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P. N. Roset

Universitat Autònoma de Barcelona

6 papers in the library · 443 citations · publishing 2000-2002

Papers

Pharmacology of MDMA in Humans

Annals of the New York Academy of Sciences September 1, 2000 Rafael de la Torre, Magı́ Farré, P. N. Roset et al. 178 citations

Recreational doses of MDMA (50 to 150 mg) in healthy volunteers cause pupil dilation, increases in systolic and diastolic blood pressure, heart rate, and pupillary diameter. Oral temperature changes are biphasic: a slight decrease at 1 hour followed by increases at 2 and 4 hours. Psychomotor performance shows slight dose-dependent impairment. Plasma cortisol and prolactin concentrations rise markedly. The drug's elimination half-life is about 8-9 hours. Peak drug concentrations and physiological effects occur between 1 and 2 hours and return to baseline 4-6 hours after administration.

Determination of MDMA and its Metabolites in Blood and Urine by Gas Chromatography-Mass Spectrometry and Analysis of Enantiomers by Capillary Electrophoresis

Journal of Analytical Toxicology April 1, 2002 Nieves Pizarro, Jordi Ortuño, Mercè Farré et al. 113 citations

A gas chromatography-mass spectrometry method simultaneously measured MDMA and its metabolites MDA, HMMA, and HMA in plasma and urine from healthy volunteers given 100 mg of MDMA. Samples were hydrolyzed, extracted with solid-phase columns, and analyzed as trifluoroacyl derivatives. Linear calibration covered plasma and urine ranges of 25–400 ng/mL and 250–2000 ng/mL for MDMA and HMMA, and 2.5–40 ng/mL and 100–1000 ng/mL for MDA and HMA. A capillary electrophoresis method using (2-hydroxy)propyl-beta-cyclodextrin as chiral selector resolved enantiomers without derivatization, with linear ranges for each enantiomer of MDMA, MDA, and HMMA. Stereoselective disposition of MDMA and MDA was confirmed, while HMMA showed an enantiomer ratio near 1 and constant over time, contradicting MDMA findings.

Cell‐Mediated Immune Response in MDMA Users After Repeated Dose Administration

Annals of the New York Academy of Sciences June 1, 2002 Roberta Pacifici, P. Zuccaro, Magı́ Farré et al. 58 citations

Repeated use of MDMA ('ecstasy') causes time-dependent immune dysfunction similar to a single dose, but the second dose extends the period of impaired immunocompetence. The drug decreases CD4 T-helper cells, increases natural killer (NK) cells, and reduces lymphocyte responsiveness to stimulation. In poor metabolizers, MDMA accumulation produces greater immunomodulatory effects, including significant differences in NK cell function. Recreational MDMA users show long-term alterations: reduced lymphocytes, T cells, and CD4 cells (though within normal limits), and NK cells reduced to one-third of healthy levels. Over two years, a subgroup showed statistically significant decreases in immune parameters, potentially increasing susceptibility to infection and immune disorders.

Sweat Testing of MDMA with the Drugwipe(R) Analytical Device: A Controlled Study with Two Volunteers

Journal of Analytical Toxicology March 1, 2001 Roberta Pacifici, Magı́ Farré, Simona Pichini et al. 50 citations

After a single 100 mg oral dose of MDMA, the Drugwipe immunochemical strip test detected the drug in sweat from two volunteers as early as 2 hours and up to 12 hours later. However, one volunteer showed a faint positive result before dosing, when plasma and urine were negative, and this persisted beyond 48 hours. Gas chromatography-mass spectrometry measured peak plasma concentrations of MDMA and its metabolite HMMA at 2-4 hours, with levels above 20 ng/mL and 40 ng/mL respectively still present at 24 hours. Urine remained positive for both substances over 48 hours. These results suggest sweat testing with Drugwipe may be useful for monitoring MDMA use.

Immunomodulating Activity of MDMA

Annals of the New York Academy of Sciences September 1, 2000 Roberta Pacifici, P. Zuccaro, Magı́ Farré et al. 44 citations

MDMA (ecstasy) use produces neurochemical, behavioral, and endocrine changes similar to acute stress, acting as a chemical stressor. In rats, MDMA rapidly suppressed lymphocyte proliferation, decreased circulating lymphocytes, and increased plasma corticosterone. In humans, acute MDMA caused time-dependent immune dysfunction: CD4+ T-cells and lymphocyte responsiveness to stimulation decreased, while natural killer cells increased; total leukocyte count remained unchanged. Cortisol rose similarly to the rat model, suggesting MDMA triggers corticotrophin-releasing factor release from the hypothalamus, activating the HPA axis and sympathetic nervous system. These findings indicate MDMA ingestion may increase risk for immune system-related diseases.

Non‐linear pharmacokinetics of MDMA (‘ecstasy’) in humans

British Journal of Clinical Pharmacology February 1, 2000 Rafael de la Torre, Magı́ Farré, Jordi Ortuño et al.

MDMA (ecstasy) shows nonlinear pharmacokinetics in humans: as the dose increases, plasma concentrations rise disproportionately, meaning small dose increases lead to much higher drug levels. In a controlled trial with 14 healthy volunteers given 50–150 mg, urinary recovery of the metabolite HMMA stayed constant while MDMA recovery rose, suggesting saturation or inhibition of the demethylenation metabolic step. Nonrenal clearance was dose-dependent while urinary clearance remained constant. This nonlinearity occurs regardless of CYP2D6 genotype, implying that even moderate dose increases in recreational use can produce unexpectedly high plasma concentrations, raising the risk of acute toxicity for all users, not just the 10% genetically deficient in CYP2D6.