Quick Comparison
| Agmatine Sulfate | Reishi | |
|---|---|---|
| Half-Life | 2-3 hours | Bioactive compounds accumulate with daily use |
| Typical Dosage | 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. | 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. |
| Administration | Oral (powder, capsules). Take on empty stomach for best absorption. | Oral (capsules, powder, tincture, tea). Dual-extract preferred. Bitter taste in powder/tea form. |
| Research Papers | 10 papers | 8 papers |
| Categories |
Mechanism of Action
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.
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
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.
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
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.
Reishi →
Known as the 'mushroom of immortality' in Chinese medicine, Reishi (Ganoderma lucidum) is an adaptogenic mushroom primarily used for stress reduction, immune support, and sleep improvement. Unlike the stimulating effects of Cordyceps or Lion's Mane, Reishi is calming and is best taken in the evening. Its triterpene compounds modulate the HPA axis and support GABAergic relaxation.