5-HTP
5-Hydroxytryptophan
5-Hydroxytryptophan (5-HTP) is a naturally occurring amino acid and direct precursor to serotonin, derived primarily from the seeds of Griffonia simplicifolia. It is widely used to support mood regulation, improve sleep quality, reduce anxiety, and aid in appetite control, with clinical evidence supporting its role in mild-to-moderate depression and fibromyalgia.
Mechanism of Action
5-HTP crosses the blood-brain barrier and is converted to serotonin (5-HT) via aromatic L-amino acid decarboxylase, bypassing the rate-limiting hydroxylation step that tryptophan requires. Increased central serotonin availability modulates mood, appetite, and sleep via 5-HT1A, 5-HT2A, and other serotonin receptor subtypes. Serotonin is subsequently converted to melatonin in the pineal gland, contributing to 5-HTP's sleep-promoting effects.
Evidence by Health Goal(17 goals)
Dosing Protocols
30-45 minutes before bed; or split with one dose mid-afternoon and one before bed
Cycle: Use continuously for 4-6 weeks, then assess; consider 1-2 week breaks every 2-3 months to prevent receptor downregulation
Start at 50mg to assess tolerance. Taking with a carbohydrate-rich snack (without protein) may enhance brain uptake. Doses up to 300mg/day have been used clinically for depression and appetite suppression, but should be medically supervised.
Safety & Side Effects
5-HTP has a well-established safety profile at doses of 50-200mg/day and is available over-the-counter in most countries, though it is regulated as a medicine in some European nations. The primary serious risk is serotonin syndrome when combined with serotonergic drugs; long-term use beyond 12 weeks without medical supervision is not well-studied and may suppress endogenous tryptophan hydroxylase activity.
Possible Side Effects
- !Nausea and gastrointestinal discomfort, especially at doses above 100mg or on an empty stomach
- !Drowsiness and daytime sedation, particularly at higher doses
- !Diarrhea or loose stools, common during initial use or dose escalation
- !Vivid or unusual dreams when taken before sleep
- !Headache, typically transient during the first week of use
- !Decreased appetite and early satiety at therapeutic doses
- !Serotonin syndrome risk at high doses or when combined with serotonergic agents
Interactions
- -Contraindicated with MAOIs and SSRIs/SNRIs due to significant serotonin syndrome risk - can be life-threatening
- -Additive serotonergic effect with tramadol, triptans, and dextromethorphan - avoid concurrent use
- -May enhance sedative effects of benzodiazepines, sleep aids (e.g., zolpidem), and antihistamines
- -Carbidopa (used in Parkinson's therapy) inhibits peripheral decarboxylation of 5-HTP, dramatically increasing CNS conversion and serotonin levels - use only under medical supervision
- -May potentiate effects of St. John's Wort and SAMe, increasing serotonin syndrome risk with combined supplementation
Cost & Where to Buy
Widely available as an OTC supplement; 100mg capsules from reputable brands (e.g., NOW Foods, Natrol, Jarrow) typically cost $10-20 for a 60-120 count bottle. Higher-cost options include pharmaceutical-grade or certified purity products.
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