Is Naltrexone a Controlled Drug? A Pharmacological Overview

In 2023, an estimated 28.9 million people aged 12 or older in the U.S. had an alcohol use disorder (AUD) [1.7.1]. For those seeking treatment, a common question arises: Is naltrexone a controlled drug? The answer is no, it is not a controlled substance [1.2.1].

Quick Summary

Naltrexone is not a controlled drug because it has no potential for abuse or addiction [1.2.1, 1.2.3]. It functions as an opioid antagonist, blocking the euphoric effects of alcohol and opioids to aid in treating substance use disorders [1.3.1].

Key Points

• Not a Controlled Substance: Naltrexone is not a controlled drug under the DEA because it is a non-addictive opioid antagonist with no abuse potential [1.2.1, 1.2.3].

• Blocks Euphoria: It works by blocking opioid receptors in the brain, which prevents the user from feeling the euphoric effects of opioids and alcohol [1.3.1].

• Dual FDA Approval: Naltrexone is FDA-approved to treat both Alcohol Use Disorder (AUD) and to prevent relapse in Opioid Use Disorder (OUD) [1.4.5].

• Opioid-Free Period is Mandatory: Patients must be free from short-acting opioids for 7-10 days before starting naltrexone to avoid severe precipitated withdrawal symptoms [1.4.1].

• Oral and Injectable Forms: It is available as a daily oral pill (e.g., ReVia) and a once-monthly injection (Vivitrol), which can improve adherence [1.4.2].

• Lower Overdose Risk During Treatment: By blocking opioid effects, it reduces the risk of overdose from typical opioid use, but risk increases significantly after treatment stops [1.6.1].

• Accessible Prescription: Unlike methadone, any licensed healthcare provider can prescribe naltrexone, increasing its accessibility for patients [1.2.1].

Understanding Naltrexone's Classification

One of the most critical questions for patients and providers is about the legal and pharmacological status of naltrexone. According to the U.S. Drug Enforcement Agency (DEA), naltrexone is not classified as a controlled substance [1.2.1]. This is because it is a full opioid antagonist, which means it blocks the euphoric effects or "high" associated with opioids and alcohol [1.2.1, 1.3.3]. Unlike opioid agonists or partial agonists, it does not activate opioid receptors and therefore has no potential for abuse, dependence, or addiction [1.2.3, 1.3.1]. Because it is not a controlled substance, any physician or licensed provider can prescribe it without special waivers, making it more accessible than medications like methadone [1.2.1, 1.2.5].

The Pharmacology of an Opioid Antagonist

Naltrexone's mechanism of action is central to its non-controlled status. It is a competitive antagonist at opioid receptors, primarily the mu-opioid receptor, but also the kappa and delta receptors to a lesser extent [1.3.2, 1.3.3].

• For Opioid Use Disorder (OUD): When a person takes naltrexone, it occupies the opioid receptors in the brain. If they then use an opioid like heroin or oxycodone, the opioid cannot bind to these receptors, and its euphoric effects are blocked [1.3.1]. This reduces cravings and helps prevent relapse [1.3.1].
• For Alcohol Use Disorder (AUD): The rewarding effects of alcohol are partly mediated by the body's own endogenous opioids (endorphins) [1.3.3]. Naltrexone blocks these same receptors, which dampens the pleasurable feelings associated with drinking alcohol. This action reduces the urge to drink and helps people maintain sobriety or reduce their alcohol consumption [1.3.1, 1.4.1].

FDA-Approved Uses for Naltrexone

Naltrexone is a versatile medication approved by the Food and Drug Administration (FDA) for treating two primary conditions as part of a comprehensive treatment plan that includes counseling [1.4.1, 1.4.5].

1. Alcohol Use Disorder (AUD): Both oral tablets and the extended-release injection are approved for AUD. It helps reduce heavy drinking days and supports abstinence by making alcohol consumption less rewarding [1.3.1, 1.7.2].
2. Opioid Use Disorder (OUD): It is used for the prevention of relapse to opioid dependence following detoxification [1.4.4]. A critical requirement is that patients must be completely free of opioids for at least 7 to 10 days before starting naltrexone to avoid precipitating a severe withdrawal syndrome [1.4.1].

Forms of Naltrexone: Oral vs. Injectable

Naltrexone is available in two main forms:

• Oral Naltrexone (e.g., ReVia): This is a tablet typically taken once daily [1.4.2]. Its effectiveness can be limited by the need for daily adherence; forgetting a dose can increase relapse risk [1.5.3, 1.10.2].
• Injectable Extended-Release Naltrexone (Vivitrol): This is administered as an intramuscular injection in the gluteal muscle once a month (every four weeks) by a healthcare professional [1.3.2, 1.4.2]. This form eliminates the need for daily pills, which can significantly improve medication adherence and treatment retention [1.4.5, 1.10.2].

