Oxiracetam (4-Hydroxy-2-oxopyrrolidine-N-acetamide or ISF-2522) is a water-soluble Ampakine nootropic in the racetam-class of compounds. Oxiracetam is considerably more potent than the original racetam, Piracetam.[i]
Oxiracetam was the 3rd racetam nootropic and developed in the 1970’s. It is chemically derived from Piracetam (2-oxo-1-pyrrolidinoacetamide) where the main difference is the addition of a hydroxyl group. Oxiracetam, similar to other racetam nootropics, has a pyrrolidone nucleus at its core.
Oxiracetam modulates AMPA-sensitive glutamate receptors, and increases neurotransmitter release.[ii]
A favorite racetam among the nootropics community. Neurohackers use Oxiracetam to boost memory and learning, support brain health and for its mild stimulant properties.
Oxiracetam helps:
- Brain Optimization: Oxiracetam significantly improves cognition and memory, sensory perception and reflexes. Focus and concentration get a boost. And recall is easier.
- Neurotransmitters: Oxiracetam enhances choline-acetyltransferase (ChAT) in your brain.[iii] ChAT is the enzyme responsible for acetylcholine (ACh). ACh is the neurotransmitter critical for encoding new memories, reasoning, concentration, cognition and neuroplasticity.
- Brain Energy: Oxiracetam modulates AMPA-receptors in your brain. Ampakines provide a stimulant-effect by influencing glutamate receptors. Without any of the side effects associated with stimulants.[iv] Oxiracetam also seems to boost ATP synthesis in brain cells.[v]
Overview
Oxiracetam (4-Hydroxy-2-oxopyrrolidine-N-acetamide or ISF-2522) is in the racetam-family of nootropic compounds. It is a water-soluble ampakine nootropic. AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic) refers to one of three glutamate receptors in your brain.[vi]
The racetam-class of nootropics have a pyrrolidone nucleus at their core. But Oxiracetam has the addition of a hydroxyl group. And Oxiracetam is a Cholinergic compound, meaning it affects acetylcholine levels in the brain.
Oxiracetam is sold as an over-the-counter, unrestricted compound in much of the world including the United States.
One of the older synthetic nootropic compounds, it is known as a cognitive enhancer. And for its stimulatory effects.
Oxiracetam is considered to be more potent than Piracetam. As an ampakine nootropic, it helps increase attention span, alertness and boosts memory. Including the ability to form long-term memories even if taken after the initial memory formation.[vii]
Ampakines tend to have a stimulant effect. But do not produce the same stimulant side effects as Ritalin or coffee from prolonged use.
Oxiracetam vs. Piracetam: What’s the Difference?
Oxiracetam was developed in the 1977 as a derivative of Piracetam.
Oxiracetam and Piracetam are both water-soluble. The half-life and nootropic benefits are similar.
The potency of Oxiracetam seems to be about 5-times that of Piracetam. So it’ll take less to get the same nootropic effect.
Both Oxiracetam and Piracetam are cognitive enhancers. And both have neuroprotective qualities. Both racetams are able to improve learning and memory. And both are able to repair brain damage.
Oxiracetam has additional benefits not shared with Piracetam. Oxiracetam provides more of a stimulatory effect than Piracetam. Some even compare it to Modafinil.
Many prefer Oxiracetam over Piracetam. But if you’re a first-time user of Oxiracetam, start with a lower dose and see how you react to it. And make sure you stack it with a good choline source to avoid the racetam-headache and irritability sometimes associated with racetams.
How does Oxiracetam Work in the Brain?
Oxiracetam boosts brain health and function in several ways. But two in particular stand out.
- Oxiracetam boosts memory and cognition. Oxiracetam modulates AMPA receptors in the brain. These receptors work like control channels, overseeing and regulating synaptic transmission. Oxiracetam also increases the density of binding sites for neurotransmitters on AMPA receptors.[viii]
The result of these actions is a stimulant-effect without any of the negative side effects associated with stimulants. And there is clinical evidence that this stimulant action has an effect on memory and cognition.
One double-blind, placebo controlled trial was done with 65 patients diagnosed with primary degenerative dementia. Patients were given 800 mg of Oxiracetam twice daily for 12 weeks, or a placebo. Subjects were tested before the trial, and after 6 and 12 weeks of treatment.
The researchers found a significant difference in favor of Oxiracetam based on a ‘quality of life scale’, and several neurological tests for memory.[ix]
Oxiracetam also seems to prevent an imbalance of acetylcholine activity when NMDA receptors are malfunctioning.[x] AMPA and NMDA receptors work together for the flow of glutamate necessary for learning and memory processes. Including Long-Term Potentiation that is associated with neuroplasticity that allows long-term memories to form.
