Social Cognitive and Affective Neuroscience
October 4, 2013
Cédric M. Hysek, Yasmin Schmid, Linda D. Simmler et al.
356 citations
MDMA (ecstasy) enhances emotional empathy and prosocial behavior in men but impairs recognition of negative emotions like fear, anger, and sadness, especially in women. In a placebo-controlled, double-blind crossover trial with 32 healthy volunteers, MDMA increased explicit and implicit emotional empathy on the Multifaceted Empathy Test and boosted prosocial choices on the Social Value Orientation test in men. It did not affect cognitive empathy but worsened identification of negative facial expressions on the Face Emotion Recognition Task, particularly in women. MDMA also raised plasma cortisol, prolactin, and oxytocin levels, markers linked to social behavior. These effects may explain MDMA's recreational sociability and its potential therapeutic use in psychotherapy for social dysfunction or PTSD.
PLoS ONE
May 4, 2012
Cédric M. Hysek, Linda D. Simmler, V.g. Nicola et al.
158 citations
Taking the antidepressant duloxetine before MDMA (ecstasy) blocks many of the drug's effects. In a controlled experiment with 16 healthy volunteers, duloxetine prevented MDMA from raising blood pressure, heart rate, and norepinephrine levels, and also reduced the subjective drug experience. This happened even though duloxetine increased MDMA concentrations in the blood. Laboratory tests on human cells confirmed that duloxetine stops MDMA from releasing the neurotransmitters serotonin and norepinephrine. These findings indicate that MDMA's psychological effects depend on its ability to release both serotonin and norepinephrine, and suggest duloxetine could help treat dependence on stimulant drugs.
Journal of Psychopharmacology
July 22, 2014
Yasmin Schmid, Cédric M. Hysek, Linda D. Simmler et al.
154 citations
A low dose of MDMA (75 mg) enhanced emotional empathy for positive emotional situations and reduced recognition of sad faces, but did not affect cognitive empathy, social cognitive inferences, or moral judgment. Methylphenidate (40 mg) had no effects on emotional processing, empathy, or mental perspective-taking. MDMA increased subjective feelings of closeness, openness, and trust, along with plasma oxytocin and prolactin levels. These social-cognitive effects likely contribute to MDMA's popularity as a party drug.
Clinical Pharmacology & Therapeutics
June 15, 2011
C.m. Hysek, Linda D. Simmler, M. Ineichen et al.
153 citations
Blocking the norepinephrine transporter with reboxetine reduces the cardiovascular and subjective stimulant effects of MDMA (ecstasy) in humans, even though MDMA and its active metabolite reach higher concentrations in the blood. In a double-blind, placebo-controlled crossover study with 16 healthy adults, reboxetine lowered MDMA-induced increases in plasma norepinephrine, blood pressure, heart rate, drug high, stimulation, and emotional excitement. The findings indicate that transporter-mediated norepinephrine release is essential for MDMA's cardiovascular and stimulant-like effects.
The International Journal of Neuropsychopharmacology
October 8, 2013
Cédric M. Hysek, Linda D. Simmler, Nathalie Schillinger et al.
125 citations
Taking methylphenidate (Ritalin) with MDMA (ecstasy) does not produce stronger psychoactive effects than either drug alone, but it does increase cardiovascular strain and adverse effects. In a double-blind, placebo-controlled crossover trial with healthy subjects, methylphenidate alone produced psychostimulant effects but did not enhance MDMA's mood-elevating effects. MDMA (125 mg) increased positive mood more than methylphenidate (60 mg), while methylphenidate enhanced activity and concentration more than MDMA. The drugs also differently affected emotion recognition: methylphenidate improved recognition of sad and fearful faces, whereas MDMA reduced recognition of negative emotions. Acute tolerance developed to MDMA but not methylphenidate. The drugs did not alter each other's pharmacokinetics.
The Journal of Clinical Endocrinology & Metabolism
June 30, 2011
Linda D. Simmler, Cédric M. Hysek, Matthias E. Liechti
91 citations
MDMA (ecstasy) increases plasma copeptin, a marker for vasopressin secretion, in women but not in men. In a randomized placebo-controlled crossover trial with 16 healthy subjects, MDMA (125 mg) significantly elevated copeptin levels in women at 60 and 120 minutes, an effect prevented by pretreatment with duloxetine, which blocks MDMA-induced release of serotonin and norepinephrine. MDMA also tended to increase urine sodium and osmolality, indicating renal water retention, despite increased water intake. This sex difference in vasopressin secretion may explain why hyponatremia is more common in female ecstasy users.
British Journal of Pharmacology
March 8, 2012
C.m. Hysek, Yasmin Schmid, Anna Rickli et al.
81 citations
The α₁- and β-adrenoceptor antagonist carvedilol reduced MDMA-induced increases in blood pressure, heart rate, and body temperature in healthy subjects, but did not affect the subjective or psychotropic effects of MDMA, such as drug liking, high, or stimulation. Carvedilol also did not alter plasma exposure to MDMA. These findings suggest that α₁- and β-adrenoceptors contribute to the cardiostimulant and thermogenic effects of MDMA in humans but not to its psychological effects, indicating carvedilol could be useful for treating cardiovascular and hyperthermic complications associated with ecstasy use.
Molecular Psychiatry
November 5, 2025
Dino Luethi, Grant C. Glatfelter, Eline Pottie et al.
1 citation
Psychedelic-like effects of ring-substituted amphetamines are primarily mediated by 5-HT 2A receptors. Small lipophilic substituents at the 4-position of 2,5-dimethoxyamphetamine enhance clinical potency. This study examined 4-alkylated 2,5-dimethoxyamphetamines (methyl, ethyl, propyl, butyl, amyl) for in vitro receptor activity and in vivo effects in mice using the head-twitch response (HTR) assay. Increasing 4-alkyl chain length raised affinity at 5-HT 2A receptors. The 4-propyl analog showed the highest potencies for 5-HT 2A receptor activation (1–9 nM) in vitro; other chain lengths ranged from 2–56 nM. In mice, maximal HTR counts varied from 23 to 119, with potencies from 0.42 to 2.76 mg/kg.