Piracetam Research

Piracetam and Down Syndrome

1. Wilsher CR et al. Piracetam and dyslexia: effects on reading tests. J Clin Psychopharm 7(4): 230-237, 1987. 225 dyslexic children between 7 and 12 years old, all with normal IQs, enrolled in double-blinded, placebo controlled study. Authors report significant improvement in reading and comprehension.
2. Volavka J et al. Effect of piracetam on EEG spectra of boys with learning disorders. Psychopharm 72: 185-188, 1981. Studied EEG changes by piracetam on 30 children with learning disorders. Changes in delta waves, no change between left and right hemispheres. Same effect as seen with amphetamines. (Note: learning disorders are associated with EEG slowing, and the effect of piracetam is similar to that of ritalin per these authors.)
3. Ackerman PT et al. A trial of piracetam in two subgroups of students with dyslexia. J Learning Disab 24(9): 542-549, 1991. 53 children with dyslexia, categorized as dysphonetic (could not associate sounds with phonic representations) or phonetic (could associate). Piracetam helped phonetic group improve word recognition; no other differences noted. Both groups given tutoring with the piracetam.
4. Di Ianni M et al. The effects of piracetam on children with dyslexia. J. Clin. Psychopharm 5:272-278, 1985. Piracetam improved verbal meaning and increased reading speed.
5. Levinson HN Dramatic favorable responses of children with learning disabilities or dyslexia and attention deficit disorder to antimotion sickness medications: Four case reports. Percep Motor Skill 73:723-738, 1991. (The title explains the gist of the article.)

1. Stegink AJ The clinical use of piracetam, a new nootropic drug. Arzneim.-Forsch. 22:975-979, 1972. (German) Double-blinded with placebo study on patients in nursing home. Attention improved, no other effects seen.
2. Faleni J Pharmacol 5(30), 1974 80% of senile dementia patients showed improvement after piracetam treatment for 11 weeks.
3. Friedman E et al. Clincal Response to choline plus piracetam in senile dementia: relation to red-cell choline levels. New Eng J Med 1981 Jun 11; 304(24): 1490-1. This is actually a "letter" rather than a full paper, and consisted giving 10 patients with presenile dementia piracetam and choline for 7 days in a non-controlled study. 3 of the 10 had "marked improvement" cognitively, but no description of the cognitive tests or whether the testing was blinded is mentioned. The 3 who responded had higher choline red blood cell levels than the 7 who didn't respond.
4. Chouinard G et al. Piracetam in elderly psychiatric patients. Psychopharm 81:100-106,1983. Piracetam improved scores in various memory tests in patients with "mild diffuse cerebral impairment." 12 week treatment.
5. Growdon JH et al. Piracetam combined with lecithin in the treatment of Alzheimer's disease. Neurobiol of Aging 7:269-276, 1986. Piracetam was administered alone or with lecithin (phosphatidylcholine) in a double-blinded test. No effect was seen, with or without lecithin, on cognition or memory test scores.
6. Corona GL et al. Clinical and biochemical responses to therapy in Alzheimer's disease and multi-infarct dementia. Eur. Arch. Psychiatr. Neurol. Sci. 239:79-86, 1989. Patients with either AD or multi-infarct dementia were given either piracetam or piracetam with choline. This was not paired with placebos. Despite biochemical changes, there was no change in memory performance.
7. Nicholson CD Pharmacology of nootropics and metabolically active compounds in relation to their use in dementia. Psychopharm 101:147-159, 1990. Review of literature to date on this topic. "Despite [piracetam's] interesting animal pharmacology, convincing evidence that piracetam is an effective agent against the cognitive symptoms of primary dementia is still awaited....In general, the trials have not been performed in well-defined patient collectives, but rather in patients with ill-defined psycho-organic brain syndromes." (A very good article.)
8. Heiss W-D et al. Abnormalities of energy metabolism in Alzheimer's disease studied with Positron Emission Tomography. Ann NY Acad Sci, 1991. Using piracetam created an increase in glucose metabolism by brain cells in patients with A.D., but not in normal patients.
9. Croisile B et al. Long-term and high-dose piracetam treatment of Alzheimer's disease. Neurology 43: 301-305, 1993. 1 year, double-blinded with placebo study of 30 A.D. patients treated with piracetam. No improvement in dementia noted, but there was a significant slowing of deterioration.
10. Weinstock M The pharmacology of Alzheimer's Disease based on the cholinergic hypothesis: an update. Neurodegen 4: 349-356, 1995. A "where we are now" review of the literature, briefly touching upon piracetam as increasing alertness but without effect on memory or improving cognition.
11. Zs.-Nagy, I On the possible role of nootropica in geriatric prevention and therapy. Annals NY Acad Sci 444-452, 1996. Has an interesting section on the history of nootropica; reviews briefly all the nootropic drugs' uses in senile dementia.

