5HTP & SAM-E
5-HTP (5-hydroxytryptophan) is a direct biochemical precursor to serotonin. In the body, tryptophan is converted to 5-HTP, and 5-HTP is then converted into serotonin (5-HT) by the enzyme aromatic L-amino-acid decarboxylase (AADC) (1). Because it sits one step away from serotonin, adding 5-HTP can raise serotonergic tone, which is why people take it for mood/sleep—but it also means it can cause serotonergic side effects in susceptible people, and it can be risky combined with other serotonin-raising drugs/supplements due to serotonin syndrome potential (1).
SAM-e (S-adenosyl-L-methionine) is the body’s primary methyl-donor molecule, used in a huge number of methylation reactions that affect neurotransmitters, phospholipids, DNA/RNA, and more (2). In psychiatry literature, SAM-e is discussed as having antidepressant effects via downstream effects on monoamine systems (including serotonin pathways)—so even though it’s not “a serotonin pill” the way 5-HTP is, it can still shift neurotransmitter dynamics.
Because 5-HTP directly raises serotonin (it’s converted into serotonin in the body), and SAM-e can also shift monoamine/serotonin pathways via methylation and antidepressant-like effects, both can meaningfully change brain chemistry in a short time (1). In people who are already sensitized (like many in PFS/PSSD/PAS communities), that kind of serotonergic push is a commonly suspected reason for “crash” reports—worsened mood/anxiety, sleep disruption, agitation, sexual symptoms, or a general flare—especially if combined with other serotonin-acting agents. There’s also a known general risk with serotonin-elevating supplements of serotonin toxicity in susceptible situations, which is why multiple medical sources warn about stacking serotonergic products.
(1) https://pmc.ncbi.nlm.nih.gov/articles/PMC7796270/
(2) https://psychiatryonline.org/doi/10.1176/appi.ajp.2009.09081198
Crash Anecdotes:
https://www.reddit.com/r/PSSD/comments/1l2h42t/dont_try_5_htp_it_hit_like_ssris/
https://www.reddit.com/r/PSSD/comments/o6ax8p/have_anyone_tried_same/
My Personal Risk Ranking:
High Risk of Permanent Worsening (for PFS/PSSD/PAS):
If you currently have PFS/PSSD/PAS, this substance may carry a high risk of worsening symptoms—potentially in a lasting way—and is best avoided.
Given the uncertainty and the potential severity of outcomes, the risk may not be worth the advertised benefits.