- Oxiracetam boosts the availability of acetylcholine (ACh) in the brain. Leading to improved short-term and long-term memory. And eliminating ‘brain fog’. Oxiracetam does this by boosting the sensitivity of ACh receptors.
Oxiracetam enhances protein kinase C (PKC) which affects M1 acetylcholine receptors. Oxiracetam even demonstrates the ability to repair these receptors when damaged.[xi] More ACh results in better memory and learning.
How things go bad
Glutamate is an excitatory relative of GABA. While GABA has a calming effect, glutamate stimulates. Glutamate is the most common neurotransmitter in the central nervous system.
Glutamate is a pivotal neurotransmitter in the brain. It links the brain circuits involved in memory, learning and perception.
↓ Too little glutamate can cause problems with memory, learning and perception
↓ AMPA and NMDA receptors wear out or die
↓ Acetylcholine levels decline
↓ Cholinergic neurons wear or die out
All of these changes can happen at any age. And are a product of the food we eat, what we drink, lifestyle habits, the air we breathe and more.
So Oxiracetam can help for age-related cognitive decline, as well as a student looking to do better in school. By boosting acetylcholine and controlling glutamate in the brain.
Oxiracetam to the rescue
Clinical studies have looked at using Oxiracetam to treat Alzheimer’s, ADHD, dementia, concussions and other brain disorders. Many of these trials demonstrated Oxiracetam’s ability to improve learning, spatial learning performance, memory, recall and quality of life scores.
Oxiracetam works similar to other racetams by targeting the neurotransmitters acetylcholine (ACh) and glutamate. ACh has a significant impact on memory formation and recall. And glutamate plays a role in memory formation, motivation and attention.
Oxiracetam encourages the use of acetylcholine in your brain. So when using Oxiracetam you must ensure you have adequate choline levels available to make acetylcholine. Most neurohackers stack Oxiracetam with a choline supplement like Alpha GPC or CDP-Choline.
Oxiracetam is used to boost short and long-term memory, eliminate brain fog, improve attention and focus, and the ability to learn.
How does Oxiracetam feel?
Nootropics users report that Oxiracetam clears brain fog, improves focus and motivation. Especially when learning new material or working through a tedious task.
You could see a significant improvement in recall. Reading is easier giving you the ability to get through more pages faster and retain the information for later.
And some report an improvement in mood which could be the result of more acetylcholine available for use in the brain.
Oxiracetam does have a stimulant-effect so try not to take it too late in the day as it may interfere with a good night’s sleep.
You should be able to experience the effects of Oxiracetam soon after you take it. It’s water-soluble so it’s digested and enters your cells quickly. And unlike other stimulants, there is no “crash” once Oxiracetam leaves your system.
The Research
Researchers worked with 96 patients diagnosed with dementia for 12 months. Patients were treated with 1600 mg per day of Oxiracetam or a placebo. And were assessed at 2, 6 and 12 months of the trial.
The patients treated with Oxiracetam showed a significant improvement in reaction time and cognition. The placebo group experienced a worsening of conditions. The study authors concluded that Oxiracetam favorably acts on the symptoms of dementia. And can improve information processing, reaction times and attention.[xii]
Oxiracetam helps Traumatic Brain Injury
Traumatic brain injury (TBI) is a major public health issue affecting 1.7 million Americans each year.[xiii] TBI can be caused by sports injuries, work accidents, car and motorcycle accidents, falls, and your wife hitting you over the head with a frying pan.
Many survivors end up with long-term or even permanent neurocognitive dysfunction. Affecting cognition, motor function (movement) and personality. These disabilities are estimated to cost $9.2 billion in lifetime medical costs and $51.2 billion in productivity losses.[xiv]
In a brain subjected to TBI there is glutamate toxicity, free-radical injury to brain cells, electrolyte imbalances, mitochondrial dysfunction, inflammation, apoptosis (cell death) and stroke.[xv]
In one study done with 30 Wistar rats, researchers looked at the role Oxiracetam could have on TBI. The animals were randomly divided into 3 groups. Rats in the treatment group were given 100 mg/kg of Oxiracetam for 21 days. Neurologic impairment scores were measured on days 1, 4, 7, 14 and 21.
The researchers found the treatment group has significantly less brain impairment after 7, 14 and 21 days. And concluded that Oxiracetam shows promise in decreasing neural injury caused by TBI. Increasing learning ability, memory and space cognition.[xvi]
Oxiracetam Improves Cognition and Memory
Researchers worked with 43 patients to evaluate the effects of Oxiracetam on ‘organic brain syndrome’ (OBS). OBS is brain dysfunction that is not attributable to a specific disease like Alzheimer’s or dementia.
This double-blind, placebo-controlled study had one group of patients taking 800 mg of Oxiracetam twice a day for 8 weeks, and the other group took a placebo.
In OBS patients with mild to moderate cognitive impairment, Oxiracetam improved cognition, logic and attention. The placebo group experienced no change in cognitive impairment.[xvii]
Another study with memory impaired rats showed that Oxiracetam restored acetylcholine receptors. Restoring learning and memory as a result.[xviii]
Dosage Notes
Recommended Oxiracetam dosage is 750 – 1,500 mg per day. Divided in two equal doses. One Oxiracetam dose in the morning, and one in the early afternoon.
Oxiracetam is sold in tablet, capsule and powder form. Tablets and capsules are usually 750 mg each.
Since Oxiracetam boosts the efficiency of acetylcholine in your brain, you should stack it with a good choline source like Alpha GPC or CDP Choline.
Side Effects
Oxiracetam non-toxic. So is considered well-tolerated and safe.
Side effects are rare but can include anxiety, fatigue, headaches, nervousness and nausea. Side effects are often a result of unusually high doses of the nootropic.
Headaches from using Oxiracetam typically happen when you forget to combine it with a good choline supplement. Headaches are often a symptom of a choline deficit in your brain.
Available Forms
Oxiracetam is sold in tablet, capsule and powder form. Tablets and capsules are usually 750 mg each.
Nootropics Expert Recommendation
Oxiracetam 750 – 1,500 mg per day
We recommend using Oxiracetam as a nootropic supplement.
Your body does not make Oxiracetam on its own. So to get its benefits you must take it as a supplement.
Oxiracetam is especially helpful for those suffering from lack of energy, brain fog and the inability to focus. Oxiracetam influences AMPA and NMDA receptors in your brain. Improving the efficiency of the neurotransmitter glutamate. This excitatory brain chemical is responsible for sending signals between neuron in the brain. And plays a critical role in learning and forming memories.
Oxiracetam is also particularly useful to students and executives who want to boost cognition, learning and memory. It boosts the efficiency of the neurotransmitter acetylcholine (ACh) in your brain. ACh is critical for encoding new memories, reasoning, concentration, cognition and growth of new synapses (neuroplasticity).
Oxiracetam also helps improve verbal fluidity and sociability. Words seem to come easily, and vocabulary you didn’t know you had access to come into play.
You should stack Oxiracetam with a good choline supplement like Alpha GPC or CDP-Choline. It helps boost neural acetylcholine, so demands the presence of more choline in your brain.
You can safely boost daily intake of Oxiracetam to 2,800 mg if needed.
[i] Banfi S., Fonio W., Allievi E., Pinza M., Dorigotti L. “Cyclic GABA-GABOB analogues. IV. Activity on learning and memory.” Farmaco Sci. 1984 Jan;39(1):16-22. (source)
[ii] Marchi M., Besana E., Raiteri M. “Oxiracetam increases the release of endogenous glutamate from depolarized rat hippocampal slices.” The European Journal of Pharmacology. 1990 Aug 28;185(2-3):247-9. (source)
[iii] Mochizuki D., Sugiyama S., Shinoda Y. “[Biochemical studies of oxiracetam (CT-848) on cholinergic neurons].” in Japanese Nihon Yakurigaku Zasshi. 1992 Jan;99(1):27-35. (source)
[iv] Copani A., Genazzani A.A., Aleppo G., Casabona G., Canonico P.L., Scapagnini U., Nicoletti F. “Nootropic drugs positively modulate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-sensitive glutamate receptors in neuronal cultures.” Journal of Neurochemistry. 1992 Apr;58(4):1199-204. (source)
[v] Gabryel B., Trzeciak H.I., Pudełko A., Cieślik P. “Influence of piracetam and oxiracetam on the content of high-energy phosphates and morphometry of astrocytes in vitro.” Polish Journal of Pharmacology. 1999 Nov-Dec;51(6):485-95. (source)
[vi] Purves D., Augustine G.J., Fitzpatrick D., et al., editors. “Glutamate Receptors” Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates; 2001. (source)
[vii] Mondadori C., Möbius H.J., Borkowski J. “The GABAB receptor antagonist CGP 36,742 and the nootropic oxiracetam facilitate the formation of long-term memory.” Behavioral Brain Research. 1996 May;77(1-2):223-5. (source)
[viii] Nicoletti F., Casabona G., Genazzani A.A., Copani A., Aleppo G., Canonico P.L., Scapagnini U. “Excitatory amino acids and neuronal plasticity: modulation of AMPA receptors as a novel substrate for the action of nootropic drugs.” Functional Neurology. 1992 Sep-Oct;7(5):413-22. (source)
