Naltrexone: Definition, Mechanism of Action, Uses, Dosage, Side Effects, Alternatives

If you or someone you love is battling opioid or alcohol addiction, finding a treatment that actually helps you stay sober is life-changing. Naltrexone is a non-addictive medication that blocks the brain’s reward response to alcohol and opioids, helping reduce cravings and lower the risk of relapse. It’s especially effective after detox when paired with therapy and structured support.

According to the North Carolina Department of Health and Human Services, over 4,000 overdose deaths occurred in the state in 2021, the highest on record, driven primarily by opioids. Medications like naltrexone are necessary tools in preventing relapse and saving lives.

Taken daily by pill or monthly by injection, naltrexone supports long-term recovery without the risk of dependence. Side effects are typically mild but include nausea or headache. For others, medications like buprenorphine, methadone, or acamprosate may be recommended based on personal needs and treatment goals. Used properly, naltrexone is one of the most effective tools in preventing relapse and reducing overdose risk.

What Is Naltrexone?

Naltrexone is a non-addictive prescription medication classified as an opioid antagonist. It works by blocking opioid receptors in the brain, preventing substances like opioids and alcohol from producing euphoric effects. Naltrexone reduces the risk of returning to heavy drinking by 17% compared to placebo (relative risk = 0.83; 95% CI, 0.76 to 0.90) according to Yancey, J. “Opioid Antagonists for the Treatment of Alcohol Dependence” published by the American Family Physician.

Common brand names include ReVia, Depade, and the extended-release injectable version, Vivitrol. Naltrexone is widely used in medication-assisted treatment (MAT) for individuals with alcohol dependence and opioid use disorder. Unlike opioid-based treatments, naltrexone does not cause physical dependence or lead to misuse, making it a reliable option for those seeking long-term recovery support.

What Is the Mechanism of Action of Naltrexone?

The mechanism of action of Naltrexone binds primarily to mu-opioid receptors in the brain to block the effects of opioids. This blockade prevents opioids from activating the brain’s reward system, reducing reinforcement and the urge to use. Naltrexone also influences neurotransmitter regulation by dampening dopamine release, which plays a central role in the cycle of addiction and cravings. Its oral formulation has a bioavailability of approximately 5-40%, while the extended-release injection provides steady plasma levels over time. The oral form has a half-life of about 4 hours, while its active metabolite, 6-β-naltrexol, has a half-life of 13 hours, resulting in extended receptor blockade that supports relapse prevention.

What is Naltrexone Used for in Addiction Treatment in North Carolina?

Naltrexone is primarily used in the treatment of opioid addiction and alcohol use disorder in North Carolina as part of medication-assisted treatment. It supports relapse prevention by eliminating the pleasurable effects of alcohol and opioids, helping patients remain abstinent. Individuals with opioid use disorder who receive extended-release naltrexone are less likely to relapse when actively engaged in therapy. In alcohol use disorder, naltrexone has been shown to significantly reduce cravings and drinking frequency, especially when combined with behavioral interventions. 

According to the Substance Abuse and Mental Health Services Administration (SAMHSA), between 2017 and 2019, approximately 4.7% of individuals aged 12 or older in North Carolina, about 405,000 people, experienced alcohol use disorder in the past year. By targeting the biological and psychological components of addiction, naltrexone strengthens recovery outcomes during addiction treatment across both substance categories.

How Is Naltrexone Consumed?

Naltrexone is consumed as a daily oral tablet or as a long-acting monthly injection, depending on individual needs and treatment plans. The oral tablet, commonly sold under the brand name ReVia, is typically taken once per day. The injectable form, Vivitrol, is administered as an intramuscular injection once every four weeks by a healthcare professional. Consistent adherence is crucial to ensure the medication’s effectiveness in reducing cravings and preventing relapse.

• Oral Tablet: Taken once daily at a dose of 50 mg, usually at the same time each day.

• Intramuscular Injection: Administered by a provider every 4 weeks (380 mg per dose).

• Adherence Requirements: Daily use or timely monthly injections are essential for optimal results.

What Are the Side Effects of Naltrexone?

The side effects of naltrexone are mild and include nausea, headache, and fatigue. Naltrexone is generally well tolerated, but like all medications, it does have side effects. Most side effects are mild and decrease over time, though some people experience more serious reactions. 

The side effects of Naltrexone include:

Common Side Effects (≥10% of users):

• Headache

• Nausea and/or vomiting

• Abdominal pain or cramps

• Anxiety or nervousness

• Difficulty sleeping (insomnia)

• Low energy or fatigue

• Joint and muscle pain​

Less Common Side Effects (<10% of users):

• Loss of appetite

• Diarrhea or constipation

• Increased thirst

• Increased energy

• Feeling down or a depressed mood

• Irritability

• Dizziness

• Skin rash

• Delayed ejaculation or decreased sexual potency

• Chills​

Can You Use Naltrexone Long-Term?

Yes, naltrexone can be used long-term. It is generally considered safe for extended use in treating alcohol or opioid use disorders. However, regular monitoring of liver function is recommended, especially with oral formulations, as the drug is processed by the liver. Long-term studies have supported its safety and effectiveness in maintaining recovery.

What Happens if You Stop Naltrexone Suddenly?

Stopping naltrexone does not lead to withdrawal symptoms. However, it increases the risk of relapse because the medication no longer blocks the euphoric effects of opioids or alcohol. For this reason, discontinuing naltrexone should be done under medical guidance to ensure continued support and safety.

Are There Alternatives to Naltrexone for Addiction?

