Two questions I get A LOT from people who are new to Biohacking and haven't yet tried smart drugs is:
Which smart drug supplements actually work and have science behind them?
Which Nootropic should I get start with?
My answer to both questions is the same: Piracetam
It has significant body of scientific evidence behind it, over 600 human studies and academic papers are published about Piracetam on Pubmed. Although a few insights from my own extensive experience are included, this article is mostly going to focus on decoding what the human studies are saying about Piracetam and how this squares up with the anecdotal experiences of the Biohacking community. For more of my own personal experiences, thoughts and comparisons please see the written and video reviews of the different Piracetam products in the sidebar.
Piracetam is the Godfather of the Racetam family of synthetically created smart drugs, they come from laboratories and don’t appear in the natural world. There’s two important reasons why I spend so much time researching, writing about and personally consuming Racetams:
Significant Body of Research - The Racetams have been used in many clinical trials, double blind, placebo controlled studies and meta analysis papers. Research is ongoing as well, at any given time multiple major universities or institutions around the world are studying the Racetams, in 2014 alone over 20 new peer reviewed studies or scientific papers were produced.
Iteration and Public Demand - The Racetams are evolving, with new derivatives of Piracetam being developed and experimented with, like Noopept and Sunifiram. This development is being driven by consumer demand from both the Biohacker community, voracious novelty junkies eager to try new smart drugs, and by those dealing with cognitive decline, who need them to combat aging and maintain their dignity.
A significant objective of Biohacking is maintaining, training and upgrading the human memory, which our capacity to live productive, happy lives completely depends upon. In this aim, I believe the commercial popularity of Piracetam, demonstrates that it is likely a worthwhile tool.
That’s kind of some funnilly worded, indecisive language to use isn’t it? As one pours over the studies and papers published about this smart drug, it’s clear that scientific research is done for sick people trying to get well, not healthy people trying to get an unfair competitive advantage to really kick ass in life. The ROI for the universities and scientific institutions is in treating aging diseases, not increasing productivity and as a result the published literature is littered with inconclusive statements about Piracetam’s dubious value to healthy people.
However, a number of anecdotal experiences speak in grand terms to Piracetam’s capacity as a transformative upgrade tool for the memories of otherwise healthy, young people. It has an uncanny, yet frequently reported effect of bringing back once forgotten memories, both good and bad. One Biohacker reported:
“I as well find Piracetam gives me access to more of my memory. One of it's wonderful effects. Great for writing a paper or doing any sort of creating and for just a general feeling of intellectual enhancement. Imagine more of your memory stores into conscious awareness! That is an amazing thing! If it brings bad memories up, just gives one a chance to work-through some stuff that is in the background of the mind and effecting one in some way, which is a good, enriching, rewarding process to go through”
Another self experimenter agreed:
“I have also had a FLOOD of memories reintroduced to my consciousness since taking piracetam. The memories are good, neutral, and bad. It a very strange, but interesting experience. I recently had a flood of memories and emotions of a childhood daycare experience.”
On the darker side of the spectrum, a PTSD sufferer reported:
“...when I take piracetam all the bad memories seem to find there way back into my head especially a night right before I go to sleep. Its tough to deal with, but the benefits are so good that not taking piracetam is a hard thing to do.”
Getting back into the published research data...
A noteworthy meta analysis was published in 2002, diving deep into the data of 19 double blind, placebo controlled studies, totalling over 1400 human participants. To quote the abstract:
“...the results of this analysis provide compelling evidence for the global efficacy of piracetam in a diverse group of older subjects with cognitive impairment.”
A placebo controlled, human study of dyslexics and non-dyslexics stated “...It was found, using a double-blind cross-over technique, that dyslexics significantly increased their verbal learning by 15.0%...”
The evidence that Piracetam enhances the memory capacity of the young and healthy is not as strong, however a double blind study of 16 humans found that a dosage of 1200 milligrams daily, produced a statistically significant increase in working memory and verbal learning after 2 weeks in healthy college students.
It's memory increasing effects are attributed to improving the function of the neurotransmitter acetylcholine.
There’s already so much written online about Piracetam, I’d like to highlight a few interesting findings from recent studies.
According to a 2013 University of Frankfurt paper, Piracetam is something of a Mitochondria hack.
