R‐(‐)2,5‐dimethoxy‐4‐iodoamphetamine (DOI) Blunts the Discriminative Stimulus Properties of Oxycodone
Leah M Salinsky, R. Fox, Noelle C Anastasio, Kathryn A. Cunningham
The FASEB Journal May 1, 2022 DOI: 10.1096/fasebj.2022.36.s1.r5549 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical behavioral pharmacology experiment (drug discrimination paradigm) Peer reviewed |
|---|---|
| Intervention | Oxycodone |
| Key findings | The authors tested the hypothesis that the psychedelic 5-HT2A receptor agonist DOI would disrupt the discriminative stimulus properties of oxycodone, using a drug discrimination paradigm described as a rigorous laboratory procedure for modeling drugs' interoceptive effects and assessing ligand potency, effectiveness, and abuse liability. The abstract states the hypothesis and approach but does not report results. |
Abstract
A record ~100,000 fatalities due to drug overdoses was reported in the U.S. for the twelve months preceding April 2021. Opioids account for most deaths, and recurrent opioid use may lead to the development of opioid use disorder (OUD), a debilitating chronic disorder. Current medication‐assisted OUD treatment (e.g., buprenorphine) mitigates withdrawal, reduces mortality, and reduces intake of abused opioids. Still, the opioid epidemic crystalized the need to identify novel non‐opioid therapeutics to improve the odds of successful OUD recovery. In the last decade, there has been a resurgence of interest in serotonergic psychedelics for the treatment of psychiatric disorders, including substance use disorders. Psychedelic compounds act through agonist actions at the serotonin (5‐HT) 5‐HT2A receptor (5‐HT2AR) and there is some literature to suggest functional interactions between 5‐HT2AR and opioids. We tested the hypothesis that the psychedelic 5‐HT2AR agonist R‐(‐)2,5‐dimethoxy‐4‐iodoamphetamine (DOI) will disrupt the discriminative stimulus properties of the commonly misused prescription opioid oxycodone. The drug discrimination paradigm is a rigorous laboratory procedure for modeling the interoceptive effects of drugs and is widely recognized as useful in establishing ligand potency and effectiveness in vivo, as well as interrogating abuse liability.