(Note: myoclonus refers to the spasm or twitching of a muscle or group of muscles, and is not associated with a loss of consciousness. It can be a part of many neurologic diseases and can be cortical (epileptic) or subcortical. This appears to be the current main focus of attention of piracetam by UCB Pharma. "Paroxysmal" disorders are those with a sudden onset of a symptom, such as a seizure.)

1. Kunneke PS. A controlled clinical trial on the effect of piracetam in epileptic children. Br J Clin Practice 33(9): 266-271, 1979. 16 children with epilepsy and learning disorders given piracetam or placebo for 6 weeks. No effect on severity or frequency of seizures noted. Researchers report a positive effect on visual perception and on memory as tested by digit spans.
2. Brown, P et al. Effectiveness of piracetam in cortical myoclonus. Movement Disorders 8(1): 63-68, 1993. 21 patients with cortical myoclonus were evaluated in a double-blind, controlled study with placebo. Piracetam markedly helped myoclonus. No interaction seen between piracetam and anticonvulsants. Note: sudden withdrawal of piracetam caused worsening of myoclonus and seizures.
3. Ikeda A et al Clinical trial of piracetam in patients with myoclonus: Nationwide multiinstitution study in Japan. Movement Disorders 11(6): 691-700, 1996. 60 adults studied, with good results.
4. Van Vleymen V and Van Zandijke M Piracetam in the treatment of myoclonus: an overview. Acta Neurol Belg 96: 270-280, 1996. This paper summarizes all trials and case reports known to the authors to date. It showed efficacy in several types of myoclonus, there was no obvious interaction with anticonvulsants, and adverse effects were rare.
5. Guerrini R et al. Cortical myoclonus in Angelman syndrome. Ann Neurol Jul;40(1):39-48, 1996. 11 patients with Angelman syndrome, ages 3 to 28 years. All had myoclonus with abnormal EEG activity. 5 were given piracetam, with good results for all five patients.
6. Dulac O et al. Myoclonus and epilepsy in childhood: 1996 Royaumont meeting. Epilepsy Research 30:91-106, 1998. This paper is a terrific resource for the description and etiology of all types of myoclonus. However, the portion dealing with treatment takes up only 2 full pages. Piracetam gets a brief mention: "In various types of cortical myoclonus including progressive myoclonic epilepsy and post anoxic myoclonus, it has marked effect on over one third of the cases...but is poorly effective against thalamocortical and subcortical myoclonus."
7. Donma MM. Clinical efficacy of piracetam in treatment of breath-holding spells. Ped Neuro 18(1): 41-45, 1998. 39 children ages 6 to 36 months of age were given piracetam for 2 months, and showed piracetam to be successful in stopping breath-holding spells from causing a loss of consciousness.

1. Huber, W et al. Piracetam as an adjuvant to language therapy for aphasia: a randomized double-blind placebo-controlled pilot study. Arch Phys Med Rehabil 78: 245-250, 1997. 24 adults with stroke or brain injury resulting in moderate to severe aphasia were given piracetam along with speech therapy for 6 weeks. Piracetam had a significant effect on written language but not on spoken language. Total mean scores on an aphasia scale were higher with the group on piracetam.
2. De Deyn PP et al. Treatment of acute ischemic stroke with piracetam. Members of the Piracetam in Acute Stroke Study (PASS) Group. Stroke 28(12):2347-52, 1997. A multicenter, randomized, double-blind trial to test whether piracetam conferred benefit when given within 12 hours of the onset of acute ischemic stroke to a large group of patients. Piracetam did not influence outcome when given within 12 hours of the onset of acute ischemic stroke. Another study is underway decreasing the time interval to 7 hours.

