Addiction
May 22, 2007
Roberta Pacifici, Piergiorgio Zuccaro, Magı́ Farré et al.
39 citations
People who use both MDMA (ecstasy) and cannabis show long-term changes in immune function, including lower levels of interleukin-2 and higher levels of anti-inflammatory transforming growth factor beta-1, along with fewer total lymphocytes, CD4 cells, and natural killer cells. These immune alterations persisted over one year. Regular users of both drugs had a higher rate of mild infections compared to occasional users and those who used only cannabis or neither drug. Cannabis-only users showed intermediate immune changes. The findings suggest that sustained disruption of immune balance may lead to poorer general health and greater susceptibility to infections.
Frontiers in Pharmacology
July 11, 2017
Drew J. Puxty, Johannes G. Ramaekers, Rafael de la Torre et al.
33 citations
A single 75 mg dose of MDMA produces a dissociative state, marked by feelings of depersonalization and derealization, in healthy recreational users. Blocking the 5-HT2 receptor with ketanserin did not prevent this effect, indicating that the 5-HT2 receptor does not mediate MDMA-induced dissociation. Heart rate correlated with the dissociative state after MDMA alone, but not when ketanserin was given, suggesting heart rate changes do not directly cause dissociation. Cortisol levels and MDMA blood concentrations showed no clear relationship with dissociation. The exact neurobiological mechanism remains unknown and may be relevant to MDMA's therapeutic use.
Pharmaceuticals
January 28, 2021
Esther Papaseit, Eulàlia Olesti, Clara Pérez‐mañá et al.
30 citations
Mephedrone, a synthetic cathinone and popular new psychoactive substance, produces euphoria and well-being and increases cardiovascular effects when self-administered orally or intranasally by healthy experienced drug users. In this observational study, ten participants took a single dose orally (100–200 mg, mean 150 mg) or intranasally (50–100 mg, mean 70 mg). Although the oral route sometimes produced greater subjective effects, concentrations of mephedrone in oral fluid and total amounts in urine were considerably higher after intranasal administration. Controlled clinical trials are needed to confirm these results.
Frontiers in Pharmacology
January 28, 2020
Esther Papaseit, Clara Pérez-mañá, Elizabeth B. de Sousa Fernandes Perna et al.
27 citations
Combining mephedrone with alcohol amplifies cardiovascular effects and intensifies euphoria and well-being compared to either drug alone, while mephedrone reduces the sedative effects of alcohol. In a double-blind, placebo-controlled trial with 11 male volunteers, the combination increased blood pressure, heart rate, and subjective feelings of euphoria. Mephedrone alone and alcohol alone were also tested. The results suggest that the abuse liability of mephedrone is greater when taken with alcohol, similar to other psychostimulants like amphetamines and MDMA.
Biology
August 17, 2021
Lourdes Poyatos, Esther Papaseit, Eulàlia Olesti et al.
26 citations
Methylone, a synthetic cathinone and beta-keto analogue of MDMA, produces acute subjective and physiological effects similar to MDMA but less intense. In an observational-naturalistic study of 14 healthy poly-drug users who self-administered oral doses (methylone 100-300 mg, mean 187.5 mg; MDMA 75-100 mg, mean 87.5 mg), methylone showed a prototypical psychostimulant and empathogenic profile. Oral fluid concentrations of both substances peaked at 2 hours, with MDMA levels matching those from controlled studies. The findings indicate that methylone's abuse potential is comparable to MDMA's in recreational users.
Journal of Psychopharmacology
August 25, 2016
EB de Sousa Fernandes Perna, Esther Papaseit, Clara Pérez‐mañá et al.
26 citations
Mephedrone, a recreational drug similar to MDMA, impairs short-term spatial memory one hour after intake but improves critical tracking performance four hours later. When combined with alcohol, mephedrone reduces reaction time compared to alcohol alone, but does not counteract alcohol's impairing effects on divided attention or spatial memory. Alcohol alone impairs both short- and long-term spatial memory and divided attention. The findings suggest mephedrone enhances psychomotor performance while harming memory, and its stimulatory effects are insufficient to offset alcohol-induced deficits on most cognitive tasks.
