Search Results (72)

Background: Tapentadol is an atypical opioid with a dual mechanism as a mu agonist and norepinephrine reuptake inhibitor. This study characterized tapentadol use in the United States (US) using three databases. Methods: Drug distribution data from 2010 to 2020 were extracted from the Drug Enforcement Administration (DEA)’s Automated Reports and Consolidated Orders System (ARCOS), including use per region (mg/person) and business activity (i.e., pharmacy). Tapentadol prescription claims from the Medicare and Medicaid programs for 2010–2020 were also examined. Results: The distributed amount of tapentadol was 3.5 tons in 2020. Distribution was over twice as high in southern (South Atlantic = 29.0 mg/person, East South Central = 28.8) relative to Pacific (12.9) or New England (12.8) states. Tapentadol use decreased nationally between 2012 and 2020 by −53.8%. Adult diabetes prevalence was significantly associated with tapentadol distribution in 2012 (r(50) = +0.44, p < 0.01) and 2020 (r(50) = +0.28, p < 0.05). Tapentadol prescribing to Medicaid patients declined −55.2% from the peak year, 2011, until 2020. Tapentadol prescribed by Nurse Practitioners accounted for over one-sixth (18.0%) of 2019 in Medicare. Conclusions: There has been a substantial decline over the past decade in tapentadol distribution and prescribing. However, the substantial regional differences may warrant further attention by opioid stewardship programs. Full article

Background: “Chemsex” involves the intake of a range of drugs (e.g., synthetic cathinones, gamma-hydroxybutyric acid/gamma-butyrolactone (GHB/GBL), ketamine, methamphetamine, “poppers”, type V phosphodiesterase (PDE) inhibitors, MDMA/ecstasy, cocaine, cannabis, and occasionally a few other molecules as well, to enhance and prolong sexual experiences. This paper aims to provide an overview of the clinical pharmacology of the vast range of drugs that are being used for chemsex with a focus on both the medical and psychopathological disturbances that they can produce. Methods: A narrative literature review was conducted using Pubmed, Scopus, and Web of Science databases. A total of 273 papers published up to January 2025 were screened; articles were selected based on relevance to chemsex/sexualized used behaviour and related substances. Both human and preclinical studies were considered. Results: The use of stimulants is likely related to the need to increase as much as possible both sexual arousal and performance but also to increase social interactions. Furthermore, the empathogenic/entactogenic activities of some MDMA-like “love drugs” facilitate the occurrence of “feeling closer/more intimate” emotional sensations, and GHB/GBL may provide the user with a subjective sensation of disinhibition, hence facilitating condomless meetings with a higher number of random partners. Conversely, ketamine may be used to both enjoy its psychotropic dissociative characteristics and facilitate the potentially painful receptive anal intercourse and/or fisting experiences. Most typically, these drugs are consumed in combination, with polydrug exposure possibly facilitating the occurrence of serotonergic syndrome, seizures, drug–drug pharmacokinetics’ interaction, and sympathomimetic overstimulation. Following these polydrug exposures, a range of psychopathological conditions have at times been reported. These issues may lead to misuse of opiates/opioids, gabapentinoids, and/or antipsychotics. Conclusions: Further actions should aim at reducing the stigma that prevents individuals from accessing necessary healthcare and support services. A multidisciplinary approach that combines medical, psychological, and social support remains key to managing the complex challenges posed by chemsex-related drug use. Full article

Objectives: Mucositis is a debilitating side effect of cancer therapy that adversely affects quality of life, cost of care, and the outcome of cancer therapy. Oral mucositis-related pain may be treated with numerous modalities but often includes opioids. The effects of opiate treatment on painful UM and its overall influence on the burden of illness (BOI) in cancer patients remain unknown. Methods: This study utilized the 2017 United States (US) National Inpatient Sample (NIS) database. The exposure was opioid treatment for chemo-induced ulcerative mucositis (UM), oral mucositis-induced pain, and the main outcomes included in-hospital mortality and BOI, length of hospital stays (LOS), and total hospital charges. Multivariable regression analysis was used to examine the relationship between outcomes and the key independent variable, opioid use, adjusting for propensity scores. Results: In the propensity score-adjusted analysis, UM patients with opioid treatment had 0.51 times lower total charges (95% CI: 0.42–0.76) and 0.67 times shorter LOS (95% CI: 0.51–0.87) than the UM patients without opioid treatment. However, there was no association between opioid treatment and in-hospital mortality. In the sensitivity analysis, the effect estimates were comparable in the propensity score-adjusted analysis, the decile-adjusted model, and the full model with the non-propensity score estimated method. Conclusions: Cancer patients with chemotherapy-induced UM-prescribed opioid analgesics for treating pain are associated with a lower BOI. Opioid pain medications are commonly provided to cancer survivors; estimating the BOI among them is crucial in supportive care research. Full article