1. Mondadori C Do piracetam-like compounds act centrally via peripheral mechanisms?Brain Res 435: 310-314, 1987. Removing the adrenal glands inactivates any effect of piracetam; therefore, adrenal steroids moderate piracetam's actions somehow.
2. Ennaceur A et al. A new one-trial test for neurobiological studies of memory in rats: effects of piracetam and pramiracetam. Behav Brain Res 33: 197-207, 1989. Giving piracetamto rats gives significant amount of retention of recognition of previously introduced objects at 24 hour intervals ("promnesic" effect). Piracetam conjectured to have no effect on working memory but may improve reference memory.
3. Mondadori C et al. Blockade of the nootropic action of piracetam-like nootropics by adrenalectomy. Behav Brain Res 34: 155-158, 1989. Adrenalectomized rats do not respond to piracetam at any dosage. Confirms earlier theory of adrenal steroids.
4. Laszy J and Sarkadi A Hypoxia-induced sleep disturbance in rats. Sleep 13(3): 205-217, 1990. Rats were placed in chambers with low oxygen amounts (hypoxia) which caused a disturbance in the sleep cycle. Piracetam almost fully restored the cycle, even with the oxygen still low. Hypoxic sleep disturbance is a model of hypoxic brain damage, so piracetam may reverse brain damage caused by hypoxia.
5. Mondadori C Involvement of a steroidal component in the mechanism of action of piracetam-like nootropics. Brain Res 506: 101-108, 1990. Piracetam's mechanism of action may be due to intervention in steroid-sensitive gene transcription/protein synthesis.
6. Mondadori C Aldosterone receptors are involved in the mediation of the memory-enhancing effects of piracetam. Brain Res 524: 203-207, 1990. Expands further on the same topic.
7. de Angelis L Memory storage and effect of repeated treatment with rubidium chloride. J Intern'l Med Res 19: 395-402, 1991. Piracetam improved memory of rats in this study, but not as well as strychnine or rubidium chloride.
8. Paula-Barbosa MM et al. The effects of piracetam on lipofuscin of the rat cerebellar and hippocampal neurons after long-term alcohol treatment and withdrawal. Alcohol Clin Exp Res 15(5): 834-838, 1991. Large amounts of lipofuscin (granules of lipid residuals from metabolism in individual cells) in nerve cells is a characteristic of nervous system aging. It can also be seen early on in chronic alcohol consumption. Piracetam treatment in rats reduces lipofuscin accumulation by improving enzymatic activity in cell digestive processes.
9. Chleide E et al. Enhanced resistance effect of piracetam upon hypoxia-induced impaired retention of fixed-interval responding in rats. Pharmacol Biochem. Behav 40: 1-6, 1991. Hypoxic rats given tasks, then repeated with either piracetam or saline. Pir-treated rats performed tasks better than saline-treated rats. (Note: this paper has a nice discussion on the mechanism of action of piracetam on memory; authors concluded piracetam facilitates memory retrieval. --LL)
10. Stancheva SL et al. Age-related changes of the effects of a group of nootropic drugs on the content of rat brain biogenic monoamines. Gen Pharmac 22(5): 873-877, 1991. Age-related decrease in the content and turnover rate of biogenic amines (precursors to neurotransmitter chemicals) are examined in senile rats. (Note: don't ask me how they knew the rats were senile.) Piracetam increased the level of amines, and facilitated learning and memory.
11. Nalini K et al. Effects of piracetam on retention and biogenic amine turnover in albino rats. Pharmacol Biochem Behav 42: 859-864, 1992. Piracetam caused a decrease in all neurogenic amines and metabolites in these rats, but there was an overall decreased turnover of brain amines. Increased memory retention noted.
12. Nicoletti, F et al. Excitatory amino acids and neuronal plasticity. Funct Neurol 7: 413-422, 1995. In cultured neurons, piracetam enhanced the stimulation of the influx of calcium ions.
13. Cohen SA and Muller WE. Effects of piracetam on NMDA receptor properties in the aged mouse brain. Pharmacol 47: 217-222, 1993. Piracetam increased the number of specific N-Methyl-D-Aspartate receptors in senile rat brains. The receptors involved appear to be part of the memory process.
14. Rose S Cell-adhesion molecules, glucocorticoids and long-term-memory formation. Trends Neurosci 18(11): 502-506, 1995. Chicks were used to show that the transition of short-term to long term memory may involve the enhanced synthesis of glycoprotein cell-adhesion molecules (CAMs). Steroids enhance this synthesis. The author proposes (but does not test the theory) that nootropics such as piracetam may work by influencing this steroid-enhanced mechanism.
15. Jordaan B et al. Cerebral blood flow effects of piracetam...in the baboon model compared with... acetazolamide. Arzneim-Forsch/Drug Res 46(II): 844-847, 1996. Using SPECT imaging of the brain, piracetam is shown to cause increased blood flow to the occipital area and the left side of the brain.
16. Verbnyi, YI et al. Piracetam-induced changes in the functional activity of neurons as a possible mechanism for the effects of nootropic agents. Neurosci Behav Physiol 26(6): 507-515, 1996. Piracetam had significant effects on electrical activity of neurons of pond snails, which was mediated by an increase in intracellular calcium. (A lot of research on piracetam has been done in Russia; this is a rare paper from Russia in that it made it into an English translation.)
17. Muller WE et al. Effects of piracetam on membrane fluidity in the aged mouse, rat and human brain. Biochem Pharmacol 53: 135-140, 1997. Reduced fluidity of brain cell membranes has been postulated to be responsible for impaired cognitive functions. This paper shows piracetam can increase membrane fluidity in aged rats given piracetam orally for several weeks, and was associated with improved avoidance-learning in those rats. (Human brain cells were taken from autopsy cases and soaked in piracetam in a tube for this study, and showed increased fluidity of membranes also.)
18. Verbnyi Y et al. Piracetam-induced changes in the functional activity of neurons as a possible mechanism for the effects of nootropic agents.

