Development and validation of a bioanalytical method for the simultaneous determination of heroin, its main metabolites, naloxone and naltrexone by LC-MS/MS in human plasma samples: Application to a clinical trial of oral administration of a heroin/naloxone formulation.

A bioanalytical method using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated for simultaneous quantification of heroin, its main metabolites and naloxone. In addition, naltrexone was detected qualitatively. This method was used to analyse human plasma samples from a clinical trial after oral administration of a heroin/naloxone formulation in healthy volunteers. O-methylcodeine was used as an internal standard. Samples were kept in an ice-bath during their processing to minimize the degradation of heroin. A short methodology based on protein precipitation with methanol was used for sample preparation. After protein precipitation, only the addition of a formic acid solution was needed to elute heroin, 6-monoacetylmorphine, morphine, naloxone and naltrexone. Morphine metabolites were evaporated to dryness and reconstituted in a formic acid solution. Chromatographic separation was achieved at 35 °C on an X-Bridge Phenyl column (150 × 4.6 mm, 5 µm) using a gradient elution with a mobile phase of ammonium formate buffer at pH 3.0 and formic acid in acetonitrile. The run time was 8 min. The analytes were monitored using a triple quadrupole mass spectrometer with positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode. The method was found to be linear in a concentration range of 10-2000 ng/mL for M3G and 10-1000 ng/mL for the rest of compounds. Quality controls showed accurate values between -3.6% and 4.0% and intra- and inter-day precisions were below 11.5% for all analytes. The overall recoveries were approximately 100% for all analytes including the internal standard. A rapid, specific, precise and simple method was developed for the determination of heroin, its metabolites, naloxone and naltrexone in human plasma. This method was successfully applied to a clinical trial in 12 healthy volunteers.

Prevalencia del consumo de fármacos psicoactivos en una población de obesos / Prevalence of psychoactive drug consumption in an obese population

Objetivo Determinar la prevalencia de consumo de psicofármacos en una población de obesos. Material y métodos Recogimos datos procedentes de las historias clínicas de pacientes diagnosticados de obesidad y visitados por el Servicio de Endocrinología y Nutrición y por el Servicio de Psiquiatría del Hospital del Mar en el periodo comprendido entre junio del 2005 y mayo del 2006.Material y métodos Las variables recopiladas fueron datos antropométricos, epidemiológicos y toxicológicos. También investigamos la frecuencia de patología concomitante. Resultados El consumo de fármacos psicoactivos en los pacientes con obesidad fue del 37%, siendo los más utilizados los antidepresivos (27%), los ansiolíticos, los sedantes y los hipnóticos y los antiepilépticos. Además, el 15% de los pacientes estaba recibiendo tratamiento con 2 o más psicofármacos, siendo la combinación más frecuente la asociación de antidepresivos con antiepilépticos. Conclusiones La prevalencia de consumo de fármacos psicoactivos en nuestra muestra fue superior a los datos de prevalencia observados en la población general. En el caso de los antidepresivos, el consumo fue 3 veces superior respecto a la población general (AU)

Objective To establish the prevalence of psychoactive drug consumption in an obese population. Material and methods We collected data from the clinical records of obese patients attending the Endocrinology and Nutrition Department and Psychiatry Department of Hospital del Mar between June 2005 and May 2006 (n=259). We recorded anthropometric, epidemiological and toxicological data. We also investigated the prevalence of concomitant diseases in this population. Results Psychoactive drugs were consumed by 37% of obese patients, mainly antidepressants (27%), anxiolytics, sedatives and hypnotics, and anticonvulsants. Moreover, 15% of all patients received combination treatment with two or more psychoactive drugs, mostly the association of an antidepressant and an antiepileptic drug. Conclusion The prevalence of psychoactive drug consumption in our sample was higher than prevalence data observed in the general population, with antidepressant consumption being three-fold higher (AU)

[Prevalence of psychoactive drug consumption in an obese population]. / Prevalencia del consumo de fármacos psicoactivos en una población de obesos.

OBJECTIVE: To establish the prevalence of psychoactive drug consumption in an obese population. MATERIAL AND METHODS: We collected data from the clinical records of obese patients attending the Endocrinology and Nutrition Department and Psychiatry Department of Hospital del Mar between June 2005 and May 2006 (n=259). We recorded anthropometric, epidemiological and toxicological data. We also investigated the prevalence of concomitant diseases in this population. RESULTS: Psychoactive drugs were consumed by 37% of obese patients, mainly antidepressants (27%), anxiolytics, sedatives and hypnotics, and anticonvulsants. Moreover, 15% of all patients received combination treatment with two or more psychoactive drugs, mostly the association of an antidepressant and an antiepileptic drug. CONCLUSION: The prevalence of psychoactive drug consumption in our sample was higher than prevalence data observed in the general population, with antidepressant consumption being three-fold higher.

