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

Naltrexone is a non-addictive medication used to block the effects of opioids and reduce cravings in individuals recovering from opioid or alcohol dependence. Available as a daily pill of 50mg or a monthly intramuscular injection of 380 mg, Naltrexone is used in many treatment plans to reduce alcohol and opioid cravings and support recovery. 

In Florida, where opioids caused 5,940 deaths in 2021, accounting for 76% of all drug-related fatalities, medications like Naltrexone are important. Naltrexone works by binding to mu-opioid receptors in the brain, stopping the dopamine surges that reinforce addiction. Side effects of Naltrexone, like nausea or fatigue, are usually mild, though some experience liver issues or injection-site reactions. 

Alternatives for Naltrexone include Acamprosate for alcohol cravings, Disulfiram to trigger aversion, or Buprenorphine for opioid withdrawal, each matched to individual recovery needs.

What Is Naltrexone?

Naltrexone, available under brand names such as Revia (oral tablet) and Vivitrol (extended-release injection), is an opioid antagonist that blocks opioid receptors in the brain, preventing the euphoric and sedative effects of opioids and alcohol. It is classified as a non-addictive medication used in medication-assisted treatment for opioid use disorder and alcohol dependence. 

Naltrexone helps reduce cravings and the risk of relapse. According to a study by the National Institute on Drug Abuse (NIDA) titled “Medications to Treat Opioid Use Disorder,” 2022, naltrexone is effective in preventing relapse, with extended-release formulations improving adherence rates in treatment programs.

What Is The Chemical Composition Of Naltrexone?

The chemical composition of naltrexone is C20H23NO4, with a molecular weight of 341.4 g/mol. Naltrexone is a synthetic opioid antagonist derived from oxymorphone and formulated as naltrexone hydrochloride to enhance solubility for oral and injectable use. 

According to a study by the National Center for Biotechnology Information (NCBI) titled “Physicochemical Properties of Naltrexone Hydrochloride,” 2021, the drug has a melting point of 168-170°C and a solubility of 50 mg/mL in water, making it suitable for extended-release formulations used in medication-assisted treatment.

How Is Naltrexone Consumed?

Naltrexone is consumed in oral tablet and intramuscular injection forms. Each form of administration is designed to improve adherence and support long-term success in medication-assisted treatment.

The forms in which naltrexone is consumed are explained below:

• Oral Tablet (ReVia): The oral tablet form is a daily medication taken at 50 mg per dose. It requires consistent adherence to maintain opioid receptor blockade. According to the National Institute on Drug Abuse (NIDA), titled “Medications for Opioid Use Disorder,” oral naltrexone is effective in preventing relapse but has lower adherence rates compared to extended-release formulations.
• Intramuscular Injection (Vivitrol): The intramuscular injection is a long-acting formulation given once every four weeks at a 380 mg dose. It provides a sustained blockade of opioid receptors, eliminating the need for daily dosing. Research from the National Institute on Drug Abuse (NIDA) states that extended-release naltrexone increases treatment retention by 30% to 40%.

What Is The Mechanism Of Action Of Naltrexone?

The mechanism of action of naltrexone is opioid receptor antagonism, which blocks the effects of opioids and alcohol by competitively binding to mu-opioid receptors. As an opioid receptor antagonist, it prevents opioids from activating reward pathways, eliminating their euphoric and sedative effects. 

For those struggling with alcohol dependence, naltrexone helps reduce cravings by influencing neurotransmitters like dopamine. The oral form has a half-life of 4 hours, while the injectable version lasts 5-10 days, offering up to 30 days of opioid blockade with extended-release options.

How Is Naltrexone Used In Addiction Treatment?

Naltrexone is used in addiction treatment programs in Florida for opioid and alcohol use disorders. It is used as part of medication-assisted treatment alongside therapy and counseling to block opioid receptors and reduce the rewarding effects of alcohol.

The uses of naltrexone in addiction treatments are as follows:

Alcohol Use Disorder

Alcohol use disorder (AUD) is a chronic condition where individuals compulsively consume alcohol despite its adverse effects. Naltrexone is commonly used to reduce cravings and prevent relapse in AUD treatment. As an opioid receptor antagonist, it blocks alcohol-induced dopamine release, making drinking less rewarding. 

In Florida, 4.2% of adults are affected by Alcohol Use Disorder, according to a report by the Substance Abuse and Mental Health Services Administration (SAMHSA), stating average prevalence during 2016 to 2019. 

Naltrexone has been shown to reduce alcohol consumption by 50% to 60% and decrease relapse rates by 40%, according to the National Institute on Alcohol Abuse and Alcoholism (NIAAA) in 2024. 

Opioid Use Disorder

Opioid use disorder (OUD) involves compulsive opioid use that leads to physical dependence and withdrawal symptoms. Naltrexone helps treat OUD by blocking opioid receptors, preventing the euphoric effects of opioids, and reducing cravings. 

In Florida, 0.9% of adults struggle with Opioid Use Disorder, according to SAMHSA. According to the National Institute on Drug Abuse (NIDA), extended-release naltrexone reduces opioid relapse rates by 65%.