1. Grekas D et al. Piracetam as a potent inhibitor of plasma thromboxane B2 during hemodialysis. Nephron 52: 372-373, 1989. Dialysis causes unwanted blood clotting by the unintentional creation of thromboxanes, which stimulate platelet cells to clump together and clot the blood. Piracetam inhibits the production of thromboxane B₂, and therefore may be useful in dialysis.
2. Grekas D A pilot study of piracetam in cuprophan hemodialysis. Artificial Organs 13(5):422-426, 1989. Piracetam has an antiplatelet effect during blood-membrane interaction. (Note: this paper also references others I was unable to find that state piracetam also has an antiplatelet effect in strokes and during transplants of kidneys and removal of spleens. --LL)
3. Murayama M Decompression-inducible platelet aggregation and hemostasis. Thrombosis Research 54: 493-498, 1989. Texas Green frogs were used to study decompression effects on blood clotting. Frogs were exposed to the barometric pressure equivalent to the summit of Mt. Everest. Piracetam was found to block the platelet clumping normally produced by this type of decompression. (Note: this is my favorite study. Not only do they specify that this is the Texas green frog, but the best quote of all these papers is here: "Now it is generally known that there are great similarities between frog and man." The only problem is, I don't know what a Texas green frog would be doing at the top of Mt. Everest.)
4. Murayama M Decompression-induced hemostasis in mice. Thrombosis Research 57: 813-816, 1990. Piracetam inhibited decompression-induced hemostasis in mice.
5. Moriau M et al. Treatment of the Raynaud's phenomenon with piracetam. Arzneimittelforschung 43(5):526-35, 1993. A very nice paper in which piracetam was shown to be helpful in relieving the symptoms of Raynaud's syndrome, probably through inhibition of platelet function and increasing red blood cell membrane deformability. Piracetam was well tolerated.
6. El-Hazmi MAF et al. Piracetam is useful in the treatment of children with sickle cell disease. Acta Haematol 96: 22-226, 1996. A well-done controlled, double-blinded test showing improvement of children with sickle cell anemia while taking piracetam. Of note is that the children were on the drug for 1 year with no toxic side effects.

1. Gouliaev AH and Senning A Piracetam and other structurally related nootropics. Brain Res Rev, 1994; 19: 180-222. (This is an excellent review article. The section on piracetam by itself is only 6 pages, though. --LL)
2. Vernon MW and Sorkin EM Piracetam: An overview of its pharmacological properties and a review of its therapeutic use in senile cognitive disorders. Drugs and Aging 1(1): 17-35, 1991. (Another excellent review article, and goes greatly into detail about its actions in the body as well as what is known about its use in presenile dementia.)
3. Pranzatelli MR and Nadi S Mechanism of action of antiepileptic and antimyoclonic drugs. In "Negative Motor Phenomena," ed. Fahn S et al, Advances in Neurology Vol 67, 329-360 Lippincott-Raven, 1995. This article contains a couple of pages on piracetam, summarizing what's known about it's mechanism of action.
4. Mondadori C Nootropics: Preclinical results in the light of clinical effects; Comparison with tacrine. Critical Reviews in Neurobiol 10: 357-370, 1996. A review of clinical effects of nootropics in memory enhancement, and compared to tacrine, a cholinesterase inhibitor and the only drug registered to date in the US for Alzheimer's disease. Mondadori, who has several studies published on piracetam, concludes: "Given the observed overall positive effects of the nootropics and their occasionally quite distinct effects in individual patients, this category of compounds would appear useful. The results available so far give no indication that tacrine is superior to the nootropics, or vice-versa."
5. Tacconi MT and Wurtman RJ Piracetam: Physiologic disposition and mechanism of action. In Advances in Neurology Vol 43, 675-685, Raven Press, NY 1986. At the time, a very nice review of the literature to date.