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This article reviews the cohort study published in the World Journal of Gastroenterology , which reported low rates of Helicobacter pylori ( H. pylori ) infection among esophageal cancer (EC) patients, coupled with proton pump inhibitor (PPI) overuse. These findings suggest a potential protective role of H. pylori against EC and indicate a possible association between PPI use and increased cancer risk. In light of these findings, our article examines the complex relationship between H. pylori and esophageal precancerous lesions, exploring the potential underlying mechanisms. We also address growing concerns regarding PPI overuse, including its potential effects on cancer therapy efficacy and the risk of drug interactions. Ultimately, this article highlights the urgent need for further research to evaluate the safety and efficacy of PPIs in cancer patients and to better understand their broader implications., Competing Interests: Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Alcohol is the most consumed and abused psychoactive drug globally, but the molecular mechanisms driving alcohol action and its associated behaviors in the brain remain enigmatic. Here, we have discovered a transmembrane protein TMEM132B that is a GABA A receptor (GABA A R) auxiliary subunit. Functionally, TMEM132B promotes GABA A R expression at the cell surface, slows receptor deactivation, and enhances the allosteric effects of alcohol on the receptor. In TMEM132B knockout (KO) mice or TMEM132B I499A knockin (KI) mice in which the TMEM132B-GABA A R interaction is specifically abolished, GABAergic transmission is decreased and alcohol-induced potentiation of GABA A R-mediated currents is diminished in hippocampal neurons. Behaviorally, the anxiolytic and sedative/hypnotic effects of alcohol are markedly reduced, and compulsive, binge-like alcohol consumption is significantly increased. Taken together, these data reveal a GABA A R auxiliary subunit, identify the TMEM132B-GABA A R complex as a major alcohol target in the brain, and provide mechanistic insights into alcohol-related behaviors., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

Aim: To evaluate tapentadol abuse cases by analyzing real-world data and identifying under-reporting countries from Southeast Asian Region (SEAR) to enhance vigilance., Method: A retrospective, observational study from 2013 to March 2024 using VigiBase was conducted., Result: Tapentadol-related abuse falls within the System Organ Class (SOC) categories of psychiatric disorder, nervous system disorder and injury, poisoning, and procedural complications. These are further categorized into Preferred Terms (PT) such as anxiety, delirium, Central Nervous System toxicity, depressive disorder, drug abuse, dependence/withdrawal syndrome, and overdose using the Medical Dictionary for Regulatory Activities (MedDRA) system. Among the 11 countries in the SEAR, India is the only country to report cases of tapentadol-related abuse, no Individual Case Safety Reports (ICSRs) related to tapentadol abuse have been submitted from other SEAR nations. Out of 127 ICSRs concerning tapentadol-related adverse events reported in India, 20 cases involved abuse. Focusing on the ICSRs submitted in India, the reported adverse reactions included anger(n = 1,10%), anxiety (n = 2, 10%), delirium (n = 1, 5%), drug abuse (n = 4, 20%), drug dependence/withdrawal syndrome (n = 7, 35%), intentional overdose (n = 2, 10%), depressive disorder (n = 1, 5%), euphoric mood (n = 1, 5%), and product misuse (n = 1, 5%) indicating a concerning pattern of substance abuse., Conclusion: Stringent regulatory actions are needed to curb this practice in India, such as rescheduling tapentadol from Schedule H (Prescription drugs) to Schedule X(Narcotic drugs) in India could offer more regulatory oversight and measures to reduce risks related to abuse, addiction, and dependence while enhancing patient safety in pain management practices. Additionally, tapentadol should be closely monitored in other SEAR countries due to its potential for dependence. This study also emphasizes the importance of encouraging SEAR countries to report more Adverse Drug Reactions (ADRs), which would facilitate the implementation of more rigorous regulatory measures.

Etomidate, an ultrashort-acting non-barbiturate sedative derived from imidazole, exerts potent inhibitory effects on the central nervous system. It is commonly employed for the induction of intravenous general anaesthesia or assisted anaesthesia. Recently, etomidate has emerged as an alternative to narcotics and novel psychoactive substances, leading to an increasing trend of abuse. Chronic overdose of etomidate can result in irreversible brain damage and various mental disorders. Severe cases may manifest as mental disturbances, behavioural disorders, self-mutilation and even death. The toxicological mechanisms of etomidate remain poorly understood. Additionally, there is limited information on the clinical symptoms and histopathological changes associated with etomidate poisoning and standardized detection methods for etomidate in blood, urine and hair are lacking. Consequently, further research on toxicological pathology and the development of reliable testing methods is crucial. This study reviews the metabolism, distribution, adverse reactions, poisoning manifestations, toxicology mechanisms and testing methods of etomidate., Competing Interests: Declarations of Conflicting InterestsThe author(s) declares no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Tianeptine ( 1 ) is an unusual antidepressant in that its mechanism of action appears to be independent from any activity at serotonin receptors or monoamine transporters. In fact, tianeptine has been shown to be a moderately potent agonist for the mu opioid receptor (MOR) and to a lesser extent the delta opioid receptor (DOR). Additionally, tianeptine's efficacy may be related to its action on glutamate-mediated pathways of neuroplasticity. Regardless of which neurotransmitter system is primarily responsible for the observed efficacy, the MOR agonist activity is problematic with respect to abuse liability. Increasing numbers of case reports have demonstrated that tianeptine is indeed being used recreationally at doses far beyond what are considered therapeutically relevant or safe, and scheduling reclassifications or outright bans on tianeptine products are ongoing around the world. It is the aim of this review to discuss the medicinal chemistry and pharmacology of tianeptine and to summarize this intriguing discrepancy between tianeptine's historical use as a safe and effective antidepressant and its emerging potential for abuse.

Nan Bao detox capsule (NBDC), derived from ancient Chinese opioid detox protocols, shows promising therapeutic potential in substance abuse disorders, particularly for attenuating methamphetamine (MA) addiction. This study aimed to identify active ingredients, evaluate therapeutic efficacy in an MA addiction rat model and delineate pharmacodynamic mechanisms using metabolomics. In vitro phytochemical profiling characterized 258 drug-related compounds, with 87 prototype entities mainly identified in rat plasma. NBDC significantly attenuated METH-induced behavioural anomalies and modulated neurotransmitter levels, notably increasing brain DA and serotonin (5-HT) content with concomitant upregulation of D1 dopamine receptor (DRD1) and 5-HT1A receptor (5-HT1AR) expression, ameliorating hippocampal pathology. Metabolomic analysis identified histamine receptor as a potential target and revealed the involvement of NBDC in metabolic pathways associated with cocaine addiction, amphetamine abuse and Parkinson's disease. Conclusively, NBDC presents a promising therapeutic agent for mitigating MA addiction through a synergistic interplay of multiple constituents, pharmacological targets and metabolic pathways., (© 2024 The Author(s). Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

