Sex/gender differences in spontaneous reports to a French Addictovigilance centre.

To specify psychoactive substances and related complications observed in spontaneous reports (SRs) in women versus men, we assessed SRs on substance-linked acute toxicity sent to a French Addictovigilance centre. Over the period 2021-2022, 880 SRs were analysed (33.4% concerned women). Severe complications concerned more men than women (70.3% versus 59.5%; p = 0.0014). In women, the main implicated substances were psychoactive medications (opioids, benzodiazepines). The most frequently reported complication was suicidal behaviour (14.6% versus 7.8%, p = 0.002). In men, SRs concerned mainly illicit substances (cocaine, amphetamines) or misuse of opioid maintenance therapy or nitrous oxide. The main complications in men were infections (12.97% versus 5.4%, p = 0.0006) and neurological troubles (37.6% versus 23.5%, p < 0.0001).Our data highlight sex/gender disparities in substance use and complications, in agreement with recent literature and French national Addictovigilance data.

Isotonitazene, a synthetic opioid from an emerging family: The nitazenes.

From 2019, in the United States and Europe, the synthetic opioid market has diversified with the appearance of the 2-benzylbenzimidazole family, commonly named "nitazenes". In vitro studies show that these synthetic opioids have much higher affinities on µ-opioid receptors: 100 times more than morphine, and slightly higher than fentanyl for isotonitazene, increasing the risk of overdose. In south of France, isotonitazene (IZN) was identified for the first time in March 2023. In this context, there were 9 reports concerning the use of IZN in the south of France over a short period (March-April 2023), with identification of IZN in 4 cases and suspicion in others. They concerned 6 men and 3 women, with a mean age of 44.9±2 years. When available (2 cases), the product had been purchased from a dealer. IZN was identified on sample in 2 cases of overdose. Isotonitazene was also identified in biological samples in 2 cases: 1 case of overdose and coma requiring hospitalization with a favorable outcome (urinary analysis), and a death with post-mortem identification. This was the first identification of this product in France. The immediate broadcast of the alert limited the risks for users and made it possible to quickly inform regional and national health authorities. IZN is under intensive surveillance by the EMCDDA and classified as a narcotic in France since 2021. The analysis of the literature made it possible to identify cases of overdoses requiring very high doses of naloxone and deaths. The emergence of these synthetic opioids constitutes an important signal, due to their superior effects to heroin, their incomplete response to naloxone and the current difficulty in identifying them (devices for analyzing products in the reduction of risks, toxicology laboratories).

Patterns of ketamine use among people with substance use disorder in France: Multisource analysis of the data from the French Addictovigilance Network.

BACKGROUND: Due to its psychoactive effects, ketamine has become a drug used for non-medical purpose. OBJECTIVES: To assess the latest trends in ketamine use among people with substance use disorder and to characterize its clinical complications using complementary health data sources of the French Addictovigilance Network. METHODS: First, we extracted all reports involving ketamine from 2012 to 2021 from the database of the OPPIDUM program (i.e., a multicentric program conducted in collaboration with hundreds of substance abuse treatment facilities that collects data on drugs used by subjects with substance use disorders). We described the reports globally and the changes from 2012 to 2021. Second, we extracted all cases involving ketamine from July 2020 to December 2022 from the French National Pharmacovigilance Database (BNPV). We identified the cases related to ketamine use among people with substance use disorder and described them. RESULTS: There was a 2.5-fold increase in the number of ketamine users with substance use disorder in the OPPIDUM program, from 35 (0.7%) subjects in 2012 to 89 (1.7%) subjects in 2021. There was an increase in the proportion of subjects who were daily users, had distress upon discontinuation, and presented addiction. There were 238 cases related to ketamine use among people with substance use disorder in the French National Pharmacovigilance Database from July 2020 to December 2022. Among them, 94 (39.5%) cases involved ketamine use disorder, 20 (8.4%) cases involved urinary tract and kidney symptoms, and 13 (5.5%) cases involved hepatobiliary symptoms. CONCLUSION: The trend observed over 10 years reflects the growth in ketamine use among people with substance use disorder, although it does not allow to estimate the rates of non-medical use of ketamine in the general population. Ketamine-induced uropathy and cholangiopathy are reported in ketamine users with substance use disorder, especially in case of repeated and/or prolonged use of high doses.

Functional vitamin B12 deficiency is a consistent feature in hospital admissions for neurological disorders due to the use of nitrous oxide.

