Médecine de l'addiction: naissance d'une nouvelle discipline

Les addictions ont fortement consolidé leur place dans le champ de la médecine à la fin du 20e siècle parce que la certitude de leurs fondements neurobiologiques était désormais acquise et que les preuves de l'efficacité des stratégies de prévention et de traitement étaient suffisantes. La médecine de l'addiction couvre un champ très large de l'activité médicale allant de la prévention de l'usage à risque, en passant par le dépistage des formes peu sévères de dépendance au traitement des formes les plus graves, chroniques et invalidantes. Cette activité médicale prend place dans une grande diversité de lieux de soins, en médecine de premier recours, particulièrement dans les cabinets de médecine de famille, mais aussi aux urgences et en pédiatrie. La médecine de l'addiction est très présente en psychiatrie où ses formes sont souvent sévères. Malgré cela, aujourd'hui seul un patient sur dix touché par une problématique d'addiction est traité. C'est la raison pour laquelle la Suisse, comme c'est le cas aux Etats-Unis et aux Pays-Bas par exemple, doit se doter d'un système promouvant une médecine de l'addiction à «large spectre», permettant d'identifier et de traiter la grande diversité des troubles rencontrés dans les lieux de soins les plus touchés. En Suisse, les médecins sont actuellement insuffisamment préparés pour assumer ce rôle. C'est aux disciplines concernées de proposer des filières de formation. Cette stratégie contribuera à améliorer les compétences de l'ensemble du corps médical dans ce domaine, avec pour conséquence d'offrir au plus grand nombre de patients touchés par les addictions les traitements les plus efficaces

Dépendances: nouveautés en médecine 2008 [Addiction]

L'actualité 2008 des dépendances est centrée sur l'avancée des neurosciences psychiatriques dans le domaine des addictions mais aussi sur les clarifications nécessaires face à la complexité des comorbidités psychiatriques des addictions, notamment en cas de schizophrénie. Enfin, le praticien trouvera des considérations utiles pour la prescription de traitements de substitution chez des patients VIH en trithérapie. The highlights 2008 in the addiction field are correlated to the progress of psychiatric neurosciences. Clarifications are also necessary towards the psychiatric comorbidities (schizophrenia) with the addictions. Then, useful considerations are given for the prescription of substitution treatment among HIV patients under tritherapy.

A one-year monitoring of nicotine use in sport: frontier between potential performance enhancement and addiction issues.

Tobacco consumption is a global epidemic responsible for a vast burden of disease. With pharmacological properties sought-after by consumers and responsible for addiction issues, nicotine is the main reason of this phenomenon. Accordingly, smokeless tobacco products are of growing popularity in sport owing to potential performance enhancing properties and absence of adverse effects on the respiratory system. Nevertheless, nicotine does not appear on the 2011 World Anti-Doping Agency (WADA) Prohibited List or Monitoring Program by lack of a comprehensive large-scale prevalence survey. Thus, this work describes a one-year monitoring study on urine specimens from professional athletes of different disciplines covering 2010 and 2011. A method for the detection and quantification of nicotine, its major metabolites (cotinine, trans-3-hydroxycotinine, nicotine-N'-oxide and cotinine-N-oxide) and minor tobacco alkaloids (anabasine, anatabine and nornicotine) was developed, relying on ultra-high pressure liquid chromatography coupled to triple quadrupole mass spectrometry (UHPLC-TQ-MS/MS). A simple and fast dilute-and-shoot sample treatment was performed, followed by hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-MS/MS) operated in positive electrospray ionization (ESI) mode with multiple reaction monitoring (MRM) data acquisition. After method validation, assessing the prevalence of nicotine consumption in sport involved analysis of 2185 urine samples, accounting for 43 different sports. Concentrations distribution of major nicotine metabolites, minor nicotine metabolites and tobacco alkaloids ranged from 10 (LLOQ) to 32,223, 6670 and 538 ng/mL, respectively. Compounds of interest were detected in trace levels in 23.0% of urine specimens, with concentration levels corresponding to an exposure within the last three days for 18.3% of samples. Likewise, hypothesizing conservative concentration limits for active nicotine consumption prior and/or during sport practice (50 ng/mL for nicotine, cotinine and trans-3-hydroxycotinine and 25 ng/mL for nicotine-N'-oxide, cotinine-N-oxide, anabasine, anatabine and nornicotine) revealed a prevalence of 15.3% amongst athletes. While this number may appear lower than the worldwide smoking prevalence of around 25%, focusing the study on selected sports highlighted more alarming findings. Indeed, active nicotine consumption in ice hockey, skiing, biathlon, bobsleigh, skating, football, basketball, volleyball, rugby, American football, wrestling and gymnastics was found to range between 19.0 and 55.6%. Therefore, considering the adverse effects of smoking on the respiratory tract and numerous health threats detrimental to sport practice at top level, likelihood of smokeless tobacco consumption for performance enhancement is greatly supported.

