Hysek and Liechti Effects of MDMA on the pupillary light reflex on its own and after pretreatment with reboxetine, duloxetine, clonidine, carvedilol, and doxazosin Cédric M. Hysek and Matthias E. Liechti* Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Internal Medicine, University Hospital and University of Basel, Switzerland Running title: MDMA and pupillary function *Corresponding author: Matthias E. Liechti, Division of Clinical Pharmacology and Toxicology, University Hospital Basel, Hebelstrasse 2, CH-4031 Basel. Phone: +41 61 328 68 68; Fax: +41 61 265 45 60; E-mail:
[email protected] 1 Hysek and Liechti Abstract Rationale: Pupillometry can be used to characterize autonomic drug effects. Objective: To determine the autonomic effects of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) on pupillary function, administered alone and after pretreatment with reboxetine, duloxetine, clonidine, carvedilol, and doxazosin. Methods: Infrared pupillometry was performed in five placebo-controlled randomized clinical 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, reduced the response to light, prolonged the latency to the light reflex, and shortened the recovery time. The impaired reflex response was short-lasting and associated with subjective, cardiostimulant, and hyperthermic drug effects and returned to normal within 5-6 h after MDMA administration when plasma MDMA levels were still high. Mydriasis was associated with the changes in plasma MDMA concentration over time and longer-lasting. Both reboxetine and duloxetine interacted with the effects of MDMA on pupillary function. Duloxetine even prevented MDMA-induced impairments in the light reflex response despite having similar effects when administered alone.