Activities of clinical pharmacologists across Europe: A survey by the European association of clinical pharmacology and therapeutics.

PURPOSE: In order to explore clinical pharmacology and therapeutics (CPT) teaching and practices across continental Europe, the European Association of Clinical Pharmacology and Therapeutics (EACPT) made a survey in 2022 amongst its 27 affiliated societies. METHODS: The survey was made available online to EACPT representatives, and 47 filled-in questionnaires were received from 25 countries (one to five per country), representing all geographic areas of Europe. RESULTS: Clinical pharmacologists (CPs) spend 25%, 30%, 15%, and 25% of their time in teaching, hospital activities, committees, and research, respectively, with large variations across and within countries. CPT courses are given at Schools of Medicine in all the countries except one, mostly organized and taught by medical doctors (MDs). In Central, Western, and Southern Europe, the teachers may have medicine or pharmacy training. Therapeutic drug monitoring and pharmacovigilance were the hospital activities most frequently reported, and clinical/forensic toxicology, rounds of visits, and pharmacogenetics the least. Two-thirds of the panel think CPs should be MDs. However, the transversal nature of CPT was underlined, with patients/diseases and drugs as gravity centres, thus calling for the complementary skills of MDs and PharmDs. Besides, most respondents reported that clinical pharmacists in their country are involved in rounds of visits, pharmacovigilance, TDM, and/or pharmacogenetic testing and that collaborations with them would be beneficial. CONCLUSION: CPT comes with a plurality of backgrounds and activities, all required to embrace the different pathologies and the whole lifecycle of medicinal products, but all of them being rarely performed in any given country. The willingness to use common CPT teaching material and prescribing exams at the European level is a good sign of increasing harmonisation of our discipline Europewide.

French national addictovigilance follow-up of zolpidem between 2014 and 2020: evolution of drug abuse, misuse and dependence before and after the regulatory change.

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.

Association between NMDAR antagonists, drug abuse and dependence: A disproportionality analysis from the WHO pharmacovigilance database.

Ketamine and dextromethorphan are widely abused psychoactive substances. Inhibition of N-methyl-d-aspartate receptors (NMDARs) results in neurobehavioural effects including hallucinations, "out of body" sensations and dissociative effects. However, little is known about a possible extended addictive class effect linked to pharmacologically-related amino-adamantane derivatives (e.g., amantadine and memantine). Using a quasi-Bayesian analytic method, we investigated the potential association between the use of approved NMDAR antagonists (i.e., dextromethorphan, ketamine, amantadine and memantine) and the reporting of drug abuse and dependence in the WHO pharmacovigilance database (VigiBase®), which includes >21 million individual case safety reports collected from >130 countries. This disproportionality analysis identified a significant association for all investigated drugs: dextromethorphan (IC = 3.03 [2.97-3.09]), ketamine (IC = 1.70 [1.57-1.83]), amantadine (IC = 0.21 [0.06-0.35]) and memantine (IC = 0.27 [0.13-0.40]), suggesting a class effect for drug abuse and dependence. This first signal requires further investigations, but health professionals need to be alert to the potential of abuse of NMDAR antagonists, especially in the current "opioid epidemic" context, due to their growing interest as non-opioid antinociceptive drugs.

Medical prescription forms of opioid cough suppressants falsified by the patients before and after they switched from over-the-counter to prescription-only in France.

