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Biomedical subjects

J Camí

Publications and source records attributed to J Camí.

At least 19 recordsLinked to original sources
PubMed2004

Repeated doses administration of MDMA in humans: pharmacological effects and pharmacokinetics.

RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is increasingly used by young people for its euphoric and empathic effects. MDMA presents non-linear pharmacokinetics, probably by inhibition of cytochrome P450 isoform 2D6. Users are known to often take more than one dose per session. This practice could have serious implications for the toxicity of MDMA. OBJECTIVE: To evaluate the pharmacological effects and pharmacokinetics of MDMA following the administration of two repeated doses of MDMA (24 h apart). METHODS: A randomised, double-blind, cross-over, placebo controlled trial was conducted in nine healthy male subjects. Variables included physiological, psychomotor performance, subjective effects, endocrine response and pharmacokinetics. MDMA 100 mg or placebo was administered in two successive doses separated by an interval of 24 h. RESULTS: MDMA produced the prototypical effects of the drug. Following a second dose, plasma concentrations of MDMA increased (AUC 77% and Cmax 29%) in comparison with the first. The increase is greater than those expected by simple accumulation and indicates metabolic inhibition. The pharmacological effects after the second dose were slightly higher than those observed after the first in the majority of variables including blood pressure, heart rate, most subjective effects and cortisol concentrations. The effects were similar in the case of pupil diameter, esophoria and prolactin. CONCLUSIONS: Pharmacological effects after the second administration were higher than those following the first but lower than expected. A disproportionate increase in plasma concentrations in MDMA and MDA was observed most likely due to metabolic inhibition. This inhibition lasts at least 24 h. Further experiments need to be conducted to evaluate its duration.

Adult↗
PubMed2001

Modulation of rate of onset and intensity of drug effects reduces abuse potential in healthy males.

Low, medium, and high doses of flunitrazepam were tested in three independent randomized, double-blind, balanced cross-over, placebo-controlled trials to study the influence of rate of onset of effects and dose administered on its acute effects. Three groups of 12 healthy male volunteers received six oral doses of placebo or flunitrazepam in slow and fast onset conditions as follows: six capsules of 0.16 mg (slow) and a single capsule of 0.8 mg (fast) in the low dose trial; six 0.25 mg (slow) and a single 1.25 mg (fast) capsules for medium dose; and six 0.4 mg (slow) and a single 2 mg (fast) capsule for high dose. At each dose level, slow or fast increasing flunitrazepam plasma concentrations lead to similar peak levels, but induced differential subjective and behavioral effects. In addition to objective and subjective sedation, flunitrazepam induced some pleasurable feelings, which were more intense in the fast than in the slow conditions. At the highest dose, unpleasant sedative effects surmounted positive effects, while at the lowest dose pleasurable effects were of low intensity. At the medium dose, the balance between pleasurable and unpleasant feelings resulted in euphorigenic effects, which were evident in the fast condition but were blunted in the slow condition.

Adolescent↗
PubMed2000

Non-linear pharmacokinetics of MDMA ('ecstasy') in humans.

AIMS: 3,4-Methylenedioxymethamphetamine (MDMA, commonly called ecstasy) is a synthetic compound increasingly popular as a recreational drug. Little is known about its pharmacology, including its metabolism and pharmacokinetics, in humans in controlled settings. A clinical trial was designed for the evaluation of MDMA pharmacological effects and pharmacokinetics in healthy volunteers. METHODS: A total of 14 subjects were included. In the pilot phase six received MDMA at 50 (n=2), 100 (n=2), and 150 mg (n=2). In the second phase eight received MDMA at both 75 and 125 mg (n=8). Subjects were phenotyped for CYP2D6 activity and were classified as extensive metabolizers for substrates, such as MDMA, whose hepatic metabolism is regulated by this enzyme. Plasma and urine samples were collected throughout the study for the evaluation of MDMA pharmacokinetics. Body fluids were analysed for the determination of MDMA and its main metabolites 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxy-methamphetamine (HMMA) and 4-hydroxy-3-methoxy-amphetamine (HMA). RESULTS: As the dose of MDMA administered was increased, volunteers showed rises in MDMA concentrations that did not follow the same proportionality which could be indicative of nonlinearity. In the full range of doses tested the constant recovery of HMMA in the urine combined with the increasing MDMA recovery seems to point towards a saturation or an inhibition of MDMA metabolism (the demethylenation step). These observations are further supported by the fact that urinary clearance was rather constant while nonrenal clearance was dose dependent. CONCLUSIONS: It has previously been postulated that individuals genetically deficient for the hepatic enzyme CYP2D6 (about 10% of the Caucasian people) were at risk of developing acute toxicity at moderate doses of MDMA because the drug would accumulate in the body instead of being metabolized and inactivated. The lack of linearity of MDMA pharmacokinetics (in a window of doses compatible with its recreational use) is a more general phenomenon as it concerns the whole population independent of their CYP2D6 genotype. It implies that relatively small increases in the dose of MDMA ingested are translated to disproportionate rises in MDMA plasma concentrations and hence subjects are more prone to develop acute toxicity.

