Naltrexone, sold under the brand name Revia among others, is a medication primarily used to manage alcohol use or opioid use disorder by reducing cravings and feelings of euphoria associated with substance use disorder. It has also been found effective in the treatment of other addictions and may be used for them off-label. It is taken orally or by injection into a muscle. Effects begin within 30 minutes, though a decreased desire for opioids may take a few weeks to occur.

Side effects may include trouble sleeping, anxiety, nausea, and headaches. In those still on opioids, opioid withdrawal may occur. Use is not recommended in people with liver failure. It is unclear if use is safe during pregnancy. Naltrexone is an opioid antagonist and works by blocking the effects of opioids, including both opioid drugs as well as opioids naturally produced in the brain.

Naltrexone was first made in 1965 and was approved for medical use in the United States in 1984. Naltrexone, as naltrexone/bupropion (brand name Contrave), is also used to treat obesity. It is on the World Health Organization's List of Essential Medicines. In 2021, it was the 254th most commonly prescribed medication in the United States, with more than 1 million prescriptions.

Naltrexone has been best studied as a treatment for alcoholism. Naltrexone has been shown to decrease the quantity and frequency of ethanol consumption by reducing the dopamine release from the brain after consuming alcohol. It does not appear to change the percentage of people drinking. Its overall benefit has been described as "modest".

Acamprosate may work better than naltrexone for eliminating alcohol abuse, while naltrexone may decrease the desire for alcohol to a greater extent.

A method pioneered (starting in the 1980s) by scientist John David Sinclair (dubbed commercially the "Sinclair Method") advocates "pharmacological extinction" of problem drinking behavior by administering naltrexone alongside controlled alcohol consumption. In effect, he argues that naltrexone-induced opioid antagonism sufficiently disrupts reflexive reward mechanisms inherent in the consumption of alcohol and, given enough repetition, will dissociate positive associations formerly made with the consumption of alcohol. A review of eight naltrexone trials concluded, "Although all found benefits from naltrexone with the coping therapy, none of them found any significant benefit of naltrexone over placebo when combined with support for abstinence."

Long-acting injectable naltrexone (under the brand name Vivitrol) is an opioid antagonist, blocking the effects of heroin and other opioids, and decreases heroin use compared to a placebo. Unlike methadone and buprenorphine, it is not a controlled medication. It may decrease cravings for opioids after a number of weeks, and decreases the risk of overdose, at least during the time period that naltrexone is still active, though concern about risk of overdose for those stopping treatment remains. It is given once per month and has better adherence and effect for opioid use than the oral formulation.

A drawback of injectable naltrexone is that it requires patients with opioid use disorder and current physiological dependence to be fully withdrawn before it is initiated to avoid a precipitated opioid withdrawal that may be quite severe. In contrast, initiation of buprenorphine only requires delay of the first dose until the patient begins to manifest at least mild opioid withdrawal symptoms. Among patients able to successfully initiate injectable naltrexone, long-term remission rates were similar to those seen in clinical buprenorphine/naloxone administration.