I'm not suggesting Piracetam is worthless, but I am suggesting that individuals investigating possible routes of cognition enhancement should explore first compounds that have the strongest supporting evidence to warrant their use. For individuals searching the web for cognition enhancement who have not seen an MD specializing in attention related disorder or an otherwise qualified psychiatrist to see if they might have ADD, ADHD, or another "disorder" -- you should go check if you have one of these disorders FIRST before trying these more questionable (w/respect to their efficacy) compounds.
If one is sure he or she is not walking around with untreated ADD/ADHD, depression, etc, I would then suggest investigating the use of other compounds as supplements. The side effect profiles from these prescription drugs alone are enough to scare many people away...but these compounds work (for most patients) upon first adminstration (except for Aricept).
I also think Piracetam to be less effective than Oxiracetam, Aniracetam and Pramiracetam...and if you have a good source, go for it! Personally, I take Oxiracetam 800mg twice a day and Aniracetam 750mg twice a day.
If I had to list the most effective cognitive enhancers in healthy subjects -- based on strength of evidence (from well conducted trials by respected researcers), the most effective would go as follows:
1.
Aricept AKA donezepil HCLRef1:
Neurology. 2002 Jul 9;59(1):123-5.
Comment in:
* Neurology. 2003 Sep 9;61(5):721; author reply 721.
Donepezil and flight simulator performance: effects on retention of complex skills.
Yesavage JA, Mumenthaler MS, Taylor JL, Friedman L, O'Hara R, Sheikh J, Tinklenberg J, Whitehouse PJ.
Palo Alto Veterans Affairs Health Care System, Stanford University School of Medicine, Stanford, CA 94305-5550, USA. yesavage@stanford.edu
We report a randomized, double-blind, parallel group, placebo-controlled study to test the effects of the acetylcholinesterase inhibitor, donepezil (5 mg/d for 30 days), on aircraft pilot performance in 18 licensed pilots with mean age of 52 years. After 30 days of treatment, the donepezil group showed greater ability to retain the capacity to perform a set of complex simulator tasks than the placebo group, p < 0.05. Donepezil appears to have beneficial effects on retention of training on complex aviation tasks in nondemented older adults.
Publication Types:
* Clinical Trial
* Randomized Controlled Trial
PMID: 12105320 [PubMed - indexed for MEDLINE]
Ref 2:
Neuropsychopharmacology. 2003 Jul;28(7):1366-73. Epub 2003 May 14.
Psychoactive drugs and pilot performance: a comparison of nicotine, donepezil, and alcohol effects.
Mumenthaler MS, Yesavage JA, Taylor JL, O'Hara R, Friedman L, Lee H, Kraemer HC.
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA. msm@stanford.edu
The cholinergic system plays a major role in cognitive abilities that are essential to piloting an aircraft: attention, learning, and memory. In previous studies, drugs that enhance the cholinergic system through different pharmacologic mechanisms have shown beneficial effects on cognition; but dissimilar cognitive measures were used and samples were not comparable. A comparison within the same cognitive tasks, within comparable samples appears desirable. Toward this aim, we compared effect sizes (ES) of performance-enhancing doses of nicotine (a nicotinic receptor agonist) and donepezil (an acetylcholinesterase inhibitor) as found in our prior work on pilot performance. We also compared cholinergic ES to those of performance-impairing doses of alcohol. In three randomized, placebo-controlled trials, we assessed the flight performance of aircraft pilots in a Frasca 141 simulator, testing I: the acute effects of nicotine gum 2 mg; II: the effects of administration of 5 mg donepezil/day for 30 days; and III: the acute and 8 h-carryover effects of alcohol after a target peak BAC of 0.10%. We calculated the ES of nicotine, donepezil, and alcohol on a flight summary score and on four flight component scores. Compared to placebo, nicotine and donepezil significantly improved, while alcohol significantly impaired overall flight performance: ES (nicotine)=0.80; ES (donepezil)=1.02; ES (alcohol acute)=-3.66; ES (alcohol 8 h)=-0.82. Both cholinergic drugs showed the largest effects on flight tasks requiring sustained visual attention. Although the two tested cholinergic drugs have different pharmacologic mechanisms, their effects on flight performance were similar in kind and size. The beneficial effects of the cholinergic drugs on overall flight performance were large and the absolute (ie nondirectional) sizes were about one-fourth of the absolute ES of acute alcohol intoxication and roughly the same as the absolute 8 h-carryover ES of alcohol.
