Cannabidiol affects circadian clock core complex and its regulation in microglia cells.

Cannabis is often used by consumers for sleep disorders. Studies show that circadian rhythm could be affected by a misuse of cannabis. Recent research has connected the role of microglial cells with psychiatric disorders such as substance abuse. The aim was to show the effect of two major components of cannabis on circadian genes regulation in microglial cells. In BV-2 microglial cells, cannabidiol (CBD) induces a deregulation of circadian genes with (P-value = 0.039) or without (P-value = 0.0015) lipopolisaccharides stimulation. CBD up regulated Arntl (P = 9.72E-5) and down regulated Clock (P = 0.0034) in BV-2 cells. Temporal expression of Arntl (light and dark P = 0.0054) and Clock (light and dark P = 0.047) was confirmed to have 24 hours light and dark rhythmic regulation in dissected suprachiasmatic nucleus as well as of Cb1 cannabinoid receptor (light and dark P = 0.019). In BV-2 microglia cells, CBD also up regulated CRY2 (P = 0.0473) and PER1 (P = 0.0131). Other nuclear molecules show a deregulation of circadian rhythm in microglial cells by CBD, such as RORA, RevErbα, RORB, CREBBP, AFT4, AFT5 and NFIL3. Our study suggests that circadian rhythm in microglial cells is deregulated by CBD but not by THC. It is consistent with clinical observations of the use of therapeutic cannabis to treat insomnia.

Several clock genes polymorphisms are meaningful risk factors in the development and severity of cannabis addiction.

Circadian rhythms have been related to psychiatric diseases and regulation of dopaminergic transmission, especially in substance abusers. The relationship between them remained enigmatic and no data on the role of clock genes on cannabis dependence have been documented. We aimed at exploring the role of clock gene genotypes as potential predisposing factor to cannabis addiction, using a high throughput mass spectrometry methodology that enables the large-scale analysis of the known relevant polymorphisms of the clock genes. We have conducted a case-control study on 177 Caucasians categorizing between cannabis-addicted subjects and casual consumers based on structured interviews recorded socio-demographic data, AUDIT, Fagerström test, MINI, and medical examinations. Alcohol, opiates, and stimulants' consumption was as exclusion criteria. We report an association between several Single Nucleotide Polymorphism (SNP)s in main circadian genes SNPs, especially the gene locus HES7/PER1 on chromosome 17 and cannabis consumption as well as the development of neuropsychiatric and social disorders. This SNP's signature that may represent a meaningful risk factor in the development of cannabis dependence and its severity requires to be deeply explored in a prospective study.

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.

MDPV and α-PVP use in humans: The twisted sisters.

The new psychoactive substances phenomenon continues to represent a considerable public health challenge. Synthetic cathinones are ß-keto amphetamine analogues, also known as legal highs, research chemicals, bath salts. These drugs have surfaced as a popular alternative to other illicit drugs of abuse, such as cocaine, MDMA, and methamphetamine, due to their potent psychostimulant and empathogenic effects. Pyrovalerone cathinones (a-pyrrolidinophenones) form a distinct group of designer cathinones, such as MDPV. After being listed as an illegal product, "second generation" compounds such as α-PVP, sharing a very similar chemical structure with MDPV, were developed. Clinical effects of these compounds are individual, dose- and route of administration-dependent. Both of them have been involved in an increased number of, not only acute intoxications but also fatalities over the past few years, raising concerns in the medical field. In this paper, we will review the available data regarding the use and effects of MDPV and α-PVP in humans in order to highlight their impact on public health. Health actors and general population need to be clearly informed of potential risks and consequences of these 2 novel psychoactive substances spread and use. The literature search conducted led to the identification of potentially 83 relevant articles. All articles were screened from their abstracts to determine their relevance in the framework of the current review. This article is part of the Special Issue entitled 'Designer Drugs and Legal Highs.'

[Support for addictive behaviour among nursing staff]. / Accompagnement des conduites addictives du personnel soignant.

For the last 10 years the FIDES mission has promoted an addiction prevention policy within the Paris public hospitals group. It raises awareness among all hospital staff, provides the health professionals concerned access to comprehensive training in identifying addictive behaviour, offers support for all difficult situations and carries out studies into substance use practices.

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.

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.

[Adolescent addictive behaviors]. / Conduites addictives de l'adolescent.

Adolescence is a period with a specific risk to develop addictive behaviours. During this key period, addictions can be at the root of very damaging consequences, both on the health and social sides, which is nowadays a public health issue. Paradoxically, teenagers are often not requesting for aid and access aid with difficulty. So, first aid operators play a central role in teenagers' care, since they can detect precociously at-risk teenagers and orientate them to specialized care if necessary.

[Cocaine addiction: current data for the clinician]. / Addiction à la cocaïne : données actuelles pour le clinicien.

Cocaine remains the second most commonly used illicit drug worldwide after cannabis. Observed levels of cocaine use among countries considerably vary. An increased cocaine use is recorded in the general European population. Cocaine addiction is a worldwide public health problem, which has somatic, psychiatric, socio-economic and judicial complications. It is a multifactorial disorder variable in its clinical manifestations and heritable. Compared to the general population, there is a high prevalence of somatic and psychiatric disorders among cocaine-dependent patients. There are predictable dose-related effects of pharmacological action of cocaine and effects which are uncommon, unrelated to dose and occur randomly in this population. The number of patients entering drug treatment for primary cocaine use has been increasing in Europe for several years. However, there is no specific pharmacotherapy with established efficacy for the treatment of cocaine addiction, nor is any medication approved by regulatory authorities for such treatment. Recent controlled clinical studies and laboratory studies have highlighted some very promising medications. The perfect therapeutic platform for abstinence initiation and relapse prevention of cocaine addiction is a combination of pharmacological treatments and behavioral treatments. Targeting somatic and psychiatric comorbidity is another way to use pharmacological treatments in addictions.

[How to detect teenagers' cannabis use and what needs to be done?]. / Comment repérer chez les jeunes adolescents la consommation de cannabis que faire?

Adolescence is a period of confrontation and initiation to psychoactives drugs. Teenager's substance disorder remains an important concern for families and public authorities. The seriousness of consequences due to cannabis use, both on the health and social points, depends on the age of first use, the duration of use and the user himself. Teenagers, who do not often request to be taken care, are a population who has difficulty to access to medical treatment, even if the offer of medical treatment has increased. It is necessary to develop an early detection among vulnerable populations like teenagers, to train first aid operators to early detection strategies, as well as to increase the knowledge of the care system to improve teenagers' orientation in the care system.

[Substance abuse among health personnel, defense or temptation?]. / La consommation de substances à l'hôpital, rempart ou tentation?

The increase of the psychological burden at work influences the consumption of substances, notably tobacco and alcohol. Healthcare workers are in a high-risk sector where we observe increasing malaise. A model of prevention and support with the treatment of staff members' addictions has been put in place within the Paris public hospital system (AP-HP): the Fides mission.