Last Updated: October 31, 2023

Agmatine is a metabolite of L-Arginine. It shows promise for alleviating neuropathic pain and drug addiction and shows some potential in protecting against strokes and benefitting cognitive health.

Agmatine is most often used for

What is agmatine?

Agmatine is derived from L-arginine and is considered a neurotransmitter and neuromodulator. Animal studies suggest it can be potentially used to treat neuropathic pain and drug addiction.[1][2] Agmatine can be found in certain fermented foods, including wine.

What are agmatine’s main benefits?

Agmatine plays a role in influencing receptors associated with pain perception, but studies show it has weak general analgesic properties.[3] However, in vitro studies have suggested the neurotransmitter does show dose-dependent pain-relieving effects in the context of treating neuropathic pain.[1]

Agmatine’s effectiveness for drug addiction requires further research, but preliminary animal studies show promise in the treatment of alcohol withdrawal. These studies showed a decrease in alcohol withdrawal symptoms such as tremors and anxiety after supplementation.[2][4] Agmatine has also been studied for its potential benefits for treating cocaine addiction, but animal studies have not shown promising results.[5]. Limited human evidence suggests agmatine may show efficacy for treating depression[6] and nerve-related pain.[7][8][7]

What are agmatine’s main drawbacks?

Limited human evidence suggests that agmatine may have mild to moderate side effects like diarrhea and mild nausea, but these resolve with time or treatment secession.[6][7] Further research is needed to determine whether agmatine is safe to use.

How does agmatine work?

Agmatine is an endogenous neuromodulator derived from L-arginine with an affinity for various transmembrane receptors, including alpha-2 adrenergic, imidazoline I1, and NMDA receptors.[9]

What else is Agmatine known as?
Note that Agmatine is also known as:
  • Clonidine-displacing substance
  • 4-(aminobutyl)guanidine
  • Decarboxylated arginine
Agmatine should not be confused with:
Dosage information

There are no standard dosages for agmatine because of the lack of human evidence for its effects. However, a single human study used 1,300-2,670mg of agmatine, daily for the treatment of neuropathic pain. The estimated human dose for improving cognition is 1.6-6.4mg/kg of agmatine, taken orally. This is based off of the 10-40mg/kg dosage range for rats, and is equivalent to 109-435mg for a 150lb person. Supplementation should not exceed 6.4mg/kg of bodyweight.

Studies on agmatine use a daily dosing protocol.

Agmatine is not absorbed well when taken with dietary protein, because it uses the same transporters as arginine. Further research is needed to determine if oral agmatine supplementation provides the same benefits as were observed in animal studies.

Examine Database: Agmatine
What works and what doesn't?

Unlock the full potential of Examine

Get started

Don't miss out on the latest research

Research Breakdown

  1. ^Fairbanks CA, Schreiber KL, Brewer KL, Yu CG, Stone LS, Kitto KF, Nguyen HO, Grocholski BM, Shoeman DW, Kehl LJ, Regunathan S, Reis DJ, Yezierski RP, Wilcox GLAgmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury.Proc Natl Acad Sci U S A.(2000-Sep-12)
  2. ^Uzbay IT, Yeşilyurt O, Celik T, Ergün H, Işimer AEffects of agmatine on ethanol withdrawal syndrome in rats.Behav Brain Res.(2000-Jan)
  3. ^Li J, Li X, Pei G, Qin BYEffects of agmatine on tolerance to and substance dependence on morphine in mice.Zhongguo Yao Li Xue Bao.(1999-Mar)
  4. ^Taksande BG, Kotagale NR, Patel MR, Shelkar GP, Ugale RR, Chopde CTAgmatine, an endogenous imidazoline receptor ligand modulates ethanol anxiolysis and withdrawal anxiety in rats.Eur J Pharmacol.(2010-Jul-10)
  5. ^Cantin L, Lenoir M, Augier E, Vanhille N, Dubreucq S, Serre F, Vouillac C, Ahmed SHCocaine is low on the value ladder of rats: possible evidence for resilience to addiction.PLoS One.(2010-Jul-28)
  6. ^Shopsin BThe clinical antidepressant effect of exogenous agmatine is not reversed by parachlorophenylalanine: a pilot study.Acta Neuropsychiatr.(2013-Apr)
  7. ^Keynan O, Mirovsky Y, Dekel S, Gilad VH, Gilad GMSafety and Efficacy of Dietary Agmatine Sulfate in Lumbar Disc-associated Radiculopathy. An Open-label, Dose-escalating Study Followed by a Randomized, Double-blind, Placebo-controlled TrialPain Med.(2010 Mar)
  8. ^Rosenberg ML, Tohidi V, Sherwood K, Gayen S, Medel R, Gilad GMEvidence for Dietary Agmatine Sulfate Effectiveness in Neuropathies Associated with Painful Small Fiber Neuropathy. A Pilot Open-Label Consecutive Case Series Study.Nutrients.(2020-Feb-23)
  9. ^Halaris A, Plietz JAgmatine : metabolic pathway and spectrum of activity in brain.CNS Drugs.(2007)