French version of the addiction severity index (5th Edition): validity and reliability among Swiss opiate-dependent patients. French validation of the Addiction Severity Index.

OBJECTIVE: The aim of the study was to validate a French adaptation of the 5th version of the Addiction Severity Index (ASI) instrument in a Swiss sample of illicit drug users. PARTICIPANTS AND SETTING: The participants in the study were 54 French-speaking dependent patients, most of them with opiates as the drug of first choice. Procedure: Analyses of internal consistency (convergent and discriminant validity) and reliability, including measures of test-retest and inter-observer correlations, were conducted. RESULTS: Besides good applicability of the test, the results on composite scores (CSs) indicate comparable results to those obtained in a sample of American opiate-dependent patients. Across the seven dimensions of the ASI, Cronbach's alpha ranged from 0.42 to 0.76, test-retest correlations coefficients ranged from 0.48 to 0.98, while for CSs, inter-observer correlations ranged from 0.76 to 0.99. CONCLUSIONS: Despite several limitations, the French version of the ASI presents acceptable criteria of applicability, validity and reliability in a sample of drug-dependent patients.

Appropriateness of methadone maintenance treatment for opiate addiction: evaluation by an expert panel.

With some 30,000 dependent persons, opiate addiction constitutes a major public health problem in Switzerland. The Swiss Federal Office of Public Health (FOPH) has long played a leading role in the prevention and treatment of opiate addiction and in research on effective means of containing the epidemic of opiate addiction and its consequences. Major milestones on that path have been the successive "Methadone reports" published by that Office and providing guidance on the care of opiate addiction with substitution treatment. In view of updating the recommendations for the appropriateness of substitution treatment for opiate addiction, in particular for the prescription of methadone, the FOPH commissioned a multi-component project involving the following elements. A survey of current attitudes and practices in Switzerland related to opiate substitution treatment Review of Swiss literature on methadone substitution treatment Review of international literature on methadone substitution treatment National Methadone Substitution Conference Multidisciplinary expert panel to evaluate the appropriateness of substitution treatment. The present report documents the process and summarises the results of the latter element above. The RAND appropriateness method (RAM) was used to distil from literature-based evidence and systematically formulated expert opinion, areas where consensus exist on the appropriateness (or inappropriateness) of methadone maintenance treatment (MMT) and areas where disagreement or uncertainty persist and which should be further pursued. The major areas which were addressed by this report are Initial assessment of candidates for MMT Appropriate settings for initiation of MMT (general and special cases) Appropriateness of methadone supportive therapy Co-treatments and accompanying measures Dosage schedules and pharmacokinetic testing Withdrawal from MMT Miscellaneous questions Appropriateness of other (non-methadone) substitution treatment Summary statements for each of the above categories are derived from the panel meeting and presented in the report. In the "first round", agreement was observed for 31% of the 553 theoretical scenarios evaluated. The "second round" rating, following discussion of divergent ratings, resulted in a much higher agreement among panellists, reaching 53% of the 537 scenarios. Frank disagreement was encountered for 7% of all scenarios. Overall 49% of the clinical situations (scenarios) presented were considered appropriate. The areas where at least 50% of the situations were considered appropriate were "initial assessment of candidates for MMT", the "appropriate settings for initiation of MMT", the "appropriate settings for methadone supportive treatment" and "Appropriateness of other (non-methadone) substitution treatment". The area where there was the least consensus on appropriateness concerned "appropriateness of withdrawal from MMT" (6%). The report discusses the implications and limitations of the panel results and provides recommendations for the dissemination, application, and future use of the criteria for the appropriateness of MMT. The RAND Appropriateness Method proved to be an accepted and appreciated method to assess the appropriateness of methadone maintenance treatment for opiate addicts. In the next step, the results of the expert panel process must now be combined with those of the Swiss and international literature reviews and the survey of current attitudes and practices in Switzerland, to be synthesized into formal practice guidelines. Such guidelines should be disseminated to all concerned, promoted, used and rigorously evaluated for compliance and outcome.

