I personally don’t do well with racetams in the long term and don’t take them.  I’ve seen some negative effects with racetams, which I’ve written about, mainly to combat the hype.

This post explores some of the benefits for those who do well with it and want to take it.  I thought it would be beneficial to see what the research actually says about this class of super popular smart drugs.

I think the important thing is to ‘Self Hack’ and see if you benefit from it, especially if you have a condition that is helped by the racetams.  If you don’t notice clear benefits, I would stop taking them.

I think it’s important at Selfhacked to not allow my individual experience corrupt objective benefits of some treatment modality.

Molecular Thoughts

Introduction to Racetams

Racetams are cognitive enhancers also known as Nootropics.  Piracetam is the “original” racetam.  It is the least potent although still highly recommended, especially for those just beginning experimentation with the racetam family.

Since the discovery of Piracetam, several more potent and arguably effective derivatives have been found on the market.  Each one varies slightly from each other in its mode of action.  So this is an attempt to let you see BOTH user reported effects (what is found colloquially on the internet) alongside published research.

Unfortunately, there appears to be little research on young, cognitively healthy volunteers.

There is, however, research on the elderly, demented, schizophrenic, and those suffering from neurodegeneration caused by head trauma, stroke, and alcoholism.

Aniracetam and the Brain

Aniracetam encourages acetylcholine release (R).

Aniracetam releases serotonin and dopamine in the brain via cholinergic pathways in the prefrontal cortex (R).

Aniracetam, although not clinically proven in humans, is the best of all the racetams for reducing anxiety and depression (R).

Aniracetam is able to alleviate memory damage and learning impairments due to various traumas (R).

Aniracetam appears to inhibit the effects of cortisol via GABA (R).

Oxiracetam and the Brain

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Oxiracetam increases Long term potentiation in the hippocampus, similar to Aniracetam (animals) (R).

Oxiracetam increases memory test scores in mice. Dosed 25-50mg/kg and taken five days before training (R,R2).

In 60 elderly patients with mental disorders, Oxiracetam exhibited more statistically significant improvement in “the memory factor” (R).

Oxiracetam (100mg/kg) given immediately after a learning experience ‘post-trial’ can effectively facilitate the formation of long-term memory delectable up to 4 months after dosing (R).

This study brings to light the fact that many nootropics, including oxiracetam, show evidence of memory retention after 16-24hrs (R), which may explain the negative response in tests preformed before this 24 hr window has lapsed.

Oxiracetam reduces drug induced amnesia, when given to mice 30 minutes before drug administration (R).

Oxiracetam also slowed the decrease of acetylcholine in the cortex and hippocampus, in the drug-induced amnesia (R).

The same test performed in humans showed that Oxiracetam improved overall test performances in drug-induced amnesia (R).

Oxiracetam activates a critical enzyme underlying learning and memory processes (Protein Kinase C) (R,R2).

In mice, Oxiracetam improves scores in maze memory tests, but appears to help only untrained mice (R).

Interestingly , improved performance were seen in doses of 25mg/kg and 100mg/kg but not at the midline 50mg/kg mark (R).

Oxiracetam Can Prevent Neurodamage in Dementia

Oxiracetam is able to improve dementia in elderly patients (R,R2).

In patients with multiple forms of dementia, and those suffering from multiple strokes, 1,600mg/kg Oxiracetam taken daily for 12 weeks significantly improved ‘quality of life’ as well as scores in neuropsychological tests (R).

Oxiracetam is able to improve dementia in elderly patients in several major rating scales (R,R2).

In stroke and primary dementia patients, Oxiracetam dosed 1,200mg/kg improved social function, and verbal fluency (R,R2).

Oxiracetam can prevent Neuron Damage from Chemical Exposure

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Oxiracetam, as a pre-treatment to exposure, can prevent neuron damage from TBT (organotin trimethyltin) – a toxic biocide (R).

Oxiracetam may help with Energy Production

In test tubes, Oxiracetam has been shown to increase the production of ATP (R).

Oxiracetam Does Not Effect Sleep Once Asleep

Oxiracetam through EEG testing, does not impair sleep quality, although it may prolong the ability to actually fall asleep dose dependently (doses ranging from 25mg-50mg/kg) (R).

Pre-Natal Supplementation

Oxiracetam significantly improved the performance in the off-spring of mice when the mothers were supplemented with 50mg/kg as a prenatal injection over control (R).

Oxiracetam and Nicotine has a Synergistic Effect

The combination of Nicotine and Oxiracetam have a synergy in learning tasks.

Nicotine and Oxiracetam had synergistic effect in mice tested in both passive and active avoidance tests (active test – are tests aligned for depressive symptoms. Passive tests – are a short and long term memory assessment) (R,R2).

