Journal: Addictive Behaviors, 2026, doi: 10.1016/j.addbeh.2026.108603
Authors: Laura C. Chambers, Benjamin D. Hallowell, Andrew R. Zullo, McClaren Rodriguez, Marzan A. Khan, Justin Berk, … Francesca L. Beaudoin
Abstract:
Background: For patients who use fentanyl, higher than currently recommended maintenance doses of buprenorphine treatment for opioid use disorder (OUD) may be needed to prevent cravings and withdrawal, but some clinicians and regulators are concerned that higher doses may increase overdose risk. We evaluated buprenorphine effectiveness for overdose prevention in the fentanyl era.
Methods: We conducted a retrospective cohort study of Rhode Island residents initiating buprenorphine for OUD (October 2016‒September 2022) using statewide administrative data. On each of 365 follow-up days, patients were classified as having an active buprenorphine prescription (yes/no) and a non-fatal or fatal opioid overdose (yes/no). Follow-up was discontinued if patients died or initiated methadone or naltrexone. Generalized estimating equations compared opioid overdose risk for days with versus without an active buprenorphine prescription, controlling for potential confounders and clustering by patient.
Results: Among 8,676 patients initiating buprenorphine, most were aged 25-44 years (56.0 %) and male (61.3 %). In the 365 days following initiation, 52.6 % of person-days were covered by an active buprenorphine prescription, 1,069 patients (12.3 %) had follow-up discontinued due to methadone initiation, and 411 patients (4.7 %) experienced 545 opioid overdoses. Opioid overdose risk was 61 % lower for days with versus without an active buprenorphine prescription (adjusted risk ratio = 0.39, 95 % confidence interval = 0.31-0.49). Daily doses prescribed on days with and without an opioid overdose event were similar (P = 0.261).
Conclusions: Buprenorphine remains effective for overdose prevention in the fentanyl era among patients who remain in treatment. There was no evidence that higher doses were associated with greater overdose risk.
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Journal: Drug & Alcohol Dependence, 2026, doi: 10.1016/j.drugalcdep. 2026.113022
Authors: Vidya Eswaran, Fanghong Dong, Xiao Li, Hannah S. Szlyk, Nathaniel A. Dell, Erin Kasson, Jessica Williams, & Patricia A. Cavazos-Rehg
Abstract:
Background: People with substance use disorders (PwSUD) who experience housing insecurity have disproportionate overdose deaths. Digital interventions may improve care among PwSUD, but evidence specifically for housing-insecure PwSUD, who face unique barriers, remains limited.
Methods: We examined the efficacy of a mHealth tool (uMAT-R) among people who have misused substances and reported current housing insecurity. Substance use, cravings, access to basic needs, social disconnection, and digital literacy were assessed at baseline and 1 month and compared by uMAT-R use. Generalized estimating equations were employed to assess the efficacy of the intervention.
Results: Participants who logged into uMAT-R were less likely to report other non-opioid illicit drug use (aOR (95 %CI): 0.49(0.29, 0.85)). Similarly, those who messaged the e-coach were less likely to report using opioids (aOR(95 %CI): 0.39(0.21, 0.73)) or other illicit drugs (aOR (95 % CI): 0.53(0.30, 0.92)) during past 30-days. Significant interaction effects were found in uMAT-R use by time in cravings (Coef (95 %CI): -2.11(-4.07, -0.17)) and perceived burdensomeness (Coef(95 %CI): -2.62 (-4.91, -0.36)). Messaging an e-coach by time was significantly associated with improved health literacy (Coef (95 %CI): 0.61(0.05, 1.18)) and decreased thwarted belongingness (Coef(95 %CI): -0.36 (-0.71, -0.02).
Conclusion: Our preliminary findings suggest that people who have misused substances and experience housing insecurity may benefit from uMAT-R, which was associated with improved recovery outcomes. Future research is needed to examine the unique barriers experienced by this population and how mHealth tools can be used to provide tailored, equitable access to supportive resources to reduce barriers and promote long-term recovery.
