Comparison of patients with benzodiazepine receptor agonist-related psychiatric disorders and over-the-counter drug-related psychiatric disorders before and after the COVID-19 pandemic: Changes in psychosocial characteristics and types of abused drugs.

AIM: To investigate changes in the clinical characteristics of patients who abused benzodiazepine receptor agonists (BZRA) or over-the-counter (OTC) drugs before and after COVID-19 based on the 2018 and 2022 data of the "Nationwide Psychiatric Hospital (NPH) Survey on Drug-related Psychiatric Disorders." METHOD: A total of 446 and 155 cases, and 435 and 273 cases, who mainly abused BZRAs or OTC drugs, respectively, were extracted from the database of the two NPH Surveys. Demographic variables, education, employment, criminal record, drug use during the previous year, psychiatric diagnosis, and types of abused drugs were compared between 2018 and 2022. RESULT: A comparison of BZRA abusers revealed a decreased number of users during the previous year and an increase in the comorbidity rate of other disorders (F3 and F4 in ICD-10) in 2022. Etizolam, flunitrazepam, triazolam, and zolpidem were used most in both years, with an increase in zolpidem and a decrease in triazolam in 2022. A comparison of OTC drug abusers revealed a higher proportion of women and young patients in 2022. An increase in the comorbidity rate of F3 and F9 and a significant increase in the use of dextromethorphan products were observed in 2022, although codeine products were in the majority in both years. CONCLUSION: By comparing NPH Surveys before and after the COVID-19 pandemic, both BZRA abusers and OTC drug abusers present complex pathologies, requiring tailor-made treatment. The younger OTC drug abusers were particularly evident among women, and the abuse of dextromethorphan-containing OTC drugs has increased alarmingly.

Development of a Potential-Modulated Electrochemiluminescence Measurement System for Selective and Sensitive Determination of the Controlled Drug Codeine.

Codeine is a common analgesic drug that is a pro-drug of morphine. It also has a high risk of abuse as a recreational drug because of its extensive distribution as an OTC drug. Therefore, sensitive and selective screening methods for codeine are crucial in forensic analytical chemistry. To date, a commercial analytical kit has not been developed for dedicated codeine determination, and there is a need for an analytical method to quantify codeine in the field. In the present work, potential modulation was combined with electrochemiluminescence (ECL) for sensitive determination of codeine. The potential modulated technique involved applying a signal to electrodes by superimposing an AC potential on the DC potential. When tris(2,2'-bipyridine)ruthenium(II) ([Ru(bpy)3]2+) was used as an ECL emitter, ECL activity was confirmed for codeine. A detailed investigation of the electrochemical reaction mechanism suggested a characteristic ECL reaction mechanism involving electrochemical oxidation of the opioid framework. Besides the usual ECL reaction derived from the amine framework, selective detection of codeine was possible under the measurement conditions, with clear luminescence observed in an acidic solution. The sensitivity of codeine detection by potential modulated-ECL was one order of magnitude higher than that obtained with the conventional potential sweep method. The proposed method was applied to codeine determination in actual prescription medications and OTC drug samples. Codeine was selectively determined from other compounds in medications and showed good linearity with a low detection limit (150 ng mL-1).

Sorptive tape-spray tandem mass spectrometry using aluminum foil coated with mixed-mode microparticles.

Direct mass spectrometry (MS) is an exciting strategy in bioanalysis, enabling rapid decision-making in different scenarios. Its application is usually hindered by matrix effects and the typically low concentration of the target compounds in the biofluids. In this sense, combining a previous sample preparation step minimizes or removes these shortcomings. This article describes sorptive tape-spray tandem mass spectrometry (STS-MS/MS) based on mixed-mode particles as a strategy to combine sample preparation and MS analysis in a single device. The technique uses a sorptive tape (ST) consisting of mixed-mode polymeric microparticles (combining ionic exchange and hydrophobic interactions) coated over aluminum foil in a spatial controlled way. The tapes act as the sorptive phases to isolate the analytes from the sample matrix and substrates for STS-MS/MS. The performance of the technique has been evaluated by developing a method to determine codeine in saliva as proof of concept. The affordability of the STs elements allows the preparation of many individual phases at low cost so that several samples can be extracted simultaneously, thus increasing the sample throughput. The extraction variables were optimized following a multivariate approach. Working under the optimum conditions, the limit of detection was 0.3 µg L-1, while the intraday precision, calculated as relative standard deviation (RSD) at three concentration levels, was better than 9.4 %. The accuracy, expressed as relative recovery, was in the range of 78-98 %. The method was also applied to the analysis of real samples. Despite being a powerful strategy, the direct combination of microextraction to MS is not always affordable in all laboratories. For this reason, the STs were also combined with commercial liquid chromatography-MS working under the direct infusion mode to demonstrate the usefulness of the ST in classical extraction workflows.

