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CLINICAL TRIAL article

Front. Neurosci.
Sec. Perception Science
Volume 18 - 2024 | doi: 10.3389/fnins.2024.1492246

Eye reactions under the influence of drugs of abuse as measured by smartphones: A controlled clinical study in healthy volunteers

Provisionally accepted
Kiki W. K. Kuijpers Kiki W. K. Kuijpers 1Karl Andersson Karl Andersson 2,3Maria Winkvist Maria Winkvist 4Marieke Niesters Marieke Niesters 1Monique Van Velzen Monique Van Velzen 1Fred Nyberg Fred Nyberg 3Albert Dahan Albert Dahan 1Markku Hämäläinen Markku Hämäläinen 4*
  • 1 Leiden University Medical Center (LUMC), Leiden, Netherlands
  • 2 Skillsta Teknik, Design och Kvalitet AB, Vänge, Sweden
  • 3 Uppsala University, Uppsala, Uppsala, Sweden
  • 4 Kontigo Care AB, Uppsala, Uppsala, Sweden

The final, formatted version of the article will be published soon.

    Background: It is known that illicit and prescribed drugs impact pupil size, eye movement and function. Still, comprehensive quantitative evaluations under known ambient light conditions are lacking, when smartphones are used for monitoring.Methods: In this clinical study (NCT05731999), four medicinal products with addiction risks were administered to 48 subjects (18-70 years old, all with informed consent, 12 subjects per drug). Videos captured by smartphones at ~50 lux and ~500 lux documented the eye's reaction before and after controlled intake of single doses of oral oxycodone (20mg), lorazepam (2mg), lisdexamphetamine (70mg) and inhaled cannabis flos (65mg with 22% THC) over a 5-hour test period. Data from three observational tests, non-convergence (NC, ability to cross the eyes), nystagmus (NY), and pupillary light reflex (PLR) were converted into 24 key features that represent different eye characteristics.Results: Of the acquired data, 87-97% produced key features. At peak drug plasma concentration, oxycodone constricted pupils (p<0.001); lorazepam induced non-convergence (p<0.001); lisdexamphetamine induced dilated pupils (p<0.001), irrespective of ambient light conditions. Inhaled cannabis induced miosis (p=0.05 at ~50 lux, p=0.10 at ~500 lux), a reduced light-induced amplitude (p=0.003 at ~50 lux, p=0.3 at ~500 lux) and redness of the sclerae (p=0.14 at ~50 lux, p=0.007 at ~500 lux). The drug effect lasted at least 5 hours (p<0.005) except for inhaled cannabis (2-3h, p<0.05). Conclusions: The ocular response to oxycodone, lorazepam, lisdexamphetamine and cannabis, as measured under controlled light conditions using a smartphone-based assessment, demonstrated distinct and readily distinguishable patterns for each substance.

    Keywords: substance use disorder, Pupillometry, Opioids, Central stimulants, Benzodiazepines, Cannabis

    Received: 30 Oct 2024; Accepted: 16 Dec 2024.

    Copyright: © 2024 Kuijpers, Andersson, Winkvist, Niesters, Van Velzen, Nyberg, Dahan and Hämäläinen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Markku Hämäläinen, Kontigo Care AB, Uppsala, Uppsala, Sweden

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.