A scoping review of law enforcement drug seizures and overdose mortality in the United States.

BACKGROUND: Leveraging law enforcement drug seizure data to better respond to the overdose crisis requires an understanding of available evidence and knowledge gaps regarding relationships between drug seizures and overdose mortality. OBJECTIVE: This scoping review summarized peer-reviewed literature on associations between law enforcement drug seizures and drug-related mortality in the United States (US) in the era of illicitly-manufactured fentanyl, comparing study data sources, measures, methodologies, settings, and findings. METHODS: We identified 388 non-duplicate records from three online databases searched on May 23, 2023. After title/abstract and full-text screening by two independent reviewers, 14 studies met the criteria for inclusion. The included studies tested the association between a measure related to law enforcement drug seizures and an overdose mortality outcome in the US and were published in English, in peer-reviewed journals, during or after 2013. RESULTS: Four of 14 studies (29%) included data from the entire US, while the remaining studies focused on an individual state/city/county or a group of states/cities/counties. Synthetic opioid/fentanyl seizures represented the most frequently examined drug seizure category, and overdose deaths overall (involving any drugs) represented the most frequently examined outcome. Most studies used counts/rates of drug seizures, with fewer studies examining dosage/weight, drug combinations, the proportion of drug seizures involving a specific drug, or spatiotemporal distribution. The majority (86%) of studies reported at least one statistically significant positive association between a law enforcement drug seizure measure and an overdose mortality outcome, most consistently for fentanyl-related seizures. Results were relatively less consistent for seizures involving stimulants and other drugs. CONCLUSIONS: Studies in this review provided consistent evidence that fentanyl-related seizure measures are positively associated with overdose mortality outcomes, despite the limitations inherent in drug seizure data, even in the absence of available information regarding seizure weight or dosage.

Drug supply measures and drug overdose mortality in the era of fentanyl and stimulants.

Background: Illicitly-manufactured fentanyl and stimulants have replaced prescription opioids as the primary contributors to fatal overdoses in the United States (US), yet the street supply of these substances is challenging to quantify. Building on the foundation of prior research on law enforcement drug reports, the present study compares publicly available forensic laboratory drug report measures to identify which measures account for the most variation in drug overdose mortality between states, within states over time, and in various demographic groups. Methods: Drug reports from the National Forensic Laboratory Information System and drug overdose mortality rates from the Centers for Disease Control and Prevention were examined for all US states and the District of Columbia, 2013-2021 (459 state-years). State- and year- fixed effects models regressed drug overdose mortality rates (in the overall population and subpopulations by sex, age, and race/ethnicity) on various drug report measures, including rates per population and proportional shares of drug reports positive for fentanyl/fentanyl-related compounds, heroin, cocaine, methamphetamine, and xylazine. Results: For drug overdose death rates in the overall population and nearly all subpopulations examined by sex, race/ethnicity, and age, the model including all drug report proportional measures represented the best-performing model (as identified via the lowest Akaike Information Criterion and highest within R-squared value), followed by the model including only the fentanyl/fentanyl-related compounds proportion. Conclusions: Findings support the utility of publicly available drug report composition measures, particularly the proportion of fentanyl/fentanyl-related compounds, as predictors of drug overdose mortality in the US and in various subpopulations.

"It's Also Pushed People to a New Level of Desperation:" COVID-19 Impacts on Experiences of Persons Who Use Illicit Opioids.

The purpose of this qualitative study is to characterize the impacts of the COVID-19 pandemic on drug use experiences among persons who use illicit opioids (PWUO) in Arizona. Between 12/2020 and 05/2021, interviews were conducted via Zoom with 22 PWUO from across Arizona. Participants were recruited through Craigslist and social media ads, referrals by a local harm reduction organization, and other participants. The interviews were transcribed and analyzed using NVivo. Participants were 25-51 years of age, 36% were female, and 55% non-Hispanic White. Most reported past month use of heroin, and/or counterfeit (pressed) non-pharmaceutical fentanyl (NPF) pills. Nearly all reported changes in their drug use during the pandemic. Participants discussed profound negative impacts of social isolation with escalating mental health problems, boredom, and ease of hiding drug use from others, leading to increases in drug use. Loss of daily routines, employment difficulties, and challenges of accessing treatment due to COVID-19 restrictions were also driving factors for increased drug use. The growing availability of NPF pills during the pandemic led many individuals to transition from heroin to more frequent NPF pill use. The results emphasize the need for quality behavioral care services with an increased focus on economic and social support systems.

"They say it's fentanyl, but they honestly look like Perc 30s": Initiation and use of counterfeit fentanyl pills.

BACKGROUND: Worsening of the overdose crisis in the USA has been linked to the continuing proliferation of non-pharmaceutical fentanyl (NPF). The recent wave of NPF spread in the USA has been fueled by an increased presence of counterfeit pills that contain NPF. This qualitative study aims to characterize the motivation and practices of counterfeit NPF pill initiation and use among individuals using illicit opioids in Arizona. METHODS: Between October 2020 and May 2021, semi-structured interviews were conducted with 22 individuals meeting the following eligibility criteria: (1) 18 years or older; (2) residence in Arizona; and (3) use of illicit opioids in the past 30 days and/or opioid use disorder treatment in the past 12 months. Participants were recruited through referrals by a harm reduction organization, craigslist ads, and referrals by other participants. Interviews were conducted virtually via Zoom. Qualitative interviews were transcribed and analyzed thematically using NVivo. RESULTS: Out of 22 participants, 64% were male, and 45% were ethnic minorities. Age ranged between 25 and 51 years old. Participants noted significant recent increases in the availability of counterfeit NPF pills ("blues," "dirty oxys") that were most commonly used by smoking. The majority indicated first trying NPF pills in the past year, and the first use often occurred in situations of reduced access to heroin or pharmaceutical opioids. Participant decisions to switch over to more frequent NPF pill use or to maintain some levels of heroin use were shaped by local drug availability trends and personal experiences with NPF effects. They were also influenced by conflicting views of social acceptability of pharmaceutical-like drugs, perceived harms of NPF in terms of overdose risks and increased difficulty of quitting, and perceived benefits of switching to the non-injection route of opioid administration (e.g., from injecting heroin to smoking NPF pills). CONCLUSION: Our findings highlight the need for the implementation of novel policy, treatment, and harm reduction approaches to address the growing unpredictability of drug supply and NPF pill-specific risks, attitudes, and behaviors.

Tramadol in seized drugs containing non-pharmaceutical fentanyl: Crime lab data from Ohio, USA.

Introduction: Non-pharmaceutical fentanyl and related drugs (NPF) have contributed to increases in drug-related overdose mortality in the U.S. More data are needed to track the shifting composition of fentanyl-containing drug mixtures. The key aims of the study are to characterize the crime lab data from Montgomery County, Ohio on the increased cases of seized drugs containing mixtures of NPF and tramadol. Methods: Crime lab data on seized drugs in Montgomery County, Ohio (2015 - 2020) were analyzed to extract information on cases that tested positive for NPF and tramadol. Descriptive statistics are provided to characterize NPF/tramadol mixtures in terms of the quantity, weight, form of the drug seized (powder, tablet, capsule, residue), and the types of fentanyl analogs and other drugs identified. Results: In December 2017, the first case of NPF/tramadol mixture was identified in the amount of 0.2 g. Sub-sequently, cases containing NPF/tramadol increased significantly to 149 cases in 2018, 102 in 2019, and 134 in 2020. The total yearly amounts of seized NPF/tramadol mixtures increased to 373.27 g in 2018, 2,601.82 g in 2019, and 13,487.62 g in 2020. The majority (72.6%) of the cases were in powder form. There were 15 other drugs identified along with fentanyl with tramadol mixtures, including heroin (38.8%), 5.7% cocaine (5.7%), and methamphetamine (4.9%). Conclusions: The addition of tramadol to NPF may be viewed as a harm mitigation strategy but contributes to the overall unpredictability of the illicit drug supply. According to Ohio legal statutes, identification of schedule IV drugs such as tramadol with fentanyl (schedule II) may provide a reduction in drug-related charges from a felony to a misdemeanor. More research is needed to characterize potential sources of tramadol in NPF-containing drugs.

