State of Training, Clinical Services, and Research on Dual Disorders Across France, India, Israel, and Spain.

OBJECTIVE: This article overviews training, clinical services, and research on dual disorders across four countries: France, India, Israel, and Spain. METHODS: The current dual disorders systems in each of the four countries were reviewed, with a focus on strengths and limitations of each. RESULTS: In France, psychiatric care occurs within the public health care system and involves little training of medical graduates for managing dual disorders. Special courses and forums for specialists have recently started to meet the growing interest of physicians in learning how to manage dual disorders. The Indian health care system grapples with a large treatment gap for mental disorders, and while some treatment services for dual disorders exist, specific research and training efforts on dual disorders are just beginning. Israel has both public- and private sector services for patients with dual disorders, with specialized inpatient and emergency care for the acutely ill as well as day care and therapeutic communities for long-term management. Interest by researchers is growing, but training and education efforts in dual disorders are, however, minimal. Similar to the other countries, addiction and psychiatry disciplines are governed by separate divisions within the National Health System in Spain. There are some dual disorders services available, but they are limited in scope. While medical professionals clearly recognize the importance of dual disorders, there is no such recognition by the national and regional governing bodies. CONCLUSIONS: The common thread in various aspects of dual disorder management in each of these four countries is that there is a lower-than-desirable level of attention to dual disorders in terms of care, policy, research, and training. There are growing opportunities for training and continuing education in dual disorders management. We suggest that nations could learn from each other's experiences on how to address the issue of dual disorders.

Smoker's identity scale: Measuring identity in tobacco dependence and its relationship with confidence in quitting.

BACKGROUND AND OBJECTIVES: Persistent smoking behaviours are associated with numerous motives, explaining the absence of a single treatment for quitting. One of these motives may include that of identification. The threat of losing their smoker's identity may represent a significant obstacle to lasting abstinence. The objective of this study is to design a specific identity questionnaire and examine correlations between the degree of smoking identity and persistent smoking. METHODS: Patients attending a smoking cessation seminar completed the Modified Reasons for Smoking Scale, Barriers to smoking cessation checklist and our 6-item Smoker's Identity Scale (SIS) (n = 170 questionnaires). RESULTS: SIS showed good internal consistency, calculated by a Chronbach test (α = .785) with no redundant questions. There was a correlation between strong tobacco dependence (measured by the Fagerström questionnaire) and strong smoking identity (p = .0001). Strong identity was associated with less confidence in quitting at both 1 and 6 months (p = .037 and p = .002, respectively). We showed that identity represents an obstacle to quitting in 32% of our patients and is associated with decreased confidence in quitting. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Our study shows that measuring identity in smokers who wish to make a quit attempt may help to identify specific obstacles to abstinence. This may also help in elaborating improved quitting strategies and patient management. Further research is necessary to confirm these results.

Association between a polymorphism in the promoter of a glutamate receptor subunit gene (GRIN2A) and alcoholism.

A variable (GT)(n) repeat in the 5'-regulatory region of N-methyl-D-aspartate GRIN2A subtype has recently been identified and associated with psychiatric disorders. In this study, we examined the association of this polymorphism with alcohol dependence. Subject-control analysis included 206 alcohol-dependent and 168 control subjects. Average observed repeat numbers and genotype distributions were significantly different (P-value = 0.001) in alcohol-dependent subjects versus control subjects. Short alleles were significantly less frequent among alcohol-dependent subjects (odds ratio = 0.58, P-value = 7 × 10(-4)). These results could be replicated in an independent sample of 116 alcohol-dependent subjects. For the first time, a significant association was identified between this polymorphism and alcoholism.

Is baclofen a revolutionary medication in alcohol addiction management? Review and recent updates.

