There are two primary medications used to treat opioid dependence in the United States, methadone and buprenorphine, both of which interact with MOR. Methadone acts as a full MOR agonist, activating MOR downstream signaling in a similar manner to morphine. The activation of MOR enables methadone to reduce craving for illicit opioids and to decrease withdrawal symptoms. Buprenorphine is a partial MOR agonist, as well as an antagonist of KOR. Treatment with buprenorphine reduces craving much like methadone, but the reduced agonist activity somewhat reduces the addictive potential of the medication. Naltrexone, a MOR antagonist with high affinity for the MOR protein, is also efficacious for the treatment of opioid dependence. As a MOR antagonist, naltrexone causes rapid onset of withdrawal symptoms if given to an opioid dependent person. As a result, naltrexone is often used for rapid detoxification prior to standard buprenorphine or methadone treatment, rather than as a long term therapeutic option in most countries, Russia being a notable exception. Naloxone, another MOR antagonist, is often compounded with buprenorphine, blocking activation of MOR by buprenorphine if the medication is injected rather than taken orally [62, 63].
