Abstract 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.
Sickle cell disease (SCD) induces chronic haemolytic anaemia and intermittent vaso-occlusion that results in tissue ischaemia causing acute, severe pain episodes that can lead to frequent ...hospitalizations. These consequences can have repercussions on family, social, school and/or professional life. Here, we present some of the results of the PHEDRE study (Pharmacodépendance Et DREpanocytose-drug dependence and sickle-cell disease), which is the largest study of patients with SCD in France. This paper intends to describe characteristics of the French SCD population. We also aimed to assess the impact of the disease on the lives of patients using objective and subjective variables.
The PHEDRE study was a national multicentric observational study. Adults, adolescents and children with a confirmed SCD diagnosis were included in the study by their referring doctor. Then, they were interviewed by phone about their socioeconomic status, about the impact of the disease on their lives and about their analgesic and psychoactive drug use.
The study population consisted of 872 patients (28% were minors). Seventy-two percent of adults were active, and all minors were in school. Many patients presented criteria of severe SCD. Seventy-five percent were homozygous SS, 15% were double heterozygotes SC and 8% were heterozygotes Sβthal, 87% received specific treatment, 58% were hospitalized at least once for vaso-occlusive crisis in the past 12 months, and the number of analgesic drugs taken averaged 3.8. Seventy-five percent of patients reported academic or professional consequences related to their SCD, and 52% reported social consequences.
The impact of SCD on patients' lives can be significant, nevertheless their social integration seems to be maintained. We highlighted respect of recommendations regarding analgesic treatments and only a few patients used tobacco, alcohol or cannabis.
Clinical Trials, NCT02580565; https://clinicaltrials.gov/ Registered 16 October 2015.
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.
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%.
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.
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.
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.
Nitrous oxide (N2O) toxicity is a concern common to several medical fields. Here, retrospective study of four N2O abuses with neurological signs in the emergency practice provides a preliminary basis ...for a metabolic Discussion/Review. This latter highlights N2O 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 N2O 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 N2O toxicity. Overall, homocysteine measurements obviously help diagnosis of N2O 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).
•Recreational use of N2O can reach 100 to 300 cartridges/day, and cause neurological deterioration.•N2O by oxidising the coordinated cobalt ion disrupts cobalamin (vitamin B12)-dependent pathways.•N2O disrupts folate, methylation cycles; DNA, RNA, protein methylations; glutathione synthesis.•Laboratory markers include increased plasma homocysteine and numerous metabolites reviewed.•Treatment of abuse is cessation of N2O consumption and supplementation with vitamins B12 and B6.
•Psychostimulant use, whether free-access, prescription or illicit, is high among students.•ADHD symptoms are significantly associated with psychostimulant use in students.•ADHD screening and ...targeted prevention measures for substance use disorders are required in students.
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.
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.
Background The gamma-aminobutyric acid type B receptor agonist baclofen is approved for spasticity and is used off-label for diverse types of addictive disorders, notably alcohol dependence. Baclofen ...may induce numerous neuropsychiatric adverse drug reactions, including behavioral disinhibition. However, this precise adverse drug reaction has never been assessed using either a validated causality algorithm or a scale for manic symptoms. Methods We report a case of a 49-year-old male patient who exhibited de novo mania during treatment with baclofen for alcohol dependence. Symptoms were evaluated using the Young Mania Rating Scale, and the causality of baclofen was determined using the Naranjo algorithm. This case was also compared with other cases of baclofen-induced mania through a systematic literature review. Results Mr. X, taking 180 mg/d of baclofen, presented with mania and scored 24 of 44 on the Young Mania Rating Scale, and the imputability of baclofen was “probable” using the Naranjo algorithm (8 of 13). In addition, 4 other cases of baclofen-induced mania were reported in the literature; 3 cases had a bipolar I disorder history. Baclofen-induced manic symptoms occurred mostly during the dose-escalation phase. Conclusion Baclofen-induced manic symptoms may appear in patients with or without bipolar disorder. Particular attention is required during the dose-increase phase and in patients with a history of mood disorders.
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