Therapeutic Drug Monitoring
March 19, 2004
Rafael de la Torre, Magı́ Farré, Pere N. Roset et al.
445 citations
MDMA (ecstasy) is a widely misused psychostimulant that increases energy, euphoria, and sociability while also producing distinctive 'entactogen' effects such as feeling close to others and increased empathy. It works by promoting the release and blocking the reuptake of serotonin, dopamine, and norepinephrine. Acute toxic effects include serotonin syndrome, characterized by muscle rigidity, hyperreflexia, and hyperthermia. MDMA metabolism involves two main pathways; one is partially regulated by the polymorphic enzyme CYP2D6, but mechanism-based inhibition after two consecutive doses limits the impact of CYP2D6 genetics on acute toxicity. Metabolism may also contribute to long-term neurotoxic effects through progressive degeneration of the serotonergic system.
Journal of Clinical Psychopharmacology
August 1, 2000
Jordi Camı́, Magı́ Farré, Marta Más et al.
237 citations
In a randomized, double-blind, crossover, controlled trial with eight healthy male volunteers, MDMA at recreational doses (75 and 125 mg) produced marked euphoria and well-being, as measured by increased scores on the Addiction Research Center Inventory MBG and A scales and visual analog scales for 'stimulated,' 'good effects,' 'liking,' and 'high.' The 125 mg dose also caused mild sedation, dysphoria, and a slight decrease in performance on the digit-symbol substitution test, along with esophoria. Amphetamine (40 mg) produced similar euphoric effects but improved psychomotor performance. No hallucinations or psychoses occurred. These findings support MDMA's abuse liability.
Journal of Psychoactive Drugs
September 1, 2008
José Carlos Bouso, Rick Doblin, Magı́ Farré et al.
206 citations
In a small, prematurely terminated study, six women with chronic posttraumatic stress disorder (PTSD) from sexual assault received low doses (50–75 mg) of MDMA during psychotherapy. The treatment was psychologically and physiologically safe for all participants. The study was originally planned for 29 subjects but closed early due to political pressures. The authors present these preliminary results and call for future research with larger samples and higher doses to better assess MDMA's safety and efficacy for PTSD.
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.
Frontiers in Psychiatry
January 21, 2020
Juan José Fuentes, Francina Fonseca, Matilde Elices et al.
176 citations
A systematic review of controlled and randomized clinical trials evaluated the therapeutic potential of lysergic acid diethylamide (LSD) in psychiatry. Following PRISMA guidelines, 11 randomized-controlled trials involving 567 patients who received LSD doses from 20 to 800 mcg were identified. Despite heterogeneous study designs, positive results emerged, particularly for reducing psychiatric symptoms in alcoholism. Many authors reported significant short-term improvements, though some studies found long-term outcomes homogenized between LSD and control groups. The evidence is strongest for LSD's use in treating alcoholism, but the review notes that most older studies did not meet contemporary standards and that new, properly designed double-blind trials are needed.
Frontiers in Genetics
January 1, 2012
Rafael de la Torre, Samanta Yubero‐lahoz, Ricardo Pardo‐lozano et al.
108 citations
The metabolism of amphetamine-like psychostimulants is regulated by the polymorphic enzyme CYP2D6. Methamphetamine acts as a weak substrate and competitive inhibitor of CYP2D6, while MDMA is a high-affinity substrate and potent mechanism-based inhibitor, causing all users to phenocopy the poor metabolizer phenotype regardless of genotype. The fraction of metabolic clearance regulated by CYP2D6 for both drugs is substantially lower than in vitro studies suggest, with other cytochrome P450 isoenzymes and renal excretion contributing significantly. Overall, the clinical relevance of CYP2D6 polymorphism is lower than predicted by in vitro findings.
Chemical Research in Toxicology
August 2, 2001
Mireia Segura, Jordi Ortuño, Magı́ Farré et al.
105 citations
A new method using strong cation-exchange solid-phase extraction and high-performance liquid chromatography with electrochemical detection was validated for measuring the metabolite 3,4-dihydroxymethamphetamine (HHMA) in plasma and urine. Applied to samples from healthy volunteers given MDMA (ecstasy), HHMA appeared as a major metabolite, with peak plasma concentrations (154.5 microg/L) and overall exposure (AUC 1990.9 microg/L h) similar to those of MDMA itself. Urinary recovery of HHMA over 24 hours accounted for 17.7% of the 100 mg MDMA dose, raising total recovery of MDMA and its metabolites to 58%. The method is accurate and precise for pharmacokinetic studies, and measuring HHMA may help clarify its role in MDMA metabolism and potential neurotoxicity.
Journal of Psychopharmacology
May 20, 2006
Jiansong Yang, Masoud Jamei, Amir Heydari et al.