“In previous studies we were able to show that piracetam enhanced ATP production, mitochondrial membrane potential as well as neurite outgrowth in cell and animal models for aging and [Alzheimer's disease]. To investigate further the effects of piracetam on mitochondrial function, especially mitochondrial fission and fusion events, we decided to assess mitochondrial morphology... “
Head Strong by Dave Asprey makes the case that optimizing your Mitochondria is the ultimate performance enhancing Biohack because your Mitochondria are the fundamental energy generation mechanism that underlie everything else. From the book:
Four different well-constructed studies show that piracetam improves mitochondrial function. In fact, I believe this may be one of its important mechanisms of action, one that is overlooked in most of its descriptions. This is one of the safest pharmaceuticals on the market, and it makes your brain and your mitochondria work better. (p. 288)
This entire book was written on higher doses of those two substances [Piracetam and Phenylpiracetam] (as well as every other supplement in the book!). (p. 288)
A 2014 University of Münster study stated, in regards cognitive recovery following ischemic stroke:
“A secondary prevention with piracetam leads to a significantly better recovery of [event-related potentials] latencies...”
An extensive Italian review of Piracetam stated:
“Cognition enhancers are drugs able to facilitate attentional abilities and acquisition, storage and retrieval of information... Among other classes of drugs, piracetam-like cognition enhancers (nootropics) have never reached general acceptance, in spite of their excellent tolerability and safety.”
One of the most noticeable side effects of enhanced cognition is verbal fluency - you will become a bit more dangerous with your words, you may find yourself talking your way into and out of more trouble than you do usually.
It’s commonly reported that while on Piracetam:
- I don’t have to reach for my words, they just flow
- I don’t end up running out of things to say
- My vocabulary improves
- I’m less afraid to speak in social settings or in front of people
Which probably explains why it’s so popular in lifestyle niches where success depends highly upon one’s verbal abilities:
- Nightclub promoters
- Motivational speakers
- Podcasters or internet personalities
- Pickup artists
A german study of 78 elderly subjects stated:
“The effect of piracetam therapy with different dosages was studied in a double blind trial against placebo on its effect in psychoorganic syndrome of old age... showed statistically significant differences between piracetam therapy at a dosage of 3 X 1600 mg per day and placebo...”
A comprehensive Belgian paper stated:
“A meta-analysis has been performed including nineteen double blind, placebo controlled studies with piracetam in patients suffering from dementia or cognitive impairment ... the results of this analysis provide compelling evidence for the global efficacy of piracetam in a diverse group of older subjects with cognitive impairment.”
A 2002 meta analysis showed numerous therapeutic benefits to elderly people dealing with geriatric cognitive disorders and Dementia. a 1988 study also found that it had a measurable anti-aging effect on the brain of aged rats. Piracetam also has an inhibiting effect on brain damage resulting from alcoholism and hypoxia.
The quote the abstract of a double-blind, placebo-controlled French study:
“Thirty [human] subjects completed the 1-year study... our results support the hypothesis that long-term administration of high doses of piracetam might slow the progression of cognitive deterioration in patients with [Alzheimer's Disease].”
Mechanism of Action
The research supports that Piracetam’s primary mechanisms are:
- Increasing blood flow and oxygen consumption in parts of the brain.
- Enhancement of glucose consumption in the brain.
- Maintenance of mitochondrial membrane potential.
There’s a number of other mechanisms proposed in human and animal studies, like an Ampakinic effect noted by an Italian study. An extensive Italian review of Piracetam noted:
“...piracetam-like compounds suffer from the lack of a common, generally accepted, mechanism of action; a condition which has precluded, so far, a wide acceptance of these drugs as useful medicines.”
it improves the communication between the different hemispheres of the brain in addition to boosting the activity of the corpus callosum (the lower part of the brain that facilitates interhemispheric communication between right and left).
What does it feel like...
Pleasantly intense focus, but at the same time an energizing sensation of optimism about the work ahead of one’s self and the challenges presenting themselves. I would dare call it a more tranquilizing alternative to Ritalin and Adderall, I’ve used these popular ADHD drugs for near a decade and I’m intimately familiar with the ‘cracked out’ yet productive headspace they put me in. Piracetam produces a similar result as far as productivity and focus, but it lacks that ‘standing at the edge of cliff’ or subtle paranoia that has been a companion of mine for so long thanks to the amphetamine driven mechanisms of action in popular pharmaceuticals.
I actually find Modafinil and Piracetam to create a pretty similar productive and focused mindset, although Piracetam imbues some more body energy due to increased blood flow.
The taste of the powder is pretty bad, a friend remarked that it tastes like Cocaine mixed with dried paint, but it’s surprisingly consumable as far as smart drugs go. It dissolves uniformly in water in a matter of seconds, then you can just skull it. It’s a suspicious looking white powder that you really would want to keep out of sight of TSA agents, border guards or highway patrol officers.
First created by Belgian scientists in 1964 Piracetam is the original nootropic and very popular,
This nootropic has also been shown to have a positive effect on depression, anxiety, epilepsy, dyslexia, post-stroke aphasia, Schizophrenia, dementia, myoclonus along with cognitive decline following heart and brain surgery.
