The evolution of European legislation on doping: new challenges in the age of NPS.

The fight against doping in sport, formally started in 1960 with the constitution of the International Olympic Committee (IOC) and culminated in 1999 with the birth of the World Anti-Doping Agency (WADA), commissioned to chair various activities, including the publication of the annual list of prohibited substances and methods for doping. In Europe, as early as 1967, the Committee of Ministers of the Council of Europe adopted a resolution to stigmatise the intake of substances foreign to the body for the sole purpose of artificially and unfairly influencing sports performance. In 2002, the Council of Europe adopted an Additional Protocol to the 1989 Strasbourg Convention against Doping to ensure mutual recognition of doping controls and to strengthen the enforcement of the Convention. In Italy, the Law of 14 December 2000 n. 376 "Discipline of the health protection of sports activities and the fight against doping", defines doping as "the administration or intake of drugs or biologically or pharmacologically active substances and the adoption or submission to medical practices not justified by pathological conditions and suitable to modify the psychophysical or biological conditions of the organism in order to alter the athletic performance of athletes". The same law regulates the use of drugs or biologically or pharmacologically active substances and update an annual list in agreement with WADA. The article aims to analyse the legislation from a national perspective, offering as complete a view as possible of the current situation.

The overwhelming issue of Drug Facilitated Sexual Assaults (DFSA): the case of GHB.

Drug-facilitated sexual assaults (DFSA) currently represent overwhelming issue in its multidisciplinary approach. They occur when alcohol or drugs are used to compromise an individual's ability to consent to a sexual act. These substances facilitate a perpetrator to commit sexual assault because they inhibit a person's ability to resist and can prevent them from remembering the assault. If on the one hand alcohol remains the most commonly used drug in crimes of sexual assault, on the other hand drugs being used by perpetrators in crimes of sexual assault include, but are not limited to, Rohypnol (but also other benzodiazepines can be used), GHB (Gamma Hydroxybutyric Acid), GBL (Gamma-Butyrolactone), ketamine and others. The authors briefly examine the main issues of GHB-facilitated sexual assault in forensic investigation, drawing the attention of the whole scientific community to the importance of a correct assessment of each GHB-FSA, even when it is only suspected and by providing some practical advices.

Use of cognitive enhancers: methylphenidate and analogs.

OBJECTIVE: In the last decades, several cognitive-enhancing drugs have been sold onto the drug market. Methylphenidate and analogs represent a sub-class of these new psychoactive substances (NPS). We aimed to review the use and misuse of methylphenidate and analogs, and the risk associated. Moreover, we exhaustively reviewed the scientific data on the most recent methylphenidate analogs (methylphenidate and ethylphenidate excluded). MATERIALS AND METHODS: Literature search was performed on methylphenidate and analogs, using specialized search engines accessing scientific databases. Additional reports were retrieved from international agencies, institutional websites, and drug user forums. RESULTS: Methylphenidate/Ritalin has been used for decades to treat attention deficit disorders and narcolepsy. More recently, it has been used as a cognitive enhancer and a recreational drug. Acute intoxications and fatalities involving methylphenidate were reported. Methylphenidate was scheduled as an illegal drug in many countries, but NPS circumventing the ban and mimicking the psychostimulant effects of methylphenidate started being available: ethylphenidate, 3,4-dichloromethylphenidate, 3,4-dichloroethylphenidate, 4-fluoromethylphenidate, 4-fluoroethylphenidate, methylnaphthidate, ethylnaphthidate, isopropylphenidate, propylphenidate, 4-methylmethylphenidate, and N-benzylethylphenidate have been available in the past few years. Only little data is currently available for these substances. Many intoxications involving methylphenidate analogs were reported. To date, ethylphenidate was involved in 28 fatalities, although it was reportedly directly related to the cause of death in only 7 cases; 3,4-dichloroethylphenidate was involved in 1 death. CONCLUSIONS: The rapid expansion of methylphenidate analogs onto the drug market in the past few years makes likely the occurrence of intoxications and fatalities in the next years. Careful monitoring and systematic control of methylphenidate analogs should be undertaken to reduce the uprising threat, and education efforts should be made among high-risk populations.

