I staretd getting into nootropics about a year ago and read up on several positive reports of the benefits of racetams.
After a year of trying many different nootropics, I decided to look a little deeper for myself.
This is my own review and opinion on piracetam.
Racetam Review
The racetams are a chemical family of nootropic substances that share the 2-pyrrolidone structure. There are several different racetams that each vary in potency and qualitative effects, but they are all listed as nootropics that improve various aspects of cognitive function. However, their mode of action is not conclusive and it has not been determined that they are very effective at doing so. This is a summary of a few journal articles on the subject.
I draw on direct results and discussion from these journals, but not much on neurochemical or statistical analysis. Consult the original article for more information. I will also add information of my own where applicable for clarification.
G. Spignoli et. al. studied the effects of piracetam and oxiracetam on the utilization of acetylcholine (Ach) in the cerebral correct and hippocampus in rats (1986). It was found that they both they both increase high-affinity choline uptake at doses of 300mg/kg. Acetylcholine can be either brought back into the presynaptic terminal in two ways: via low-affinity transporter on a rather steady basis, or via NA+ dependant high-affinity transporter.
To determine the behavioral effects of piracetam, rats were injected with saline, HC-3, or HC-3 and oxiracetam. HC-3 is a drug that inhibits the synthesis of acetylcholine, effectively reducing its extracellular concentrations in the brain. Then the rats were subject to an active-avoidance test, where they had to climb a pole to avoid an electric shock. In the conditioning phase, the electric shock was preceded by an auditory signal so that the rats would learn to associate the sound with the forthcoming shock. The rats that were administered both Oxiracetam and HC-3 performed better on the test than the rats just given HC-3, showing that Oxiracetam helped mediate the effects of HC-3. The results concluded that these racetams increase the activity of the cortical cholinergic network which is involved in many cognitive processes.
A. Ennaceur and J. Delacour studied the effects of combined or separate administration of piracetam and choline in rats and found that only the rats that received 100mg/kg of choline performed better in a delayed alternation task, which was attributed to the increased levels of 5-HT that occurred with 100mg/kg of choline. (1987) They found that piracetam did not affect an improvement in the delayed alternation task. This study points to several others and states a possible explanation that piracetam only has an effect when cholinergic systems are disturbed. It should be noted that the delayed alternation task is a test of working memory, and avoidance conditioning is a test of memory and has a different neurobiological basis. Choline did not affect the memory task tested.
Also noteworthy is that the results of this study differ from many others which found that piracetam combined with choline did improve beneficial effects.
Raymond T. Bartus et. al. also studied the effects of piracetam and choline either combined separately or in combination (1981). This study specifically looked at the effects in aged rats in attempt to deduce if age-related memory disturbances could be mediated by piracetam. It found that a combination of 100mg/kf of piracetam and the same amount of choline significantly improved performance on a passive avoidance task, much better than those administered either piracetam or choline alone. This study also showed that repeated administration over the course of a week was superior to a single administration. The behavioral passive avoidance task consisted of conditioning the rats to avoid entering the dark half of a two-chambered box to avoid the shock they would receive should they enter it. They were then tested for retention of memory 24 hours later, and the piracetam was administered 30 minutes before the task initially took place.
This study suggests that piracetam co-administered with choline helps to temporarily reverse the deficit in cholinergic transmission in aged rats.
A more recent study by Maria Loscertales et. al. was done with day-old chicks in testing passive avoidance as well, but the piracetam was administered after the training to avoid the task (1998). The chicks had to remember not to peck at bead coated in a diluted aversant and were tested 24 hours later. During the training trial it was noted whether a chick pecked the bead and shook, showing a distaste for the aversant (methylanthranilate) or avoided the bead. This study aimed at determining whether piracetam facilitated the improvement of memory due to its modulation of corticosteroids as proposed by previous studies. It found that the facilitative effects of piracetam were inhibited when antagonists of the mineralocorticoid and glucocorticoid receptors were also administered. The results support previous studies that piracetam is involved in modulating long-term memory formation that requires activation of corticosteroid receptors, and conclude that piracetam increases plasma corticosteroid levels. However, the study also notes that while a dose of 100mg/kg piracetam improved memory, a dose of 300mg/kg did not. This U-shaped effect has been noted in other studies.
The last study I looked at is a human one by Stuart J. Dimond and E. Y. M. Brouwers, where subjects were given 3 X 4 capsules of 400mg piracetam per day in a double blind study (1976). It was found that no change occurred during the first 7 days, but 14 days showed an increase in verbal learning skills. 16 normal adults attending university were taken for the study and they had to learn a series of 9 words between six or seven letters each, each word was displayed for 2s at a time. Then after a 10s pause, they had to write down the words. The purpose of this study was not to show the neurochemical action, but if piracetam had any effects at all, and it appears as though it does.
Summary of the summary
Based loosely on these studies and several others on the subject, I would suspect that piracetam has a slight cognitive enhancing effect on healthy individuals. Even so, it seems to take several doses spread over the course of days to have an effect.
Furthermore, it seems it would be much more effective in older individuals where the cholinergic system is not functioning as effectively, thus the administration of piracetam to patients with Alzheimer’s is an effective way to improve reduced cognitive function, but administration of piracetam to healthy normal individuals wouldn’t make a significant impact.
On a final note, it is important to co-administer choline with piracetam to be sure not to deplete levels of choline in the brain since piracetam seems increase the turnover rate of acetylcholine in the various cholinergic systems.
