

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Substance Use and Addiction Journal

This is a narrative review of methadone and buprenorphine regulations, prescriber eligibility, dispensing models, and coverage across eight countries: the United States, Canada, the United Kingdom, Russia, France, Iran, Australia, and Portugal. The study identified several key barriers to MOUD: requirements for daily supervised dosing, restricted community prescribing, and stigmatizing drug scheduling. The authors highlight policies that improved MOUD access without compromising safety such as: 1) community pharmacy dispensing supports in the U.K. and Australia, 2) liberal buprenorphine prescribing in primary care in France, and 3) decriminalization and expansion of low-threshold public health models in Portugal and Iran.

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Drug and Alcohol Dependence

Very low nicotine cigarettes (VLNC, 0.4 mg nicotine/g tobacco) have been shown to reduce smoking behavior when compared to normal nicotine cigarettes (NNC,17 mg nicotine/g tobacco). Participants (n=208) were randomly assigned to 4 experimental groups, immediate versus gradual (over 5 weeks) transition to VLNC, and standard counseling versus facilitated extinction counseling (weekly for 5 weeks). Facilitated extinction had participants smoke only in relevant contexts (e.g., places, affects, triggers). The immediate nicotine reduction group reported less smoking satisfaction and lower completion rates (72% immediate reduction versus 88% gradual reduction, p=.02). Abstinence (biochemically verified) at 2 months post study was 29%. There were no significant differences between the 4 study groups. VLNC were beneficial in smoking cessation.

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JAMA Health Forum 

This cross-sectional study of 796 census tracts prior to the COVID-19 pandemic (2017-2019) and 792 census tracts during the COVID-19 pandemic (2020-2022) in Chicago, Illinois, assessed the extent to which there is a spatial association between neighborhood-level structural racism and opioid-involved overdose deaths. Researchers found that neighborhoods exposed to high levels of structural racism in the past (historical redlining) and present (contemporary segregation) had the highest fatal overdose incidence rates before the COVID-19 pandemic (2017-2019). Neighborhoods that experienced high levels of contemporary racism had the highest fatal overdose incidence rates during the pandemic (2020-2022). 

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Health Affairs

While medications for opioid use disorder (MOUD) is effective treatment, most patients with OUD don’t receive it and prior authorization (PA) has been a barrier to access. Researchers looked at state policies trying to address this barrier, specifically for private health insurance, between 2015 and 2022. Some states adopted “full prohibitions” against PAs while others adopted “partial prohibitions” that allowed PA under some circumstances. Overall, the number of states with at least some prohibition increased from 2 in 2015 to 22 in 2023. In addition, 7 states adopted “full prohibitions” initially, while 15 adopted “partial prohibitions”, with 4 of those 15 transitioning to “full prohibitions” later. Additional research will be needed to assess the impact of these prohibitions, but this study elucidates the current landscape of policy.

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JAMA Network

This industry-sponsored, multicenter, open-label randomized clinical trial with 729 participants, assessed if  rapid induction (RI) for initiating extended-release buprenorphine is as safe and effective as standard induction (SI) in individuals who inject opioids or use fentanyl.  RI was well tolerated and had higher retention than SI at extended-release buprenorphine injection 2 overall and in fentanyl positive participants. Administering the second extended-release buprenorphine injection 1 week after the first was well tolerated in both the RI arm and SI arm. These findings suggest support RI for extended-release buprenorphine induction in high-risk patients and demonstrate the feasibility of administering the first 2 doses at least 1 week apart.

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Health Affairs

Multiple federal policy changes since 2018 intended to increase buprenorphine prescribing in response to a persistent treatment gap for opioid use disorder (OUD) in the US. Anticipated national increases did not occur, but highly variable state-level trends provide important insights. This study used IQVIA data to examine all-payer and per payer prescribing across states during the period 2018–24.  Researchers found that highly disparate state-level changes suggest that federal policy impacts were mediated by state-specific factors. Medicaid’s key role in driving overall prescribing highlights the public health urgency of maintaining expansions and sustaining enrollment for the single adult population. 

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Addiction

Using a cross-sectional online and telephone survey of a nationally representative sample of older adults (aged 50–80 years) in the US, this study examined the prevalence of ultra-processed food addiction (UPFA) in older US adults and its association with various health domains.  It found that ultra-processed food addiction appears to be prevalent among older adults in the US, particularly among women who were in adolescence and early adulthood when the nutrient quality of the US food supply worsened. Addictive patterns of UPF intake appear to be associated with poorer physical health, mental health, and social well-being.

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JAMA Network Open 

This meta-analysis that included 13 studies assessed if alcohol consumption per capita is associated with suicide mortality and, if so, does the association differ by sex. Researchers found that a 1-L increase in alcohol consumption per capita was associated with a 3.59% increase in the suicide mortality rate. There was no evidence of a sex difference in this association. These findings suggest alcohol consumption per capita may be a useful target to consider within comprehensive national suicide prevention strategies. 

