What are the risks and recommendations for using naltrexone in patients with opioid use disorder who also use marijuana?

Naltrexone Use in Opioid Use Disorder Patients Who Also Use Marijuana

Direct Answer

Naltrexone is safe and appropriate for treating opioid use disorder in patients who use marijuana, and emerging evidence suggests intermittent marijuana use may actually improve treatment retention and adherence to naltrexone therapy. 1

Evidence for Safety and Compatibility

No Contraindication Exists

• Naltrexone can be safely prescribed to patients with concurrent marijuana use, as there are no documented drug interactions or safety concerns between naltrexone and cannabis. 2
• The CDC guidelines for opioid prescribing recommend naltrexone as medication-assisted treatment for motivated patients with opioid use disorder, without any restrictions regarding concurrent marijuana use. 2
• Naltrexone functions as a competitive mu-opioid receptor antagonist and does not interact with cannabinoid receptors in a clinically significant manner. 3

Unexpected Benefit: Improved Treatment Outcomes

• Intermittent marijuana use (defined as 1-79% cannabis-positive urine samples) was associated with superior retention in naltrexone treatment compared to both abstinent patients and consistent daily users. 1
• Patients with intermittent cannabis use showed median retention of 133 days versus only 35 days for abstinent patients in a randomized controlled trial. 1
• This improved retention remained statistically significant even after adjusting for baseline heroin use and cocaine use during treatment. 1
• Intermittent cannabis users also demonstrated greater adherence to daily naltrexone pill-taking. 1

Clinical Algorithm for Management

Patient Assessment

• Screen for opioid use disorder using DSM-5 criteria (requiring at least 2 criteria within a 12-month period). 2
• Document the pattern of marijuana use: abstinent, intermittent (occasional), or consistent daily use. 1
• Ensure patient is completely opioid-free before initiating naltrexone to avoid precipitating severe withdrawal. 3, 4
• Obtain baseline liver function tests, as naltrexone carries hepatotoxicity risk at supratherapeutic doses. 3

Treatment Initiation

• For highly motivated patients who prefer opioid-free treatment over methadone or buprenorphine maintenance, offer naltrexone regardless of marijuana use status. 2, 3
• Choose between oral naltrexone (50 mg daily) or extended-release injectable naltrexone (380 mg monthly/Vivitrol). 3
• Injectable formulations may be preferred when adherence is a concern, though oral naltrexone appears compatible with intermittent marijuana use. 1
• Combine naltrexone with behavioral therapies, as medication alone is insufficient. 2

Monitoring Considerations

• Monitor liver function tests every 3-6 months during treatment. 3
• Track treatment retention and medication adherence through pill counts or injection appointments. 1
• Be aware that naltrexone metabolites can cause false-positive oxycodone results on standard urine drug screens; confirmatory testing for noroxymorphone can distinguish this from actual opioid use. 5
• Do not dismiss patients from care due to positive marijuana screens, as this may represent a favorable prognostic indicator for naltrexone retention. 1

Important Caveats and Pitfalls

Avoid These Common Errors

• Never initiate naltrexone in patients still using opioids, as this will precipitate severe withdrawal requiring heavy sedation or even general anesthesia. 4
• Do not use naltrexone in pregnant women; offer buprenorphine (without naloxone) or methadone instead. 2
• Do not prescribe naltrexone to patients requiring opioid analgesics for pain management, as it blocks pain relief. 3
• Warn patients that discontinuing naltrexone increases overdose risk due to decreased opioid tolerance. 3

Marijuana-Specific Considerations

• While intermittent marijuana use correlates with better naltrexone retention, consistent heavy daily cannabis use (≥80% positive screens) does not show this benefit. 1
• Naltrexone itself may reduce cannabis self-administration and positive subjective effects in daily cannabis smokers, though this effect is secondary to opioid use disorder treatment. 6
• The mechanism underlying improved retention with intermittent cannabis use remains unclear and requires further study. 1

Surgical Planning

• Hold oral naltrexone for 2-3 days before elective procedures requiring opioid analgesia. 3
• Extended-release injectable naltrexone requires 24-30 days after the last injection before elective procedures. 3

Treatment Context

Naltrexone represents a second-line option after buprenorphine or methadone maintenance therapy, which have stronger evidence for preventing relapse in opioid use disorder. 2 However, for patients who are highly motivated, prefer opioid-free treatment, or cannot access agonist therapy, naltrexone is an appropriate evidence-based choice. 2, 3 The presence of marijuana use should not disqualify patients from naltrexone treatment and may actually predict better outcomes when use is intermittent rather than daily. 1