[Thirty years of nefopam abuse in France]. / Trente ans d'abus de néfopam en France.

AIM OF THE STUDY: The use of nefopam is constantly increasing in France. The objectives of this study were to quantify the intensity of the drug dependence signal, to identify the populations at risk and the risk factors of dependence. METHODS: All serious and non-serious cases of misuse, abuse, drug dependence, overdose and withdrawal syndrome reported to the French Addictovigilance Network since 1988 were reviewed. An analysis of nefopam reimbursement data from the French national EGB (échantillon généraliste des bénéficiaires) database for the period 2006-2017 was also performed. RESULTS: The drug dependence profile of nefopam is close to that of a psychostimulant. Our literature review and the analysis of spontaneous reports confirm the risk of abuse and dependence of nefopam. In addition to a frequent psychiatric history (depression, psychosis, anxiety), nearly half of the patients also present addictive disorders, including more than one-third with opioid-dependence. In almost half of the 120 reported cases, the main adverse reaction was dependence and the frequency of serious effects was greater than 40%. In nearly 70% of the reported cases, the use was associated with chronic pain, which might explain the prolonged use. Moreover, the analysis of data on the reimbursement of nefopam in the general population showed that one French person out of two, having a prescription for nefopam, presented chronic pain. However, nefopam is only indicated in the treatment of acute painful conditions. Although it does not seem to be associated with a greater risk of abuse or dependence, taking the drug orally is another very frequent off-label use that needs to be regulated. CONCLUSION: In France, the prescription of nefopam outside of its marketing authorization is regrettable, because it contributes to the development of abuse and drug dependence.

Identification and tracking of Addictovigilance signals in general practice: which interactions between the general practitioners and the French Addictovigilance Network?

Addictovigilance is a health vigilance dedicated to the survey of medicinal or illicit psychoactive substance use disorders (SUDs). France is the only European country to have a vigilance system specifically dedicated to substances with an abuse/addiction potential. The French Addictovigilance system is organized in a network of regional tertiary centres (called Abuse and Dependence Monitoring Centres, CEIP-Addictovigilance) and works in close collaboration with Regional and National health authorities. Because of the essential and unavoidable nature of their practice in the French Healthcare system, general practitioners (GPs) are key actors to identify and track Addictovigilance signals. They have been involved in several of the pharmacoepidemiological surveys implemented by the French Addictovigilance Network (FAN). Now, they increasingly participate in clinical research projects and studies. In this article, interactions between GPs and the FAN are illustrated with two examples: patients on opioid substitution treatment and patients on opioid analgesics. Collaborations between GPs and the FAN could be further potentiated. In particular, more effective communication on psychoactive SUDs including abuse/addiction is necessary to optimize the implementation of preventive measures for patients on psychoactive substances medications, and to improve the attitudes of GPs and more widely health professionals in the management of any psychoactive user suffering from SUDs. In addition, both adapted training and improved collaborative research could contribute to the optimization (safety, quality) of professional practices.

Cannabinoid hyperemesis syndrome: Review of the literature and of cases reported to the French addictovigilance network.

BACKGROUND: Cannabinoid hyperemesis syndrome is a variant of cyclical vomiting syndrome in a context of chronic cannabis usage. Our aim was to compare French cases to those identified in the international literature in order to further our knowledge of the clinical criteria, pathophysiology and treatments for cannabinoid hyperemesis syndrome. METHODS: We analysed cases reported in the international literature up to 30 June 2017, obtained from the MEDLINE, PsycINFO and The Cochrane Library databases; we selected relevant articles based on title and abstract. We also analysed cases of cannabinoid hyperemesis syndrome reported to the French addictovigilance network. RESULTS: A systematic search through the three databases enabled us to identify 137 articles. Finally, 55 articles were selected as they involved reported cases. In total, 113 cases were reported in these 55 articles. We were thus able to analyse 29 reported French cases of cannabinoid hyperemesis syndrome. Cannabinoid hyperemesis syndrome mainly affects young male subjects who have been smoking cannabis daily for several years. Taking hot baths or showers is the most effective means of relieving the symptoms, while antiemetics and dopamine antagonists do not appear to effective for relieving nausea and vomiting. CONCLUSIONS: French cases display the same characteristics as the cases identified in the international literature. The pathophysiology of cannabinoid hyperemesis syndrome is unclear and several hypotheses have been put forward in the literature. We have only begun to characterise the syndrome, though there is an outbreak of cannabinoid hyperemesis syndrome in France.

[Uro- and nephrotoxic effects of drugs of abuse: Literature review and pharmaco-epidemiological survey in France and in the Marseille area]. / Effets uro-néphrologiques des produits utilisés par les usagers de drogues : revue de la littérature et enquête pharmaco-épidémiologique en France et dans la région de Marseille.