Dépendances [Addiction]

This year review emphasizes four aspects coming from addiction psychiatry: 1. Initiation and maintenance of cannabis use. 2. Methadone and heart toxicity. 3. Suicidal behaviour in gambling. 4. Treatment of addictive disorders via internet: present and future perspectives.

Dépendances [Addiction]

The 2009 news in medicine regarding dependence confirm the bio-psycho-social field of addiction medicine and psychiatry. First a statement is made about the risk of cardiac arythmy in opioid substitution treatments. Then a review of the treatment of C hepatitis shows its importance in an addicted population. In the field of cognitive neuroscience, progress has been made in the knowledge of "craving" and of its endophenotypical components. Electronic medias related disorders are on the border of addiction: a case study is exploring this new domain. At last, recent datas are presented on the relationship between cannabis and psychosis. Les nouveautés en médecine 2009 concernant les dépendances confirment l'étendue du champ bio-psychosocial de la médecine et de la psychiatrie de l'addiction. Tout d'abord un point de situation est fait sur le risque d'arythmie cardiaque dans les traitements de substitution opiacée. Puis une revue de l'actualité du traitement de l'hépatite C dans la toxicodépendance en montre la pertinence. Sur le plan de la recherche plus fondamentale, les neurosciences cognitives progressent dans l'approche de la nature du craving et de ses composantes endophénotypiques. Les troubles liés aux médias électroniques illustrent les frontières de l'addiction : une étude de cas vient en explorer le contenu. Enfin, des données récentes sur les rapports entre cannabis et psychoses sont présentées.

Interest of qualitative and quantitative profiling of endocannabinoids for evaluation of their implication in drug addiction process