AIMS: The French Ministry of Health scheduled opioid cough suppressants as prescription-only drugs on 12 July 2017. The present study assessed the impact of this regulation on the diversion modalities of the concerned drugs and the related drug pholcodine by analysing the national OSIAP (Ordonnances Suspectes Indicateur d'Abus Possible) database. METHODS: Medical prescriptions with at least 1 mention of codeine, dextromethorphan, ethylmorphine, noscapine or pholcodine for cough suppression recorded in 2013-2019 were extracted from OSIAP. Annual mentioning rates were estimated by dividing numbers of mentions over those of prescriptions recorded the year considered. A descriptive analysis compared the characteristics of prescriptions before and after 12 July 2017. RESULTS: Overall, 832 mentions of the requested drugs were retrieved on 827 prescription forms. Codeine was the most frequent (n = 809, 8.7%) with 6 additional mentions of codeine/ethylmorphine combination, followed by dextromethorphan (n = 11, 0.1%) and pholcodine (n = 6, 0.1%). There was no mention of noscapine. Annual mentioning rates varied between 0 and 0.3% for all drugs except codeine. Codeine mentioning rates ranged between 0.3% (n = 2) and 0.7% (n = 9) before 12 July 2017 and increased to 10.1% (n = 61) thereafter in 2017, 16.1% (n = 314) in 2018, and 19.8% (n = 414) in 2019. The profile of subjects evolved accordingly with an increased male/female ratio (10.0 vs. 1.5 before) and decreased age (23 vs. 40 y before, P < .001). DISCUSSION: The sharp increase of recourse to falsified prescription forms indicates that codeine diversion continues despite restricted access, whereas the other drugs studied do not seem to have been impacted.

Increase of high-risk tramadol use and harmful consequences in France from 2013 to 2018: Evidence from the triangulation of addictovigilance data.

AIMS: The aim of this paper is to assess recent developments in non-medical tramadol use, tramadol use disorder, illegal procurement and deaths. METHODS: This study used repeated cross-sectional analysis of data collected nationwide from 2013 to 2018. Analysis was conducted through multisource monitoring of the French Addictovigilance Network of: (1) validated reports of high-risk tramadol use, (2) record systems collecting information from toxicology experts investigating analgesic-related deaths (DTA) and deaths related to substance abuse (DRAMES), and pharmacists for forged prescriptions (OSIAP), and (3) survey of drug users, with investigation of patterns of use while visiting addiction-specialised institutions (OPPIDUM). RESULTS: Despite a plateauing level of tramadol exposure in the French population, the proportion of tramadol reports increased 1.7-fold (187 cases in 2018, 3.2% (95% confidence interval [CI]: 2.74-3.63%), versus 1.9% (95% CI: 1.49-2.42% in 2013). Trends were similar in OSIAP: 11.9% of forged prescriptions in 2018 (95% CI: 10.56-13.45%); 1.7-fold increase; in OPPIDUM: 0.76% (95% CI: 0.55-1.02); 2.2-fold increase; and DRAMES: 3.2% of drug abuse-related deaths in 2018 (95% CI: 1.89-5.16) versus 1.7% in 2013 (95% CI: 0.65-3.84). Tramadol was the primary opioid in analgesic-related deaths in DTA (45% in 2018). Two profiles of high-risk tramadol users were identified: (1) patients treated for pain or with tramadol persistence when pain disappeared (mainly women; mean age 44 years), and (2) individuals with non-medical use for psychoactive effects (mainly men; mean age 36 years). CONCLUSION: The triangulation of the data obtained through addictovigilance monitoring evidenced a recent increase in high-risk tramadol use. These findings have a practical impact on the limitation of the maximal duration of tramadol prescriptions.

European association for clinical pharmacology and therapeutics young clinical pharmacologists working group: a cornerstone for the brighter future of clinical pharmacology.

The European Association for Clinical Pharmacology and Therapeutics (EACPT) is a leading society in Europe serving the European and global Clinical Pharmacology and Therapeutics community. Its specific aims include promotion of the utilisation and divulgation of the utility of clinical pharmacology services in health care delivery. EACPT currently has four active working groups (WGs): Education, Regulatory affairs, Clinical research and Young Clinical Pharmacologists (YCP WG). EACPT YCP WG was established in 2015 with the idea of improving education, research, training and networking/mobility opportunities for YCPs across Europe and globe. The main objective of the present manuscript is to provide detailed information on general characteristics, structure, chronogram, objectives, accomplishments and current/future focus areas of the EACPT YCP WG. Consequently, we tend to notably enhance EACPT YCP WG's visibility, increase the number of its members and mobility/networking options and to expand areas of activity even more. Moreover, by this we can also make clinical pharmacology more attractive to early career fellows and colleagues and empower its position alongside other medical specialties.

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.