The effects of acute aerobic and resistance exercise on mTOR signaling and autophagy markers in untrained human skeletal muscle.

PURPOSE: Aerobic (AE) and resistance (RE) exercise elicit unique adaptations in skeletal muscle. The purpose here was to compare the post-exercise response of mTOR signaling and select autophagy markers in skeletal muscle to acute AE and RE. METHODS: In a randomized, cross-over design, six untrained men (27 ± 3 years) completed acute AE (40 min cycling, 70% HRmax) and RE (8 sets, 10 repetitions, 65% 1RM). Muscle biopsies were taken at baseline, and at 1 h and 4 h following each exercise. Western blot analyses were performed to examine total and phosphorylated protein levels. Upstream regulator analyses of skeletal muscle transcriptomics were performed to discern the predicted activation states of mTOR and FOXO3. RESULTS: Compared to AE, acute RE resulted in greater phosphorylation (P < 0.05) of mTORSer2448 at 4 h, S6K1Thr389 at 1 h, and 4E- BP1Thr37/46 during the post-exercise period. However, both AE and RE increased mTORSer2448 and S6K1Thr389 phosphorylation at 4 h (P < 0.05). Upstream regulator analyses revealed the activation state of mTOR was increased for both AE (z score, 2.617) and RE (z score, 2.789). No changes in LC3BI protein were observed following AE or RE (P > 0.05), however, LC3BII protein was decreased after both AE and RE at 1 h and 4 h (P < 0.05). p62 protein content was also decreased at 4 h following AE and RE (P < 0.05). CONCLUSION: Both acute AE and RE stimulate mTOR signaling and similarly impact select markers of autophagy. These findings indicate the early adaptive response of untrained human skeletal muscle to divergent exercise modes is not likely mediated through large differences in mTOR signaling or autophagy.

Chronic doxorubicin administration impacts satellite cell and capillary abundance in a muscle-specific manner.

Anthracycline chemotherapies are effective at reducing disease recurrence and mortality in cancer patients. However, these drugs also contribute to skeletal muscle wasting and dysfunction. The purpose of this study was to assess the impact of chronic doxorubicin (DOX) administration on satellite cell and capillary densities in different skeletal muscles. We hypothesized that DOX would reduce satellite cell and capillary densities of the soleus (SOL) and extensor digitorum longus (EDL) muscles, along with muscle fiber size. Ovariectomized female Sprague-Dawley rats were randomized to receive three bi-weekly intraperitoneal injections of DOX (4 mg∙kg-1 ; cumulative dose 12 mg∙kg-1 ) or vehicle (VEH; saline). Animals were euthanized 5d following the last injection and the SOL and EDL were dissected and prepared for immunohistochemical and RT-qPCR analyses. Relative to VEH, CSA of the SOL and EDL fibers were 26% and 33% smaller, respectively, in DOX (P < 0.05). In the SOL, satellite cell and capillary densities were 39% and 35% lower, respectively, in DOX (P < 0.05), whereas in the EDL satellite cell and capillary densities were unaffected by DOX administration (P > 0.05). Proliferating satellite cells were unaffected by DOX in the SOL (P > 0.05). In the SOL, MYF5 mRNA expression was increased in DOX (P < 0.05), while in the EDL MGF mRNA expression was reduced in DOX (P < 0.05). Chronic DOX administration is associated with reduced fiber size in the SOL and EDL; however, DOX appeared to reduce satellite cell and capillary densities only in the SOL. These findings highlight that therapeutic targets to protect skeletal muscle from DOX may vary across muscles.