I think this is the best scientific presenation to support the use of Piracetam in healthy subjects.
In (1), "Nootropyl (Piracetam) ... was tested for its effect on man by administering it to normal volunteers. The subjects were given 3x4 capsules at 400 mg per day, in a double blind study. Each subject learned series of words presented as stimuli upon a memory drum. No effects were observed after 7 days but after 14 days verbal learning had significantly increased."
(2) was "A double-blind, intra-individual cross-over comparison of the mental performance of 18 aging, non-deteriorated individuals ... with reduced mental performance possibly related to disturbed alertness" "during two 4-week periods of piracetam (1-acetamide-2-pyrrolidone) and placebo administration performed using conventional and computerized perceptual-motor tasks. In a majority of these tasks the subjects did
significantly better when on piracetam than on placebo, a finding consistent with ratings completed by two independent observers." How close to normal aging, and how relevant to the youthful and healthy, is open to some question. A review (11) adds the following, not stated in the abstract: " Moderate but statistically significant improvements (up to 12% vs placebo; p < 0.05) in a range of assessments of cognition were obtained in 18 healthy individuals aged 50 years or more who received piracetam as part of an 8-week, doubleblind crossover study. However, individuals' own ratings of their mental and psychological condition did not reveal any significant differences between piracetam and placebo. "
I DO have copies of the full texts of these trials (1,2) hidden away in my files somewhere, but I'll not be able to look into them to get more details for a month or two; anyone with easy access, please do report.
(6) summarizes (4) VERY briefly thus: "Five double-blind controlled studies in normal adults have used tests of verbal learning and memory; in all the published studies piracetam was superior to placebo in verbal function {citing my (1,2,4,5,9) -MR}." (11), likewise, includes it with (1,2) as being among "A small number of placebo-controlled studies {that} have shown that piracetam improves aspects of mental performance in healthy volunteers." Unfortunately, (4) is in German and unavailable to me.
Further details are alleged to be provided by this article on piracetam by James South: "Giurgea and Salama {my (3) below -MR} report the confirmation of Dimond/Brouwer's work by Wedl and Suchenwirth in 1977 {my (4) below -MR}. Wedl found significant improvement in mental performance in a group of 17 healthy young volunteers given 3.2 grams per day Piracetam for five days." Unfortunatel again, (3) is not even a MEDLINE-indexed item; moreover, Giurgea does seem to be a somewhat 'tainted' source, as the inventor of piracetam and long-term UCB employee. Further, James South is, in my opinion, a very unreliable source of information on drugs and supplements.
If anyone has access to (4), or even (3), to help confirm any of this, it would be helpful.
(6) also includes the same statement about (5), ie, that it is one of "Five double-blind controlled studies in normal adults {in which} ... piracetam was superior to placebo in verbal function". Later, it elucidates that it was a study "involving 16 male dyslexic adolescents and 14 normal student volunteers in a 3-week double-blind trial of 4.8 g piracetam or placebo per day, {which} found that dyslexics (and normals) treated with piracetam showed a decrease in the number of trials required to reach criteria in a rote verbal learning task, while after placebo both groups showed insignificant minor changes." The abstract of (5) gives no hint of this info on the healthy control group, but the review is actually by the authors of (5). According to the JS article op cit, "Wilsher and co-workers (1979) {my (5) -MR} related their results with 4.8 grams per day Piracetam in a double blind, crossover trial to study the benefits of Piracetam for dyslexic students. Interestingly, the 14 healthy student controls, matched for IQ with the dyslexic subjects, demonstrated a significantly better result on a test measuring ability to memorize nonsense syllables while using Piracetam as compared to placebo." This is not quite the same claim as made in (6), tho' similar, and seems to be a good general confirmation.
If anyone has a convenient way to get an actual copy of (5), it would be helpful.
Another study cited by (6) as one of teh "Five double-blind controlled studies in normal adults {in which} ... piracetam was superior to placebo in verbal function" is (9); unfortunately, (6) provides no further details, and as the citation says, it was an "Unpublished doctoral dissertation, University of London School of Pharmacy." I doubt this was a very useful study IAC, as the title says it was an "acute dose"; still, anyone at the U of L should be able to get a copy; if you can, please do!