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JAMA Psychiatry

This male Swedish cohort study that included 573,855 participants assessed if there is an association between IQ and risk for alcohol use disorder, and if so, what is the nature of this association.  It found that IQ at age 18 years was associated with subsequent alcohol use disorder risk. Mendelian randomization analyses suggest a causal association, albeit with context-dependent differences; genetic liability for cognitive performance also predicted alcohol use disorder in a US-based sample. Results suggest that there was a clear impact of genetic liability for cognitive performance on alcohol disorder risk, but the association varies based on the sociocultural context.

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Agency for Healthcare Research and Quality (AHRQ) 

The AHRQ Integration Academy developed the Medications for Opioid Use Disorder Playbook as a practical guide for providing medications for opioid use disorder (MOUD) and immediate care for patients with OUD in primary care and other ambulatory care settings. It is interactive, web-based, and has the latest guidance, tools, resources, and examples that address key aspects of MOUD implementation. The MOUD Quick Start Guide covers the essentials of low-threshold care, while the balance of the Playbook offers more in-depth resources and guidance for those practices interested in working toward more comprehensive, whole-person care. The low-threshold approach ensures immediate access to MOUD, eliminating barriers for both patients and providers. 

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American College of Obstetricians & Gynecologists

Cannabis is the most commonly used illicit drug under U.S. federal law. With increasing social acceptability, accessibility, and legalization in many states, the prevalence of cannabis use among pregnant and lactating individuals has increased significantly. Substance use in pregnancy, including cannabis use, has been associated with adverse outcomes such as spontaneous preterm birth, low birth weight, and developmental delay. Clinicians should be aware of the possibility of pregnant and lactating patients' use of cannabis and be prepared to counsel and screen all patients and use evidence-based strategies to reduce cannabis use.  These include supportive home visits, psycho-behavioral strategies, or brief electronic or text messaging interventions to reduce cannabis use in pregnancy and the postpartum period to promote parental and newborn health.

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American Journal of Psychiatry

This national retrospective cohort study found that veterans with stimulant use disorder who received contingency management (CM) were 41% less likely to die in the year following treatment initiation relative to matched comparison subjects. These findings provide the strongest real-world evidence to date that CM is associated with reduced all-cause mortality, underscoring its potential as a life-saving intervention in routine care. Results support expanding access to CM across healthcare systems and public health settings.

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Science Advances

Fentanyl and its analogs are a global concern, making their accurate identification essential for public health. This article introduces Fentanyl-Hunter, a screening platform that uses a machine learning classifier and multilayer molecular network that covers more than 87% of known fentanyls to select and annotate fentanyl compounds using mass spectrometry (MS). Fentanyl-Hunter identified fentanyl members in biological and environmental samples. During biotransformation, 35 metabolites from four widely consumed fentanyl derivatives were identified. Norfentanyl was the major fentanyl compound in wastewater. Retrospective screening of these biomarkers across more than 605,000 MS files in public datasets revealed fentanyl, sufentanil, norfentanyl, or remifentanil acid in more than 250 samples from eight major countries, indicating the potential widespread presence of fentanyl.

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JAMA Network Open

Restarting methadone for patients who have had a gap in treatment is often a frustratingly slow process for both the patient and provider. This cohort study of individuals examined outcomes for patients of a public, safety-net opioid treatment program before (n=786 patients) and after (n=780 patients) implementation of a 2022 clinical protocol focused on individualized methadone restart doses based on opioid tolerance. Preimplementation restart doses were 32.8% lower than the last prior methadone dose, whereas postimplementation restart doses were only 3.4% lower than the last prior methadone dose. There was no significant change in patient safety (emergency department visits within 7 days after restart and all-cause mortality within 7 and 90 days after restart) or 90-day retention in care.

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JAMA Network Open

This survey study utilized a 3-round Delphi consensus process to identify best practices for addressing in-hospital substance use. A panel of 38 addiction experts developed 84 consensus-based and patient-centered recommendations which can inform local responses, including policies, to address in-hospital substance use. 

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JAMA Network Open 

Injectable-only buprenorphine protocols are an exciting new strategy for buprenorphine initiation, particularly in the fentanyl era. This is a cohort study of 95 patients with moderate to severe opioid use disorder who received care in a low-threshold setting in Seattle. 79% of patients included in the study were experiencing homelessness or living in permanent supportive housing. Patients selected a long-acting injectable (LAI) buprenorphine initiation protocol which included three escalating doses of LAI buprenorphine over three days, with no sublingual buprenorphine and without cessation of fentanyl/opioid use. 75% of the patients completed the protocol, and 64% received a second monthly dose of LAI buprenorphine.

