What happens when drinking alcohol while taking naltrexone (opioid receptor antagonist)?

What Happens When Drinking Alcohol on Naltrexone

Naltrexone blocks the rewarding and pleasurable effects of alcohol by antagonizing opioid receptors, which reduces the "high" associated with drinking and decreases alcohol craving, but it does not cause a disulfiram-like aversive reaction when alcohol is consumed. 1, 2

Mechanism of Action During Alcohol Consumption

• Naltrexone competitively binds to opioid receptors and blocks the effects of endogenous opioids that are released during alcohol consumption, thereby reducing the reinforcing properties of drinking 1
• The medication does not produce an aversive reaction or disulfiram-like response when combined with alcohol 1
• Patients may experience reduced euphoria or "high" from alcohol while on naltrexone, which is the intended therapeutic effect 2
• The blockade of opioid receptors results in decreased alcohol craving and reduced motivation to continue drinking once started 1, 2

Clinical Effects and Outcomes

Drinking Reduction

• Naltrexone significantly reduces the risk of relapse to heavy drinking rather than promoting complete abstinence 3, 4
• The medication lowers weekly heavy drinking rates even in non-alcoholic social drinkers 5
• Effect sizes are modest (0.15 to 0.2 range), with number needed to treat approximately 20 to prevent return to any drinking 3, 4

Safety Profile When Drinking Occurs

• There is no dangerous interaction between naltrexone and alcohol consumption itself 1, 6
• The most common side effect is nausea, which occurs in approximately 10% of patients 1, 6
• At the standard 50 mg daily dose, naltrexone does not appear hepatotoxic, though hepatocellular injury can occur at higher doses (up to 300 mg/day) 1, 4, 6

Important Clinical Considerations

Hepatotoxicity Concerns

• While naltrexone has been shown to cause hepatocellular injury, this occurs primarily at doses much higher than the standard 50 mg daily used for alcohol dependence 3, 1, 2
• Liver enzyme levels (AST/ALT) should be monitored, though at standard doses hepatotoxicity has not emerged as a significant clinical problem 6, 5
• Multiple guidelines recommend against using naltrexone in patients with alcoholic liver disease specifically due to hepatotoxicity concerns, despite lack of studies in this population 3

Treatment Effectiveness Factors

• Naltrexone efficacy is significantly enhanced when patients are compliant with medication and attend treatment sessions regularly 7
• The medication works best when combined with behavioral counseling and psychosocial support 3, 4
• Treatment compliance and attendance are critical—naltrexone shows robust effects in compliant subjects but minimal effects in those who miss visits or medication doses 7

Contraindications When Drinking May Occur

• Naltrexone is contraindicated in patients currently using opioids, as it will precipitate severe withdrawal symptoms 1
• Patients must be opioid-free for 7-10 days before starting naltrexone to avoid precipitated withdrawal 1
• The medication is not recommended for patients with existing alcoholic liver disease due to potential hepatotoxicity, though this remains controversial 3

Common Pitfalls to Avoid

• Do not confuse naltrexone with disulfiram—naltrexone does not cause illness when alcohol is consumed 1
• Do not expect naltrexone to promote complete abstinence; its primary benefit is reducing heavy drinking episodes 3, 4
• Do not use naltrexone as monotherapy; it must be combined with counseling and behavioral interventions for optimal effectiveness 3, 6
• Do not prescribe naltrexone without ensuring the patient is completely opioid-free, as this can precipitate dangerous withdrawal 1