Is there an interaction between ketamine therapy and kratom use?

Potential Interaction Between Ketamine Therapy and Kratom

Concurrent use of ketamine therapy and kratom poses significant safety concerns due to potential additive effects and drug interactions, and discontinuation of kratom is recommended at least 2 weeks before ketamine therapy. 1

Understanding the Pharmacology

Kratom

• Contains over 40 alkaloids with mitragynine and 7-OH-mitragynine as main psychoactive compounds 2
• Acts on mu, delta, and kappa opioid receptors (atypical opioid properties)
• Also affects adrenergic, serotonergic, and dopaminergic pathways
• Known to inhibit CYP2D6, CYP3A, and P-glycoprotein enzymes 3

Ketamine

• NMDA receptor antagonist that blocks glutamate 1
• Used for pain management, depression, and anesthesia
• Causes sympathetic stimulation (increases heart rate, blood pressure)
• Can increase upper airway secretions 1

Potential Interactions and Risks

1. Respiratory Effects

   • While ketamine alone has minimal respiratory depression, the combination with kratom's opioid-like effects could potentially increase this risk

2. Cardiovascular Concerns

   • Ketamine increases heart rate and blood pressure 1
   • Combined with kratom's adrenergic effects, this could lead to unpredictable cardiovascular responses

3. Drug Metabolism Interactions

   • Kratom inhibits CYP enzymes and P-glycoprotein 3
   • May alter ketamine metabolism, potentially increasing blood levels and prolonging effects

4. CNS Effects

   • Both substances affect multiple neurotransmitter systems
   • Potential for unpredictable neuropsychiatric effects

Clinical Recommendations

1. Discontinuation Timeline

   • The Society for Perioperative Assessment and Quality Improvement (SPAQI) recommends discontinuing kratom at least 2 weeks before surgical procedures 1
   • Apply this same timeline before ketamine therapy

2. Withdrawal Considerations

   • Kratom should be tapered rather than abruptly discontinued due to potential withdrawal symptoms 1
   • Withdrawal symptoms can mimic opioid withdrawal

3. Monitoring Requirements

   • If a patient has been using kratom and requires urgent ketamine therapy:
     • Close monitoring of vital signs
     • Have naloxone readily available
     • Consider lower initial ketamine doses

4. Alternative Approaches

   • For patients using kratom for pain management, discuss alternative pain management strategies
   • Consider formal opioid replacement therapy (methadone, buprenorphine) instead of kratom for those using it to manage opioid dependence

Special Considerations

• The FDA has warned against kratom use due to safety concerns 1
• Kratom is not recommended by SPAQI due to potential for serious adverse effects 1
• The combination of ketamine and kratom has not been specifically studied in clinical trials, making the interaction profile unpredictable
• Both substances have abuse potential, raising additional concerns about their combined use

Key Pitfalls to Avoid

1. Failure to identify kratom use

   • Kratom does not appear in standard drug screens
   • Specifically ask about herbal supplements and "natural" pain remedies

2. Underestimating withdrawal

   • Abrupt discontinuation of kratom can lead to significant withdrawal symptoms
   • Implement a tapering schedule when possible

3. Polypharmacy risks

   • Many kratom-associated deaths involved multiple substances 4
   • Evaluate all medications and supplements the patient is taking

In conclusion, the combination of ketamine therapy and kratom presents significant concerns for patient safety due to potential pharmacological interactions and limited clinical data. The prudent approach is to discontinue kratom at least 2 weeks before initiating ketamine therapy, with appropriate tapering to minimize withdrawal symptoms.