The combination of the two drugs improved passive avoidance more than either drug separately, and in the active avoidance test the combination (with low dose nicotine) showed improved effects never observed with nicotine alone (R).

Oxiracetam also prevented slight depressive behavior by mice when given high doses (1mg/kg) of nicotine insomnia, drowsiness and agitation (R). Because of Piracetams to anti-clotting abilities, there is an advisement to stay away from Piracetam if already on blood thinning drugs. Headache, fatique, foggy thinking are all symptoms of the Racetams that you should either stop, or have dosed too high.”>(R).

Mechanism of Oxiracetam in the Brain

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Oxiracetam increases signaling efficiency in hippocampal cells (R).

Oxiracetam increases neuron signaling efficiency by increasing the release of glutamate and D-aspartic acid in the brain (R).

Oxiracetam is a positive modulator of AMPA sensitive glutamate receptors in neurons (R).

Oxiracetam selectively increases the release of glutamate and acetylcholine in the hippocampus (R).

Injections of both piracetam and oxiracetam increase choline uptake in the hippocampus (R).

Pramiracetam and The Brain

Pramiracitam, similar to piracetam, has been tested in drug induced amnesia studies.

In healthy volunteers, Pramiracetam has been shown to reduce drug induced amnesia in both young and older subjects (R).

Studies also show that pre-administration of pramiracetam is also effective at suppressing drug induced amnesia (R).

Pramiracetam increases exploratory activity in mice when dosed at 15mg/kg, and is suppressed at 60mg/kg with the middle range 30mg/kg having no effect (R).

Pramiracetam has been shown to increase cognitive abilities and memory in young men suffering from head trauma. This improvement was maintained even after pramiracetam was discontinued (R).

Pramiracetam significantly improves objective memory in non-depressed, non-demented healthy elderly (R) .

In healthy elderly with memory loss, supplementation with pramiracetam proved more beneficial than memory training (R).

Phenylpiracetam and The Brain

Phenylpiracetam is thought to cross the blood brain barrier because of the additional phenyl group, although there is no research to validate this.

Phenylpiracetam Helps in brain injuries, stroke and epilepsy.

Phenylpiracetam daily for one year, was able to improve both functional and cognitive parameters in stroke patients (dose was 400mg) (R).

Phenylpiracetam dosed 200mg improved both neurological and psychological symptoms over the control group in individuals with diseases of the brain (R).

Epilepsy patients dosed with 100mg 2x/day phenylpiracetam improved by 12% in cognitive performance tests (R).

In individuals suffering from diseases of the brain (brain tumors or natural lesions), 200mg phenylpiracetam showed improvements in cognitive decline (R).

Anxiety and Depression

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In individuals suffering from diseases of the brain (brain tumors or natural lesions), 200mg daily phenylpiracetam resulted in improvements in depression and anxiety (R).

Technical Aspects

Both oxiracetam and aniracetam (100mg/kg) fail to significantly modify acetylcholine or choline concentrations in any tested brain region (R).

Both, however, did slow a scopalamin drug-induced decrease of acetylcholine. Oxiracetam and aniracetam did so in the hippocampus and cortex (not Ani) at doses of 50-100mg/kg. Higher and lower doses were ineffective.

Independent of increasing acetylcholine concentrations, oxiracetam appears to increase acetylcholine utilization in the cortex and hippocampus at 100-300mg/kg injections (R).

Repeated daily doses of oxiracetam was noted to increase acetylcholine utilization by 31% relative to control, and appears to be more potent and prolonged than Piracetam (R).

Injections of both piracetam and oxiracetam increase choline uptake in the hippocampus (R).

Oxiracetam does not have an effect on GABA or Serotonin levels in the brain (R).

A Comparison of the Most Well Known Racetams

All five drugs have shown an ability to increase learning, particularly in stressful situations (shock test).

The pituitary-adrenal axis is essential to the activity of the drugs (R).

Note: most of the information that you will find below is internet hearsay.  It’s not science-based.

Piracetam

  • Used for cognitive enhancement
  • Appears to have 1/10 of the potency of Aniracetam (R).
  • Water Soluble
  • Helps learning and memory retention
  • Enhances sensory perception and awareness
  • Benefits focus and concentration
  • Piracetam tends to be the weakest on learning (when comparing oxiracetam, aniracetam, and pramiracetam) (R).
  • Piracetam has been shown to work better than oxiracetam in the treatment of paranoia and agitation.

Read more about Piracetam.