[ix] Bottini G., Vallar G., Cappa S., Monza G.C., Scarpini E., Baron P., Cheldi A., Scarlato G. “Oxiracetam in dementia: a double-blind, placebo-controlled study.” Acta Neurologica Scandinavia. 1992 Sep;86(3):237-41. (source)
[x] Belfiore P., Ponzio F., Biagetti R., Berettera C., Magnani M., Pozzi O. “Oxiracetam prevents the hippocampal cholinergic hypofunction induced by the NMDA receptor blocker AP7.” Neuroscience Letters. 1992 Aug 31;143(1-2):127-30. (source)
[xi] Fordyce D.E., Clark V.J., Paylor R., Wehner J.M. “Enhancement of hippocampally-mediated learning and protein kinase C activity by oxiracetam in learning-impaired DBA/2 mice.” Brain Research. 1995 Feb 20;672(1-2):170-6. (source)
[xii] Rozzini R., Zanetti O., Bianchetti A. “Treatment of cognitive impairment secondary to degenerative dementia. Effectiveness of oxiracetam therapy.” Acta Neurol (Napoli). 1993 Feb;15(1):44-52. (source)
[xiii] Faul M, Xu L, Wald MM, Coronado VG (2010) “Traumatic Brain Injury in the United States: Emergency Department Visits, Hospitalizations and Deaths 2002–2006”. Atlanta (GA): Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. (source)
[xiv] Rutland-Brown W., Langlois J.A., Thomas K.E., Xi Y.L. “Incidence of traumatic brain injury in the United States, 2003.” Journal of Head Trauma Rehabilitation. 2006 Nov- Dec;21(6):544-8. (source)
[xv] Yi J.H., Hazell A.S. “Excitotoxic mechanisms and the role of astrocytic glutamate transporters in traumatic brain injury.”Neurochemistry International. 2006 Apr;48(5):394-403 (source)
[xvi] Li J.W., Yang D.J., Chen X.Y., Liang H.Q. “[Protective effect of oxiracetam on traumatic brain injury in rats]. in Chinese Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2013 Jul;29(4):298-300. (source)
[xvii] Moglia A., Sinforiani E., Zandrini C., Gualtieri S., Corsico R., Arrigo A. “Activity of oxiracetam in patients with organic brain syndrome: a neuropsychological study.” Clinical Neuropharmacology. 1986;9 Suppl 3:S73-8. (source)
[xviii] Magnani M., Pozzi O., Biagetti R., Banfi S., Dorigotti L. “Oxiracetam antagonizes the disruptive effects of scopolamine on memory in the radial maze.” Psychopharmacology (Berl). 1992;106(2):175-8. (source)
Just finished my first bottle very well worth it . Thanks for the video that inspired me to try it . I was searching around and really wondering why you don’t have a video on Adrafinil I haven’t tried it yet but I read it supposed to be very similar to modafinil . An idea for a future video . Thanks for your work.
Justin, my self-imposed ‘policy’ on reviewing nootropics is to keep the supplements I write about as ‘natural’ as possible. Supplements that can be purchased in most places worldwide without a prescription. And the racetams are as far as I’m willing to take this for now. Adrafinil is too closely related to a controlled substance in many countries. And the reason I haven’t and likely will not review it.
Hi Mr. Tomen,
First of all let me start by saying I absolutely love your videos. To say that they have been beneficial to my person is an understatement. I have. A question that would be of great assistance to me.
I purchased Oxiracetam, but I didn’t experience any effects. I was a bit taken back as I respond well to Piracetam. I usually take 3,500 to 4,000 mg of Piracetam to feel the congnitive effects together with choline source (usually Alpha GPC).
I tried several dosages of Oxiracetam and was unable to feel the effects. I tried 750 mg, a couple days later I increased it to 1,500 mg and that too didn’t work. I have increased it to 2,000 and 2,500 mg and nothing. Each time I have taken Oxiracetam I have also taken Alpha GPC. Do. You think I should increase the dosage further or is this just one of those medicines that I won’t be able to respond to.
I’m fairly healthy person. I do not illegal drugs and very rarely would I have a drink (once every 6 months). I’m not sure if this would help to shed some light, but in the past Huperzine A has also not worked for me. I have tried many dosages with huperzine a in the past upto 700 mcg without feeling anything whatsoever.
However, Piracetam and Primaracetam work every time, as does L-Theanine.
Any advice/suggestion is greatly appreciated.
Thanks.
Manny, don’t try and force a reaction. The reality is that you are just not meant to be using certain nootropics if you find you get no response. Every one of us is wired differently and what works for one person may have zero effect or a negative effect to the person standing next to them.