(7) is on its face supportive, at least in AAMI, which is close to 'normalcy': "A double-blind randomized trial was performed involving 162 patients with age-associated memory impairment (AAMI) ... Two intervention methods--a drug and a cognitive therapy--were assessed in combination. Three randomized parallel groups of 54 patients each, aged 55 years and over, were followed and treated for 3 months. After a placebo wash-out period of 10 days, one group received 2.4 g of piracetam, another group, 4.8g, and the third, a placebo. ... Combined therapy was most effective in patients whose baseline performance on memory tests was lowest. The best results were observed with 4.8 g of piracetam, especially when training sessions began after 6 weeks of drug treatment. This result was confirmed by the global impression of the principal investigator."
Further details are provided in a review (8): "Memory was tested by the Rey Auditory Verbal Learning Test ... and a freee-recall test developed by the principal investigator. ... {B}oth piracetam groups showed significantly greater improvement relative to baseline for global recall (immediate and delayed recall average) and immediate recall. The high-dose group also showed significantly greater improvement than the control group on delayed recall. ... the high-dose piracetam group that received memory training during the last half of the protocol showed a 35.5% improvement, whereas the placebo group with last-half memory training showed a 12% improvement."
However, (8) also presents a caveat not raised in the abstract: "These effects may be more apparent than real, though, because by chance the placebo group performed somewhat better at baseline than both piracetam groups (by an average of 1-2 items). By the end of treatment, the three groups were virtually indistinguishable in {absolute} performance on the free-recall tests. It is possible thathad the placebo group's baseline been as low as the piracetam groups', the placebo group would have shown a comparable improvement ... Indeed, the most robust effects were found in the comparison of the two groups that differed the most at baseline: the placebo and the high-dose ... group. Further, there were no significant treatment effects on the Rey test, on which baseline performace was nearly identical across the groups."
(10) is the closest thing to a genuine negative report: "Fifty-six hospitalized geriatric patients between the ages of 65 and 80 were given piracetam (Nootropil) 2400 mg/day or placebo on a double blind basis over a two month period. Every patient submitted to a battery of psychological tests before and after the two month trial ... In addition, at pretreatment, 4 and 8 weeks, the patient completed a Profiles of Mood States, a Clinical Global Evaluation was done by the investigator, and laboratory determinations were performed....There were no significant statistical differences between the two groups of patients on all measures utilized except for the Clinical Global Evaluation, where 52% of the patients on piracetam showed minimal improvement versus 25% of the placebo group (P less than 0.05)."
(8) claims the following additional informatioin about (10): the patient population had "age-related memory decline not necessarily associated with dementia or depression", making it more relevant to healthy normals. They say that piracetam "had no effect on immediate recall of stories, gemetric shapes, and designs." This may mitigate against the apparent null result on cognition, as none of these measures quite matches the variable on which positive results tend to be reported (verbal recall -- tho' stories may hve been 'verbal,' of course).
Overall, I find the results supportive of piracetam's usefulness in normal, healthy humans, esp if aged (tho' 'normal' and 'healthy' then become somewhat debatable terms). Alas, there are none of the large, long-term studies in healthy folk that I'd really like to've been performed, and none are likely to be in the future. There are several reasons for this. First, at the time when the stuff was developed, one could really get away with very little evidence before marketing a drug. Prior to the amendments to the Food, Drug, and Cosmetics Act of 1962, you didn't have to prove efficacy in the USA, and it would be many years before drugs would begin to be EXCLUDED from marketing for lack of access; European countries would take considerably longer. Cognitiive enhancement in the healthy not being a disease in need of a 'cure' by FDA standards, there is no incentive for performing such trials at the time, as you couldn't get FDA approval to market it for that purpose (tho' as we've seen in so many cases of late, it's easy enough to get approval for one indication and then pull various dirty tricks to encourage off-label use); even to do that, you'd first have to prove its utility in some disease state, which as we've seen has been difficult (perhaps beacuse it really just doesn't work in AD, etc). And of course, piracetam is now off-patent, making any such further trials all the more unlikely.
these reasons are often invoked as the reason why a supplement has never been subjected to proper trials, and then a bizarre logical mis-step is taken, in which the fact that there is a REASON why no such trials have been performed, is taken as some kind of justification for taking it, as if such trials HAD been performed, or as if some silly in vitro study were therefore sufficient evidence. This is a good way to get yourself killed, or at least ripped off. I'm constantly hammering at individuals and companies for this kind of sloppy BS. So why am I willing to let piracetam off the hook?
