Home Ingredients Oxiracetam (4-Hydroxy Piracetam)
Cognitive

Oxiracetam (4-Hydroxy Piracetam)

Synthetic — hydroxylated piracetam derivative
Evidence Level
Limited
3 Clinical Trials
5 Documented Benefits
2/5 Evidence Score

Oxiracetam is a hydroxylated piracetam analog developed in Italy in the 1980s as a cognitive enhancer. Evidence is mixed: positive trial data in mild-to-moderate dementia contradicted by negative results in pure Alzheimer's disease. The honest framing: oxiracetam may help some forms of cognitive decline, especially vascular or multi-infarct dementia, but evidence is inconsistent and rigorous modern trials are limited. The L-isomer is being developed for traumatic brain injury in China. Not FDA-approved — available as a prescription drug in Italy and a research compound elsewhere. Most consumer use is off-label experimentation in the racetam nootropic community. Approach with realistic expectations: this is not a validated cognitive enhancer for healthy adults.

Studied Dose 800 mg twice daily (1,600 mg/day) in the dementia trials; it is an unapproved drug, and the 800 to 2,400 mg/day nootropic range is off-label use.
Active Compound Oxiracetam (4-hydroxy-2-oxo-1-pyrrolidineacetamide), a hydroxyl-substituted piracetam analog; L-oxiracetam is the active enantiomer.

Benefits

Mild-moderate dementia cognitive support

A double-blind placebo-controlled trial in outpatients with mild-to-moderate senile dementia showed significant cognitive improvements at 800 mg twice daily over 90 days across multiple cognitive tests. Open follow-up suggested maintained benefits at 1 year.

Supported by Trial 1, Trial 2

Mixed evidence in Alzheimer's disease

Counter-evidence: a separate double-blind placebo-controlled trial in patients with probable Alzheimer's showed no improvement across neuropsychological tests, concluding oxiracetam is ineffective for AD-related cognitive impairment. Honest interpretation: results inconsistent across populations and trial designs.

Supported by Trial 2

Vascular and multi-infarct dementia

Some evidence suggests oxiracetam may be more effective in vascular and multi-infarct dementia than in pure Alzheimer's, possibly through effects on microcirculation and metabolic activity. Limited rigorous head-to-head comparisons available.

Supported by Trial 1, Trial 2

Craniocerebral injury (L-oxiracetam Phase 3)

A Phase 3 trial in China of injectable (intravenous) L-oxiracetam for memory and cognitive impairment after traumatic brain injury is recruiting and has reported no results. It uses an injected drug, not the oral form, so it does not show a benefit for anyone taking oxiracetam by mouth.

Supported by Trial 3

Post-stroke cognitive impairment

No post-stroke trial is cited on this page, and this use is not established. Any older reports are small and use outdated criteria.

Supported by Trial 1, Trial 2

Mechanism of action

1

Cholinergic and glutamatergic enhancement

Oxiracetam increases ACh release and modulates AMPA/NMDA glutamatergic transmission. Cholinergic effects more pronounced than piracetam. Mechanism for cognitive enhancement claims via dual neurotransmitter system support.

2

Cerebral metabolic activity enhancement

Oxiracetam increases cerebral oxygen consumption, glucose utilization, and ATP/ADP ratio in brain — particularly in hypoxic conditions. Hydroxyl group may enhance this metabolic effect vs piracetam. Mechanism for proposed neuroprotective effects in vascular cognitive impairment.

3

Phosphoinositide turnover modulation

Oxiracetam stimulates phosphoinositide turnover and protein kinase C activation — second messenger pathways involved in synaptic plasticity and learning. Mechanism distinct from typical neurotransmitter modulation; may explain longer-duration cognitive effects.

4

BBB penetration via active transport

Crosses BBB efficiently despite water-solubility — possibly via active transport. CNS bioavailability higher than expected for compound's polarity. Half-life longer than piracetam (8-10 hours) — longer cognitive effect duration.

Clinical trials

1
Oxiracetam in Mild-Moderate Dementia (Pivotal Positive)
PubMed

Double-blind placebo-controlled parallel-group clinical trial (Villardita C, Grioli S, Lomeo C, Cattaneo C, Neuropsychobiology 25(1):24-28, doi:10.1159/000118805).

60 male and female outpatients with SDAT (Alzheimer type) and multi-infarct dementia (mid) of mild-moderate degree. Oxiracetam 800 mg BID (1600 mg/day) vs placebo for 90 days. Open follow-up to 1 year for oxiracetam group.

Significant improvements in oxiracetam group vs placebo on: MMSE, Auditory Continuous Performance Test, Rey's 15 Words Test, Block Tapping Test, Mattis Word Fluency, Luria Alternating Series, Instrumental ADL. In an open (uncontrolled) 1-year follow-up, 29 of 30 patients continued; some gains held versus baseline but several measures (Digit Span Backward, Gibson's Spiral) significantly worsened by the late phase. Positive clinical trial — among more robust racetam dementia trials. Limited by older diagnostic criteria and modest sample.

2
Oxiracetam in Alzheimer's (negative)
PubMed

Double-blind placebo-controlled treatment study (Green RC, Goldstein FC, Auchus AP, Presley R, Clark WS, Van Tuyl L, Green J, Hersch SM, Karp HR 1992, Arch Neurol 49(11):1135-1136, doi:10.1001/archneur.1992.00530350049018).

24 carefully assessed patients with probable Alzheimer's disease. Broad battery of neuropsychological tests applied.