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BMC Primary Care 

This is a cross-sectional analysis of associations between housing status and mental health and substance use severity among primary care patients with co-occurring disorders. The study is a sub-analysis using data from the Collaboration Leading to Addiction Treatment and Recovery from other Stresses randomized controlled trial, which tested the Collaborative Care Model for primary care patients with OUD and co-occurring depression and/or PTSD. Of 797 patients in the study, 13% were currently unhoused, 24% were unstably housed, and 63% were stably housed. Those who were unhoused were on average younger and had not used prescribed MOUD in the past 30 days. The analysis found that being unhoused or unstably housed was significantly associated with higher PTSD symptom severity, depression symptom severity, opioid use severity, and opioid overdose risk behaviors compared to those who were stably housed.

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Drug and Alcohol Dependence Researchers compared oral methadone to sublingual buprenorphine for the management of acute opioid withdrawal. Patients at an inpatient drug treatment center in India were randomly assigned to receive either methadone or buprenorphine titrated over days 1-3 to control opioid withdrawal symptoms. Over days 4-10 medications were tapered and stopped by day 11. Completion of treatment was similar in both groups (83% methadone, 82% buprenorphine). Both subjective (SOWS) and objective (COWS) withdrawal symptoms decreased during the treatment, however the buprenorphine group had significantly greater withdrawal symptoms than the methadone group (p=0.009) at the end of treatment (day 10). Opioid craving also decreased in both groups with no significant difference between groups. Authors conclude that methadone is a safe and effective alternative to buprenorphine for management of opioid withdrawal.

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JAMA  This study performed a cross-sectional analysis of the Syringe Services Programs in the US (SSPUS) dataset to determine implementation gaps. 613 syringe service programs (SSPs) included in the dataset were geocoded to county boundaries, which were then analyzed for urbanicity and SSP need (based on HCV mortality, HIV incidence, and drug overdose mortality). The study found that most high need counties did not have an SSP: 81.2% of high HCV need counties, 69.5% of high HIV need counties, and 75.7% of high overdose need counties did not have an SSP. SSPs were more commonly located in urban counties than suburban or rural counties. The study is limited in that not all SSPs are represented within the SSPUS database; however it highlights important implementation gaps.

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Plos Mental Health

The opioid epidemic unfolded in three distinct waves, with the latest being deaths attributed to illegally manufactured synthetic opioids. Using U.S. and Canadian data, this study reviews evidence for a 'silent epidemic' alongside the opioid epidemic that is characterized by the co-ingestion of stimulants including methamphetamine and cocaine leading to an increasing number of deaths. Trends for stimulant and opioid use were analyzed using Joinpoint regression and public interest in the substances was assessed via Google Trends. While stimulant use and its role in deaths are rising, public interest in stimulants has declined since its peak in 2004-05. Co-use leads to more deaths than either drug alone. Urgent strategies are needed to reduce harm and raise awareness among health professionals, policymakers, and the public about the dangers of stimulant-opioid co-use.

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Humanities and Social Sciences Communications

This study tested the “drunk” hypothesis, which claims that alcohol promoted social bonding and cooperation, aiding the rise of complex societies. Using data from 186 non-industrial societies, they found a modest positive link between indigenous alcoholic beverages and political complexity, even after controlling for ancestry, environment, and agriculture. Results suggest traditional fermented alcohols provided social benefits that helped societal evolution. However, other factors like agriculture and religion were likely more effective drivers.

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JAMA Network Open

This cohort study of 1,683 patients assessed if there are racial and ethnic disparities in treatment referral rates among patients in the emergency department (ED) with opioid overdose.  It found a statistically significant difference in the proportion of Black patients who received an outpatient treatment referral (5.7%) compared with White patients (9.6%). These findings suggest that Black patients presenting to the ED with opioid overdose may be less likely to receive outpatient treatment referrals, underscoring the need for targeted intervention and enhanced referral processes.

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Journal of General Internal Medicine

This study used interrupted-time-series analysis to model prescriber-level trends in buprenorphine prescriptions after recent federal policy changes.  It found that the elimination of the waiver requirement to prescribe buprenorphine in December 2022 was associated with a significant increase in the number of buprenorphine prescribers, but a decrease in the mean number of patients and the mean number of prescriptions per prescriber. Changes in telehealth flexibilities and relaxed training requirements were largely not associated with prescribing changes. This study expands on prior research by providing further insight as to why waiver elimination has not increased the number of patients receiving buprenorphine, as expected.

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Journal of General Internal Medicine

The American Society of Addiction Medicine (ASAM), in collaboration with nine other medical societies and professional associations, developed evidence-based guidelines for tapering benzodiazepine (BZD) medications across various clinical settings. These guidelines were created using a modified GRADE methodology and a clinical consensus process, which included a systematic literature review and several targeted supplemental searches. The guidelines were also revised based on feedback from external stakeholders. Key recommendations include that clinicians should continually assess the risks and benefits of BZD use and tapering. They should engage in shared decision-making with patients and avoid abrupt discontinuation in individuals who may be physically dependent or at risk of withdrawal. Tapering strategies should be personalized and adjusted based on the patient’s response. Additionally, clinicians are encouraged to provide psychosocial support to help patients successfully taper off BZDs.

