I get asked often why I don’t supplement with the racetams, specifically piracetam.Piracetam, for those who don’t know, is the most popular smart drug or nootropic. People take it to enhance their cognition. When I experimented with piracetam, I temporarily got pretty bad brain fog from it and my IQ must have transiently dropped quite a bit. I now have clues why, which I’ll explain later. I tried 2 different reliable brands of piracetam (nootropil, cognitive nutrition), as well as aniracetam and oxiracetam.
I varied the dosages of piracetam and choline, as well as the types of choline. The only thing that didn’t vary was the inevitable brain fog that resulted. When I got bad results I couldn’t understand why, since piracetam is supposedly amazing. People on forums told me I must have been doing something wrong.
This was about 3 years ago. Since then I have been reading many testimonials about similar negative effects. Most of the positive reviews I see talk about “subtle” benefits, which to me seems eerily close to what a placebo feels like. On the other hand, some of the negative reports are pretty serious. People describe how they used to be extremely intelligent and came crashing down after piracetam usage. Some haven’t recovered even after a long break.
My aim with this post isn’t to demonstrate that piracetam can’t benefit anyone or that you will certainly suffer harm by taking it, since some people can benefit from it and most people will probably experience little to no harm if it’s taken on a short term basis. Rather, my aim is to show that piracetam isn’t this risk-free drug it’s made out to be and if you experience negative results you shouldn’t dismiss them lightly. It’s interesting that some people treat it like vitamin C and take it even if they don’t notice a benefit, thinking it’s risk-free. The fact that anyone can order it without a prescription in the US bolsters the impression of how safe it is. This picture I found typifies the general assumptions about piracetam:
As far as drugs go, it’s not overall more dangerous than other drugs and is probably safer than most in many ways, since it’s not toxic to the liver. But it’s still a drug and people should approach piracetam and other racetams with the same category of seriousness as other drugs with low toxicity, but with potential risks if taken long-term. The same can be said about some “natural” products that can be bought over the counter in the US like forskolin, huperzine-a and others.
If you read the case reports, you’ll see the main side effects are brain fog, sleepiness/drowsiness, irritability, sleep issues, depression, muscle twitching, headaches, sweating and cognitive impairment (issues with reading, spelling and verbal retrieval).
Possible Mechanisms Behind Negative Reports:
Brain fog, drowsiness and feeling sleepy in the day
Brain fog seems like the most common side effect. Brain fog is something that I’ve dealt with since I was an adolescent. Understanding its causes and cures have been a particular area of interest for me. I have cured my own brain fog and helped others deal with theirs. As I came to appreciate the role that oxidative stress in the hypothalamus plays in causing brain fog, it got me thinking that piracetam probably did just that, since brain fog is a common theme in people who take piracetam. Here’s what I wrote in a previous version of this post before I found these studies:
“Due to the abundant reports of brain fog, I would also add 500mg of NAC, just in case piracetam is causing oxidative stress in the brain in some way which we don’t understand yet (there’s likely more information that we don’t know about piracetam than information that we do). Though I haven’t seen any studies on piracetam causing oxidative stress in the brain, the brain fog that I felt from piracetam was similar to the brain fog that I get from other things that result from oxidative stress.”
The hypothalamus is an extremely important part of the brain and body. The hypothalamus controls fatigue, sleep, and circadian rhythms, among many other functions. The two symptoms of brain fog and drowsiness were consistent with my theory that piracetam causes oxidative stress in the hypothalamus. After some Googling, I found a few studies that confirmed my suspicions.
MDA[a marker for oxidative stress]…. increased in cortex and hippocampus and in cortex, hypothalamus and striatum by the higher dose of vinpocetine or piracetam, respectively along with decreased TAC (total antioxidant capacity)….at their high concentration, these drugs exhibit pro-oxidant properties and increase free radical production or act as a free radical….[Ref.]
The high dosage that this study speaks about is 300mg/kg. So for someone who weighs an average weight of 68kg, this would be equivalent to 20.4g, but when converted to an equivalent human dosage it would be 3.25g. This is a fairly common dosage that people take in a day. My personal experience indicates that the oxidative stress is dose dependent (in that any dose will cause OS), since I only needed to have 800mg to get brain fog.
People aren’t healthy rats, though. People are sleep deprived, stressed and engage in many other behaviors that increase oxidative stress of the hypothalamus. Many if not most people in my estimation have a hypothalamus that isn’t working optimally. This would explain why people get brain fog even when taking less than the human equivalent dosage given to rats. These interacting factors add up and maybe even synergize to cause brain fog and drowsiness by way of hypothalamic damage and dysregulation.
People who are very healthy are less likely to notice these effects, but this doesn’t mean nothing is happening under the hood. In people like me, who already have a damaged hypothalamus, the negative effects are noticeable more quickly and acutely (upon a dosage of just 800mg). This type of damage to the hypothalamus doesn’t necessarily go away in a day, but usually does.
In susceptible people who do many other things that compound the damage to the hypothalamus, long term dysregulation can occur, which explains the people who are having long term issues. Disrupt your circadian rhythm for one day (causes OS) and nothing happens; do it every day and you are at increased risk for every chronic disease.