Publication Types:
* Clinical Trial
* Randomized Controlled Trial
PMID: 12784106 [PubMed - indexed for MEDLINE]
2.
Provigil AKA modafinilPsychopharmacology (Berl). 2003 Jan;165(3):260-9. Epub 2002 Nov 1. Related Articles, Links
Cognitive enhancing effects of modafinil in healthy volunteers.
Turner DC, Robbins TW, Clark L, Aron AR, Dowson J, Sahakian BJ.
Department of Psychiatry, University of Cambridge, School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.
RATIONALE: Modafinil, a novel wake-promoting agent, has been shown to have a similar clinical profile to that of conventional stimulants such as methylphenidate. We were therefore interested in assessing whether modafinil, with its unique pharmacological mode of action, might offer similar potential as a cognitive enhancer, without the side effects commonly experienced with amphetamine-like drugs. OBJECTIVES: The main aim of this study was to evaluate the cognitive enhancing potential of this novel agent using a comprehensive battery of neuropsychological tests. METHODS: Sixty healthy young adult male volunteers received either a single oral dose of placebo, or 100 mg or 200 mg modafinil prior to performing a variety of tasks designed to test memory and attention. A randomised double-blind, between-subjects design was used. RESULTS: Modafinil significantly enhanced performance on tests of digit span, visual pattern recognition memory, spatial planning and stop-signal reaction time. These performance improvements were complemented by a slowing in latency on three tests: delayed matching to sample, a decision-making task and the spatial planning task. Subjects reported feeling more alert, attentive and energetic on drug. The effects were not clearly dose dependent, except for those seen with the stop-signal paradigm. In contrast to previous findings with methylphenidate, there were no significant effects of drug on spatial memory span, spatial working memory, rapid visual information processing or attentional set-shifting. Additionally, no effects on paired associates learning were identified. CONCLUSIONS: These data indicate that modafinil selectively improves neuropsychological task performance. This improvement may be attributable to an enhanced ability to inhibit pre-potent responses. This effect appears to reduce impulsive responding, suggesting that modafinil may be of benefit in the treatment of attention deficit hyperactivity disorder.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 12417966 [PubMed - indexed for MEDLINE]
3.
Ritalin AKA Concerta AKA methylphenidatePsychopharmacology (Berl). 1997 May;131(2):196-206.
Effects of methylphenidate on spatial working memory and planning in healthy young adults.
Elliott R, Sahakian BJ, Matthews K, Bannerjea A, Rimmer J, Robbins TW.
Department of Experimental Psychology, University of Cambridge, UK.
Previous studies of the effects of the psychomotor stimulant, methylphenidate, have concentrated on vigilance and reaction time tasks. In this study, the effects of methylphenidate on more complex aspects of cognition were studied using tasks from the CANTAB battery and related tests which have been shown to be sensitive to frontal lobe dysfunction. Twenty-eight young healthy men participated in a counterbalanced, double-blind, placebo-controlled study of the effects of methylphenidate. Cognitive assessment included tests of spatial working memory, planning, verbal fluency, attentional set-shifting and sustained attention. Methylphenidate had significant effects on performance of the tests of spatial working memory and planning but not on the attentional and fluency tests. When the drug was taken on the first test session, performance on the spatial tests was enhanced by the drug compared to placebo. However, when the drug was taken second, performance accuracy was impaired whereas response latencies were decreased. These results are consistent with a hypothesis that methylphenidate influences performance in two conflicting ways; enhancing executive aspects of spatial function on novel tasks but impairing previously established performance. This pattern of effects is discussed within the framework of dual, interacting arousal mechanisms.