Baclofen, a γ-aminobutyric acid (GABA)-B receptor agonist, represents a promising drug in alcohol addiction management. Animal models have shown its action at various stages of the process of alcohol addiction. Moreover, initial open and randomized controlled trials have shown the efficacy of 30 mg/day baclofen on alcohol craving, intake, and relapse prevention. It may also decrease alcohol withdrawal symptoms. However, these initial studies were conducted by the same Italian team; 2 American studies, using a different methodology, did not confirm these effects. Following recent reports by an alcohol-dependent French physician who treated himself with high doses (120-270 mg/day), claiming prolonged suppression of alcohol craving and absence of dependence symptoms, baclofen has since received wide media exposure in France where it has been called "the treatment for alcoholism." An open-label French study supports these findings. In addition, baclofen seems to be particularly interesting because of its safety and tolerance, even in patients with cirrhosis. Thus, baclofen should benefit from further studies of its biobehavioral mechanisms, dose-response effect, and indications in various alcoholic patient profiles.

CNR1 gene polymorphisms in addictive disorders: a systematic review and a meta-analysis.

The aim of the present work was to systematically review all association studies of cannabis receptor 1 (CNR1) polymorphisms with dependence syndrome and to perform a meta-analysis. Odds ratios (ORs) were estimated by contrasting the ratio of counts of the 'high risk' versus 'low risk' alleles in cases with dependence versus controls. Studies were analyzed by random-effects meta-analysis using pooled OR. Eleven full text articles met our eligibility criteria and nine meta-analyses were performed on three polymorphisms of CNR1: rs1049353, rs806379 and the AAT repeat. Of these, only the AAT polymorphism showed a significant association with illicit substance dependence but only in the Caucasian population samples and using a risk allele definition of ≥ 16 repeats. Our analysis showed a small effect size (OR = 1.55, P = 0.045), with strong heterogeneity (Q = 19.87, P < 0.01 with I² = 85%). In line with the polygenic model, our meta-analysis supports a minor implication for CNR1 AAT polymorphism in illicit substance dependence vulnerability. Further studies in well-phenotyped samples and using more polymorphisms are needed to conclude on the actual influence of cannabinoid receptor polymorphisms.

Association of inflammation genes with alcohol dependence/abuse: a systematic review and a meta-analysis.

The aim of the present work was to systematically review all association studies of inflammation genes with alcohol dependence/alcohol abuse (AD/AA) and to perform a meta-analysis. Odds ratios (ORs) were estimated by contrasting the ratio of counts of the 'high-risk' versus 'low-risk' alleles in AD/AA cases versus controls. Data reported in at least three published studies were available for four genetic polymorphisms [TNF-α-238 (rs361525, G/A); TNF-α-308 (rs1800629, G/A); IL-1RA (VNTR [86 bp]n); IL-10-592 (rs1800896, C/A)]. In total, nine meta-analyses were performed. Of these, only the TNF-α-238 polymorphism showed a significant association with AD/AA (OR=1.36, 95% CI: 1.05-1.76). This risk remained significant and increased slightly when we considered only patients with advanced alcohol-related liver disease (AALD) (OR=1.5, 95% CI: 1.13-1.98) but not when we considered only patients without AALD (OR=1.08, 95% CI: 0.5-2.35). Sensitivity analysis showed that this genetic association is derived from the AALD phenotype rather than from AD. Our approach is limited by our phenotype definition; some studies included chronic heavy drinkers (minimal daily consumption of 80 g for a minimal duration of 10 years) but without a standardized psychiatric assessment.

Is love passion an addictive disorder?

AIMS: Inquiry regarding the relationship between passionate love and addiction has long been a topic of intense debate. Recent advances in neurobiology now allow for an examination between these two states. METHODS: After describing the clinical distinctions between "love passion," "love addiction," and "sex addiction," we compare clinical, neuropsychological, neurobiological, and neuroimaging data on love, passion, pathological gambling (PG) and substance dependence. RESULTS: There are no recognized definitions or diagnostic criteria for "love addiction," but its phenomenology has some similarities to substance dependence: euphoria and unrestrained desire in the presence of the love object or associated stimuli (drug intoxication); negative mood, anhedonia, and sleep disturbance when separated from the love object (drug withdrawal); focussed attention on and intrusive thoughts about the love object; and maladaptive or problematic patterns of behavior (love relation) leading to clinically significant impairment or distress, with pursuit despite knowledge of adverse consequences. Limited animal and human studies suggest that brain regions (e.g., insula, anterior cingulated [ACC], orbitofrontal [OFC]) and neurotransmitters (dopamine) that mediate substance dependence may also be involved with love addiction (as for PG). Ocytocin (OT), which is implicated in social attachment and mating behavior, may also be involved in substance dependence. There are no data on the epidemiology, genetics, co-morbidity, or treatment of love addiction. CONCLUSION: There are currently insufficient data to place some cases of "love passion" within a clinical disorder, such as "love addiction," in an official diagnostic nomenclature or to firmly classify it as a behavioral addiction or disorder of impulse control. Further clinical and scientific studies are needed to improve our understanding and treatment of this condition. For these studies, we propose new criteria for evaluating addiction to love.

Dual diagnosis: prevalence, risk factors, and relationship with suicide risk in a nationwide sample of French prisoners.

BACKGROUND: Axis I psychiatric disorders (PD) and substance use disorders (SUD) are common in prison, but only few studies have focused on their association in this setting. Dual diagnosis (DD) (the co-occurrence of a SUD and any axis I disorder) is known to have a poorer prognosis and to require more intense supportive care. OBJECTIVES: The objectives of this study were (1) to describe prisoners with DD (prevalence and characteristics); (2) to compare DD prisoners with 3 other groups of prisoners: no diagnosis (ND), SUD alone, or other isolated PD; and (3) to evaluate the impact of DD on suicide risk in prison. METHOD: A random stratified strategy was used to select 23 various types of prisons and 998 prisoners. Diagnoses were assessed using a unique procedure, each prisoner being evaluated by 2 psychiatrists, 1 junior, using a structured interview (MINI 5 plus), and 1 senior, using an open clinical interview. Following interviews, clinicians met to establish a list of diagnoses. Cloninger's temperament and character inventory was also used. RESULTS: Of the prisoners, 26.3% had a DD. DD prevalence was almost 80% in prisoners with SUD, while only one-third of the prisoners with an axis I PD had co-morbid SUD. No significant differences were observed in drug use patterns between DD and SUD without co-morbid PDs. DD showed the strongest association with suicide risk [OR = 5.7 (1.7-4.6)]. CONCLUSION: DD is very frequent in prison and is a major risk factor for suicide. Systematic psychiatric/SUD screening of prisoners with either a SUD or an axis I PD should be encouraged.

Association between MTHFR 677C-T polymorphism and alcohol dependence according to Lesch and Babor typology.

Prior studies have associated 677C-T Methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with decreased enzymatic activity and modified homocysteine regulation. This study determines and compares MTHFR 677C-T distribution and examines its consequences on homocysteine metabolism and alcohol dependence in alcoholic patients classified according to the Babor and Lesch typologies. MTHFR TT genotype was more prevalent in AD patients with milder alcohol dependence (Babor type A) and with Lesch type 3, associated with depression. MTHFR TT was also associated with hyperhomocysteinemia. Determining MTHFR 677C-T genotype, folate and vitamin B12 levels could assist physicians in identifying type 3 patients and improve addictions management.

Pathways to substance-related disorder: a structural model approach exploring the influence of temperament, character, and childhood adversity in a national cohort of prisoners.

AIMS: Using Cloninger's model of personality, we aimed to specify the relative influence of the more biologically determined variables, temperament and character and more environmentally driven influence, childhood adversity in the development of addiction; and to compare patterns found among alcoholics with those found among drug addicts. METHODS: We studied a group of prisoners, at a high risk of substance abuse and past history of childhood adversity. Using a stratified random strategy we selected (i) 23 prisons among the different types of prison in France, (ii) 998 prisoners. Each prisoner was assessed by two psychiatrists--one junior, using a structured interview (MINI 5 plus), and one senior, completing the procedure with an open clinical interview. At the end of the interview the clinicians met and agreed on a list of diagnoses. Cloninger's Temperament and Character Inventory was used to measure personality. Structural equations models, which have been advocated to disentangle the respective influence of complex risk factors, were used. RESULTS: The "novelty seeking" temperament was a crucial vulnerability factor, for both alcoholics and drug addicts, in the same proportion. Character and childhood adversity played a significant part only in the development of drug abuse. CONCLUSIONS: In a prison population, a common biological loaded factor, novelty seeking is found both at the core of alcohol- and drug-related disorder whereas environmentally loaded factors play a greater role in drug problems.

