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The misuse of benzodiazepines and opioid medications is frequent in students. To improve our understanding of this behavior, we aimed to identify factors associated with separate and concomitant use of these substances. Anonymous self-reported questionnaires were e-mailed to students enrolled at a French university between March and July 2021, covering: sociodemographic characteristics, academics, psychoactive substance use, ADHD symptomatology (adulthood and childhood), and psychiatric/psychological or addiction follow-up. Factors associated with the use of benzodiazepines and opioid medications included female sex (OR = 1.41 [1.08; 1.86]) and OR = 1.38 [1.06; 1.79], respectively), older age (OR = 1.65 [1.04; 2.6] and OR = 2.17 [1.4; 3.36], respectively), current psychiatric/psychological follow-up (OR = 6.53 [5.18; 8.24] and OR= 1.5 [1.12; 2.0], respectively), ADHD symptomatology (OR= 2.33 [1.71;3.16] and OR= 1.61 [1.15; 2.24], respectively), polyconsumption (tobacco use for benzodiazepine users, OR = 1.38 [1.04; 1.82]; alcohol use OR = 1.67 [1.17; 2.39] and tobacco use OR = 1.62 [1.23; 2.14] for opioid users). These factors were even more strongly associated with the concomitant use of benzodiazepines and opioid medications: older age (OR = 3.64 [2.22; 5.99]), female sex (OR = 1.54 [1.1; 2.14]), grade repetition (OR = 1.7 [1.14; 2.54]), psychiatric/psychological follow-up (OR = 4.51 [3.35;6.06]), ADHD symptomatology (OR = 5.3 [3.69; 7.63]), polyconsumption (tobacco use OR = 2.05 [1.39; 3] and cannabis use, OR = 2.07 [1.97; 4.16]. The factors associated with the use of benzodiazepines and prescription opioids identified in this study could lead to the development of targeted prevention methods., (© 2024. The Author(s).)

Background: In many countries, nitrous oxide is used in a gas mixture (EMONO) for short-term analgesia. Cases of addiction, with significant misuse, have been reported in hospitalized patients. Patients suffering from sickle cell disease (SCD) could represent a high-risk population for substance use disorder (SUD) due to their significant pain crisis and repeated use of EMONO. The objective of the PHEDRE study was to assess the prevalence of SUD for EMONO in French SCD patients., Results: A total of 993 patients were included. Among 339 EMONO consumers, only 38 (11%) had a SUD, with very few criteria, corresponding mainly to a mild SUD due to a use higher than expected (in quantity or duration) and relational tensions with the care teams. Almost all patients (99.7%) were looking for an analgesic effect, but 68% of patients were also looking for other effects. The independent risks factors associated with at least one SUD criterion were: the feeling of effects different from the expected therapeutic effects of EMONO, at least one hospitalization for vaso occlusive crisis in the past 12 months and the presence of a SUD for at least one other analgesic drug., Conclusions: The use of EMONO was not problematic for the majority of patients. Manifestations of SUD that led to tensions with healthcare teams should alert and lead to an evaluation, to distinguish a true addiction from a pseudoaddiction which may be linked to an insufficient analgesic treatment related to an underestimation of pain in SCD patients., Trial Registration: Clinical Trials, NCT02580565. Registered 16 October 2015, https://clinicaltrials.gov/., (© 2024. The Author(s).)

We aimed to explore if psychostimulant use among student could be linked to attention deficit-hyperactivity disorder (ADHD) symptoms using a self-administered questionnaire sent by email to French students in 2021. Participants were asked about their psychostimulant use and the presence of ADHD symptoms using the Wender Utah Rating Scale and the Adult Self-Report Scale. Among the 4431 respondents, the prevalence of psychostimulant use was concerning and significantly associated with ADHD symptoms. This association could be related to undiagnosed ADHD or to psychobehavioral impairments induced by psychostimulant use underlining the need of ADHD screening and targeted prevention measures., Competing Interests: Declaration of Competing Interest OC: speaker or chairman at industry symposia (Janssen, Recordati, Indivior) The other authors have no competing interest to disclose., (Copyright © 2023. Published by Elsevier B.V.)

