Saint John's Wort

Hyperforin in Saint John's Wort (hypericum perforatum) is a potent reuptake inhibitor of Serotonin, Dopamine, Noradrenaline, GABA and Glutamate. It also stimulates capillary blood flow.

Hypericin is a weak MAOA and MAOB inhibitor at high levels (not possible to obtain through normal doses). Hypericin also has affinity for the σ1 receptor as an agonist. However, it is an antagonist at adenosine, benzodiazepine, GABAA and GABAB and inositol triphosphate.

SJW (Saint John's Wort) has been reported to have some efficacy in cases of anhedonia/depression.

SJW has been shown to decrease the release of corticotropin-releasing hormone in the paraventricular nucleus of hypothalamus (in vitro), and decreased plasma levels of adrenocorticotropic hormone and corticosterone (in vitro). Due to the flavonoid content, it modulates the HPA function, downregulates β-adrenergic receptors, upregulates 5-HT1A and 5-HT2 receptors (although one study apparently found that SJW downregulates the former). Furthermore, some of the components of SJW have been found to bind very weakly to various receptors. Major depression has elevated ACTH and cortisol, and SJW downregulates them. It also antagonizes 5-HT6 and 5-HT7, which is antidepressant. The primary liver enzymes induced by SJW include:

• CYP1A2: there is evidence that St. John's Wort may induce this enzyme as well, impacting the metabolism of drugs like clozapine (an antipsychotic) and some antidepressants.
• CYP3A4: perhaps the most significantly induced enzyme by St. John's Wort. This enzyme metabolizes a large number of drugs, including statins (for cholesterol), some calcium channel blockers, certain antidepressants, DXM, and many others.
• CYP2C9: St. John's Wort also induces this enzyme, affecting the metabolism of drugs like warfarin (a blood thinner), some NSAIDs (non-steroidal anti-inflammatory drugs), and sulfonylureas (used in diabetes treatment).
• CYP2C19: St. John's Wort may also significantly increase this enzyme, which is involved in the metabolism of certain proton pump inhibitors (used for acid reflux) and some antidepressants.
• P-Glycoprotein (P-gp): besides the CYP enzymes, St. John's Wort also induces P-glycoprotein, a transporter protein that affects the absorption and elimination of many drugs, including immunosuppressants and antiretrovirals.

There are multiple extracts of H. perforatum (SJW) available:

• LI 160 contains 0.3% hypericin derivatives, hyperforin 1-4%.
• Ze 117 is a 50% ethanolic extract with an herb-to-extract ratio of 4:1-7:1; hyperforin ≤0.2% and up to 0.3% hypericin. Definitely the best extract overall due to NE:DA:5-HT uptake inhibition ratio of 30:7:1.
• WS 5570 Perika is an 80% ethanolic extract of St. John's Wort with a plant-to-extract ratio of 3:1-7:1; 5-6% hyperforin and 0.12-0.28% hypericin. Second best after Ze 117.
• STEI 300 contains 0.2-0.3% hypericin and pseudohypericin, and 2-3% hyperforin.

Hyperforin may worsen or cause PSSD in very rare cases theoretically as it is an SRI. But pure hypericin extracts (Ze 117) have reports of helping PSSD.