Meta-analysis and review of dopamine agonists in acute episodes of mood disorder: Efficacy and safety.

The objective of this meta-analysis is to assess the efficacy and safety of partial and complete dopamine agonists in the treatment of acute mood disorder episodes. Randomized, double-blind and placebo-controlled trials of dopamine agonists in the treatment of acute mood disorder episodes were identified in the MEDLINE and PsycINFO databases and included in the meta-analysis. In monotherapy of mania, improved remission rates were found for cariprazine (odds ratio (OR): 2.08, P < 0.01) and for high-dose aripiprazole (OR: 3.00; P = 0.05), but not for low-dose aripiprazole. In bipolar depression, no improvement of remission and response rates was found for aripiprazole in monotherapy, whereas improved response rate (OR: 10.27, P < 0.01) was found for pramipexole only as an add-on to another mood stabilizer. In major depressive disorder, relatively similar improvements of remission rates were found for high-dose (OR: 1.96, p < 0.01) and low-dose aripiprazole (OR: 1.68, P = 0.01), as well as brexpiprazole (OR: 1.52, P = 0.05) as an add-on to antidepressant medication. Our meta-analysis shows that partial dopamine agonists at high doses are effective in treating acute mania. In major depressive disorder, which is resistant to classical antidepressants, low doses of partial dopamine agonists as adjunct therapy may represent a relatively safe and effective alternative.

ABCB1 C3435T polymorphism is associated with tetrahydrocannabinol blood levels in heavy cannabis users.

ABCB1 polymorphisms are known to modify drug pharmacokinetics but have yet to be studied for their role in generating and maintaining cannabis dependence. The objective of this study is to determine if ABCB1 C3435T (rs1045642) polymorphism may modulate Δ9-Tetrahydrocannabinol (THC) blood levels in a sample of heavy cannabis users. The study sample includes 39 Caucasian individuals, recruited in two French addictology centres, with isolated cannabis dependence and heavy use (defined as ≥ 7 joints per week). Each underwent clinical evaluation, cannabis blood metabolite dosage (THC, 11-OH-THC, and THC-COOH) and genotyping of ABCB1 C3435T polymorphism. In this population (males: 74.4%, average age 29.5 +/- 9), average cannabis use was 21 joints per week (median 12; range 7 - 80). T carriers (TT/CT) had significantly lower plasma THC levels (ng/ml) versus non T carriers (8 vs 15.70, significant), controlling for level of weekly use, 11-OH-THC and THC-COOH levels. Our results show that ABCB1 C3435T polymorphism may modulate serum THC levels in chronic heavy cannabis users. The exact mechanisms and roles that this may play in cannabis dependence genesis and evolution remain to be elucidated. These results should be controlled in a replication study using a larger population.

Cannabis, cannabinoids, and health.

Cannabis (also known as marijuana) is the most frequently used illicit psychoactive substance in the world. Though it was long considered to be a "soft" drug, studies have proven the harmful psychiatric and addictive effects associated with its use. A number of elements are responsible for the increased complications of cannabis use, including the increase in the potency of cannabis and an evolution in the ratio between the two primary components, Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (toward a higher proportion of Δ9-THC), Synthetic cannabinoid (SC) use has rapidly progressed over the last few years, primarily among frequent cannabis users, because SCs provide similar psychoactive effects to cannabis. However, their composition and pharmacological properties make them dangerous substances. Cannabis does have therapeutic properties for certain indications. These therapeutic applications pertain only to certain cannabinoids and their synthetic derivatives. The objective of this article is to summarize current developments concerning cannabis and the spread of SCs. Future studies must further explore the benefit-risk profile of medical cannabis use.

