Spotlight on Piracetam
Ahh, good ol’ Piracetam. If you haven’t heard about Piracetam, you are probably living in the United States (it isn’t very popular over here). Piracetam is a drug that falls into the nebulous category of nootropics. Nootropics are drugs that supposedly improve cognitive function. Not just the cognitive function of individuals with brain damage but also perfectly normal people like you and me. There has been much debate over the benefits of nootropics. Scientists are interested in piracetam to help cure diseases while common people are interested in boosting their performance.
In this spotlight I’ll be focusing on studies revolving around Piracetam’s, the first and classical nootropic. Piracetam has been used to treat a myriad of diseases with varying levels of success. More details, including my own personal tale, after the jump.
Background
Before we can hit the studies, we need some theoretical background as to why people think nootropics work. Proponents for nootropics contend that the brain is like any other organ. It requires a complex set of chemicals, precursors and micronutrients to keep it functioning at its peak. Just as your other organs need vitamins and minerals, your brain requires its own cocktail of neurotransmitter precursors and associated chemicals. The idea is that by supplementing these you can increase cognitive function. Another approach is a bit more blind. By manipulating or adjusting the action of neurons (speed up firing, increase receptor density, increase neurotransmitter production, etc) it is theorized that cognitive benefits can be gained. This approach is a bit more like firebombing your brain and hoping something works well. That said, it is hardly any different than many of the medications we use on sick people.
Piracetam is the oldest drug specifically called a nootropic. Piracetam is cholinergic, meaning it affects the Acetylcholine neurotransmitter system in the brain. Piracetam is also a cyclic derivative of GABA. Piracetam integrates itself into the plasma membrane and appears to increase membrane fluidity. The exact method of action is not yet clear but it appears piracetam affects ion channels located on the membrane. Piracetam has been implicated in a wide array of benefits ranging from increased resistance to hypoxia via increased blood flow, neuroprotective capabilities, increased metabolism in the brain, protection from neurodegenerative diseases like Alzheimers and blood clotting diseases, and a whole host of other benefits. Conversely, many studies show little to no benefit. One possible reason for this wide range of applications and results is due to the relatively unknown nature of piracetam. The exact mechanisms is unknown and possible uses are still being explored. It is a cure looking for a disease at the moment.
Vascular Dementia
One such study looked at piracetam’s ability to help mitigate the effects of vascular dementia 1. Vascular dementia is a neurodegenerative disease caused by a number of vascular problems (stroke, hemorrhaging into the brain, hypoxia, etc) and is a rampant problem for elderly. Piracetam has been shown to help increase blood flow to impaired regions 2. Unlike traditional medication which reduces clotting factors, piracetam appears to affect the flexibility of blood cells. This additional flexibility helps blood cells get to areas of impaired blood flow. Furthermore, piracetam itself helps neurons survive periods of hypoxia, radically increasing survival rates3.
For this study, the common carotid arteries were cut in mice to simulate vascular dementia. The mice with arteries cut were divided into two further groups. Half were left alone while the other half received piracetam. A control group was given a fake surgery that did not cut the artery. The mice were subjected to a water maze test to determine the benefits (if any) of piracetam.
All groups performed well and when the platform in the water was visible, indicating that there was no inherent vision impairments. However, when the platform was submerged and not visible, the group receiving piracetam performed almost as well as the control group. The group that was not receiving piracetam performed inappropriate searches of the water maze, wasting time and clearly showing cognitive deficits.
Path of mice in water maze test
Piracetam reduced neuronal cells loss, nuclei shrinkage, and dark staining of neurons seen in the ischemic group. The ischemic group also exhibited intense localization of pro-apoptotic proteins (BAX and P53). The appearance of these proteins is never a good sign for a cell and generally signals the end of life. The piracetam treated group, however, showed no localization of these proteins, similar to the control group. Piracetam is clearly improving cognitive function and neuronal functionality in an environment that should be actively impairing it.
Coronary artery bypass grafting
A similar study looked at piracetam usage after performing coronary artery bypass grafting on patients4. Coronary artery bypass grafting is an effective method to stabalize ventricular dysfunction but is often associated with post-operation cognitive decline. Piracetam was given to patients before their surgery. Patients receiving the piracetam showed statistically significant increases over controls in both short-term and medium-term cognitive protection. The study concedes that the test pool of patients was small (~100) and that more testing is needed. It does, however, look to be a promising treatment for a problem which currently has no viable treatment at all.
Myoclonuses
Another study showed that high dosages of piracetam helped drastically improve myoclonuses (involuntary twitching of muscles)5. The man had a severe case of Spinocerebellar ataxia type 2 and was resistant to other treatment options. High dosages of piracetam improved the patients myoclonuses and seemed to improve alertness, although it is questionable if the alertness was due to piracetam or the removal of benzodiazepines (I suspect the later).
AMPA Receptors
On a molecular level, it has been shown that piracetam potentiates AMPA Receptors6. As I touched on in my article about Glial Cells, AMPA receptors are thought to play a key part in synaptic plasticity and learning. Increasing the sensitivity of these receptors may increase the speed at which new synapses become full strength, or old synapse connections change weights, facilitating learning. Recent work has shown that AMPA receptors, in addition to modulating plasticity, may trigger larger pathways that play a role in Alzheimers and other neural diseases.
