Biological Psychiatry
November 29, 2014
Yasmin Schmid, Florian Enzler, Peter Gasser et al.
425 citations
In a double-blind, placebo-controlled crossover study, 200 μg of lysergic acid diethylamide (LSD) given to 16 healthy subjects produced pronounced alterations in consciousness lasting 12 hours, including visual hallucinations, audiovisual synesthesia, and positively experienced derealization and depersonalization. LSD increased subjective well-being, happiness, closeness to others, openness, and trust, and decreased prepulse inhibition (PPI) of the acoustic startle response, a measure of sensorimotor gating. It also significantly increased blood pressure, heart rate, body temperature, pupil size, and plasma levels of cortisol, prolactin, oxytocin, and epinephrine. All adverse effects subsided within 72 hours, with no severe acute adverse effects observed. LSD produces empathogenic mood effects similar to methylenedioxymethamphetamine and alters sensorimotor gating in a human model of psychosis, supporting its potential use in psychotherapy and translational psychiatric research.
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.
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.
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.
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.