La sustancia psicoactiva ilícita que se emplea con mayor frecuencia en el mundo es la cannabis. Aunque se consideró por largo tiempo una droga "suave", los estudios han probado los efectos dañinos asociados con su empleo. Hay algunos elementos que son responsables del aumento de las complicaciones del empleo de cannabis, como el incremento en la potencia de ella y una evolución en la relación entre los dos componentes principales, el delta-9-tetrahidrocannabinol y el cannabidiol (con un porcentaje más importante de delta-9-tetrahidrocannabinol). El empleo de cannabinoides sintéticos (CS) ha tenido un rápido aumento en los últimos años, especialmente entre los usuarios frecuentes de cannabis, ya que tienen la ventaja de producir efectos psicoactivos similares a esta droga. La composición y las propiedades farmacológicas de los CS los hacen sustancias peligrosas. Para ciertas indicaciones la cannabis también tiene propiedades terapéuticas, pero esto se aplica sólo para ciertos cannabinoides y sus derivados sintéticos. El objetivo de este artículo es resumir el progreso actual relacionado con la cannabis y la difusión de los CS. Se requieren futuros estudios que promuevan la exploración del perfil de riesgo-beneficio del empleo medicinal de la marihuana.

Le cannabis (connu aussi sous le nom de marijuana) est la substance psychoactive la plus fréquemment utilisée dans le monde. Longtemps considérée comme une drogue « douce ¼, des études ont prouvé les effets addictifs et psychiatriques nocifs associés à son utilisation. Un certain nombre d'éléments sont responsables de l'augmentation des complications liées à l'utilisation du cannabis, comme l'augmentation de sa puissance et une évolution du rapport entre les deux principaux composants, le Δ9-tetrahydrocannabinol (Δ9-THC) et le cannabidiol (avec une proportion plus importante de Δ9-THC). L'utilisation des cannabinoïdes synthétiques (CS) a rapidement progressé ces dernières années, principalement parmi les utilisateurs fréquents de cannabis, les CS apportant des effets psychoactifs similaires à ceux du cannabis. Cependant, leur composition et leurs propriétés pharmacologiques en font des substances dangereuses. Le cannabis a bien des propriétés thérapeutiques pour certaines indications. Ces applications thérapeutiques concernent seulement certains cannabinoïdes et leurs dérivés synthétiques. L'objectif de cet article est de résumer les développements actuels concernant le cannabis et la progression de l'utilisation des CS. Il faut entreprendre de nouvelles études pour mieux étudier le profit bénéfice-risque de l'usage médical du cannabis.

Neuropsychological Impairment in Detoxified Alcohol-Dependent Subjects with Preserved Psychosocial Functioning.

BACKGROUND: Chronic alcoholism and its related cognitive impairments are associated with increased social, relational, and professional deficits which have a variable overall impact on social integration. These impairments are known to have varying severities and have rarely been studied among healthy alcohol-dependent subjects with preserved psychosocial functioning. Thus, the objective of this study is to describe neuropsychological performance in this particular population. METHOD: Twenty-nine socially adjusted alcohol-dependent men, hospitalized for a first or second withdrawal and abstinent for 3 weeks minimum, were compared to 29 healthy non-alcoholic controls. All subjects underwent clinical and psychiatric examination, neuropsychological tests of memory (M), working memory (WM), and executive functions (EF). Comparisons were performed using Student's t-tests or Mann-Whitney U tests. RESULTS: No group differences were found on the Self-Reported Social Adjustment Scale (SAS-SR) or in the Mini-Mental State Examination. Compared to controls, patients had greater episodic, spatial, and WM deficits as well as slightly altered executive functions. In contrast, their executive functions (spontaneous flexibility, criteria generation, rule maintenance, and inhibitory control) were relatively preserved. CONCLUSION: Our sample of socially and professionally integrated alcoholic patients shows fewer cognitive deficits than described in previous studies. Our results suggest that early on, alcohol-dependent subjects develop compensatory adaptation processes to preserve social function and adaptation. Minor cognitive impairments should be screened early in the disease to integrate cognitive interventions into the health-care plan to thus eventually prevent further socio-professional marginalization.

Genetics and psychotic disorders: A fresh look at consanguinity.

