What are the primary pharmacological treatments for opioid use disorder (OUD), and how do they differ in their pharmacology?

• A. Methadone (full opioid agonist), Buprenorphine (partial mu-agonist with ceiling effect), Naltrexone (opioid antagonist); Naltrexone initiation requires detoxification.
• B. Buprenorphine (partial mu-agonist with ceiling), Methadone (full agonist), Naltrexone (agonist at kappa).
• C. Naloxone (antagonist), Methadone (antagonist), Naltrexone (partial agonist).
• D. Buprenorphine-naloxone is used to treat OUD because it increases injection risk.

Answer: (A)

The main idea is that treating opioid use disorder relies on three pharmacologic strategies that act differently at opioid receptors: a full agonist, a partial agonist with a ceiling effect, and an antagonist. Methadone is a full mu-opioid receptor agonist, meaning it activates the receptor to fully relieve withdrawal and cravings, but with careful dosing to avoid overdose. Buprenorphine is a partial mu-opioid agonist; it activates the receptor but to a lesser degree and with a high enough affinity to block other opioids, plus a ceiling effect that limits respiratory depression risk. Naltrexone is an antagonist at mu (and other opioid receptors); it blocks the effects of any opioids, so it won’t produce relief from withdrawal or cravings unless opioids are fully cleared first. Because naltrexone can precipitate withdrawal if opioids remain in the system, initiation requires detoxification.

The other options mischaracterize the pharmacology: one lists Naltrexone as an agonist at kappa, which isn’t correct for its mechanism; another assigns antagonist or partial-agonist labels inaccurately to the wrong drugs; and the last falsely states that buprenorphine-naloxone increases injection risk, whereas it is designed to deter misuse by injection.