Does St. John's Wort (Hypericum perforatum) increase dopamine levels?

Does St. John's Wort Increase Dopamine?

Yes, St. John's Wort (Hypericum perforatum) can increase dopamine levels through multiple mechanisms, primarily through its active constituent hyperforin, which inhibits the synaptosomal uptake of dopamine and other neurotransmitters. 1

Mechanisms of Action on Dopamine

St. John's Wort affects dopamine through several pathways:

1. Dopamine Reuptake Inhibition:

   • Hyperforin, a major constituent of St. John's Wort, is a potent inhibitor of dopamine uptake with an IC50 value of about 0.05-0.10 μg/ml 1
   • This inhibition increases dopamine availability in the synaptic cleft

2. Dopamine-β-hydroxylase Inhibition:

   • Alcoholic extracts of St. John's Wort inhibit dopamine-β-hydroxylase (the enzyme that converts dopamine to norepinephrine) with an IC50 of 0.1 μmol/l 2
   • This inhibition may lead to increased dopamine levels by preventing its conversion to norepinephrine

3. Enhancement of Dopaminergic Function:

   • St. John's Wort extract (LI 160) has been shown to enhance dopamine-mediated inhibition of prolactin release 3
   • Hyperforin contributes to this facilitatory effect on dopamine function

Clinical Relevance

The dopaminergic effects of St. John's Wort contribute to its pharmacological profile:

• Antidepressant Effects: The dopamine-enhancing properties may contribute to its antidepressant efficacy 4

• Drug Interactions: St. John's Wort is a potent inducer of cytochrome P450 enzymes (particularly CYP3A4) and P-glycoprotein 5, which can lead to decreased plasma concentrations of numerous medications:

  • Antidepressants (amitriptyline)
  • Immunosuppressants (cyclosporine)
  • Cardiovascular drugs (digoxin, warfarin, phenprocoumon)
  • Antivirals (indinavir)
  • Anticancer drugs (irinotecan)
  • Benzodiazepines (alprazolam)
  • Statins (simvastatin)
  • Oral contraceptives

Important Considerations for Use

Drug Interactions

St. John's Wort should be held for at least 2 weeks prior to surgery due to:

• Multiple constituents with long half-lives (such as hypericin)
• Its effect of inducing cytochrome P450 3A4 (CYP3A4), which may reduce plasma concentrations of drugs metabolized by this enzyme 6

Specific Medication Interactions

• May decrease imatinib plasma concentration, potentially requiring dose increases in patients receiving both substances 6
• Can reduce the effectiveness of oral contraceptives 6

Serotonergic Effects

St. John's Wort affects multiple neurotransmitter systems beyond dopamine:

• Inhibits the synaptosomal uptake of serotonin, dopamine, and noradrenaline with approximately equal affinity 4
• Is contraindicated in patients receiving monoamine oxidase inhibitors or serotonin reuptake inhibitors due to risk of serotonin syndrome 6

Conclusion

St. John's Wort does increase dopamine levels through multiple mechanisms, primarily through reuptake inhibition by hyperforin and inhibition of dopamine-β-hydroxylase. However, its use should be approached with caution due to numerous significant drug interactions and its effects on multiple neurotransmitter systems.