Aniracetam

  • Memory and cognition booster
  • 2-5x more potent than Piracetam
  • Fat Soluble
  • Has an effect on dopamine and serotonin receptors. Will decrease anxiety.
  • Potentially enhances mood
  • Can help with Verbal Fluency
  • Does not have a long lasting effect in the body making supplementation spaced out throughout the day more effective.
  • Stimulates AMPA receptors more effectively than Piracetam
  • Increases right brain thinking

Oxiracetam

  • Enhances logical thinking. Is faster acting and stronger than both Piracetam and Aniracetam
  • Water Soluble
  • Slightly stimulatory, giving a little bit of energy
  • Helpful for advanced logic thinking tasks such as math
  • Stimulatory but will not disrupt your sleep
  • Helps with motivation
  • Unlike Aniracetam, Oxiracetam doesn’t offer mood enhancement
  • Oxiracetam has been shown to exhibit more improvement in memory than piracetam (R).
  • Using Oxiracetam short term doesn’t seem to show long term effects, however long term usage does (R).
  • Oxiracetam 25-50mg/kg, outperformed piracetam 100mg/kg in memory tests in mice.  Positive results on the tests was only evident in groups taking the drug five days before training (R,R2).
  • Oxiracetam and Aniracetam increase Long-term potentiation in the hippocampus (R).

Pramiracetam

  • Considered the strongest of all the Racetams. Overall brain enhancement.
  • Fat soluble
  • Often compared to Ritalin for increased memory and focus.
  • Enhances general cognition
  • Helps with long term memory
  • Improved Sensory Perception
  • Best of all for extremely sharp focus
  • Pramiracetam outperforms piracetam and compares equally or outperforms aniracetam in memory enhancement tests (R,R2).

Phenylpiracetam

  • Structurally similar to Pramiracetam just with a phenyl group added.
  • Increases memory & problem solving skills
  • Suppresses anxiety and fear response
  • Supposedly increases cold tolerance (haven’t seen the study) but people on the internet claim it helps

DOSING

In general the racetam class I; Pi-, Ani-, and Oxi-, have little side effects and toxicity with doses up to 12g for 8 weeks (R,R2).

 Aniracetam: 100mg  – 1,500mg/day. Average dose 750mg 3x per day.

Aniracetam is rapidly absorbed and seems to be quickly metabolized by the body, making dosing through out the day more beneficial (R).

It also appears to be taken up in fasted states although it is fat soluble.

Typical dosage seems to be in the 100-1,500mg range.

 Oxiracetam: 1,200-2,400mg

Supplementation of Oxiracetam tends to be in the dosage range of 1,200-2,400mg taken over the course of a day, either in two to three evenly spread dosing periods (such as three doses of 400mg or 800mg).

Oxiracetam seems to be about as strong as Aniracetam. However, Oxiracetam is more bioavailable and therefore stays in the body longer, so you don’t have to take it as often. Oxiracetam’s bioavailability ranges from 68 to 82 percent (R).

Pramiracetam: 1,200mg/day

Currently, the evidence using pramiracetam in humans uses either 400mg  3x/day, or 600mg 2x/day.

Phenylpiracetam: 200 – 600mg/day

Phenylpiracetam is taken at a dosage of 100-200mg at high doses. It is recommended to start with 50mg first.

The dose of 100-200mg/day is usually dived throughout the day totaling somewhere between 200-600mg/day.

Downsides and Adverse Effects

Piracetam inhibits steroid synthesis in general in the body (R) This inhibition of actions applies to Aniracetam, Oxiracetam, and Pramiracetam (R,R2,R3).

Those whom have had their adrenals removed will not have the benefit from Piracetam’s effects (R).

Studies on Alzheimer’s with oxiracetam have not found a significant effect (R).

Oxiracetam does not impair sleep quality, although it may prolong the ability to actually fall asleep which is dose dependent (R).

Although Aniracetam is known to reduce depression, it has been shown ineffective in reducing depression in younger mice (R).

Phenylpiracetam is excitatory and may disturb your sleep (R).

Where to Buy Racetams:

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5 COMMENTS

  • Student

    There is no evidence that racetams inhibit steroid synthesis. The studies indicate that when steroid biosynthesis is chemically suppressed by aminoglutethimide, another agent altogether, and aldosterone receptors are blockaded by epoxymexrenone there is no memory enhancing effect. These are no results of racetams. They counteract the affect of racetams, indicating a common mechanism of action.

    1. Christobal DeLicia

      Please Brett, you “felt” they were not safe? That’s like someone afraid of flying talking about airplanes not “feeling” safe. It reminds me of the “natural is better” fallacy. If you have any scientific data, please include it. I welcome a discussion but saying they didn’t feel safe is killing the discussion, not contributing. Piracetam has been safely used since the ’50s, for epilepsy.

  • Brett

    My experience is similar to yours, Joe. I didn’t feel racetams were beneficial or safe. I view them as second tier research chemicals from decades back, not cutting edge nootropics.

  • Chrono Cross

    Very interesting post!

  • Dylan

    Nice write-up Joe. Have you changed your views on nootropics? I remember not too long ago you seemed to be against them especially piracetam.

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