Introduction: Misuse of inhaled nitrous oxide is a growing concern in France. It is known to alter concentrations of vitamin B12, which is required as a cofactor for methionine synthase and methylmalonyl-CoA mutase activity. Hence, measurement of the concentrations of cobalamin metabolism biomarkers, including vitamin B12, homocysteine, and methylmalonic acid, could assist in the management of patients with a complex clinical presentation or in those who deny the consumption of nitrous oxide.Methods: We retrospectively collected clinical and biological data in patients hospitalized for nitrous oxide use in a university hospital in southern France between January 2020 and October 2022.Results: Thirty-one patients were identified during 34 months; 79% were men with a median age of 23.7 years. Most (97%) presented with peripheral polyneuropathy and/or myelopathy. The median vitamin B12 concentration was 134.6 pmol/L, with 17 of 31 patients having values less than 145 pmol/L (the lower limit of the normal range). The median plasma folate concentration was 20.1 nmol/L, which is within the normal range. The median plasma homocysteine concentration was 87.7 µmol/L (normal range <15 µmol/L), and the median plasma methylmalonic acid concentration was 3.8 µmol/L (normal range <0.5 µmol/L).Conclusion: Nitrous oxide use is an emerging public health problem in France, as shown by the number of patients admitted to our hospital. The presence of a functional vitamin B12 deficiency was a consistent feature that could be helpful in diagnosis in complex cases.

[Increase of overdose and deaths related to methadone during COVID-19 epidemic in 2020]. / Augmentation des surdoses et décès en lien avec la consommation de méthadone durant la crise sanitaire liée au COVID-19 en 2020.

INTRODUCTION: Due to the risk of overdoses increase especially with methadone, a reinforced monitoring has been set up by the French Addictovigilance Network following the first lockdown related to coronavirus disease 2019 (COVID-19). In this context, we managed a specific study to analyze overdoses related to methadone in 2020 compared to 2019. MATERIAL AND METHODS: We analyzed methadone-related overdoses which occurred in 2019 and 2020 from two sources: DRAMES program (deaths with toxicological analysis) and the French pharmacovigilance database (BNPV) (overdoses that did not lead to death). RESULTS: Data from DRAMES program in 2020 show methadone as the first drug involved in deaths as well as an increase in deaths: in number (n=230 versus n=178), in proportion (41% versus 35%) and number of deaths per 1000 exposed subjects (3.4 versus 2.8). According to BNPV, the number of overdose increased in 2020 compared to 2019 (98 versus 79; i.e., 1.2-fold increase) particularly during several target periods: first lockdown, end of lockdown/summer period and second lockdown. In 2020, a higher number of cases were observed in April (n=15) and May (n=15). Overdoses and deaths occurred in subjects enrolled in treatment programs or not (naïve subjects/occasional users who obtained methadone from street market or family/friends). Overdoses resulted from different factors: overconsumption, multiple drug use with depressants drugs or cocaine, injection, consumption for sedative, recreational purposes or voluntary drug poisoning. DISCUSSION/CONCLUSION: All these data show an increase of morbidity and mortality related to methadone during COVID-19 epidemic. This trend has been observed in other countries.

Alprazolam misuse: Analysis of French Addictovigilance Network data from 2011 to 2020.

OBJECTIVES: Alprazolam, a high-potency and short-acting anxiolytic benzodiazepine, is one of the most misused benzodiazepines in France. In the context of various reports on alprazolam misuse during the COVID-19 pandemic, the objective of this study was to assess alprazolam abuse potential by analyzing French addictovigilance and international data. METHODS: Data collected from 2011 to 2020 using the following epidemiological tools of the French Addictovigilance Network were analyzed: spontaneous reports (SRs), OPPIDUM (addiction care center data), OSIAP (falsified prescriptions), DRAMES (substance-related deaths), and chemical submission surveys. Moreover, the VigiBase™ database was analyzed to evaluate alprazolam abuse liability worldwide. RESULTS: During the study period, 675 SRs concerning alprazolam misuse were recorded (sex ratio: Ì´1; median age: 39 years). The desired effects were intensification of the therapeutic anxiolytic effect, euphoric effect, and management of substance withdrawal. Alprazolam was the third and first benzodiazepine listed in OPPIDUM and OSIAP surveys. Analysis of the SR and OPPIDUM data showed a recent increase in the alprazolam-opioid combination. In DRAMES data, alprazolam was directly linked to 11 deaths (associated with opioids in 10/11). VigiBase™ data analysis highlighted that France was the third country with the most cases of alprazolam misuse. The disproportionality analysis showed that in France, alprazolam was associated with higher risk of misuse and dependence compared with other benzodiazepines: reporting odds ratio=1.43, (95% CI: 1.04-1.95) and=1.97 (95% CI:1.50-2.59), respectively. CONCLUSIONS: This study highlighted an increase in various signals of alprazolam abuse in France, and an increased use of the alprazolam-opioid combination that was also linked to most of the recorded alprazolam-linked deaths. These signals have been reported also in the international literature, and should be thoroughly investigated.