The word opium derives from the ancient Greek word ὄπιον (ópion) for the juice of any plant, but today means the air-dried seed capsule latex of Papaver somniferum. Alkaloid chemistry began with the isolation of morphine from crude opium by Friedrich Wilhelm Adam Sertürner in 1804. More than a century later, Hungarian pharmacist János Kabay opened new perspectives for the direct isolation of morphine from dry poppy heads and straw without the labor-intensive harvesting of opium. In 2015, Kabay’s life and achievements obtained official recognition as constituting a «Hungarikum», thereby entering the national repository of matters of unique cultural value. To this day, the study of Papaver alkaloids is a focus of medicinal chemistry, the (perhaps unstated) aspiration of which is to obtain an opioid with lesser abuse potential and side effects, while retaining good analgesic properties. We begin this review with a brief account of opiate biosynthesis, followed by a detailed presentation of semisynthetic opioids, emphasizing the efforts of the Alkaloida Chemical Company, founded in 1927 by János Kabay, and the morphine alkaloid group of the University of Debrecen. Full article

The misuse of opioids and opiates has remained a persistent issue since the 19th century. The recent resurgence of non-fentanyl synthetic opioids, such as U-type opioids and nitazenes, has further exacerbated the ongoing crisis. Identifying these synthetic opioids presents many challenges, including the emergence of new substances, the lack of standards, and the presence of structural isomers. This highlights the need for a robust structural characterisation strategy in forensic laboratories. To address these challenges, we developed a methodology to identify a U-type opioid sample received by Kosmicare from the European Union-funded SCANNER project, which was suspected to be either U-48800 or U-51754. Our innovative approach combined gas chromatography coupled with mass spectrometry (GC-MS), nuclear magnetic resonance spectroscopy (NMR), and molecular dynamics to characterise the questioned sample unequivocally. While the GC-MS analysis suggested a potential match with the mass spectrum of U-51754 and its structural isomer U-48800, NMR analysis confirmed the presence of U-48800 in the sample, which was further validated through molecular dynamics experiments. These experiments provided additional insights, confirming the structural features underlying the obtained NMR profile. The presented methodology offers a valuable solution for cases involving the identification of isomers, which are currently one of the most significant challenges in identifying new psychoactive substances. Full article

Background/Objectives: Using a combination of analgesics allows for the use of lower doses of each, therefore, lowering risk of side effects. The study aims to estimate the bioavailability (pharmacokinetics of enantiomers and metabolites, as well as linearity and sex-related effects) of fixed doses combinations of Ibuprofen/Tramadol via an intravenous (IV) vs. oral route, and it is interesting to bridge the gap of equipotent doses by different routes. Methods: This was a randomized, open-label, crossover, five-period pharmacokinetics clinical trial, in which a single dose of each formulation [four different strengths of Ibuprofen 400 mg/Tramadol HCl (30, 31.5, 33, 37.5 mg), intravenous; Ibuprofen/Tramadol HCl 400 mg/37.5 mg, granules for oral solution], were administered to healthy volunteers. Enantiomers of Ibuprofen, of Tramadol, and of its main active metabolite O-desmethyl-Tramadol (M1) were measured, and pharmacokinetic parameters (maximal concentration (Cmax) and area under the concentration curve (AUC)) were estimated. Given the exploratory nature of the study, the sample size was small to provide sufficient power for comparisons of differences across all subgroups. The study was registered at Spanish register of clinical trials (REec), EudraCT code: 2017-001303-77. Results: Twelve subjects were recruited. Different patterns of rate and amount of the studied analytes are shown for oral and the several strengths of IV drugs tested. Ibuprofen, with an absolute oral bioavailability of 91%, showed an equivalent AUC of oral and IV administration. Tramadol showed an absolute oral bioavailability of 80%. Conclusions: Intravenous administration of Tramadol produces higher bioavailability (Cmax and AUClast) of the parent drug and lower of M1, than oral route. Dose normalized Cmax and AUClast of Tramadol and M1 were into the bioequivalence interval. Upon our pharmacokinetics study results, the intravenous dose of Tramadol should not be reduced when switching from oral dosing. No significant differences attributable to sex, once corrected by weight, were found. Full article

Background/Objectives: Approximately one in five individuals will experience major depressive disorder (MDD), and 30% exhibit resistance to standard antidepressant treatments, resulting in a diagnosis of treatment-resistant depression (TRD). Historically, opium was used effectively to treat depression; however, when other medications were introduced, its use was discontinued due to addiction and other hazards. Recently, kappa opioid receptor (KOR) antagonism has been proposed as a potential mechanism for treating TRD. The main research question is whether commonly used psychotropic medications possess KOR antagonist properties and whether this characteristic could contribute to their efficacy in TRD. Methods: We investigated the antinociceptive effects of many psychotropic medications and their interactions with the opioid system. Mice were tested with a hotplate or tail-flick after being injected with different doses of these agents. Results: The antidepressants mianserin and mirtazapine (separately) induced dose-dependent antinociception, each yielding a biphasic dose–response curve. Similarly, the antidepressant venlafaxine produced a potent effect and reboxetine produced a weak effect. The antipsychotics risperidone and amisulpride exhibited a dose-dependent antinociceptive effect. The sedative–hypnotic zolpidem induced a weak bi-phasic dose-dependent antinociceptive effect. All seven psychotropic medications elicited antinociception, which was reversed by the non-selective opiate antagonist naloxone and, separately, by the kappa-selective antagonist Nor-BNI. Conclusions: Clinical studies are mandatory to establish the potential efficacy of augmentation of the treatment with antidepressants with these drugs in persons with treatment-resistant depression and the optimal dosage of medications prescribed. We suggest a possible beneficial effect of antidepressants with kappa antagonistic properties. Full article

Background: There is clinical concern about the combined use of alcohol and opiates. Several lines of evidence support an interaction between alcohol and the endogenous opioid system. Thus, we hypothesized that ethanol, by causing the release of opioid peptides, may sensitize the system to the action of exogenous opioids such as morphine. Objectives: In this study, using the place conditioning paradigm, a model of reward, we determined whether a morphine challenge would alter the pre-established preference induced by ethanol conditioning in mice, and whether this response was mediated by the mu opioid receptor (MOP). Given that ethanol exposure stimulates the release of opioid peptides, we also assessed the role of beta-endorphin (β-END) and enkephalins (ENKs) in this response. Methods: Mice lacking MOPs, β-END, and/or ENKs, and their respective wild-type controls were tested for preconditioning place preference on day 1. Mice were then conditioned with ethanol (2 g/kg) versus saline on days 2 to 4 and then tested under a drug-free state for postconditioning place preference on day 5. On day 8, mice received a single injection of morphine (5 mg/kg) and were tested for place preference. On the test days, mice were placed in the central chamber and allowed to explore the chambers. The amount of time that mice spent in the drug-paired chamber was recorded. Results: We found that a challenge dose of morphine given on day 8 enhanced the conditioned place preference (CPP) response in mice previously conditioned with ethanol. This response was abolished in MOP-null mice, confirming the role of MOPs in this response. Although this enhanced response was not altered in mice lacking either β-END or ENKs compared to their wild-type littermates/controls, it was completely blunted in mice lacking both β-END and enkephalins. Conclusions: Together, these results suggest that these opioid peptides jointly mediate the crosstalk between the rewarding actions of morphine and ethanol. Full article

