Single doses of piracetam affect 42-channel event-related potential microstate maps in a cognitive paradigm.
Michel CM, Lehmann D.
Department of Neurology, University Hospital, Zurich, Switzerland.
We examined whether a single administration of piracetam produces dose-dependent effects on brain functions in healthy young men. In 6 subjects, 42-channel event-related EEG potential maps (ERP) were recorded during a task requiring subjects to watch single digits presented in a pseudorandom order on a screen and to press a button after all triplets of three consecutive odd or even digits. The ERP maps to the three digits of the correctly detected triplets were analyzed in terms of their mapped ERP field configuration (landscape). Different landscapes of the maps indicate different configuration of the activated neural population and therefore reflect different functional microstates of the brain. In order to identify these microstates, adaptive segmentation of the map series based on their landscapes was done. Nineteen time segments were found. These segments were tested for direct effects on brain function of three single doses of piracetam (2.9, 4.8 or 9.6 g) and a placebo given double-blindin balanced order. Piracetam mainly affected the map landscape of the time segments following the triplet's last digit. U-shaped dose-dependent effects were found; they were strongest after [single doses of] 4.8 g piracetam. Since these particular ERP segments are recognized to be strongly correlated to cognitive functions, the present findings suggest that single medium [4.8 g] doses of piracetam selectively activate differently located or oriented neurons during cognitive steps of information processing.
The above study demonstrates that the optimum dosage of PIRACETAM for COGNITION is individual doses of 4.8 grams PIRACETAM, per each dose.
Piracetam relieves symptoms in progressive myoclonus epilepsy:a multicentre, randomised, double blind, crossover study comparing the efficacy and safety of three dosages of oral piracetam with placebo.
Koskiniemi M, Van Vleymen B, Hakamies L, Lamusuo S, Taalas J.
Haartman Institute, Department of Virology, University of Helsinki, Finland.
To compare the efficacy, tolerability, and safety of three daily dosage regimens of oral piracetam in patients with progressive myoclonus epilepsy.
Twenty patients (12 men, eight women), aged 17-43 years, with classical Unverricht-Lundborg disease were enrolled in a multicentre, randomised, double blind trial of crossover design in which the effects of daily doses of 9.6 g, 16.8 g, and 24 g piracetam, given in two divided doses, were compared with placebo. The crossover design was such that patients received placebo and two of the three dosage regimens of piracetam, each for two weeks, for a total treatment period of six weeks and thus without wash out between each treatment phase. The primary outcome measure was a sum score representing the adjusted total of the ratings of six components of a myoclonus rating scale in which stimulus sensitivity, motor impairment, functional disability, handwriting, and global assessments by investigators and patients were scored. Sequential clinical assessments were made by the same neurologist in the same environment at the same time of day.
Treatment with 24 g/day piracetam produced significant and clinically relevant improvement in the primary outcome measure of mean sum score (p=0.005) and in the means of its subtests of motor impairment (p=0.02), functional disability (p=0.003), and in global assessments by both investigator (p=0.002) and patient (p=0.01). Significant improvementin functional disability was also found with daily doses of 9.6 g and 16.8 g.The dose-effect relation was linear and significant. More patients showed clinically relevant improvement with the highest dosage and, in individual patients, increasing the dose improved response. Piracetam was well tolerated and adverse effects were few, mild, and transient.
This study provides further evidence that piracetam is an effective and safe medication in patients with Unverricht-Lundborg disease. In addition, it shows that a dose of 24 g is highly beneficial, more effective than lower doses and that a dose-effect relation exists.There is considerable variation in optimal individual dosage.
The above study demonstrates that PIRACETAM is SAFE when taken at doses up to and including 24 grams total daily; and PIRACETAM’s therapeutic effects are dosage dependent.
Int J Psychophysiol. 1999 Oct;34(1):81-7.
Single-dose piracetam effects on global complexity measures of human spontaneous multichannel EEG.
Kondakor I, Michel CM, Wackermann J, Koenig T, Tanaka H, Peuvot J, Lehmann D.
The KEY Institute for Brain-Mind Research, University Hospital of Psychiatry, Zurich, Switzerland.
