Agmatine
An arginine metabolite that modulates NMDA, opioid, and nitric-oxide pathways. Modest pain, mood, and neuroprotection effects.
Moderate for neuropathic pain (Keynan et al.). Modest evidence for mood (antidepressant adjunct, especially SSRI-resistant cases). Emerging for opioid tolerance / dependence support. Effects: weeks for pain; days for mood.
Agmatine is produced from arginine by gut bacteria and human tissue. It interacts with multiple neurotransmitter systems — modulating NMDA receptors, blocking voltage-gated calcium channels, enhancing certain opioid effects, and supporting nitric oxide synthesis. Promising small-trial evidence for neuropathic pain, mood (antidepressant adjunct), and recovery from opioid tolerance / addiction. Popular in nootropic and pre-workout stacks. Generally safe, but the multi-system effects mean interaction caution.
- Form
- Agmatine sulfate capsules or powder.
- Dose
- 500 mg–2 g/day. Split AM/PM at higher doses.
- Timing
- With or without food. AM and pre-workout for nootropic / performance use.
- Schedule
- Daily, often cycled (5 on / 2 off — tolerance can build).
- Side effects
- Mild GI upset, headache. Mild blood-pressure lowering.
- Interactions
- Antihypertensives — additive BP lowering. Opioids — modulates tolerance and may reduce required dose. NMDA-active drugs — interaction. SSRIs — possible additive serotonergic.
- Contraindications
- Hypotension. Pregnancy / breastfeeding. On narrow-therapeutic-window meds without provider input.
- Lab markers
- BP.
- Food sources
- Trace amounts in fermented foods (kimchi, miso) — far below supplemental doses.
Pairs with
L-arginine, L-citrulline (nitric oxide stack). SSRIs / SNRIs (potential additive antidepressant — under provider supervision).
within Bioactive amines & polyamines