Purpose: To assess (I) whether, in autopsy-proven lethal intoxications with opiates/opioids, a dilatation of the common bile duct (CBD) is still visible in postmortem computed tomography (PMCT) and (II) if a dilatation of the CBD might also be measurable for other substance groups (e.g., stimulants, hypnotics, antipsychotics, etc.). Methods: We retrospectively measured the CBD using PMCT in cases with lethal intoxication (n = 125) and as a control group in cases with a negative toxicological analysis (n = 88). Intoxicating substances were classified into the subgroups (opiates, opioids, stimulants, hypnotics, antipsychotics, gasses, and others). Significance between the study and control groups was tested with the Mann–Whitney U test, and correlations were examined by using crosstables. Results: There was a statistically significant difference between the CBD diameters in the intoxication group overall, when compared to the CBD diameter in the control group (p < 0.001). For both subgroups of “opiates” and “opioids”, there was a strong statistically significant difference between the CBD diameter (being wider) in those groups compared to the control group (both p = 0.001). For the three subgroups “hypnotics”, “stimulants”, and “psychotropic drugs”, there was no statistically significant difference between the CBD diameters in the intoxication subgroups when compared with the control group. The other subgroups were too small for statistical analysis. Conclusion: A dilated common bile duct in postmortem computed tomography might be used as an indication for a lethal opioid or opiate intoxication only in regard to the specific case circumstances or together with other indicative findings in a postmortem investigation. Full article

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. Full article

Background: There is a growing concern that opioids and benzodiazepines can depress the respiratory drive and could contribute to worsening respiratory failure and higher exacerbation frequency in COPD. However, the relationship between the exacerbation rate and medication taken is poorly understood in patients with chronic respiratory failure due to COPD. Methods: As part of a service evaluation project, we analysed 339 patients with COPD who were established on long-term non-invasive ventilation (LT-NIV) at our tertiary centre. We investigated the relationship between benzodiazepine and opioid prescription and clinical outcomes as well as their impact on the exacerbation rate and overall survival following setup. Results: Before LT-NIV setup, 40 patients took benzodiazepines and 99 patients took opioids. Neither benzodiazepine nor opioid use was associated with changes in daytime blood gases, overnight hypoxia or annual exacerbations before NIV setup, but patients taking opioids were more breathless as assessed by modified Medical Research Council scores (3.91 ± 0.38 vs. 3.65 ± 0.73, p < 0.01). Long-term NIV significantly reduced the number of yearly exacerbations (from 3.0/2.0–5.0/ to 2.8/0.71–4.57/, p < 0.01) in the whole cohort, but the effect was limited in those who took benzodiazepines (from 3.0/2.0–7.0/ to 3.5/1.2–5.5/) or opioids (3.0/2.0–6.0/ to 3.0/0.8–5.5/). Benzodiazepine use was associated with reduced exacerbation-free survival and overall survival (both p < 0.05). However, after adjustment with relevant covariates, the relationship with exacerbation-free survival became insignificant (p = 0.12). Opioids were not associated with adverse outcomes. Conclusions: Benzodiazepines and opiates are commonly taken in this cohort. Whilst they do not seem to contribute to impaired gas exchange pre-setup, they, especially benzodiazepines, may limit the benefits of LT-NIV. Full article

Background: Toxicological analysis of patients with acute recreational drug poisoning can improve our understanding of substance use patterns, clinical symptoms, and improve treatment. Patient history alone may be incomplete or misleading. The objective was to assess the differences in patient history and analytical results, to describe the clinical characteristics, implications and hospital management, and to describe the drug use pattern over time. Methods: A retrospective study including all patients admitted to our toxicology unit with recreational drug toxicity and analytical testing from October 2014 to December 2022. Results: 872 patients were included. Patient history revealed a median of one ingested substance class: opiates/opioids, benzodiazepines/Z-drugs, and Pregabalin were predominant. Urine analysis revealed a median of three ingested substance classes (p < 0.001). Benzodiazepines/Z-drugs, Pregabalin, and THC were severely underreported. Agitation and aggression, anxiety, hallucinations, and psychosis were frequent, associated with cocaine, cathinone/phenethylamine, and amphetamine/MDMA detection and required sedation. Coma was also frequent, associated with opiate/opioid, benzodiazepine/Z-drug, GBL/GHB, and Pregabalin detection and required intubation, and/or application of Naloxone and/or Flumazenil. Twelve patients arrived in cardiac arrest; all were positive for opiates/opioids. Four patients died: three with Benzodiazepines/Z-drugs, Pregabalin and opiates/opioids detected, one with cathinones/phenethylamines detected. While cathinones/phenethylamines and synthetic cannabinoid receptor agonists were mainly detected between 2014–2016, detection decreased significantly between 2017–2022 after NPS legislation passed. Pregabalin detection increased. Conclusions: Patient history is inaccurate, and patients frequently underreport ingested drugs. Opiates and opioids are still the main cause of morbidity and mortality. Pregabalin is increasingly abused. NPS legislation effectively decreased cathinone/phenethylamine and synthetic cannabinoid receptor agonist overdoses. Full article

