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Psilocybin and 5-HTP and L-tryptophan

No data

Serotonin precursor supplement · also: 5-hydroxytryptophan, griffonia, tryptophan, l-tryptophan

There is no reported interaction between 5-HTP or L-tryptophan and psilocybin on its own; the real concern is adding these supplements to an SSRI, SNRI or MAOI.

No characteristic interaction reported with psilocybin alone.

Claims re-checked against the cited sources:

Why it happens

5-HTP and L-tryptophan are serotonin precursors that increase serotonin synthesis. Psilocin acts directly as a 5-HT2A agonist and does not rely on the serotonin transporter or on releasing serotonin, so the additive serotonin load from psilocybin is likely small. The serotonin syndrome risk with these supplements comes mainly from stacking them with drugs that raise serotonin, such as SSRIs, SNRIs or MAOIs.

What is known

Thin. The serotonin syndrome concern with 5-HTP comes mainly from combining it with other serotonergic drugs, not from 5-HTP alone.

2006
A review of 5-HTP supplementation lists serotonin syndrome and eosinophilia-myalgia syndrome as the main safety issues. Turner, Loftis & Blackwell, Pharmacology & Therapeutics 2006
2020
5-HTP can cause dose-dependent gastrointestinal effects, with nausea and vomiting reported at doses above 100 mg. Maffei, International Journal of Molecular Sciences 2020
2022
Review authors describe psilocybin's action as direct serotonin receptor agonism that does not compete with or rely on serotonin transporter activity. Sarparast et al., Psychopharmacology 2022 (systematic review)

Safety guidance

  • 5-HTP on its own with mushrooms has no known interaction.
  • The idea of taking 5-HTP afterwards to 'replenish serotonin' comes from MDMA and does not fit how psilocin works.
  • If you take an SSRI, SNRI or MAOI, do not add 5-HTP or tryptophan supplements; ask your prescriber first.
  • Nausea is common with both mushrooms and higher 5-HTP doses, so combining them can make it worse.
Do not stop a prescribed medication on your own. Stopping or skipping a prescribed drug to take mushrooms can be more dangerous than either alone. Talk to whoever prescribes it.

When to seek help

Get urgent medical help if you develop agitation with fever, heavy sweating, muscle twitching or jerking, rigidity or a racing heart, especially if you also take an antidepressant or MAOI. Emergency red flags.

Common questions

Is it safe to take 5-HTP the day after mushrooms?

No interaction is documented, but there is also no evidence it helps: psilocin does not deplete serotonin the way MDMA is thought to.

Does 5-HTP plus mushrooms cause serotonin syndrome?

Not on its own as far as is known. The documented risk with 5-HTP is when it is stacked on other serotonergic drugs such as SSRIs or MAOIs.

Is L-tryptophan different from 5-HTP here?

Both are serotonin precursors and the same reasoning applies; no study of either with psilocybin is cited here.

Sources

  1. [1]Turner et al., 'Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan' (2006)

How we research this: sources, evidence grading, review and updates.

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