First, everyone agrees that the stuff is nearly free of side effects (mild and similar to placebo in incidence), and acute toxicity information suggests that it's safer than most SUPPLEMENTS (ie, LD-50 >8 g/kg iv in rats, >10 g/kg orally in rats, dogs, and mice (12)). And while I hate to repeat a half-remembered rumor, IIRC someone (Dean and Morgenthaler?) reported an (anonymous?) FDA official saying that piracetam couldn't possibly have any beneficial effects, because its toxicity is so low!
Second, I've been using it for some years now in relative ignorance of the true state of the research, and in combination wiht a background dose of 500 mg pyroglutamate, I've been pleased with the results, which seem to include greater mental energy, the drive to remain on-task, and some enhancement of creativity consistent with the reports (in rats and schizophrenic humans) of enhanced interhemispheric communication.
And third, I'm now getting a brand that I consider to have reliable QC (Relentless Improvement) at a much cheaper price than the UCB Nootropyl.
So putting these 3 factors together: granted its low cost and safety, I'm willing to abandon my usual caution and simply say that if these are placebo effects, I'm OK with that . But I would still like more information if available, and urge others to provide any quality information to which they have access.
-Michael
1.Psychopharmacology (Berl). 1976 Sep 29;49(3):307-9.
Increase in the power of human memory in normal man through the use of
drugs.
Dimond SJ, Brouwers EM.
PMID: 826948 [PubMed - indexed for MEDLINE]
2. Acta Psychiatr Scand. 1976 Aug;54(2):150-60.
Piracetam-induced improvement of mental performance. A controlled study
on normally aging individuals.
Mindus P, Cronholm B, Levander SE, Schalling D.
PMID: 785952 [PubMed - indexed for MEDLINE]
3. C. Giurgea, M. Salama (1977) "Nootropic drugs" Prog. Neuro-Pharmac. 1.235-47. [Cited by James South article].
4. Nervenarzt. 1977 Jan;48(1):58-60.
[Effects of the GABA-derivative piracetam: a double-blind study in
healthy probands (author's transl)]
Wedl W, Suchenwirth RM.
PMID: 846621 [PubMed - indexed for MEDLINE]
5. Wilsher C, Atkins G, Manfield P.
Piracetam as an aid to learning in dyslexia. Preliminary report.
Psychopharmacology (Berl). 1979 Sep;65(1):107-9.
PMID: 116285 [PubMed - indexed for MEDLINE]
6. Wilsher CR, Taylor EA.
Piracetam in developmental reading disorders: A review.
European Child & Adolescent Psychiatry. 1994 Apr;3(2):59-71
http://dx.doi.org/10.1007/BF01977668
7. Int Psychogeriatr. 1994 Fall;6(2):155-70.
Drug therapy and memory training programs: a double-blind randomized trial of general practice patients with age-associated memory impairment.
Israel L, Melac M, Milinkevitch D, Dubos G.
PMID: 7865703 [PubMed - indexed for MEDLINE]
8. McDaniel MA, Maier SF, Einstein GO.
"Brain-specific" nutrients: a memory cure?
Psychological Science in the Public Interest. 2002 May; 3(1):12-38.
http://www.psycholog...pdf/pspi312.pdf
9. Hyde, J.R.G. (1980). The Effect of an Acute Dose of Piracetam on Human Pe~ormance. Unpublished doctoral dissertation, University of London School of Pharmacy. [Cited by (6)].
10. Abuzzahab FS Sr, Merwin GE, Zimmermann RL, Sherman MC.
A double blind investigation of piracetam (Nootropil) vs placebo in geriatric memory.
Pharmakopsychiatr Neuropsychopharmakol. 1977 Mar;10(2):49-56.
PMID: 360232 [PubMed - indexed for MEDLINE]
11. Noble S, Benfield P
Piracetam: A Review of its Clinical Potential in the Management of Patients with Stroke
CNS Drugs. 1998 Jun;9(6):497-511.
http://www.ingentaco...000006/art00006
12: Gouliaev AH, Senning A.
Piracetam and other structurally related nootropics.
Brain Res Brain Res Rev. 1994 May;19(2):180-222. Review.
PMID: 8061686 [PubMed - indexed for MEDLINE]
I only could get to citation three before running out of energy trying to play devil's advocate on this...