Publication Types:
* Clinical Trial
* Randomized Controlled Trial
PMID: 9201809 [PubMed - indexed for MEDLINE]
The rest seem to be too poorly documented to warrant being classified as a true "cognitive enhancer" -- *however, I may change my position on this....
We need to conduct research in healthy volunteers to say more about other compounds. Is that a fair statement?
Obviously a healthy subject is not a demented subject, but we can suspect many aspects of memory function is much of the same for both; and starting with evidence from demented subjects then moving to healthy subjects might not always be the best route...but Piracetam has been demonstrated to be ineffective at treating Alzheimers disease, and also seems to have weak results elsewhere...the other racetams seem to be more effective than Piracetam...
Adam/Dude, I have quoted 2 studies from 2006. One of these studies showed significant effect with piracetam supplementation.
I think it's best to investigate the peer reviewed data first on the matter, to put things into perspective; before we browse through Pubmed (a place with many poorly conducted trials). It is WAY too easy to get a study published in Pubmed to possibly take all of the research published there seriously.
http://bmj.bmjjourna...ull/323/7303/42Education and debate
Systematic reviews in health care
Assessing the quality of controlled clinical trials
This is the first in a series of four articles
Peter Jüni, research fellow a, Douglas G Altman, professor of statistics in medicine b, Matthias Egger, senior lecturer in epidemiology and public health medicine c.
a Department of Social and Preventive Medicine, University of Bern, Bern, 3012 Switzerland, b Imperial Cancer Research Fund Medical Statistics Group, Centre for Statistics in Medicine, Institute of Health Sciences, Oxford OX3 7LF, c Medical Research Council Health Services Research Collaboration, Department of Social Medicine, University of Bristol, Bristol BS8 2PR
Correspondence to: M Egger m.egger@bristol.ac.uk
The quality of controlled trials is of obvious relevance to systematic reviews. If the "raw material" is flawed then the conclusions of systematic reviews cannot be trusted. Many reviewers formally assess the quality of primary trials by following the recommendations of the Cochrane Collaboration and other experts. 1 2 However, the methodology for both the assessment of quality and its incorporation into systematic reviews and meta-analysis are a matter of ongoing debate.3-5 In this article we discuss the concept of study quality and the methods used to assess quality.
Conclusions
There is ample evidence that many trials are methodologically weak and increasing evidence that deficiencies translate into biased findings of systematic reviews. The assessment of the methodological quality of controlled trials and the conduct of sensitivity analyses should therefore be considered routine procedures in systematic reviews and meta-analysis. Although composite quality scales may provide a useful overall assessment when comparing populations of trials, such scales should generally not be used to identify trials of apparent low quality or high quality in a given systematic review. Rather, the relevant methodological aspects should be identified a priori and assessed individually. This should include the generation and concealment of treatment allocation, blinding, and handling of attrition in the analysis. Other ways of investigating and dealing with bias in systematic reviews will be discussed and illustrated later in this series.37
Piracetam has been in clinical use for over 40 years.
I think Piracetam has established itself as a safe drug to protect the brain and perhaps enhance membrane fluidy (thus enhance the effecitiveness of other drugs)...however, I don't think much of the Piracetam research conducted thus far would fit selection criteria for meta analysis for a proper Cochrane review.
Drugs such as Aricept (donezepil HCL), Provigil (modafinil), and are (Ritalin) methylphenidate are documented to be effective at augmenting cognitive function (in individuals with disorders AND healthy subjects), by very well conducted researchers in well conducted trials.
Also, a pattern that I find to interesting is that all drugs that demonstrate
real beneficial effects in healthy subjects also demonstrate such results in demented, elderly subjects, or individuals afflicted with an attention related disorer. Piracetam has not shown any significant benefits (only conflicting data) for individuals suffering from Alzheimer's disease or related dementia, whereas Oxiracetam and Aniracetam seem to show some benefit, at least more than Piracetam.
