The Norepinephrine Transporter Inhibitor Reboxetine Reduces Stimulant Effects of MDMA (“Ecstasy”) in Humans

  title={The Norepinephrine Transporter Inhibitor Reboxetine Reduces Stimulant Effects of MDMA (“Ecstasy”) in Humans},
  author={C. M. Hysek and LD Simmler and Michael Ineichen and Eric Grouzmann and MC Hoener and Rudolf Brenneisen and Joerg Huwyler and Melanie Liechti},
  journal={Clinical Pharmacology \& Therapeutics},
This study assessed the pharmacodynamic and pharmacokinetic effects of the interaction between the selective norepinephrine (NE) transporter inhibitor reboxetine and 3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) in 16 healthy subjects. The study used a double‐blind, placebo‐controlled crossover design. Reboxetine reduced the effects of MDMA including elevations in plasma levels of NE, increases in blood pressure and heart rate, subjective drug high, stimulation, and emotional excitation… 

Duloxetine Inhibits Effects of MDMA (“Ecstasy") In Vitro and in Humans in a Randomized Placebo-Controlled Laboratory Study

The findings confirm the important role of MDMA-induced 5-HT and NE release in the psychotropic effects of MDMA and suggest duloxetine may be useful in the treatment of psychostimulant dependence.

Interactions between Bupropion and 3,4-Methylenedioxymethamphetamine in Healthy Subjects

A role for the transporter-mediated release of norepinephrine in the cardiostimulant effects of MDMA is indicated but the results do not support a modulatory role for dopamine in the mood effects of ecstasy.

Effects of the α2-Adrenergic Agonist Clonidine on the Pharmacodynamics and Pharmacokinetics of 3,4-Methylenedioxymethamphetamine in Healthy Volunteers

The present findings do not support a role for α2-adrenergic receptor agonists in the prevention of psychostimulant dependence and indicate that vesicular release of norepinephrine, which is inhibited by clonidine, does not critically contribute to the effects of MDMA in humans.

Safety pharmacology of acute MDMA administration in healthy subjects

MDMA administration was overall safe in physically and psychiatrically healthy subjects and in a medical setting, however, the risks of MDMA are likely higher in patients with cardiovascular disease and remain to be investigated in Patients with psychiatric disorders.

&agr;1-Adrenergic Receptors Contribute to the Acute Effects of 3,4-Methylenedioxymethamphetamine in Humans

The results indicate that &agr;1-adrenergic receptors contribute to the acute cardiostimulant and to a minor extent possibly also to the thermogenic and euphoric effects of MDMA in humans.

Distinct acute effects of LSD, MDMA, and d-amphetamine in healthy subjects

Investigation of the acute autonomic, subjective, and endocrine effects of single doses of LSD, MDMA, and d-amphetamine in 28 healthy subjects indicates clearly distinct acute effects and may assist the dose-finding in substance-assisted psychotherapy research.

Sex differences in the effects of MDMA (ecstasy) on plasma copeptin in healthy subjects.

MDMA increased plasma copeptin, a marker for AVP secretion, in women but not in men, which may explain why hyponatremia is typically reported in female ecstasy users.

Prediction of MDMA response in healthy humans: a pooled analysis of placebo-controlled studies

Although MDMA plasma concentration was the strongest predictor, several personality traits and mood state variables additionally explained variance in the response to MDMA, confirming that both pharmacological and non-pharmacological variables influence the response of MDMA.

(MDMA): current perspectives

Even though MDMA is listed as a Schedule I compound by the Drug Enforcement Agency, MDMA-assisted psychotherapy for patients with chronic, treatment-resistant posttraumatic stress disorder is currently under investigation and initial results show efficacy for this treatment approach, although considerably more research must be formed to confirm such efficacy.

3,4-methylenedioxymethamphetamine (MDMA): current perspectives

  • J. Meyer
  • Psychology, Biology
    Substance abuse and rehabilitation
  • 2013
MDMA-assisted psychotherapy for patients with chronic, treatment-resistant posttraumatic stress disorder is currently under investigation, and initial results show efficacy for this treatment approach, although considerably more research must be performed to confirm such efficacy and to ensure that the benefits of MDMA-assisted therapy outweigh the risks to the patients.



Which neuroreceptors mediate the subjective effects of MDMA in humans? A summary of mechanistic studies

The results indicate that the overall psychological effects of MDMA largely depend on carrier‐mediated 5‐HT release, while the more stimulant‐like euphoric mood effects of ecstasy appear to relate, at least in part, to dopamine D2 receptor stimulation.

The serotonin uptake inhibitor citalopram reduces acute cardiovascular and vegetative effects of 3, 4-methylenedioxymethamphetamine (‘Ecstasy’) in healthy volunteers

It is suggested that physiological effects of MDMA in humans are partially due to an interaction of MDMA with the serotonin carrier and a subsequent release of serotonin.

MDMA (Ecstasy) and human dopamine, norepinephrine, and serotonin transporters: implications for MDMA-induced neurotoxicity and treatment

The affinity of ecstasy for the human SERT in transfected cells does not clarify the apparent selective toxicity of MDMA for serotonin neurons, although conceivably, its higher efficacy for stimulating 5-HT release may be a distinguishing factor.

Cannabis Coadministration Potentiates the Effects of “Ecstasy” on Heart Rate and Temperature in Humans

Results show that THC mediates heart rate increase independent of sympathetic (catecholaminergic) activity, probably through direct cannabinoid receptor type 1 (CB1) agonism in cardiac tissue.

Pharmacological Interaction between 3,4-Methylenedioxymethamphetamine (Ecstasy) and Paroxetine: Pharmacological Effects and Pharmacokinetics

It seems that paroxetine could interact with MDMA at pharmacodynamic (serotonin transporter) and pharmacokinetic (CYP2D6 metabolism) levels, whereas MDMA alone produced the prototypical effects of the drug.

Acute psychological and physiological effects of MDMA (“Ecstasy”) after haloperidol pretreatment in healthy humans

Effects of a β-blocker on the cardiovascular response to MDMA (Ecstasy)

The results of this study indicate that β-blockers may prevent increases in heart rate but not hypertensive and adverse effects of MDMA.

The effects of fluoxetine on the subjective and physiological effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans

These results suggest that blockade of 5-HT reuptake by fluoxetine can dampen the effects of MDMA and further supports the role of5-HT in its behavioral effects in humans.