Oxidative stress to the hypothalamus and dysregulation fits in perfectly with the description of symptoms described by a piracetam retailer: “If I take too much, with or without a choline source, I get a bit tired, or tense, or foggy - especially if I’m not well rested and well fed when I go higher into my “personal” dosing range.”
Besides OS, piracetam seems to interact with the hypothalamus in other ways. For example, I found this study that showed it decreased serotonin in the hypothalamus (and in the striatum and brain stem) and increased dopamine turnover. Hypothalamic function is responsive to—and regulated by—levels of all three classical monoamine neurotransmitters, i.e. noradrenaline, dopamine and serotonin.
Decreased serotonin in the hypothalamus decreases its activation, perhaps additionally explaining the drowsiness. The effects can get complex because they can be different with dosing and individual variation. All we can really say is that it’s likely interacting with the hypothalamus by changing serotonin and dopamine, and it’s possible that these changes could account for the drowsiness and hypothalamic dysregulation in people. There’s obviously still a lot of question marks here.
Irritability, sleep onset issues and sweating
Irritability, sleep onset issues and sweating are also common side effects. Some of piracetam’s effects are mediated by aldosterone/mineralcorticoid receptors. These receptors are activated by aldosterone and cortisol. Increased activation of this receptor explains the common side effects of irritability and sleep issues from piracetam. These issues are experienced by people with stress and/or overusage of stimulants, which results in excessive cortisol release and therefore excessive mineralcorticoid receptor activation. So piracetam may be just simply additive in this regard.
The following can increase cortisol levels: psychological stress, intense prolonged exercise, sleep deprivation, stimulants(caffeine, etc..), excess sodium, fasting, food allergies, Adrenal glandular, Licorice, Rehmannia, Lj100, RSV, Foskolin, physical trauma, injuries, body fat (subcutaneous adipose tissue regenerates cortisol from cortisone), train commuting, sex, severe calorie restriction, alcoholism, (Hypoestrogenism and melatonin supplementation increase cortisol levels in postmenopausal women), etc….
Adapted from studies on piracetam:
Aldosterone receptors are involved in the mediation of the memory-enhancing effects of piracetam…. Adrenalectomy blocks the memory-improving effect of piracetam-like compounds in mice…… 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.
Muscle problems and headaches
Some people report permanent muscle twitching, even after they ceased piracetam. Piracetam interacts with the body’s cholinergic system. In some regions of the brain (and probably body) it decreases acetylcholine. Most people usually have less than optimal levels of this all-important neurotransmitter. Decreasing it even more can not only decrease intelligence, but also cause muscle spasms and headaches, which is why people also supplement with choline.
I suspect that the people getting headaches and muscle spasms weren’t taking enough choline or if they were then they were taking too much. Acetylcholine also interacts with sweat glands, possibly also explaining this side effect. Hypothalamic dysregulation can also explain increased sweating.
Cognitive issues with reading, spelling and verbal retrieval, etc…
It’s ironic, but there are many reports that describe spelling and reading issues. I found this on a forum once and I found it interesting, although I must say that I haven’t been able to find the study done on physicists. What I take away from this is: coordination between brain region’s isn’t necessarily great and possibly explains some cognitive deficits related to reading, spelling and verbal retrieval.
“Here is one that you won’t hear on most forums: Reduce your usage of piracetam/oxiracetam/etc. The racetams increase coordination between different brain areas, thereby increasing a brain wave pattern called “alpha waves”. Sounds good doesn’t it???
What most people don’t understand is that the brain does its best work (most complex processing of information) when in a “beta wave” state. In contrast to the “beta” name, beta waves are actually of higher frequency than alpha waves. This means that there is less coordination between large sections of brain tissue. This is actually a good thing and I will explain why: Each brain area can be seen as a small parallel processor which is specific for a certain type of information. A small chunk of brain area from the occipital lobe of your brain processes only one aspect of visual information, and nothing else.
Now, the racetams force larger brain areas to process info that they were never intended to process. This means that instead of an area of 5 mm cubic processing the equation “5+5=?”, you would then have an area of 10 mm cubic processing this same task. As you can gather from this, it would be much better to have 2000 small parallel processors working on separate chunks of info and have a really good system in place to combine the information from the separate processors, then to use very large brain areas to process very simple concepts. In a study, physicists were given piracetam before attempting difficult physics problems; it was found to actually decrease their ability to process complex information (I don’t have the reference for this off-hand, but you can look it up on pubmed if you are interested).
The alpha waves associated with piracetam are associated with repetitive and moreso automatic tasks. They are really good for concentration if you are doing regular 9-5 jobs, but for intense study sessions, exams and complex material, I would keep their use to a minimum. This is my first post in this forum but I am very knowledgeable in this particular area (schooling in neuroscience).”
- Piracetam: Case Reports of Harm to get a background.
- Mitigating Piracetam’s Side Effects
- Piracetam Study on Healthy Humans is Rubbish
If you have been harmed by piracetam in some way, feel free to share your experience so that other people will be forewarned about possible risks/side effects.
Piracetam damages the hypothalamus. Functions of the hypothalamus: