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Harm Reduction Journal May 2024Mortality related to opioid overdose in the U.S. has risen sharply in the past decade. In California, opioid overdose death rates more than tripled from 2018 to 2021,...
BACKGROUND
Mortality related to opioid overdose in the U.S. has risen sharply in the past decade. In California, opioid overdose death rates more than tripled from 2018 to 2021, and deaths from synthetic opioids such as fentanyl increased more than seven times in those three years alone. Heightened attention to this crisis has attracted funding and programming opportunities for prevention and harm reduction interventions. Drug checking services offer people who use drugs the opportunity to test the chemical content of their own supply, but are not widely used in North America. We report on qualitative data from providers and clients of harm reduction and drug checking services, to explore how these services are used, experienced, and considered.
METHODS
We conducted in-depth semi-structured key informant interviews across two samples of drug checking stakeholders: "clients" (individuals who use drugs and receive harm reduction services) and "providers" (subject matter experts and those providing clinical and harm reduction services to people who use drugs). Provider interviews were conducted via Zoom from June-November, 2022. Client interviews were conducted in person in San Francisco over a one-week period in November 2022. Data were analyzed following the tenets of thematic analysis.
RESULTS
We found that the value of drug checking includes but extends well beyond overdose prevention. Participants discussed ways that drug checking can fill a regulatory vacuum, serve as a tool of informal market regulation at the community level, and empower public health surveillance systems and clinical response. We present our findings within three key themes: (1) the role of drug checking in overdose prevention; (2) benefits to the overall agency, health, and wellbeing of people who use drugs; and (3) impacts of drug checking services at the community and systems levels.
CONCLUSION
This study contributes to growing evidence of the effectiveness of drug checking services in mitigating risks associated with substance use, including overdose, through enabling people who use and sell drugs to test their own supply. It further contributes to discussions around the utility of drug checking and harm reduction, in order to inform legislation and funding allocation.
Topics: Humans; Harm Reduction; Female; Qualitative Research; Male; Opiate Overdose; Adult; San Francisco; Drug Users; Opioid-Related Disorders; Drug Overdose
PubMed: 38734643
DOI: 10.1186/s12954-024-01014-w -
Molecules (Basel, Switzerland) Apr 2024Cisplatin is a potent compound in anti-tumor chemotherapy; however, its clinical utility is hampered by dose-limiting nephrotoxicity. This study investigated whether...
Unraveling the Nephroprotective Potential of Papaverine against Cisplatin Toxicity through Mitigating Oxidative Stress and Inflammation: Insights from In Silico, In Vitro, and In Vivo Investigations.
Cisplatin is a potent compound in anti-tumor chemotherapy; however, its clinical utility is hampered by dose-limiting nephrotoxicity. This study investigated whether papaverine could mitigate cisplatin-induced kidney damage while preserving its chemotherapeutic efficacy. Integrative bioinformatics analysis predicted papaverine modulation of the mechanistic pathways related to cisplatin renal toxicity; notably, mitogen-activated protein kinase 1 (MAPK1) signaling. We validated protective effects in normal kidney cells without interfering with cisplatin cytotoxicity on a cancer cell line. Concurrent in vivo administration of papaverine alongside cisplatin in rats prevented elevations in nephrotoxicity markers, including serum creatinine, blood urea nitrogen, and renal oxidative stress markers (malondialdehyde, inducible nitric oxide synthase (iNOS), and pro-inflammatory cytokines), as tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein 1 (MCP-1), and interleukin-6 (IL-6). Papaverine also reduced apoptosis markers such as Bcl2 and Bcl-2-associated X protein (Bax) and kidney injury molecule-1 (KIM-1), and histological damage. In addition, it upregulates antioxidant enzymes like catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) while boosting anti-inflammatory signaling interleukin-10 (IL-10). These effects were underlined by the ability of Papaverine to downregulate MAPK-1 expression. Overall, these findings show papaverine could protect against cisplatin kidney damage without reducing its cytotoxic activity. Further research would allow the transition of these results to clinical practice.
Topics: Cisplatin; Papaverine; Oxidative Stress; Animals; Rats; Inflammation; Humans; Kidney; Male; Apoptosis; Antineoplastic Agents; Protective Agents; Antioxidants; Cytokines; Computer Simulation; Biomarkers
PubMed: 38731418
DOI: 10.3390/molecules29091927 -
Molecules (Basel, Switzerland) Apr 2024The synthesis of stereochemically pure oximes, amines, saturated and unsaturated cyanomethyl compounds, and methylaminomethyl compounds at the C9 position in...
The synthesis of stereochemically pure oximes, amines, saturated and unsaturated cyanomethyl compounds, and methylaminomethyl compounds at the C9 position in 3-hydroxy--phenethyl-5-phenylmorphans provided μ-opioid receptor (MOR) agonists with varied efficacy and potency. One of the most interesting compounds, (2-((1,5,9)-5-(3-hydroxyphenyl)-2-phenethyl-2-azabicyclo[3.3.1]nonan-9-yl)acetonitrile), was found to be a potent partial MOR agonist (EC = 2.5 nM, %E = 89.6%), as determined in the forskolin-induced cAMP accumulation assay. Others ranged in potency and efficacy at the MOR, from nanomolar potency with a C9 cyanomethyl compound (EC = 0.85 nM) to its totally inactive diastereomer, and three compounds exhibited weak MOR antagonist activity (the primary amine , the secondary amine , and the cyanomethyl compound ). Many of the compounds were fully efficacious; their efficacy and potency were affected by both the stereochemistry of the molecule and the specific C9 substituent. Most of the MOR agonists were selective in their receptor interactions, and only a few had δ-opioid receptor (DOR) or κ-opioid receptor (KOR) agonist activity. Only one compound, a C9-methylaminomethyl-substituted phenylmorphan, was moderately potent and fully efficacious as a KOR agonist (KOR EC = 18 nM (% E = 103%)).
Topics: Oximes; Stereoisomerism; Structure-Activity Relationship; Amines; Receptors, Opioid, mu; Humans; Animals; Molecular Structure; CHO Cells; Morphinans
PubMed: 38731416
DOI: 10.3390/molecules29091926 -
Journal of Pharmaceutical and... Aug 2024New psychoactive substances (NPS) are uncontrolled analogues of existing drugs or newly synthesized chemicals that exhibit psychopharmacological effects. Due to their...
New psychoactive substances (NPS) are uncontrolled analogues of existing drugs or newly synthesized chemicals that exhibit psychopharmacological effects. Due to their diverse nature, composition, and increasing prevalence, they present significant challenges to the healthcare system and drug control policies. In response, healthcare system laboratories have developed analytical methods to detect NPS in biological samples. As a Regional Reference Centre, the Sicilian CRQ Laboratory (Regional Laboratory for Quality Control) developed and conducted an External Quality Assessment (EQA) study to assess, in collaboration with the Istituto Superiore di Sanità (ISS), the ability of different Italian laboratories to identify NPS and traditional drugs of abuse (DOA) in biological matrices. Two blood samples were spiked with substances from various drug classes, including synthetic cannabinoids, cathinones, synthetic opiates, and benzodiazepines, at concentrations ranging from 2 to 10 ng/mL. The blood samples were freeze-dried to ensure the stability of DOA and NPS. Twenty-two laboratories from the Italian healthcare system participated in this assessment. The information provided by the laboratories during the registration in an in-house platform included a general description of the laboratory, analytical technique, and the chosen panels of analytes. The same platform was employed to collect and statistically analyze the data and record laboratory feedback and comments. The evaluation of the results revealed that the participating laboratories employed three different techniques for analyzing the samples: GC-MS, LC-MS, and immunoenzymatic methods. Approximately 90 % of the laboratories utilized LC-MS techniques. Around 40 % of false negative results were obtained, with the worst results in the identification of 5-chloro AB PINACA. The results showed that laboratories that used LC-MS methods obtained better specificity and sensitivity compared to the laboratories using other techniques. The results obtained from this first assessment underscore the importance of external quality control schemes in identifying the most effective analytical techniques for detecting trace molecules in biological matrices. Since the judicial authorities have not yet established cut-off values for NPS, this EQA will enable participating laboratories to share their analytical methods and expertise, aiming to establish common criteria for NPS identification.
Topics: Psychotropic Drugs; Humans; Substance Abuse Detection; Italy; Quality Control; Laboratories; Illicit Drugs
PubMed: 38728951
DOI: 10.1016/j.jpba.2024.116175 -
Annals of Cardiac Anaesthesia Jan 2024Cardiac surgeries often result in significant postoperative pain, leading to considerable use of opioids for pain management. However, excessive opioid use can lead to... (Meta-Analysis)
Meta-Analysis
Cardiac surgeries often result in significant postoperative pain, leading to considerable use of opioids for pain management. However, excessive opioid use can lead to undesirable side effects and chronic opioid use. This systematic review and meta-analysis aimed to evaluate whether preoperative intrathecal morphine could reduce postoperative opioid consumption in patients undergoing cardiac surgery requiring sternotomy. We conducted a systematic search of Cochrane, EMBASE, and MEDLINE databases from inception to May 2022 for randomized controlled trials that evaluated the use of intrathecal morphine in patients undergoing cardiac surgery. Studies that evaluated intrathecal administration of other opioids or combinations of medications were excluded. The primary outcome was postoperative morphine consumption at 24 h. Secondary outcomes included time to extubation and hospital length of stay. The final analysis included ten randomized controlled trials, with a total of 402 patients. The results showed that postoperative morphine consumption at 24 h was significantly lower in the intervention group (standardized mean difference -1.43 [-2.12, -0.74], 95% CI, P < 0.0001). There were no significant differences in time to extubation and hospital length of stay. Our meta-analysis concluded that preoperative intrathecal morphine is associated with lower postoperative morphine consumption at 24 h following cardiac surgeries, without prolonging the time to extubation. The use of preoperative intrathecal morphine can be considered part of a multimodal analgesic and opioid-sparing strategy in patients undergoing cardiac surgery.
Topics: Humans; Cardiac Surgical Procedures; Morphine; Injections, Spinal; Analgesics, Opioid; Randomized Controlled Trials as Topic; Pain, Postoperative; Length of Stay
PubMed: 38722114
DOI: 10.4103/aca.aca_48_23 -
Healthcare Policy = Politiques de Sante Feb 2024Opioid agonist therapy (OAT) is a key element in the response to opioid-related harms in Canada. In May 2018, Health Canada rescinded the requirement for obtaining a...
Opioid agonist therapy (OAT) is a key element in the response to opioid-related harms in Canada. In May 2018, Health Canada rescinded the requirement for obtaining a federal exemption for methadone prescribing. This comparative analysis examined provincial OAT policies and policy changes in response to this federal policy change. Policies and changes were regionalized; despite having lower rates of opioid-related harms, eastern provinces had looser regulatory regimes compared with western provinces, which became even looser after the federal policy change. Diverse knowledge and policy networks need to be fostered to bridge this east-west divide in substance use care policy.
Topics: Humans; Methadone; Canada; Opioid-Related Disorders; Health Policy; Opiate Substitution Treatment; Analgesics, Opioid
PubMed: 38721734
DOI: 10.12927/hcpol.2024.27228 -
Psychopharmacology Jul 2024Medications are urgently needed to treat symptoms of drug withdrawal and mitigate dysphoria and psychiatric comorbidities that drive opioid abuse and relapse. ITI-333 is...
RATIONALE
Medications are urgently needed to treat symptoms of drug withdrawal and mitigate dysphoria and psychiatric comorbidities that drive opioid abuse and relapse. ITI-333 is a novel molecule in development for treatment of substance use disorders, psychiatric comorbidities, and pain.
OBJECTIVE
Characterize the preclinical profile of ITI-333 using pharmacological, behavioral, and physiological assays.
METHODS
Cell-based assays were used to measure receptor binding and intrinsic efficacy of ITI-333; animal models were employed to assess effects on opioid reinstatement, precipitated oxycodone withdrawal, and drug abuse liability.
RESULTS
In vitro, ITI-333 is a potent 5-HT receptor antagonist (K = 8 nM) and a biased, partial agonist at μ-opioid (MOP) receptors (K = 11 nM; lacking β-arrestin agonism) with lesser antagonist activity at adrenergic α (K = 28 nM) and dopamine D (K = 50 nM) receptors. In vivo, ITI-333 blocks 5-HT receptor-mediated head twitch and MOP receptor-mediated effects on motor hyperactivity in mice. ITI-333 alone is a naloxone-sensitive analgesic (mice) which suppresses somatic signs of naloxone-precipitated oxycodone withdrawal (mice) and heroin cue-induced reinstatement responding without apparent tolerance or physical dependence after chronic dosing (rats). ITI-333 did not acutely impair gastrointestinal or pulmonary function (rats) and was not intravenously self-administered by heroin-maintained rats or rhesus monkeys.
CONCLUSIONS
ITI-333 acts as a potent 5-HT receptor antagonist, as well a biased MOP receptor partial agonist with low intrinsic efficacy. ITI-333 mitigates opioid withdrawal/reinstatement, supporting its potential utility as a treatment for OUD.
Topics: Animals; Mice; Male; Substance Withdrawal Syndrome; Rats; Humans; Rats, Sprague-Dawley; Receptors, Opioid, mu; Serotonin 5-HT2 Receptor Antagonists; Substance-Related Disorders; Opioid-Related Disorders; Dose-Response Relationship, Drug; Oxycodone; Analgesics, Opioid; Self Administration; Cricetulus; CHO Cells
PubMed: 38710856
DOI: 10.1007/s00213-024-06578-w -
Journal of the American Society For... Jun 2024Cannabinoids and opioids are the most prominently used drugs in the world, with fentanyl being the main cause of drug overdose-related deaths. Monitoring drug use in...
Cannabinoids and opioids are the most prominently used drugs in the world, with fentanyl being the main cause of drug overdose-related deaths. Monitoring drug use in groups as well as in individuals is an important forensic concern. Analytical methods, such as mass spectrometry (MS), have been found most useful for the identification of drug abuse on a small and large scale. Pulsed fiber laser 2D galvoscanner laser-generated nanomaterial (PFL 2D GS LGN) was obtained from monoisotopic silver-109. Nanomaterial was used for laser desorption/ionization mass spectrometry of selected illicit drug standards with standard high-resolution reflectron-based time-of-flight MALDI apparatus. Δ-THC, 11-OH-THC, 11-COOH-THC, fentanyl, codeine, 6-monoacetylmorphine (6-MAM), heroin, tramadol, and methadone were chosen as test compounds. Illicit drugs were tested in a concentration range from 100 μg/mL to 10 pg/mL, equating to 50 μg to 50 fg per measurement spot. For all analyzed compounds, identification and quantification by silver-109-assisted laser desorption/ionization (LDI) MS was possible, with uncommon [M + Ag] and [M - H] ions present for certain structures. The results of the quantitative analysis of drugs using silver-109 PFL 2D GS LGN for LDI MS are presented. Laser-generated NPs are proven to be useful for the analysis of selected drugs, with exceptionally good results for fentanyl monitoring in a broad range of concentrations.
Topics: Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Illicit Drugs; Silver; Metal Nanoparticles; Lasers; Substance Abuse Detection; Humans; Fentanyl; Morphine Derivatives; Cannabinoids
PubMed: 38709655
DOI: 10.1021/jasms.3c00454 -
Journal of Substance Use and Addiction... Aug 2024Medications for opioid use disorder (MOUD) including methadone (MMT), buprenorphine (BUP), and naltrexone (NTX) are safe and effective. However, there are significant...
INTRODUCTION
Medications for opioid use disorder (MOUD) including methadone (MMT), buprenorphine (BUP), and naltrexone (NTX) are safe and effective. However, there are significant negative perceptions surrounding MOUD, creating barriers to uptake. While research on MOUD stigma has largely focused on provider and patient experiences, fewer studies have explored MOUD perceptions among the general public. Given that MOUD stigma expressed by social ties surrounding individuals with OUD can influence treatment choices, we assessed MOUD perceptions among U.S. adults to determine how beliefs impacted treatment preference. We further explored how MOUD perceptions may be amplified among racialized groups with histories of experiencing drug-related discrimination.
METHODS
The study collected survey data from a diverse sample of U.S. adults (n = 1508) between October 2020 and January 2021. The survey measured knowledge of MOUD and non-medication treatments, relative agreement with common MOUD perceptions, and treatment preferences. Multinomial logistic regression analysis tested associations with treatment preference, stratified by race/ethnicity.
RESULTS
Descriptive results indicated that across groups, many respondents (66.8 %) had knowledge of MOUD, but believed MOUD was a "substitute" for opioids and had some degree of concern about misuse. Multivariable results showed knowledge of non-medication treatments was positively associated with MOUD preference among White (MMT OR = 3.16, 95 % CI = 1.35-7.39; BUP OR = 2.69, CI = 1.11-6.47), Black (MMT OR = 3.91, CI = 1.58-9.69), and Latino/a (MMT OR = 5.12, CI = 1.99-13.2; BUP OR = 3.85, CI = 1.5-9.87; NTX OR = 4.51, CI = 1.44-14.06) respondents. Among White respondents, we identified positive associations between MOUD experience and buprenorphine preference (OR = 4.33, CI = 1.17-16.06); non-medication treatment experience and preference for buprenorphine (OR = 2.86, CI = 1.03-7.94) and naltrexone (OR = 3.17, CI = 1.08-9.28). Concerns around misuse of methadone were negatively associated with methadone preference among White (OR = 0.65, CI = 0.43-0.98) and Latino/a (OR = 0.49, CI = 0.34-0.7), and concerns around misuse of buprenorphine was negatively associated with preference for MOUD among White (MMT OR = 0.62, CI = 0.39-0.99; BUP OR = 0.48, CI = 0.3-0.77; NTX OR = 0.6, CI = 0.36-0.99) and Latino/a (BUP OR = 0.59, CI = 0.39-0.89) respondents.
CONCLUSIONS
This analysis offers critical insights into treatment perceptions beyond the patient population, finding that negative beliefs around MOUD are common and negatively associated with preferences for medication-based treatment. These findings highlight implications for public support of evidence-based treatment and lay the groundwork for future interventions addressing public stigma toward MOUD.
Topics: Humans; Male; Opioid-Related Disorders; Female; Adult; United States; Methadone; Naltrexone; Buprenorphine; Opiate Substitution Treatment; Middle Aged; Health Knowledge, Attitudes, Practice; Social Stigma; Analgesics, Opioid; Young Adult; Patient Preference; Surveys and Questionnaires; Ethnicity; Narcotic Antagonists
PubMed: 38703949
DOI: 10.1016/j.josat.2024.209361 -
BMJ Open May 2024Opioid overdoses in the USA have increased to unprecedented levels. Administration of the opioid antagonist naloxone can prevent overdoses. (Observational Study)
Observational Study
BACKGROUND
Opioid overdoses in the USA have increased to unprecedented levels. Administration of the opioid antagonist naloxone can prevent overdoses.
OBJECTIVE
This study was conducted to reveal the pharmacoepidemiologic patterns in naloxone prescribing to Medicaid patients from 2018 to 2021 as well as Medicare in 2019.
DESIGN
Observational pharmacoepidemiologic study SETTING: US Medicare and Medicaid naloxone claims INTERVENTION: The Medicaid State Drug Utilisation Data File was utilised to extract information on the number of prescriptions and the amount prescribed of naloxone at a national and state level. The Medicare Provider Utilisation and Payment was also utilised to analyse prescription data from 2019.
OUTCOME MEASURES
States with naloxone prescription rates that were outliers of quartile analysis were noted.
RESULTS
The number of generic naloxone prescriptions per 100 000 Medicaid enrollees decreased by 5.3%, whereas brand naloxone prescriptions increased by 245.1% from 2018 to 2021. There was a 33.1-fold difference in prescriptions between the highest (New Mexico=1809.5) and lowest (South Dakota=54.6) states in 2019. Medicare saw a 30.4-fold difference in prescriptions between the highest (New Mexico) and lowest states (also South Dakota) after correcting per 100 000 enrollees.
CONCLUSIONS
This pronounced increase in the number of naloxone prescriptions to Medicaid patients from 2018 to 2021 indicates a national response to this widespread public health emergency. Further research into the origins of the pronounced state-level disparities is warranted.
Topics: United States; Humans; Medicaid; Naloxone; Medicare; Narcotic Antagonists; Retrospective Studies; Practice Patterns, Physicians'; Drug Prescriptions; Male
PubMed: 38692729
DOI: 10.1136/bmjopen-2023-078592