A great diversification of drugs of abuse has been observed in recent years, both in the populations using them and in the types of drugs. Although dependency and psychiatric disorders associated with the abuse of these substances is well known, somatic complications, uro-nephrotoxicity in particular, are less recognized. We propose here an overview of the products used by drugs abusers in France, through the analysis of the national pharmaco-epidemiological study Observation des produits psychotropes illicites ou détournés de leur utilisation médicamenteuse (OPPIDUM). Among the 5003 patients who participated in this survey, 84% were on prescribed psychoactive substances, with indicators of abuse in 28% of cases; more than half of these patients had also been using drugs of abuse (mainly cannabis) in the previous week. We then describe the main urological and renal toxicities of these drugs, in particular of heroin, cocaine, cannabis, ecstasy, LSD, amphetamine, new designer drugs, ketamine and opiate substitution treatment. We finally present a pharmaco-epidemiological survey of patients hospitalized for drugs complications in nephrology at the university hospital of Marseille. Between 2000 and 2015, 22 patients aged 18 to 57 years were hospitalized for renal adverse effects of drugs of abuse, such as glomerulonephritides, focal segmental glomerulosclerosis, acute kidney injury or chronic kidney disease. The somatic complications of drugs participate in their dangerousness and should be a red flag. They should be systematically reported to the addictovigilance national network to allow the improvement of information given to the patients and the medical community, and to adapt the prevention and risk reduction policies.

[The current aspects of the use of ecstasy/MDMA in France]. / Les aspects actuels de l'usage de l'ecstasy/MDMA en France.

Methylenedioxymethamphetamine (MDMA), the active compound of ecstasy, has been used for several years, especially by young adults to benefit of psychostimulant properties. By raising the level of neuromodulators in the synapsis, MDMA can cause psychiatric and physical injuries. After reduced supplies in 2009 (number of ecstasy seizures equal to 10 percent of those recorded in 2002), judicial authorities now observed an increased availability (a half more part of seizures in 2012 than 2010). From its "Spontaneous Notifications" data base and "deaths in connection with the abuse of medicine and substances (DRAMES)", "observation of illegal drugs and misuse of psychotropic medications" (OPPIDUM), and "observation of drug dependencies in ambulatory medicine" (OPEMA) national inquiries, the French Addictovigilance network (CEIP-A) highlighted the increasing consumption of MDMA. The way of use appeared quite unchanged: users were mainly young men between 25 and 30 years; they favored an occasional use but mainly combined other products such as alcohol, cannabis and other stimulants. Severity of the clinical cases, based on hospital care and forensic data, could be consistent with the higher amounts of MDMA measured in pills.

Patterns of Methylphenidate Use and Assessment of Its Abuse among the General Population and Individuals with Drug Dependence.

PURPOSE: The aim of this study was to describe the extent of methylphenidate (MPH) abuse and characterize its patterns by following several cases involving intravenous administration of crushed MPH tablets. METHODS: First, a drug reimbursement database (covering 4 million inhabitants) was explored to assess the magnitude of MPH abuse among the general population, and second, a specific study based on individuals with drug dependence was performed to describe abusers' characteristics (n = 64), patterns of abuse and clinical implications. RESULTS: From 2005 to 2011, the number of patients who were dispensed MPH at least once increased by 166%. The patients with 'deviant' patterns of MPH consumption were mainly male adults with opiate maintenance treatment reimbursements. MPH abusers had precarious living conditions. Half of them consumed MPH daily by intravenous route and reported amphetamine-like effects (cardiovascular events, weight loss, psychiatric adverse events). CONCLUSION: Given the increase of MPH use, it is important to warn the scientific community about possible MPH abuse, especially in individuals with drug dependence. This study has facilitated public health intervention and dissemination of information related to MPH abuse among health care professionals at local and national levels.

Illicit drugs or medicines taken by parachuting.

Parachuting (also called bombing) is a method of drug delivery where illicit drugs or medicines are ingested after wrapping the substance. There are little data describing parachuting in the literature. To provide a description of this practice, all cases of parachuting reported to the national addictovigilance network up to 31 December 2014 were identified from spontaneous reports and specific surveillance programs. Cases were described according to the type of substance used, patient age and gender, type of complications, context of use and year of the event. Forty-five cases of parachute use were identified and most (n = 43) occurred after 2011. Patients were mostly men (60%), and mean age was 28.9 years. The context of use, known in 19 cases, was mostly recreational. Complications were present in 24 cases, of which eight were serious. The substance was supposed to be 3,4-methylenedioxymethamphetamine (MDMA) in the majority of cases (64.4%); research chemicals were more involved in the most recent years. The physical form was mainly granular (51.6%). The wrappers were a cigarette paper (nine cases) and in one case plastic package; in the other cases, the term of parachute was used without further details. The reason for use was not explained in the majority of cases; two patients indicated using a parachute for faster effect than with a methadone capsule. Clinicians should be aware of this delivery form as the results suggest that it is common and can involve a great variability of drugs.