The globus pallidus externus (GPe) is a central component of the basal ganglia circuit that acts as a gatekeeper of cocaine-induced behavioral plasticity. However, the molecular and circuit mechanisms underlying this function are unknown. Here, we show that GPe parvalbumin-positive (GPe PV ) cells mediate cocaine responses by selectively modulating ventral tegmental area dopamine (VTA DA ) cells projecting to the dorsomedial striatum (DMS). Interestingly, GPe PV cell activity in cocaine-naive mice is correlated with behavioral responses following cocaine, effectively predicting cocaine sensitivity. Expression of the voltage-gated potassium channels KCNQ3 and KCNQ5 that control intrinsic cellular excitability following cocaine was downregulated, contributing to the elevation in GPe PV cell excitability. Acutely activating channels containing KCNQ3 and/or KCNQ5 using the small molecule carnosic acid, a key psychoactive component of Salvia rosmarinus (rosemary) extract, reduced GPe PV cell excitability and impaired cocaine reward, sensitization, and volitional cocaine intake, indicating its therapeutic potential to counteract psychostimulant use disorder., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aimed to evaluate the changes in quality of life (QoL) over a 12-month period among opiate users in Romania, identifying factors that contribute to a worsening of their condition. By examining these dynamics, the research intended to inform targeted interventions and support mechanisms to mitigate the negative outcomes associated with opiate use. Conducted as a longitudinal cohort analysis, this study enrolled 74 participants diagnosed with opioid use disorders from multiple healthcare settings in Romania. The WHOQOL-BREF instrument was utilized to assess QoL, with data collection spanning from 1 January 2023 to 31 December 2023. Ethical compliance with the Declaration of Helsinki was maintained, and participants provided informed consent. Statistical analysis was performed using SPSS, focusing on the impact of demographic and behavioral variables on QoL. Over the 12-month period, significant improvements were observed in all QoL domains: physical (51.68 to 58.39, p < 0.001), psychological (49.34 to 55.32, p < 0.001), social (46.21 to 53.66, p < 0.001), and environmental (47.85 to 54.17, p < 0.001). Methadone compliance significantly influenced positive outcomes across all domains. Compliant participants exhibited higher mean scores compared to non-compliant users, with respective increases in the physical domain from 52.47 to 60.21 ( p < 0.001), psychological from 50.93 to 58.32 ( p < 0.001), social from 48.36 to 57.14 ( p < 0.001), and environmental from 47.82 to 55.79 ( p < 0.001). Additionally, education showed a protective effect, particularly enhancing environmental QoL (estimate = 0.33, p = 0.013). Methadone compliance and higher education levels were identified as significant predictors of improved QoL among opiate users, demonstrating the critical importance of adherence to treatment protocols and the supportive role of education in enhancing life quality. These findings highlight the necessity for integrated treatment programs and educational interventions to improve the well-being of individuals battling opioid addiction, advocating for policy enhancements and supportive measures tailored to this demographic.

Background: illegal drugs significantly contribute to global health issues, with health complications often occurring not only in regular users with Substance Use Disorders (SUDs) but also in first-time and occasional users., Methods: this study examines five clinical cases from a public hospital in Ibiza, Spain, where patients presented with acute psychiatric symptoms due to recreational drug use., Results: Contrary to previous studies on SUDs, our patients typically had higher education levels and stable employment. Most of them used multiple substances, with cannabis, cocaine, and alcohol being the most frequently used. There was also a common occurrence of consuming drugs with uncertain contents. Upon admission, typical symptoms included aggression, hallucinations, mood swings, and disorientation in time and space., Conclusions: Our findings underscore the significant mental health risks posed by illicit drugs, even for individuals with no prior psychiatric history. Factors like the drug's potency, frequency and amount of use, past mental health issues, personality traits, and previous traumatic experiences might influence the onset of these symptoms.

Drug abuse has become a global health problem over the past few years. Opioid abuse increased with an increase in the prescription of opioids for pain management. Many other classes of drugs are also abused and misused like anti-depressants, stimulants, hallucinogens, anti-psychotic, and anticholinergic drugs. One of the major reasons is that patients falsely diagnosed with depression, anxiety, and severe pain are prescribed these drugs, which are likely to be addictive. Abuse-deterrent formulations are one means to control drug abuse and overdose of prescription opioids. In this review, we explained how abuse-deterrent technology works, key ingredients used in abuse-deterrent formulations, a brief about marketed opioid drug products with abuse-deterrent properties, and the stand of regulatory agencies in the approval process of opioid drug products. In the end, it summarized that pharmaceutical industries and the FDA put their efforts into reducing drug abuse by encouraging the development of ADFs. Most available drug product having abuse-deterrent features contains Polyethylene oxide, which degrades at high temperatures. It requires the attention of the researcher to find an alternate ingredient or process to overcome said problem. From a regulatory point of view, only a few regulatory agencies have published their guidance on ADFs. It is important to convey other regulatory organizations' perspectives on ADFs as well.

Objective: The authors examined the initial implementation of the Indiana Adolescent Addiction Access (AAA) program, modeled on the widely disseminated Child Psychiatry Access Program framework. The AAA program developed a statewide consultation helpline to connect health care providers with adolescent addiction specialists., Methods: The AAA line was staffed by a coordinator, who fielded initial questions, and on-call clinical specialists (social workers, nurse practitioners, psychiatrists, and psychologists), who were paged to complete telephone consultations and provide care recommendations. When necessary, AAA providers offered urgent clinical assessments and initiated treatment. Descriptive analyses were performed for key variables over the first 21 months of AAA operations., Results: From July 2021 to March 2023, a total of 125 consultations were completed. Most callers were health care providers (71%) or parents (27%). Calls pertained to youths ages 10-18 years (mean±SD age=16.4±1.3; 62% of callers were male, 84% White, and 11% Black), with concerns around cannabis (63%), opioids (38%), and other substances. About 26% of calls related to an overdose, and 41% of cases were rated as severe. Recommendations included starting new medications (17%) or outpatient therapy (86%), and 17% of consultations resulted in urgent evaluations., Conclusions: The Indiana AAA program helps overcome key barriers to adolescent substance use treatment. Increasing the capacity to initiate medication for opioid use disorder and other treatment rapidly through consultation and direct care is a promising, scalable approach for preventing overdose deaths among youths., Competing Interests: The authors report no financial relationships with commercial interests.

Construction workers in South Africa are an at-risk group for HIV/AIDS. Substance misuse, other than alcohol, is associated with poor decision-making, risky lifestyle behaviour, and non-use of condoms. Substance misuse is also associated with harmful and hazardous alcohol consumption and depression. The Drug Use Disorders Identification Test (DUDIT) is a widely used screening tool to detect drug abuse. The present study examines both the psychometric properties of the DUDIT and the prevalence of drug abuse among construction workers. A field study involving 496 male workers at 18 construction sites of seven construction companies in the Western Cape province of South Africa, was undertaken. Descriptive statistics, reliability, and exploratory and confirmatory factor analyses were used to determine the prevalence of substance use, and the dimensionality, reliability and construct validity of the DUDIT. Approximately 10% of participants reported some form of substance use. Four hundred and sixty-seven employees (94.2%) were determined not to have drug-related problems (DUDIT score < 6). Of the at-risk employees (score >5), 5.0% ( n = 25) were classified as 'possibly having a drug-related problem' (score 6-24) and 0.8% ( n = 4) as 'possibly highly dependent on drugs' (score 25 or more). Of the 47 employees who reported drug use, 29 (61.7%) were classified as having a medium to high risk in relation to drug use. The internal consistency of the DUDIT was very good. The DUDIT reported a one-factor factorial structure, and the model fit indices indicated good model fit to the data. All factor loadings were significant, but there was some evidence of collinearity. Concurrent validity was demonstrated. DUDIT items 1 and 10 require further investigation due to their poor performance compared to the other items. The contribution of these two items needs to be investigated using item response theory (IRT).

Background: Due to its psychoactive effects, ketamine has become a drug used for non-medical purpose., Objectives: To assess the latest trends in ketamine use among people with substance use disorder and to characterize its clinical complications using complementary health data sources of the French Addictovigilance Network., Methods: First, we extracted all reports involving ketamine from 2012 to 2021 from the database of the OPPIDUM program (i.e., a multicentric program conducted in collaboration with hundreds of substance abuse treatment facilities that collects data on drugs used by subjects with substance use disorders). We described the reports globally and the changes from 2012 to 2021. Second, we extracted all cases involving ketamine from July 2020 to December 2022 from the French National Pharmacovigilance Database (BNPV). We identified the cases related to ketamine use among people with substance use disorder and described them., Results: There was a 2.5-fold increase in the number of ketamine users with substance use disorder in the OPPIDUM program, from 35 (0.7%) subjects in 2012 to 89 (1.7%) subjects in 2021. There was an increase in the proportion of subjects who were daily users, had distress upon discontinuation, and presented addiction. There were 238 cases related to ketamine use among people with substance use disorder in the French National Pharmacovigilance Database from July 2020 to December 2022. Among them, 94 (39.5%) cases involved ketamine use disorder, 20 (8.4%) cases involved urinary tract and kidney symptoms, and 13 (5.5%) cases involved hepatobiliary symptoms., Conclusion: The trend observed over 10 years reflects the growth in ketamine use among people with substance use disorder, although it does not allow to estimate the rates of non-medical use of ketamine in the general population. Ketamine-induced uropathy and cholangiopathy are reported in ketamine users with substance use disorder, especially in case of repeated and/or prolonged use of high doses., (© 2024 The Authors. Fundamental & Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of Société Française de Pharmacologie et de Thérapeutique.)