Adverse events of recreational cannabis use during pregnancy reported to the French Addictovigilance Network between 2011 and 2020.

Cannabis is the main illicit psychoactive substance used by pregnant women in France. The aim of the present national survey was to describe adverse events (AEs) of recreational cannabis use during pregnancy reported to the French Addictovigilance Network (FAN). Spontaneous reports (SRs) of AEs related to recreational cannabis use during pregnancy were collected by the FAN between 01/01/2011 and 31/01/2021 (excluding cannabidiol and synthetic cannabinoids). Over the study period, 160 SRs involved cannabis use alone or in association with tobacco (59% of all SRs) which increased. Among the 175 maternal AEs, the most commons were psychiatric AEs experienced by 96 (64.9%) women, in particular cannabis use disorders (n = 89, 60.1%), dependence (n = 54, 36.5%) and abuse (n = 21, 14.2%). Among the 57 fetal AEs, the most common were heart rhythm disorders that affected 25 (16.9%) fetuses and intrauterine growth restriction (IUGR) (n = 20, 13.5%). Among the 140 neonatal AEs, the most common were IUGR experienced by 39 (26.3%) newborns and prematurity (n = 32, 21.6%). Twelve cases of congenital malformations were observed and 4 intrauterine/neonatal deaths. Furthermore, some of these AEs (n = 13) were unexpected. Cannabis use during pregnancy has problematic consequences for both mothers and infants who need close monitoring.

Ten-year trends in hospitalizations related to cocaine abuse in France.

In France, the abuse/misuse of psychoactive substances, including cocaine, is monitored via spontaneous notifications, and under-reporting is its main limitation. Therefore, the French national hospital discharge database (Programme de Médicalisation des Systèmes d'information [PMSI]) was used to identify all hospital stays possibly due to complications related to cocaine use. The objective was to determine the main trends in the rate of cocaine-related hospitalizations from 2010 to 2019 by age category and by areas. Relevant PMSI data were extracted using the International Classification of Diseases (10th edition). In France, hospitalizations for cocaine-related complications increased by fourfold (2461 in 2010, 9843 in 2019, +300%). This increase was similar in men and women and was observed in each age category. Patients were mainly men (75% in 2010 and in 2019), with a median age of 38.5 and 35.2 years for men and women, respectively, in 2019. Cocaine poisoning in pediatric patients (0-9 years) concerned less than 10 patients in 2010 and 21 patients in 2019. PMSI data analysis shows an overall increase of cocaine-related hospitalizations in France from 2010 to 2019 that can be linked in part to an increasing recreational use. The increase of pediatric cases of cocaine poisoning suggests a trivialization of cocaine consumption.

Abuse and misuse of second-generation antipsychotics: An analysis using VigiBase, the World Health Organisation pharmacovigilance database.

The study aim was to assess the abuse/misuse potential of second-generation antipsychotics (SGAPs) using VigiBase data. We extracted individual case safety reports of "Drug abuse, dependence and withdrawal" involving SGAPs up to June 2018. We assessed disproportionate reporting by calculating the information component, considering the lower end of the 95% credibility interval for the information component (IC025 ), and the proportional reporting ratio. We identified 1683 individual case safety reports recorded as "abuse, dependence and withdrawal" involving SGAPs, mainly quetiapine (n = 1089) and olanzapine (n = 209). The disproportional reporting indicators highlighted an association between "Drug abuse and dependence", and quetiapine, olanzapine and ziprasidone, as indicated by the IC025 (2.263, 0.259 and 1.051, respectively) and proportional reporting ratio values (3.929, 1.020 and 1.334, respectively). The abuse/misuse potential is confirmed for quetiapine and olanzapine and highlighted for the first time for ziprasidone. Physicians should consider these risks when prescribing these antipsychotics, especially to patients with history of drug abuse.

