Pharmacokinetic and pharmacodynamic effects of methylphenidate and MDMA administered alone or in combination
Cédric M. Hysek, Linda D. Simmler, Nathalie Schillinger, Nicole Meyer, Yasmin Schmid, Massimiliano Donzelli, Eric Grouzmann, Matthias E. Liechti
The International Journal of Neuropsychopharmacology October 8, 2013 DOI: 10.1017/s1461145713001132 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, placebo-controlled, crossover study Peer reviewed |
|---|---|
| Population | Healthy subjects |
| Interventions | Methylphenidate MDMA |
| Dose | 60 mg methylphenidate, 125 mg MDMA |
| Topics | MDMA |
| Keywords | Methylphenidate Pharmacology Dopamine Stimulant Pharmacodynamics Norepinephrine transporter Crossover study Dextroamphetamine |
| Citations | 125 |
| Registration | NCT01465685 |
| Key points | Combined use of methylphenidate and MDMA does not enhance psychoactive effects but increases cardiovascular and adverse effects. |
Abstract
Methylphenidate and 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') are widely misused psychoactive drugs. Methylphenidate increases brain dopamine and norepinephrine levels by blocking the presynaptic reuptake transporters. MDMA releases serotonin, dopamine and norepinephrine through the same transporters. Pharmacodynamic interactions of methylphenidate and MDMA are likely. This study compared the pharmacodynamic and pharmacokinetic effects of methylphenidate and MDMA administered alone or in combination in healthy subjects using a double-blind, placebo-controlled, crossover design. Methylphenidate did not enhance the psychotropic effects of MDMA, although it produced psychostimulant effects on its own. The haemodynamic and adverse effects of co-administration of methylphenidate and MDMA were significantly higher compared with MDMA or methylphenidate alone. Methylphenidate did not change the pharmacokinetics of MDMA and vice versa. Methylphenidate and MDMA shared some subjective amphetamine-type effects; however, 125 mg of MDMA increased positive mood more than 60 mg of methylphenidate, and methylphenidate enhanced activity and concentration more than MDMA. Methylphenidate and MDMA differentially altered facial emotion recognition. Methylphenidate enhanced the recognition of sad and fearful faces, whereas MDMA reduced the recognition of negative emotions. Additionally, the present study found acute pharmacodynamic tolerance to MDMA but not methylphenidate. In conclusion, the combined use of methylphenidate and MDMA does not produce more psychoactive effects compared with either drug alone, but potentially enhances cardiovascular and adverse effects. The findings may be of clinical importance for assessing the risks of combined psychostimulant misuse. Trial registration identification number: NCT01465685 (http://clinicaltrials.gov/ct2/show/NCT01465685).
Comparable studies
Other randomized controlled trials on MDMA, most cited first.
Citations in the library
Cited by 72
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- Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study. Psychopharmacology November 1, 2018
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- LSD Acutely Impairs Fear Recognition and Enhances Emotional Empathy and Sociality Neuropsychopharmacology June 1, 2016
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Cites 14
- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
- Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs BMC Pharmacology March 3, 2006
- Psilocybin Biases Facial Recognition, Goal-Directed Behavior, and Mood State Toward Positive Relative to Negative Emotions Through Different Serotonergic Subreceptors Biological Psychiatry May 9, 2012
- Duloxetine Inhibits Effects of MDMA (“Ecstasy") In Vitro and in Humans in a Randomized Placebo-Controlled Laboratory Study PLoS One May 4, 2012
- The Norepinephrine Transporter Inhibitor Reboxetine Reduces Stimulant Effects of MDMA (“Ecstasy”) in Humans Clinical Pharmacology & Therapeutics June 15, 2011
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