Naltrexone’s most common side effect is nausea, affecting about 10% of people who take it. Headache (7%), dizziness (4%), and fatigue (4%) round out the most frequently reported issues, based on an FDA safety study of roughly 570 people taking the oral form for alcohol dependence. Most of these effects are mild and tend to ease as your body adjusts to the medication over the first few weeks.
Digestive Side Effects
Nausea is the side effect people notice first and complain about most. It can come with vomiting and stomach pain, especially in the early days of treatment. Starting naltrexone before your body has fully cleared alcohol or opioids makes these symptoms worse, which is why providers typically wait until detox is complete before prescribing it.
For most people, the stomach-related discomfort is worst in the first week and gradually fades. Taking the pill with food can help blunt the nausea. If digestive symptoms persist beyond the first couple of weeks, that’s worth raising with your prescriber, since adjusting the dose or timing sometimes makes a difference.
Mood and Emotional Changes
Naltrexone works by blocking opioid receptors in the brain, which are involved in how you experience pleasure and reward. This has raised understandable concern about whether the drug causes depression or emotional flatness. The evidence is more reassuring than you might expect.
In controlled trials of people being treated for alcohol dependence, naltrexone did not increase rates of depression compared to placebo. There have been occasional reports of dysphoria (a general sense of unease or dissatisfaction) in healthy volunteers and former opioid users, but these appear to be uncommon. One placebo-controlled study lasting eight weeks found no overall increase in mood disturbance among healthy subjects on naltrexone, though one participant had to leave due to severe dysphoria.
Some people describe feeling emotionally “blunted,” as if positive experiences don’t hit quite as hard. This makes biological sense given how the drug interacts with your brain’s reward system. It’s not the same as clinical depression, but it can feel unsettling if you’re not expecting it.
Liver Safety
Naltrexone carries a warning about potential liver injury. Cases of hepatitis and significant liver dysfunction have been observed both in clinical trials and in post-marketing reports. More commonly, people experience transient, symptom-free elevations in liver enzymes that resolve on their own.
Your provider will likely check your liver function with blood tests before starting naltrexone and periodically during treatment. Signs of liver trouble to watch for include unusual fatigue, yellowing of the skin or eyes, dark urine, or pain in the upper right side of your abdomen.
Injection Site Reactions With Vivitrol
The injectable form of naltrexone (sold as Vivitrol) is given once a month as a shot in the gluteal muscle. Pain, tenderness, swelling, and bruising at the injection site are common and expected. What’s less expected is how severe these reactions can occasionally become.
In clinical trials, one patient developed a hardened area that kept growing for four weeks and eventually turned into dead tissue requiring surgical removal. Post-marketing reports have documented additional cases of cellulitis, abscesses, and tissue death at injection sites, some requiring surgical cleanup and resulting in significant scarring. These severe outcomes are rare, but they’re more likely if the injection accidentally goes into the fat layer beneath the skin rather than into the muscle.
If redness, swelling, or pain at the injection site keeps getting worse rather than improving over the days following a shot, that needs prompt medical attention.
Vivid Dreams With Low-Dose Naltrexone
Low-dose naltrexone (LDN), typically used off-label at a fraction of the standard dose, has a distinctive side effect profile. The most talked-about effect is unusually vivid dreaming. This happens because naltrexone influences dopamine and your body’s natural opioid system, which in turn affects serotonin. All three of these chemical messengers play roles in how your brain generates dream content during REM sleep.
Higher serotonin activity stimulates visual pathways during sleep, while dopamine appears to fuel the hallucinatory quality of dreams. LDN may also deepen and lengthen REM sleep cycles, which means you’re spending more time in the dream-rich phase of sleep. If you wake up during one of these deeper REM periods (say, from an alarm), you’re more likely to remember a vivid dream. For most people, this is more unusual than unpleasant, and some consider it a sign of improved sleep quality.
Sexual Function Effects
Naltrexone’s effect on sexual function runs counter to what many medications do. Rather than suppressing libido or performance, it appears to enhance certain aspects of sexual response. In a randomized, double-blind study of 20 healthy men aged 20 to 29, those taking naltrexone experienced significantly more orgasms (an average of 3.4 versus 2.6 on placebo) and rated both arousal and orgasmic intensity higher.
Separate research in middle-aged men with unexplained erectile difficulties found that six out of seven reported restored erectile function after starting naltrexone, along with improved nocturnal erections. The likely explanation is that your body’s natural opioids normally put a brake on certain sexual responses, and blocking those opioids with naltrexone releases that brake. This is generally experienced as a positive effect rather than a problem, though some people find the change surprising.
Precipitated Withdrawal
This isn’t a side effect in the traditional sense, but it’s the most dangerous thing that can happen with naltrexone. If you take naltrexone while opioids are still active in your system, it can trigger sudden, severe withdrawal within minutes. Because naltrexone rips opioids off the brain’s receptors all at once, the resulting withdrawal is far more intense than the gradual withdrawal that happens when you simply stop taking opioids.
Symptoms include agitation, confusion, dilated pupils, profuse sweating, and dangerous spikes in blood pressure. Published case reports describe patients requiring intensive care monitoring after precipitated withdrawal, including one who developed a hypertensive emergency needing continuous IV treatment. The injectable form poses an even greater risk because it can’t be removed once administered, meaning the withdrawal can persist for days or weeks rather than hours.
This is why providers require a period of opioid abstinence, typically 7 to 14 days depending on the opioid, before starting naltrexone. A urine drug screen is standard before the first dose to confirm opioids have cleared your system.