Quick Comparison
| 5-HTP | Agmatine Sulfate | |
|---|---|---|
| Half-Life | 2-5 hours | 2-3 hours |
| Typical Dosage | Standard: 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: 500-2000 mg daily in 1-3 doses. For mood: 1000-2000 mg. For pain: 1000-2500 mg. Take on empty stomach. Agmatine sulfate is the most common supplement form. May enhance the effects of some nootropics and medications — research interactions. |
| Administration | Oral (capsules, tablets). Take with food to reduce GI side effects. Evening dosing preferred for sleep benefits. | Oral (powder, capsules). Take on empty stomach for best absorption. |
| Research Papers | 10 papers | 10 papers |
| Categories |
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.
Agmatine Sulfate
Agmatine is a polyamine neuromodulator with multiple targets: (1) NMDA receptor antagonist at the polyamine binding site (GluN1/GluN2B) — reduces excitotoxicity, pain signaling, and blocks the receptor's open channel. (2) Imidazoline I1 and I2 receptor agonist — I1 in the rostral ventrolateral medulla reduces sympathetic tone; I2 modulates monoamine oxidase and provides anxiolytic/antidepressant effects. (3) Selective nNOS (neuronal nitric oxide synthase) inhibitor — reduces peroxynitrite formation and oxidative stress while preserving eNOS (endothelial) function for vascular health. (4) Alpha-2 adrenergic receptor agonist — reduces norepinephrine release from locus coeruleus, promoting calm. (5) Modulates opioid receptors — enhances mu-opioid analgesia, potentiates delta-opioid, and may reduce tolerance via nitric oxide and NMDA mechanisms.
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).
Agmatine Sulfate
Common
Mild gastrointestinal discomfort, diarrhea at high doses.
Serious
May potentiate opioid medications (increased sedation risk). May lower blood pressure.
Rare
Headache, nausea.
Full Profiles
5-HTP →
5-Hydroxytryptophan is the immediate precursor to serotonin, derived from the seeds of Griffonia simplicifolia. By providing the rate-limiting intermediate in serotonin synthesis, 5-HTP effectively raises brain serotonin levels. Used for mood support, anxiety, sleep, and appetite control. More effective than L-Tryptophan because it bypasses the rate-limiting enzyme step.
Agmatine Sulfate →
A metabolite of L-arginine produced by decarboxylation. Agmatine is an endogenous neuromodulator that acts on multiple receptor systems — it blocks NMDA receptors, activates imidazoline receptors, inhibits nitric oxide synthase, and modulates opioid signaling. This makes it useful for neuropathic pain, mood, stress resilience, and as a complement to other nootropics. Also enhances insulin sensitivity and nitric oxide production.