Back in
1991 (don't forget Piracetam was synthesized in the 1960s, yet still in 1991, the effects were STILL not proven by science...twenty years after the development of piracetam and no real evidence!)
Drugs Aging. 1991 Jan;1(1):17-35.
Piracetam. An overview of its pharmacological properties and a review of its therapeutic use in senile cognitive disorders.
Vernon MW, Sorkin EM.
Adis International Drug Information Services, Auckland, New Zealand.
Piracetam is the first of the so-called 'nootropic' drugs, a unique class of drugs which affect mental function. In animal models and in healthy volunteers, the drug improves the efficiency of the higher telencephalic functions of the brain involved in cognitive processes such as learning and memory. The pharmacology of piracetam is unusual because it protects against various physical and chemical insults applied to the brain. It facilitates learning and memory in healthy animals and in animals whose brain function has been compromised, and it enhances interhemispheric transfer of information via callosal transmission. At the same time, even in relatively high dosages it is devoid of any sedative, analeptic or autonomic activities. How piracetam exerts its effects on memory disorders is still under investigation, although among other proposed mechanisms of action it is thought to facilitate central nervous system efficiency of cholinergic neurotransmission. Results from trials involving elderly patients with senile cognitive disorders have been equivocal, as have the results obtained when piracetam has been combined with acetylcholine precursors. Piracetam seems to be almost completely devoid of adverse effects, and is extremely well tolerated. In conclusion, opinion is divided as to the benefits of piracetam in the treatment of senile cognitive decline. Although double-blind studies in the elderly have produced mixed results, some such trials (particularly those involving larger numbers of patients) have reported favourable findings, thus offering some reason for cautious optimism in a notoriously difficult area of therapeutics. However, further investigations of piracetam alone and in combination therapy are required before any absolute conclusions can be drawn.
Publication Types:
* Review
PMID: 1794001 [PubMed - indexed for MEDLINE]
A recent study: 2005:
Wiad Lek. 2005;58(9-10):528-35.
Alzheimer's disease therapy--theory and practice
[Article in Polish]
Gabryelewicz T, Barcikowska M, Jarczewska DL.
Z Zakladu Badawczo-Leczniczego Chorob Zwyrodnieniowych GUN IMDiK PAN w Warszawie.
Alzheimer's disease (AD), a progressive degenerative disorder of the brain, affects a significant proportion of elderly population. The pharmacotherapy of AD is evolving rapidly. However, many doctors suggest the treatment which does not provide benefits in patients with the disease. The primary aim of this article was to review avaiable data on the patophysiologic background of AD and thus the most commonly used therapeutic agents, specifically cholinesterase-inhibitors (rivastigmine), Ginkgo biloba, piracetam and selegiline. Relevant double-blind, randomized, placebo-controlled studies were identified through a comprehensive search of Medline, NICE, Embase and CENTRAL databases. CONCLUSIONS: Only inhibitors of acetylcholinesterase are approved in mild and moderate stages of AD treatment. There is no evidence that Ginkgo biloba, selegiline, piracetam provide cognitive or behavioural improvement.
PMID: 16529064 [PubMed - in process]
2004
Int J Neuropsychopharmacol. 2004 Sep;7(3):351-69. Epub 2004 Jul 1. Related Articles, Links
Evidence-based pharmacotherapy of Alzheimer's disease.
Evans JG, Wilcock G, Birks J.
Cochrane Dementia and Cognitive Improvement Group, University of Oxford, UK.