[Severe distal ischemic syndrome after buprenorphine volunteer intra-arterial injection]. / Syndrome ischémique distal sévère après injection intra-artérielle volontaire de buprénorphine.

High dosage buprenorphine (HDB) is a sublingual maintenance treatment of opioid dependence which have proved its substantial Public Health results, but it is also known to be frequently abused and diverted, in particular for intravenous injection, with deleterious consequences. Intra-arterial use is more rarely reported with this substance, just like its complications, mainly ischemic, potentially necrotic, phenomena. We report here such a case, with a 30 years-old man suffering from severe ischemia of the thumb, the forefinger and the middle finger few hours after direct injection of a suspension of buprenorphine crushed tablets in right radial arteria. A treatment combining surgery (video-thoracoscopic thoracic sympathectomy) and medicines (heparin, iloprost and piribedil mesilate), permitted a semi-complete digital rehabilitation (only forefinger pulp necrosis persisted and required a distal amputation), and the patient was discharged after 2 weeks.

Cannabis body packing: two case reports.

INTRODUCTION: Body packing is a well-known means of narcotic carriage across international borders. The most common drugs carried are cocaine and heroin. CASE DESCRIPTIONS: We describe 2 cases of cannabis body packing which occurred the same year in the South of France, one with complications: a 45-year-old male went to emergency for abdominal pain. A plain abdominal x-ray revealed multiple foreign bodies in the gastrointestinal tract. It was confirmed by abdominal CT. The laparatomy confirmed peritonitis secondary to colonic perforation, and 34 filled condoms packages were extracted. After calling poison centre, toxicological analysis was performed on one package. The resin wrapped in cellophane contained 15% tetrahydrocannabinol (THC). The patient was discharged on day 12. DISCUSSION/CONCLUSION: Cannabis body packing is rarely reported, and the only known complications have a mechanic etiology. Plain abdominal x-ray is the best method for detection and it can be confirmed by abdominal CT and toxicological analysis. Cannabis is the most important illicit drug used in the word. Also cannabis body packing is probably underestimated. Health care practitioners should be aware of the possibility of body packing when someone coming back from abroad complains of abdominal pain.

[Accidental cannabis poisoning in children: experience of the Marseille poison center]. / Intoxications accidentelles par cannabis chez l'enfant: expérience du centre antipoison de Marseille.

OBJECTIVE: To assess the frequency and severity of accidental cannabis poisoning in children. METHODS: A retrospective study of cases of accidental cannabis poisoning in people aged under 18 years old, reported to the Marseille poison center from 1993 through 2007. We excluded cases where cannabis was definitively ruled out, and neonatal withdrawal syndromes in newborns from cannabis users. RESULTS: We collected 93 cases, including 56 boys and 37 girls, 86% of whom were younger than 3 years. The principal form was cannabis resin (hashish), reported in 80% of the cases and belonging to one of the parents or a household member. In almost all cases, the poisoning took place at the child's home. The frequency has risen in recent years, with 2/3 of the cases occurred in the second half of the study period. Five serious cases were reported, two with convulsions. CONCLUSION: Considering the observed increase in cases each year, mostly benign but potentially serious, prevention and information efforts have to be improved for drug users with young children and for healthcare professionals led to manage this kind of accident.

[Abuse of licit and illicit psychoactive substances in children and teenagers in the PACA Region (Southeastern France)]. / Usage abusif des produits psychoactifs licites ou illicites chez l'enfant et l'adolescent dans la région PACA (Sud-Est de la France).

INTRODUCTION: The abuse of licit and illicit psychoactive substances in children and teenagers represents a public health problem. MATERIALS AND METHODS: The aim of this study was to evaluate the extent of this phenomenon and its growth in the PACA (Provence-Alpes-Côte d'Azur) region (Southeastern France). The cases identified during the 10-year period 1992-2002 by the CEIP (Centre d'Evaluation et d'Information sur la Pharmacodépendance) were studied retrospectively. RESULTS: One hundred and ninety-one cases were identified. In most instances, abuse involved a first experience or was sporadic. The users were often boys (70%). The substances were solvents (48.7%) used collectively (33%) during recreational activities (74%). Illicit drugs accounted for 28.2% of the cases involving a first experience (89%), with polyconsumption accounting for 50%, cannabis 57.6%, ecstasy 25.9%, and LSD (lysergic acid diethylamide) 12.1% of cases. Medicines were also used (16%), the most frequent being benzodiazepines (51.6%). CONCLUSION: The study confirms the abuse of licit and illicit psychoactive substances in children and teenagers and provides information regarding the substances available in this region of France.