Emotional Effects of Methylphenidate and MDMA in Healthy Subjects

This study compares the interactive emotional/subjective effects of single doses of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") and methylphenidate, a dopamine (DA) and norepinephrine (NE) transporter blocker, in healthy subjects. The primary goal is to determine the role of transporter mediated DA and NE release in the subjective response to MDMA in humans. The investigators hypothesize that methylphenidate will attenuate the subjective response to MDMA.

3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is widely used by young people for its euphoric effects. MDMA releases serotonin (5-HT), dopamine (DA), and norepinephrine (NE). 5-HT release mainly contributes to the subjective effects of MDMA whereas NE release is involved in the cardiovascular and psychostimulant effects of MDMA. DA is also likely to be involved in the rewarding and reinforcing effects of drugs of abuse. However, the functional role of DA in the subjective effects of MDMA in humans is largely unclear. To determine the role of the DA transporter (DAT) in the response to MDMA in humans the investigators test the effects of the DA and NE transporter blocker methylphenidate on the subjective effects of MDMA. The investigators use a randomized double-blind placebo-controlled cross-over design with four experimental sessions. methylphenidate or placebo will be administered before MDMA or placebo to 16 healthy volunteers. Subjective and cardiovascular responses will be repeatedly assessed throughout the experiments and plasma samples are collected for pharmacokinetics. The primary hypothesis is that methylphenidate will significantly reduce the subjective effects of MDMA.

Eligibility Criteria:
Inclusion Criteria:

* Sufficient understanding of the German language
* Subjects understand the procedures and the risks associated with the study
* Participants must be willing to adhere to the protocol and sign the consent form
* Participants must be willing to refrain from taking illicit psychoactive substances during the study.
* Participants must be willing to drink only alcohol-free liquids and no xanthine-containing liquids (such as coffee, black or green tea, red bull, chocolate) after midnight of the evening before the study session. Subjects must agree not to smoke tobacco for 1 h before and 4 hours after MDMA administration.
* Participants must be willing not to drive a traffic vehicle in the evening of the study day.
* Women of childbearing potential must have a negative pregnancy test at the beginning of the study and must agree to use an effective form of birth control. Pregnancy tests are repeated before each study session.
* Body mass index: 18-25 kg/m2

Exclusion Criteria:

* Chronic or acute medical condition including clinically relevant abnormality in physical exam, laboratory values, or ECG. In particular: Hypertension (\>140/90 mmHg). Personal or first-grade history of seizures. Cardiac or neurological disorder.
* Current or previous psychotic or affective disorder
* Psychotic or affective disorder in first-degree relatives
* Prior illicit drug use (except THC-containing (tetrahydrocannabinol) products) more than 5 times or any time within the previous 2 months.
* Pregnant or nursing women.
* Participation in another clinical trial (currently or within the last 30 days)
* Use of medications that are contraindicated or otherwise interfere with the effects of the study medications (monoamine oxidase inhibitors, antidepressants, sedatives etc.)