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5-HTP (5-hydroxytryptophan)

Direct serotonin precursor with preliminary RCT signal for sleep onset and low mood: short trial bodies, real interaction profile.

Why

5-hydroxytryptophan is the direct metabolic precursor of serotonin, isolated from Griffonia simplicifolia seeds. The Cochrane review of 5-HTP and tryptophan for depression found small RCTs suggesting benefit over placebo, but trial quality was generally low and the authors called for larger studies. A separate small body of work supports use for sleep onset, particularly when combined with GABA.

How it works

Crosses the blood-brain barrier and is decarboxylated to serotonin (5-HT), bypassing the rate-limiting tryptophan hydroxylase step. Some peripheral conversion to serotonin in the gut wall accounts for common GI side effects.

Expected onset · Sleep effects often within days; mood effects over 2–4 weeks

How to take

Dosage

Mood: 150–300 mg/day divided. Sleep: 100–200 mg 30–45 min before bed. Start at 50 mg to test tolerance.

Timing

Sleep dose at bedtime; mood doses divided across the day

On the label

Look for Griffonia simplicifolia seed extract with stated 5-HTP content. Pharmaceutical-grade material with third-party purity testing matters here.

Ideal for

Adults with mild low mood or initial-insomnia symptoms, not on serotonergic medications.

Safety

Risk of serotonin syndrome if combined with SSRIs, SNRIs, MAOIs, tramadol, triptans, or St John's wort; avoid. Common GI side effects (nausea, loose stools). Carbidopa interaction in Parkinson's disease (peripheral conversion blocked). Historical concern about eosinophilia-myalgia syndrome traces to a contaminated tryptophan batch in 1989, not 5-HTP itself, but quality sourcing remains important. Avoid in pregnancy and breastfeeding.

Evidence

At a glance

Cochrane 2002 SR (108 trials assessed, 2 met inclusion): 5-HTP and tryptophan appeared better than placebo for depressive symptoms, but trial quality was low and the authors recommended larger studies before clinical use. Sleep-onset data is limited to small open and crossover trials. Real interaction profile keeps this in the preliminary tier despite mechanistic plausibility.

Where to get it

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