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Magı́ Farré

Universitat Autònoma de Barcelona, Hospital Universitari Germans Trias i Pujol

50 papers in the library · 3,697 citations · publishing 2000-2024

Papers

Acute Effects of the Novel Psychoactive Drug 2C-B on Emotions

BioMed Research International January 1, 2015 Débora González, Marta Torrens, Magı́ Farré 44 citations

A single 20 mg dose of 2C-B in healthy recreational users produced positive subjective effects, including euphoria and well-being, along with reduced anger. However, it increased reactivity to negative emotional stimuli and impaired recognition of happy facial expressions. Speech became more emotional, noticeable to others. Mild increases in blood pressure and heart rate occurred. The authors conclude that 2C-B's emotional profile fits an entactogen with psychedelic properties.

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.

Potential Use of Ayahuasca in Grief Therapy

OMEGA - Journal of Death and Dying May 30, 2017 Débora González, Maria Carmo Carvalho, Jordi Cantillo et al. 43 citations

People who took ayahuasca reported lower levels of grief compared to those who attended peer-support groups, as measured by the Present Feelings Scale of the Texas Revised Inventory of Grief. The ayahuasca group showed benefits in psychological and interpersonal dimensions. Qualitative responses described emotional release, biographical memories, and experiences of contact with the deceased. Some benefits were identified regarding the ayahuasca experiences. These results provide preliminary data about the potential of ayahuasca as a therapeutic tool for grief.

GC–MS Quantification Method for Mephedrone in Plasma and Urine: Application to Human Pharmacokinetics

Journal of Analytical Toxicology October 3, 2016 Eulàlia Olesti, Mitona Pujadas, Esther Papaseit et al. 41 citations

Mephedrone, a synthetic cathinone increasingly used by young people and linked to acute intoxication and fatalities, was studied in a controlled clinical trial. A gas chromatography-mass spectrometry method was developed to measure mephedrone in human plasma and urine. Six healthy men received 150 mg of mephedrone orally. Peak plasma concentration averaged 122.6 ng/mL, reached within 0.5–2 hours, and the drug was eliminated rapidly with a half-life of 2.2 hours. Less than 15% of the dose appeared unchanged in urine, and concentrations varied widely among individuals.

The Shipibo Ceremonial Use of Ayahuasca to Promote Well-Being: An Observational Study

Frontiers in Pharmacology May 5, 2021 Débora González, Jordi Cantillo, Irene Hidalgo Pérez et al. 39 citations

People who took part in an Indigenous Shipibo healing program involving ayahuasca ceremonies showed significant increases in psychological well-being, happiness, and quality of life that lasted up to 12 months. A subgroup analysis indicated the improvements were due to the program rather than the passage of time. A relationship was found between decentering—the ability to observe thoughts and feelings objectively—and enhanced psychological well-being.

Combined immunomodulating properties of 3,4‐methylenedioxymethamphetamine (MDMA) and cannabis in humans

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.

MDMA interactions with pharmaceuticals and drugs of abuse

Expert Opinion on Drug Metabolism & Toxicology March 31, 2020 Esther Papaseit, Clara Pérez‐mañá, Marta Torrens et al. 34 citations

MDMA (ecstasy) is a widely used recreational stimulant. Users often combine it with other drugs to enhance effects, reduce toxicity, or manage comedowns, which increases the risk of severe toxicity. This review covers known interactions between MDMA and other pharmaceuticals or drugs of abuse, offering clinical recommendations. The authors note that few published studies exist and documented clinically significant interactions are scarce. Experimental evidence shows that interactions are especially relevant when MDMA is taken with drugs metabolized by the CYP2D6 enzyme, due to MDMA's inhibitory effect, and during repeated MDMA use.

MDMA-Induced Dissociative State not Mediated by the 5-HT2A Receptor

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.

Spice drugs: los cannabinoides como nuevas drogas de diseño

Adicciones September 1, 2009 Cristina Mustata, Marta Torrens, Ricardo Pardo et al. 33 citations

Since 2004, herbal smoking blends sold under the brand Spice drugs have been available online and in smart shops, advertised as aromatic incense not for human use. Users report effects similar to cannabis, and forensic analyses have identified potent synthetic cannabinoid agonists such as JWH-018, CP 47497, JWH-073, and HU-210 in these products. Very little data exist on their pharmacological properties in animals, and no information on their toxicity is available. Their pharmacology, toxicology, and safety in humans remain largely unknown, with only user reports from Internet forums. Neither the plant ingredients nor the identified cannabinoids are listed in the UN 1961 or 1971 controlled substance conventions. Some countries have recently taken legal action to prohibit or control these products.

Acute Pharmacological Effects of Oral and Intranasal Mephedrone: An Observational Study in Humans

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.

Pharmacological effects of methylone and MDMA in humans

Frontiers in Pharmacology February 17, 2023 Lourdes Poyatos, Clara Pérez‐mañá, Olga Hladun et al. 26 citations

Methylone, a common synthetic cathinone used as a substitute for MDMA, produces similar acute effects in humans. In a controlled trial with 17 experienced psychostimulant users, a single 200 mg oral dose of methylone increased blood pressure and heart rate and induced pleasurable effects including stimulation, euphoria, wellbeing, enhanced empathy, and altered perception. Methylone's effect profile resembled MDMA's but with a faster onset and earlier disappearance of subjective effects. The findings suggest methylone's abuse potential is comparable to that of MDMA in humans.

