Health and social problems associated with recent Novel Psychoactive Substance (NPS) use amongst marginalised, nightlife and online users in six European countries.

Continued diversification and use of new psychoactive substances (NPS) across Europe remains a public health challenge. The study describes health and social consequences of recent NPS use as reported in a survey of marginalised, nightlife and online NPS users in the Netherlands, Hungary, Portugal, Ireland, Germany and Poland (n = 3023). Some respondents were unable to categorise NPS they had used. Use of ‘herbal blends’ and ‘synthetic cannabinoids obtained pure’ was most reported in Germany, Poland and Hungary, and use of ‘branded stimulants’ and ‘stimulants/empathogens/nootropics obtained pure’ was most reported in the Netherlands. Increased heart rate and palpitation, dizziness, anxiety, horror trips and headaches were most commonly reported acute side effects. Marginalised users reported substantially more acute side effects, more mid- and long-term mental and physical problems, and more social problems. Development of country-specific NPS awareness raising initiatives, health and social service needs assessments, and targeted responses are warranted

Signal transduction in cells of the immune system in microgravity

Life on Earth developed in the presence and under the constant influence of gravity. Gravity has been present during the entire evolution, from the first organic molecule to mammals and humans. Modern research revealed clearly that gravity is important, probably indispensable for the function of living systems, from unicellular organisms to men. Thus, gravity research is no more or less a fundamental question about the conditions of life on Earth. Since the first space missions and supported thereafter by a multitude of space and ground-based experiments, it is well known that immune cell function is severely suppressed in microgravity, which renders the cells of the immune system an ideal model organism to investigate the influence of gravity on the cellular and molecular level. Here we review the current knowledge about the question, if and how cellular signal transduction depends on the existence of gravity, with special focus on cells of the immune system. Since immune cell function is fundamental to keep the organism under imnological surveillance during the defence against pathogens, to investigate the effects and possible molecular mechanisms of altered gravity is indispensable for long-term space flights to Earth Moon or Mars. Thus, understanding the impact of gravity on cellular functions on Earth will provide not only important informations about the development of life on Earth, but also for therapeutic and preventive strategies to cope successfully with medical problems during space exploration

The effect of gravity on microtubule self-organisation

The molecular processes by which gravity biological systems are effected by gravity are not understood. Theoreticians have proposed this might mise through the bifurcation properties of certain types of non-linear chemical reactions that self-organise by reaction and diffusion. We have found that in-vitro preparations of microtubules, an important element of the cellular skeleton, show this type of behaviour. The solutions self-organise and the morphology that arises depend upon the sample orientation, with respect to gravity, at a critical moment at an early stage in the development of the self-organised state. As predicted by theories of this type, no self-organisation occurs when the microtubules are assembled under low gravity conditions. At a molecular level this behaviour results fiom an interaction of gravity with macroscopic concentration and density fluctuations arising from processes of microtubule contraction and elongation. Numerical simulations of reaction and diffusion in a population of microtubules, leads to macroscopic self-organisation when a small effect somehow creates an asymmetry in the direction of microtubule growth. This can arise either by a force that slightly favours some microtubule orientations or by an asymmetry in molecular transport and diffusion such as may arise in the presence of gravity

Virgin olive oil color and perceived quality among consumers in emerging olive-growing countries

Five virgin olive oil samples were evaluated by 122 consumers for their color acceptability and expected quality on 9-point structured scales. A description of the attributes expected in the different oils was obtained from the responding consumers by means of a check-all-that-apply questionnaire consisting of a list of 17 possible virgin olive oil attributes. Hierarchical cluster analysis led to the identification of two consumer clusters with distinct behavior. Whereas one consumer cluster attributed higher quality to those oils that were greener in color, which they described as tasty, rich-flavored, strong-tasting, herb-flavored and expensive, consumers in the other cluster assumed that greener olive oils were of a poorer quality, as they described them as strange-tasting, strong-tasting, herb-tasting and defective. Despite the contrasting perception of a virgin olive oil’s green color, the respondents, irrespective of cluster, presumed that the virgin olive oil that was the yellowest in color was of poor quality and cheap, also assuming that it had a milder taste than the other oils.<br><br>122 consumidores evaluaron el color de 5 muestras de aceite de oliva virgen, midiendo su aceptabilidad y la calidad esperada por medio de una escala estructurada de 9 puntos y describiéndolas por medio de preguntas “marque todo lo que corresponde” que consiste en una lista de 17 términos posibles para atributos de aceites de oliva extra vírgenes. Mediante un análisis de conglomerados jerárquico se identificó a dos grupos de consumidores Los consumidores de ambos grupos consideraron que los aceites más amarillos eran de baja calidad, describiéndolos como baratos y de gusto suave. Un grupo de consumidores asignó puntuaciones de calidad alta a todos los aceites con colores verdes, describiéndolos como sabrosos, aromáticos, con gusto fuerte, con sabor a hierba y caros. El otro grupo de consumidores consideró que los aceites de color verde más intenso eran también de baja calidad, describiéndolos como con sabor extraño, con gusto fuerte, con sabor a hierba y defectuosos. Este estudio demuestra que en los países con olivicultura emergente pero con poca tradición de consumo de aceite de oliva, los consumidores aún no tienen preferencias comerciales claras sobre el color de este producto, aunque coinciden en rechazar y considerar como de baja calidad a los aceites de oliva amarillos posiblemente por asociarlos con los aceites de semillas que habitualmente se encuentran en el mercado