Oxiracetam ineffective in reducing cognitive impairment due to Alzheimer's disease. Broad battery of neuropsychological tests failed to reveal any improvement in treated group OR in any individual treated patient when individual scores analyzed. Negative clinical trial in Alzheimer's disease. Honest interpretation: oxiracetam efficacy varies across study designs, populations, and assessment methods. Conservative conclusion: weak overall efficacy for AD specifically.

3
L-Oxiracetam Injectable Trial in Brain Injury (Recruiting, No Results)

Phase 3 randomized double-blind positive drug/placebo parallel-controlled multicenter trial (NCT04205565, Nanjing Yoko Biomedical sponsor).

Patients with mild-to-moderate craniocerebral injury (GCS 10-15) for memory and cognitive impairment. L-oxiracetam injection (active enantiomer) vs racemic oxiracetam injection vs placebo, IV daily.

No results. This is a registry entry for a recruiting trial, not evidence of benefit. It studies an intravenous (injectable) drug, which is the wrong route for an oral product, and no outcomes have been reported.

Side effects and drug interactions

Common Potential side effects

Generally well-tolerated; safety profile similar to piracetam.
Headache (relatively common).
Insomnia (stimulating profile — avoid late in day).
Nausea, GI upset.
Dizziness, nervousness.
Pregnancy/lactation: avoid.
Renal impairment: dose adjustment.
Long-term safety in healthy people is unstudied: the only longer data come from elderly dementia patients taking it as a drug.

Important Drug interactions

Anticoagulants: mild antiplatelet effect possible.
Stimulants: theoretical additive CNS activation.
Cholinergic medications: theoretical additive effects.
Most medications: compatible at typical doses.
No significant CYP450 interactions documented.

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Frequently asked questions about Oxiracetam (4-Hydroxy Piracetam)

What is oxiracetam?

Oxiracetam is a racetam nootropic often described as mildly stimulating, studied for memory, focus, and logical thinking. It is not an approved supplement or drug in the US, though it has been studied clinically elsewhere.

What is oxiracetam used for?

It is researched for cognitive support, including attention and memory, and is popular among nootropic users for focus and mental energy. Evidence in healthy people is limited.

How much oxiracetam is used?

Doses in research and community use are often around 800 to 2,400 mg per day, split. As with other racetams, quality and legal status vary, so caution is warranted.

Is oxiracetam safe?

Short-term use is generally reported as tolerated, with possible headache or restlessness. Long-term and self-directed use carries uncertainty, and it is not an approved US supplement, so consult a healthcare professional.

What is the recommended dosage of Oxiracetam?

The clinically studied dose is 800 mg twice daily (1,600 mg/day) in the dementia trials; it is an unapproved drug, and the 800 to 2,400 mg/day nootropic range is off-label use. Always follow the product label and check with a healthcare provider for personal advice.

Is Oxiracetam safe, and does it have side effects?

For most healthy adults, Oxiracetam is well tolerated at studied doses. Reported effects can include: Generally well-tolerated; safety profile similar to piracetam. Headache (relatively common). It may also interact with some medications. Oxiracetam is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Oxiracetam interact with any medications?

Possible interactions include: Anticoagulants: mild antiplatelet effect possible. Stimulants: theoretical additive CNS activation. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Oxiracetam?

NutraSmarts rates the evidence for Oxiracetam as Limited (2 out of 5). It is backed by 3 clinical trials and 4 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(4 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Maina G, Fiori L, Torta R, Fagiani MB, Ravizza L, Bonavita E, Ghiazza B, Teruzzi F, Zagnoni PG, Ferrario E Oxiracetam in the treatment of primary degenerative and multi-infarct dementia: a double-blind, placebo-controlled study Neuropsychobiology. 1989;21(3):141-5. doi:10.1159/000118567.PubMedUsed to support: In 289 analyzed patients with primary degenerative, multi-infarct or mixed dementia, oxiracetam 800 mg twice daily for 12 weeks beat placebo on dementia and complaint scales (IPSC-E, Blessed, NMICS). A positive but old trial in elderly dementia patients, not healthy nootropic users.
  2. Villardita C, Grioli S, Lomeo C, Cattaneo C, Parini J Clinical studies with oxiracetam in patients with dementia of Alzheimer type and multi-infarct dementia of mild to moderate degree Neuropsychobiology. 1992;25(1):24-8. doi:10.1159/000118805.PubMedUsed to support: In 60 outpatients with mild-to-moderate Alzheimer-type or multi-infarct dementia, oxiracetam 800 mg twice daily beat placebo on several cognitive tests over 90 days. In an uncontrolled 1-year extension some gains held but several measures worsened. A small, old, disease-population trial.
  3. Bottini G, Vallar G, Cappa S, Monza GC, Scarpini E, Baron P, Cheldi A, Scarlato G Oxiracetam in dementia: a double-blind, placebo-controlled study Acta Neurol Scand. 1992;86(3):237-41. doi:10.1111/j.1600-0404.1992.tb05077.x.PubMedUsed to support: In 65 patients with primary degenerative, multi-infarct or mixed dementia, oxiracetam 800 mg twice daily for 12 weeks improved a quality-of-life scale and some neuropsychological tests versus placebo. A positive but small and old trial in a dementia population, not healthy adults.
  4. Green RC, Goldstein FC, Auchus AP, Presley R, Clark WS, Van Tuyl L, Green J, Hersch SM, Karp HR Treatment trial of oxiracetam in Alzheimer's disease Arch Neurol. 1992;49(11):1135-6. doi:10.1001/archneur.1992.00530350049018.PubMedUsed to support: In 24 patients with probable Alzheimer's disease, a double-blind placebo-controlled trial found oxiracetam produced no improvement on a broad battery of neuropsychological tests, neither in the treated group nor in any individual patient, concluding it is ineffective for Alzheimer's cognitive impairment.