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Pharmacokinetic interactions of cannabidiol and oxycodone after oral administration in rats

Alexandria Senetra
University of Florida

Co-Authors: Michelle A. Kuntz1, Siva Rama Raju Kanumuri1, Yi-Hua Chiang1, Ariana C. Brice-Tutt1, Niall P. Murphy1, Adriaan W. Bruijnzee1, Marcelo Febo1, Barry Setlow1, John K. Neubert1, Christopher R. McCurdy1, Abhisheak Sharma1
1University of Florida

Cannabinoids and opioids share many pharmacologic properties and may act synergistically. Cannabidiol (CBD) exhibits analgesic and anti-inflammatory properties, but a major concern is its potential to interact with prescription drugs, specifically, opioids. Oxycodone is a commonly prescribed opioid used to treat moderate to severe pain. Recent studies show patients using both CBD and oxycodone concomitantly report greater analgesia. Cannabinoid consumption has been shown to cause impairment of a wide range of cognitive functions in a dose-related manner, along with exhibiting adverse effects in the cardiovascular, respiratory, neural, and psychological systems. Due to the depressant effects of both CBD and opioids, co-administration of these substances can suppress the central nervous system to dangerous levels, as well as increase the risk of opioid use disorder. To date, there have been no studies to assess the pharmacokinetic interactions of opioids and CBD. This study was performed to investigate the potential interactions of CBD and oxycodone. A single oral dose of CBD (25 mg/kg), oxycodone (1.4 mg/kg), or combination of both was administered to male Sprague-Dawley rats (N=4). Blood samples were collected up to 24 hours post administration. When administered concomitantly, CBD had a 1.3-fold lower exposure (AUC), while oxycodone had a 24-fold higher exposure (AUC) than when each drug was administered alone. The metabolites, 7OH-CBD, 7COOH-CBD, noroxycodone, and noroxymorphone had a 1.2-, 1.4-, 2.9-, and 1328-fold lower exposure (AUC), respectively with concomitant administration. A delayed absorption phase for both CBD and oxycodone was exhibited in rats when dosed concomitantly. These results uncover the pharmacokinetic interactions between CBD and oxycodone that could manifest as interactions at a physiological level, which may also extend to other prescription opioids.

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