Agmatine
Summary
Agmatine is decarboxylated arginine. One randomised trial in lumbar disc radiculopathy found 2.67 g/day for 14 days improved pain and quality of life more than placebo, though only 61 of 99 people were analysed. Other human data are tiny uncontrolled case series in nerve pain, depression and OCD. Diarrhoea and nausea appeared at 3.56 g/day.
Key facts
- Decarboxylated arginine; acts on imidazoline and alpha-2 receptors, NMDA receptors and nitric oxide synthase[4]
- Lumbar disc radiculopathy: 2.67 g/day for 14 days improved average pain 26.7% versus 6.0% on placebo, and quality of life 70.8% versus 20.0%[1]
- In dose escalation, 3 people on 3.56 g/day had mild-to-moderate diarrhoea and mild nausea that stopped when dosing ended[1]
- Preclinical studies show agmatine can raise or lower blood pressure and heart rate depending on dose and route[4]
- 3 graded human outcomes on this page
- October 13, 2026
How it works
ProposedAgmatine binds imidazoline I1 and I2 receptors and alpha-2 adrenoceptors (it was first identified as clonidine-displacing substance), blocks NMDA glutamate receptors, acts on serotonergic receptors and modulates nitric oxide synthase. Its pain and mood effects in people are thought to involve NMDA blockade, but this is not established.[4][5]
What the human research says
Human trials only, one row per outcome. The form column shows what each trial actually tested. Grades follow our evidence-grading policy.
At a glance: strongest evidence per outcome
| Outcome | Grade | Effect | Strongest evidence | Rows |
|---|---|---|---|---|
| Nerve pain | Grade D | Improved | RCT · n = 61 · 2010 | 2 rows |
| Mood | Grade D | Mixed | Open-label · n = 5 · 2026 | 1 row |
Every graded row
| Outcome | Effect | Grade | Best evidence | PMID |
|---|---|---|---|---|
| Pain and quality of life in lumbar disc radiculopathy | Improved | Grade D | RCT · n = 61 · 2010 Adults with herniated lumbar disc-associated radiculopathy in Israel (99 randomised; 31 agmatine and 30 placebo analysed) Form: Agmatine sulfate · Dose: 2.67 g/day · Duration: 14 days Average pain improved 26.7% from baseline with agmatine versus 6.0% with placebo, and quality of life 70.8% versus 20.0% (both P ≤ 0.05). No treatment-related adverse events. | 20447305 (opens PubMed)Source [1] |
| Neuropathic pain in painful small fiber neuropathy | Improved | Grade D | Open-label trial · n = 11 · 2020 Adults with painful small fiber neuropathy (8 diabetic) resistant to standard drugs (USA) Form: Agmatine sulfate (AgmaSet capsules) · Dose: 2.67 g/day · Duration: 2 months Neuropathic pain scores fell 46.4% on average (26.0 rating points); every completer improved to some extent. | 32102167 (opens PubMed)Source [2] |
| Obsessive-compulsive symptoms added to SSRIs | Mixed | Grade D | Open-label trial · n = 5 · 2026 Adults with treatment-resistant OCD on stable SSRIs (USA) Form: Agmatine sulfate · Dose: 650 mg/day for 1 week, then 1,300 mg/day · Duration: 112 days 2 of 5 patients had a clinically meaningful (≥25%) drop in Y-BOCS score; no discontinuations, and mild transient stomach upset in 2. | 41717561 (opens PubMed)Source [3] |
Forms
| Form | Elemental % | Absorption (human data) | GI tolerance | Studied for |
|---|---|---|---|---|
| Agmatine sulfate (capsules or powder) | Varies[1] | No human pharmacokinetic data were found in the cited sources.[1] | Normal safety tests up to 3.56 g/day for 21 days; diarrhoea and nausea in 3 people at that dose. A 5-year self-report by the two developers at 2.67 g/day found normal blood and urine tests (n = 2, uncontrolled).[1][6] | Nerve-pain trials (2.67 g/day) and an OCD case series (0.65–1.3 g/day) |
Studied doses
Doses studied in human trials ranged from 650–1,300 mg/day of agmatine sulfate (OCD case series, 16 weeks) to 2.67 g/day (radiculopathy trial, 14 days; small fiber neuropathy, 2 months), with 3.56 g/day for up to 21 days in a safety phase.[1][2][3]
Interactions
Published interactions only: each row cites a source. No row means none was found in our sources, not that a combination is safe.
