Naltrexone is a medication that blocks opioid receptors in the brain, reducing the rewarding effects of alcohol and opioids. It’s FDA-approved for treating both alcohol use disorder and opioid use disorder, and it’s also used in combination with another drug for weight management. At standard doses, it doesn’t cause a high, isn’t addictive, and works by changing how your brain responds to certain substances rather than replacing them.
How Naltrexone Works in the Brain
Your brain has opioid receptors that respond to both external opioids (like heroin or prescription painkillers) and your body’s own natural opioids (endorphins). These receptors play a key role in feelings of pleasure and reward. Naltrexone parks itself on these receptors, primarily the mu-opioid receptor, and blocks other molecules from activating them.
This blocking action has two practical consequences. First, if someone takes an opioid while on naltrexone, they won’t feel the usual high because the drug can’t reach its target. Second, when someone drinks alcohol, their brain normally releases endorphins that contribute to the pleasurable buzz. Naltrexone intercepts that signal, making alcohol feel less rewarding over time. The medication also influences stress hormone pathways that drive the urge to drink.
Naltrexone for Alcohol Use Disorder
For alcohol, naltrexone doesn’t make you sick if you drink (that’s a different medication, disulfiram). Instead, it dulls the reward. Drinking feels less satisfying, which gradually weakens the cycle of craving and consumption. Some people use it while still drinking, with the goal of reducing heavy drinking days over time rather than requiring complete abstinence from day one.
A large U.S. trial called the COMBINE study, which enrolled 1,383 people, found that naltrexone increased abstinent days from 75% to about 81% and reduced the likelihood of a heavy drinking day from 73% to 66% compared to placebo. Those numbers may sound modest, but for someone struggling with daily heavy drinking, they can represent a meaningful shift. Not every trial has shown a benefit, though. A Veterans Affairs study of 627 people with severe, chronic alcohol dependence found no significant advantage over placebo, suggesting that naltrexone works better for some populations than others.
Treatment typically lasts at least 3 to 4 months. If you become fully abstinent during that time, your doctor may stop the medication and monitor you monthly for up to a year. If heavy drinking continues early in treatment, a longer course is usually recommended, since many people relapse within months of stopping.
Naltrexone for Opioid Use Disorder
For opioid dependence, naltrexone serves as a relapse prevention tool. It doesn’t ease withdrawal or satisfy cravings the way methadone or buprenorphine do. Instead, it removes the incentive to use by making opioids ineffective. If you take heroin or a prescription opioid while on naltrexone, you won’t feel the effects.
A trial published in the New England Journal of Medicine followed people leaving the criminal justice system who had histories of opioid dependence. Those receiving monthly naltrexone injections relapsed at a rate of 43% over 24 weeks, compared to 64% for those getting standard community treatment. The median time to relapse doubled, from 5 weeks to 10.5 weeks. One important caveat: once treatment stopped, the protective effect faded. By one year after the treatment ended, opioid-negative urine rates were identical in both groups at 46%.
The biggest hurdle with naltrexone for opioid use is getting started. You must be completely opioid-free for a minimum of 7 to 10 days before your first dose. If any opioids are still in your system, naltrexone will trigger precipitated withdrawal, a rapid and intense version of withdrawal that can include dilated pupils, sweating, restlessness, severe nausea, vomiting, diarrhea, muscle aches, anxiety, and insomnia. Unlike natural withdrawal that builds gradually, precipitated withdrawal hits within minutes and can take a full day or longer to resolve.
Oral Pills vs. Monthly Injection
Naltrexone comes in two forms. The oral tablet is taken daily at 50 mg. The injectable form (sold as Vivitrol) delivers 380 mg into the muscle once every four weeks and provides 3 to 4 times the total drug exposure compared to taking the daily pill over the same period.
The injection solves one of the biggest problems with the oral version: adherence. It’s easy to skip a pill, especially on a day when cravings are strong. A monthly shot removes that daily decision. For opioid use disorder in particular, the injectable form is often preferred because a single lapse in taking the oral pill can lead to immediate relapse.
Naltrexone for Weight Management
Naltrexone is also used in a combination tablet with bupropion, sold under the brand name Contrave, for chronic weight management. The two drugs target different parts of the brain’s appetite system. Bupropion stimulates neurons in the hypothalamus that suppress appetite. Those same neurons, however, release endorphins that create a feedback loop shutting down their own appetite-suppressing activity. Naltrexone blocks that feedback loop, allowing the appetite suppression to continue working.
This combination also acts on the brain’s reward pathways that drive food cravings, particularly for calorie-dense foods. The medication is prescribed alongside diet and exercise for adults with obesity or those who are overweight with at least one weight-related health condition.
Low-Dose Naltrexone for Chronic Pain
At very low doses, typically around 4.5 mg (roughly one-tenth of the standard dose), naltrexone appears to work through an entirely different mechanism. Rather than simply blocking opioid receptors, low-dose naltrexone (LDN) targets specific immune cells in the central nervous system called microglia. When these cells become overactive, they pump out inflammatory molecules that increase pain sensitivity, fatigue, cognitive fog, sleep problems, and mood disturbances.
LDN appears to calm these immune cells, reducing central nervous system inflammation. It also suppresses inflammatory markers throughout the body. This has made it an area of interest for conditions like fibromyalgia, chronic fatigue syndrome, and certain autoimmune disorders. LDN is not FDA-approved for these uses, and the evidence base is still limited to small studies, but it has gained a following among patients and some clinicians. Side effects at this low dose tend to be minimal, with the dosage sometimes reduced to 3 mg if any issues arise.
Common Side Effects
At standard doses, the most frequently reported side effects are headache, nausea, dizziness, sleep disturbances, anxiety, diarrhea, and rash. Nausea is especially common in the first week or two and often improves as your body adjusts.
The naltrexone label includes a warning about dose-dependent liver toxicity. In practice, clinically meaningful liver enzyme elevations occur in roughly 1% of patients, and several studies have found that the rate of these elevations is similar to what’s seen with placebo. Most liver enzyme changes during treatment are mild and resolve on their own, even without stopping the medication. Still, because naltrexone is frequently prescribed to people who already have liver risk factors from heavy drinking or injection drug use, liver function is typically monitored during treatment.
Who Should Not Take Naltrexone
The most critical restriction is for anyone currently using opioids. This includes prescription painkillers, heroin, methadone, and buprenorphine. Taking naltrexone while opioids are in your system triggers precipitated withdrawal, which can be severe enough to require emergency care. The required opioid-free window is at least 7 to 10 days before starting treatment.
Precipitated withdrawal can also worsen existing psychiatric conditions like anxiety and depression, destabilize blood sugar control in people with diabetes, and spike blood pressure in those with hypertension. In rare cases, it has been associated with disorientation, hypomania, and psychosis. People with acute hepatitis or significant liver disease are also generally not candidates for naltrexone therapy.