Objectives: Students represent a population at risk for substance abuse. That risk may have been exacerbated by the COVID-19 pandemic. We aimed to describe substance abuse among students and to compare consumption according to the university field., Methods: A self-administered questionnaire was sent by email to all students at the University of Lille, France, between March and July 2021. This anonymous questionnaire included questions about sociodemographic characteristics, university courses and the use of psychoactive substances (frequency, reasons, routes of administration) since the first university year., Results: Among the 4431 students who responded (response rate 6.1%), eighty percent declared having used alcohol since the first university year, 34% cannabis, 15.4% benzodiazepines, 14.7% opioid drugs, 7.5% cocaine, 6.8% nitrous oxide and 6.5% MDMA. More than 20% of the users of cannabis, benzodiazepines, amphetamines and cocaine reported having already felt dependent. Recreational use was described by more than 10% of benzodiazepine or opioid drug users. Nitrous oxide use was significantly more frequent in the health and sport field ( p  < 0.001). Tobacco, benzodiazepine, cannabis and MDMA uses were significantly more frequent in the humanities and social sciences/art, language and literature fields ( p  < 0.001)., Conclusion: Prevention measures focusing on alcohol, cannabis, illicit psychostimulants, nitrous oxide and prescription drugs are required in the student population.

Background: Recreational use of nitrous oxide (N 2 O) leads to neurological disorders including combined subacute degeneration of spinal cord, psychological disorders, and thrombosis. Serum or urine N 2 O assays could not be routinely performed. Hence, it is necessary to investigate other biological markers such as metabolic markers. We aimed here to challenge the three main biological markers used for the diagnosis of nitrous oxide abuse as total vitamin B12, homocysteine, and methylmalonic acid., Methods: We retrospectively collected clinical and biological data from 52 patients with known, documented chronic N 2 O abuse and associated clinical signs (peripheral neuropathy disability score or thrombosis event). Sera and plasma total vitamin B12, methylmalonic acid (MMA), and homocysteine were performed to identify the most specific marker of chronic N 2 O intoxication and related clinical outcomes., Results: Plasma homocysteine was almost consistently increased in case of N 2 O chronic consumption, whereas MMA increase and total vitamin B12 decrease are not systematically found. Our results showed that none of the markers are correlated with levels of N 2 O consumptions. However, homocysteine and MMA are correlated with clinical severity, but MMA seems to be a better marker of clinical severity., Conclusion: There is no specific marker of nitrous oxide abuse according to levels of consumption, total vitamin B12 decrease could not be used either as consumption or as severity marker. However, we showed that homocysteine is consistently increased and could be used as marker of recent N 2 O consumption. On the other hand, we showed that MMA could be used as a marker of clinical gravity., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

In the last few years, there has been an increase in the recreational use of nitrous oxide (N2O), which can lead to neurological symptoms such as sensory or motor disorders. The literature links these symptoms to a functional inactivation of vitamin B12 by oxidation of its cobalt ion, which prevents the vitamin B12 from acting as a cofactor for methionine synthase. Thus, demyelination related to methionine deficiency could be responsible for the neurological disorders associated with N2O consumption, including the combined sclerosis of the spinal cord. We aimed to study the correlation between the plasma methionine levels and clinical severity observed in N2O users. We retrospectively collected clinical and biological data from 93 patients who chronically consumed N2O. The patients were divided into four groups based of the severity of their clinical symptoms (based on their Peripheral Neuropathy Disability (PND) score). The plasma amino acids measurement, including methionine, were performed systematically by liquid chromatography coupled with mass spectrometry. Plasma methionine is significantly correlated with the clinical severity (Spearman coefficient: −0.42; p-value < 10−5), however, the average methionine level in the four groups is within the physiological values (N: 16−23 µmol/L). There is a significant inverse correlation between plasma methionine and homocysteine (Spearman coefficient: −0.57; p-value < 10−9), which confirms the action of nitrous oxide on the methionine synthase. A decrease in plasma methionine cannot be imputed as the only mechanism involved in the pathophysiology of the neurological disorders in nitrous oxide consumption. In addition, there are few therapeutic indications for the use of methionine. Thus, we should be careful concerning the potential use of methionine in nitrous oxide consumption. As a consequence, other pathophysiological mechanisms probably need to be identified in order to find potential therapeutic targets.