Oral administration of cannabis and Δ-9-tetrahydrocannabinol (Thc) preparations: A systematic review

Background and objective: Changes in cannabis legalization regimes in several countries have influenced the diversification of cannabis use. There is an ever-increasing number of cannabis forms available, which are gaining popularity for both recreational and therapeutic use. From a therapeutic perspective, oral cannabis containing Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) is a promising route of administration but there is still little information about its pharmacokinetics (PK) effects in humans. The purpose of this systematic review is to provide a general overview of the available PK data on cannabis and THC after oral administration. Methods: A search of the published literature was conducted using the PubMed database to collect available articles describing the PK data of THC after oral administration in humans. Results: The literature search yielded 363 results, 26 of which met our inclusion criteria. The PK of oral THC has been studied using capsules (including oil content), tablets, baked goods (brownies and cookies), and oil and tea (decoctions). Capsules and tablets, which mainly correspond to pharmaceutical forms, were found to be the oral formulations most commonly studied. Overall, the results reflect the high variability in the THC absorption of oral formulations, with delayed peak plasma concentrations compared to other routes of administration. Conclusions: Oral THC has a highly variable PK profile that differs between formulations, with seemingly higher variability in baked goods and oil forms. Overall, there is limited information available in this field. Therefore, further investigations are required to unravel the unpredictability of oral THC administration to increase the effectiveness and safety of oral formulations in medicinal use

UHPLC-MS/MS analysis of cannabidiol metabolites in serum and urine samples. Application to an individual treated with medical cannabis

No analytical assay is currently available for the simultaneous determination of CBD major metabolites in serum or urine samples of individuals treated with medical cannabis or CBD-based pharmaceuticals. We developed and validated a method using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC–MS/MS) for quantifying cannabidiol (CBD) and its metabolites, cannabidiol-7-oic acid (7-COOH-CBD), 7- hydroxycannabidiol (7-OH-CBD), 6-alpha-hydroxycannabidiol (6-α–OH–CBD) and 6-beta-hydroxycannabidiol (6-β–OH–CBD) in serum and urine samples of an individual treated with medical cannabis. The ionization was performed by electrospray in negative mode to reach the sensitivity required to detect trace amounts, with limits of quantification ranging from 0.05 to 0.1 ng/mL. The method is accurate (average inter/intra-day error, <15%), precise (inter/intra-day imprecision, <15%) and fast (8 min run time) and it is an essential tool to investigate CBD pharmacokinetics and pharmacodynamics in individuals treated with medical cannabis or with CBD-based medical preparations

Neurocognitive performance following acute mephedrone administration, with and without alcohol

Recreational use of mephedrone, alone and in combination with alcohol, has increased over the past years. Pharmacological properties of mephedrone share similarities with methylenedioxymethamphetamine (MDMA), but its effect on neurocognitive function has not been well established in humans. The present study assessed the effect of mephedrone alone and after co-administration with alcohol on neurocognitive function. It was hypothesised that mephedrone would improve psychomotor performance but impair memory performance, when administered alone. Neurocognitive performance was expected to be impaired following mephedrone when combined with alcohol. Eleven participants received single doses of 200 mg mephedrone or placebo combined with 0.8 g/kg alcohol or placebo. Neurocognitive performance was assessed at baseline (T0), at one hour (T1) and four hours after (T2) mephedrone administration, by means of the Divided Attention Task (DAT), Critical Tracking Task (CTT), and the Spatial Memory Test (SMT). Mephedrone intoxication impaired short-term spatial memory at T1 and improved critical tracking performance at T2 Mephedrone alone did not affect divided attention, but did show an interaction with alcohol on reaction time at T2 Reaction time decreased when mephedrone was combined with alcohol as compared to alcohol alone. Alcohol intoxication impaired both short- and long-term spatial memory at T1 and divided attention at T1 and T2 Critical tracking performance was not affected by alcohol intoxication. The current findings support the hypothesis that mephedrone improves psychomotor performance, impairs spatial memory and does not affect divided attention performance. Stimulatory effects of mephedrone were not sufficient to compensate for the impairing effects of alcohol on most performance parameters