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Drug and Alcohol Dependence

People who experience a nonfatal opioid overdose are at increased risk of subsequent overdose but is also a potential moment to intervene. In this cohort study, they used statewide data from Connecticut to assess differences in overdose outcomes in the year following a nonfatal overdose by treatment type received. Overall, 56% of patients received no treatment, while 35% received medication for opioid use disorder (MOUD) (25% buprenorphine and 11% methadone) and 21% received inpatient treatment (detox and/or extended inpatient). Both methadone (aHR=0.41) and buprenorphine (aHR=072) were associated with decrease in subsequent overdose, whereas neither detox nor prolonged inpatient treatment were associated with decreased overdose. These findings further support the importance of MOUD and the need to increase access to treatment in this high-risk population.

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The Journal of Neuroscience

Cocaine use disorder (CUD) is a highly heritable condition for which there are no effective treatments. Testing the many human genetic variants linked to CUD requires a cost-effective, genetically tractable model. This study showed that bitter-sensing neurons prevent cocaine self-administration in Drosophila. Disrupting Drosophila bitter perception enables a model for experience-dependent cocaine preference. The findings underscore the potential of Drosophila as a crucial tool for identifying the genetic mechanisms underlying CUD, aiding in the discovery of new therapeutic targets, and contributing to the development of effective treatments for this highly heritable disease.

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Scientific Reports

This study compared memory performance in patients treated with methadone or buprenorphine for drug abuse to healthy controls using the Wechsler Memory Scale. Healthy controls performed better than both treatment groups in mental control. Methadone patients scored higher than controls in personal and general information, while buprenorphine patients scored lower in associate learning. Longer buprenorphine treatment was linked to better overall memory scores, and patients on methadone for over two years showed better awareness of place and time compared to long-term buprenorphine users. Overall, neither medication showed major negative effects on memory except for mental control, which was impaired in both groups. Buprenorphine appeared to better preserve memory function over time than methadone.

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JAMA Network Open

Among Medicaid-insured adults with buprenorphine use, this cross-sectional study examined if changes in buprenorphine dispensing were greater among those residing in states with the highest vs lowest decreases in Medicaid enrollment after “Medicaid unwinding” began in April 2023. Researchers used 2017-2023 data from a national prescription dispensing database that included 754,675 person-years from 569,069 patients. They found that patients in states with the highest decreases in Medicaid enrollment were more likely to decrease buprenorphine use, discontinue buprenorphine therapy, and use private insurance or cash to pay for buprenorphine prescriptions. The finding that Medicaid unwinding was associated with disruptions in buprenorphine therapy raises concerns about the potential for increased opioid-related morbidity and mortality.

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Journal of Addiction Medicine

Loneliness is a major public health concern, especially among individuals with problematic substance use (PSU), but little research has focused on vulnerable groups like US military veterans. This study, using data from the National Health and Resilience in Veterans Study, found that nearly half of veterans with PSU (47.4%) experience clinically significant loneliness. Factors contributing to loneliness included being unmarried, higher psychological distress (depression and PTSD), a history of suicide attempts, physical disability, smaller social networks, and lower purpose in life and optimism. The analysis highlighted that depressive and PTSD symptoms had the strongest impact on loneliness, followed by social network size and sense of purpose. Furthermore, veterans with depressive symptoms who had a strong sense of purpose were less likely to feel lonely. The study underscores the need for strategies targeting psychological distress, fostering social connections, and enhancing purpose to help alleviate loneliness in this population.

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New England Journal of Medicine

In 2020, alcohol use was responsible for over 740,000 new cancer cases worldwide. In response, The International Agency for Research on Cancer (IARC) released a two-part handbook assessing the effectiveness of public policy measures in reducing alcohol-related cancer risk. The report found that reducing or stopping alcohol consumption lowers the risk of certain cancers and that several policy interventions, such as increasing alcohol taxes; setting minimum pricing; restricting sales by time, place, and age; implementing total sales bans; and enacting strong marketing restrictions, effectively reduce alcohol consumption. Government-run alcohol monopolies and coordinated national strategies were also associated with decreased use. However, bans on alcohol discounts produced inconsistent results. These findings align with the WHO’s Global Alcohol Action Plan and SAFER initiative, highlighting the importance of targeted, enforceable strategies to reduce alcohol-related harm globally. 

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Substance Use and Addiction Journal

Xylazine in the unregulated drug supply produces significant morbidity and this paper describes utilizing a multidisciplinary team to develop protocols for inpatient setting to manage patients with xylazine exposure. Protocols developed included use of scheduled clonidine or tizanidine to manage withdrawal with hold parameters. As there is no FDA approved immunoassay screen, they recommended assuming xylazine exposure in areas with high prevalence and limited testing. The team also developed guidelines for cases in which surgical interventions would be considered, when to culture wounds, antibiotic usage, and consistent wound care based on size and clinical characteristics. In addition, they developed standardized discharge instructions, including referral to substance use disorder treatment, harm reduction and education around xylazine test strip use.  

