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Effects of MDMA alone and after pretreatment with reboxetine, duloxetine, clonidine, carvedilol, and doxazosin on pupillary light reflex

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Abstract

Rationale

Pupillometry can be used to characterize autonomic drug effects.

Objective

This study was conducted to determine the autonomic effects of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), administered alone and after pretreatment with reboxetine, duloxetine, clonidine, carvedilol, and doxazosin, on pupillary function.

Methods

Infrared pupillometry was performed in five placebo-controlled randomized studies. Each study included 16 healthy subjects (eight men, eight women) who received placebo–MDMA (125 mg), placebo–placebo, pretreatment–placebo, or pretreatment–MDMA using a crossover design.

Results

MDMA produced mydriasis, prolonged the latency, reduced the response to light, and shortened the recovery time. The impaired reflex response was associated with subjective, cardiostimulant, and hyperthermic drug effects and returned to normal within 6 h after MDMA administration when plasma MDMA levels were still high. Mydriasis was associated with changes in plasma MDMA concentration over time and longer-lasting. Both reboxetine and duloxetine interacted with the effects of MDMA on pupillary function. Clonidine did not significantly reduce the mydriatic effects of MDMA, although it produced miosis when administered alone. Carvedilol and doxazosin did not alter the effects of MDMA on pupillary function.

Conclusions

The MDMA-induced prolongation of the latency to and reduction of light-induced miosis indicate indirect central parasympathetic inhibition, and the faster recovery time reflects an increased sympathomimetic action. Both norepinephrine and serotonin mediate the effects of MDMA on pupillary function. Although mydriasis is lasting and mirrors the plasma concentration–time curve of MDMA, the impairment in the reaction to light is associated with the subjective and other autonomic effects of MDMA and exhibits acute tolerance.

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Acknowledgments

We thank Y. Schmid, A. Rickli, A. Fink, R. Brugger, V. Nicola, C. Bläsi, L. Baselgia, S. Müller, and S. Purschke for their assistance in the study management, L. Simmler, M. Donzelli, and R. Brenneisen for the determination of plasma MDMA levels, and M. Arends for the editorial assistance. This work was supported by the Swiss National Science Foundation (grant no. 323230_126231) and University of Basel (grant no. DPH2037).

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The authors report no biomedical financial interest or potential conflict of interest.

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  1. Division of Clinical Pharmacology and Toxicology, Departments of Biomedicine and Internal Medicine, University Hospital Basel and University of Basel, Hebelstrasse 2, CH-4031, Basel, Switzerland

    Cédric M. Hysek & Matthias E. Liechti

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  1. Cédric M. Hysek
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  2. Matthias E. Liechti
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Correspondence to Matthias E. Liechti.

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Hysek, C.M., Liechti, M.E. Effects of MDMA alone and after pretreatment with reboxetine, duloxetine, clonidine, carvedilol, and doxazosin on pupillary light reflex. Psychopharmacology 224, 363–376 (2012). https://doi.org/10.1007/s00213-012-2761-6

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