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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MDMA, methylphenidate, placebo | Experimental | Cross-over within-subjects design with all treatment conditions tested in the same subject. This design has 1 arm but two (actually 4) treatment conditions in the same subject. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 3,4-Methylenedioxymethamphetamine | Drug | 125 mg per os, single dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| Subjective effect during 24 hours | subjective effects are repetitively assessed by standardized questionnaires. | 24 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Blood pressure (mmHg)during 10 hours | 10 hours | |
| Neuroendocrine plasma levels during 10 hours | neuroendocrine parameters assessed: prolactin, cortisol, epinephrine, norepinephrine, oxytocin, pro-vasopressin, vasopressin, estrogen,and progesterone |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Matthias E Liechti, MD | University Hospital, Basel, Switzerland | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Basel | Basel | Canton of Basel-City | 4000 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29912955 | Derived | Vizeli P, Liechti ME. Oxytocin receptor gene variations and socio-emotional effects of MDMA: A pooled analysis of controlled studies in healthy subjects. PLoS One. 2018 Jun 18;13(6):e0199384. doi: 10.1371/journal.pone.0199384. eCollection 2018. | |
| 24103254 | Derived | Hysek CM, Simmler LD, Schillinger N, Meyer N, Schmid Y, Donzelli M, Grouzmann E, Liechti ME. Pharmacokinetic and pharmacodynamic effects of methylphenidate and MDMA administered alone or in combination. Int J Neuropsychopharmacol. 2014 Mar;17(3):371-81. doi: 10.1017/S1461145713001132. Epub 2013 Oct 8. |
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| ID | Term |
|---|---|
| D018817 | N-Methyl-3,4-methylenedioxyamphetamine |
| D008774 | Methylphenidate |
| ID | Term |
|---|---|
| D000662 | Amphetamines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D000588 | Amines |
| D009930 |
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| Methylphenidate | Drug | 1 hour before MDMA/placebo 60 mg methylphenidate per os, single dose |
|
|
| Placebo | Drug | capsules identical to MDMA or methylphenidate |
|
| 10 hours |
| MDMA plasma levels during 24 hours | 24 hours |
| Heart rate (beats/min)) during 10 hours | 10 |
| Emotional and cognitive empathy | emotional empathy is going to be assessed by the Multifaceted Empathy Test (MET). cognitive empathy is going to be assessed by the Facial Emotion Recognition Task and the MET. | 5 hours |
| Prosocial behavior | Effects on prosociality will be assessed by the Social Value Orientation slide-measurement test. | 5 hours |
| Genetic polymorphisms | Effects of genetic polymorphisms on the response to MDMA | assessed after study completion |
| Organic Chemicals |
| D010648 | Phenylacetates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |