Place of therapeutic cannabis in France and safety data: A literature review.

OBJECTIVES: To date, very few cannabis-based specialities are authorised on the French market despite a growing demand from patients and health professionals. The objective of this study is to review the tolerance profile and the French legislative status of the two main cannabinoids used for therapeutic purposes: tetrahydrocannabiol (THC) associated with psychoactive effects and non-psychoactive cannabidiol (CBD). METHODS: This review is based on relevant articles retrieved by a search in Google Scholar and PubMed databases and on an assessment of the legal texts and summaries of product characteristics available in France. RESULTS: Evidence for the tolerability of CBD during chronic use is reassuring, but a significant risk of drug interactions exists. THC use appears to be associated with a higher proportion of serious adverse effects, including neuropsychological and cardiovascular effects. Inhaled cannabis appears to be associated with greater toxicity than the oral route. These data are presented together with the pharmacokinetic and pharmacodynamic data of THC and CBD. CONCLUSION: The literature reports several frequent but rarely serious adverse effects of CBD during chronic use as well as a significant risk of drug interactions. THC use seems to be associated with a higher proportion of serious adverse effects compared to CBD, particularly at the neuropsychological and cardiovascular levels. Health professionals should be up to date on the particularities of therapeutic cannabis in terms of efficacy, safety and drug interactions.

[Anti-pneumococcal vaccine: justifications and results]. / Vaccin anti-pneumococcique: justifications et résultats.

The frequency and severity of pneumococci infections, the isolation of invasive serotypes and the fact that certain serotypes develop cross-resistance to antibiotics constitute justifications for anti-pneumococci vaccination. A 23-valence vaccine (Pneumo 23) has been marketed since 1983. A meta-analysis of 9 randomized studies concluded that anti-pneumococci vaccination reduces the overall incidence of pneumococci pneumonia with bacteremia. The efficacy of the vaccine was demonstrated on 4 parameters: proven pneumococci pneumonia, proven pneumococci pneumonia and serotypes contained in the anti-pneumococci vaccine, presumed pneumococci pneumonia, presumed pneumococci pneumonia and serotypes contained in the anti-pneumococci vaccine. The efficacy of the vaccine was significant only for low-risk subjects. The protective effect was not demonstrated against pneumonia whatever the cause and against bronchitis. Other case-control or retrospective studies have also been reported. The results have been somewhat contradictory but there is a demonstration of the usefulness of vaccination in patients over 65 years of age with a moderate risk (living in institution, obstructive bronchopneumonary disease, heart failure). Vaccination is advocated not only after splenectomy and in subjects with sickle cell anemia, but also in frequently hospitalized subjects, particularly those with respiratory failure and smokers. Vaccination is also recommended in case of nephrotic syndrome or an osteomeningeal breach. In at-risk children under 2 years of age, antibiotic prophylaxis is recommended in association with vaccination. The data of revaccination is not clearly determined.

Reliable quantification of bisphenol A and its chlorinated derivatives in human urine using UPLC-MS/MS method.

Bisphenol A (BPA), a widespread man-made chemical classified as an endocrine disruptor, is increasingly considered as a major cause of concern for human health. Chlorine present in drinking water may react with BPA to form chlorinated derivatives (ClxBPA), which have demonstrated a heightened level of estrogenic activity. If many epidemiological studies report that more than 90% of people have detectable BPA levels in their urine, then no such study has been undertaken regarding ClxBPA. The purpose of this work is to propose a highly sensitive and accurate analytical method adapted to large-scale biomonitoring studies aimed at assessing exposure to BPA and ClxBPA through the use of human urine. To achieve this, we have comprehensively validated a method using salting-out assisted liquid/liquid extraction (SALLE) coupled to UPLC-MS/MS and isotope dilution quantification, to measure unconjugated BPA and ClxBPA in human urine according to the accepted guidelines. Deutered BPA as well as deutered 2,2'-DCBPA was used as internal standards. The matrix calibration curve ranged from 0.05 to 1.60 ng mL(-1) and from 0.5 to 16.0 ng mL(-1) for ClxBPA and BPA respectively, and provided good linearity (r²>0.99). This method was precise (the intra- and inter-day coefficients of variation were <20% at three different concentrations: 0.05 ng mL(-1), 0.2 ng mL(-1), 0.8 ng mL(-1) and 0.5 ng mL(-1), 2 ng mL(-1), 8 ng mL(-1) for ClxBPA and BPA, respectively) and accurate (bias ranged from -13% to +12%). The limit of quantification, validated at 0.05 ng mL(-1) and 0.5 ng mL(-1) for ClxBPA and BPA respectively when using 300 µL of urine, was found to be suitable for the concentration existing in real samples. The matrix effect and the BPA cross-contamination were also investigated in this study. The analytical method developed in this study is in accordance with the requirements applicable to biomonitoring of BPA and ClxBPA in human urine.