Global complexity of 47-channel resting electroencephalogram (EEG) of healthy young volunteers was studied after intake of a single dose of a nootropic drug (piracetam, Nootropil UCB Pharma) in 12 healthy volunteers.Four treatment levels were used: 2.4, 4.8, 9.6 g piracetam and placebo. Brain electric activity was assessed through Global Dimensional Complexity and Global Omega-Complexity as quantitative measures of the complexity of the trajectory of multichannel EEG in state space. After oral ingestion (1-1.5 h), both measures showed significant decreases from placebo to 2.4 g piracetam. In addition, Global Dimensional Complexity showed a significant return to placebo values at 9.6 g piracetam. The results indicate that a single dose of piracetam dose-dependently affects the spontaneous EEG in normal volunteers, showing effects at the lowest treatment level. The decreased EEG complexity is interpreted as increased cooperativity of brain functional processes.
The above study demonstrates that PIRACETAM’s therapeutic effects are dosage dependent, with the greatest therapeutic effects occurring with the 9.6 gram dosage.
Psychiatry Res. 1993 Dec;50(4):275-82.
Space-oriented EEG segmentation reveals changes in brain electric field maps under the influence of a nootropic drug.
Lehmann D, Wackermann J, Michel CM, Koenig T.
Department of Neurology, University Hospital, Zurich, Switzerland.
Map landscape-based segmentation of the sequences of momentary potential distribution maps (42-channel recordings) into brain microstates during spontaneous brain activity was used to study brain electric field spatial effects of single doses of piracetam (2.9, 4.8, and 9.6 g Nootropil UCB [Piracetam] and placebo)in a double-blind study of five normal young volunteers. Four 15-second epochs were analyzed from each subject and drug condition. The most prominent class of microstates (covering 49% of the time) consisted of potential maps with a generally anterior-posterior field orientation. The map orientation of this microstate class showed an increasing clockwise deviation from the placebo condition with increasing drug doses (Fisher's probability product, p < 0.014). The results of this study suggest the use of microstate segmentation analysis for the assessment of central effects of medication in spontaneous multi-channel electroencephalographic data, as a complementary approach to frequency-domain analysis.
The above study also demonstrates that PIRACETAM’s therapeutic effects are dosage dependent, with the greatest therapeutic effects occurring with the 9.6 gram dosage.
Global dimensional complexity of multi-channel EEG indicates change of human brain functional state after a single dose of a nootropic drug.
Wackermann J, Lehmann D, Dvorak I, Michel CM.
Department of Neurology, University Hospital, Zurich, Switzerland.
Viewing the multi-channel EEG as a sequence of momentary field maps corresponds to the concept of a trajectory in K-dimensional state space (K = number of channels). This approach permits a quantitative, single value measure of complexity of the brain state trajectory, the global correlation dimension that describes the ensemble characteristics of all recorded channels. In 5 normal volunteers, 4 records of 16-channel resting EEG were obtained during each of 4 randomized sessions (double blind design) after a single dose of placebo or 2.9 g or 4.8 g or 9.6 g piracetam. The global correlation dimension of a 40 sec epoch from each record was estimated, using 50 computational runs with 8192 point pairs. The results were combined for the two intermediate doses and averaged over repeated records. The dimensionality decreased from placebo (median = 5.89) to low dose (median = 5.72) to high dose (median = 5.59), significant in a Friedman ANOVA at P < 0.02, with significant differences between placebo vs. high and low vs. high dose. Thus, the subtle change of brain global functional state after a single dose of piracetam is reflected by the non-linear measure of global dimensional complexity of the multi-channel EEG.
Again, the above study demonstrates that PIRACETAM’s therapeutic effects are dosage dependent, with the greatest therapeutic effects occurring with the 9.6 gram dosage; and reports “significant differences between low vs. high dose”.
Arzneimittelforschung. 1993 Feb;43(2):110-8.
Platelet anti-aggregant and rheological properties of piracetam. A pharmacodynamic study in normal subjects.
Moriau M, Crasborn L, Lavenne-Pardonge E, von Frenckell R, Col-Debeys C.
Department of Internal Medicine, University of Louvain (UCL), St.-Luc University Clinics, Brussels, Belgium.
The random administration of four different single oral doses of piracetam (Nootropil, CAS 7491-74-9)--1.6 g, 3.2 g, 4.8 g and 9.6 g--at fixed intervals of 2 weeks to 5 healthy subjects has confirmed and explicited its platelet anti-aggregant and rheological properties after doses of 4.8 g and 9.6 g. The effect on platelet aggregation occurs through inhibition of thromboxane synthetase or anti-thromboxane A2 activity together with a reduction in the plasma level of von Willebrand's factor (F.VIIIR:vW). The rheological effect is related to the action of piracetam on cell membrane deformability (red cells, white cells and platelets) and to its simultaneous effect in reducing by 30-40% plasma levels of fibrinogen and von Willebrand's factor. In addition, it exerts a direct stimulant effect on prostacyclin synthesis in healthy endothelium. These effects are greatest between 1 and 4 h after dosage, and then diminish progressively to disappear between 8 and 12 h after administration. This explains the need to divide the total daily dose into 3 intakes at 8-hourly intervals. This study confirms the presence of four sites of action of piracetam: the vessel wall, platelets, plasma and cell membranes (RBC, WBC), which provide the basis for the potentially important antithrombotic activity of piracetam.