Drug-facilitated sexual assaults (DFSA): a serious underestimated issue.

OBJECTIVE: Drug-facilitated sexual assault (DFSA) is a nonconsensual sexual act in which the victim is incapacitated or unconscious due to the effects of alcohol, a drug and/or other intoxicating substances. Dozens of drugs (including ethanol) can potentially be used to commit sexual assaults, but γ-Hydroxybutyric acid (GHB) and flunitrazepam are the most common "date rape drugs". MATERIALS AND METHODS: Multidisciplinary databases were browsed using the following search terms: "drug-facilitated sexual assault", "chemical submission", "date rape", "rape drugs", and "drink-spiking". Moreover, a search for reports was conducted on Institutional websites to identify documentation published by international agencies or institutions. Articles and reports were independently evaluated by each author. RESULTS: There are no accurate estimates of the number of DFSA occurring each year, although assaults are increasingly reported. Many DFSA, however, are still not reported. Victims are reluctant to report incidents because of embarrassment, guilt or perceived responsibility, or because they do not clearly remember the assault. Moreover, most of the drugs typically used in sexual assaults are rapidly metabolized, making them undetectable in routine drug screenings. CONCLUSIONS: Most of the substances involved in DFSA, with the exception of alcohol, are under international control and scheduled under the United Nations Single Convention on Narcotic Drugs of 1961 and the Convention on Psychotropic Substances of 1971. However, several psychotropic substances and antihistamines used in sexual assaults are still not under international control, allowing for trafficking, often via the Internet and courier. The absence of international control makes it difficult to obtain accurate data on the nature and the extent of the problem.

Deriving a quantitative chirality measure from molecular similarity indices.

A versatile new method has been developed as a continuous symmetry measure for chiral compounds. The application of principal component analysis (PCA) to the complete N x N pairwise similarity matrices (electrostatic potential and shape indices) of a series of dihydropyridine calcium channel antagonists allowed to single out a chirality component and to compute a chirality score in terms of the between-enantiomers difference on the component value. The possibility to have chirality defined continuously at the series level could be of importance in eudismic analyses where the relative potency of two enantiomers is studied as well as in QSAR studies dealing with chiral molecules in order to improve the power of the generated models.

Predicting logP of pesticides using different software.

We compared experimental and calculated logP values using a data set of 235 pesticides and experimental values from four different sources: The Pesticide Manual, Hansch Manual, ANPA and KowWin databases. LogP were calculated with four softwares: HyperChem, Pallas, KowWin and TOPKAT. Crossed comparison of the experimental and calculated values proved useful, especially for pesticides. These are harder to study than simpler organic compounds. Structurally they are complex, heterogeneous and similar to drugs from a chemical point of view. They offer an interesting way to verify the goodness of the different methods. Other studies compared several logP predictors using a single set of experimental values taken as a reference. Here we discuss the utility of the different logP predictors, with reference to experimental data found in different databases. This offers three advantages: (1) it avoids bias due to the assumption that one single data set is correct; (2) a given predictor can be developed on the same data set used for evaluation; (3) it takes account of experimental variability and can compare it with the predictor's variability. In our study Pallas and KowWin gave the best results for prediction, followed by TOPKAT.

Factors influencing predictive models for toxicology.

Comparisons of different models to predict toxicity and evaluation of the predictive power of a model are affected by the variability of the data. We assessed this problem by considering experimental toxicity data and chemical descriptors. We evaluated several toxicological end-points (Oncorhynchus mykiss, Daphnia magna, Acceptable Daily Intake, Anas Platyrhynchos, Colinus virginianus and Muridae) in the case of pesticides and also considered the availability of toxicological data. We calculated hundreds of molecular descriptors (divided into constitutional, electrostatic, geometrical, quantum-chemical and topological ones) for the selected compounds using CODESSA, HyperChem and Pallas. Molecular descriptors may vary depending on the conformation of the molecules and on the software used. We evaluated the extent of this variability, and compared it with the variability of the experimental toxicological values.