St. John's Wort

St. John’s Wort (Hypericum perforatum) is an herbal antidepressant that can act in SSRI-like ways. Its active constituents—especially hyperforin—are linked to inhibition of monoamine reuptake (serotonin, norepinephrine, dopamine) and broader neurochemical effects, which is why it can noticeably shift mood, anxiety, sleep, and libido in some people (1). It also has a major “hidden” pharmacology issue: many preparations strongly induce CYP3A4 and P-glycoprotein via PXR activation, which can lower blood levels of a wide range of medications and create unpredictable interactions (2).

For PFS/PSSD/PAS, St. John’s Wort is controversial because you’ll find both anecdotes of improvement and many reports of flares/crashes—likely because it can meaningfully push serotonergic systems and overall CNS signaling (3). It’s also considered higher-risk because combining it with other serotonergic agents (SSRIs/SNRIs/MAOIs, some migraine meds, etc.) can raise the risk of serotonin toxicity/serotonin syndrome, and mainstream medical sources explicitly warn about this interaction (4). Practical takeaway for your site: high-risk to experiment with in sensitized individuals—if someone is already unstable, most should avoid it rather than “testing” it.

https://www.ncbi.nlm.nih.gov/books/NBK557465/

https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.14936

https://www.stuffthatworks.health/post-ssri-sexual-dysfunction-pssd/treatments/st-john-wort

https://my.clevelandclinic.org/health/drugs/9304-st--johns-wort

Crash Anecdotes:

https://www.reddit.com/r/PSSD/comments/1mz5c76/st_johns_wart_gave_me_pssd/

https://www.reddit.com/r/PSSD/comments/146yi02/st_johns_wort_crashed_me/

My Personal Risk Ranking:

High Risk of Permanent Worsening (for PFS/PSSD/PAS):

If you currently have PFS/PSSD/PAS, St. John’s Wort may carry a moderate-to-high risk of worsening symptoms—potentially in a lasting way—because it can act in SSRI-like ways and strongly shift serotonin-related signaling. Given the number of community “crash” reports (despite a few improvement stories) and its high interaction potential, it’s generally best avoided, especially during stabilization.