Background: Kratom is a substance that alters one’s mental state and is used for pain relief, mood enhancement, and opioid withdrawal, despite potential health risks. In this study, we aim to analyze the social media discourse about kratom to provide more insights about kratom’s benefits and adverse effects. Also, we aim to demonstrate how algorithmic machine learning approaches, qualitative methods, and data visualization techniques can complement each other to discern diverse reactions to kratom’s effects, thereby complementing traditional quantitative and qualitative methods. Methods: Social media data were analyzed using the latent Dirichlet allocation (LDA) algorithm, PyLDAVis, and t-distributed stochastic neighbor embedding (t-SNE) technique to identify kratom’s benefits and adverse effects. Results: The analysis showed that kratom aids in addiction recovery and managing opiate withdrawal, alleviates anxiety, depression, and chronic pain, enhances mood, energy, and overall mental well-being, and improves quality of life. Conversely, it may induce nausea, upset stomach, and constipation, elevate heart risks, affect respiratory function, and threaten liver health. Additional reported side effects include brain damage, weight loss, seizures, dry mouth, itchiness, and impacts on sexual function. Conclusion: This combined approach underscores its effectiveness in providing a comprehensive understanding of diverse reactions to kratom, complementing traditional research methodologies used to study kratom. Full article

The prevalence of patients on buprenorphine therapy presenting for elective surgery has increased. Buprenorphine is a widely used medication for the management of patients with chronic pain. It is also used as maintenance therapy for patients with a history of opioid use disorder (OUD). Due to the lack of a standardized protocol for managing patients on buprenorphine perioperatively, we performed a retrospective analysis to compare pain score outcomes and postoperative opiate requirements between patients who continued buprenorphine versus patients who discontinued buprenorphine. We identified 35 patients: 11 continued buprenorphine and 24 discontinued buprenorphine. The average Post-Anesthesia Care Unit (PACU) pain score was 5.59 for those who continued buprenorphine and 7.54 for those who discontinued preoperative buprenorphine (p value 0.0339). The average postoperative morphine milligram equivalent (MME) use was 86.13 for those who continued preoperative buprenorphine and 107.70 for those who discontinued buprenorphine (p value 0.6439). The results from our study correlate with several previous studies, which showed lower PACU pain scores in patients who continued buprenorphine. There is a benefit of decreased postoperative pain when preoperative buprenorphine is continued, and a decreased possibility for relapse in those with a history of OUD. Full article

Laparoscopic cholecystectomy (LC) is the gold standard of treatments for symptomatic gallstone disease. The aim of this study is to determine if postoperative opiate use is reduced with transversus abdominus plane (TAP) and rectus sheath (RS) regional anaesthetic blocks compared to port site local anaesthetic (LA) infiltration. A prospective, randomised cohort study was conducted of adult patients who underwent an emergency LC between 25 April 2022 and 25 May 2023. An amount of 40 mL of 0.375% ropivacaine was infiltrated as either TAP and RS blocks or to port sites. Patient demographics, operative data, and postoperative opioid use were collected from the medical record. In total, 138 patients were enrolled in this study: 73 patients allocated to the LA to port sites cohort (52.9%) and 65 patients in the TAP and RS cohort (43.5%). The most common indication for surgery was acute cholecystitis. The average amount of opiate analgesia use was 115.2 mg in the LA group compared to 61.2 mg in the TAP and RS group (p < 0.05). Optimisation of postoperative pain allows for early recovery, improved patient satisfaction, and improved cost-effectiveness for the health service. With a trend towards multimodal analgesia, the uptake of TAP and RS regional anaesthesia may help to achieve this goal. Full article