Characterization of Codeine Treatment Responders Among Patients with Refractory or Unexplained Chronic Cough: A Prospective Real-World Cohort Study.

PURPOSE: Codeine is a narcotic antitussive often considered for managing patients with refractory or unexplained chronic cough. This study aimed to evaluate the proportion and characteristics of patients who responded to codeine treatment in real-world practice. METHODS: Data from the Korean Chronic Cough Registry, a multicenter prospective cohort study, were analyzed. Physicians assessed the response to codeine based on the timing and degree of improvement after treatment initiation. Follow-up assessments included the Leicester Cough Questionnaire and cough severity visual analog scale at six months. In a subset of subjects, objective cough frequency was evaluated following the initiation of codeine treatment. RESULTS: Of 305 patients, 124 (40.7%) responded to treatments based on anatomic diagnostic protocols, while 181 (59.3%) remained unexplained or refractory to etiological treatments. Fifty-one subjects (16.7%) were classified as codeine treatment responders (those showing a rapid and clear response), 57 (18.7%) as partial responders, and 62 (20.3%) as non-responders. Codeine responders showed rapid improvement in objective cough frequency and severity scores within a week of the treatment. At 6 months, responders showed significantly improved scores in cough scores, compared to non-responders. Several baseline parameters were associated with a more favorable treatment response, including older age, non-productive cough, and the absence of heartburn. CONCLUSIONS: Approximately 60% of chronic cough patients in specialist clinics may require antitussive drugs. While codeine benefits some, only a limited proportion (about 20%) of patients may experience rapid and significant improvement. This underscores the urgent need for new antitussive drugs to address these unmet clinical needs.

Narcotic analgesics.

There is documentation of the use of opium derived products in the ancient history of the Assyrians: the Egyptians; in the sixth century AD by the Roman Dioscorides; and by Avicenna (980-1037). Reference to opium like products is made by Paracelsus and by Shakespeare. Charles Louis Derosne and Fredrich Wilhelm Adam Serturner isolated morphine from raw opium in 1802 and 1806 respectively, and it was Sertürner who named the substance morphine, after Morpheus, the Greek God of dreams. By the middle 1800s, Opium and related opioid derived products were the source of a major addiction in USA, and to some extent in the United Kingdom. Opioid products are of major therapeutic value in the treatment of pain from injury, post surgery, intractable pain conditions, and some forms of terminal cancer.

Development and validation of a brief screening tool for over-the-counter codeine dependence.

BACKGROUND: Low-dose codeine is sold without a prescription in countries like the UK, Ireland, and South Africa. Due to misuse concerns, exploring pharmacy screening tools to identify those at risk and needing additional support is vital. OBJECTIVES: The study aims to develop and validate a brief screening tool that assesses the risk of codeine dependence with language appropriate for routine use in community pharmacies. METHOD: Scale development and validation occurred over two studies. In Study 1, scale item generation was based on structured analyses of psychosocial and pharmacy variables from frequent over-the-counter codeine consumers (N = 795). CFA was used to assess the cohesiveness of the resultant four-item Codeine Dependence Scale (CDS). ROC analyses were used to assess the performance of the CDS against risk cases identified by the Severity of Dependence Scale; identifying an optimal cut-off value of ≥2 as representing individuals at risk of codeine dependence. In Study 2, this CDS threshold was assessed against positive DSM-5 Opioid Use Disorder (OUD) cases related to codeine use assessed using the AUDADIS-IV. RESULTS: With a cut-off score of ≥2, the CDS has sensitivity and specificity of 76% and 48%, respectively, against a DSM-5 codeine-related OUD diagnosis using the AUDADIS-IV. For identification of any codeine-related OUD (as measured by the AUDADIS-IV) 15 months after baseline, the CDS achieved an overall correct classification rate of 52%; 72% for positive cases. CONCLUSIONS: The CDS exhibits reasonable cross-sectional and longitudinal sensitivity but low specificity, partly due to its brevity. However, the inclusive nature of the CDS is not a negative for application as a screening tool in a pharmacy setting as individual CDS items represent critical conversation points with a pharmacist, regardless of the screening outcome. The non-confronting nature of CDS items make the scale a viable option for pharmacy-based SBI in countries where codeine remains OTC.

