Methylphenidate and the risk of acute central nervous system oxygen toxicity: a rodent model and observational data in human divers

Ivan Gur, Yehuda Arieli, Yinnon Matsliah

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: The effects of methylphenidate, a stimulant often prescribed for the treatment of attention-deficit/hyperactivity disorder (ADHD), on the development of central nervous system oxygen toxicity (COT) have not been experimentally evaluated. Methods: The records of all pure-oxygen-rebreather divers evaluated at our institution from 1975-2022 were assessed. Cases of COT were defined as a new onset of tinnitus, tunnel vision, myoclonus, headache, nausea, loss of consciousness, or seizures resolving within 15 minutes from breathing normobaric air, and matched 4:1 with similar controls. Any medications issued to the diver in the preceding three months, including methylphenidate, were recorded. In the animal arm of this study, male mice were exposed to increasing doses of methylphenidate orally, with subsequent exposure to hyperbaric O₂ until clinically evident seizures were recorded. Results: Seventy-five cases of COT were identified in divers, occurring at a median of 80 (range 2-240) minutes after dive initiation at a median depth of 5 m (2-13). Hypercarbia was documented in 11 (14.7%) cases. Prescription of methylphenidate in the preceding three months was not associated with increased risk (OR 0.72, 95% CI 0.16-3.32) of COT. In mice, increasing methylphenidate exposure dose was associated with significantly longer mean COT latency time being 877 s (95% CI 711-1,043) with doses of 0 mg·kg⁻¹; 1,312 s (95% CI 850-1,773) when given 0.75 mg·kg⁻¹; and 1,500 s (95% CI 988-2,012) with 5 mg·kg⁻¹ (F = 4.635, P = 0.014). Conclusions: Observational human data did not demonstrate an association between methylphenidate and an increased risk of COT. Methylphenidate exposure in mice prolongs COT latency and may have protective effects against COT.

Original languageEnglish
Pages (from-to)168-175
Number of pages8
JournalDiving and Hyperbaric Medicine
Volume54
Issue number3
DOIs
StatePublished - 30 Sep 2024
Externally publishedYes

Bibliographical note

Publisher Copyright:
Copyright: This article is the copyright of the authors who grant Diving and Hyperbaric Medicine a non-exclusive licence to publish the article in electronic and other forms.

Keywords

  • ADHD
  • Attention deficit hyperactivity disorder
  • Diving
  • Hyperbaric oxygen
  • Seizures

ASJC Scopus subject areas

  • General Medicine

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