89 citations
A physiologically-based model of drug metabolism predicted that a typical recreational dose of MDMA (ecstasy) inactivates most hepatic CYP2D6 within an hour, and that recovery to basal CYP2D6 levels takes at least 10 days. The analysis suggests that genetic polymorphism of CYP2D6 and coadministration of CYP2D6 inhibitors may have less impact on MDMA's pharmacokinetics and acute toxicity risk than previously thought, consistent with clinical observations showing no obvious link between inherited CYP2D6 deficiency and acute MDMA intoxication.
PLoS ONE
June 27, 2014
Kim P. C. Kuypers, Rafael de la Torre, Magı́ Farré et al.
88 citations
A single 75 mg dose of MDMA selectively enhances emotional empathy—the ability to share and understand others' feelings—without affecting cognitive empathy (understanding others' mental states), trust, or reciprocity in social interactions. This effect was not altered by adding pindolol, a drug that blocks the 5-HT1A serotonin receptor. Oxytocin nasal spray, a hormone often linked to social bonding, had no effect on any empathy or social interaction measure. Changes in emotional empathy were unrelated to oxytocin levels in the blood. The findings suggest that MDMA's empathy-enhancing effects do not depend on peripheral oxytocin and may instead involve other receptors such as serotonin 2A or vasopressin 1A.
Psychopharmacology
January 14, 2020
Débora González, Jordi Cantillo, Irene Hidalgo Pérez et al.
73 citations
In a bereaved sample attending Shipibo ayahuasca ceremonies in Peru, grief severity decreased substantially from baseline to 12 months, with large effect sizes (Cohen's d = 0.84 at 15 days, 1.38 at 3 months, 1.16 at 6 months, and 1.39 at 12 months). Reductions in grief were linked to lower experiential avoidance (r = 0.55) and greater decentering (r = -0.47). The ceremonial use of ayahuasca appears to have therapeutic value for grief, with acceptance and decentering as mediating psychological processes.
British Journal of Pharmacology
January 1, 2005
Isabel Escobedo, Esther O’shea, Laura Orío et al.
68 citations
MDMA itself does not cause the immediate release of dopamine or serotonin in the mouse brain; instead, peripheral injection of MDMA reduced striatal dopamine and modestly reduced serotonin one hour after the last dose, but direct injection into the striatum did not produce these acute effects. The metabolite HHMA also did not contribute to acute dopamine depletion, as its effects differed from MDMA after peripheral injection. Long-term dopamine loss seven days later was not due to MDMA itself, since only very high intrastriatal doses caused such loss, and HHMA did not alter striatal dopamine after peripheral injection. HHMA crossed the blood–brain barrier but was not detected in brain after peripheral MDMA, suggesting it is metabolized to other active compounds.
Journal of Analytical Toxicology
July 1, 2003
Simona Pichini, M.d. Sánchez Navarro, Roberta Pacifici et al.
66 citations
After a single 100-mg dose of MDMA, the drug appears in sweat within 1.5 hours and peaks at 24 hours, but the amount varies up to 30-fold between individuals, ranging from 3.2 to 1326.1 ng per patch. Only traces of the metabolite MDA are detected. An onsite sweat strip test is positive at 1.5 hours, though 18% false-negative results occur in the first 6 hours. Sweat patch and onsite strip testing offer noninvasive ways to monitor MDMA use.
Journal of Psychoactive Drugs
June 1, 2017
Álvaro José Palma-Conesa, Mireia Ventura, Liliana Galindo et al.
65 citations
New psychoactive tryptamines, which mimic the effects of regulated hallucinogens, pose a potential public health risk. Analysis of 25,296 samples submitted to a harm-reduction organization from 2006 to 2015 identified 436 tryptamines, of which 232 (53.21%) were not regulated. The most common unregulated tryptamine was 4-AcO-DMT, for which no human studies exist. Unregulated tryptamines were more likely to contain a single unadulterated substance. The number of tryptamine samples increased over time, and there were significant differences between client expectations and actual analysis results for regulated versus unregulated groups. Further research is needed to address health risks.
Frontiers in Pharmacology
March 13, 2018
Esther Papaseit, Marta Torrens, Mireia Ventura et al.
61 citations
2C-B, a psychedelic similar to mescaline, acts on serotonin receptors and produces mild psychedelic and stimulant-like effects. In an observational study, 16 healthy experienced users took 10–20 mg orally. The drug increased blood pressure and heart rate, elevated scores on scales for euphoria, liking, and stimulation, and altered perceptions of distances, colors, shapes, and lights. Five participants reported mild hallucinations. Peak 2C-B levels in saliva occurred at 1 hour, and peak cortisol at 3 hours. The effects resemble those of other serotonin-acting drugs.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.