Association of tramadol use with risk of hip fractures in patients with osteoarthritis: A systematic review and meta-analysis of observational studies.

OBJECTIVE: Many studies have reported conflicting results for the use of tramadol with the risk of fractures, especially hip fractures. This systematic review and meta-analysis study aimed to evaluate the association of tramadol use versus codeine use with the risk of hip fracture for the first time. METHODS: PubMed, Scopus, Google Scholar, and Web of Science databases were searched with specific keywords to find studies that examined the association of tramadol use with hip fracture risk in patients with osteoarthritis up to May 2023. The risk of hip fracture secondary to tramadol versus codeine use was estimated based on age and sex. This systematic review was conducted based on the PRISMA checklist. Heterogeneity between studies was evaluated using Cochran's Q and I2 tests. Egger's test was used to check publication bias. The Newcastle-Ottawa Checklist (NOS) was used to assess the quality of the studies. FINDINGS: Ten studies with 1,939,293 participants were reviewed. The majority of participants were female. Based on the study evaluation checklist, most studies were of good quality. Tramadol use significantly increases the overall risk of hip fracture. (HR: 1.32, 95% CI: 1.14, 1.51, P: 0.001, I2:19.3%) Tramadol use significantly increases the risk of hip fracture in men (HR: 1.48, 95% CI: 1.24, 1.73, P: 0.001 I2:35%) and age ≤65 years (HR: 1.63, 95% CI: 1.45, 1.80, P: 0.001, I2:0%). CONCLUSION: The use of tramadol significantly increases the risk of hip fracture. This increased risk of hip fracture was greater in males younger than 65 years.

Exploring Perceptions About Paracetamol, Tramadol, and Codeine on Twitter Using Machine Learning: Quantitative and Qualitative Observational Study.

BACKGROUND: Paracetamol, codeine, and tramadol are commonly used to manage mild pain, and their availability without prescription or medical consultation raises concerns about potential opioid addiction. OBJECTIVE: This study aims to explore the perceptions and experiences of Twitter users concerning these drugs. METHODS: We analyzed the tweets in English or Spanish mentioning paracetamol, tramadol, or codeine posted between January 2019 and December 2020. Out of 152,056 tweets collected, 49,462 were excluded. The content was categorized using a codebook, distinguishing user types (patients, health care professionals, and institutions), and classifying medical content based on efficacy and adverse effects. Scientific accuracy and nonmedical content themes (commercial, economic, solidarity, and trivialization) were also assessed. A total of 1000 tweets for each drug were manually classified to train, test, and validate machine learning classifiers. RESULTS: Of classifiable tweets, 42,840 mentioned paracetamol and 42,131 mentioned weak opioids (tramadol or codeine). Patients accounted for 73.10% (60,771/83,129) of the tweets, while health care professionals and institutions received the highest like-tweet and tweet-retweet ratios. Medical content distribution significantly differed for each drug (P<.001). Nonmedical content dominated opioid tweets (23,871/32,307, 73.9%), while paracetamol tweets had a higher prevalence of medical content (33,943/50,822, 66.8%). Among medical content tweets, 80.8% (41,080/50,822) mentioned drug efficacy, with only 6.9% (3501/50,822) describing good or sufficient efficacy. Nonmedical content distribution also varied significantly among the different drugs (P<.001). CONCLUSIONS: Patients seeking relief from pain are highly interested in the effectiveness of drugs rather than potential side effects. Alarming trends include a significant number of tweets trivializing drug use and recreational purposes, along with a lack of awareness regarding side effects. Monitoring conversations related to analgesics on social media is essential due to common illegal web-based sales and purchases without prescriptions.

The impact of a restricted pregabalin prescription policy on drug utilization: An observational multicenter study.