Evolution of medication consumption in a working environment in France: Results of the four waves of the "Drugs and Work" study (1986-2016).

OBJECTIVES: Previous studies in the working environment have underlined the high prevalence of drug consumption. The aim of this study was to present the main characteristics of this consumption in French workers and to identify changes from the 1986, 1996, 2006 and 2016 surveys. METHODS: The design was a repeated cross-sectional study in 1986, 1996, 2006 and 2016. At each wave, demographic and socio-professional characteristics, self-reported consumption of medications during the week before the occupational medical visit, and perceived difficult working conditions and extraprofessional problems were collected among a sample of workers. Factors associated with consumption of any drug and of main therapeutic classes were investigated through multivariate logistic regression models, using 2016 as the reference for investigating temporal trends. RESULTS: Prevalence of use of any drug was significantly higher in 2016, with marked changes observed in comparison with 1986: absolute decrease of psychotropic (-5.1%, p < 0.0001), antibiotics (-2.7%, p < 0.0001) and cardiovascular drug use (-3.8%, p < 0.0001), increase of analgesic use (+8.3%, p < 0.0001). Difficult working conditions, age and female gender were independently associated with analgesic drug use, and extraprofessional problems and female gender associated with psychotropic drug use. CONCLUSIONS: This analysis of self-reported drug use in the working environment illustrates the global patterns of medication use in a French active population over 3 decades. The favorable development in the level of consumption of psychotropic drugs should not underestimate the attention to be paid to the determinants of chronic consumption, or possible transfers to less stigmatized medications.

Comment on: An Insight Into Z-Drug Abuse and Dependence: An Examination of Reports to the European Medicines Agency Database of Suspected Adverse Drug Reactions.

After the publication of an article discussing the methodological options to detect the diversion potential of prescription drugs, this letter presents the multidimensional functioning of the French Addictovigilance System. This system aims at monitoring all substances with abuse potential, relying on a network of experts specialized in clinical and fundamental pharmacology. For more than 25 years, we have created collaborations with partners at the interface with field data related to substance use and the potential related disorders. When relevant depending on the context, these data sources are explored and crossed to analyze the abuse potential of one given substance. This organizational approach is useful to detect early Addictovigilance warning signals and to take appropriate measures. Generalizing such a multidimensional approach outside France appears an appealing option to move towards more effective Addictovigilance systems at the international level.

Patterns of gabapentin and pregabalin use and misuse: Results of a population-based cohort study in France.

AIMS: The aim of this study was to assess the use and factors associated with the misuse of gabapentin and pregabalin in the general French population, through a cohort study in the EGB (General Sample of Beneficiaries), a national representative sample of the French general population. METHODS: New users of gabapentin and pregabalin were identified from June 2006 to December 2014, and new users of duloxetine served as control group. Misuse was defined as a use of higher daily doses than recommended. Cox proportional hazard regression models were performed to identify associated factors of misuse. RESULTS: Misuse was more frequent in the 8692 new users of pregabalin (12.8%) than in the 1963 gabapentin (6.6%) or the 3214 duloxetine new users (9.7%) (P < 0.001). Factors associated with misuse were pregabalin (hazard ratio [HR] 1.48; 95% confidence interval [CI] [1.29-1.69]), age (HR[18-45] versus > 70 years 1.98 [1.70-2.31] and HR[58-70] versus > 70 years 1.25 [1.06-1.47]), multiple prescribers (HR2 or 3 versus 1 prescriber 1.29 [1.15-1.45]; HR4 or more versus 1 prescriber 1.54 [1.30-1.83]), cancer (1.28 [1.11-1.47]), multiple sclerosis (1.53 [1.07-2.18]), neuropathy (1.85 [1.19-2.89]), depression (1.26 [1.07-1.49]) and methadone (2.61 [1.16-5.84]). After this first episode of drug misuse, 11.6% of gabapentin and 10.7% of pregabalin misusers developed a primary addiction. CONCLUSION: In a cohort of new users, misuse is more likely to occur in new users of pregabalin, with different associated factors of misuse compared to gabapentin and duloxetine. Health professionals and prescribers must be aware of this misuse potential, which could lead to abuse and dependence.

