Quick Comparison

5-HTPReishi
Half-Life2-5 hoursBioactive compounds accumulate with daily use
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: 1000-3000 mg daily of extract. Dual-extract (water + alcohol extraction) preferred to capture both polysaccharides and triterpenes. Take in the evening due to calming effects. Spore oil: 500-1000 mg daily. Effects build over 2-4 weeks.
AdministrationOral (capsules, tablets). Take with food to reduce GI side effects. Evening dosing preferred for sleep benefits.Oral (capsules, powder, tincture, tea). Dual-extract preferred. Bitter taste in powder/tea form.
Research Papers10 papers8 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.

Reishi

Reishi's triterpenes (ganoderic acids A, C, D, H; ganoderenic acids) modulate the HPA axis by reducing CRH and ACTH release, lowering cortisol via glucocorticoid receptor feedback. Ganoderic acids have direct sedative effects through GABA-A receptor modulation (possibly allosteric at the benzodiazepine site) and 5-HT2A/2C serotonergic modulation. Beta-(1,3)-(1,6)-glucan polysaccharides bind Dectin-1 and complement receptor 3 (CR3) on macrophages, natural killer cells, and dendritic cells, activating NF-kB and MAPK signaling for immune modulation. Reishi inhibits histamine release from mast cells via Fc epsilon RI downregulation and stabilizes mast cell membranes (anti-allergic effect). Antioxidant properties involve upregulation of superoxide dismutase (SOD1/SOD2), catalase, and glutathione peroxidase. Ganoderic acids may also inhibit 5-alpha-reductase and ACE.

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).

Reishi

Common

Digestive discomfort, dry mouth, dizziness.

Serious

Rare hepatotoxicity reported — avoid with liver disease. May interact with blood thinners and immunosuppressants.

Rare

Allergic reaction, nosebleeds.

Full Profiles