Yes, there are several alternatives to naltrexone for treating opioid and alcohol use disorders.  For opioid use disorder, buprenorphine or methadone are alternatives that are associated with significantly longer treatment retention and lower rates of overdose compared to naltrexone; for example, the average treatment duration was 149.7 days for buprenorphine/methadone versus 74.4 days for naltrexone, and long-term use of buprenorphine/methadone resulted in a 76% reduction in overdose at 3 months according to “Comparative Effectiveness of Different Treatment Pathways for Opioid Use Disorder” published by the JAMA Network. 

The medications that are alternatives to Naltrexone for addiction:

• Buprenorphine: A partial opioid agonist used for opioid use disorder; it reduces cravings and withdrawal symptoms with a lower risk of misuse.

• Methadone: A full opioid agonist that prevents withdrawal and reduces cravings in opioid-dependent individuals; highly regulated and effective for long-term treatment.

• Acamprosate: Used for alcohol use disorder; helps restore chemical balance in the brain and supports abstinence by reducing post-acute withdrawal symptoms.

• Disulfiram (Antabuse): Creates an aversive reaction when alcohol is consumed, discouraging drinking through negative reinforcement. Disulfiram is another alternative and, in supervised settings, has been found to be superior to naltrexone in preventing relapse among alcohol-dependent men with family support, 86% remained abstinent for a year on disulfiram versus 44% on naltrexone in one study according to De Sousa, A. et. al. in “A one-year trial of naltrexone vs disulfiram in alcohol treatment”.

• Topiramate: An anticonvulsant that reduces alcohol cravings and promotes abstinence, though not FDA-approved specifically for alcohol use disorder.

• Gabapentin: Originally for seizures and nerve pain, it has shown promise in reducing alcohol cravings and improving sleep and anxiety in early recovery.

How Does Naltrexone Differ from Buprenorphine and Methadone for Opioid Use Disorder?

Naltrexone differs from buprenorphine and methadone in how they work and whom they benefit; however, all are used to treat opioid use disorder.

Here is a table highlighting the differences between Naltrexone, Buprenorphine, and methadone:

Who Should Avoid Taking Naltrexone?

The people who should avoid taking Naltrexone include people taking opioids, people with hepatitis, liver failure, pregnant women, and those who are allergic. 

The following people should avoid naltrexone:

• Individuals Currently Using Opioids: Taking naltrexone while opioids are still in the system leads to precipitated withdrawal, a rapid and severe onset of withdrawal symptoms.

• People with Acute Hepatitis or Liver Failure: Naltrexone is processed by the liver, so those with serious liver disease should not use it due to the risk of hepatotoxicity.

• Pregnant Individuals: Naltrexone use during pregnancy is not well studied; it should only be used if clearly needed and prescribed by a physician.

• People Allergic to Naltrexone: Those with a known hypersensitivity to naltrexone or any of its components should avoid the medication.

Can You Use Naltrexone if You Have Opioid Use Disorder?

Yes, you can use naltrexone if you have opioid use disorder, but only after completing opioid detoxification. Taking naltrexone with opioid use disorder or while opioids are still present in the body causes precipitated withdrawal by displacing opioids from the brain’s opioid receptors. This is why individuals must be opioid-free for at least 7–10 days before starting treatment with naltrexone. As of July 2023, an estimated 2.48% of individuals aged 12 and older in North Carolina, approximately 231,113 people, were reported to have an opioid use disorder according to the NC DHHS, showing an imperative need for quality treatment options. Natrexone saves lives and is an important tool for those struggling. 

Can You Drink Alcohol While on Naltrexone?

Yes, you can drink alcohol while on naltrexone because the medication does not cause illness upon alcohol consumption, unlike disulfiram. Instead, naltrexone reduces the rewarding effects of alcohol, helping to decrease cravings and the desire to drink. This makes it easier for individuals to reduce or abstain from alcohol use over time. In 2021, over 6,300 deaths in North Carolina were attributed to excessive alcohol use, making it the third leading preventable cause of death in the state according to the NC DHHS. Thus showing the significant need for medications that help with alcohol abuse.

Do You Need a Prescription for Naltrexone in North Carolina?

Yes, you need a doctor’s prescription for Naltrexone in North Carolina. It is a prescription-only medication and must be prescribed by a licensed healthcare provider to ensure proper usage, dosage, and monitoring.

How Long Does Naltrexone Stay in Your System?

Naltrexone stays in your system for 24 hours to weeks. It has a half-life of 4–6 hours for the oral form and 5–10 days for the extended-release injectable (Vivitrol).

It is typically detectable in:

• Urine: up to 6 days (oral), longer for injection

• Blood: up to 24 hours (oral), 2–4 weeks (injection)

• Saliva: limited data

• Hair: potentially up to 90 days

Does Naltrexone Work for Alcohol Addiction?

Yes, Naltrexone works for alcohol addiction by blocking opioid receptors in the brain, which reduces the pleasurable effects of alcohol and helps decrease cravings. It supports long-term recovery from alcohol addiction by reducing the risk of relapse.

How Soon After Stopping Opioids Can I Start Naltrexone?

After stopping opioids, you can start naltrexone 7 to 10 days, depending on the type and amount used. Starting too soon causes precipitated withdrawal, so detoxification must be confirmed before beginning treatment.

Can I Take Naltrexone While on Suboxone or Methadone?

No, you cannot take Naltrexone while on Suboxone or Methadone. Naltrexone blocks opioid receptors and triggers precipitated withdrawal if taken with Suboxone (buprenorphine) or methadone, which are opioid-based treatments. You must fully detox from these medications before using naltrexone.

Can Naltrexone Be Taken with Benzodiazepines?

Yes, Naltrexone can be taken with benzodiazepines, but with caution. Naltrexone does not directly interact with benzodiazepines, but combining it with other sedatives should be monitored by a healthcare provider to manage risks related to sedation or mental health.