Detecting the diverted use of psychoactive drugs by adolescents and young adults: A pilot study.

PURPOSE: The increasing trend of diversion of nonprescription drugs (NPDs) by adolescents or young adults is worrying. We implemented this pilot study before a national investigation to identify requests for suspected recreational use of psychoactive drugs made by young subjects to community pharmacies. METHODS: Thirty-eight French community pharmacies were asked to complete questionnaire (with age, gender of subjects; name, form, quantity of drugs) for each suspect request formulated by subjects under 26. Besides, pharmacists were asked about the regulatory measures they thought useful to decrease this diverted use by young people. Nineteen pharmacies participated. The study covered from December 12, 2016 to January 23, 2017. RESULTS: Forty-one requests mentioning 51 drugs were reported. They concerned males (85%) aged 20 years old on average, including 6 minors. The most frequent age class was that comprised between 18 and 20 years old. Codeine-containing drugs (29 reports) and promethazine (17 reports), the main components of the popular cocktail "Purple drank," were the most requested, followed by dextromethorphan (3 reports). Fifteen drugs were requested in syrup form. One request concerned the prescription drug ketamine. Pharmacists suggested to schedule the concerned NPDs to prescription-only drugs and to increase the education of students as well as the public. CONCLUSIONS: Codeine and promethazine, the main components of the popular cocktail Purple drank, were the most requested. Suspect requests of psychoactive drugs made by adolescents or young adults in community pharmacies should be carefully surveyed and combined to the monitoring of falsified prescriptions.

What is the Current Knowledge About the Cardiovascular Risk for Users of Cannabis-Based Products? A Systematic Review.

PURPOSE OF REVIEW: The purpose of the study was to examine the published evidence on the cardiovascular risk related to the use of cannabis-based products by performing a systematic review of recent literature. RECENT FINDINGS: The World Health Organization (WHO) emphasizes that cannabis use represents a risky behavior as it may lead to many adverse effects, and in particular, cardiovascular effects. A systematic review of articles published between January 1, 2011 and May 31, 2016 was performed in agreement with the PRISMA statement. Articles presenting data on humans exposed to cannabis-based products and suffering from any cardiovascular condition were eligible for inclusion. The inclusion process was based on a search algorithm and performed in a blinded standardized manner. Overall, 826 articles were found in the literature search, 115 of which remained after performing the inclusion procedure. These were 81 case reports, 29 observational studies, 3 clinical trials, and 2 experimental studies. A total of 116 individuals was the subject of case reports. The mean age was 31 years (95%CI = 29-34), and patients were more frequently men (81.9%) than women (18.1%). They mainly suffered from ischemic strokes or myocardial infarctions. Data provided by the 29 included observational studies evidenced an association between exposure to cannabis-based products and cardiovascular disease. Currently, this evidence is stronger for ischemic strokes than for any other cardiovascular diseases. While the data are limited, there is some suggestion that cannabis use may have negative cardiovascular consequences, particularly at large doses.

Early signal of diverted use of tropicamide eye drops in France.

AIMS: Tropicamide is a mydriatic drug used as eye-drops for diagnostic or therapeutic purposes. From 2013, a diverted use by intravenous route has been suspected in Eastern Europe in opioids users. To date, no signal of misuse has been identified in France. The aims of this study were to investigate any early signals of a diverted use of tropicamide eye drops and to collect information regarding motives for the misuse and tropicamide-induced effects. METHODS: Information was obtained at three levels: (1) at regional level (Midi-Pyrénées area), from reimbursement data and pharmacists' reports on suspicious requests; (2) at national level: from reimbursement data and prescriptions suggesting possible abuse from the OSIAP (Ordonnances Suspectes, Indicateur d'Abus Possible) survey; and (3) at international level: from VigiBase® reports and Web sources. Beta-blocker eye-drops were used as comparators. RESULTS: In France, in 2014-2015, 17 (0.91%, 95% CI [0.53-1.46%]) falsified prescriptions involving tropicamide were identified in the OSIAP survey (compared with 0%, 95% CI [0-0.19%] for beta-blockers). Moreover, 37 other suspicious prescriptions were presented in 2015 (notified in 2016). In Midi-Pyrénées, seven patients aged 35-49 were reimbursed for 19-45 vials of 10 ml, in a year. Since September 2014, the regional Addictovigilance Centre has received 91 notifications of suspicious requests to obtain tropicamide. In VigiBase® , two cases were identified but none in France. An increased interest in tropicamide-related Internet searches was observed from Russia and Ukraine. CONCLUSIONS: These results represent the first early warnings of a tropicamide diverted use in France. Tropicamide abusers would seek euphoria or hallucinations. The high doses involved in intravenous administration could lead to serious complications.