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Journal of the American Medical Association

This 12-week randomized clinical trial in 261 treatment-seeking youth aged 16 to 25 years assessed if varenicline, when added to brief, remotely delivered behavioral support, was efficacious and well tolerated for nicotine vaping cessation in youth.  Researchers found that continuous abstinence rates were higher in the varenicline group than in the placebo group in the last month of treatment (51% vs 14%) and at 6-month follow-up (28% vs 7%). Treatment-emergent adverse events did not differ significantly between groups. Varenicline, when added to brief cessation counseling, is well tolerated and promotes nicotine vaping cessation compared with placebo in youth with addiction to vaped nicotine.

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Harm Reduction Journal

Implementation of harm reduction intervention policies by local governments may be met with caution because of concern about potential backlash from communities and erosion of public trust. The authors conducted two studies to assess the influence of perceptions of government support for comprehensive drug policies (including harm reduction) on public trust in local government. In both a field study and an experimental study, the authors found that public trust was positively associated with increased perception of government support for comprehensive drug policies. The authors note residents recognized harm reduction policies as a step to address the issue of drug use, and these findings may ease some concerns about public pushback for local government officials when considering these policies. 

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JAMA Internal Medicine

While medication for opioid use disorder (MOUD) is effective, many patients with OUD do not receive it, particularly in hospitalized settings. In this randomized trial they evaluated the Substance Use Treatment and Recovery Team (START) model, a team of an addiction medicine provider and a care manager, and provided motivational interviewing, discharge planning and telephone follow-up for one month. Patients who received the START intervention were more likely to receive MOUD (aRR=2.10) and connect to OUD care after discharge (aRR=1.49). In addition, these patients were more likely to have an OUD-focused discharge plan (aRR=1.8), initiate or continue MOUD post discharge (aRR=1.71), and see a clinician for OUD post discharge (aRR=1.89). These findings support use of hospital-based addiction consult services to address this healthcare gap.

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Cancer

Smoking prevalence peaked in the 50s and 60s but has declined following the US Surgeon General’s report in 1964 on its health risk. As 85% of lung cancer is attributable to smoking, the authors evaluated this impact by assessing lung cancer deaths averted, and person-years of life (PYL) gained between 1970 and 2022 using cancer mortality data from the CDC. The authors estimated 3,856,240 lung cancer deaths were averted and 76,275,550 PYL were gained during the study period (average of 19.8 PYL gained per death averted). The deaths averted were higher in men (2,246,610), but average PYL gained per death averted was higher in women (22.4 years). Lung cancer deaths averted accounted for 51.4% of the estimated decrease in overall cancer deaths.  The findings highlight the importance of tobacco controls and interventions and need for ongoing efforts to decrease tobacco use. 

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JAMA Psychiatry

This study examined the prevalence of prescription stimulant use, prescription stimulant misuse, and prescription stimulant use disorder (PSUD) among adults aged 18 to 64 years in the US. Researchers found that 25.3% of adults in the study reported misuse, and 9.0% had PSUD. Among those with PSUD, 72.9% solely used their own prescribed stimulants, 87.1% used amphetamines, 42.5% reported no misuse, and 63.6% had mild PSUD. The prevalence of misuse was 3.1 times higher and the prevalence of PSUD was 2.2 times higher among those using prescription amphetamines than among those using methylphenidate. Regardless of prescription stimulant misuse status, screening for and treating PSUD is needed for US adults aged 18 to 64 years using prescription stimulants, especially those receiving prescription amphetamines. 

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JAMA Network Open

This cross-sectional study examined how Medicaid managed care plans (MCPs) cover and manage medications for alcohol use disorder (AUD). A content analysis of publicly available data from all 241 comprehensive Medicaid MCPs in 2021 revealed that 103 plans (42.7%) covered all approved medications (acamprosate, naltrexone, and disulfiram) for AUD. Prior authorization and quantity limits were used rarely, except for injectable naltrexone. This study suggests that expanding medication use for AUD and providing patient-centered care may be undermined by insurance coverage limitations.

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Health Affairs

During the COVID-19 pandemic, the Drug Enforcement Administration (DEA) temporarily allowed for prescribing of controlled substances via telehealth and extended the policy through the end of 2025. With concern about potential adverse outcomes with this policy, there is debate about making it permanent. The authors utilized commercial and Medicaid claims data to assess newly diagnosed substance use disorders (SUD) after initiation of stimulants via telehealth versus in-person visits to inform this policy decision. In unadjusted analysis, patients initiated on stimulants via telehealth visits had higher rates of non-ADHD psychiatric comorbidities and new diagnoses of SUD in the year following initiation. In the adjusted analysis, controlling for psychiatric comorbidities, they did not find a difference in SUD outcomes. The authors suggest additional research to inform policy decisions.