Dementia is an acquired global impairment of cognitive capacities. Approximately 5% of people aged over 65 yr are affected by dementia, and some 70% of cases are thought to be due primarily to Alzheimer's disease. Descriptions of the clinical manifestations of Alzheimer's disease have been increasingly refined in the last decade but there is no diagnostic test for what remains fundamentally a pathologically defined condition. At the present time interventions for Alzheimer's disease are limited to those that modify the manifestations of the disease, and foremost amongst the candidates available are the cholinesterase inhibitors. The rationale for the use of cholinergic drugs for Alzheimer's disease lies in enhancing the secretion of, or prolonging the half-life of, acetylcholine in the brain. Several potential compounds have been tested, but short half-lives and a high incidence of cholinergic and other adverse effects have eliminated most. Only three are widely licensed for use, donepezil, galantamine and rivastigmine. Their efficacy is relatively modest. These drugs have been tested in 32 randomized, placebo-controlled trials. The trials assess cognitive function primarily, and in addition they may assess global function, activities of daily living, quality of life and behavioural disturbance typically over 3 or 6 months. The performance of each drug is summarized in a Cochrane review, a systematic review carried out according to strict guidelines. There was a significant benefit in favour of treatment compared with placebo for cognition and activities of daily living, but withdrawals due to adverse events were significantly higher for treatment than placebo for all three drugs. There is little evidence from direct comparisons between the three drugs. There are several economic analyses of the cost-effectiveness of these drugs, but the findings cannot be considered robust owing to inadequate data. A range of other pharmacological treatments have been tested, including selegiline, piracetam, vitamin E, Ginkgo biloba, anti-inflammatory drugs and hormone replacement therapy, but, so far, Cochrane reviews have not established the efficacy of these interventions for Alzheimer's disease. A Cochrane review of memantine shows benefits on cognitive and global function of the same order of magnitude as seen for the cholinesterase inhibitors.Memantine has been licensed in Europe for treatment of patients with moderately severe to severe Alzheimer's disease.
Publication Types:
* Review
PMID: 15228642 [PubMed - indexed for MEDLINE]
Neurology. 1993 Feb;43(2):301-5.
Long-term and high-dose piracetam treatment of Alzheimer's disease.
Croisile B, Trillet M, Fondarai J, Laurent B, Mauguiere F, Billardon M.
Department of Neurology, Hopital Neurologique, Lyon, France.
Preclinical research suggests that piracetam (a nootropic drug) may improve cognitive functions, but previous studies have failed to demonstrate a clear benefit for the treatment of Alzheimer's disease (AD). We report a 1-year, double-blind, placebo-controlled, parallel-group study with a high dose of piracetam (8 g/d per os) in 33 ambulant patients with early probable AD. Thirty subjects completed the 1-year study. No improvement occurred in either group, but our results support the hypothesis that long-term administration of high doses of piracetam might slow the progression of cognitive deterioration in patients with AD. The most significant differences concerned the recall of pictures series and recent incident and remote memory. The drug was well-tolerated.
Publication Types:
* Clinical Trial
* Randomized Controlled Trial
PMID: 8437693 [PubMed - indexed for MEDLINE]
Abstract: Sixty children with dyslexia (41 boys, 19 girls; ages 9 to 13) were enrolled in a 10-week summer tutoring program that emphasized word-building skills. They were randomly and blindly assigned to receive either placebo or piracetam, a purportedly memory-enhancing drug that has been reported to facilitate reading skill acquisition. The children were subtyped as "dysphonetic" or "phonetic" on the basis of scores from tests of phonological sensitivity and phoneme-grapheme correspondence skills. Of the 53 children who completed the program, 37 were classified as dysphonetic and 16 as phonetic. The phonetic group improved significantly more in word-recognition ability than the dysphonetic group. Overall, the children on medication did not improve more than the nonmedicated ones in any aspect of reading.
The phonetic subgroup on piracetam gained more in word recognition than any subgroup but did not improve significantly more than the phonetic subgroup on placebo. Results are discussed in relation to findings from previous studies of piracetam in children with dyslexia.[2]
1.
Abbreviated Journal Title: J Learn Disabil
Date Of Publication: 1991 Nov
Journal Volume: 24
Page Numbers: 542 through 549
Country of Publication: UNITED STATES
Language of Article: Eng
Special Journal List:
Issue/Part/Supplement: 9
ISSN: 0022-2194
Prescription-only drugs such as , , and have the most strong evidence to support their use to improve short and long term memory functions -- in healthy subjects...
Edited by nootropikamil, 09 July 2006 - 09:47 PM.