Strokes are possible complications of cannabinoids use.

It is critically important to identify all factors that may play a role in the recent increase of the incidence of stroke among the young population. Considering the worldwide use of cannabinoids (cannabis and synthetic cannabinoids), the recent legalization of their consumption in some countries, and their supposed involvement in cardiovascular events, we evaluated their role in the occurrence of neurovascular complications among the young. Ninety-eight patients were described in the literature as having a cannabinoids-related stroke (85 after cannabis use and 13 after synthetic cannabinoids). The distribution by type of stroke was as follows: 4 patients with an undetermined type of stroke, 85 with an ischemic stroke and/or a transient ischemic attack, and 9 with a hemorrhagic stroke. The mean age of patients was 32.3±11.8years (range 15-63), and the majority of them were male with a sex ratio of 3.7:1. Cannabis was often smoked with tobacco in 66% of cases. Most of the patients with cannabinoids-related strokes were chronic cannabis users in 81% of cases, and for 18% of them, there was a recent increase of the amount of cannabis consumption during the days before the occurrence of stroke. Even if the prognosis of stroke was globally favorable in 46% of cases, with no or few sequelae, 5 patients died after the neurovascular event. One striking element reported in the majority of the reports was a temporal relationship between cannabinoids use, whether natural or synthetic, and the occurrence of stroke. However, a temporal correlation does not mean causation, and other factors may be involved. Cannabis may be considered as a risk factor of stroke until research shows evidence of an underlying mechanism that, alone or in association with others, contributes to the development of stroke. As of today, reversible cerebral vasoconstriction triggered by cannabinoids use may be a convincing mechanism of stroke in 27% of cases. Indeed, despite the widespread use of cannabinoids, the low frequency of neurovascular complications after their use may be due to a genetic predisposition to their neurovascular toxicity in some individuals. Further studies should focus on this point. More importantly however, this low frequency may be underestimated because the drug consumption may not be systematically researched, neither by questioning nor by laboratory screening. Besides this vascular role of cannabinoids in the occurrence of stroke, a cellular effect of cannabis on brain mitochondria was recently suggested in an experimental study. One of the mechanisms involved in young cannabis users with stroke may be the generation of reactive oxygen species leading to an oxidative stress, which is a known mechanism in stroke in humans. It is useful to inform the young population about the real potential risk of using cannabinoids. We suggest to systematically ask all young adults with stroke about their drug consumption including cannabinoids, to screen urine for cannabis or to include a specific diagnostic test to detect synthetic cannabinoids, and to obtain non-invasive intracranial arterial investigations (i.e. CT-angiography or cerebral MRA) in order to search for cerebral vasoconstriction. However, several questions remained unresolved and further research is still needed to assess the pathophysiological mechanisms involved in young cannabinoids users with stroke. This article is part of a Special Issue entitled "Cannabinoids and Epilepsy".

[Surveillance system on drug abuse: Interest of the French national OPPIDUM program of French addictovigilance network]. / Dispositif pharmacoépidémiologique de surveillance des substances psychoactives : intérêts du programme national OPPIDUM du Réseau français d'addictovigilance.