Does Insurance Cover Naltrexone Treatment?

Yes, most insurance covers Naltrexone treatment in Florida. Medicaid, Medicare, and most private insurance plans like Florida Blue (Blue Cross Blue Shield of Florida), UnitedHealthcare, and Cigna, provide coverage for Naltrexone. Coverage varies based on the plan, provider network, and whether oral or injectable Naltrexone is prescribed.

What Are The Side Effects Of Naltrexone?

The side effects of naltrexone are nausea, headache, dizziness, fatigue, insomnia, vomiting, anxiety, abdominal pain, loss of appetite, and muscle cramps. While most side effects are mild and temporary, severe reactions include liver toxicity, elevated liver enzymes, severe allergic reactions, and injection site reactions in the extended-release intramuscular formulation. 

Common Side Effects Of Naltrexone

The common side effects of naltrexone are as follows:

• Nausea: Nausea occurs when the stomach is empty. Eating small meals and staying hydrated helps reduce the effects of naltrexone.
• Headache: A Headache is a temporary discomfort caused by using naltrexone from changes in brain chemistry. Drinking water and resting alleviate these symptoms.
• Dizziness: Dizziness is caused by changes in circulation and neurotransmitter activity. Standing up slowly and staying hydrated helps prevent dizziness.
• Fatigue: Fatigue is a temporary drop in energy as the body adjusts to naltrexone. Regular exercise and a healthy diet help combat fatigue in most cases.
• Insomnia: Insomnia is indicated by difficulty falling or staying asleep, especially in the first weeks of naltrexone usage. Establishing a bedtime routine and avoiding caffeine improve sleep.
• Abdominal Pain: Digestive discomfort due to mild stomach irritation is a common effect while using naltrexone. Taking naltrexone with food helps reduce discomfort in most cases.
• Muscle Cramps: Individuals on naltrexone treatment experience involuntary muscle contractions in the legs or back. Hydration, stretching, and magnesium help ease cramps.
• Injection Site Reactions: Pain, swelling, or redness at the injection site for extended-release forms of naltrexone is often reported, but applying a cold compress helps reduce inflammation instantly.

Severe Side Effects of Naltrexone

The severe side effects of naltrexone are as follows:

• Liver Toxicity: Liver damage, especially in individuals with pre-existing conditions, is one of the most common serious side effects of naltrexone. Individuals suffer from jaundice, dark urine, and abdominal pain. Regular liver function tests are necessary to monitor and treat these conditions.
• Severe Allergic Reactions: Allergic reactions include rash, swelling of the face or throat, and difficulty breathing, and require immediate medical attention.
• Injection Site Necrosis: Rare tissue damage at the injection site, causing pain or ulceration. Proper injection techniques can help prevent this.
• Depression: Some individuals experience persistent sadness or loss of interest during naltrexone treatment. Monitoring is important, especially for those with a history of mental health issues.
• Suicidal Thoughts: Suicidal thoughts occur in rare cases, and immediate medical evaluation is necessary if this develops.
• Increased Blood Pressure: Some individuals experience elevated blood pressure due to naltrexone, causing headaches or dizziness. Regular monitoring is advised.
• Hallucinations: Hallucinations are rare but serious side effects, causing confusion or distorted perceptions. Medical evaluation and discontinuation are required to evaluate and manage the symptoms.
• Respiratory Issues: Difficulty breathing or wheezing, especially in those with lung conditions. Immediate medical attention is necessary.

Does Naltrexone Make You Sleepy?

No, naltrexone does not cause sleepiness, but drowsiness and fatigue are reported in some individuals. While it does not have sedative properties, some users experience mild fatigue as their body adjusts to the medication. 

What Are The Alternatives To Naltrexone?

Alternatives to naltrexone are Buprenorphine, Methadone, Acamprosate, Disulfiram (Antabuse), Topiramate, and Gabapentin. Each has unique mechanisms of action and benefits. The choice of medication depends on individual needs, medical history, and treatment goals.

The alternatives to naltrexone are as follows:

• Buprenorphine: Buprenorphine is a partial opioid agonist that eases withdrawal and cravings without intense euphoria. Mostly combined with naloxone (Suboxone), it reduces opioid relapse by 60% to 70% according to a study by the National Institute on Drug Abuse (NIDA) titled “Medications for Opioid Use Disorder.”
• Methadone: Methadone is a full opioid agonist that prevents withdrawal and stabilizes brain chemistry. According to the National Institute on Drug Abuse (NIDA), methadone reduces opioid-related mortality by 50% and lowers illicit opioid use.
• Acamprosate: Acamprosate is a glutamate modulator that restores brain balance after alcohol dependence. Research from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) titled “Treatment of Alcohol Use Disorder,” 2023, found that acamprosate increases abstinence rates by 30% to 50% in individuals undergoing treatment for alcohol dependence.
• Disulfiram (Antabuse): Disulfiram causes nausea, flushing, and palpitations if alcohol is consumed. Works as an aversion therapy. According to the National Center for Biotechnology Information (NCBI), titled “Pharmacological Interventions for Alcohol Use Disorder,” 2011, disulfiram reduces drinking frequency by 40% to 50% when used in supervised treatment programs.
• Topiramate: Topiramate is an anti-epileptic that affects GABA and glutamate to reduce binge drinking. According to a study by NCBI titled “Neuroscientific Basis of Treatment for Substance Use Disorders,” 2022, topiramate reduces heavy drinking episodes by 20% to 30%.
• Gabapentin: Gabapentin is a neuromodulator that helps with alcohol withdrawal and relapse prevention. A study by NCBI titled “Alcohol Use Disorder and Pharmacological Treatments,” 2016, found that gabapentin reduces alcohol cravings by 30% to 40% and helps manage withdrawal-related anxiety.