Background: Neurovascular interfaces, specifically the blood-brain barrier (BBB) and blood-retinal barrier (BRB), play pivotal roles in maintaining the homeostasis of the central nervous system (CNS). For a long time, these structures were seen only as a way of protection, but we currently know that they have a critical role in CNS (dys)function. Several studies have identified neurovascular alterations in early stages of brain and eye diseases, contributing to the pathophysiology of such conditions. More recently, interesting data have also highlighted the importance of neurovasculature in psychiatric disorders., Methods: Using the PubMed database, we brought together the evidence concerning the changes in BBB and BRB under psychiatric conditions, with a focus on anxiety, major depressive disorder (MDD), attention-deficit/hyperactivity disorder (ADHD) and drug abuse, specifically related with methamphetamine (METH) and cocaine consumption., Results: We summarized the main findings obtained from in vitro and animal studies, as well as clinical research that has been undertaken to identify neurovascular abnormalities upon such neuropsychiatric disorders. The drivers of barrier alterations were examined, namely the role of neuroinflammation, while reporting putative barrier-associated biomarkers of these disorders., Conclusion: This review underscores the critical need for a deeper understanding of BBB and BRB function in neuropsychiatric conditions and their potential as therapeutic targets while elucidating the key players involved. The innovative approaches to managing these complex disorders are also addressed while bridging the gap concerning what is currently known regarding the association between neuropsychiatric conditions and their vascular implications., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Despite considerable efforts, there remains no FDA-approved medications for cocaine use disorder (CUD). One strategy to mitigate cocaine craving and relapse is to elevate dopamine (DA). The DA transport inhibitor and releaser d -amphetamine has been shown to decrease cocaine self-administration (SA), although it has abuse liability. Recently, several modafinil analogues reduced cocaine SA in rats and monkeys, including JJC8-088, characterized as "cocaine like" in rats, and JJC8-091, characterized as "atypical" and not SA by rats. The present studies evaluated the reinforcing effects of both compounds in monkeys under several conditions. For Experiment 1, four male cocaine-experienced rhesus monkeys self-administered cocaine (0.001-0.3 mg/kg/injection), JJC8-088 (0.001-0.3 mg/kg/injection), and JJC8-091 (0.1-3.0 mg/kg/injection) under a progressive-ratio (PR) schedule of reinforcement. Both JJC compounds functioned as reinforcers with equal reinforcing strength to cocaine. Although JJC8-091 was less potent than cocaine, JJC8-088 and cocaine had similar potencies. For Experiment 2, one male and two females drug-naïve cynomolgus monkeys responded on a fixed-ratio schedule of food reinforcement. JJC8-091 was self-administered at rates higher than saline in all three monkeys. In Experiment 3, monkeys from Experiment 2 responded under a concurrent drug vs. food choice paradigm and given access to cocaine or JJC8-091 under these conditions. At doses equal to or one-half log-units higher than doses used in Experiment 2, cocaine, but not JJC8-091, was chosen over food. Together, these results demonstrate that while JJC8-091 may be reinforcing under some conditions, its reinforcing strength, in the presence of an alternative reinforcer, is substantially less than cocaine. Significance Statement JJC8-088 and JJC8-091 have shown efficacy is reducing cocaine self-administration in rats and in nonhuman primates. This study found that both compounds maintained self-administration in monkeys responding under several conditions. However, when given access to an alternative reinforcer during the self-administration session, JJC8-091 was not reinforcing, suggesting that JJC8-091 may be a viable candidate for CUD since, in the human population, alternatives to drug use are often available., (U.S. Government Work not Protected by U.S. Copyright.)

Nitrous oxide is an anesthetic medication which can also be recreationally abused in the form of whippet canisters. Its prolonged abuse can interfere with Vitamin B12 metabolism and lead to its functional deficiency. We report a case of a 30-year-old male who presented with generalized weakness and was found to have subacute combined degeneration (SCD) of the spinal cord. His laboratory workup showed low Vitamin B12 with elevated homocysteine and methylmalonic Co-A levels, and further questioning revealed prolonged nitrous oxide abuse. Nitrous oxide causes functional inactivation of methylcobalamin by rendering it unable to function as a coenzyme for methionine synthase enzyme. This leads to the decreased production of methionine and subsequent production of myelin. This case describes nitrous oxide abuse as an important etiology to be considered in patients presenting with weakness and myeloneuropathy and describes important imaging findings., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Amidst far-reaching COVID-19 effects and social constraints, this study leveraged wastewater-based epidemiology to track 38 conventional drugs and 30 new psychoactive substances (NPS) in northern Taiwan. Analyzing daily samples from four Taipei wastewater plants between September 2021 and January 2024-encompassing club reopenings, holidays, Lunar New Year, an outbreak, and regular periods-thirty-one drugs were detected, including 5 NPS. Tramadol, zolpidem tartrate, CMA, and MDPV were newly detected in Taiwanese sewage with frequency of 1.4 %- 89.0 %. Conventional drug use typically increased post-pandemic, aside from benzodiazepines and methadone. Methamphetamine showed 100 % frequency, indicating ongoing daily consumption despite COVID-19 measures. Methamphetamine and morphine's consumption dipped then rose around club reopening, hinting at limited access. The consumption trend of methadone appeared to compensate for the use of morphine. Ketamine and NPS demonstrated similar patterns throughout the entire period. NPS as party drugs seemed influenced by an unstable supply chain and complexities in implementation. Benzodiazepines, commonly abused alongside synthetic cathinones in Taiwan exhibited an opposing trend to NPS while aligned with acetaminophen, suggesting elevated stress and anxiety levels during the pandemic. No significant differences were observed in drug consumption between weekdays and weekends, potentially indicating that COVID-19 measures blurred the traditional distinctions between these timeframes. ENVIRONMENTAL IMPLICATION: New psychoactive substances refer to chemically modified variants of controlled drugs designed to mimic the effects of the original drugs while evading modern detection methods, categorizing them as hazardous materials. The study presents a sewage monitoring project conducted from 2021 to 2024, collecting samples from four WWTPs to analyze NPS and conventional drug trends during and after the COVID-19 pandemic. The findings uncovered connections between drug consumption patterns and pandemic-related policies. In light of the persistent drug abuse and their environmental presence, the results bear critical importance for both environmental and public health. We provide a thorough assessment of these relationships and prioritize areas for future research., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Pai-Shan Chen reports financial support was provided by National Science and Technology Council., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim: To identify incidence, type of drug abuse study clinical and angiographic profile in very young population presenting with acute coronary syndrome (ACS)., Materials and Methods: All consecutive patients less than 30 years with ACS included and segregated into Group 1 and 2 (with and without drug abuse respectively) RESULT: n = 153; n = 17 in group 1 of whom 35.29 % consumed opium, 17.64 % energy drinks, 17.64 % whey protein supplements, 17.64 % inhaled marijuana, 5.88 % heroin and spasmoproxyvon and 23.52 % multi-substance abusers. STEMI, Single vessel disease and urban domicile were predominant. Rising trends of drug abuse were identified in prospective (28.20 %) versus retrospective (5.30 %) timeframe (p = 0.011)., Conclusion: Rising trends of drug abuse, a potentially modifiable risk factor of ACS in the young are alarming. Strict regulations are needed to curb this menace., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Shibba Chhabra reports was provided by Dayanand Medical College and Hospital. NONE., (Copyright © 2024 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Background: The experience of homelessness has been linked with developing poor health outcomes. Little is known about the risk of recurrent stroke among these individuals. This study investigated the correlates of developing recurrent stroke and subsequent mortality among Veterans with housing instability., Methods: Using a national sample of Veterans from the U.S. Department of Veterans Affairs who had an indicator of housing instability between 2014-2018 (n=659,987), we identified 15,566 Veterans who experienced incident stroke. We compared characteristics of Veterans who experienced incident stroke and did and did not experience recurrent stroke and conducted logistic regressions using a discrete-time survival framework to assess two outcomes: recurrent stroke and all-cause mortality., Results: Among our cohort, 91.3% did not experience recurrent stroke while 8.7% did during the observation period. The receipt of any level of primary care outpatient visits was associated with a reduction in the odds of recurrent stroke. Several medical diagnoses were also associated with increased odds of recurrent stroke, including hypertension (aOR 1.35, 95% CI 1.15-1.59), diabetes (aOR 1.21, 95% CI 1.07-1.36), and renal disease (aOR 1.17, 95% CI 1.02, 1.35). Veterans who used any level of VA Homeless Programs had reduced odds of all-cause mortality (high level: aOR 0.65, 95% CI 0.60-0.71; low level: aOR 0.66, 95% CI 0.60-0.73)., Conclusion: Our study found several predictors of developing recurrent stroke and subsequent death in a population of Veterans experiencing housing instability. Implications include the need to monitor closely high-risk patients who have experienced incident stroke and have other co-occurring needs., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Chen Lin reports financial support was provided by US Department of Veterans Affairs. Ann E Montgomery, Aerin DeRussy, Joshua Richman reports financial support was provided by US Department of Veterans Affairs. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

The treatment landscape for opioid use disorder (OUD) faces challenges stemming from the limited efficacy of existing medications, poor adherence to prescribed regimens, and a heightened risk of fatal overdose post-treatment cessation. Therefore, there is a pressing need for innovative therapeutic strategies that enhance the effectiveness of interventions and the overall well-being of individuals with OUD. This study explored the therapeutic potential of nor-Levo-α-acetylmethadol (nor-LAAM) to treat OUD. We developed sustained release nor-LAAM-loaded poly (lactic-co-glycolic acid) (PLGA) microparticles (MP) using a hydrophobic ion pairing (HIP) approach. The nor-LAAM-MP prepared using HIP with pamoic acid had high drug loading and exhibited minimal initial burst release and sustained release. The nor-LAAM-MP was further optimized for desirable particle size, drug loading, and release kinetics. The lead nor-LAAM-MP (F4) had a relatively high drug loading (11 wt%) and an average diameter (19 μm) and maintained a sustained drug release for 4 weeks. A single subcutaneous injection of nor-LAAM-MP (F4) provided detectable nor-LAAM levels in rabbit plasma for at least 15 days. We further evaluated the therapeutic efficacy of nor-LAAM-MP (F4) in a well-established fentanyl-addiction rat model, and revealed a marked reduction in fentanyl choice and withdrawal symptoms in fentanyl-dependent rats. These findings provide insights into further developing long-acting nor-LAAM-MP for treating OUD. It has the potential to offer a new effective medication to the existing sparse armamentarium of products available to treat OUD., Competing Interests: Declaration of competing interest The nor-LAAM-MP technology described in this publication has been filed as a patent application through Virginia Commonwealth University (VCU). Qingguo Xu, Matthew Banks, Diane Ingabire, Chaolong Qin, Tuo Meng, and Aji Alex Moothedathu Raynold are the co-inventors who are subject to certain rules and restrictions under VCU policy. The terms of this arrangement are being managed by VCU in accordance with its conflict-of-interest policies., (Copyright © 2023. Published by Elsevier B.V.)

Drug addiction is associated with significant health risks, including cardiovascular complications, cancer, and mental disorders. Illicit drugs, such as cannabinoids and opioids, including prescription medications, are widely consumed and have profound health consequences. Understanding the health effects of the toxic elements in these substances is critical for overdose prevention and effective recovery strategies. This study aimed to determine toxic elements, including arsenic (As), cadmium (Cd), mercury (Hg), and nickel (Ni), in cannabinoid and opioid drugs and in biological samples (whole blood, scalp hair, and serum) from 311 male drug abuse patients aged 15-60 years with a history of drug abuse. The participants were categorized into three age groups. The comparative analysis involved 113 reference subjects of the same age groups. The sample preparation employed microwave-assisted acid digestion, and the toxic elements were quantified using atomic absorption spectrophotometry. Accuracy was ensured using certified reference materials for hair, whole blood, and serum samples. Drug-addicted subjects had significantly higher concentrations of toxic elements (arsenic, cadmium, mercury, and nickel) in biological samples than referent subjects (p > 0.001). Elevated levels of these toxic elements may increase susceptibility to infections, possibly due to malnutrition, drug-related effects, and additional contaminants. These findings necessitate further studies to explore the long-term health outcomes, potential treatment options, and broader socioeconomic impacts of substance abuse. This study serves as a baseline for future research in this critical public health field., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Biological sex disparities manifest at various stages of drug addiction, including craving, substance abuse, abstinence, and relapse. These discrepancies are underpinned by notable distinctions in neurobiological substrates, encompassing brain structures, functions, and neurotransmitter systems implicated in drug addiction. Neuronal biomarkers, such as neurotransmitters, signaling proteins, and genes may be associated with the diagnosis, prognosis, and treatment outcomes in both biological sexes afflicted by drug abuse. Sex differences in the neural reward system, mainly through dopaminergic transmission during drug abuse, can be attributed to modifications in neurotransmitter systems and signaling pathways. This results in distinct patterns of neural activation and responsiveness to addictive substances in males and females. Sex hormones, the estrus/menstrual cycle, and cerebral neurochemistry contribute to the progression of psychological and physiological dependence in both male and female individuals grappling with addiction. Moreover, the alteration of sex hormone balance and neurotransmitter release plays a pivotal role in substance use disorders, subsequently modulating cognitive functions pertinent to reward, including memory formation, decision-making, and locomotor activity. Comparative investigations reveal distinctions in brain region volume, gene expression, neuronal firing, and circuitry in substance use disorders affecting individuals of both biological sexes. This review examines prevalent substance use disorders to elucidate the impact of sex hormones as therapeutic biomarkers on the mesocorticolimbic neurotransmitter systems via diverse mechanisms within the addicted brain. We underscore the imperative necessity of considering these variations to gain a deeper comprehension of addiction mechanisms and potentially discern sex-specific neuronal biomarkers for tailored therapeutic interventions., Competing Interests: Declaration of competing interest The authors declare that the review was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Estrogen related receptors (ERRs) agonist GSK-9089 (DY-131) reported to pose a potential in increasing exercise endurance. High resolution mass spectrometry (HRMS) based analysis has utmost importance in the detection, identification, or characterization of a molecule including its metabolites in human body. In this study, in vitro metabolism profile of GSK-9089 was investigated after incubation with liver microsomes and S9 fractions. Additionally, in vivo metabolites of the molecule were identified in plasma, urine, and faeces samples of rats. Structures of all the potential metabolites were revealed by employing an in silico tool and HRMS based analysis through data-dependent and data-independent mining strategies. Nine unknown metabolites of GSK-9089 have been identified which were found to be present in a trace amount in in vivo matrices. Most of the in vitro and in vivo phase I metabolites of the molecule were formed after imine bond hydrolysis followed by deamidation, oxidation, and N-oxidation. The molecule underwent phase II metabolism to generate more polar metabolites mainly through glucuronide, sulfate conjugation biotransformation reactions. The in vitro and in vivo metabolites of GSK-9089 could be useful to identify the abuse of this ERRs agonist in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ketamine has recently become an anesthetic drug used in human and veterinary clinical medicine for illicit abuse worldwide, but the detection of illicit abuse and inference of time intervals following ketamine abuse are challenging issues in forensic toxicological investigations. Here, we developed methods to estimate time intervals since ketamine use is based on significant metabolite changes in rat serum over time after a single intraperitoneal injection of ketamine, and global metabolomics was quantified by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Thirty-five rats were treated with saline (control) or ketamine at 3 doses (30, 60, and 90 mg/kg), and the serum was collected at 21 time points (0 h to 29 d). Time-dependent rather than dose-dependent features were observed. Thirty-nine potential biomarkers were identified, including ketamine and its metabolites, lipids, serotonin and other molecules, which were used for building a random forest model to estimate time intervals up to 29 days after ketamine treatment. The accuracy of the model was 85.37% in the cross-validation set and 58.33% in the validation set. This study provides further understanding of the time-dependent changes in metabolites induced by ketamine abuse., (© 2024. The Author(s).)

Substance use disorder is a major concern, with few therapeutic options. Heparan sulfate (HS) and chondroitin sulfate (CS) interact with a plethora of growth factors and their receptors and have profound effects on cellular signaling. Thus, targeting these dynamic interactions might represent a potential novel therapeutic modality. In the present study, we performed mass spectrometry-based glycomic and proteomic analysis to understand the effects of cocaine and methamphetamine (METH) on HS, CS, and the proteome of two brain regions critically involved in drug addiction: the lateral hypothalamus and the striatum. We observed that cocaine and METH significantly alter HS and CS abundances as well as sulfate contents and composition. In particular, repeated METH or cocaine treatments reduced CS 4-O-sulfation and increased CS 6-O-sulfation. Since C4S and C6S exercise differential effects on axon growth, regeneration, and plasticity, these changes likely contribute to drug-induced neural plasticity in these brain regions. Notably, we observed that restoring these alterations by increasing CS 4-0 levels in the lateral hypothalamus by adeno-associated virus delivery of an shRNA to arylsulfatase B (N-acetylgalactosamine-4-sulfatase) ameliorated anxiety and prevented the expression of preference for cocaine in a novelty induced conditioned place preference test during cocaine withdrawal. Finally, proteomics analyses revealed a number of aberrant proteins in METH- and cocaine-treated versus saline-treated mice, including myelin proteolipid protein, calcium/calmodulin-dependent protein kinase type II subunit alpha, synapsin-2, tenascin-R, calnexin, annexin A7, hepatoma-derived growth factor, neurocan, and CSPG5, and oxidative phosphorylation among the top perturbed pathway. Taken together, these data support the role of HS, CS, and associated proteins in stimulants abuse and suggest that manipulation of HSPGs can represent a novel therapeutic strategy., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The enormous consequences of drugs include suicides, traffic accidents, and violence, affecting the individual, family, society, and country. Therefore, it is necessary to constantly identify and monitor the drug abuse rate among school-going youth. A geospatial dashboard is vital for the monitoring of drug abuse and related crime incidence in a decision support system., Objective: This paper mainly focuses on developing MyAsriGeo, a geospatial drug abuse risk assessment and monitoring dashboard tailored for school students. It introduces innovative functionality, seamlessly orchestrating the assessment of drug abuse usage patterns and risks using multivariate student data., Methods: A geospatial drug abuse dashboard for monitoring and analysis was designed and developed in this study based on agile methodology and prototyping. Using focus group and interviews, we first examined and gathered the requirements, feedback, and user approval of the MyAsriGeo dashboard. Experts and stakeholders such as the National Anti-Drugs Agency, police, the Federal Department of Town and Country Planning, school instructors, students, and researchers were among those who responded. A total of 20 specialists were involved in the requirement analysis and acceptance evaluation of the pilot and final version of the dashboard. The evaluation sought to identify various user acceptance aspects, such as ease of use and usefulness, for both the pilot and final versions, and 2 additional factors based on the Post-Study System Usability Questionnaire and Task-Technology Fit models were enlisted to assess the interface quality and dashboard sufficiency for the final version., Results: The MyAsriGeo geospatial dashboard was designed to meet the needs of all user types, as identified through a requirement gathering process. It includes several key functions, such as a geospatial map that shows the locations of high-risk areas for drug abuse, data on drug abuse among students, tools for assessing the risk of drug abuse in different areas, demographic information, and a self-problem test. It also includes the Alcohol, Smoking, and Substance Involvement Screening Test and its risk assessment to help users understand and interpret the results of student risk. The initial prototype and final version of the dashboard were evaluated by 20 experts, which revealed a significant improvement in the ease of use (P=.047) and usefulness (P=.02) factors and showed a high acceptance mean scores for ease of use (4.2), usefulness (4.46), interface quality (4.29), and sufficiency (4.13)., Conclusions: The MyAsriGeo geospatial dashboard is useful for monitoring and analyzing drug abuse among school-going youth in Malaysia. It was developed based on the needs of various stakeholders and includes a range of functions. The dashboard was evaluated by a group of experts. Overall, the MyAsriGeo geospatial dashboard is a valuable resource for helping stakeholders understand and respond to the issue of drug abuse among youth., (©Ahmad Mustafa Al-Aboosi, Siti Norul Huda Sheikh Abdullah, Rozmi Ismail, Khairul Nizam Abdul Maulud, Lutfun Nahar, Khairul Akram Zainol Ariffin, Meng Chun Lam, Muhamad Lazim bin Talib, Suzaily Wahab, Mahadzir Elias. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 30.07.2024.)

The increasing prevalence of substance misuse in modern culture is contributing to the growth in neonatal abstinence syndrome (NAS) cases in India. NAS can be challenging to diagnose due to nonspecific symptoms and maternal suppression of drug history. Only a few reports of NAS have been published from India. This is a case series of three newborns from India who all had symptoms like restlessness, high-pitched crying, excessive sweating, vigorous sucking, tremors, and diarrhea. The investigations did not lead to any conclusions. In the first case, the mother was treated with a combination of psychotropic medications, including selective serotonin reuptake inhibitors (SSRIs), atypical antipsychotics, and tricyclic antidepressants. In the second case, the mother was a nicotine addict, while in the third case, the mother had an opiate addiction. It was only after being asked several times that the abuse background of the last two cases was revealed. As a result, three cases of NAS were diagnosed, successfully managed with phenobarbitone, and discharged., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Malwade et al.)

Addiction, characterized by compulsive drug-seeking behavior and impaired self-control, remains a significant public health concern. Understanding the neurobiology of addiction is crucial for identifying novel therapeutic targets and further developing effective treatments. Recently, the apelin/APJ system, an emerging signaling pathway, has attracted attention for its involvement in various neuropsychiatric disorders. The cross-talk between the apelin/APJ system and hypothalamic mu opioid signaling, as well as its heterodimerization with kappa opioid receptors (KORs), supports the potential relevance of this system to addiction. Moreover, several protective effects of apelin against various addictive substances, including methamphetamine, morphine, and alcohol, underscore the need for further investigation into its role in substance use disorder. Understanding the contribution of the apelin/APJ system in addiction may offer valuable insights into the underlying neurobiology and pave the way for novel therapeutic interventions in substance use disorders. This review provides a concise overview of the apelin/APJ system, emphasizing its physiological roles and highlighting its relevance to addiction research., Competing Interests: Competing Interests The authors declare that no competing and financial interests exist., (© 2024 Kerman University of Medical Sciences.)

The article presents a systematic literature review on the use and the psychiatric implications of over-the-counter drugs (OTC), prescription-only-medications (POM), and new psychoactive substances (NPS) within custodial settings. The searches wer carried out on 2 November 2022 on PubMed, Scopus, and Web of Science in line with PRISMA guidelines. A total of 538 records were identified, of which 37 met the inclusion criteria. Findings showed the most prevalent NPS and OTC and POM classes reported in prisons were synthetic cannabinoids receptor agonists (SCRAs) and opioids, respectively. NPS markets were shown to be in constant evolution following the pace of legislations aimed to reduce their spread. The use of such substances heavily impacts the conditions and rehabilitation of persons in custody, with consequent physical and mental health risks. It is important to raise awareness of the use and misuse of such substances in prisons (i) from an early warning perspective for law enforcement and policy makers (ii) to prompt doctors to cautiously prescribe substances that may be misused (iii) to improve and increase access to treatment provided (iv) to add such substances to routine toxicological screening procedures (v) to improve harm reduction programmes., Competing Interests: Declaration of Competing Interest S.F. was a member of the UK Advisory Council on the Misuse of Drugs (ACMD; 2011–2019) and is currently a member of the EMA Advisory Board (Psychiatry). Se. F. is a member of the UK’s Independent Advisory Panel on Deaths in Custody. M.G. has been a consultant and/or a speaker and/or has received research grants from Angelini, Doc Generici, Janssen-Cilag, Lundbeck, Otsuka, Pfiser, Servier, Recordati. C.J.M. is a member of the ACMD’s Novel Psychoactive Substances and Technical Committees. C.S., V.G., M.A., Mi. A., S.G., G.G., d’A.G, D.C.F., C.R., C.C., P.M., G.A.: nothing to be declared., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Substance use disorder (SUD) exacerbates the impact of Long-COVID, particularly increasing the risk of taste and olfactory disorders. Analyzing retrospective cohort data from TriNetX and over 33 million records (Jan 2020-Dec 2022), this study focused on 1,512,358 participants, revealing that SUD significantly heightens the likelihood of experiencing taste disturbances and anosmia in Long-COVID sufferers. Results indicated that individuals with SUD face a higher incidence of sensory impairments compared to controls, with older adults and women being particularly vulnerable. Smokers with SUD were found to have an increased risk of olfactory and taste dysfunctions. The findings underscore the importance of early screening, diagnosis, and interventions for Long-COVID patients with a history of SUD, suggesting a need for clinicians to monitor for depression and anxiety linked to sensory dysfunction for comprehensive care., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: The abuse of prescription drugs and over-the-counter medicines has been a major issue addressed as a serious public health problem worldwide. This study explored factors contributing to substance abuse in Korea by examining the status of substance abuse among Korean adults and evaluating their knowledge, attitudes, and intentions toward substance abuse., Methods: Data were collected online from a sample of participants 19 years old or older from May 20 to June 1, 2020 (n=1,020). The survey consisted of questions on demographics, perceptions of drug risk, motives for drug use, and attitudes toward drug addiction treatment. Principal component and multiple logistic regression analyses were used to explore the factors contributing to the perception of drug abuse., Results: In the multivariate regression analysis, overconfidence in handling drug usage, acceptance of addictive substances, and affirmation of public support for drug abuse were associated with opioid abuse (Nagelkerke R2=0.486), and additionally affirmation of legal cannabis usage and motivation to use diet pills were associated with diet pill abuse (Nagelkerke R2=0.569)., Conclusion: The findings of this study suggest that the actual situation of substance abuse among Korean adults increases awareness of and attitudes toward drug use related to substance abuse.

Inhalation of crack and freebase results in alveolar hemorrhage. In severe courses of the disease, progressive respiratory insufficiency may lead to respiratory failure and acute respiratory distress syndrome (ARDS). Computed tomography of the thorax reveals bilateral consolidation and ground-glass pattern leaving a subpleural gap. This case report of a 48-year-old male patient highlights the importance of a thorough medical history while ruling out infectious causes., (© 2024. The Author(s).)

Background: Buprenorphine is under scrutiny because of the development of xerostomia and caries. The purpose of this article was to inform dental care professionals about the oral effects of buprenorphine and to increase knowledge and awareness of medication-assisted treatment in the management of opioid use disorder (OUD)., Case Description: In 2022, the US Food and Drug Administration issued a warning about xerostomia and caries associated with the use of transmucosal (sublingual and buccal formulations) buprenorphine. Dental health care professionals should instruct patients taking buprenorphine on how to prevent these dental issues by means of rinsing with water and swallowing once the drug has been completely dissolved, followed by toothbrushing at least 1 hour after taking the drug. In addition, a fluoride supplement should be prescribed., Practical Implications: It is imperative for dentists to recognize buprenorphine as medication-assisted treatment and to recognize a patient as having an OUD. While taking buprenorphine, the patient should have more frequent oral health care appointments, including home care instructions and caries risk assessment to monitor for caries and xerostomia so that treatment, if indicated, could be initiated as soon as possible. In addition, the dentist's role in OUD is to make sure patients follow the treatment recommendations and use the buprenorphine and to not have them discontinue because of potential caries risk., Competing Interests: Disclosures Drs. Segelnick and Weinberg did not report any disclosures., (Copyright © 2024 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Nitrous oxide (N 2 O), also known as laughing gas, has a euphoric effect and is becoming increasingly popular as a recreational inhalant drug. Deaths caused by recreational nitrous oxide abuse are rare, but may still occur. Although some methods for the quantification of N 2 O by GC-MS have been reported, elimination of carbon dioxide interference and the choice of a suitable internal standard remain current limitations to accurate N 2 O quantification. Here, a validated method using headspace-gas chromatography-mass spectrometry (HS-GC-MS) is described that allows the quantification of N 2 O in human blood samples: sodium hydroxide is used to remove carbon dioxide, and n-pentane is chosen as a suitable internal standard. Collectively, the validation results show a good linear relationship of N 2 O in blood within the concentration range of 0.02 ∼ 0.5 mL/mL and an LOD of 0.005 mL/mL. Subsequent application of the validated method to two real mortality cases due to N 2 O intoxication provided reference values for blood concentrations in forensic cases. Other biological specimens (gaseous samples and tissues) of the deceased were also analyzed to demonstrate that the deaths were caused by asphyxia due to the inhalation of N 2 O., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Limited prospective data exist about the impact of stimulant therapy for attention-deficit hyperactivity disorder (ADHD) during adolescence on the risk for later prescription drug misuse (PDM; i.e., of benzodiazepines, opioids, and stimulants)., Methods: National longitudinal multicohort panels (baseline cohort years 2005-2017) of U.S. 12th grade students (N=11,066; ages 17 and 18 years) from the Monitoring the Future study were surveyed via self-administered questionnaires and followed up biennially during young adulthood (ages 19-24). A multivariable analysis was used to assess whether adolescents' lifetime history of stimulant therapy for ADHD was associated with subsequent PDM., Results: Overall, 9.9% of adolescents reported lifetime stimulant therapy for ADHD at ages 17 and 18. No significant differences were found in the adjusted odds of later incidence or prevalence of past-year PDM during young adulthood between adolescents with lifetime stimulant therapy and adolescents with no stimulant therapy. Over the 5-year follow-up, past-year PDM during young adulthood was most prevalent among adolescents who reported both stimulant therapy and prescription stimulant misuse (53.1%) and those who reported prescription stimulant misuse only (51.5%). Compared with adolescents in a control group without lifetime stimulant therapy or misuse, adolescents reporting prescription stimulant misuse had significantly higher adjusted odds of later incidence and prevalence of PDM during young adulthood., Conclusions: Adolescents' stimulant therapy for ADHD was not significantly associated with increased risk for later PDM during young adulthood. In contrast, adolescents' misuse of prescription stimulants strongly predicted later PDM. Monitoring adolescents for prescription stimulant misuse may help identify and mitigate the risk for future PDM., Competing Interests: Dr. Wilens reports consultant work for 3D Therapeutics; receiving book royalties from Cambridge University Press, Elsevier, and Guilford Press; having a licensing agreement with 3D Therapeutics and Ironshore; and serving as a clinical consultant to Bay Cove Human Services, Gavin House, Massachusetts General Hospital, Major and Minor League Baseball, and the National Football League. The other authors report no financial relationships with commercial interests.

Background and Aims: Whether alcohol-related DNA methylation has a causal effect on psychiatric disorders has not been investigated. Furthermore, a comprehensive investigation into the causal relationship and underlying mechanisms linking alcohol consumption and psychiatric disorders has been lacking. This study aimed to evaluate the causal effect of general alcohol intake and pathological drinking behaviors on psychiatric disorders, alcohol-associated DNA methylation on gene expression and psychiatric disorders, and gene expression on psychiatric disorders., Design: Two-sample design Mendelian randomization (MR) analysis. Various sensitivity and validation analyses, including colocalization analysis, were conducted to test the robustness of the results., Setting: Genome-wide association study (GWAS) data mainly from GWAS and Sequencing Consortium of Alcohol and Nicotine use (GSCAN), Genetics of DNA Methylation Consortium (GoDMC) and Psychiatric Genomics Consortium (PGC) with European ancestry., Participants: The GWAS summary data on general alcohol intake (drinks per week, n = 941 280), pathological drinking behaviors (including alcohol use disorder [AUD, n = 313 959] and problematic alcohol use [PAU, n = 435 563]) and psychiatric disorders (including schizophrenia, major depressive disorder and bipolar disorder, n = 51 710-500 199) were included. Alcohol-related DNA methylation CpG sites (n = 9643) and mQTL data from blood (n = 27 750) and brain (n = 1160), BrainMeta v2 and GTEx V8 eQTL summary data (n = 73-2865) were also included., Measurements: Genetic variants were selected as instrumental variables for exposures, including drinks per week, AUD, PAU, alcohol-related DNA methylation CpG sites (mQTL) and genes selected (eQTL)., Findings: Pathological drinking behaviors were associated with an increased risk of psychiatric disorders after removing outliers or controlling for alcohol consumption. MR analysis identified 10 alcohol-related CpG sites with colocalization evidence that were causally associated with psychiatric disorders (P = 1.65 × 10 -4 -7.52 × 10 -22 ). Furthermore, the expression of genes (RERE, PTK6, GATAD2B, COG8, PDF and GAS5) mapped to these CpG sites in the brain, led by the cortex, were significantly associated with psychiatric disorders (P = 1.19 × 10 -2 -3.51 × 10 -7 )., Conclusions: Pathological drinking behavior and alcohol-related DNA methylation appear to have a causal effect on psychiatric disorders. The expression of genes regulated by the alcohol-related DNA methylation sites may underpin this association., (© 2024 Society for the Study of Addiction.)

Background: The availability and use of broadband internet play an increasingly important role in health care and public health., Objective: This study examined the associations between broadband internet availability and use with drug overdose deaths in the United States., Methods: We linked 2019 county-level drug overdose death data in restricted-access multiple causes of death files from the National Vital Statistics System at the US Centers for Disease Control and Prevention with the 2019 county-level broadband internet rollout data from the Federal Communications Commission and the 2019 county-level broadband usage data available from Microsoft's Airband Initiative. Cross-sectional analysis was performed with the fixed-effects regression method to assess the association of broadband internet availability and usage with opioid overdose deaths. Our model also controlled for county-level socioeconomic characteristics and county-level health policy variables., Results: Overall, a 1% increase in broadband internet use was linked with a 1.2% increase in overall drug overdose deaths. No significant association was observed for broadband internet availability. Although similar positive associations were found for both male and female populations, the association varied across different age subgroups. The positive association on overall drug overdose deaths was the greatest among Hispanic and Non-Hispanic White populations., Conclusions: Broadband internet use was positively associated with increased drug overdose deaths among the overall US population and some subpopulations, even after controlling for broadband availability, sociodemographic characteristics, unemployment, and median household income., (©Ioannis Karakis, Genti Kostandini, Konstantinos Tsamakis, Velma Zahirovic-Herbert. Originally published in the Online Journal of Public Health Informatics (https://ojphi.jmir.org/), 26.06.2024.)

Background: Mental health disparities have been documented among lesbian, gay, and bisexual (LGB) adults in the United States. Substance use disorders and suicidal ideation have been identified as important health concerns for this population. However, the interrelationships among these factors are not well understood., Objective: This study aims to investigate the interrelationships among mental health, substance use disorders, and suicidal ideation among LGB adults in the United States using a population-based statewide survey., Methods: Our study was an observational cross-sectional analysis, and the data for this study were collected from a sample of LGB adults who participated in the statewide survey. The survey collected information on mental health, substance use disorders, and suicidal ideation using validated measures. Descriptive statistics and inferential data analysis were conducted to explore the interrelationships among these factors., Results: The results showed that LGB adults who reported higher levels of depression and drug abuse and dependence also reported higher levels of suicidal tendency and mental illness. Inferential data analysis using χ 2 tests revealed significant differences in depression score (χ 2 =458.241; P<.001), drug abuse and dependence score (χ 2 =458.241; P<.001), drug abuse and dependence score (χ 2 2 =363.722; P<.001) among the 3 sexual identity groups. Inferential data analysis showed significant associations between sexual identity and mental health outcomes, with bisexual individuals reporting the highest levels of depression, drug abuse and dependence, suicidal tendency, and mental illness.2 2 =67.795; P<.001), and mental illness score (χ 2 2 =363.722; P<.001) among the 3 sexual identity groups. Inferential data analysis showed significant associations between sexual identity and mental health outcomes, with bisexual individuals reporting the highest levels of depression, drug abuse and dependence, suicidal tendency, and mental illness., Conclusions: This study provides important insights into the interrelationships among mental health, substance use disorders, and suicidal ideation among LGB adults in the United States. The findings underscore the need for targeted interventions and research aimed at addressing the mental health needs of sexual minority populations. Future research should aim to better understand the underlying mechanisms driving these disparities and develop culturally sensitive and tailored interventions that meet the unique needs of LGB individuals. Reducing stigma and discrimination against sexual minority populations is also crucial to improving their mental health outcomes., (©Alex Siu Wing Chan, Hon Lon Tam, Florence Kwai Ching Wong, Gordon Wong, Lok Man Leung, Jacqueline Mei Chi Ho, Patrick Ming Kuen Tang, Elsie Yan. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 25.06.2024.)

Purpose: Investigate if the type of substance use disorder (SUD) in adolescence predicts SUDs in adulthood and examine sex and racial/ethnic differences in the persistence of SUDs., Methods: Data are from the Northwestern Juvenile Project, a 15-year longitudinal study of 1829 youth randomly sampled from detention in Chicago, IL (1995-1998). Interviewers assessed SUDs using structured diagnostic interviews., Results: Compared with females without an SUD at detention, females with cannabis alone, comorbid alcohol and cannabis, or SUDs other than alcohol and cannabis at detention had higher odds of having an SUD 5 years later (25%, 32%, and 36% vs. 15%, adjusted odds ratio [AOR] = 1.94, 95% confidence interval [CI] 1.11-3.40; AOR = 2.76, 95% CI 1.58-4.83; AOR = 3.46, 95% CI 1.56-7.66, respectively). Males and females with SUDs other than alcohol and cannabis at detention had greater odds of having an SUD 15 years later, compared with those without an SUD at detention (males: 36% vs. 14%, AOR = 2.98, 95% CI 1.14-7.83; females: 29% vs. 8%, AOR = 4.77, 95% CI 1.85-12.30). Among youth with an SUD at detention, males were more likely than females to have an SUD 15 years later (AOR = 1.84, 95% CI 1.03-3.29); non-Hispanic White and Hispanic males were more likely to persist than Black males (AOR = 3.32, 95% CI 1.50-7.35; AOR = 2.32, 95% CI 1.04-5.18, respectively)., Discussion: The type of SUD during adolescence matters. Youth with SUDs such as cocaine and opioids fared the worst. Healthcare providers must collaborate with correctional officials to increase service provision., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Overdose Fatality Review (OFR) is an important public health tool for shaping overdose prevention strategies in communities. However, OFR teams review only a few cases at a time, which typically represent a small fraction of the total fatalities in their jurisdiction. Such limited review could result in a partial understanding of local overdose patterns, leading to policy recommendations that do not fully address the broader community needs., Objective: This study explored the potential to enhance conventional OFRs with a data dashboard, incorporating visualizations of touchpoints-events that precede overdoses-to highlight prevention opportunities., Methods: We conducted 2 focus groups and a survey of OFR experts to characterize their information needs and design a real-time dashboard that tracks and measures decedents' past interactions with services in Indiana. Experts (N=27) were engaged, yielding insights on essential data features to incorporate and providing feedback to guide the development of visualizations., Results: The findings highlighted the importance of showing decedents' interactions with health services (emergency medical services) and the justice system (incarcerations). Emphasis was also placed on maintaining decedent anonymity, particularly in small communities, and the need for training OFR members in data interpretation. The developed dashboard summarizes key touchpoint metrics, including prevalence, interaction frequency, and time intervals between touchpoints and overdoses, with data viewable at the county and state levels. In an initial evaluation, the dashboard was well received for its comprehensive data coverage and its potential for enhancing OFR recommendations and case selection., Conclusions: The Indiana touchpoints dashboard is the first to display real-time visualizations that link administrative and overdose mortality data across the state. This resource equips local health officials and OFRs with timely, quantitative, and spatiotemporal insights into overdose risk factors in their communities, facilitating data-driven interventions and policy changes. However, fully integrating the dashboard into OFR practices will likely require training teams in data interpretation and decision-making., (©Amey Salvi, Logan A Gillenwater, Brandon P Cockrum, Sarah E Wiehe, Kaitlyn Christian, John Cayton, Timothy Bailey, Katherine Schwartz, Allyson L Dir, Bradley Ray, Matthew C Aalsma, Khairi Reda. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 11.06.2024.)

