Piracetam was the original nootropic, developed "by scientists at the Belgian pharmaceutical company UCB led by Dr Corneliu E. Giurgea"[1] on 1964. It has been regarded as an elixir of the mind, bestowing upon the individual a sense of heightened awareness, quickness of thought, increased memory[4], and artist like creativity. It is sold as a dietary supplement yet is synthetic in its composition.
Safety
Toxicological Data on Ingredients: Piracetam: ORAL (LD50): Acute: 2000 mg/kg [Mouse][9]
Warning
It is my personal opinion that this dietary supplement should be avoided long term, due to issues with choline supplementation. Piracetam stimulates the intake of Acetylcholine in Muscaranic receptors[1] without sentiment to reserves (even at time depleting ACh[2]), this stimulation makes it necessary for individuals to increase their dietary intake of Choline through Acetylcholine precursors[1] (Lecithin, Choline, Alpha GPC, DMAE). It however is not a simple process, leaving the individual through countless iterations of trial and error to find that individualized golden ratio of Piracetam to Choline. There are threads on various forums dedicated to this assistance, but it is both a financially and time costly process. Alpha GPC, one of the most bioavailable precursors, can sell for approximately $30 for 60 capsules. The benefits might be worth it, but it is not recommended to start when pressing cognitive matters are afoot. In addition, most of the research is focused on learning disabilities and age related cognitive decline rather than cognitive increase in normal individuals.
In addition, the effects on ADHD are uncertain, certain studies mention the increase in ADHD symptoms in ADHD children[5][8] while another shows beneficial effects[6].
Mechanism of Action
Piracetam works in a number of ways. One of the most effective mechanism related to the creativity is the stimulation of the corpus callosum[1][10]. This area is located between the two hemispheres of the brain and is associated with the interlinking of the information produced by these two hemispheres. It is held that both hemispheres work in seperate fashions, one belief is that the left hemisphere works more as a linear computer, while the right works more as a parallel computer[7]. By increasing the capacity for interweaving information across these two structures, it is possible to produce a higher cognitive capacity as information is processed more rapidly through different mediums.
In addition, to the increase of this area, it appears to stimulate various structures in the brain which are related to language processing[3].
Research
"In an attempt to gain some insight into possible approaches to reducing age-related memory disturbances, aged Fischer 344 rats were administered either vehicle, choline, piracetam or a combination of choline or piracetam. Animals in each group were tested behaviorally for retention of a one trial passive avoidance task, and biochemically to determine changes in choline and acetylcholine levels in hippocampus, cortex and striatum. Previous research has shown that rats of this strain suffer severe age-related deficits on this passive avoidance task and that memory disturbances are at least partially responsible. Those subjects given only choline (100 mg/kg) did not differ on the behavioral task from control animals administered vehicle. Rats given piracetam (100 mg/kg) performed slightly better than control rats (p<0.05), but rats given the piracetam/choline combination (100 mg/kg of each) exhibited retention scores several times better than those given piracetam alone. In a second study, it was shown that twice the dose of piracetam (200 mg/kg) or choline (200 mg/kg) alone, still did not enhance retention nearly as well as when piracetam and choline (100 mg/kg of each) were administered together. Further, repeated administration (1 week) of the piracetam/choline combination was superior to acute injections. Regional determinations of choline and acetylcholine revealed interesting differences between treatments and brain area. Although choline administration raised choline content about 50% in striatum and cortex, changes in acetylcholine levels were much more subtle (only 6–10%). No significant changes following choline administration were observed in the hippocampus. However, piracetam alone markedly increased choline content in hippocampus (88%) and tended to decrease acetylcholine levels (19%). No measurable changes in striatum or cortex were observed following piracetam administration. The combination of choline and piracetam did not potentiate the effects seen with either drug alone, and in certain cases the effects were much less pronounced under the drug combination. These data were discussed as they relate to possible effects of choline and piracetam on cholinergic transmission and other neuronal function, and how these effects may reduce specific memory disturbances in aged subjects. The results of these studies demonstrate that the effects of combining choline and piracetam are quite different than those obtained with either drug alone and support the notion that in order to achieve substantial efficacy in aged subjects it may be necessary to reduce multiple, interactive neurochemical dysfunctions in the brain, or affect activity in more than one parameter of a deficient metabolic pathway.[4]"
"Background and Purpose—In a prospective, double-blind, placebo-controlled study, it was investigated whether piracetam improves language recovery in poststroke aphasia assessed by neuropsychological tests and activation PET measurement of cerebral blood flow.
Methods—Twenty-four stroke patients with aphasia were randomly allocated to 2 groups: 12 patients received 2400 mg piracetam twice daily, 12 placebo. Before and at the end of the 6-week treatment period in which both groups received intensive speech therapy, the patients were examined neuropsychologically and studied with H215O PET at rest and during activation with a word-repetition task. Blood flow was analyzed in 14 language-activated brain regions defined on reconstructed surface views from MRI coregistered to the PET images.
Results—Before treatment, both groups were comparable with respect to performance in language tasks and to type and severity of aphasia. In the piracetam group, increase of activation effect was significantly higher (P<0.05) in the left transverse temporal gyrus, left triangular part of inferior frontal gyrus, and left posterior superior temporal gyrus after the treatment period compared with the initial measures. The placebo group showed an increase of activation effect only in the left vocalization area. In the test battery, the piracetam group improved in 6 language functions, the placebo group only in 3 subtests."[3]
"The effect of Piracetam (UCB 6215, 2-pyrrolidoneacetamide) on learning mediated by transcommissural information flow was studied in hooded rats. Acquisition of monocular pattern discrimination was faster in drug-treated rats (100 mg/kg, 30 min before training) than in untreated controls. Subsequent relearning with one hemisphere functionally eliminated by cortical spreading depression showed that the strength of the primary engram formed under Piracetam in the hemisphere contralateral to the trained eye remained unaffected but that the secondary trace (in the ipsilateral hemisphere) was considerably improved and almost equalled the primary one (savings increased from 20-30% to 50-60%). Learning with uncrossed optic fibers was unaffected by the drug. Interhemispheric transfer of lateralized visual engrams acquired during functional hemidecortication was facilitated by Piracetam administration preceding the five transfer trials performed with the untrained eye open (imperative transfer). Piracetam was ineffective when the trained eye was open during transfer trials (facultative transfer). After a visual engram had been lateralized by 5 days of monocular overtraining, Piracetam facilitated formation of the secondary engram induced by 3 interocular transfer trials. It is concluded that Piracetam enhances transcommissural encoding mechanisms activated in the initial stage of monocular learning and in some forms of interhemispheric transfer, but does not affect the transcommissural readout. This effect is interpreted as a special case of the Piracetam-induced facilitation of the phylogenetically old mechanisms of redundant information storage which improve liminal or subnormal learning." [10]References
[1] Wikipedia Entry: Piracetam
[2] Piracetam Diminishes Hippocampal Acetylcholine Levels in Rats
[3] Piracetam Improves Activated Blood Flow and Facilitates Rehabilitation of Poststroke Aphasic Patients
[4] Profound effects of combining choline and piracetam on memory enhancement and cholinergic function in aged rats
[5] Effect of Piracetam on attention deficit and hyperactivity disorder
[6] Therapeutic efficacy of nootropil different doses in attention deficit hyperactivity disorder
[7] Brain Hemispheres and Problem Solving
[8] The Effect Of Piractam in the development of Attentional Disturbances; Hyperactivity and absent-mindedness in children with Developmental Retardation
[9] Piracetam Material Safety Data Sheet
[10] Piracetam-induced facilitation of interhemispheric transfer of visual information in rats.
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