Background: The Saudi Food and Drug Authority (SFDA) classified pregabalin as a controlled substance in 2018; however, whether this policy change has affected pregabalin use is unclear. This study examined the trends in pregabalin prescriptions before and after the SFDA restriction. In addition, the co-prescription of controlled analgesics and the use of pregabalin for approved indications were also evaluated. Method: A cross-sectional study was conducted on outpatient pregabalin prescriptions from three healthcare centers in Saudi Arabia. Interrupted time series analysis was used to assess changes over time in pregabalin prescriptions and the number of patients receiving pregabalin. June 2016 to June 2017 was identified as the pre-restriction period, and July 2018 to July 2019 as the post-restriction period. Results: In this study, 77,760 pregabalin prescriptions were identified. There were 9,076 patients on pregabalin in the pre-restriction period with 16,875 prescriptions, compared with 7,123 patients and 19,484 prescriptions post-restriction. The total number of pregabalin users decreased by 21.5% post-restriction, and prescriptions increased by 15.5%. There was no significant change in the monthly trends in pregabalin prescriptions before and after the restriction. However, the of tramadol and acetaminophen/codeine prescriptions in patients who were using pregabalin increased in the post-restriction period by 21% and 16.1%, respectively. Conclusion: Pregabalin use was reduced after the SFDA-enforced prescription restriction was implemented. This was accompanied by increased narcotics use in the post-implementation phase.

The roles of vicarious trauma exposure and perceived social support in codeine syrup misuse among Black men living in prisons.

Using General Strain Theory, this study investigates the effects of vicarious trauma exposure and perceived social support on nonmedical codeine syrup misuse among Black incarcerated men nearing community re-entry. Data were drawn from the Helping Incarcerated Men project, a study examining mental health, substance misuse, and human immunodeficiency virus (HIV) risk behaviors among Black men living in prisons who were within 180 days of release. A total of 200 Black men self-reported demographics (i.e., age and length of incarceration after age 18), vicarious trauma exposure (e.g., ever witnessing an assault with a weapon and a sudden accidental death), perceived social support, and nonmedical codeine syrup misuse. Findings from the logistic regression analysis showed witnessing an assault with a weapon and a sudden accidental death increased the likelihood of codeine syrup misuse. Perceived social support was not associated with codeine syrup misuse. Implications for practice and future research are discussed.

Lean/Sizzurp Ingredients, Use, and Coping With Mental Health Symptoms.

The substance combination of codeine and promethazine, commonly termed lean/sizzurp, has been identified as a method that some individuals use to cope with PTSD and other mental health symptomology. A sample of 1423 adults with self-reported past year lean use was recruited from substance-related Reddit pages to complete a survey about lean, including information about using lean to cope with emotions, thoughts, or feelings. To be included in the sample, persons needed to: (1) be ⩾18 years old, (2) report past year lean use, (3) complete lean use screeners, and (4) pass data quality checks (eg, bot detection). As Reddit is an online forum, no geographic restrictions were placed on study participation. Data on demographic characteristics, lean use, and mental health disorder symptomology were captured from participants. Logistic regression models included anxiety, depression, and trauma as independent variables along with covariates to examine using lean to cope with emotions, thoughts, or feelings in the past 30 days. Most participants were male (n = 1102; 77.4%), with an average age of 26.9 (SD = 5.2) years. Most participants used included codeine as an ingredient in lean (n = 1060; 74.5%); promethazine was added as an ingredient by 31.7% of the sample (n = 451), and the combination of codeine and promethazine was included as ingredients by 13.5% (n = 192) of the sample. Participants with anxiety, lifetime trauma exposure, and who were female had increased odds of using lean to cope with emotions, thoughts, or feelings in the past 30 days. Those with depression and unstable housing exhibited decreased odds of using lean to cope with emotions, thoughts, or feelings in the past 30 days. This study recruited persons via social media to learn more about lean use, especially lean use to cope with mental health symptoms; future population-level studies are needed.

Knowledge, Attitude, and the Practice of Community Pharmacists to Dispense Opioid-Related and Opioid-Containing Medication in Eastern Province, Saudi Arabia.