A 2010 study stated that it was actually better at treating depression than enhancing memory:
“...It was also effective in the treatment of cognitive disorders of cerebrovascular and traumatic origins; however, its overall effect on lowering depression and anxiety was higher than improving memory.”
A senior member on Drugs-Form.com noted in regards to it’s antidepresant effect:
“I definitely did notice that piracetam provided a mood stabilizing effect, and that I would be unusually upbeat despite stress. Negative emotions still occur, but it seems like long lasting bad moods aren't as common”
Piracetam is sold under a variety of names worldwide: Nootropyl, Nootropil, Lucetam, Oikamid, Geratam, Biotropil, Breinox, Dinagen, Noostan.
Racetams can cause headaches when taken in high dosages since they deplete the essential neurotransmitter acetylcholine, this is fixed by increasing choline intake (Choline, Choline Bitrate or probably the best Alpha-GPC).
Piracetam None Responders?
Others will try Piracetam, get a nice productivity buzz for a few hours that's comparable to a cup or two of coffee but when they try to push the dosage up they get headaches, brain fog or run into a tolerance curve quickly. This is part of the reason why the Piracetam source I recommend offers a very flexible 100% money back guarantee.
However, on the other end of the user experience spectrum, a number of anecdotal reports speak in grand terms to Piracetam's capacity as a transformative upgrade tool for the minds of otherwise healthy, young people. It has an uncanny, yet frequently reported effect of bringing back once forgotten memories, both good and bad.
The good news is that for the vast majority of people who try Piracetam, it has a significant, almost immediately noticeable effect on productivity, focus and memory, indeed this is reason it is the most popular smart drug.
The reason for this inconsistency is complex, Piracetam, while frequently sold as a supplement, is a drug with a range of very complex interactions in our neurobiology. To maximize it's effect there really needs to be several high quality cofactors present in your biology.
The Piracetam rabbit hole really goes very deep, yet unfortunately most people who take it just barely poke their heads in it.
Piracetam, a choline source and ALCAR are a favorite of holistic biohackers but there's a specific protocol that should be followed.
Start taking Piracetam on it's own at the recommended dosage 3-4 grams daily and begin pushing the dosage up to the point that you either start getting Piracetam headaches or the Piracetam starts to lose it's effect. Quality control is actually pretty important when it comes to the Piracetam itself; it's very important to make sure you are only consuming Pharmaceutical grade Piracetam as verified by a 3rd party lab's certificate of analysis (COA). I will link below this video the highest quality, verified Piracetam source that I actually buy my Piracetam from. If and when this changes in the future I will update the video description and annotations in Youtube.
Then add a Choline source, at a 1:4 ratio (1 gram Alpha GPC : 4 grams Piracetam). This will potentiate the Piracetam and get rid of the headaches, you could even experiment with pushing the dosage up. If you can't afford supplemental Choline, an excellent (and cheap) dietary source of Choline is egg yolks. Since you are probably taking at Racetams at higher dosages, you are going to need to eat 4-8 eggs a day to get sufficient Choline, which is kind of a lot of eggs. Eggs are perfectly healthy for you but they I just don't think they taste great so I prefer Alpha GPC.
Then add ALCAR at a dosage starting at 500 milligrams daily and push the ALCAR dosage up by 100 milligrams daily, some biohackers take up to 1 gram of ALCAR daily in this three part stack. Remember how we said that Piracetam has these interactions with very complex neuro biological systems? One such example is the ACh system; our neuroplasticity mechanisms to learn and develop personally along with the peripheral nervous system throughout our bodies depend profoundly on this system. Since Piracetam dials up and puts increased demands on the ACh system without ALCAR supplementation eventually you will face diminishing cognitive enhancement from Piracetam. Sometimes you hear reports of people starting to take Piracetam and for 2-3 months they get awesome results from it, yet eventually it loses it's effect for them.
A 2013 Brazilian study investigated how Piracetam and ALCAR positively affect membrane permeability "These results shed new light into... the mechanisms underlying the protection against [membrane permeability transition] and cell death by the compounds l-carnitine and piracetam."
Over the course of a +15 page discussion a diverse group of Biohackers have reached an interesting conclusion about Piracetam none response. A Swiss study, Aldosterone receptors are involved in the mediation of the memory-enhancing effects of piracetam, stated:
"The blockade of the memory-enhancing effects of piracetam resulting from adrenalectomy can be abolished by substitution with either corticosterone or aldosterone."
Aldosterone is a compound intimately involved with adrenal function, so Piracetam none response is tied to adrenal dysfunction, a challenge faced by so many people in our high stress, high stimulus world.
The crowdsourced data on this is that as much as 88.88% of the Piracetam none responders failed a simple flashlight-mirror-pupil dilation test, indicating low levels of the hormone aldosterone.
