Quick Comparison

5-HTPLemon Balm
Half-Life2-5 hours3-5 hours (rosmarinic acid)
Typical DosageStandard: 50-200 mg daily. For mood: 50-100 mg 2-3 times daily. For sleep: 100-300 mg 30-60 minutes before bed. Start low — some people are very sensitive. Take with food to reduce nausea.Standard: 300-600 mg extract daily for anxiety/cognition. For sleep: 300-600 mg 30-60 minutes before bed. Cyracos is the most studied extract (standardized to rosmarinic acid). Tea: 2-4 cups daily. Can be combined with valerian for sleep.
AdministrationOral (capsules, tablets). Take with food to reduce GI side effects. Evening dosing preferred for sleep benefits.Oral (capsules, tea, tincture). Cyracos extract is most studied. Pleasant lemon-mint taste in tea form.
Research Papers10 papers8 papers
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Mechanism of Action

5-HTP

5-HTP readily crosses the blood-brain barrier via the large neutral amino acid transporter (LAT1/SLC7A5), unlike serotonin itself which cannot. Once in the brain, aromatic L-amino acid decarboxylase (AADC, also called DOPA decarboxylase) converts 5-HTP to serotonin (5-hydroxytryptamine) using pyridoxal-5-phosphate (active vitamin B6) as a cofactor. This completely bypasses tryptophan hydroxylase (TPH2), the rate-limiting enzyme in the normal serotonin synthesis pathway from dietary L-tryptophan. The result is a reliable, dose-dependent increase in serotonin across multiple brain regions including the dorsal raphe nucleus, hippocampus, and prefrontal cortex. Elevated serotonin activates 5-HT1A autoreceptors (calming), 5-HT2A/2C postsynaptic receptors (mood modulation), and 5-HT3 receptors (gut-brain signaling). In the pineal gland, serotonin is converted by arylalkylamine N-acetyltransferase (AANAT) to N-acetylserotonin, then by hydroxyindole O-methyltransferase (HIOMT) to melatonin — explaining the sleep-promoting effects.

Lemon Balm

Lemon balm inhibits GABA-transaminase (GABA-T), the enzyme that converts GABA to succinic semialdehyde in the GABA shunt, increasing GABA availability in synaptic terminals and producing anxiolytic effects via GABA-A (alpha2, alpha3 subunits) and GABA-B receptors. Rosmarinic acid provides antioxidant effects via Nrf2 activation and anti-inflammatory effects through COX-2 and NF-kB inhibition. Lemon balm inhibits acetylcholinesterase (AChE) at the catalytic site, mildly increasing acetylcholine in the hippocampus and cortex — explaining cognitive enhancement at moderate doses via muscarinic M1 and nicotinic receptor activation. At higher doses, GABAergic effects dominate, producing sedation useful for sleep. Additional mechanisms may include 5-HT2A antagonism and muscimol-like GABA-A modulation from trace constituents.

Risks & Safety

5-HTP

Common

Nausea, diarrhea, stomach cramps.

Serious

Serotonin syndrome when combined with SSRIs, SNRIs, MAOIs, or tramadol — DO NOT combine without medical supervision.

Rare

Eosinophilia-myalgia syndrome (historical concern from contaminated L-tryptophan, not confirmed with modern 5-HTP).

Lemon Balm

Common

Very well-tolerated. Mild drowsiness at higher doses.

Serious

May reduce thyroid hormone levels — caution with hypothyroidism.

Rare

Nausea, abdominal pain.

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