Objectives: This study was done to evaluate the knowledge of community pharmacists-working in Saudi Arabia-regarding over-the-counter opioid-related and opioid-containing medications. Materials and Methods: A quantitative cross-sectional study was conducted using an online questionnaire that was distributed through social media and taken to the community pharmacists in person. A total of 101 responders were reached in a period of around 3 weeks. Results: Most of the pharmacists working in community pharmacies in Saudi Arabia are non-Saudi (85.15%), males (88.12%), and the majority are holders of bachelor's degrees (85.15%). More than half of the participants spend a considerably sufficient time with the patient 6-10 minutes (60.4%). The availability of a private counseling room in community pharmacies is significantly low (21.78%). Only (69.41%) of participants always counsel the patient before dispensing opioid-related medications. Most of the participants (84.76%) believe that all over-the-counter opioid-related and opioid-containing medications should be restricted to avoid drug abuse. Conclusion: A little neglect from pharmacists' side regarding dispensing such medications was observed; thus, there is a significant need to raise their awareness regarding over-the-counter opioid abuse.

Modulatory effects of Cannabis sativa co-administration with tramadol and codeine on cognitive function in male rats.

Most teenagers mix up various psychoactive cocktail substances in combinations to get intoxicated. The role of the mixture combination of codeine (CDE), tramadol (TMD), and Cannabis sativa (CNB) on brain cognition, purinergic, cholinergic, and antioxidant enzyme activities remains unknown. This study sought to assess the mechanism of action of combinations of CDE+ TMD+ CNB on the function and activities of the brain of male Wistar rats. Forty-eight male Wistar rats were divided into 8 groups, n = 6. Group 1 served as a control, groups 2, 3, and 4 were exposed to CDE (2 mg/kg bw), TMD (10 mg/kg bw), and CNB (200 mg/kg bw), while groups 5, 6, 7, and 8 were co-administered with CDE+TMD, CNB+ TMD, CNB+CDE, and CNB+TMD+CDE orally for 28 days. This study revealed the effect of prolonged administration of CNB, TMD, and CDE on the suppression of cognitive function, acetyl-cholinesterase (AChE), butyl-cholinesterase (BChE), monoamine oxidase (MAO) enzyme activities, and antioxidant enzyme activities in rats' brains when compared against control rats (P < 0.05). However, the activities of ectonucleosides (NTPdase), adenosine deaminase (ADA), and malondialdehyde levels produced in the brain of rats were significantly elevated (P < 0.05). This study reported the mechanism behind the neurotoxicity of CNB, TMD, and CDE on rats' cognitive, cholinergic, purinergic, and antioxidant enzymes as a consequence of the drastic reduction in cholinesterase enzyme activities leading to neurotransmitter poisoning.

Understanding the Dynamics of More Restrictive Medicines Policy: A Case Study of Codeine Up-Scheduling in Australia.

BACKGROUND: There has been increasing concern over opioid-related harms across the world. In Australia in 2018, codeine-containing products were up-scheduled from over-the-counter access at pharmacies, to requiring a prescription. The drug regulator's decision to up-schedule was contentious and widely debated, due to the potentially large impact on consumers and healthcare professionals. This study aimed to analyse influences on the codeine up-scheduling policy. METHODS: This retrospective policy analysis used the Advocacy Coalition Framework (ACF) to understand how policy actors with shared beliefs formed adversarial coalitions to shape policy. Data were drawn from documents (regulator policy documents, public submissions, news reports, organisational media releases and position statements) and semi-structured interviews with 15 key policy actors. Codes were generated relating to policy processes and actor beliefs; broad themes included the role of health professionals, perceptions of opioids, impact on consumers, and the role of government in healthcare. RESULTS: Two coalitions in this policy subsystem were identified: (1) supportive [with respect to the up-scheduling], and (2) opposing. The key evident beliefs of the supportive coalition were that the harms of codeine outweighed the benefits, and that government regulation was the best pathway for protecting consumers. The opposing coalition believed that the benefits of codeine accessible through pharmacists outweighed any harms, and consumers should manage their health without any more intervention than necessary. The policy decision reflected the influence of the supportive coalition, and this analysis highlighted the importance of their public health framing of the issue, the acceptability of their experts and supporting evidence, and the perceived legitimacy of the up-scheduling process. CONCLUSION: Understanding these coalitions, their beliefs, and how they are translated through existing policy processes and institutions provides insight for those interested in influencing future health policy. Specific lessons include the importance of strategic frames and advocacy, and engagement with formal policy processes.