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Addiction

Buprenorphine labeling identifies 16 mg as the “target dose,” supported by prior evidence that higher doses (≥16 mg) were associated with increased retention in treatment. Studies comparing doses above 16 mg to 16 mg, particularly in the era of fentanyl, have been very limited. The authors conducted a cohort study to look at retention for those receiving 24, 32, and 40 mg compared to 16 mg. Overall, higher doses were associated with increased retention, as follows: 1) 24 mg was more effective than 16 mg at 1 (aOR=1.52) and 18 months (aOR=1.17), 2) 32 mg was more effective than 24 mg at 6 (aOR=1.06), 12 (aOR=1.09), and 18 months (aOR=1.12), and 3) 40 mg was more effective than 24 mg at 12 (aOR=1.10) and 18 months (aOR=1.18). The authors suggest updates to label language and recommendations are prudent, while also supporting more research on long-term treatment with these higher doses.

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Journal of the American Medical Association

Utilizing a multistaged probability-based survey, this study assessed the prevalence of illicit substance use, treatment, nonfatal overdose, and naloxone possession among 3,200 adults experiencing homelessness in California from October 2021 to November 2022.  An estimated 37% of respondents reported using any illicit substance regularly (≥ 3 times per week) in the last 6 months; methamphetamine use (33%) was the most common. Of those who reported regular use, an estimated 21% wanted but were unable to receive treatment. Approximately 20% of participants reported a nonfatal overdose, and 25% reported being in possession of naloxone. Substance use and nonfatal overdose were common among people experiencing homelessness in California. There was a high unmet need for substance use treatment and naloxone.

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JAMA Psychiatry 

This randomized clinical trial explored if glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide reduces alcohol consumption and craving in adults with alcohol use disorder (AUD). Relative to placebo, low-dose semaglutide reduced the amount of alcohol consumed during a posttreatment laboratory self-administration procedure. Over the course of nine weeks of treatment, semaglutide led to reductions in some but not all measures of weekly consumption, significantly reduced weekly alcohol craving relative to placebo, and led to greater relative reductions in cigarettes per day in a subgroup of participants with current cigarette use. These results justify larger clinical trials of incretin therapies for AUD.

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JAMA Network Open

This cohort study of 11.6 million people who were studied for a median of five years investigated if individuals who have hospital-based (emergency department or hospitalization) care for a cannabis use disorder (CUD) were at increased risk of death. Researchers found that individuals with incident hospital-based care for a CUD were at a 2.8-fold increased risk of death within five years relative to the general population. These results suggest that individuals who require hospital-based care for a CUD may be at increased risk of premature death.

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American Journal of Psychiatry

A commonly held model of addiction posits that as addictions develop, there is progression from positive reinforcement to negative reinforcement to ameliorate withdrawal symptoms. In this study, researchers examined the subjective response to alcohol among persons with and without alcohol use disorder (AUD) and with or without comorbid depression. Regardless of the presence of comorbid depression, persons with AUD reported pleasurable effects, including stimulation and hedonic reward, after consumption of alcohol. In contrast, among those without AUD, the positive effects were less substantial. Participants did report reduction in negative affect, but the effects were relatively small. These findings suggest that positive reinforcement is sustained in the progression of AUD and the reward-sensitive stage may exist along with negative reinforcement. 

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JAMA Network Open

The accumulation of fentanyl in fat is likely responsible for the risk of precipitated withdrawal when buprenorphine is initiated. Low dose initiation (LDI) of buprenorphine attempts to minimize this risk. This retrospective study included 126 individuals making 175 LDI attempts in an outpatient setting. Patients chose either a 4 day or 7 day LDI protocol with buprenorphine monoproduct. Both protocols begin with buprenorphine 0.5mg, increasing to 8mg tid. Overall LDI was successful in 34% of attempts (with no difference between the protocols) and one month retention on buprenorphine was 21%. Repeated LDI attempts were less likely to be successful (second attempt aOR 0.3). Unhoused people had lower odds of success (OR 0.4). The authors conclude that people with OUD using fentanyl attempting outpatient LDI of buprenorphine had low odds of success.

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JAMA Psychiatry

This longitudinal cohort study examined the association of state-level medical and recreational cannabis laws with cannabis use disorder (CUD) and cannabis poisonings in the adult population with employer-sponsored health insurance. The study showed that from 2011 to 2021, states with legalized medical cannabis experienced 42.7% and 88.6% increases in CUD and cannabis poisoning, respectively, compared to states without legalized medical cannabis. States with legalized recreational cannabis experienced a 31.6% increase in cannabis poisoning compared to states without legalized recreational cannabis. Thus, state medical cannabis legalization was associated with increased CUD and cannabis poisonings, and state recreational cannabis legalization was associated with increased cannabis poisoning in the adult population with employer-sponsored health insurance.

