Quick Comparison
| Agmatine Sulfate | Black Seed Oil | |
|---|---|---|
| Half-Life | 2-3 hours | 6-8 hours (thymoquinone) |
| 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: 1-3 teaspoons oil daily, or 500-1000 mg standardized extract (minimum 2% thymoquinone). Take with food. Cold-pressed oil retains more bioactives. Taste is peppery/bitter — capsules available for those who dislike the taste. |
| Administration | Oral (powder, capsules). Take on empty stomach for best absorption. | Oral (oil, softgels, capsules). Cold-pressed oil preferred. Take with food. |
| Research Papers | 10 papers | 9 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.
Black Seed Oil
Thymoquinone is the primary bioactive, providing neuroprotection through multiple mechanisms: it scavenges reactive oxygen species (superoxide, hydroxyl radical, peroxynitrite) and upregulates Nrf2/ARE pathway, increasing glutathione (via GCLC, GSS), superoxide dismutase (SOD1/SOD2), and catalase. It inhibits NF-kB by preventing IkB-alpha degradation and blocking p65 nuclear translocation, reducing neuroinflammation and pro-inflammatory cytokine release. Thymoquinone inhibits acetylcholinesterase (AChE) at the peripheral anionic site, increasing synaptic acetylcholine. It modulates GABA-A receptors (positive allosteric modulation at benzodiazepine site), providing anxiolytic effects. Thymoquinone protects neurons from amyloid-beta toxicity by reducing oxidative stress and inhibiting beta-secretase (BACE1). It reduces tau hyperphosphorylation by inhibiting GSK-3beta and CDK5.
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.
Black Seed Oil
Common
Mild gastrointestinal discomfort, burping.
Serious
May lower blood pressure and blood sugar — caution with relevant medications. May slow blood clotting.
Rare
Allergic reaction, contact dermatitis with topical use.
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.
Black Seed Oil →
Extracted from Nigella sativa seeds, black seed oil contains thymoquinone — a compound with potent anti-inflammatory, antioxidant, and neuroprotective properties. Used in traditional Middle Eastern medicine for over 2,000 years, modern research supports cognitive benefits through anti-neuroinflammation, acetylcholinesterase inhibition, and GABA modulation. Also supports metabolic health and immune function.