It is important to assess drug abuse liability in 'real life' using different surveillance systems. OPPIDUM ('Observation of illegal drugs and misuse of psychotropic medications') surveillance system anonymously collects information on drug abuse and dependence observed in patients recruited in specialized care centers dedicated to drug dependence. The aim of this article is to demonstrate the utility of OPPIDUM system using 2015 data. OPPIDUM is a cross-sectional survey repeated each year since 1995. In 2015, 5003 patients described the modality of use of 10,159 psychoactive drugs. Among them, 77% received an opiate maintenance treatment: 68% methadone (half of them consumed capsule form) and 27% buprenorphine (39% consumed generic form). Brand-name buprenorphine is more often injected than generic buprenorphine (10% vs. 2%) and among methadone consumers 7% of methadone capsule consumers have illegally obtained methadone (vs. 9% for syrup form). The proportion of medications among psychoactive drugs injected is important (42%), with morphine representing 21% of the total psychoactive drugs injected and buprenorphine, 16%. OPPIDUM highlighted emergent behaviors of abuse with some analgesic opioids (like tramadol, oxycodone or fentanyl), pregabalin, or quetiapine. OPPIDUM highlighted variations of drugs use regarding geographic approaches or by drug dependence care centers (like in harm reduction centers). OPPIDUM clearly demonstrated that collection of valid and useful data on drug abuse is possible, these data have an interest at regional, national and international levels.

Three Complementary Approaches to Characterize Buprenorphine Misuse.

BACKGROUND: In France, buprenorphine has been available for opioid maintenance therapy since 1996 and since then its misuse has been continuously evaluated by the French health authorities. OBJECTIVES: To characterize buprenorphine misuse in Languedoc-Roussillon (LR) region, using three different approaches. METHODS: Three different data sources were analyzed : (i) spontaneous reports (NotS) of buprenorphine misuse or dependence, (ii) a specific periodic survey from specialized care centers (OPPIDUM) over 11 years (2002-2012) and (iii) a drug reimbursement database (DRB). RESULTS: A total of 209 spontaneous reports were collected. The main type of buprenorphine misuse was use by an unintended route of administration. The main complications notified were directly related to the injection of buprenorphine. NotS enabled the collection of data about severe clinical complications or new diversion phenomenon. The OPPIDUM LR survey revealed a decrease in the buprenorphine misuse indicator through the study period. The DRB analysis identified one subgroup of patients with a buprenorphine deviant behavior, characterized by a significantly greater number of dispensing episodes, pharmacies, prescribers, daily dose and switch between buprenorphine forms (princeps and generic). The DRB analysis provides data on buprenorphine diversion in the context of outpatients care. CONCLUSION: The three complementary approaches allowed us to characterize buprenorphine misuse in LR area. The three approaches are complementary because each data source provides different types of information.

Pregabalin use disorder and secondary nicotine dependence in a woman with no substance abuse history.

This is an addictovigilance report of a pregabalin use disorder case in a young female patient who secondarily presented a tobacco use disorder after smoking initiation combined with pregabalin intake. Pregabalin was first prescribed for anxiety. Concomitant use of pregabalin with tobacco led to a synergic effect of both substances. She presented a craving behavior for pregabalin, with a tolerance phenomenon and a withdrawal syndrome between pregabaline intakes. The patient had a history of depressive disorder, personality disorder and anorexia, but never had any history of substance use disorder. This case report is noteworthy for 3 reasons: 1: this is one of the first report of pregabalin use disorder in a patient without any substance abuse disorder (licit or illicit), with the exception of a personal vulnerability factors to substance abuse; 2: the patient presented characteristics of pregabalin use disorder at usual dose (below 300mg per day), with drug-seeking behavior, tolerance phenomenon and intense craving with these moderate doses; 3: concomitant use of pregabalin with tobacco led to a synergic effect of both substances.

Signal identification in addictovigilance: the functioning of the French system.