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American Journal of Psychiatry

This narrative review discusses five clinically relevant and prevalent behavioral addictions that are common and often co-occur with psychiatric disorders such as depression and anxiety. Gambling disorder is the only behavioral addiction recognized as a clinical disorder in DSM-5, and Internet gaming disorder is included as a condition requiring further research. ICD-11 categorizes gambling and gaming disorders as disorders due to addictive behaviors. Additional behavioral addictions may include compulsive sexual behavior disorder, compulsive buying-shopping disorder, and problematic use of social media. Validated diagnostic instruments exist, with empirical support varying across conditions. No medications have approved indications from regulatory bodies for behavioral addictions, and cognitive-behavioral therapy has the most empirical support for efficacious treatment. Treatment optimization involving pharmacotherapy, psychotherapy, neuromodulation, and their combination warrants additional investigation.

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Treatment Failure Versus Failed Treatments: The Risks of Embracing Treatment Refractory Addiction [Dr. David Fiellin]

The Concept of Treatment-Refractory Addiction: A Call to the Field [Dr. Eric Strain]

The Concept of Treatment-Refractory Addiction: Implications for Addiction Treatment Systems and Research [Dr. Edward Nunes & Dr. Thomas McLellan]

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National Academies of Sciences, Engineering, and Medicine

To inform the next edition of the Dietary Guidelines for Americans (DGA), Congress tasked the National Academies with convening an expert committee to independently review the evidence on the relationship between moderate alcohol consumption and eight health outcomes including obesity, cancer, and cardiovascular disease. This controversial report found that a pattern of moderate drinking was associated with 18 percent fewer cardiovascular disease deaths, a 16 percent lower risk of all-cause mortality, and a 10 percent heightened risk of breast cancer for women.

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Psychological Medicine

Using data from the EU-GEI case-control study and UK Biobank, researchers examined the independent and combined effect of heavy cannabis use and schizophrenia polygenic risk score (PRS), on risk for psychosis. Schizophrenia PRS and cannabis use independently increased risk of psychosis. Schizophrenia PRS was not associated with patterns of cannabis use. It was associated with lifetime and daily cannabis use without psychosis, but the effect was substantially reduced when cannabis use disorder (CUD) PRS was included in the model. Regular users of high-potency cannabis had the highest odds of being a case independently of schizophrenia PRS. Regular use of high-potency cannabis remains a strong predictor of psychotic disorder, independent of schizophrenia PRS. Schizophrenia PRS does not seem to be associated with heavy cannabis use. These are important findings, at a time of increasing use and potency of cannabis worldwide. 

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Addiction

This is an observational study using cross-sectional data from the American College Health Association–National College Health Assessment III. It measured the association between university-level prevalence of attention deficit/hyperactivity disorder (ADHD) medication treatment and prevalence of prescription stimulant misuse (PSM) among college students.  Among university students in the United States, there appears to be a positive association between attending universities with a greater prevalence of ADHD medication treatment and risk of prescription stimulant misuse (PSM). This study provides further support for the possibility that ADHD medication treatment prevalence is a risk factor for PSM.

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Clinical Chemistry

This study of xylazine pharmacokinetics used plasma samples from 28 patients who had urine screens positive for xylazine and fentanyl. The patients were being treated for skin lesions, most commonly, then shortness of breath or opioid overdose. At least two subsequent plasma samples were analyzed for xylazine and xylazine metabolites by LC-MS/MS. The median terminal half-life for xylazine in plasma was 12 hours (range 6-21 hours). Animal studies show xylazine to be extensively metabolized, with little unchanged xylazine eliminated in urine. The two most abundant metabolites were oxo-x and sulfone-x, which did not have a window of detection longer than xylazine. Researchers had no information as to the timing or route of xylazine ingestion or if additional xylazine was consumed during the study period. These factors could affect the accuracy of the results.

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Addiction

This retrospective cohort study aimed to determine if opioid agonist therapy (OAT) in Scotland is protective against suicide, and measure trends in suicide rates in those with opioid dependence over time. The study included 46,453 individuals who received at least one prescription for OAT between 2011 and 2020 with over 304,000 person-years (pys) of follow-up. Results suggested that people with opioid dependence in Scotland have a greater risk of suicide than the general population. Treatment is protective, with rates of suicide lower among those on opioid agonist therapy. Suicide rates have decreased over time, during a period in which drug-related death rates in Scotland have risen to globally high levels.

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Alcohol Clinical and Experimental Research

Using data from the Monitoring the Future study, which enrolled cohorts of high school seniors annually starting in 1976, this analysis evaluated alcohol drinking patterns in adults 35-60 and potential association with their drinking patterns at age 18. Overall, the reported mean number of drinks at a time ranged from 1.7 to 1.4, and the mean maximum number of drinks ranged from 3.2 to 2.3. The reported number of drinks was generally lower at older ages. Those who reported binge drinking at 18 versus those who did not report a significantly higher mean (2.3 vs. 1.3) and maximum (4.0 vs. 2.3) number of drinks as adults. Additionally, they were more likely to report binge drinking (39.5% vs 19.1%) and high-intensity drinking (10.5% vs 4.4%) as adults. Further, this association was even stronger in older age groups, suggesting adolescent binge drinking is a risk factor across the lifespan.

