IntroductionNitrous oxide has become over the last few years a public health problem in many countries. France has a dedicated health monitoring system dedicated to the surveillance of the abuse, dependence and consequences associated with the use of psychoactive substances coordinated by the French National Agency for the Safety of Medicines and Health Products.We present the French national survey of nitrous oxide.Materials and methodsWe analyzed all the cases with nitrous oxide from 2012 to 2021: number of notifications, characteristics of the subjects and consumption, consequences reported and their evolutions over time. In addition, we have made a special focus on the four main complications reported.ResultsA total of 525 cases were received with an exponential increase since 2019. We observed changes in the characteristics of the notifications with an increase in the proportion of women [42.7% in 2021 vs. 30.8% in 2020 (p = 0.02)]; an increase in the quantities consumed (use of cylinders); a negative evolution of the contexts of use with a search for self-therapeutic effects and use in violent contexts; an increasing trend of the severity of cases [78.1% in 2021 vs. 70.0% in 2020 (p = 0.07)].The main effects were substance use disorders and/or associated criteria (82.5%), neurological disorders (75.4%), psychiatric symptoms (15.4%) and cardiovascular events (8.6%). In terms of evolution, we observed a significant increase in cases with a use disorder and an increase in neurological complications. Moreover, new serious effects, notably cardiovascular events were reported.DiscussionThe combination of high availability, varied effects from euphoria to relief of discomfort in a stressful global pandemic context and the development of dependence could explain the rapid growth of consumption and the seriousness of the cases.It must now be taken into account that (i) Substance use disorders are associated with nitrous oxide consumption; (ii) clinicians must consider “nitrous oxide” in young subjects presenting different types of manifestations; and (iii) stopping consumption is imperative and is the first treatment. In this context, an addictological assessment must also be carried out.
Background Since the appearance of zolpidem on the market, the occurrence of serious cases of abuse, misuse and dependence have come to the attention of authorities. In view of the increase in the number and severity of cases among zolpidem users and the predominant presence of zolpidem in falsified prescriptions, the French Health Authorities implemented part of the narcotics regulation for zolpidem in April 2017. The objective of this article was to describe the evolution of the abuse, dependence and misuse of zolpidem. Methods We used three data sources: (i) zolpidem is a reimbursable and strictly prescription drug in France. Medic’AM is a public database that indicates the number of tablets reimbursed each month in France for each reimbursable drug. This database has been analyzed as a proxy of the exposure of the French population to zolpidem; (ii) all French cases of drug dependence or abuse reported by health professionals (regulatory obligation) and (iii) an epidemiological tool based on the surveillance of falsified prescriptions over two periods: the 3-year period before the regulatory measure (2014–16) and the 3-year period after the regulatory measure (2018–20). Results This regulatory change had two immediate consequences: a sharp decline in falsified prescriptions and a decrease of ∼57% between the two study periods in the zolpidem reimbursement data. Markers of problematic consumption remained after the regulatory change with worsening cases, particularly for people who were genuinely dependent and/or had comorbidities or misusers for whom zolpidem was the substance of interest, whose proportion increased significantly in the addictovigilance notification system, from 43.6% (N = 107) to 59.3% (N = 127) (P < 0.01). Conclusions Further monitoring is needed in light of these persistent markers of problematic consumption.
Zopiclone, like zolpidem, is under surveillance in France due to its potential for dependence, abuse and misuse. However, part of the narcotics regulation was implemented in 2017 in France for zolpidem only, which has led to an increase in the number of zopiclone consumers. The objective of this article is to present French addictovigilance data regarding the evolution of the abuse, dependence and misuse profiles of zopiclone. We used the following 3 data sources over two periods: the 3-year period before the regulatory measure regarding zolpidem (2014–2016) and the 3-year period after the regulatory measure (2018–2020): (i) Medic'AM, a public database which provides a good overview of the number of boxes of zopiclone reimbursed in France; (ii) all French cases of drug dependence or abuse reported by health professionals to the French Addictovigilance Network (FAN); and (iii) a national epidemiological tool based on the surveillance of falsified prescriptions. Between the first and the second study periods (i) despite an increase in the exposure of the population to zopiclone, the proportion of reports to the FAN remained stable; (ii) the proportion of misusers increased significantly (p < 0.01), from 27% (n = 31) to 48.3% (n = 72); (iii) the profile of problematic users remained comparable with persistence of markers of problematic use; and (iv) there was a significant increase (p = 0.01) in zopiclone fraud for obtention, from 26.1% (n = 30) to 40.9% (n = 61), which mainly concerned nomadism. Prescribers should remain cautious in providing zopiclone prescriptions.
Background: The French national drug regulatory authority stated, in 2017, that a secured prescription pad must be used for zolpidem prescriptions. This study aimed to evaluate the evolution of the problematic consumption of zolpidem at the individual level since the new regulation. Methods: Two nationwide populations of at-risk users of zolpidem were recruited: one in general practitioner (GP) offices and one in specialized care centers dedicated to drug dependence (SCDDs). Participants were asked about their zolpidem consumption before and after the regulation change. The primary outcome was the evolution of problematic zolpidem consumption, as defined by at least one of the following criteria: overconsumption, fraudulent ways of obtaining, effects sought other than hypnotic, and modes of administration other than oral. Results: A total of 243 participants were included: 125 from GP offices and 118 from SCDDs. In the GP population, the prevalence of patients who were identified as problematic consumers decreased from 24.8% to 20.8% (p = 0.593), whereas the prevalence decreased from 73.7% to 51.7% in the SCDD population (p < 0.001). The most prevalent criteria for problematic status were overconsumption and fraudulent ways. Conclusions: The new French regulation of zolpidem had different impacts among two different populations of at-risk zolpidem consumers.
Background: Slamming has been increasing internationally for ten years, mostly among men who have sex with men. Slamming consists of injecting psychostimulants (including new psychoactive substances–NPS) intravenously to increase sexual performance. Objective: The objective of our work was to analyse drug–drug interactions related to slamming. Methods: Drawing upon a reported case of a slam session describing hour by hour the intake of substances, we performed a drug-interaction analysis using international references and a comprehensive literature review. High doses of sildenafil, GBL and 3-MMC were reported during the 40-hour session described. The specific drug-interaction research was performed using 9 references and 65 of the 209 records identified in the literature review. Results: Pharmacological data regarding nonmedicated substances were scarce. Regarding pharmacodynamics, the risk was high at the cardiovascular level and was related to the vasodilatation effect of sildenafil and the adrenergic and serotoninergic properties of stimulants; this risk may increase with usual treatment (involving other vasodilators or central depressants). Regarding pharmacokinetics, the major interactions concerned metabolism by CYP3A4 and CYP2C9, leading to interactions, particularly with HIV medication. Conclusion: This innovative work provides pharmacological information on drugs that are commonly used in slamming, allowing the development of effective medical-management protocols and the provision of risk-reduction counselling.
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