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.
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.
Journal of Clinical Psychopharmacology
July 13, 2013
Cédric M. Hysek, Anja E. Fink, Linda D. Simmler et al.
57 citations
Blocking α₁-noradrenergic receptors with the drug doxazosin reduces MDMA-induced increases in blood pressure and body temperature, and moderately lessens positive mood, but enhances rapid heart rate. In a randomized, double-blind, placebo-controlled crossover study with 16 healthy participants, doxazosin (8 mg daily for 3 days before MDMA 125 mg) altered several acute effects of MDMA. The findings suggest that α₁-adrenergic receptors play a role in the cardiovascular stimulant effects of MDMA and, to a minor extent, its thermogenic and euphoric effects in humans.
Pharmacogenetics and Genomics
June 2, 2016
Yasmin Schmid, Patrick Vizeli, Cédric M. Hysek et al.
52 citations
Genetic variants in the CYP2D6 enzyme, which metabolizes MDMA (ecstasy), alter the drug's pharmacokinetics and effects. In a pooled analysis of eight double-blind, placebo-controlled crossover studies involving 139 healthy individuals (70 men, 69 women), people with poor CYP2D6 metabolism had 15% higher peak concentrations of MDMA and 50% higher peak concentrations of its active metabolite, while the inactive metabolite was 50-70% lower, compared to extensive metabolizers. Blood pressure and subjective drug effects also increased more rapidly in poor metabolizers. However, these differences are small because MDMA itself inhibits CYP2D6 activity.
Neuroendocrinology
January 1, 2014
Julia Seibert, Cédric M. Hysek, Carlos A. Penno et al.
52 citations
MDMA (ecstasy) but not methylphenidate (Ritalin) acutely alters several steroid hormones over 24 hours. In 16 healthy adults given single doses of MDMA (125 mg), methylphenidate (60 mg), both drugs together, or placebo on separate days, MDMA raised cortisol, corticosterone, 11-dehydrocorticosterone, and 11-deoxycorticosterone, and tended to increase aldosterone, while leaving cortisone, DHEA, DHEAS, androstenedione, and testosterone unchanged. Methylphenidate alone did not affect any steroid levels and did not modify MDMA's effects. These results indicate that serotonin release, not dopamine or norepinephrine stimulation, drives acute activation of the hypothalamic-pituitary-adrenal axis by these drugs.
European Neuropsychopharmacology
December 4, 2014
Yasmin Schmid, Cédric M. Hysek, Katrin H. Preller et al.
39 citations
In a double-blind, placebo-controlled crossover study with 30 healthy adults, a single 40 mg dose of methylphenidate increased subjective ratings of sexual arousal when viewing explicit erotic pictures and led participants to press a button to prolong viewing of implicit sexual stimuli, whereas a 75 mg dose of MDMA did not alter sexual arousal. Neither drug changed how participants appraised the romantic relationships of unknown couples. Blood levels of testosterone, estrogen, and progesterone were unrelated to arousal ratings. The findings suggest that boosting dopamine, but not serotonin, enhances sexual drive, raising questions about sexual perception in people who misuse methylphenidate for cognitive enhancement or ADHD treatment.
British Journal of Pharmacology
September 6, 2013
Cédric M. Hysek, Yasmin Schmid, Anna Rickli et al.
7 citations
A 125 mg dose of MDMA, a common recreational amount, produces only a moderate increase in body temperature in controlled clinical settings where risk factors like high ambient temperature, physical exertion, and dehydration are avoided. Severe hyperthermia, a rare but life-threatening complication of recreational MDMA use, typically requires additional permissive factors such as repeated or high doses, crowded conditions, or hyperthyroidism. The drug carvedilol, which blocks both α- and β-adrenoceptors, reduced MDMA-induced thermogenesis in humans and reversed established hyperthermia in rats, but its utility for treating severe MDMA toxicity in emergency settings remains unknown and requires further evaluation in case reports or series.