Opioid misuse in community pharmacy patients with chronic non-cancer pain.

AIMS: Community pharmacists could contribute to identify people misusing prescription opioids, which may be associated with hospitalizations, substance use disorders and death. This study investigated prescription opioid misuse in community pharmacy patients and the factors potentially associated with high Prescription Opioid Misuse Index (POMI) scores. METHODS: In this cross-sectional study, pharmacy students asked patients with opioid prescriptions to fill in a questionnaire (including the POMI) in community pharmacies in a French region, in April 2019. Eligible patients were adults with chronic non-cancer pain who consented to participate. RESULTS: In total, 414 patients (62.4% women; mean age: 58.00 years ± 16.00) were included. The prescribed opioids were mainly weak opioids (73.2%; paracetamol/tramadol: 35%). Strong opioids (32.6%) included oxycodone (11.95%), fentanyl (9%) and morphine (9%). The median morphine milligram equivalent (MME) was 40 mg/day (IQR25-75 : 20-80). The POMI score (0 to 6) was ≥4 in 16% of patients who were younger (P < .01), more urban (P = .03), with higher pain visual analogue scale (VAS) score (P < .01) and MME (P < .01), and treated more frequently with strong opioids (P = .04). In multivariate analysis, age (ORfor 10y : 0.68 (95% CI: 0.56-0.82, P < .0001)), VAS (OR2units : 1.78 (95% CI: 1.26-2.40, P = .0008)), and MME (>100 mg, OR: 2.65 (95% CI: 1.14-4.41, P = .0194)) were significantly associated with POMI scores ≥4. CONCLUSIONS: The high proportion of patients with high POMI scores underlines the interest of prescription opioid misuse screening in community pharmacies, in order to help these patients and refer them to pain specialists, if needed.

Chemsex practice in France: An update in Addictovigilance data.

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.

Adverse reactions with levamisole vary according to its indications and misuse: A systematic pharmacovigilance study.

Levamisole was initially prescribed for the treatment of intestinal worms. Because of immunomodulatory properties, levamisole has been used in inflammatory pathologies and in cancers in association with 5-fluorouracil. Levamisole is misused as a cocaine adulterant. Post-marketing reports have implicated levamisole in the occurrence of adverse drug reactions (ADRs) and its use is now limited in Europe and North America. In contrast, all other parts of the World continue to use single-dose levamisole as an anthelmintic. The aim of this study was to identify ADRs reported after levamisole exposure in VigiBase, the World Health Organisation's pharmacovigilance database, and analyse their frequency compared to other drugs and according to levamisole type of use. METHODS: All levamisole-related ADRs were extracted from VigiBase. Disproportionality analyses were conducted to investigate psychiatric, hepatobiliary, renal, vascular, nervous, blood, skin, cardiac, musculoskeletal and general ADRs associated with levamisole and other drugs exposure. In secondary analyses, we compared the frequency of ADRs between levamisole and mebendazole and between levamisole type of use. RESULTS: Among the 1763 levamisole-related ADRs identified, psychiatric disorders (reporting odds ratio with 95% confidence intervals: 1.4 [1.2-2.6]), hepatobiliary disorders (2.4 [1.9-4.3]), vasculitis (6.5 [4.1-10.6]), encephalopathy (22.5 [17.4-39.9]), neuropathy (4.3 [2.9-7.1]), haematological disorders, mild rashes and musculoskeletal disorders were more frequently reported with levamisole than with other drug. The majority of levamisole-related ADRs occurred when the drug was administrated for a non-anti-infectious indication. CONCLUSION: The great majority of the levamisole-related ADRs concerned its immunomodulatory indication and multiple-dose regimen. Our results suggest that single-dose treatments for anthelmintic action have a good safety profile.

Management of Pregabalin Use Disorder: A Case Series.

