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.

Development and validation of a single LC-MS/MS assay following SPE for simultaneous hair analysis of amphetamines, opiates, cocaine and metabolites.

The two major challenges in hair analysis are the limited amount of samples usually available and the low targeted concentrations. To overcome these limitations, a liquid chromatography-electrospray-tandem mass spectrometry method (LC-ESI-MS/MS) allowing the simultaneous analysis of 17 amphetamines (amphetamine, BDB, m-CPP, dexfenfluramine, DOB, DOM, ephedrine, MBDB, MDA, MDEA, MDMA, methamphetamine, methylphenidate, 4-MTA, norephedrine, norfenfluramine and PMA), 5 opiates (morphine, codeine, heroin, ethylmorphine, and 6AM), cocaine and 5 metabolites [ecgonine methyl ester (EME), benzoylecgonine (BZE), anhydroecgonine methyl ester (AME), cocaethylene, and norcocaine] has been developed. The validation procedure included linearity, intra-day and inter-day variability and accuracy for 5 days (5 replicates at 3 concentration levels). Proficiency studies were used to check the accuracy of the method. As a result, all amphetamines, opiates and cocaine derivatives were satisfactory identified by 2 MRM transitions in 15 min. Calibration curves were performed by a quadratic 1/X weighted regression. The calibration model fits from 0.05 to 10 ng/mg. The limits of detection (LODs) range between 0.005 and 0.030 ng/mg. Precision has been checked by intra-day and inter-day RSD, and associated relative bias, which were lower than 25% for the limits of quantifications (LOQs) and lower than 20% for the other levels tested. This method was routinely applied to hair samples: two positive results of adult drug addicts are presented.