In our diets Aldosterone comes via Potassium, so beating Piracetam none response could be as simple as supplementing Potassium or increasing consumption of dietary sources:
Following this process, over approximately 3-4 weeks, you'll optimize your stack for your individual brain chemistry. I hope you will implement the Piracetam Protocol and won't waste anymore Piracetam and more importantly your time.
One of the reasons Piracetam is so popular is that it’s a pretty consistent experience, you can take it 7 days a week and you won't run into tolerance curve, as long as you aren't doing it at extreme dosages.
Addiction or Dependence?
I’ve cycled on and off Piracetam about 4 times in the past 3 years, it’s one of the least addictive things I’ve ever consumed. However, when you go off it there is a noticeable dip as you return to your cognitive baseline, similar to if you always drink coffee in the mornings and then one morning you don’t drink coffee. I combat this dip with brain training, exercise, meditation, reading and coffee.
Jonathan's Review of Piracetam: The Original Nootropic - Highly Recommend
Anyone who's spent much time researching Nootropics has likely come across the godfather of smart drugs, Piracatam.
I personally need to do about 4 capsules (3400 Milligrams) to get that 'Limitless' feeling, where you feel very focused, intent on completing the task at hand and slightly wired up.
Science recommends you take Piracatam in conjunction with an acetylcholine booster. Alpha GPC while a little more expensive, but as a nootropic is more bioavaliable and is absorbed across the blood brain barrier. So I would recommend take Piracatam with Alpha GPC.
I've heard reports that Piracatam sometimes gets you a little too wired up and even cause anxiety. I personally like that wired feeling where I am ploughing through tasks. I did however notice a few times when I was fired up getting a little frustrated with people around me who where, um, slower than me. I can imagine that if you where taking Piracatam in high dosages daily and had a roommate or domestic partner who was NOT it might over time cause some social tension.
Make sure you are taking Piracatam with a beverage or small snack. One time I was taking a couple capsules on an empty stomach, I was super focused on what I was doing so I didn't want to take a break to grab a glass of water or snack from the kitchen. I could feel a burbs, when it came out I actually coughed a white cloud of Piracatam in my home office.
There have been some scientific papers linking Piracatam as being effective helping people who are dealing with alcoholism. On the flip side though it increases blood and oxygen flow to brain which means that hypothetically you will get drunk faster if you are taking Piracatam at the same time. A few weeks ago I was having margaritas with friends at the 4 Seasons, I did piracatam while having a few margaritas and was quickly in no state to drive home. So my experience would seem to confirm this hypothesis. Which ironically also makes Piracatam something of a party favor.
Piracatam by Nutrivene is also a pretty good value, 2 bottles will run you about $36. Which is the same price or cheaper than some other 'cocktail nootropics' out there which produce the same or less actually mindpower results. For the productivity and focus buzz it gives you it's certainly more economical than visiting a coffee shop daily or an energy drink habit.
Choline or Alpha GPC, are the classic Racetam cofactors, The Longecity.org crowdsourced recommended Piracetam-Choline ratio is 4:1
Potassium, a Swiss study suggests that Potassium will potentiate the effects of the Racetams. Which is easy to test because of how easy it is to up the Potassium in one's diet by eating a little more Spinach or white beans. I got into an interesting discussion about this on Longecity.
L-Carnitine, a 2013 Brazilian study investigated how Piracetam and L-CAR positively affect membrane permeability "These results shed new light into... the mechanisms underlying the protection against [membrane permeability transition] and cell death by the compounds l-carnitine and piracetam."
Vinpocetine, is suggested by a 2013 Russian study of brain ischemia patients.
The abstracts of the large scale studies done on Piracetam, consistently mention it's excellent tolerability and lack of negative side effects. For example, a Belgian 12 week clinical trial of over 900 human subjects were administered 24 grams daily, it found no adverse effects of Piracetam or toxicity.
It actually has no LD50, the measure of a given substance that you need to give a rat to kill it, you don't need to give a rat much caffeine or amphetamines before it will drop dead due to the toxicity of these substances. In the case of Piracetam, the toxicity is so low they were able to pump the stomach's of the rats full and they didn't die.
The most common side effects are headaches, which in the vast majority of the cases can be addressed by
- Lowering the Piracetam dosage
- Increasing your ACh precursor intake
- Addressing the Aldosterone potentiation issue explained above
Other reported side effects are increased libido, and hypersexuality - doesn't sound that bad to me!
Alcohol, this is one smart drug that you really don't want to drink on. It increases blood flow to the brain, so you can expect to get drunk a whole lot easier. I once had 4 stiff margaritas on a date, while dosed on over 4 grams of Piracetam, I got really drunk and made an ass of myself - sorry Kendra!