Pharmacokinetic and pharmacodynamic effects of methylphenidate and MDMA administered alone or in combination

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).

Effects of methylphenidate and MDMA on appraisal of erotic stimuli and intimate relationships

“…For example, MDMA has been shown to acutely alter related components of social cognition including recognition of facial emotions (Bedi et al, 2010;Hysek et al, 2012a;Hysek et al, 2013;Hysek et al, 2014;Kirkpatrick et al, 2014) and emotional empathy (Hysek et al, 2013;Kuypers et al, 2014;Schmid et al, 2014). Additionally, changes in 5-HT levels may influence cognitions sustaining intimate relationships.…”

Development of a high‐speed MALDI‐triple quadrupole mass spectrometric method for the determination of 3,4‐methylenedioxymethamphetamine (MDMA) in oral fluid

“…Furthermore, sample amount used for measurements could be further downscaled and costs for eluents required for LC-MS analysis could be omitted. MDA was detected in samples collected 3 h after administration at a time corresponding to the maximal plasma exposure of MDMA (Hysek et al, 2014a) and when MDA levels close to maximum are already reached (Hysek et al, 2011). Samples collected at the time of intake (t=0h) and 24 h after administration were negative for MDA.…”

“…This was investigated by analyzing spiked samples containing MPh and MDMA at different concentration ratios. MPh was chosen for that experiment because it was co-administered in the study from which the oral fluid samples for applicability testing were received (Hysek et al, 2014a). MPh suppressed the MDMA signal intensity (Figure 1) but ion-suppression was still within guideline regulations.…”

“…16 participants received MDMA or placebo in combination with methylphenidate and/or placebo (Hysek et al, 2014a). Concentrations of MDMA in oral fluid were assessed.…”

“…The resulting method should be validated according to international guidelines. Furthermore, its applicability should be proven by analyzing OF samples from a double-blind, placebo-controlled, crossover study with ingestion of 125 mg of MDMA (Hysek et al, 2014a).…”