Naltrexone shows modest benefits for nicotine cravings and smoking cessation, but the evidence is mixed and the effects appear to depend heavily on who’s taking it. In clinical trials, naltrexone improved quit rates overall compared to placebo over 12 weeks of treatment, delayed the time to a first cigarette, and reduced the number of cigarettes smoked. But the benefits were not equal across all groups, and naltrexone is not FDA-approved for smoking cessation.
How Naltrexone Works Against Nicotine
Naltrexone is an opioid receptor blocker, most commonly prescribed for alcohol use disorder and opioid dependence. Its potential role in smoking cessation comes from the way nicotine hijacks the brain’s reward system. When you smoke, nicotine triggers a release of feel-good chemicals partly through the same opioid pathways that naltrexone blocks. By sitting on those receptors, naltrexone may dampen the pleasurable “hit” you get from a cigarette, making smoking less satisfying and easier to walk away from.
This is the same basic principle behind its use in alcohol treatment: if the substance stops feeling rewarding, the drive to use it weakens over time.
What Clinical Trials Actually Show
In a 12-week trial published in the Journal of Clinical Psychopharmacology, naltrexone (50 mg daily) paired with a nicotine patch significantly improved quit rates compared to placebo. People on naltrexone also held out longer before their first cigarette, averaging 21 days versus 15 days for the placebo group. During active treatment, those taking naltrexone smoked fewer cigarettes per week.
Those are meaningful differences, but they come with an important caveat: the improvements were driven almost entirely by men. Male participants on naltrexone had a 30% quit rate compared to 17% on placebo, and they smoked roughly 32 cigarettes per week versus about 50 for men on placebo. That’s a striking reduction. Women, however, saw no benefit from naltrexone in this trial. Their quit rates were actually slightly higher on placebo (28%) than on naltrexone (20%), and their weekly cigarette counts were nearly identical in both groups.
Interestingly, at least one other study found the opposite pattern, with women responding more favorably to naltrexone than men. The inconsistency across trials suggests that sex-based differences in how naltrexone affects nicotine cravings are real but not yet well understood. Hormonal differences in the opioid system may play a role, but researchers haven’t pinned down a clear explanation.
Why It Works Better for Some People
One group that may benefit most from naltrexone during a quit attempt is people who also drink heavily. An exploratory study found that among smokers who were also heavy drinkers, naltrexone significantly reduced heavy drinking episodes and showed a trend toward higher smoking quit rates: 80% for naltrexone versus 52% for placebo. The researchers proposed that cutting back on heavy drinking removed a major trigger for smoking, creating a positive feedback loop. If alcohol is one of your primary smoking triggers, naltrexone’s dual action on both habits could be especially useful.
For people who don’t drink much or at all, the evidence for naltrexone as a standalone smoking aid is weaker. It appears to take the edge off cravings for some people, but not reliably enough to compete with first-line treatments.
Naltrexone Compared to Approved Options
The FDA has approved three types of medication for smoking cessation: nicotine replacement products (patches, gum, lozenges, inhalers, nasal spray), bupropion (Zyban), and varenicline (Chantix). Naltrexone is not on that list. Any use for nicotine cravings is off-label, meaning a doctor can prescribe it but it hasn’t met the regulatory bar for this specific purpose.
One trial tested whether adding naltrexone to varenicline would improve outcomes for heavy-drinking smokers. It backfired. At 26 weeks, the group taking varenicline alone had a 45% quit rate, while the combination group managed only 27%. The researchers described the addition of naltrexone as having an “iatrogenic effect,” meaning it actually worsened smoking outcomes. The combination did show a slight advantage for reducing alcohol consumption, but at the cost of making it harder to quit cigarettes. This is an important finding if you’re considering naltrexone alongside an existing quit-smoking medication.
Side Effects to Expect
Naltrexone’s most common side effects are nausea, headache, and joint or muscle pain. Nausea tends to be worst during the first week or two and often fades as your body adjusts. In smoking cessation trials, nausea was actually associated with better pill-taking adherence in the naltrexone group, possibly because people interpreted the side effect as a sign the medication was working.
Because naltrexone blocks opioid receptors, you cannot take opioid pain medications while using it. If you need surgery or have a condition requiring opioid-based pain relief, this is a significant consideration.
The Bottom Line on Effectiveness
Naltrexone is not a first-choice medication for nicotine cravings, and the research doesn’t support it as a reliable standalone treatment. Where it shows the most promise is in specific situations: men trying to quit smoking, smokers who also drink heavily, or people looking for an option that might address both alcohol and tobacco use at the same time. In those cases, it has shown real, measurable benefits over placebo.
If you’re interested in trying naltrexone for smoking, it would typically be used alongside nicotine replacement therapy rather than on its own. The clinical trials used a dose of 50 mg once daily combined with a nicotine patch. It should not be combined with varenicline, given the evidence that this pairing reduces quit rates. Because its use for smoking is off-label, you’ll need a prescriber who’s familiar with the research and willing to discuss whether your specific profile makes you a good candidate.