Naltrexone is a medication with two FDA-approved uses: treating alcohol dependence and blocking the effects of opioids. It works by attaching to the same receptors in the brain that opioids target, effectively shutting down the rewarding “buzz” that alcohol and opioids produce. Beyond these approved uses, lower doses of naltrexone have gained attention for managing chronic pain and inflammatory conditions, though that use remains off-label.
How Naltrexone Works in the Brain
When you drink alcohol or take opioids, your brain releases its own natural opioid-like chemicals. These chemicals trigger a surge of dopamine in your brain’s reward center, creating feelings of pleasure and reinforcing the behavior. Naltrexone blocks the receptors those chemicals latch onto, primarily a type called the mu-opioid receptor. At the standard 50 mg daily dose, it blocks roughly 90% of those receptors.
The practical result: alcohol and opioids simply don’t feel as rewarding. People on naltrexone often describe drinking as less satisfying, which makes it easier to stop after one drink or avoid drinking altogether. For someone recovering from opioid addiction, naltrexone prevents any high from occurring if they relapse.
Alcohol Dependence
Naltrexone is one of the most widely studied medications for alcohol use disorder. In a meta-analysis of randomized controlled trials, people taking naltrexone had a 14% lower relapse rate and a 10% higher abstinence rate compared to those on placebo after 12 weeks of treatment. Naltrexone-treated patients also drank about one fewer standard drink per drinking day.
Those numbers may sound modest, but in addiction treatment, even small reductions in heavy drinking days translate into meaningful improvements in liver health, relationships, and daily functioning. Naltrexone works best as part of a broader plan that includes counseling or behavioral support. The FDA label for the oral form (sold as ReVia) states explicitly that it hasn’t been shown to provide benefit on its own, without a management plan around it.
When compared to acamprosate, the other major medication for alcohol relapse prevention, naltrexone showed a slight edge in delaying both the first drink and full relapse in a head-to-head trial. Combining the two medications produced the lowest relapse rates overall, significantly better than placebo or acamprosate alone.
Opioid Use Disorder
For opioid addiction, naltrexone serves as a relapse prevention tool after someone has already gone through detox. Unlike methadone or buprenorphine, which activate opioid receptors at low levels to reduce cravings, naltrexone blocks those receptors entirely. This means it doesn’t carry any risk of dependence itself, but it also means you must be completely free of opioids before starting it.
That opioid-free requirement is the biggest practical hurdle. You need to wait at least 7 days after your last use of short-acting opioids (like heroin or oxycodone) and 10 to 14 days after long-acting opioids (like methadone). Starting too early triggers precipitated withdrawal, a sudden and intense version of withdrawal symptoms that can be severe. The standard initiation process for the injectable form takes 12 to 14 days, though newer rapid-start protocols have shown promise, with about 63% of patients successfully starting treatment compared to 36% with the standard approach.
Naltrexone for opioid use disorder comes in two forms: a daily 50 mg pill and a monthly 380 mg injection given in a clinic. The injectable version, sold as Vivitrol, removes the daily decision to take a pill, which can be a significant advantage for people early in recovery.
Weight Management
Naltrexone is also part of an FDA-approved weight loss combination sold under the brand name Contrave. This pairs naltrexone with bupropion, an antidepressant that also reduces appetite. The two drugs work on overlapping brain pathways: bupropion stimulates appetite-suppressing signals, while naltrexone blocks a feedback loop that would normally shut those signals down. Together, they produce a stronger and more sustained effect on hunger and cravings for food than either drug alone.
Low-Dose Naltrexone for Chronic Pain
At much lower doses, typically 0.5 to 4.5 mg daily (compared to the standard 50 mg), naltrexone appears to work in a fundamentally different way. Rather than blocking opioid receptors around the clock, these tiny doses are thought to briefly nudge the immune system and reduce inflammation. This use is entirely off-label, meaning the FDA hasn’t approved it for these conditions, but clinical interest has grown substantially.
Low-dose naltrexone (often called LDN) has been studied in fibromyalgia, neuropathic pain, complex regional pain syndrome, chronic pelvic pain, and headache disorders. It has also been investigated in inflammatory and immune-related conditions like inflammatory bowel disease, multiple sclerosis, and rheumatoid arthritis. Most studies showing benefit used doses between 3.0 and 4.5 mg daily, and treatment typically starts at 0.5 to 1.5 mg with gradual increases. Some people with sensitivity to neuropsychiatric side effects respond better at the lower end of that range.
The evidence for LDN is still early stage, mostly from small trials and case series rather than large definitive studies. But the low side effect profile and low cost have made it an attractive option for patients and clinicians looking for alternatives, particularly for conditions where standard treatments have fallen short.
Common Side Effects
At the standard dose, the most frequently reported side effects are nausea, headache, dizziness, and fatigue. Stomach-related symptoms like cramping, vomiting, diarrhea, or constipation are also common, especially in the first few weeks. Many of these improve as your body adjusts. Anxiety, irritability, difficulty sleeping, and joint or muscle pain have also been reported.
More serious but less common reactions include confusion, hallucinations, and blurred vision. The most significant safety concern is liver toxicity at high doses. Signs to watch for include unusual tiredness, pain in the upper right side of your abdomen lasting more than a few days, dark urine, or yellowing of the skin or eyes. Naltrexone is generally considered acceptable for people with compensated liver disease under close monitoring, but it should be avoided in people with severe liver impairment.
Important Safety Considerations
The single most critical thing to understand about naltrexone is that it blocks opioids completely. If you’re taking naltrexone and attempt to override the blockade by using large amounts of opioids, you risk a fatal overdose. Your tolerance drops while on naltrexone, so doses that might not have been dangerous before could become lethal, particularly if you stop taking naltrexone and relapse.
You should also carry information noting that you take naltrexone. In an emergency where you need pain relief, standard opioid painkillers won’t work effectively, and medical teams need to know this to choose appropriate alternatives. This applies to planned surgeries as well, where naltrexone typically needs to be stopped in advance.