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Journal: Translational Psychiatry, 2026, doi: 10.1038/s41398-026-03830-z
Authors: Sonia G. Ruiz, Samuel Paskewitz, & Arielle Baskin-Sommers
Abstract:
Insensitivity to costs during cost-benefit decision-making consistently has been related to substance use severity. However, little work has manipulated cost information to examine how people evaluate and compare multiple costs. Further, no work has examined how the consideration of cost information varies across different contexts. We administered a new loss-frame variant of a probabilistic learning task in a diverse community sample enriched for substance use (N = 137). Individuals with more years of regular substance use tended not to repeat choices after they avoided losses, choosing similarly regardless of whether they had avoided or incurred a loss. Computational modeling parameters indicated that they were more inconsistent in their use of expected values to guide choice. These results contribute to our conceptualization of substance use severity by suggesting that inconsistency in using cost information, rather than insensitivity to costs, may inform choices to continue using substances despite incurring negative consequences.
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Journal: Annals of General Psychiatry, 2026, doi: 10.1186/s12991-025-00627-0
Authors: John W. Figg, Caitland A. Love, Vasu Sorathia, Mia Engelbart, Ana Turner, & Amanda Elton
Abstract:
Benzodiazepines (BZDs) are a widely prescribed class of psychoactive drugs known for their rapid anxiolytic, anticonvulsant, and sedative effects. Introduced as safer alternatives to barbiturates, BZDs quickly gained popularity across clinical settings but have since become a subject of public health concern due to rising rates of misuse, dependence, and overdose, particularly when co-administered with opioids. This narrative review explores the historical development, pharmacologic mechanisms, clinical indications, and adverse outcomes associated with BZD use, while highlighting emerging areas of research such as pharmacogenetics (PGx) and genome-wide association studies (GWAS). BZDs act as positive allosteric modulators of the GABAA receptor, enhancing inhibitory neurotransmission. This mechanism underlies both their therapeutic efficacy and their potential for physiological dependence and misuse. Clinical applications span acute anxiety, insomnia, seizure management, and alcohol withdrawal; however, long-term use carries significant risks including cognitive decline, fall-related injuries, paradoxical excitation, and withdrawal syndromes. Reinforcement and neuroadaptation processes within the mesolimbic dopamine system contribute to BZD addiction, especially with chronic exposure. Regulatory responses include Schedule IV classification under the Controlled Substances Act and FDA black box warnings. Despite declining prescription rates in recent years, misuse, including nonmedical use and use of illicit designer BZDs, remains prevalent, especially among older adults and those with comorbid psychiatric or substance use disorders. Pharmacogenomic studies have identified genetic polymorphisms in hepatic enzymes (e.g., Cyp2c19 and Cyp3a4) and GABAA receptor subunits (e.g. Gabra2) that may influence BZD metabolism, efficacy, and addiction vulnerability, suggesting potential for personalized medicine approaches. In conclusion, the dual nature of BZDs, as essential tools in acute care and potential contributors to substance use disorders, demands a balanced, evidence-informed approach. Continued research, improved prescriber education, and integration of genetic insights into clinical care may help mitigate harm while preserving therapeutic benefit.
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Journal: Toxicology Reports, 2026, doi: 10.1016/j.toxrep.2026.102202
Authors: Karen Lin, Yehao Sun, Rhea Raghu, Parth Suharu, Felix Effah, & Irfan Rahman
Abstract:
Hemp-derived cannabinoids (CBDs) such as Δ8- and Δ10-tetrahydrocannabinol (THC) in cannabis e-cigarettes have been growing in popularity among youth, causing great concern for their health effects. Previous novel lung injury outbreaks, such as E-cigarette or Vaping Use-Associated Lung Injury (EVALI), were associated with the rising use of e-cigarettes and vaping products. Toxicological studies have revealed that chronic exposure to cannabis vapor can cause adverse brain and pulmonary effects. Hemp products are classified as cannabis and set a limit of no more than 0.3 % Δ9-THC, while products containing more than 0.3 % are defined as ‘marijuana.’ This has led to the proliferation of hemp-derived intoxicating cannabinoids, such as Δ8- and Δ10-THC, in addition to cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), and Δ9-THC appearing in combination products. CBD frequently serves as a significant component of hemp-derived formulations, making it a central consideration for toxicological and regulatory evaluation as well. This phenomenon poses significant health risks to youth because these newer THC isomers and products are currently unregulated and not well-researched, yet they are still widely available. Therefore, we have examined the pharmacology, toxicity, potential therapeutic uses and possible health risks of several THC and hemp-derived cannabinoids. This review draws insightful highlights to the public health consequences of secondary exposures to CBD and THC, and their molecular mechanisms of action. It underscores the urgency for a regulatory oversight over unregulated cannabinoid markets to prevent toxicity of vaping-related health crises and other rapidly emerging cannabis health disorders, like the cannabinoid hyperemesis syndrome (CHS).
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