Can You Take Disulfiram And Naltrexone Together?

Yes, you can take disulfiram and naltrexone together, but this combination should be used with caution and under medical supervision. Disulfiram works by causing severe reactions to alcohol consumption, while naltrexone reduces alcohol cravings and blocks its euphoric effects. 

When combined, they improve treatment adherence for individuals with alcohol use disorder, but the risk of side effects, including liver toxicity and increased depressive symptoms, is higher. 

Can You Take Acamprosate And Naltrexone Together?

Yes, you can take acamprosate and naltrexone together, as they target different aspects of alcohol use disorder and enhance treatment effectiveness. Naltrexone blocks opioid receptors to reduce alcohol’s euphoric effects, while acamprosate modulates glutamate neurotransmission, stabilizing brain chemistry altered by chronic alcohol use. 

A 2023 NIAAA study titled “Treatment of Alcohol Use Disorder” found that combining acamprosate and naltrexone increases alcohol-free days by up to 30% compared to using either alone.

How Does Naltrexone Work For Alcohol Addiction Treatment in Florida?

Naltrexone works for alcohol addiction treatment by blocking opioid receptors, reducing alcohol’s rewarding effects, and decreasing cravings. It prevents the release of dopamine triggered by alcohol consumption, making drinking less pleasurable. This process helps individuals undergoing alcohol addiction treatment control alcohol intake and supports relapse prevention. 

Who Should Avoid Taking Naltrexone?

Those who should avoid taking naltrexone have conditions like current opioid use, liver disease, pregnancy and breastfeeding, severe kidney disease, active alcohol use in an extended-release form, severe depression, or suicidal thoughts. Since naltrexone is not suitable for everyone, certain individuals should avoid its use due to potential health risks and adverse reactions. 

Those who should avoid taking naltrexone have the following conditions:

• Current Opioid Use: Naltrexone triggers sudden withdrawal if opioids are still in the system. It should only be started after 7 to 10 days opioid-free. The FDA states detox is mandatory before treatment.
• Liver Disease: Naltrexone worsens liver conditions like hepatitis or cirrhosis. It raises liver enzymes in 5% to 10% of users, according to the National Center for Biotechnology Information (NCBI). Liver function tests are required before and during naltrexone treatment.
• Pregnancy and Breastfeeding: Naltrexone is classified as an FDA Pregnancy Category C drug, meaning there is insufficient human data to confirm safety during pregnancy. Animal studies suggest potential fetal risks, and they pass into breast milk. 
• Severe Kidney Disease: Since naltrexone and its metabolites are excreted through the kidneys, individuals with renal impairment experience delayed drug clearance, increasing the risk of drug accumulation and toxicity.
• Active Alcohol Use in Extended-Release Form: The extended-release intramuscular injection (Vivitrol) should be used cautiously in individuals who continue to drink alcohol, as it increases the risk of liver toxicity and psychiatric side effects.
• Severe Depression or Suicidal Thoughts: Naltrexone has been associated with increased depressive symptoms in some individuals. Those with a history of severe depression or suicidal ideation must be closely monitored for mood changes during treatment.

Is Naltrexone A Controlled Substance?

No, naltrexone is not a controlled substance because it does not produce euphoria, physical dependence, or addiction. As an opioid receptor antagonist, it blocks the effects of opioids and alcohol without activating reward pathways in the brain.]

Do You Need A Prescription For Naltrexone in Florida?

Yes, you need a doctor’s prescription for naltrexone in Florida. Because it is a prescription-only medication regulated by healthcare authorities, it must be obtained through a licensed healthcare provider who assesses the patient’s medical history and ensures opioid detoxification before initiating treatment. 

Can You Overdose On Naltrexone?

No, you cannot overdose on naltrexone in the same way as opioids or other depressants because it does not cause respiratory depression or sedation. However, taking excessive doses leads to liver toxicity, nausea, vomiting, and dizziness. 

Can You Stop Taking Naltrexone Suddenly?

Yes, you can stop taking naltrexone suddenly because it does not cause withdrawal or physical dependence. However, discontinuing it increases relapse risk, as opioid and alcohol cravings return without receptor blockade. 

How Long Does Naltrexone Stay In Your System?

Naltrexone stays in your system for 4 to 6 hours after an oral dose and 5 to 10 days after an extended-release injection due to its longer half-life. It is detected in urine for up to 24 hours, blood for 24-48 hours, saliva for up to 12 hours, and hair for up to 90 days. Detection varies based on dosage, metabolism, and test sensitivity.