Naltrexone vs. Other MAT Medications: A Comparison

Medication-Assisted Treatment (MAT) for OUD often involves naltrexone, buprenorphine, or methadone. They differ significantly in their classification and mechanism.

Feature	Naltrexone	Buprenorphine	Methadone
Controlled Status	No, not a controlled substance [1.2.2].	Yes, Schedule III controlled substance.	Yes, Schedule II controlled substance [1.2.2].
Mechanism	Opioid Antagonist (blocks receptors) [1.2.2].	Partial Opioid Agonist (activates receptors partially) [1.2.2].	Full Opioid Agonist (fully activates receptors).
Abuse Potential	None. It is not addictive [1.3.1].	Lower than full agonists, but potential exists.	High. Can produce euphoria and dependence.
Administration	Oral pill or monthly injection by any licensed prescriber [1.2.1].	Sublingual film or tablet, often from specially certified prescribers.	Dispensed daily at specialized opioid treatment programs (OTPs).
For Use In	Patients who are fully detoxified from opioids (7-10 days opioid-free) [1.4.1].	Patients in moderate withdrawal or for maintenance.	Patients in any stage of withdrawal or for maintenance [1.5.3].

Key Safety Information and Side Effects

The most critical safety warning for naltrexone is that it must not be started in individuals who are currently physically dependent on opioids [1.6.1]. Taking naltrexone while opioids are still in the system will trigger precipitated withdrawal, a rapid and severe onset of withdrawal symptoms including agitation, vomiting, diarrhea, and muscle pain [1.9.1, 1.9.3].

Common Side Effects Include:

• Nausea, vomiting, or diarrhea [1.6.5]
• Headache [1.6.5]
• Dizziness [1.8.2]
• Fatigue or trouble sleeping [1.6.5]
• Anxiety [1.8.2]
• Muscle or joint pain [1.6.5]
• Injection site reactions for Vivitrol (pain, swelling, redness) [1.6.2]

Serious Risks:

• Liver Damage: While the risk is low at recommended doses, naltrexone carries a warning for hepatotoxicity, especially at very high doses. Your doctor may monitor liver function [1.11.1, 1.11.2].
• Overdose Risk After Treatment: After stopping naltrexone, a person's tolerance to opioids will be reduced. Relapsing and using the same amount of opioids as before treatment can lead to a fatal overdose [1.3.1, 1.6.1].
• Depression or Suicidal Thoughts: Mood changes can occur, and it's important to report any new or worsening depression to a healthcare provider [1.6.2].

Conclusion

To directly answer the question: Is naltrexone a controlled drug? No, it is not. Its status as a non-addictive, non-narcotic opioid antagonist makes it a distinct and accessible option in the treatment of Alcohol and Opioid Use Disorders [1.2.3]. It works by blocking the pleasurable effects of these substances, thereby reducing cravings and supporting recovery. When used correctly as part of a comprehensive treatment program, and with careful attention to the mandatory opioid-free period before initiation, naltrexone is a safe and effective tool for many individuals on their path to recovery.

For more information, a valuable resource is the Substance Abuse and Mental Health Services Administration (SAMHSA).

Frequently Asked Questions

Is naltrexone addictive?

No, naltrexone is not addictive. It is an opioid antagonist and does not produce any euphoric effects, physical dependence, or withdrawal symptoms upon stopping [1.8.3].

What happens if you drink alcohol while taking naltrexone?

Naltrexone reduces the pleasurable and rewarding effects of alcohol, which typically diminishes the desire to keep drinking. However, it does not prevent the intoxicating effects like impaired judgment and coordination [1.8.3].

What happens if you use opioids while on naltrexone?

Naltrexone blocks the euphoric effects of opioids, so you will not feel the 'high' [1.8.3]. Attempting to override this blockade by taking large amounts of opioids is extremely dangerous and can lead to serious injury, coma, or a fatal overdose [1.6.1].

How long do you need to be opioid-free before starting naltrexone?

You must be free of short-acting opioids (like heroin and oxycodone) for at least 7 to 10 days and long-acting opioids (like methadone) for 10 to 14 days before starting naltrexone to prevent precipitated withdrawal [1.3.1, 1.8.3].

Can I get naltrexone over the counter?

No, naltrexone is not an over-the-counter medication. It requires a prescription from a licensed healthcare provider [1.2.3].

What is the difference between naltrexone and naloxone (Narcan)?

Naltrexone is a medication used for long-term treatment to prevent relapse in alcohol and opioid use disorders. Naloxone (Narcan) is a fast-acting antagonist used in emergency situations to rapidly reverse an opioid overdose [1.2.3].

Can naltrexone cause liver damage?

Naltrexone has a warning for potential liver damage, particularly at doses higher than recommended. However, at standard therapeutic doses, the risk of serious liver problems is considered low. Your doctor may perform liver function tests before and during treatment [1.11.1, 1.11.2].