Pregabalin is indicated for the treatment of partial epilepsy, generalized anxiety disorder, and neuropathic pain. The first reports on pregabalin use disorder have been published in Europe in 2010 and notified to the French Addictovigilance Network (FAN) in 2011. The management of pregabalin use disorder is challenging due to the risks associated with the abrupt withdrawal and lack of guidelines. In this retrospective observational study, the management of pregabalin use disorder was analyzed in eight cases reported to the addictovigilance center of Montpellier, France, between 2019 and 2020. Most of these patients had a history of illicit psychoactive substance use. During the withdrawal period, patients experienced mainly psychiatric problems, nervous system symptoms, general disorders, and gastrointestinal symptoms. Multiple strategies were proposed for these patients to manage pregabalin withdrawal, such as hospitalization and pregabalin gradual dose reduction with or without adjuvant medications. Two patients relapsed and the others were lost to follow up. Although other reports of pregabalin use disorder have been published, recommendations or guidelines for its management are not yet available. The current case series and the previous reports suggest that the use of adjunctive therapy may be useful to limit the risk of convulsions and anxiety.

Adverse events of recreational cannabis use reported to the French addictovigilance network (2012-2017).

AIMS: To describe the adverse events (AEs) of recreational cannabis use in France between 2012 and 2017. METHODS: AEs related to recreational cannabis use, alone or in combination with alcohol and/or tobacco reported to the French Addictovigilance Network were analysed (excluding cannabidiol and synthetic cannabinoids). RESULTS: Reporting of AEs tripled between 2012 (n = 179, 6.3%, 95% confidence interval [CI] = 5.4-7.2) and 2017 (n = 562, 10.1%, 95% CI = 9.3-10.9), reaching 2217 cases. They concerned mainly men (76.4%) and users aged between 18 and 34 years (18-25: 30.9%; 26-34: 26.3%, range: 12-84 years). Cannabis was mainly inhaled (71.6%) and exposure was most often chronic (64.2%). Many types of AEs were reported: psychiatric (51.2%), neurological (15.6%), cardiac (7.8%) and gastrointestinal (7.7%), including unexpected AEs (n = 34, 1.1%). The most common effect was dependence, ranging from 10.1% (95% CI = 7.9-12.3) to 20.3% (95% CI = 17.3-23.2) over the study period. Cannabinoid hyperemesis syndrome (n = 87, 2.8%) emerged from 2015. Deaths accounted for 0.2% of all AEs (4 men and 3 women aged on average 35 years). A chronic pattern of cannabis use was reported in 4 of them (intracranial hypertension in the context of lung cancer, suicide, cerebral haematoma, neonatal death with concomitant chronic alcohol use), while in the other cases the toxicological analysis identified cannabis use (ruptured aneurysm and unknown aetiology). CONCLUSION: This study showed a multitude of AEs related to recreational cannabis use, including unexpected AEs and deaths. It highlights the problem of dependence and the emergence of cannabinoid hyperemesis syndrome.

Bacterial infections in people who inject psychoactive substances: An observational study in a French university hospital.

AIM OF THE STUDY: To describe bacterial infections in injection drug users (IDUs) hospitalized at Montpellier University Hospital, France, and to identify factors that might influence the development of local or systemic infections. METHODS: This cross-sectional observational monocentric study prospectively included bacterial infections in IDUs hospitalized at Montpellier University Hospital between 2012 and 2018. Types of infection (local or systemic) were described and compared to identify specific features (injection practices). RESULTS: The study included 144 bacterial infections (56% of local infections and 44% of systemic infections) concerning 117 IDUs. The most common infection types were abscesses (50%), skin and soft tissue infections (33%), bacteremia/sepsis (20%), endocarditis (17%), and bone and joint infections (16%). Patients were mainly men (n=94; 80%), and the median age was 40 years [IQR25-75: 34-47]. Four deaths related to systemic infection were reported. The most frequent injected substances were cocaine, opioid maintenance treatments (OMT), and opioids. According to the multivariate analysis, factors associated with the occurrence of systemic infections were number of injection (OR 2.59 [1.07-6.27]; P=0.034) and injection of at least one opioid (OR 3.52 [1.28-9.72]; P=0.015). CONCLUSION: Different types of bacterial infections, local or systemic, are observed in IDUs. Skin infections are quite common, but other infection types also are reported, with sometimes serious consequences. It is already known that injection practices are contributing factors in infection development, but the type of injected psychoactive substance(s) also may have an influence.

Substance use among refugees in three Lebanese camps: A cross-sectional study.