Abuse Potential of Cathinones in Humans: A Systematic Review

Journal of Clinical Medicine February 15, 2022 Lourdes Poyatos, A Acuna Torres, Esther Papaseit et al. 26 citations

Cathinone, mephedrone, methylone, and diethylpropion produce stimulant and euphorigenic effects similar to amphetamines and MDMA, with varying intensities that may correspond to different levels of abuse potential. This systematic review of 18 studies (5 on cathinone, 7 on mephedrone, 1 on methylone, 5 on diethylpropion) found that all four substances induce desirable and reinforcing effects that could lead to misuse and addiction. The authors conclude that further investigation is needed to minimize and prevent their impact on society and public health.

A Comparison of Acute Pharmacological Effects of Methylone and MDMA Administration in Humans and Oral Fluid Concentrations as Biomarkers of Exposure

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.

Neurocognitive performance following acute mephedrone administration, with and without alcohol

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.

MDMA-induced indifference to negative sounds is mediated by the 5-HT2A receptor

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.

Inhibition ofMDMA‐induced increase in cortisol does not prevent acute impairment of verbal memory

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.

Methylone and MDMA Pharmacokinetics Following Controlled Administration in Humans

International Journal of Molecular Sciences November 23, 2022 Lourdes Poyatos, Alfredo Fabrizio Lo Faro, Diletta Berardinelli et al. 22 citations

After controlled oral doses of 50–200 mg methylone given to 12 male volunteers, plasma concentrations increased in proportion to dose. Maximum concentrations ranged from 153 ng/mL at the lowest dose to 604 ng/mL at the highest dose. The drug was absorbed rapidly, reaching peak levels in 1.5–2 hours, and had a half-life of about 6 hours. Its metabolite HMMC reached peak concentrations 10–14 times lower than methylone. Unlike MDMA, methylone showed linear pharmacokinetics across the dose range. A validated LC-MS/MS method was used to measure methylone, MDMA, and their metabolites in plasma.

Acute Effects of 2C-E in Humans: An Observational Study

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.

Key interindividual determinants in MDMA pharmacodynamics

Expert Opinion on Drug Metabolism & Toxicology January 5, 2018 Esther Papaseit, Marta Torrens, Clara Pérez‐mañá et al. 20 citations

MDMA (ecstasy) produces amphetamine-like euphoria and well-being, increases empathy, and induces pro-social effects that drive recreational use and suggest therapeutic potential. This review examines interindividual differences in MDMA's pharmacodynamics, focusing on sex-gender, race-ethnicity, genetic differences, interactions, acute toxicity, and therapeutic use. Acute MDMA effects are more pronounced in women than men. Very limited data exist on race-ethnicity effects. MDMA metabolism involves polymorphic enzymes that slightly alter plasma concentrations and effects. The small number of subjects in acute-effect trials limits evaluation of interindividual factors and prevents clear conclusions about their influence, which should be considered in therapeutic studies.

Restorative Retelling for Processing Psychedelic Experiences: Rationale and Case Study of Complicated Grief

Frontiers in Psychology May 3, 2022 Débora González, Marc Aixalà, Robert A. Neimeyer et al. 15 citations

A woman suffering from complicated grief after her mother's suicide participated in an ayahuasca ceremony followed by Restorative Retelling sessions to process the psychedelic experience. The case report describes how ayahuasca evoked key psychological content related to her loss, and how the adapted Restorative Retelling technique helped integrate that content into autobiographical memory, fostering meaning-making. Evaluations before the ayahuasca experience and after Restorative Retelling suggest reductions in symptoms of complicated grief and general psychopathology. The authors propose that Restorative Retelling can effectively process and integrate psychedelic experiences, though they note limitations of a single case.

Acute Pharmacological Effects and Oral Fluid Biomarkers of the Synthetic Cannabinoid UR-144 and THC in Recreational Users

Biology March 24, 2021 Nunzia la Maida, Esther Papaseit, Lucía Martínez de Soto et al. 14 citations

Synthetic cannabinoid UR-144, monitored by the EU Early Warning System since 2012 for severe adverse effects, shows a similar cardiovascular profile to delta-9-tetrahydrocannabinol (THC) but with less intense subjective effects. In an observational study, 16 volunteers smoked joints containing either UR-144 (1 or 1.5 mg) or cannabis (10 or 20 mg THC). Both substances significantly increased systolic and diastolic blood pressure and heart rate. UR-144 produced lower scores on visual analog scales for stimulant-like and high effects compared to cannabis, and no hallucinogenic effects were observed. UR-144 was detectable in oral fluid, peaking at 20 minutes after smoking, offering a non-invasive biomarker of consumption. These preliminary findings require confirmation in larger samples.

Depressive mood ratings are reduced by MDMA in female polydrug ecstasy users homozygous for the l-allele of the serotonin transporter

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.

Peripheral endocannabinoid concentrations are not associated with verbal memory impairment during MDMA intoxication

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.

Psychedelic-assisted grief therapy: a mixed-method case study

Mortality December 5, 2024 Pablo Sabucedo, Chris Evans, Donald W. Nicholson et al. 1 citation

A woman in her thirties grieving her father's death from cancer underwent nine sessions of Meaning Reconstruction Therapy that included two ayahuasca sessions and subsequent integration sessions. The intervention prevented the development of complicated grief. Analysis of therapy session content and psychometric measures taken before, after, and at a three-month follow-up suggests that meaning reconstruction, psychological flexibility, and maintaining a continuing bond with the deceased were key processes driving the improvement.

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.