L-Arginine abrogates maternal and pre-pubertal codeine exposure-induced impaired spermatogenesis and sperm quality by modulating the levels of mRNA encoding spermatogenic genes.

Introduction: Although, codeine has been demonstrated to lower sperm quality; the effects of maternal and prepubertal codeine exposure on male offspring is yet to be reported. In addition, the effect of arginine on codeine-induced decline in sperm quality has not been explored. This study investigated the impact of maternal and prepubertal codeine exposure on spermatogenesis and sperm quality in F1 male Wistar rats to study the effect that codeine may have during recreational use in humans. Also, the effect of arginine supplementation on codeine-induced alteration in spermatogenesis and sperm quality was evaluated. Methods: Female rats were treated with either 0.5 ml distilled water or codeine orally for eight weeks, and then mated with male rats (female:male, 2:1). The F1 male offsprings of both cohorts were weaned at 3 weeks old and administered distilled water, codeine, arginine, or codeine with arginine orally for eight weeks. Results: Prepubertal codeine exposure in rats whose dams (female parents) were exposed to codeine delayed puberty and reduced the weight at puberty. Prepubertal codeine exposure exacerbated maternal codeine exposure-induced reduced total and daily spermatid production, sperm count, sperm motility, and normal sperm form, as well as impaired sperm plasma membrane integrity and increased not intact acrosome and damaged sperm DNA integrity. These perturbations were accompanied by a decrease in mRNA levels encoding spermatogenic genes, testicular testosterone and androgen receptor (AR) concentrations, and upregulation of sperm 8-hydroxydeoxyguanosine (8OHdG). Prepubertal arginine supplementation mitigated codeine-induced alterations. Discussion: This study provides novel experimental evidence that maternal and prepubertal codeine exposure reprogramed spermatogenesis and sperm quality of male FI generation by decreasing mRNA levels encoding spermatogenic genes and AR via oxidative stress-mediated signaling, which was abrogated by prepubertal arginine supplementation.

Opioid poisoning in Newcastle over the last three decades: From heroin to prescription opioids.

OBJECTIVE: Opioid-related harm has risen in recent decades, but limited research describes the clinical burden of opioid poisoning to Australian EDs. We aimed to investigate hospital presentations with opioid poisoning over three decades. METHODS: This is an observational series of prospectively collected data investigating presentations of opioid poisoning to an ED in Newcastle (1990-2021). Type of opioid, naloxone administration, intubation, intensive care unit (ICU) admission, length of stay and death were extracted from the unit's database. RESULTS: There were 4492 presentations in 3574 patients (median age 36, 57.7% female), increasing from an average of 93 presentations annually in the first decade to 199 in the third decade. Deliberate self-poisonings accounted for 3694 presentations (82.2%). Heroin dominated the 1990s, peaking in 1999 before decreasing. Prescription opioids then rose, with codeine (usually in paracetamol combination) predominating until 2018, after which oxycodone presentations exceeded them. Methadone consistently increased from six presentations annually in the first decade to 16 in the last decade. Naloxone was administered in 990 (22.0%) presentations and 266 (5.9%) were intubated, most frequently following methadone and heroin exposures. ICU admissions increased from 5% in 1990 to 16% in 2021. Codeine exposures resulted in less severe effects, whereas methadone had more severe effects overall. The median length of stay was 17 h (interquartile range 9-27 h). There were 28 deaths (0.6%). CONCLUSION: Opioid presentations increased in number and severity over three decades as the type of opioid changed. Oxycodone is currently the main opioid of concern. Methadone poisoning was the most severe.

The therapeutic potential of opioids in narcolepsy type 1: A systematic literature review and questionnaire study.