The above study also demonstrates that PIRACETAM’s therapeutic effects are dosage dependent, with the greatest therapeutic effects occurring with the 4.8 g and 9.6 g dosages; and illustrates the need for the total daily dosage to be split into 2 or 3 individual dosages (e.g. 4.8g twice daily).
"You may very well find that your irritability is U-Shaped Curve dosage dependant as opposed to Linear, in that too little (e.g. 2.4 grams) and too much (e.g. 1 Kg) may cause you to become irritable, but in the middle (e.g. 9.6 grams) does not" - ScienceGuy
"Regarding TOLERANCE - Whilst some TOLERANCE may develop, as a consequence of my many years personal and professional experience with utlization of PIRACETAM at 4.8 grams 2 - 3 times daily dosage I am of the opinion that any such TOLERANCE is distinctly limited and with this dosage regimen consistent therapeutic efficacy is in fact sustained indefinitely with consistent use" - ScienceGuy
"Piracetam is also filtered almost solely through the kidneys" - ScienceGuy
- take beef organ kidney supplement with piracetam
"PIRACETAM's LONG-TERM SAFETY can be somewhat ascertained from its TOXICITY STUDIES which in fact demonstrate that PIRACETAM is extremely NON-TOXIC to the extent that its TOXICITY is practically NON-EXISTENT." - ScienceGuy
"Piracetam usually signals the calcium ions in your brain to release glutamate into your post synaptic space (in small amounts). I'm trying to find a good food/beverage that helps take care of the low calcium ion concentration problem. So far the best I have come up with is calcium from milk (better than calcium tablet supplementation). Too much calcium can cause glutamate to be released in excess amounts and kill neurons." - Hyperspace21
"It is somewhat IRONIC that I take my PIRACETAM with MILK. Although I cannot claim credit for doing so for the purposes of INCREASING CALCIUM IONS within the brain; I have been doing so to avoid STOMACH UPSET." - ScienceGuy
Please kindly note the following regarding PIRACETAM TOXICITY:
Brain Res Brain Res Rev. 1994 May;19(2):180-222.
Piracetam and other structurally related nootropics.
Gouliaev AH, Senning A.
Department of Chemistry, Aarhus University, Denmark.
Extract from Full Text
The racetams possess a very low toxicity... LD50 > 10 g/kg p.o. (mice, rats and dogs)
[LD50 is a TOXICITY MEASUREMENT comprising the amount of a material, given all at once, which causes the death of 50% (one half) of a group of test animals.]
Advances in Neurology 1986; 43: 675-85
Piracetam: physiological disposition and mechanism of action
Tacconi MT, Wurtman RJ.
Extract from Full Text
PIRACETAM apparently is virtually non-toxic.... Rats treated chronically with 100 to 1,000 mg/kg orally for 6 months and dogs treated with as much as 10g/kg orally for 1 year did not show any toxic effect.
"These CLINICAL TOXICITY STUDIES demonstrated no toxic effects whatsoever even when PIRACETAM was administered at a dosage PER ORALLY of 10g / Kg to dogs for 1 year!
The HUMAN EQUIVALENT DOSAGE (HED) for this (via BSA calculation) = 5.4g / Kg
Therefore, for a 76Kg Man a DOSAGE of 410 GRAMS (or 0.41 Kg) PIRACETAM would in fact be completely NON-TOXIC and SAFE
Please note that I am NOT suggesting that anyone take PIRACETAM at a dosage of 410 GRAMS; however, this does demonstrate that PIRACETAM is virtually non-toxic and as such total daily dosages of 9.8 grams and higher are wholly SAFE." - ScienceGuy
"namely take the full dose (e.g. 4.8g BID, total 9.8g) of PIRACETAM; and stack the OTHER RACETAMS with this at whatever dosages for the respective OTHER RACETAMS you find works well with the full dose PIRACETAM, which will likely be a reduced dosage
I personally stack 100mg PRAMIRACETAM and 200mg OXIRACETAM with 10g PIRACETAM daily" - ScienceGuy
Alcohol. 1995 May-Jun;12(3):279-88.