Psychopharmacology
July 22, 2017
Kim P. C. Kuypers, Rafael de la Torre, Magı́ Farré et al.
24 citations
MDMA reduced the arousal normally elicited by negative sounds, and this effect was blocked by pre-treatment with ketanserin, a 5-HT2 receptor antagonist, indicating the involvement of the serotonin 2A receptor. The drug did not produce a bias toward emotional or social stimuli in the tasks used. MDMA increased both positive and negative mood ratings and elevated oxytocin plasma concentrations. The reduction in arousal to negative sounds was unrelated to subjective arousal levels. This decrease in defensive arousal may contribute to MDMA's therapeutic effects.
British Journal of Pharmacology
September 4, 2012
Kim P. C. Kuypers, Rafael de la Torre, Magı́ Farré et al.
23 citations
MDMA acutely impairs memory, but this effect is not caused by the rise in cortisol that MDMA also triggers. In a placebo-controlled, within-subject experiment with 17 polydrug MDMA users, blocking the cortisol increase with metyrapone (a cortisol synthesis inhibitor) did not prevent the memory deficit produced by a 75 mg dose of MDMA. Memory was tested at peak drug concentrations. The finding suggests that the neuropharmacological mechanism behind MDMA-induced memory impairment is independent of cortisol.
Frontiers in Pharmacology
March 18, 2020
Esther Papaseit, Marta Torrens, Mireia Ventura et al.
20 citations
2C-E, a psychedelic phenylethylamine similar to mescaline, acts as a partial agonist at serotonin 2A, 2B, and 2C receptors and inhibits norepinephrine and serotonin uptake. In an observational study, ten recreational psychedelic users self-administered single oral doses of 2C-E (6.5–25 mg). The drug induced alterations in perception, hallucinations, and euphoric mood, with saliva concentrations peaking 2 hours after administration. The effects resembled those of 2C-B and other serotonin-acting drugs.
Biomedicine & Pharmacotherapy
March 24, 2022
Francisco Madrid-Gambin, Àlex Gomez‐gómez, Arnau Busquets-García et al.
14 citations
Consumption of ayahuasca increases N-acyl-ethanolamine endocannabinoids, decreases 2-acyl-glycerol endocannabinoids, and alters several large-neutral amino acids (LNAAs) in human plasma. Most LNAAs were inversely associated with nine of eleven subscales of the 5-Dimension Altered States of Consciousness Rating Scale, except tryptophan, which was positively associated. Several endocannabinoids and hexosylceramides were directly associated with ayahuasca alkaloids. Enrichment analysis confirmed dysregulation in pathways involved in serotonin and dopamine synthesis. A crosstalk between circulating LNAAs and subjective effects is suggested, independent of alkaloid concentrations, providing insights into the metabolic fingerprint and mechanism of action underlying ayahuasca experiences.
Scientific Reports
January 12, 2018
Kim P. C. Kuypers, Rafael de la Torre, Magı́ Farré et al.
12 citations
MDMA's mood effects depend partly on a genetic variation in the serotonin transporter gene (5-HTTLPR). People with the short variant of this gene typically show more anxiety and negative mood, while those with two long alleles (l-group) tend to be less anxious. In a pooled analysis of four placebo-controlled studies with 63 polydrug ecstasy users, MDMA (75 mg) generally improved mood but also increased anxiety and confusion. Unexpectedly, the l-group reported higher anxiety regardless of MDMA or placebo. MDMA reduced depressive feelings only in females from the l-group, suggesting a sex- and genotype-dependent effect.
Psychopharmacology
November 16, 2017
Eline Haijen, Magı́ Farré, Rafael de la Torre et al.
9 citations
MDMA impaired verbal memory 90 minutes after administration in a word learning task, replicating earlier findings with the same dose (75 mg). Contrary to expectations, MDMA did not affect endocannabinoid concentrations (anandamide and 2-AG) in blood, and the 5-HT2 receptor blocker ketanserin did not block MDMA-induced memory impairment. Ketanserin alone increased AEA concentrations 180 minutes after administration. The findings suggest that peripherally measured endocannabinoids are not involved in the verbal memory deficit during MDMA intoxication.
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.