Personal
And now we get to the personal part of this spotlight. About a year ago I discovered piracetam through some friends that swore by it. After some research at the library and online (the few scientific articles I could find without a University access to publications) I decided to give piracetam a try for myself. Piracetam is one of the safest chemicals to injest. Overdose is virtually impossible, extra is metabolized and urinated out. The benefits sounded impressive and the price was just right. Piracetam is often prescribed in Europe and available over the counter as a supplement in many places overseas. I was curious.
So, did it work? I did feel more mentally alert, had better image recall (ie. pseudo-photographic memory) and had the most vivid dreams of my life. I have never before remembered dreams much at all. While I was taking piracetam I was overwhelmed each morning by perfect recollection of the most bizarre, vivid dreams I have ever had. Furthermore, I felt distinctly refreshed in the morning. Clear headed. Normally I require a shower and coffee to get to that mental clearheadedness. With piracetam, I was clearheaded as soon as I had woken up. I felt more motivated and used a larger vocabulary, both in everyday speech and in my head.
The effects were very subtle though. There was no clear distinct line between normal and improved. How do you judge “improved cognitive function”? Was this all placebo?
Perhaps, I have no way to tell. It felt like it was working. My head certainly told me something was going on. Besides the subtle effects I felt (or imagined), I discovered I would routinely get a pounding headache in the afternoon if I did not maintain my blood sugar. This makes sense as piracetam has been shown to increase neural ATP production and consumption, increased blood flow. It also appears to deplete acetlycholine faster than normal (by increasing the density of acetylcholine receptors7), which is why many internet enthusiast forums recommend taking a supplement of Lecithin (which contains phosphocholine, a precursor to acetylcholine). A combination of maintaining good blood sugar levels (ie. eating normally, not missing meals) and taking a spoonful of lecithin seemed to keep the headaches at bay.
I find this substance, infact the whole notion of nootropics, highly interesting. Who wouldn’t want to pop a pill that can add a little edge, a broader vocabulary, better image recollection? Who doesn’t want to perform a little better? We have long trained muscles and organs to compete in sports, it is about time we started treating our brain like another muscle and boosting its performance.
References
1 He Z, Liao Y, Zheng M, Zeng F, Guo L, Piracetam Improves Cognitive Deficits Caused by Chronic Cerebral Hypoperfusion in Rats. Cellular and Molecular Neurobiology (2007), 10.1007/s10571-007-9165-x
2 Platt D, Horn J, Summa JD, On the efficacy of piracetam in geriatric patients with acute cerebral ischemia: a clinically controlled double-blind study. Arch Gerontol Geriatr (1993) 2:149–164
3 Gabryel B, Adamek M, Pudelko A, Malecki A, Trzeciak HI, Piracetam and vinpocetine exert cytoprotective activity and prevent apoptosis of astrocytes in vitro in hypoxia and reoxygenation. NeuroToxicol (2002) 1:19–31, 10.1016/S0161-813X(02)00004-9
4 Ildiko Szalma, Agnes Kiss, Laszlo Kardos, Geza Horvath, Erika Nyitrai, Zita Tordai and Laszlo Csiba , Piracetam Prevents Cognitive Decline in Coronary Artery Bypass: A Randomized Trial Versus Placebo. The Annals of Thoracic Surgery (2006) 4:1430-1435.
5 De Rosa A, Striano P, Barbieri F, Suppression of myoclonus in SCA2 by piracetam. Movement Disorders (2006) 1:116-118, 10.1002/mds.20683
6 O’Neill M, Witkin J, AMPA Receptor Potentiators: Application for Depression and Parkinson’s Disease. Current Drug Targets (2007) 8:603-620(18)
7 Pilch H and Müller W, Piracetam elevates muscarinic cholinergic receptor density in the frontal cortex of aged but not of young mice. Psychopharmacology (1988) 1:74-78, 10.1007/BF00735884
June 9th, 2008 at 7:08 pm
I have to point out that I am highly unsettled by your last comment.
“it is about time we started treating our brain like another muscle and boosting its performance.”
Your comparing apples and oranges. You shouldn’t “treat your brain like other muscles” because they work completely different. Do you know how we keep our brain in a healthy, working condition? We think!
June 10th, 2008 at 8:12 am
The only fundamental difference between your brain and your muscle is the function that they perform. They both share similar underlying mechanisms to continue to operate. Both undergo metabolism, both respond to signaling cascades, both require a complex cocktail of trophic factors for life. Your brain is merely a collection of cells, just as your muscle is a collection of cells. Why treat them differently?
Yes, has been shown that you can help to keep brain performance up by merely stimulating it. This is a property of the self-organizing, plastic ability of our brain.
But can you cure alzheimers just by thinking about it? Plaque buildup is mutually exclusive from the brains ability for self-reflection. How about schizophrenia? Therapy is used to help patients cope with the symptoms of their disease. Only medication can actually treat the symptoms becaues the disease is rooted in their genetics and a product of molecular biology. Thinking alone will do nothing.
Our brain is not special. It is merely another collection of cells doing their job. They may be doing it extremely well, but they are infact just cells. And that means they are liable to tweaking just as the rest of our body.