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.
Current Pharmaceutical Design
September 12, 2012
Rocío Martín‐Santos, José Alexandre S. Crippa, Albert Batalla et al.
288 citations
Delta-9-tetrahydrocannabinol (THC), but not cannabidiol (CBD), produces marked acute behavioral and physiological effects. In a randomized, double-blind, placebo-controlled trial with 16 healthy male volunteers, oral THC (10 mg) caused anxiety, dysphoria, positive psychotic symptoms, physical and mental sedation, subjective intoxication, and increased heart rate relative to placebo and CBD. CBD (600 mg) showed no differences from placebo on any symptomatic or physiological measure, indicating it is safe and well tolerated. The two main cannabis constituents thus have quite different acute effects.
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.
Human Psychopharmacology Clinical and Experimental
March 1, 2012
Ornella Corazza, Fabrizio Schifano, Pierluigi Simonato et al.
157 citations
Methoxetamine, a dissociative drug related to ketamine, has a much longer duration of action and intensity of effects, and its availability on the web represents a new recreational trend. The analysis of online, non-peer-reviewed material carries methodological limitations. The online availability of information on novel psychoactive drugs like methoxetamine constitutes a pressing public health challenge, requiring better international collaboration and novel forms of intervention to address this fast-growing phenomenon.
Annals of the New York Academy of Sciences
August 1, 2006
Sergio Abanades, Magı́ Farré, Mireia Segura et al.
124 citations
Gamma-hydroxybutyrate (GHB) produces dose-related changes in subjective effects, showing a mixed stimulant-sedative pattern: initial feelings of euphoria, high, and liking, followed by mild-to-moderate sedation with impaired performance and balance. Single oral doses of 40, 50, 60, and 72 mg/kg were given to eight volunteers. Mean peak plasma concentrations ranged from 79.1 to 130.1 μg/L. Physiological and subjective effects were dose-dependent and related to plasma concentrations. Urinary excretion was mainly related to dose. The results suggest high abuse liability at the doses typically consumed.
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.
Current Clinical Pharmacology
May 1, 2011
Ornella Corazza, Fabrizio Schifano, Magı́ Farré et al.
98 citations
Bromo-Dragonfly (B-fly) is a potent, long-lasting hallucinogenic drug similar to LSD, associated with acute intoxications and fatalities in several countries. This paper reviews its pharmacology, chemistry, toxicology, and behavioral effects using both scientific literature and web sources. The authors critically discuss the potential for misuse and the methodological limitations of analyzing non-peer-reviewed online material. They conclude that online information about novel psychoactive drugs like B-fly poses a public health challenge and call for better international collaboration to address this growing phenomenon.
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.
Journal of Clinical Psychopharmacology
December 1, 2007
Sergio Abanades, Magı́ Farré, Diego Barral et al.
69 citations
A single oral dose of gamma-hydroxybutyric acid (GHB) at 40 or 60 mg/kg produces euphoria and pleasurable effects with slightly higher ratings than those from flunitrazepam (1.25 mg) or ethanol (0.7 g/kg) in healthy male recreational club drug users. GHB shows a biphasic time profile: an initial stimulant-like effect as plasma concentrations rise, followed by a later sedative effect unrelated to its kinetics. GHB increases blood pressure and pupil diameter, while flunitrazepam produces marked sedation. Both GHB and flunitrazepam impair psychomotor performance, including digit symbol substitution and balance tasks, whereas ethanol only mildly affects balance. The findings suggest a high abuse liability of GHB and flunitrazepam in this population.
Journal of Clinical Psychopharmacology
September 12, 2008
Brian O’Mathúna, Magı́ Farré, Amin Rostami‐hodjegan et al.
68 citations
MDMA (ecstasy) strongly inhibits the liver enzyme CYP2D6, which is responsible for metabolizing many drugs. In a controlled trial with 15 healthy men, a single 1.5 mg/kg oral dose of MDMA increased blood levels of the probe drug dextromethorphan about tenfold and reduced its breakdown product dextrorphan. The urinary metabolic ratio rose nearly 100-fold, and two-thirds of participants temporarily showed a metabolic profile typical of poor metabolizers. CYP2D6 activity recovered after 10 days, with a half-life of 46.6 hours. Users should be warned that MDMA can dangerously alter the metabolism of other medications.
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.
Therapeutic Drug Monitoring
February 1, 2007
Sergio Abanades, Magı́ Farré, Mireia Segura et al.
66 citations
After a single oral dose of 50 mg/kg sodium GHB, mean peak plasma concentrations reached 83.1 μg/mL at 30 minutes, then declined to 0.9 μg/mL at 6 hours. GHB appeared in oral fluid at levels one-third to one-fourth of plasma concentrations, with a half-life of about 1.2 hours compared to 0.7 hour in plasma. Less than 2% of the dose was excreted in urine, and sweat contained only low concentrations. Subjective effects followed a mixed sedative-stimulant pattern, peaking between 1 and 1.5 hours and lasting 2 hours, and were related to plasma concentrations. Oral fluid and sweat were not suitable for monitoring GHB consumption.
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.
Journal of Psychopharmacology
January 21, 2008
Susana de Sola Llopis, Mónica Miguélez-Pan, Jordi Peña‐Casanova et al.
58 citations
Recreational ecstasy use, often alongside cannabis, is linked to lasting cognitive deficits. Over two years, regular ecstasy users performed worse than cannabis-only users and non-users on tests of verbal fluency, working memory, and processing speed. Heavier users (more than 100 tablets) also showed impairments in episodic memory. These deficits persisted across the study period. The findings suggest that ecstasy, possibly combined with cannabis, causes subtle but lasting cognitive harm, though pre-existing differences between groups cannot be ruled out.
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.
Addiction Biology
March 3, 2016
Laura Blanco‐Hinojo, Jesus Pujol, Ben J. Harrison et al.
52 citations
Chronic cannabis use is associated with reduced motivation, and this study examined how it affects functional connectivity between the basal ganglia and brain regions involved in internal (frontal cortex) and external (sensory cortices) motivation signals. Resting-state fMRI in 28 chronic cannabis users and 29 controls showed that cannabis exposure attenuated the positive correlation between the striatum and limbic frontal-basal ganglia circuits, and attenuated the negative correlation between the striatum and the fusiform gyrus, which is important for recognizing significant visual features. These connectivity alterations were linked to lower arousal in response to affective pictures. Changes tended to normalize after one month of abstinence, indicating that cannabis impairs fine-tuning of the motivation system, but this effect is reversible.
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.