3,4-Methylenedioxyamphetamine↗
PubMed2000

Immunomodulating activity of MDMA.

MDMA (3,4-methylenedioxymethamphetamine) use can cause neurochemical, behavioral and endocrine alterations, similar to those produced by exposure to acute stress, suggesting its potential as a "chemical stressor." It is known that stressful stimuli can produce a depression of immune function and an alteration in immune cells distribution. In vitro exposure to MDMA resulted in a modulation of several immune functional parameters such as T-cell regulatory function, cytotoxic T-lymphocyte activity, natural killer cell activity and macrophage function. Administration of MDMA in rats produced a rapid and sustained suppression of induced lymphocytes proliferation and a significant decrease in circulating lymphocytes. These alterations in rat immune function were accompanied by a significant rapid increase in plasma corticosterone concentrations. It was postulated that the result of altered induced proliferation response of lymphocytes could have been due to a combined effect of direct action of MDMA on lymphocytes and to the activation of the hypothalamic pituitary adrenal axis (HPA axis) and/or the sympathetic nervous system (SNS) via central mechanisms. In humans, acute MDMA treatment produced a time-dependent immune dysfunction associated with MDMA plasma concentrations. Although total leukocyte count remained unchanged, there was a decrease in CD4+ T-cells and functional responsiveness of lymphocytes to mitogenic stimulation, while percentage of natural killer cells significantly increased. A rise of cortisol plasma concentrations similar to that observed in the rat model supported the hypothesis of MDMA-induced release of corticotrophin-releasing factor from the median eminence of the hypothalamus and subsequent HPA axis and SNS activation. The present findings indicate that MDMA ingestion may represent a potential health hazard for an increased risk of immune system-related diseases.

Animals↗
PubMed1999

Response patterns of the Spanish version of the 49-item short form of the Addiction Research Center Inventory after the use of sedatives, stimulants, and opioids.

This report examines the validity of the Spanish version of the 49-item short form of the Addiction Research Center Inventory (ARCI) for measuring subjective effects after the use of sedatives, stimulants, and opioids. Data from four clinical trials in which this questionnaire was used have been analyzed. The Spanish ARCI short form was found to be sensitive in measuring subjective effects after the administration of alcohol, triazolam, and flunitrazepam (sedatives), cocaine (stimulants), and morphine, pentazocine, and naloxone (opioids) and to distinguishing among them. The response patterns were similar to those previously reported for the same drugs with the English version of ARCI. It is concluded that Spanish version of the 49-item short form of ARCI is a valid instrument for assessing the subjective effects of psychoactive drugs in the Spanish-speaking population context.

Administration, Oral↗
PubMed1999

Quantification of 3,4-methylenedioxymetamphetamine and its metabolites in plasma and urine by gas chromatography with nitrogen-phosphorus detection.

A gas chromatographic method with nitrogen-phosphorus detection involving a solid-liquid extraction phase was developed and validated for the simultaneous quantification of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) in plasma. A modification of this method was validated for the analysis of MDMA, MDA, 4-hydroxy-3-methoxymethamphetamine (HMMA) and, 4-hydroxy-3-methoxyamphetamine (HMA) in urine. Under the analytical conditions described, the limits of detection in plasma and urine were less than 1.6 microg/l and 47 microg/l, respectively, for all the compounds studied. Good linearity was observed in the concentration range evaluated in plasma (5-400 microg/l) and urine (100-2000 microg/l) for all compounds tested. The recoveries obtained from plasma were 85.1% and 91.6% for MDMA and MDA, respectively. Urine recoveries were higher than 90% for MDMA and MDA, 74% for HMMA, and 64% for HMA. Methods have been successfully used in the assessment of plasma and urine concentrations of MDMA and its main metabolites in samples from clinical studies in healthy volunteers.

Chromatography, Gas↗
PubMed1999

Quantification of amphetamine plasma concentrations by gas chromatography coupled to mass spectrometry.

We developed a fast and sensitive method for identification and quantification of plasma concentrations of amphetamine using gas chromatography with mass spectrometry detection (GC-MS). Amphetamine-d8 served as internal standard. The method involves a single extraction procedure and an easy treatment of the samples that allowed no losses during the evaporation process. Derivatisation of amphetamine with N-methyl-bis(trifluoroacetamide), a potent acylating agent, provides many advantages to the method compared with common derivatisation reactions usually used for amphetamines. The limits of detection and quantification following this method were 0.43 and 1.42 ng/ml, respectively. The assay has been successfully employed in the quantification of amphetamine in plasma samples from healthy volunteers at four different doses.