Piracetam impedes hippocampal neuronal loss during withdrawal after chronic alcohol intake.
Brandão F, Paula-Barbosa MM, Cadete-Leite A.
Department of Anatomy, Porto Medical School, Portugal.
In previous studies we have demonstrated that prolonged ethanol consumption induced hippocampal neuronal loss. In addition, we have shown that withdrawal after chronic alcohol intake augmented such degenerative activity leading to increased neuronal death in all subregions of the hippocampal formation but in the CA3 field. In an attempt to reverse this situation, we tested, during the withdrawal period, the effects of piracetam (2-oxo-1-pyrrolidine acetamide), a cyclic derivative of gamma-aminobutyric acid, as there is previous evidence that it might act as a neuronoprotective agent. The total number of dentate granule, hilar, and CA3 and CA1 pyramidal cells of the hippocampal formation were estimated using unbiased stereological methods. We found out that in animals treated with piracetam the numbers of dentate granule, hilar, and CA1 pyramidal cells were significantly higher than in pure withdrawn animals, and did not differ from those of alcohol-treated rats that did not undergo withdrawal. These data suggest that piracetam treatment impedes, during withdrawal,the pursuing of neuronal degeneration.
Piracetam in elderly psychiatric patients with mild diffuse cerebral impairment
G Chouinard, L Annable, A Ross-Chouinard, M Olivier, F Fontaine
PMID: 6415738 DOI: 10.1007/BF00429000
In a 12-week double-blind study, piracetam at two dose levels (2.4 and 4.8 g/day) was compared to placebo in the treatment of 60 elderly psychiatric patients with mild diffuse cerebral impairment, but no signs of focal brain lesion. The psychiatric illness, schizophrenia or affective disorder, of patients selected was in remission at the time of the study. Monthly evaluations by the nurse revealed that piracetam improved overall functioning, particularly alertness, socialization, and cooperation, relative to the control group. Patients treated with 2.4 g/day piracetam also showed significant improvement in scores for the full IQ and the memory quotient on the Wechsler Adult Intelligence and Memory Scales; greater response was seen in those with lower initial scores. Piracetam at 4.8 g/day had a more rapid onset of action on behavioral variables than 2.4 g/day, but its therapeutic effect tended to diminish at 12 weeks, possibly as the result of overstimulation. Piracetam did not appear to interfere with concomitant psychotropic maintenance medication or affect the psychiatric illness itself.
The glutamatergic system is the only receptor system which piracetam seems to have a direct effect on. Piracetam binds to some glutamate receptors, although this may not be at all relevant in normal doses. Despite this, one review contends that the glutamatergic system may play a central role in piracetam's nootropic activity.
One of the main supporting pieces of evidence for this hypothesis is that the memory-enhancing effects of piracetam can be easily blocked by NMDA channel blockers. Both ketamine and MK-801 antagonize the nootropic effect. In a Russian study, it was found that piracetam potentiated the response to glutamate and aspartate through the glycine site of the NMDA receptor, and this effect may be obscured by the presence of glycine. This would indicate a direct effect at the glycine site, and another 2-pyrrolidinone derivative, HA-966, exhibits antagonistic properties at the glycine site. Again, this effect has not been demonstrated to be relevant in normal doses. Piracetam also prevents the age-related decrease in NMDA receptor density, but this could easily be due to nonspecific action.
Piracetam may also have important effects on AMPA receptors. As is the case with NMDA receptors, it increases the density of AMPA receptor sites. More importantly, piracetam increases the efficiency, but not potency, of AMPA-induced calcium influx and antagonizes the effect of the L-type calcium channel blocker nifedipine. This represents a promising and largely unexplored mode of action, since positive modulation of AMPA receptors is also an effect shared by other cognition enhancers such as the ampakines and aniracetam.
