5-HTP

Also known as: 5-hydroxytryptophan, griffonia seed extract, oxitriptan

Grade B — Moderate Evidenceamino acidserotonin precursor
50–300 mgEvening for sleep; split doses for mood. Take with carbohydrate for brain uptake.

5-Hydroxytryptophan (5-HTP) is the direct precursor to serotonin, the neurotransmitter most associated with mood, sleep, and well-being. Derived from the seeds of the African plant Griffonia simplicifolia, 5-HTP crosses the blood-brain barrier and is converted to serotonin. While effective for mood and sleep, it carries serious interaction risks with serotonergic medications — combining 5-HTP with SSRIs, SNRIs, or MAOIs can cause potentially life-threatening serotonin syndrome.

TL;DR: Direct serotonin precursor. Effective for mood and sleep but DANGEROUS with serotonergic medications.

😊Mood🌙Sleep
Last reviewed: 2026-03-11

Evidence

Grade B

Studies

3

Interactions

4

Forms

1

Evidence Rating: Grade B — Moderate Evidence

Some RCTs with positive results, or strong observational evidence. More research may refine our understanding.

Cycling Protocol

8 weeks on/4 weeks off

Chronic serotonin precursor loading may deplete dopamine and catecholamines; cycling prevents imbalance

Interaction Warnings

SSRIs/SNRIsHigh Risk

Risk of serotonin syndrome — potentially life-threatening. DO NOT combine.

MAOIsHigh Risk

CONTRAINDICATED — severe serotonin syndrome

TramadolHigh Risk

Serotonin syndrome risk

St. John's WortHigh Risk

Additive serotonergic; risk of serotonin syndrome

⚠️ Important Notes

  • NEVER combine with SSRIs, SNRIs, or MAOIs
  • Start at lowest dose
  • Add B6 (P5P) as cofactor for serotonin synthesis

Clinical Evidence (3 studies)

5-HTP for depression: Cochrane review

Shaw K et al. (2002) — Cochrane Database Syst Rev

Positive effects in good-quality RCTs

View on PubMed

5-HTP reduced carbohydrate intake and body weight

Cangiano C et al. (1992) — Am J Clin Nutr

RCT: reduced carbohydrate intake and body weight

View on PubMed

5-HTP improved fibromyalgia symptoms

Puttini PS & Caruso I (1992) — J Int Med Res

Placebo-controlled trial: improved fibromyalgia symptoms

View on PubMed

Alternatives to Consider

These supplements target similar goals and may be worth considering alongside or instead of 5-HTP.

L-Theanine

Grade B

Amino acid from green tea. Promotes calm focus (alpha brain waves) without drowsiness. Excellent safety profile.

🌙 Sleep

NAC (N-Acetyl Cysteine)

Grade B

Precursor to glutathione (master antioxidant). Strong evidence for respiratory health, liver support, and psychiatric conditions.

😊 Mood

Glycine

Grade B

Inhibitory amino acid that improves sleep quality by lowering core body temperature. Also supports collagen synthesis.

🌙 Sleep

Related Supplements

Magnesium Glycinate

Grade A — Strong Evidence

Highly bioavailable form of magnesium. Strong evidence for sleep quality, muscle relaxation, and stress reduction. Most adults are deficient.

Ashwagandha

Grade A — Strong Evidence

Ayurvedic adaptogen with strong clinical evidence for cortisol reduction (15-30%), stress relief, and exercise performance.

Vitamin B6

Grade A — Strong Evidence

Essential coenzyme for neurotransmitter synthesis (serotonin, GABA, dopamine). Strong evidence for PMS. Deficiency common in those on OCP or with poor diet.

L-Theanine

Grade B — Moderate Evidence

Amino acid from green tea. Promotes calm focus (alpha brain waves) without drowsiness. Excellent safety profile.

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⚕️ Important Disclaimer

This information is for educational purposes only. It is not medical advice. Always consult a healthcare provider before starting any supplement regimen, especially if you take medications or have health conditions.

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