Background and Purpose: Although several case series have described nitrous-oxide-associated neurological disorders, a comprehensive assessment of exposure characteristics (e.g., time to onset, level of exposure) in substance abusers has not been performed. The aim of this study was to describe the onset patterns of recreational use of nitrous-oxide-induced neurological disorders., Methods: All cases of neurological disorders related to nitrous oxide recreational use reported to the Hauts-de-France addictovigilance center between January 2019 and August 2020 were selected. Only cases requiring hospitalization with informative data to perform the nitrous oxide causality assessment were included., Results: A total of 20 cases from five hospitals were included. The male-to-female ratio was 6:1 and the median age was 19 years (range 16-34). The neurological presentation (myeloneuropathy 64%, 7/11; sensorimotor neuropathy 36%, 4/11) included for all patients gait disorders due to proprioceptive ataxia and limb hypoesthesia. The median dose used per occasion was 100 cartridges (range 5-960; n = 19). The median time from the start of nitrous oxide use to the onset of neurological symptoms was 6 months (range 0.7-54; n = 16). The cumulative dose was significantly higher in patients with damage to all four limbs than in patients with lower limb symptoms only (p = 0.042)., Conclusions: A low intermittent exposure may be sufficient to cause neurological damage in some subjects, suggesting that, at the population level, there is no safe exposure to nitrous oxide in recreational settings. The severity of neurological impairment could increase once used at high doses and for prolonged durations of nitrous oxide., (© 2022 European Academy of Neurology.)

Background: Complications related to Chemsex practice (consumption of psychoactive substances in sexual context) were first assessed by the French Addictovigilance Network in 2014. In response to the deaths reported in 2016, a new expert report was commissioned to update the complications and evolution of Chemsex-related practices in France., Methods: Between January 2008 and August 2017, all Chemsex cases collected through the French Addictovigilance Network's epidemiological tools were analyzed. Comparison of data between two periods (before and after 2014) was performed to assess the evolution of practices., Results: Over the entire survey period, 235 Chemsex cases were identified, all of them in men, with a mean ± SD age of 39 ± 11 years, including 24 deaths (10.2%). An increase in the number of reported cases was observed from one in 2008 to 50 in the first 8 months of 2017. The main medical histories include human immunodeficiency virus (HIV; 45%) and hepatitis C (20%) infections, and substance use disorders (36%). In those 235 cases, 345 psychoactive substances were identified, mainly cathinones. Polydrug use was reported in 75% of cases. The main complications were substance use disorders (63%), acute neurological or cardiovascular intoxications (50%), various psychiatric disorders (39%), and viral and bacterial infections (18%). γ-Butyrolactone (GBL) was present in 95% of comas. An increase in the number of deaths was observed during the survey period., Conclusion: The French Addictovigilance Network, via this pharmacoepidemiological surveillance, warns public health authorities in order to support harm reduction programs and the management of Chemsexers., (© 2021 Société Française de Pharmacologie et de Thérapeutique.)