It has been reported that autism is a hypoglutamatergic disorder. Therefore, it was of interest to assess the efficacy of piracetam, a positive modulator of AMPA-sensitive glutamate receptors in autistic disorder. About 40 children between the ages three and 11 years (inclusive) with a DSM IV clinical diagnosis of autism and who were outpatients from a specialty clinic for children were recruited. The children presented with a chief complaint of severely disruptive symptoms related to autistic disorder. Patients were randomly allocated to piracetam + risperidone (Group A) or placebo + risperidone (Group B) for a 10-week, double-blind, placebo-controlled study. The dose of risperidone was titrated up to 2 mg/day for children between 10 and 40 kg and 3 mg/day for children weighting above 40 kg. The dose of piracetam was titrated up to 800 mg/day. Patients were assessed at baseline and after 2, 4, 6, 8 and 10 weeks of starting medication. The measure of the outcome was the Aberrant Behavior Checklist-Community (ABC-C) Rating Scale (total score). The ABC-C Rating Scale scores improved with piracetam. The difference between the two protocols was significant as indicated by the effect of group, the between subjects factor (F = 5.85, d.f. = 1, P = 0.02). The changes at the endpoint compared with baseline were: -11.90 +/- 3.79 (mean +/- SD) and -5.15 +/- 3.04 for group A and B respectively. A significant difference was observed on the change in scores in the ABC-C Rating Scale in week 10 compared with baseline in the two groups (t = 6.017, d.f. = 38, P < 0.0001). The results suggest that a combination of atypical antipsychotic medications and a glutamate agent such as piracetam, might have increase synergistic effects in the treatment of autism.
Piracetam-induced changes in the functional activity of neurons as a possible mechanism for the effects of nootropic agents.
Verbnyi YaI, Derzhiruk LP, Mogilevskii AYa.
Physical-Technical Low Temperature Institute, National Academy of Sciences of Ukraine, Khar'kov.
Studies were carried out on the effects of piracetam (4-20 mM) on the electrical activity of identified neurons in the isolated central nervous system of the pond snail in conditions of single-electrode intracellular stimulation and recording. Piracetam-induced changes were seen in 60-70% of the neurons studied. Different parameters showed different sensitivities to piracetam: the most frequent changes were in the action potential generation threshold, the slope and shape of the steady-state voltage-current characteristics of neuron membranes, and the appearance of piracetam-induced transmembrane ion currents. Nifedipine and cadmium ions, both of which are calcium channel blockers, generally reversed or weakened the effects of piracetam on the changes seen in test cells. This indicates that the effects of piracetam result from its action on calcium channels; selective changes in calcium channels may determine which piracetam-induced effects appear at the cellular level. It is hypothesized that the piracetam-sensitive cellular plasticity mechanisms may make a significant contribution to its nootropic action at the behavioral level.
Piracetam and other structurally related nootropics
Alex Haahr Gouliaeva,
Alexander SenningPosted Image, b
a Department of Chemistry, Aarhus University, Langelandsgade 140, DK-8000 Aarhus C, Denmark
b Department of Chemistry and Chemical Engineering, The Engineering Academy of Denmark, Building 376, DK-2800 Lyngby, Denmark
Nearly three decades have now passed since the discovery of the piracetam-like nootropics, compounds which exhibit cognition-enhancing properties, but for which no commonly accepted mechanism of action has been established. This review covers clinical, pharmacokinetic, biochemical and behavioural results presented in the literature from 1965 through 1992 (407 references) of piracetam, oxiracetam, pramiracetam, etiracetam, nefiracetam, aniracetam and rolziracetam and their structural analogues. The piracetam-like nootropics are capable of achieving reversal of amnesia induced by e.g., scopolamine, electrocon-vulsive shock and hypoxia. Protection against barbiturate intoxication is observed and some benefit in clinical studies with patients suffering from mild to moderate degrees of dementia has been demonstrated. No affinity for the α1-, α2-, β-, muscarinic, 5-hydroxytryptamine-, dopamine, adenosine-A1, μ-opiate, γ-aminobutyric acid (GABA) (except for nefiracetam (GABAA)), benzodiazepine and glutamate receptors has been found. The racetams possess a very low toxicity and lack serious side effects. Increased turnover of different neurotransmitters has been observed as well as other biochemical findings e.g., inhibition of enzymes such as prolylendopeptidase. So far, no generally accepted mechanism of action has, however, emerged. We believe that the effect of the racetams is due to a potentiation of already present neurotransmission and that much evidence points in the direction of a modulated ion flux by e.g., potentiated calcium influx through non-l-type voltage-dependent calcium channels, potentiated sodium influx through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor gated channels or voltage-dependent channels or decreases in potassium efflux. Effects on carrier mediated ion transport are also possible.
[Comparative study of the indices of the antidepressive activity of potassium orotate andpiracetam].
[Article in Russian]
Karkishchenko NN, Khaĭtin MI.
It has been established in mouse experiments that potassium orotate (100 mg/kg) and piracetam (500 mg/kg) given in chronic oral doses have an antidepressant activity according to the "behavioral despair" test. It has been demonstrated that antidepressant activity of potassium orotate (20 and 50 mg/kg) and piracetam (50 and 100 mg/kg) is associated with a psychostimulant effect.