The French addictovigilance network (addictovigilance: surveillance of addiction), composed of 13 Addictovigilance Centres, was set up in 1990 in order to achieve reliable surveillance and evaluation of abuse and dependence cases due to psychoactive substances (alcohol and tobacco excepted). The detection of safety signals is one of the roles of the addictovigilance centres. Signals from spontaneous reports need to be analyzed before further communication. In addictovigilance, signals may be linked to adverse effects (deaths, pathological signs), to products (new psychoactive substances with potentially dangerous effects) or to practices (new administration routes, new contexts of use). These signals are provided by numerous partners among whom the addictovigilance network has to raise awareness about information that may possibly be an alert signal. The watchful attitude of all partners will make it possible that signals will be, after analyze, considered as true alerts. The addictovigilance network collects data, assess the potential for addiction of psychoactive drugs to provide information on the risk of addiction and give opinions for public health decisions (harm reduction or prevention programs, psychoactive substances control, health alerts).

Cannabidiol (CBD): Confronting consumers' expectations of therapeutic benefits with pharmacological reality.

In recent years, the increase in cannabidiol (CBD) sales in Europe has raised questions regarding the legal status of this product, as well as its safety of use. Consumers seem to be looking for solutions to various health issues. However, the scientific reality is much more nuanced. The European CBD market emerged in Switzerland in 2016 and subsequently expanded across the continent. This expansion has been facilitated by the establishment of delta-9-tetrahydrocannabinol (THC) concentration limits for these products. However, the current market offers a diverse range of CBD products, often lacking clear information on raw materials, product concentrations and recommended dosages. Regulating these products is challenging, as the appropriate classification of CBD remains uncertain. CBD products are in high demand worldwide, with many people seeking alternative treatments for medical conditions or general health and well-being benefits. However, the use of CBD products often relies on self-medication and lacks sufficient scientific evidence. Improved communication between patients and healthcare professionals is needed to ensure informed decisions and address potential interactions with other medications. Scientific evidence on CBD is currently limited and the efficacy of CBD-containing products has only been proven in clinical trials for Epidyolex® as an add-on therapy. There is no consensus on the long-term safety, appropriate dosage, schedules or administration routes for CBD. Health claims associated with CBD are not consistent with the available scientific research, which is still in its early stages. Further clinical research is needed to establish the efficacy and safety of CBD in various medical conditions. The enthusiasm surrounding CBD-based products should be tempered by the limited scientific evidence of their efficacy, the inadequacy of patient expectations, regulatory concerns and potential drug interactions.

The opioid epidemic: A worldwide exploratory study using the WHO pharmacovigilance database.

BACKGROUND AND AIMS: The current opioid epidemic in the United States began 20 years ago and has become the leading cause of accidental deaths in the country. This crisis prompted us to explore trends in opioid abuse and dependence worldwide. We sought to identify other countries at high-risk of opioid use disorders, using the World Health Organization's (WHO) pharmacovigilance database. METHODS: We performed a disproportionality analysis using VigiBase, the WHO Global Individual Case Safety Report (ICSR) database. Five opioids used worldwide were included: oxycodone, fentanyl, morphine, tramadol, and codeine. We extracted all ICSRs associated with the drugs of interest, considered as suspect medication and recorded up until 5 June 2021, using the narrow Standardised MedDRA Query (SMQ) for drug abuse and dependence. Countries with at least one ICSR for each of the five opioids were retained. The relationship between the use of a drug (i.e. an opioid) and the occurrence of an adverse drug reaction (i.e. drug abuse and dependence) for each country was assessed by calculating the information component (IC) and its 99.9% CI [IC0005 ; IC9995 ], using a quasi-Bayesian confidence propagation neural network (BCPNN). A hierarchical cluster analysis (Ward's method) of the IC0005 value for each of the five opioids was performed to identify subgroups of countries with similar reported risks of opioid abuse and dependence. RESULTS: Among 21 countries, the optimal number of clusters was calculated to be four, each with a Jaccard index >0.5 (0.95, 0.78, 0.65 and 0.75, respectively). Six countries with the highest signals of drug abuse and dependence were identified in cluster 1, with significant CIs for the five opioids of interest (IC0005 > 0), ranging from 0.9 to 5.8 for the lower endpoint. CONCLUSIONS: There appear to be four distinct clusters of countries with similar opioid abuse and dependence profiles. The group with the highest reported risk for the opioids oxycodone, fentanyl, morphine, tramadol and codeine includes Australia, Canada, France, Germans, the United Kingdom and the United States.