Olanzapine (OLZ), a second-generation antipsychotic drug, is effective in the treatment of acute psychosis, schizophrenia, agitation, bipolar mania, and other psychiatric problems. Antipsychotics are prescribed drugs, which lead the drug abuser to illegal methods of access. This behavior also demonstrates the association of OLZ with criminal involvement, commonly observed at forensic crime scenes. The acute toxicity and even death resulting from OLZ exposure have been highlighted in numerous studies. Therefore, developing analytical techniques to detect OLZ is essential for forensic toxicology. This study aimed to develop a specific and reliable LC-MS/MS method for OLZ detection and quantification in hair samples. The method was validated in terms of selectivity, linearity, limit of detection (LOD), limit of quantification (LOQ), trueness, precision, and uncertainty. The range of linearity was between 0.1-100 ng/mg, with LOD and LOQ values established at 0.036 ng/mg and 0.1 ng/mg, respectively. All validation results are within acceptable parameters. The validated method has been applied to authentic hair samples. The variation of OLZ concentrations in 12 hair segments (2 from Case 1 and 10 from Case 2) from two drug-positive patients, ranging from 0.131 to 0.460 ng/mg, is presented in this study. Although several studies have been conducted to determine OLZ in hair samples using segmental analysis via hair solubilization, this study is the first to determine OLZ in hair samples after "digestion" with comparative parameters prior to chromatographic analysis., (© 2024 The Author(s). Drug Testing and Analysis published by John Wiley & Sons Ltd.)

Misuse of prescription opioid drugs is the leading cause of the opioid crisis and overdose-related death. Abuse deterrent formulations (ADFs) have been developed to discourage attempts to tamper with the formulation and alter the ingestion methods. However, abusers develop complex extraction strategies to circumvent the ADF technologies. For comprehensive deterrence of drug abuse, we develop tannic acid nanoparticles (NPs) that protect encapsulated opioids from solvent extraction and thermal challenge (crisping), complementing the existing formulation strategy to deter injection abuse. Here, we develop a hybrid ADF tablet (NP-Tab), consisting of iron-crosslinked tannic acid NPs encapsulating thebaine (model opioid compound), xanthan gum, and chitosan (gel-forming polymers), and evaluate its performance in common abuse conditions. NP-Tab tampered by crushing and suspended in aqueous solvents forms an instantaneous gel, which is difficult to pull or push through a 21-gauge needle. NPs insulate the drug from organic solvents, deterring solvent extraction. NPs also promote thermal destruction of the drug to make crisping less rewarding. However, NP-Tab releases thebaine in the simulated gastric fluid without delay, suggesting that its analgesic effect may be unaffected if consumed orally as prescribed. These results demonstrate that NP-Tab can provide comprehensive drug abuse deterrence, resisting aqueous/organic solvent extraction, injection, and crisping, while retaining its therapeutic effect upon regular usage., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The authors reviewed the literature on finance-based interventions used to improve clinical and psychosocial outcomes among adults experiencing mental disorders, substance use disorders, or both., Methods: A systematic review of the peer-reviewed literature, published from 1900 to 2022, was conducted. Only studies with participants with a mental disorder or a substance use disorder, a structured finance-based intervention or program, a quantitative dependent variable in a behavioral health outcomes domain, and a defined research design were included. Studies were rated with a quality assessment tool, and overall evidence (levels I-VII) for the outcomes was rated., Results: In total, 544 articles were identified, screened for eligibility, and reduced to 55 articles. These articles were rated by two independent raters, and 18 articles were ultimately included. Of these 18 articles, four reported findings of randomized controlled trials (RCTs), one conducted a secondary analysis of an RCT, and the remaining articles were observational studies. The most studied intervention was representative payeeship, which reduced substance use and enhanced money management, showing the strongest evidence for improving outcomes among adults with behavioral health conditions. Weaker evidence suggested that financial education and assistance interventions could improve health care utilization and other psychosocial outcomes among individuals with mental or substance use disorders., Conclusions: Level II-V evidence indicates that finance-based interventions can improve outcomes among adults experiencing behavioral health conditions. Further research is needed to assess the impact of interventions beyond representative payee programs on objectively measured outcomes., Competing Interests: The authors report no financial relationships with commercial interests.

β-Phenyl-γ-aminobutyric acid (phenibut) is an analog of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) that was first synthesized in Russia in the early 1960s. It is marketed as a nootropic (smart drug) to improve cognitive performance, and to treat generalized and social anxiety, insomnia, and alcohol withdrawal. The use of phenibut is legal in the USA and it is widely available online without a prescription. Increased public awareness of phenibut has led to a growing number of reports of acute intoxication and withdrawal. In this review, we describe the pharmacology of phenibut, the presentation and management of acute intoxication, and regulatory issues, placing particular emphasis on the treatment of acute withdrawal, for which there are no comparative studies. Among 29 cases of phenibut withdrawal, patients were successfully treated with baclofen, benzodiazepines, and phenobarbital, as individual agents or in various combinations. Ancillary medications included antipsychotics, dexmedetomidine, gabapentin, and pregabalin. After stabilization, a number of patients did well on baclofen tapers, whereas others were weaned off benzodiazepines or phenobarbital. Phenobarbital may be preferred over baclofen, or used as an added agent, in patients at risk for seizures. As long as phenibut remains legal, cases of phenibut intoxication and withdrawal are likely to increase. As urine or plasma drug screening for phenibut is not widely available, it is vital that clinicians obtain a detailed medication history in patients presenting to the emergency department with nonspecific symptoms that may represent phenibut intoxication or withdrawal. Further, clinicians may wish to consult an addiction specialist or toxicologist in these situations., (© 2024, The American College of Clinical Pharmacology.)

Background: There is evidence linking use of controlled substances with perpetration of interpersonal violence. While the United States constitution protects the right to own a firearm, federal law prohibits firearm purchase and possession by persons believed to be at high risk for violence, including those who use controlled substances unlawfully., Methods: We report here the results of a 13-year prospective observational study on the risk of violent crime associated with a history of criminal drug charges in a cohort of 79,678 legal purchasers of handguns in California in 2001. The main outcomes were post-purchase charges for any violent crime, violent Crime Index crimes (murder, rape, robbery, aggravated assault), and firearm-related violent crimes. The main exposure of interest was a history of pre-purchase charge(s) for drug-related offenses; we examined as a secondary exposure a history of marijuana-related charges. We estimated adjusted hazard ratios (aHR) with 95 % confidence intervals (CI) using Cox proportional hazards multiple events models., Results: We found that legal handgun purchasers in California with a history of drug-related charges, even those with marijuana charges only, had triple the risk of a post-purchase violent crime charge compared to purchasers with no criminal charges (drug charges only: aHR=2.9, 95 % CI 2.2-3.8; marijuana charges only: aHR=3.3, 95 % CI 1.8-6.0). In addition, a criminal history of drug charges only vs. no criminal history was associated with increased risk of one or more violent crime charges after the first post-purchase arrest event (aHR=1.6, 95 % CI 1.2-2.3)., Conclusion: It is incumbent on researchers and policy makers to understand the nature and causes of this risk in order to take effective steps towards mitigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)