PMID: 3996568 [PubMed - indexed for MEDLINE]
New aspects in mechanisms of antihypoxic piracetam action.
Wustmann C, Fischer HD, Rudolph E, Schmidt J.
Institute of Pharmacology and Toxicology, Medical Academy Carl Gustav Carus, Dresden, DDR.
A long-term piracetam treatment leads to an improved stimulus-effect-coupling of potassium stimulated dopamine release: The maximum effect of the potassium stimulus is already obtained in presence of much lower Ca++-concentrations (Ca++-economizing effect) than normally. In consequence of the improved stimulus-effect-coupling by piracetam treatment the dose-dependent inhibitory effect of the calcium antagonist flunarizine on the fractional efflux rate of dopamine is decreased. The volume of vesicular structures is not involved in the piracetam effect.
With healthy adrenals, and particularly healthy levels of the hormone "aldosterone," your pupils will constrict, and will stay small the entire time you shine the light from the side. In adrenal insufficiency, the pupil will get small, but within 30 seconds, it will soon enlarge again or obviously flutter in it’s attempt to stay constricted. Why does this occur? Because adrenal insufficiency can also result in low aldosterone, which causes a lack of proper amounts of sodium and an abundance of potassium. This imbalance causes the sphincter muscles of your eye to be weak and to dilate in response to light.
Aldosterone receptors are involved in the mediation of the memory-enhancing effects of piracetam.
Mondadori C, Häusler A.
Pharmaceutical Research Department, CIBA-GEIGY Limited, Basel, Switzerland.
The blockade of the memory-enhancing effects of piracetam resulting from adrenalectomy can be abolished by substitution with either corticosterone or aldosterone. However, corticosterone substitution does not reinstate these effects if the aldosterone receptors are blocked by the aldosterone antagonist epoxymexrenon.
Adrenalectomy, corticosteroid replacement and their importance for drug-induced memory-enhancement in mice.
Häusler A, Persoz C, Buser R, Mondadori C, Bhatnagar A.
Research Department, Pharmaceuticals Division, CIBA-GEIGY Ltd., Basel, Switzerland.
Adrenalectomy blocks the memory-improving effect of piracetam-like compounds in mice. If this blockade is due to the removal of endogenous corticosteroids, replacement therapy with exogenous corticosteroids should reinstate the effects on memory. The present experiments were designed to determine the appropriate replacement dose (concentration in the drinking fluid) for corticosterone and aldosterone, the main corticosteroids in mice. Based on the effects of corticosterone on thymus weight, replacement with 3 micrograms/ml corticosterone given in the drinking fluid (0.9% NaCl) for one week was found to be appropriate. The appropriate replacement dose for aldosterone was found by giving aldosterone to adrenalectomized (ADX) mice in the drinking fluid in combination with 3 micrograms/ml corticosterone. The combination of 3 micrograms/ml corticosterone + 30 ng/ml aldosterone resulted in a plasma ratio of corticosterone/aldosterone which most closely approximated the ratio seen in sham-ADX control animals. The physiologic adequacy of the corticosteroid replacement doses resulting from this study were clearly demonstrated in subsequent behavioral experiments where blockade of the memory-enhancing effects of piracetam by adrenalectomy were overcome by replacement with either 3 micrograms/ml corticosterone or 30 ng/ml aldosterone given in the drinking fluid.
So, when I discovered that aldosterone insufficiency was easy to test with the pupil reflex test, and that aldosterone was also indicated in piracetam's mechanism of action, it was not hard to infer that the reason Piracetam can work wonderfully for a few months and then seem to have negative effects in the same person may be directly connected to the function of that person's adrenals, and specifically, their levels of aldosterone.
I believe that Piracetam places an extra strain on the adrenals, and this explains the paradoxical brain fog and drowsiness that so many users report: and the mystery of its unreliability/inconsistency. When a person's adrenals are already strained, be it from lack of sleep and too much stress, or something more sinister, like hypothyroid or addison's disease, the use of a -racetam places extra stress on levels of aldosterone and corticosterone, and when these hormones are already in shortage, usage only exacerbates negative symptoms of aldosterone deficiency.
So far, a few of the treatments I am exploring include, but are not limited to:
These are all aimed at improving the function of the thyroid/HPA Axis. I believe that when the HPA axis is restored to healthy functioning, piracetam will have a consistent positive effect in the user.