BACKGROUND: There is a strong link between conflict exposure and ill health, including substance use. However, this widely acknowledged problem has not been studied yet in refugee camps in Lebanon. AIM: To investigate substance use among civilians following war or displacement, and to assess its association with socio-demographic characteristics. METHOD: Cross-sectional observational study carried out in three Palestinian camps in Lebanon using the World Health Organization Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). Participants were Palestinian adults born in Lebanon and Palestinian and Syrian adults recently displaced from Syria due to war. The percentage of people reporting substance use and the associations between lifetime and last three months substance use and demographic features were assessed using a multivariate logistic regression. RESULTS: In general, lifetime substance use was higher among Palestinians born in Lebanon compared to Syrians and Palestinians displaced from Syria (OR 7.241, 95% CI [3.781-13.869], P <0.0001). Results from ASSIST score during last three months showed that moderate and high-risk use of cannabis and cocaine were higher among Palestinians born in Lebanon than Palestinians and Syrians displaced from Syria. The multivariate analysis showed that women had lower lifetime (OR 0.188, 95%CI [0.080-0.442], P <0.0001) and lower last three months substance use than men, whereas single people were more likely to use substances than married people (OR: 2.78, 95%CI [1.588-4.866], P <0.0001). Tobacco was significantly associated with higher risk of substance use. CONCLUSION: These findings suggest a higher rate of lifetime substance use among Palestinians born in Lebanon than in Palestinians and Syrians recently displaced from Syria. Substance use is influenced by different socio-demographic factors in the two groups of refugees. However, many factors other than socio-demographic characteristics and refugee status may influence substance use, particularly quality of life and health status that should be assessed in future studies.

Health consequences of cocaine use in France: data from the French Addictovigilance Network.

As the number and severity of complications related to cocaine use reported to the French Addictovigilance Network have increased, the French health authorities requested a national epidemiologic study of the data collected by this network from 2010 to 2016. For this purpose, the spontaneous reports (SRs) linked to cocaine notified by health professionals were analyzed as well as the data from the pharmacoepidemiological surveys OPPIDUM (observation of illegal drugs and misuse of psychotropic medications) and DRAMES (deaths related to the abuse of licit and illicit psychoactive substances). In total, 1 265 SRs were analyzed (510% increase from 2010 to 2016). Users were mainly men (952/1 261; 75%), with a median age of 35.0 years [IQ25-75 : 28-42]. Cocaine was consumed through the intranasal route by 52% of users (416/797), followed by intravenous administration (32%, 253/797) and inhalation (24%, 190/797). The use of cocaine powder and crack cocaine was reported in 70% (475/674) and 23% (154/674) of SRs, respectively. Cocaine was consumed with other psychoactive substances and alcohol in 47% (603/1265) and 60% (387/649) of cases, respectively. The main cocaine-related complications were psychiatric complications (29%), neurologic complications (24%) and cardiovascular complications (23%). Analysis of the OPPIDUM survey data showed that in 2016, 15.9 and 2.4% of the included subjects consumed cocaine or crack cocaine the week preceding the survey, the highest rate for the 2006-2016 period. The DRAMES survey indicated that cocaine-related deaths increased by threefold from 2014 to 2016. These data confirm that cocaine use in France is worrying with an increase in the number of severe complications and deaths.

Use of new psychoactive substances to mimic prescription drugs: The trend in France.

Among the expanding world of New Psychoactive Substances (NPS), Designer Medicines (DM) are designed to mimic psychoactive drugs and might lead to adverse events of various severity. The DM category includes designer benzodiazepines (DB), phenmetrazine, modafinil, methylphenidate analogs, and novel synthetic opioids (NSO). To investigate DM-related complications in France, all data on NPS collected in the French Addictovigilance network database through spontaneous reports (SRs) and the annual survey on deaths related to the abuse of licit and illicit psychoactive substances (DRAMES survey) between 2009 and 2017 were analyzed. From 2009-2017, about 800 cases of NPS-related abuse or somatic complications were reported to the French Addictovigilance Network, including 71 fatal cases (9%). DM use progressively increased over the years, particularly after 2013 (4% of all SRs on NPS in 2011 versus 14 % in 2017). Moreover, DM were implicated in 17 % of NPS-related deaths in France, just after cathinones (43 %) and dissociative drugs (22 %). NSO, DB and phenidate analogs were identified in 42 %, 25 % and 25 % of all DM-related death reports, respectively. DM seem to interest a new target group of users that includes mainly patients and healthy people rather than substance users. The availability on the Internet of compounds mimicking therapeutic drugs is a worrying phenomenon that could lead to their uncontrolled use.