What is the mechanism of action for naltrexone?

Naltrexone is a pure opiate receptor antagonist and works by primarily binding at the mu opioid receptors. By binding to these receptors, it blocks the euphoric (pleasurable or "high") effects linked with alcohol use or opioids. Naltrexone itself has little or no effect in the absence of alcohol or opiates.

It is not addictive and does not cause withdrawal symptoms when used in people not physically dependent on opioids or alcohol.

Learn more: Is naltrexone a controlled substance?

Naltrexone (and its active metabolite 6-beta-naltrexol) are competitive antagonists to the mu opioid receptors, but also have action at the kappa and delta receptors to a lesser extent. Structurally, naltrexone is a cyclopropyl derivative of oxymorphone similar in structure to naloxone and nalorphine.

Naltrexone (Vivitrol injection, generic tablets) is approved by the FDA for the treatment of patients with Opioid Use Disorder (OUD) or alcohol dependence (following detoxification), alongside a counseling and support treatment plan.

Opioid Use Disorder

Naltrexone works in opioid use disorder by producing a complete but reversible block of the effects of the opioid, such as physical dependence, respiratory depression, miosis (pinpoint pupils), analgesia (pain relief), euphoria (pleasurable effects), drug craving and tolerance.

Opioids include the common pain relievers like hydrocodone, morphine, codeine or oxycodone, and illicit drugs such as heroin. It will not affect the use of cocaine or other non-opioid drugs of abuse.

As a pure antagonist, naltrexone may cause a mild to severe withdrawal in people who are physically dependent on opiates or pentazocine. Patients should stop using opioids or drinking alcohol before starting naltrexone treatment. Attempts to overcome opioid antagonism with large doses of opioids may lead to life threatening opioid intoxication or fatal overdose.

Related Questions

• What is low dose naltrexone (LDN)?
• What happens if you drink alcohol while taking naltrexone?
• What to avoid when taking naltrexone?

Alcohol Use Disorder

Naltrexone is thought to work in alcohol use disorder by blocking the effects of endogenous opiates made naturally by the body (like endorphins) which making alcohol ingestion less pleasurable. This action helps to reduce alcohol consumption.

• Alcohol ingestion stimulates release of endogenous opiate agonists (endorphins) produced in our brain.
• Endorphins are small molecules that circulate throughout the body. These molecules increase some of the rewarding effects associated with alcohol ingestion by binding at opiate receptors.

In clinical studies, treatment with naltrexone supported abstinence, prevented relapse and decreased alcohol consumption. However, the effect was modest and not uniform in all patients.

Bottom Line

• Naltrexone is a full opiate receptor antagonist and works by binding primarily at the mu opioid receptors. By binding to these receptors, it blocks the euphoric (pleasurable or "high") effects associated with alcohol use or opioids.
• Naltrexone (and its active metabolite 6-beta-naltrexol) are competitive antagonists to the mu opioid receptors, but also have action at the kappa and delta receptors to a lesser extent. In alcohol use disorder it works by blocking endogenous endorphins at the opioid receptor site.
• It is approved by the FDA to treat patients with Opioid Use Disorder (OUD) or alcohol dependence (following detoxification), alongside a counseling and support treatment plan.

This is not all the information you need to know about naltrexone for safe and effective use and does not take the place of your doctor’s directions. Review the full product information and discuss this information and any questions you have with your doctor or other health care provider.