Can naltrexone be taken with kratom?

Naltrexone and Kratom: Contraindicated Combination

No, naltrexone should not be taken with kratom due to the high risk of precipitating severe opioid withdrawal. Kratom contains mitragynine and 7-hydroxymitragynine, which act as partial mu-opioid receptor agonists, and naltrexone is a competitive opioid receptor antagonist that will displace these compounds from opioid receptors, triggering acute withdrawal 1, 2.

Critical Safety Concerns

Precipitated Withdrawal Risk

• Naltrexone administration in kratom users precipitates acute opioid withdrawal syndrome, documented in multiple case reports where patients experienced severe withdrawal symptoms immediately after receiving naltrexone while using kratom 1, 2
• The withdrawal occurs because naltrexone competitively displaces kratom's active alkaloids from mu-opioid receptors, similar to what occurs with traditional opioids 1, 2
• Kratom users consuming more than 5-15 grams daily are at particularly high risk for withdrawal syndrome upon abrupt cessation or antagonist administration 3

Mechanism of Interaction

• Kratom's primary alkaloids (mitragynine and 7-hydroxymitragynine) function as partial mu-opioid receptor agonists and antagonists at kappa- and delta-opioid receptors 4
• Naltrexone has a 4-hour plasma half-life with an active metabolite (6-β-naltrexol) lasting 13 hours, providing sustained opioid receptor blockade 3
• The antagonist effects of naltrexone persist for 2-3 days after oral administration and 24-30 days after extended-release injection 3

Clinical Management Approach

If Patient Is Currently Using Kratom

• Discontinue kratom completely before initiating naltrexone 3
• Wait at least 7-10 days after last kratom use before starting naltrexone to allow complete clearance and avoid precipitated withdrawal 1, 2
• Screen for withdrawal symptoms during this waiting period, as chronic kratom users may experience withdrawal upon discontinuation 1, 2

If Patient Is on Naltrexone and Considering Kratom

• Strongly advise against kratom use - the Society for Perioperative Assessment and Quality Improvement explicitly does not recommend use of kratom due to its opioid-like properties and potential for neurologic effects including seizures 3
• Kratom will have reduced or no effect due to opioid receptor blockade by naltrexone 3
• Patients may attempt to overcome the blockade by using higher kratom doses, increasing toxicity risk 3

Alternative Treatment Strategy

• Consider buprenorphine/naloxone instead of naltrexone for kratom use disorder, as multiple case series demonstrate successful treatment outcomes 4, 5, 6
• Buprenorphine induction doses typically range from 1-16 mg for kratom dependence, with stabilization doses between 4-20 mg 4
• In the largest case series (n=28), 82% of patients achieved negative mitragynine tests by 12 weeks on buprenorphine/naloxone maintenance 4

Additional Warnings

Naltrexone-Specific Contraindications

• Naltrexone should not be used concomitantly with any opiate medications or opioid-like substances, per AGA guidelines 3
• This contraindication extends to kratom given its opioid receptor activity 1, 2
• Patients requiring emergency opioid analgesia while on naltrexone may need higher doses or alternative pain management due to receptor blockade 7

Kratom-Specific Risks

• Kratom has been associated with hepatotoxicity, raising concerns for additive liver injury when combined with other hepatotoxic medications 1
• The FDA warns against kratom use due to safety concerns including seizures and neurologic effects 3
• Kratom may inhibit platelet aggregation and should be discontinued before surgical procedures 3