[Caffeine: a nutrient, a drug or a drug of abuse]. / Cafeína: un nutriente, un fármaco, o una droga de abuso.

Coffee, tea, chocolate and caffeinated drinks are the main sources of caffeine, which is consumed in almost all ages and socioeconomic levels. Caffeine acts as a non-selective adenosine receptor antagonist in the central nervous system. Its main effects are as psychostimulant, acting in addition on the respiratory, muscular and cardiovascular systems. Basically, caffeine is metabolized by the hepatic cytochrome P-450 1A2 enzymes (CYP1A2). Several drugs can interact with its metabolism. The observed interindividual differences of its effects can be explained by variations in its metabolism. The main therapeutic use of caffeine is bronchodilator in respiratory diseases. Other possible uses are under investigation. Acute or chronic consumption of caffeine can induce several adverse effects, including intoxication that can be lethal. Finally, caffeine can be considered a drug of abuse. It has positive reinforcing actions, produces tolerance, and a withdrawal syndrome after stopping its consumption. Caffeine can cause different mental disorders such as dependence, which is not included in the DSM-IV-R, withdrawal syndrome and intoxication. Depending on its use, caffeine can be considered a nutrient, a drug or a drug of abuse.

Bioavailability and antioxidant effects of olive oil phenolic compounds in humans: a review.

Olive oil, the main source of fat in the Mediterranean diet, is a functional food which besides having a high level of monounsaturated fatty acid contains several minor components with biological properties. For some olive oil minor components, such as the antioxidant phenolic compounds, a large body of studies, mainly experimental or in animal models, have been performed. Randomized, controlled, clinical trials in humans are required to provide evidence that olive phenolic compounds contribute significantly to health benefits in order to give recommendations at population level. Here, we summarize the state of the art of the body of knowledge, and to which extent we have evidence, of the bioavailability and of the antioxidant benefits of olive oil phenolic compounds in humans.

Postprandial LDL phenolic content and LDL oxidation are modulated by olive oil phenolic compounds in humans.

Olive oil phenolic compounds are potent antioxidants in vitro, but evidence for antioxidant action in vivo is controversial. We examined the role of the phenolic compounds from olive oil on postprandial oxidative stress and LDL antioxidant content. Oral fat loads of 40 mL of similar olive oils, but with high (366 mg/kg), moderate (164 mg/kg), and low (2.7 mg/kg) phenolic content, were administered to 12 healthy male volunteers in a cross-over study design after a washout period in which a strict antioxidant diet was followed. Tyrosol and hydroxytyrosol, phenolic compounds of olive oil, were dose-dependently absorbed (p<0.001). Total phenolic compounds in LDL increased at postprandial state in a direct relationship with the phenolic compounds content of the olive oil ingested (p<0.05). Plasma concentrations of tyrosol, hydroxytyrosol, and 3-O-methyl-hydroxytyrosol directly correlated with changes in the total phenolic compounds content of the LDL after the high phenolic compounds content olive oil ingestion. A 40 mL dose of olive oil promoted a postprandial oxidative stress, the degree of LDL oxidation being lower as the phenolic content of the olive oil administered increases. In conclusion, olive oil phenolic content seems to modulate the LDL phenolic content and the postprandial oxidative stress promoted by 40 mL olive oil ingestion in humans.

Construcción de un cuestionario para la Valoración de los Efectos Subjetivos de Sustancias con Potencial de Abuso (VESSPA): Evaluación del éxtasis1 / Development and validation of a new questionnaire for the evaluation of the subjective effects induced by substances with abuse potential (vesspa-see): evaluation of ecstasy

Se construye y valida un instrumento para medir los efectos subjetivos producidos por la 3,4-metilenodioximentanfetamina (MDMA). Tras la construcción de un banco de ítems, posteriores reducciones y un análisis factorial, se obtuvo un cuestionario de 36 ítems al que se le denominó VESSPA (Valoración de Efectos Subjetivos de Sustancia con Potencial de Abuso). El cuestionario consta de 6 escalas: 'Sedación', 'Somatización Ansiosa', 'Cambios de Percepción', 'Placer y Contacto Social', 'Actividad y Energía' y escala de 'Sintomatología Psicótica'. Respecto a la fiabilidad se obtuvo una consistencia interna entre 0.67 y 0.86, así como un índice de correlación del testretest entre 0.79 y 0.91, según la escala. En cuanto a la validez se aplicaron tres pruebas: correlaciones entre escalas del VESSPA y del ARCI (Addiction Research Center Inventory-49 item short form), puntuación de las diferentes escalas frente a otras condiciones simuladas (alcohol, cannabis, cocaína y LSD) y respuesta del cuestionario en situación experimental en un ensayo clínico en el que se administró MDMA y alcohol. Los resultados demuestran que el cuestionario VESSPA es un instrumento válido y fiable para medir los efectos farmacológicos de la MDMA y de otros psicofármacos, y puede ser utilizado también en ensayos clínicos (AU)