Introduction: In the middle of the 90's, the discovery of endogenous ligands for cannabinoid receptors opened a new era in this research field. Amides and esters of arachidonic acid have been identified as these endogenous ligands. Arachidonoylethanolamide (anandamide or AEA) and 2-Arachidonoylglycerol (2-AG) seem to be the most important of these lipid messengers. In addition, virodhamine (VA), noladin ether (2-AGE), and N-arachidonoyl dopamine (NADA) have been shown to bind to CB receptors with varying affinities. During recent years, it has become more evident that the EC system is part of fundamental regulatory mechanisms in many physiological processes such as stress and anxiety responses, depression, anorexia and bulimia, schizophrenia disorders, neuroprotection, Parkinson disease, anti-proliferative effects on cancer cells, drug addiction, and atherosclerosis. Aims: This work presents the problematic of EC analysis and the input of Information Dependant Acquisition based on hybrid triple quadrupole linear ion trap (QqQLIT) system for the profiling of these lipid mediators. Methods: The method was developed on a LC Ultimate 3000 series (Dionex, Sunnyvale, CA, USA) coupled to a QTrap 4000 system (Applied biosystems, Concord, ON, Canada). The ECs were separated on an XTerra C18 MS column (50 × 3.0 mm i.d., 3.5 μm) with a 5 min gradient elution. For confirmatory analysis, an information-dependant acquisition experiment was performed with selected reaction monitoring (SRM) as survey scan and enhanced produced ion (EPI) as dependant scan. Results: The assay was found to be linear in the concentration range of 0.1-5 ng/mL for AEA, 0.3-5 ng/mL for VA, 2-AGE, and NADA and 1-20 ng/mL for 2-AG using 0.5 mL of plasma. Repeatability and intermediate precision were found less than 15% over the tested concentration ranges. Under non-pathophysiological conditions, only AEA and 2-AG were actually detected in plasma with concentration ranges going from 104 to 537 pg/mL and from 2160 to 3990 pg/mL respectively. We have particularly focused our scopes on the evaluation of EC level changes in biological matrices through drug addiction and atherosclerosis processes. We will present preliminary data obtained during pilot study after administration of cannabis on human patients. Conclusion: ECs have been shown to play a key role in regulation of many pathophysiological processes. Medical research in these different fields continues to growth in order to understand and to highlight the predominant role of EC in the CNS and peripheral tissues signalisation. The profiling of these lipids needs to develop rapid, highly sensitive and selective analytical methods.

A one-year monitoring of nicotine use in sport: frontier between potential performance enhancement and addiction issues

Tobacco consumption is a global epidemic responsible for a vast burden of disease. With pharmacological properties sought-after by consumers and responsible for addiction issues, nicotine is the main reason of this phenomenon. Accordingly, smokeless tobacco products are of growing popularity in sport owing to potential performance enhancing properties and absence of adverse effects on the respiratory system. Nevertheless, nicotine does not appear on the 2011 World Anti-Doping Agency (WADA) Prohibited List or Monitoring Program by lack of a comprehensive large-scale prevalence survey. Thus, this work describes a one-year monitoring study on urine specimens from professional athletes of different disciplines covering 2010 and 2011. A method for the detection and quantification of nicotine, its major metabolites (cotinine, trans-3-hydroxycotinine, nicotine-N′-oxide and cotinine-N-oxide) and minor tobacco alkaloids (anabasine, anatabine and nornicotine) was developed, relying on ultra-high pressure liquid chromatography coupled to triple quadrupole mass spectrometry (UHPLC-TQ-MS/MS). A simple and fast dilute-and-shoot sample treatment was performed, followed by hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-MS/MS) operated in positive electrospray ionization (ESI) mode with multiple reaction monitoring (MRM) data acquisition. After method validation, assessing the prevalence of nicotine consumption in sport involved analysis of 2185 urine samples, accounting for 43 different sports. Concentrations distribution of major nicotine metabolites, minor nicotine metabolites and tobacco alkaloids ranged from 10 (LLOQ) to 32,223, 6670 and 538 ng/mL, respectively. Compounds of interest were detected in trace levels in 23.0% of urine specimens, with concentration levels corresponding to an exposure within the last three days for 18.3% of samples. Likewise, hypothesizing conservative concentration limits for active nicotine consumption prior and/or during sport practice (50 ng/mL for nicotine, cotinine and trans-3-hydroxycotinine and 25 ng/mL for nicotine-N′-oxide, cotinine-N-oxide, anabasine, anatabine and nornicotine) revealed a prevalence of 15.3% amongst athletes. While this number may appear lower than the worldwide smoking prevalence of around 25%, focusing the study on selected sports highlighted more alarming findings. Indeed, active nicotine consumption in ice hockey, skiing, biathlon, bobsleigh, skating, football, basketball, volleyball, rugby, American football, wrestling and gymnastics was found to range between 19.0 and 55.6%. Therefore, considering the adverse effects of smoking on the respiratory tract and numerous health threats detrimental to sport practice at top level, likelihood of smokeless tobacco consumption for performance enhancement is greatly supported.

Addictions [Addiction].