OBJECTIVE: Narcolepsy type 1 is a primary sleep disorder caused by deficient hypocretin transmission leading to excessive daytime sleepiness and cataplexy. Opioids have been suggested to increase the number of hypocretin-producing neurons. We aimed to assess opioid use and its self-reported effect on narcolepsy type 1 symptom severity through a literature review and questionnaire study. METHODS: We systematically reviewed literature on opioid use in narcolepsy. We also recruited 100 people with narcolepsy type 1 who completed an online questionnaire on opioid use in the previous three years. The main questionnaire topics were the indication for use, and the possible effects on narcolepsy symptom severity. Structured follow-up interviews were conducted when opioid use was reported. RESULTS: The systematic literature review mainly showed improvements in narcolepsy symptom severity. Recent opioid use was reported by 16/100 questionnaire respondents, who had used 20 opioids (codeine: 7/20, tramadol: 6/20, oxycodone: 6/20, fentanyl: 1/20). Narcolepsy symptom changes were reported in 11/20. Positive effects on disturbed nocturnal sleep (9/20), excessive daytime sleepiness (4/20), hypnagogic hallucinations (3/17), cataplexy (2/18), and sleep paralysis (1/13) were most pronounced for oxycodone (4/6) and codeine (4/7). CONCLUSIONS: Opioids were relatively frequently used compared to a similarly young general Dutch sample. Oxycodone and, to a lesser extent, codeine were associated with self-reported narcolepsy symptom severity improvements. Positive changes in disturbed nocturnal sleep and daytime sleepiness were most frequently reported, while cataplexy effects were less pronounced. Randomised controlled trials are now needed to verify the potential of opioids as therapeutic agents for narcolepsy.

Trends in adverse drug reactions related to oral weak opioid analgesics in therapeutic use in adults: A 10-year French vigilances retrospective study.

AIM: To describe the symptoms, patient demographics, and trends over time of adverse drug reactions (ADRs) related to weak opioid analgesics reported to the French vigilance networks. METHODS: Retrospective study of data from French Poison Control Centers and Pharmacovigilance Centers databases of weak opioid analgesics-related ADRs cases, with high causality score, in adults, in therapeutic analgesic use, without co-exposure, between 2011 and 2020. RESULTS: The number of cases was 388 in the Poisonings database and 155 in the Pharmacovigilance database; ratio of the number of these cases to all reported cases during the study period was 0.02% and 0.03%, respectively. Tramadol was most often involved (74% and 56.1%, respectively), followed by codeine (26% and 38.7%, respectively). There was no significant variation in the number of cases reported. Cases most often involved young adults (median age: 40 years) and mostly women (76%). Gastrointestinal symptoms were mostly reported (80% and 65%, respectively) as described in the Summary of Products Characteristics. Patterns of ADRs were comparable in both databases, except for codeine-associated acute pancreatitis and anaphylaxis that were reported in the Pharmacovigilance database. No fatality was observed. Severity was more often observed in the Pharmacovigilance database (30%) than in the Poisonings database (moderate toxicity: 7%). CONCLUSION: ADRs mostly occurred among young women using tramadol, without significant variation in the number of reported cases over time. Serious ADRs were more frequently reported to the Pharmacovigilance database, particularly for codeine. Women seemed to be at greater risk of ADRs.

Detection of Three Opioids (Morphine, Codeine and Methadone) and Their Metabolites (6-Monoacetylmorphine and 2-Ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine) in Larvae of Lucilia sericata Species by UHPLC-TF-MS and Validation.

Insects on corpses could be a useful tool for the detection of exogenous substances such as drugs of abuse. The identification of exogenous substances in carrion insects is critical for proper estimation of the postmortem interval. It also provides information about the deceased person that may prove useful for forensic purposes. High-performance liquid chromatography coupled with Fourier transform mass spectrometry is a highly sensitive analytical technique that can identify substances even at very low concentrations, such as in the case of searching for exogenous substances in larvae. In this paper, a method is proposed for the identification of morphine, codeine, methadone, 6-monoacetylmorphine (6-MAM) and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in the larvae of Lucilia sericata, a common carrion fly widely distributed in temperate areas of the world. The larvae, which were reared on a pig meat substrate, were killed once they reached their third stage by immersion in hot water at 80 °C and aliquoted into 400 mg samples. The samples were fortified with 5 ng of morphine, methadone and codeine. After solid-phase extraction, the samples were processed with a liquid chromatograph coupled to a Fourier transform mass spectrometer. This qualitative method has been validated and tested on larvae from a real case. The results lead to the correct identification of morphine, codeine, methadone and their metabolites. This method could prove useful in cases where toxicological analysis must be conducted on highly decomposed human remains, where biological matrices are very limited. Furthermore, it could help the forensic pathologist to better estimate the time of death, as the growth cycle of carrion insects can undergo changes if exogenous substances are taken.