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JAMA Network

This population-based retrospective cohort study assessed whether the use of buprenorphine/naloxone is associated with lower risk of treatment discontinuation and mortality compared with methadone. It included 30,891 individuals initiating treatment for the first time during the study period and found that  the risk of treatment discontinuation was higher among recipients of buprenorphine/naloxone compared with methadone (88.8% vs 81.5% within 24 months). The risk of mortality was low while in either form of treatment (0.08% vs 0.13%).  Individuals receiving methadone had a lower risk of treatment discontinuation compared with those who received buprenorphine/naloxone. The risk of mortality while receiving treatment was similar between medications.

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JAMA Network Open 

This cross-sectional study using health care claims data from 35,451 US adults with an opioid use disorder diagnosis assessed whether buprenorphine treatment using doses higher than Food and Drug Administration recommendations is associated with subsequent acute health care utilization. Those receiving higher maximum doses of buprenorphine (i.e., doses above 16 mg and 24 mg) had significantly lower rates of acute care utilization than their peers receiving FDA-recommended doses (between 8 mg and 16 mg). These results suggest that higher doses of buprenorphine are associated with lower acute care utilization and could provide benefits to patients, particularly those using fentanyl who might need these higher doses.

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The Lancet Regional Health Americas

In the context of the opioid overdose epidemic, great efforts have been made to increase access to medication for opioid use disorder (MOUD), specifically buprenorphine. Initiation of buprenorphine in emergency departments (ED) has been a focus of these efforts. While initiation has been increasing, only 3-15% of persons treated in EDs fill a prescription. In this summary literature review, authors examined potential barriers and facilitators to initiation. Having care-coordination with streamlined and easy connection to outpatient treatment was associated with increased initiation. Conversely, the absence of care-coordination was associated with decreased uptake. Additionally, provider training and comfort increased uptake as did flexibility in induction strategies. 

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National Academy of Sciences Engineering Medicine

This report from the National Academies of Sciences, Engineering, and Medicine urges the federal government to provide policy guidance to states that have legalized cannabis, close regulatory loopholes on intoxicating products derived from hemp, and create a public health campaign aimed at parents and vulnerable populations, among other measures that would protect public health and reduce the harms of rising cannabis use. Federal action includes closing regulatory loopholes for hemp-derived cannabinoids, a cannabis public health campaign, best practices for cannabis policy, and improved cannabis public health data and allowing research. State action includes required training for cannabis retail staff, automatically expunging criminal records, a model for state cannabis policy, and setting product standards. 

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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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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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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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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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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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JAMA Network Open 

This British study included 135,103 older (median age 64) adults and compared drinking patterns with mortality during a median follow-up of 12 years. Compared to occasional drinkers, low-risk drinkers had higher cancer mortality (HR, 1.11), moderate-risk drinkers had higher all-cause and cancer mortality (HRs, 1.10 and 1.15), and high-risk drinking had higher all-cause, cancer, and cardiovascular mortality (HRs, 1.33, 1.39, and 1.21). These results contrast with earlier studies showing protective effects of low- to moderate-risk drinking. Researchers used occasional drinkers as the control group, where previous studies used abstainers including former drinkers with residual health effects. There was a small protective effect of drinking only with meals and drinking wine. In conclusion, the authors failed to find a protective effect of low-risk drinking on mortality.

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JAMA Network Open

This systematic review of 283 articles explored the reasons physicians give for not addressing substance use and addiction in their clinical practice. The institutional environment (81.2% of articles) was the most common reason given for physicians not intervening in addiction, followed by lack of skill (73.9%), cognitive capacity (73.5%), and knowledge (71.9%). These findings suggest that efforts should be directed at creating institutional environments that facilitate the delivery of evidence-based addiction care while improving access to education and training opportunities for physicians to practice the necessary skills.

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Subscribe to The ASAM Weekly to read the guest editorial: 

Guest Editorial: Rapid Initiation of Injectable Extended-Release Naltrexone for Opioid Use Disorder: A Time for Paradigm Shift in Treatment Protocols

This project has been funded as a whole or in part with Federal funds from the National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, under Contract No. 75N95020C00028.

JAMA Psychiatry

This is a survey study of 4,674 participants from US households that examined the association between social vulnerability and mental health and substance use disorders and related treatment in the US noninstitutionalized population of adults aged 18 years and older. Large increases in several mental health and substance use disorders and corresponding decreases in treatment were found in the most socially vulnerable communities. The findings suggest that routine measurement of social vulnerability might assist in developing more comprehensive care models that integrate medical and social care for mental health and substance use disorders.

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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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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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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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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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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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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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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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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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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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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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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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