Nitrous oxide (N 2 O) toxicity is a concern common to several medical fields. Here, retrospective study of four N 2 O abuses with neurological signs in the emergency practice provides a preliminary basis for a metabolic Discussion/Review. This latter highlights N 2 O abuse as pathology of DNA/RNA/protein methylations, for instance consistent with impairments of protein arginine methyltransferases involved in myelinogenesis and myelopathy in patients. Basically, pathogenesis starts with oxidation by N 2 O of coordinated cobalamine cobalt ions at enzyme sites with impairments of vitamin-B12-dependent pathways. Methionine synthase (methylcobalamine) and methymalonyl-CoA mutase (adenosylcobalamine) are inactivated and cofactor-depleted, respectively. The number of impacted pathways (folate cycle, methylation cycle, S-adenosylmethionine-dependent methyltransferases, transulfuration pathway, Krebs cycle fueling by methylmalonyl-CoA, glutathione synthesis) explains the variety of potential research/laboratory markers, and may provide new clues and future angles to explore N 2 O toxicity. Overall, homocysteine measurements obviously help diagnosis of N 2 O abuses. Additional markers may include vitamin-B12, methionine, methylmalonate, dimethylglycine, sarcosine, S-adenosylmethionine to S-adenosylhomocysteine ratio, various S-adenosylamino acids, S-adenosylmethionine-dependent cellular methylations, and additional analytes (propionylcarnitine, propionylglycine, cystathionine and derived metabolites, methylated amino acids [eg arginine], betaine)., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Misuse/abuse of pregabalin is increasing worldwide. French Poison Control Centers (PCCs) recently received several unusual calls regarding the recreational use of pregabalin in adolescents. This study aims to describe this new and specific population of pregabalin misusers., Methods: We extracted all cases of pregabalin intentional exposures reported to the French National Database of Poisonings (FNDP) from 2004 to 2020. We compared the proportion of recreational exposure to pregabalin between adolescents (10-17 years) and adults (>18 years). We reviewed all cases of pregabalin recreational exposures in adolescent in order to describe the characteristics of this population., Results: During the study period, 382 cases of acute intentional exposure to pregabalin were reported in adolescents and 1188 in adults, 94/382 (24.6%) and 43/1188 (3.6%) were pregabalin recreational use, respectively ( p  < .0001). Almost all cases of pregabalin recreational use in adolescent were reported from 2018 (86/94; 91%). Most of those adolescent patients were males (male/female ratio - 5.3:1) and the median age was 15 years (range: 11-17.8). They were homeless or living in migrant shelters in most of the cases (73/90, 81%). Two-third of these exposures (62/94; 66%) involved other toxicant(s) than pregabalin. Most of the patients remains asymptomatic (10/94; 11%), or developed minor to moderate neurological symptoms (76/94; 81%). Eight developed severe symptoms (8/94; 8%) including coma (5/8) or generalized seizures (2/8). Five patients (5/8) required oro-tracheal intubation. No fatality was reported., Conclusions: We observed a sharp increase in pregabalin recreational use in adolescents in France. It should lead to prevention campaigns, targeted at the population at risk described in this study.

Poppers are legal and largely used in France despite severe side effects, such as methaemoglobinaemia (MetHbia). Our work aimed to assess the prevalence of poppers consumers among patients with a MetHbia higher than or equal to 5% in French university hospitals and its evolution before and after the legalization of poppers in France. We conducted a national multicentre observational retrospective study. All patients for whom at least one MetHbia measurement was performed from 2012 to 2017 in university hospitals where the French addictovigilance network (FAN) is implanted were included. For each MetHbia measurement exceeding or equal to 5%, a return to the clinical file was made by the FAN to assess poppers consumption. We calculated the prevalence of MetHbia exceeding or equal to 5% and 25% and the prevalence of poppers consumption before and after the legalization. A total of 239 (0.14%) patients had a MetHbia level exceeding or equal to 5% with 25 (10.46%) cases of poppers consumption. Poppers consumption represented 68.4% (13 out of 19) of cases with MetHbia greater than or equal to 25%. Poppers consumption among patients with MetHbia exceeding or equal to 5% increased after the legalization from 4.76% to 11.67% (prevalence ratio PR = 2.45, 95% CI = [0.98-8.37], p -value = 0.190). The proportion of patients with a MetHbia level of 25% or more increased after the legalization from 4.76% to 8.63% (PR = 1.81, 95% CI = [0.68-6.82], p -value = 0.374). The use of poppers is very frequently reported by patients with MetHbia greater than or equal to 25%.