The news in addiction medicine in 2013 are presented according to the new version of the DSM (DSM-5); new data on cannabinoid, highlight hypotheses on self-medication; a current status about treatment of the addiction via the internet is shown; and new therapeutic perspectives emerge from the knowledge on traumatic antecedents in addictive populations.

Addictions [Addiction].

Les nouveautés en médecine 2012 pour les dépendances sont présentées sur trois axes d'actualité : tout d'abord dans le champ des neurosciences avec les travaux sur les processus d'extinction de la mémoire addictive. Puis dans le champ clinique avec une réflexion sur le traitement des addictions à l'hôpital psychiatrique. Enfin, dans le domaine de l'enseignement, un développement d'e-learning avec un patient virtuel présente un grand intérêt en psychiatrie de l'addiction. This year, the actuality about addiction is on psychopharmacology, in the controversy about the prescription of baclofene to reduce the craving for alcohol. More results from controlled studies are expected. The development of smartphones to access toe-Health skills is questionable, especially in matterofevaluation of these programs. Despite of encouraging results, open questions are remaining for clinicians, to be compared with clinical practice. Finally, it is necessary to keep in touch with translational neurosciences; in fact, research is showing that populations of addicts present a deficit in matter of empathy. This is the cause of a handicap in the social relationships. At a lower level, a difficulty to take the other's place could be the cause of this deficit at a higher level. Rehabilitation perspectives could come out of this discovery.

Controversies about the enhanced vulnerability of the adolescent brain to develop addiction.

Adolescence, defined as a transition phase toward autonomy and independence, is a natural time of learning and adjustment, particularly in the setting of long-term goals and personal aspirations. It also is a period of heightened sensation seeking, including risk taking and reckless behaviors, which is a major cause of morbidity and mortality among teenagers. Recent observations suggest that a relative immaturity in frontal cortical neural systems may underlie the adolescent propensity for uninhibited risk taking and hazardous behaviors. However, converging preclinical and clinical studies do not support a simple model of frontal cortical immaturity, and there is substantial evidence that adolescents engage in dangerous activities, including drug abuse, despite knowing and understanding the risks involved. Therefore, a current consensus considers that much brain development during adolescence occurs in brain regions and systems that are critically involved in the perception and evaluation of risk and reward, leading to important changes in social and affective processing. Hence, rather than naive, immature and vulnerable, the adolescent brain, particularly the prefrontal cortex, should be considered as prewired for expecting novel experiences. In this perspective, thrill seeking may not represent a danger but rather a window of opportunities permitting the development of cognitive control through multiple experiences. However, if the maturation of brain systems implicated in self-regulation is contextually dependent, it is important to understand which experiences matter most. In particular, it is essential to unveil the underpinning mechanisms by which recurrent adverse episodes of stress or unrestricted access to drugs can shape the adolescent brain and potentially trigger life-long maladaptive responses.

Addiction and arousal: the hypocretin connection

The hypocretins, also known as orexins, are two neuropeptides now commonly described as critical components to maintain and regulate the stability of arousal. Several lines of evidence have raised the hypothesis that hypocretin-producing neurons are part of the circuitries that mediate the hypothalamic response to acute stress. Intracerebral administration of hypocretin leads to a dose-related reinstatement of drug and food seeking behaviors. Furthermore, stress-induced reinstatement can be blocked with hypocretin receptor 1 antagonism. These results, together with recent data showing that hypocretin is critically involved in cocaine sensitization through the recruitment of NMDA receptors in the ventral tegmental area, strongly suggest that activation of hypocretin neurons play a critical role in the development of the addiction process. The activity of hypocretin neurons may affect addictive behavior by contributing to brain sensitization or by modulating the brain reward system. Hypocretinergic cells, in coordination with brain stress systems may lead to a vulnerable state that facilitates the resumption of drug seeking behavior. Hence, the hypocretinergic system is a new drug target that may be used to prevent relapse of drug seeking