Consanguineous unions refer to marriages between related individuals who share a common ancestor. These unions are still commonplace in certain regions of the world such as the southern coast of the Mediterranean, throughout the Middle East and South-East Asia. According to available data, couples of second cousins or closer and their offspring currently represent 10.4% of the world's population, thus resulting in increased frequencies of autosomal recessive disorders. Furthermore, consanguinity may be implicated in the increased frequency of multifactorial pathologies such as mental disorders. The few existing epidemiological studies in consanguineous and/or geographically isolated populations confirm that there is a significant association between consanguinity and mental disorders and a higher risk of schizophrenia or bipolar disorders among offspring from consanguineous couples. There exists a strong and complex genetic component in the predisposition to psychotic disorders that has been confirmed in numerous studies. However, the genetic basis of these disorders remains poorly understood. GWAS studies (Genome Wide Association Studies) over the past 10 years have identified a few weak associations, thus refuting the "common diseases-common variants" hypothesis. A model implicating numerous rare variants has been supported by the recent discovery of CNVs (Copy Number Variants) and their statistically significant association with psychiatric disorders such as schizophrenia, bipolar disorders and autism. The study of consanguineous families may contribute to identifying rare variants in homogenous populations who have conserved certain alleles. Major developments in molecular biology techniques would facilitate these studies as well as contributing to identifying major genes. These results emphasize the need for genetic counseling in high-risk communities and the importance of implementing preventive actions and raising awareness concerning the risk of consanguineous unions.

Genetic Influences in Cannabis Use Disorder and Psychosis: Dopamine and Beyond.

Cannabis consumption has radically changed over the last several decades. Tetrahydrcannbidiol concentrations are rising, cannabidiol concentrations falling and cannabis is becoming legalized in several regions of the globe. Concerns have been raised as to the impact of increased cannabis exposure within the general population on public health. One of the more serious concerns is the potential relationship between cannabis consumption and psychosis. Research has shown a relationship between increasing cannabis use and increasing psychosis risk. This risk is moderated by other factors such as stress and a family history of psychosis. Within this context, it is important to determine potential markers for future psychosis risk. Genetic and epigenetic research in cannabis and psychosis is in its early stages. One common denominator between cannabis use disorder and psychosis is dopamine dysfunction. Research has begun to link heightened dopamine reactivity with the psychotomimetic effects of cannabis. Studies in COMT and DRD2 polymorphisms have failed to show greater associations with transition to psychosis. Studies of AKT1 have shown slightly more promising results. Genome-wide association studies have recently been published some indicating novel polymorphisms. These may pave the way to alternate hypotheses to explain the missing links between cannabis use and increased risk of psychosis. Such knowledge may eventually lead to new pharmacotherapies in addition to the means of screening patients for psychosis risk.

The Synthetic Cannabinoids Phenomenon.

« Spice ¼ is generally used to describe the diverse types of herbal blends that encompass synthetic cannabinoids on the market. The emergence of smokable herbal products containing synthetic cannabinoids, which mimic the effects of cannabis, appears to become increasingly popular, in the new psychoactive substances landscape. In 2014, the existence of 134 different types of synthetic cannabinoids were reported by the European Union Early Warning System. These drugs are mainly sold online as an alternative to controlled and regulated psychoactive substances. They appear to have a life cycle of about 1-2 years before being replaced by a next wave of products. Legislation controlling these designer drugs has been introduced in many countries with the objective to limit the spread of existing drugs and control potential new analogs. The majority of the synthetic cannabinoids are full agonists at the CB1 receptor and do not contain tobacco or cannabis. They are becoming increasingly popular in adolescents, students and clubbers as an abused substance. Relatively high incidence of adverse effects associated with synthetic cannabinoids use has been documented in the literature. Numerous fatalities linked with their use and abuse have been reported. In this paper, we will review the available data regarding the use and effects of synthetic cannabinoids in humans in order to highlight their impact on public health. To reach this objective, a literature search was performed on two representative databases (Pubmed, Google Scholar), the Erowid Center website (a US non-profit educational organization that provides information about psychoactive plants and chemicals), and various governmental websites. The terms used for the database search were: "synthetic cannabinoids", "spice", "new psychoactive substances", and/or "substance use disorder", and/or "adverse effects", and/or "fatalities". The search was limited to years 2005 to 2016 due to emerging scientific literature at this period Health professionals should take into account that limited scientific evidence is available regarding the effect of synthetic cannabinoids use in humans. It thus urges to launch more systematic epidemiological studies, to develop and validate screening procedures, and to investigate the neurobiological and psychological correlates and risk factors associated to synthetic cannabinoids use and misuse.