Acetamides↗
PubMed1999

Cardiovascular and neuroendocrine effects and pharmacokinetics of 3, 4-methylenedioxymethamphetamine in humans.

The cardiovascular and neuroendocrine effects and pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") were assessed in a double-blind, randomized, crossover, and controlled (placebo and amphetamine) clinical trial. Eight men with experience in the recreational use of MDMA participated in four 10-h experimental sessions with a 1-week washout period. Single oral doses of 125 mg and 75 mg of MDMA, 40 mg of amphetamine, and placebo were given. Both MDMA doses significantly increased blood pressure (increases of 40 mm Hg in systolic blood pressure), heart rate (increases of 30 beats/min), and pupillary diameter (mydriasis) as compared with placebo. Oral temperature did not show significant changes in any drug-active condition. Plasma cortisol levels showed a statistically significant increase after MDMA administration. Prolactin levels only increased after high dose of MDMA. Cmax values for 125-mg and 75-mg MDMA doses were 236.4 and 130.9 ng/ml, and Tmax was observed at 2.4 and 1.8 h, respectively. Elimination half-life was 8.6 h and 7.7 h for high and low MDMA doses, respectively. Amphetamine half-life was 15 h. Between 8 and 9% of the doses of MDMA appeared in plasma in the form of 3,4-methylenedioxyamphetamine. The important cardiovascular effects observed after MDMA administration in laboratory conditions at rest (increases of 40 mm Hg in systolic blood pressure and 30 beats/min in pulse rate) could be relevant in terms of toxicity in real-life conditions (e.g., crowded places and physical activity).

3,4-Methylenedioxyamphetamine↗
PubMed1998

Abuse liability of flunitrazepam among methadone-maintained patients.

Abuse liability and acute subjective and psychomotor effects of flunitrazepam were assessed in ten methadone-maintained males with history of benzodiazepine and alcohol use, who voluntarily participated in a double-blind, controlled, cross-over, randomized clinical trial. There were six experimental sessions in which a single oral dose of flunitrazepam 1, 2, and 4 mg; triazolam 0.5 and 0.75 mg; and placebo was given. Evaluations included physiological measures; psychomotor performance tasks (simple reaction time, Digit Symbol Substitution Test, balance task, Maddox-wing device); and self-administered subjective effects questionnaires [Addiction Research Center Inventory (ARCI), Profile of Mood States (POMS), a series of visual analog scales (VAS)]. All drugs but flunitrazepam 1 mg caused an impairment of psychomotor tasks. Effects were more evident with the highest doses of both drugs. Only flunitrazepam 4 mg produced a significant decrease in balance time. Triazolam 0.75 mg induced increases in sedation measured by ARCI-PCAG, depression in POMS, and VAS-drowsiness scores. Flunitrazepam 4mg caused euphoria-related effects as measured by increases in ARCI-MBG and "high" scores in the VAS. Our findings of flunitrazepam-induced euphoria in methadone-maintained subjects together with epidemiological evidence of flunitrazepam abuse by opioid dependents, suggest that it may be included in the group of benzodiazepines with a relatively high abuse potential.

Adult↗
PubMed1997

[Spanish scientific production in biomedicine and health sciences during the period 1990-1993 (Science Citation Index and Social Science Citation Index) and comparison to period 1986-1989].

BACKGROUND: In 1993 a first study on the scientific production of Spain in 1986-1989 on Biomedicine and Health Sciences, through the Science Citation Index (SCI) was published. The analysis attained the level of centres, with special emphasis in those related to the Health Care System. This paper analyses the period 1990-1993, offers a wider coverage including the Social Science Citation Index (SSCI) database, and compares both time periods. MATERIAL AND METHODS: Documents indexed by SCI and SSCI, CD-ROM version, with at least one Spanish address, published in biomedical and medical journals during the years 1990, 1991, 1992 and 1993, have been studied. Quantitative and qualitative bibliometric indicators for the analysis by subject matter, geographic distribution, institutional sector and centre of origin have been used. Global data were also analysed according to economic and human resources. RESULTS: A total of 21,434 documents were studied, of which 67.9% were journal articles. The highest contributors were Universities (48.8% of the documents) and Hospitals (45.3%). The autonomous communities of Madrid (31.9%) and Catalonia (26.9%) concentrate more than half the production-developed principally by hospitals-followed by Andalucía (11.7%) and C. Valenciana (7.8%). The most active disciplines were biochemistry/molecular biology (13%), neurosciences/neurology (8.4%), pharmacology/pharmacy (8.4%) and medicine, general/internal (7.9%). Comparing the results with period 1986-1989, some of the differences observed could be explained by the fact of MEDICINA CLINICA being included in SCI since 1992. An increase in the number of citable items (72.9%), number of journals used (from 1,086 to 1,346) and international cooperation rate (13.5% to 18.3%) was detected. The institutional sectors with the highest growth rate were Hospitals (92.9%) and Consejo Superior de investigaciones Cientificas (CSIC) (119.3%). Scientific production and visibility of publications (measured as impact factor of journals used) grew in most disciplines, being the quantitative increase greater in cancer/oncology, gastroenterology/hepatology, genetics/heredity and cardiovascular system. No substantial changes as to geographic distribution of documents or most active centres were observed. CONCLUSIONS: Spanish scientific activity grew steadily every year and its visibility improved, being the Health sector one of the main actors. When comparing both four-year period. Spain moved up from the seventh to the sixth position in the ranking of EU countries according to its scientific output in biomedicine and health sciences.

