Does kratom affect neuroplasticity after ketamine administration?

Kratom May Interfere with Ketamine-Induced Neuroplasticity

Kratom should be discontinued before ketamine administration as it may interfere with ketamine's neuroplasticity effects through its action on opioid receptors and cannabinoid pathways. 1, 2

Mechanism of Interference

Ketamine's therapeutic effects depend on its ability to induce rapid neuroplasticity changes:

• Ketamine functions as an NMDA receptor antagonist that interferes with normal excitatory effects of glutamate and aspartate 1
• Recent research shows ketamine produces measurable gray matter microstructural changes within 24 hours in key brain regions, which correlate with improvements in depression 3
• These neuroplasticity effects are crucial to ketamine's therapeutic action

Kratom may interfere with these mechanisms through:

1. Opioid receptor activity: Kratom's active alkaloids (mitragynine and 7-hydroxymitragynine) act as partial agonists at mu-opioid receptors and antagonists at kappa and delta receptors 4, 5

2. Cannabinoid system interaction: Chronic mitragynine exposure has been shown to upregulate CB1 receptor expression in the hippocampus and ventral tegmental area, similar to morphine 2

3. Multiple neurotransmitter effects: Kratom affects adrenergic, serotonergic, and dopaminergic pathways 4, 6, potentially interfering with ketamine's mechanism of action

Clinical Implications

The Society for Perioperative Assessment and Quality Improvement (SPAQI) recommends discontinuing kratom use, noting:

• Opioid and stimulant-like properties
• Potential for withdrawal syndrome with chronic use
• Risk of neurologic effects including seizures 1

Ketamine's therapeutic effects depend on its ability to enhance neuroplasticity, which may be compromised by kratom's effects on similar neural pathways:

• Research shows mitragynine induces cognitive impairments in mice that resemble both THC and morphine effects 2
• These cognitive impairments involve CB1 receptor mechanisms that could interfere with ketamine's neuroplasticity effects 2

Recommendations for Clinical Practice

1. Discontinue kratom before ketamine treatment:

   • Follow SPAQI guidelines recommending discontinuation 1
   • Allow sufficient washout period (minimum 2 weeks) to minimize interference

2. Monitor for withdrawal symptoms:

   • Kratom can cause physical and psychological dependence 4
   • Patients may experience classic opioid withdrawal symptoms upon cessation

3. Consider potential drug interactions:

   • Kratom modulates cytochrome P450, P-glycoprotein, and UGT enzymes 4
   • This may affect ketamine metabolism and clearance

4. Assess for comorbid substance use:

   • Kratom risks are often compounded by polysubstance abuse 4
   • Screen for other substances that may affect ketamine response

Conclusion

While direct studies examining kratom's effect on ketamine-induced neuroplasticity are limited, the available evidence suggests potential interference through overlapping receptor systems. The safest approach is to discontinue kratom before ketamine treatment to maximize the potential for neuroplasticity and therapeutic benefit.