Medicines
- Blood-pressure medicines acting on alpha-2 or imidazoline receptorsReviewAgmatine binds the same imidazoline and alpha-2 receptors and was first identified as clonidine-displacing substance; preclinical work shows it can raise or lower blood pressure and heart rate. No human combination studies exist.[4]
- Other blood-pressure medicinesReviewBecause preclinical studies show dose-dependent blood-pressure effects in either direction, combined effects are unpredictable; untested in people.[4]
- NMDA-receptor blockersReviewAgmatine blocks NMDA receptors, so effects could add up; no human combination data.[4][5]
- Antidepressants (SSRIs)ReviewAgmatine acts on serotonergic receptors. In a 5-patient OCD series it was added to stable SSRIs without discontinuations; combined safety has not been tested in a controlled trial.[3][4]
Who should be careful
- Pregnancy, breastfeeding and children
- Human studies enrolled adults only, so there are no safety data for these groups.[1][2][3]
- People on blood-pressure or heart-rate medicines
- Agmatine acts on the receptors targeted by clonidine-type drugs and can shift blood pressure either way in preclinical studies.[4]
Talk to your pharmacist or clinician before starting a supplement, especially if you take prescription medicines.
How to read the label
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Frequently asked questions
What is agmatine?
A compound the body makes from arginine. Supplements contain agmatine sulfate.[4][5]
Does agmatine help sciatica-type nerve pain?
One 14-day trial in disc-related radiculopathy found more pain relief than placebo, but only 61 of 99 people were analysed and the developer co-authored it.[1]
Does agmatine help depression or OCD?
Evidence is limited to a few case reports in depression and a 5-patient OCD series in which 2 improved meaningfully. No controlled trials exist.[3][7]
What side effects have been reported?
Mild-to-moderate diarrhoea and nausea at 3.56 g/day, and mild stomach upset at 1.3 g/day.[1][3]
Does agmatine affect blood pressure?
Possibly. It acts on the same receptors as clonidine, and preclinical studies show it can push blood pressure up or down.[4]
Sources
- [1]Safety 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 Trial.. Pain Med, 2010. RCT
- [2]Evidence for Dietary Agmatine Sulfate Effectiveness in Neuropathies Associated with Painful Small Fiber Neuropathy. A Pilot Open-Label Consecutive Case Series Study.. Nutrients, 2020. open-label
- [3]Agmatine augmentation in treatment-resistant obsessive-compulsive disorder: a prospective open-label case series.. Front Psychiatry, 2026. open-label
- [4]Exploring the Cardiovascular Impacts of Agmatine: A Systematic Review.. Med Sci (Basel), 2025. systematic-review
- [5]Agmatine: clinical applications after 100 years in translation.. Drug Discov Today, 2013. review
- [6]Long-term (5 years), high daily dosage of dietary agmatine--evidence of safety: a case report.. J Med Food, 2014. observational
- [7]The clinical antidepressant effect of exogenous agmatine is not reversed by parachlorophenylalanine: a pilot study.. Acta Neuropsychiatr, 2013. observational
What changed
- Independent adversarial review: developer co-authorship named explicitly on the radiculopathy trial; the 5-year safety report is now labelled as an uncontrolled self-report by the two developers.
- Second-pass self-review: every PMID re-checked against NCBI esummary (title, year, no retraction or expression-of-concern flag), every dose, n and duration re-read against the PubMed abstract or PMC full text, grades held conservative, and interactions limited to what a cited source supports.
- First draft. Source titles and years taken from NCBI E-utilities esummary; abstracts read for every evidence row.