Databases, Bibliographic↗
PubMed1997

[Medicina Clinica (1992-1993) seen through the Science Citation Index].

BACKGROUND: MEDICINA CLINICA has been indexed in the Science Citation Index (SCI) database since 1992, listed in the category Medicine, General & Internal, and its impact factor in 1993 was 0.909. Two years as source journal in the SCI database provide enough information to assess its contribution to the international scientific scenario. MATERIAL AND METHODS: Publications of Spanish authors in MEDICINA CLINICA during 1992 and 1993 were retrieved from the SCI. Document types, geographic distribution, institutional sectors, subjects and most productive centers were analyzed. All documents retrieved from the SCI were compared manually with those published in the journal itself. Citations received until November 1996 were collected and reference patterns assessed. RESULTS: MEDICINA CLINICA was in the upper third of the list of journals of its category ranked by their impact factor. As other general medical journals, it was characterized by the publication of a high number of letters to the editor (48% of documents) and of articles susceptible of being classified in other disciplines according to their contents. Main topics of documents authored by Spanish authors included: Infectious Diseases (15%), Pharmacy/Pharmacology (8.8%), Cancer/Oncology (7.2%), Cardiovascular System (4.9%), Epidemiology/Public Health (4.5%), Endocrinology/Metabolism (4%) and Neurosciences/Neurology (4%). Only 32% of studies corresponding to citable items had been carried out in Barcelona, the city in which the journal is published, 19.5% in Madrid, and almost 9% in Andalucia. Around 66% of articles and only 25% of letters have received at least one citation, with a mean number of citations of 2.83 for articles and 1.3 for letters. Self-citations from other documents published in the same journal were high (77.8% for articles) as compared with citations received from other international SCI journals. Reference patterns found in MEDICINA CLINICA were similar to those of high-ranking journals of the same category. The comparison of documents published in MEDICINA CLINICA to those retrieved from SCI showed a lack of consistency in document types. In respect to the authors' last names, potential problems due to heterogeneity of the bibliographic names of Spanish authors are added to SCI-derived typing errors. CONCLUSIONS: MEDICINA CLINICA appears open to a broad spectrum of authors, centers and topics. Highly productive health centers in MEDICINA CLINICA are also highly productive in other international journals. Differences between what is published in the journal and how this information is indexed in the SCI database constitute an important obstacle, not only for the journal's visibility, but also for a comprehensive retrieval of the authors' output. Changes in the classification of documents and consistent criteria in the use of bibliographic names of authors are recommended.

Databases, Bibliographic↗
PubMed1997

Cocaine and alcohol interactions in humans: neuroendocrine effects and cocaethylene metabolism.

The effects of 100 mg of intranasal cocaine in acute alcohol intoxication (0.8 g/kg) were evaluated in eight experienced and nondependent healthy volunteers in a double-blind double-dummy, controlled, randomized, crossover clinical study. The combination of alcohol and cocaine produced greater increases in HR, rate-pressure product and pleasurable-related subjective effects (euphoria, well-being) compared with the effects of cocaine. The drug combination reduced the alcohol-induced sedation, but feelings of drunkenness were not significantly counteracted. Cardiovascular changes induced by the combination condition caused an increase in myocardial oxygen consumption that may be related to an increased risk of cardiovascular toxicity. The augmented subjective euphoria may explain why the drug combination is more likely to be abused than is cocaine or alcohol alone. Plasma cortisol concentrations were significantly higher after concomitant alcohol and cocaine use than with cocaine alone. The administration of cocaine did not alter alcohol-induced hyperprolactinemia. Although cocaine produced a slight decrease in plasma concentrations of prolactin when administered alone, it did not antagonize the effects of alcohol on prolactin secretion when alcohol and cocaine were given simultaneously. The combination increased cocaine and norcocaine plasma concentrations, and induced the synthesis of cocaethylene and norcocaethylene. The enhancement of cocaine effects in the drug combination may be due to initially increased cocaine plasma levels followed by the additive effect of cocaethylene, although a pharmacodynamic interaction could not be excluded.

Adrenocorticotropic Hormone↗