St. John's Wort
St. John’s Wort (Hypericum perforatum) is an herbal product commonly used for mood support. Its best-studied active constituents—especially hyperforin—are associated with inhibition of monoamine reuptake (serotonin, norepinephrine, dopamine) and broader neurochemical effects, which is why it can noticeably affect mood, anxiety, sleep, and libido in some people. A major practical issue is drug interactions: many preparations can induce CYP3A4 and P-glycoproteinvia PXR activation, potentially lowering blood levels of a wide range of medications and creating unpredictable interaction risk.
In PFS/PSSD/PAS discussions, St. John’s Wort is often treated as a higher-variance, higher-risk herb because it can meaningfully shift serotonergic and monoaminergic signaling in an SSRI-like direction. Community reports include both improvement stories and many accounts of symptom flares/crashes, which may reflect individual sensitivity, product variability, and the fact that it can strongly push central nervous system signaling. It also carries a well-recognized safety concern when combined with other serotonergic agents (SSRIs/SNRIs/MAOIs and other serotonin-acting drugs), where mainstream medical sources warn about increased risk of serotonin toxicity/serotonin syndrome.
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 (Community Reports):
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/
How to Interpret This Page
This page summarizes anecdotal reports and community observations, not medical evidence. “Risk” here refers to how frequently severe or prolonged symptom worsening is reported, not to proven causation or population-wide probability. Individual responses vary widely, and absence of issues in some users does not rule out significant reactions in others.
Risk Signal Based on User Reports
Reports of Severe and Sometimes Lasting Worsening (for PFS/PSSD/PAS):
Among individuals who already have PFS/PSSD/PAS, St. John’s Wort is commonly mentioned in community reportsas preceding symptom worsening, sometimes described as prolonged. Concerns typically center on SSRI-like serotonergic effects (mood/anhedonia shifts, emotional blunting, sleep disruption, sexual symptoms) and the unpredictability introduced by product variability and drug–drug interactions. Because outcomes appear highly variable and crashes are repeatedly reported, many in these communities view avoidance—especially during unstable periods—as a more conservative choice.
For individuals without these conditions, St. John’s Wort is widely used, but significant side effects and interactions can still occur. Given its potent enzyme-inducing properties and the known risk when combined with serotonergic medications, careful interaction screening is important for anyone considering it.
Evidence basis: Established pharmacology and interaction literature; mainstream medical safety guidance; anecdotal reports (online forums, self-reports); no controlled studies examining PFS/PSSD/PAS-specific outcomes.