I’m excited to bring you something very different than what we usually cover here on Unfinished Man. Today we’re going to talk about drugs. No, not those kinds of drugs, but instead a range of “smart drugs” – also known as Nootropics – which a person can use to improve memory, learning, and overall brain function. I’ve been fascinated with them for years, and asked John Holcomb of if he would mind sharing some information with our readers.
John was kind enough to put together this highly detailed article on which nootropics are available on the market, how each of them works, and why more people haven’t heard of them. It’s a lengthy read, but don’t let the wall of text dissuade you. Once you start reading, I promise you’ll be glued to your screen.
What are Nootropics?
Nootropics are a topic most have little knowledge of outside of scare articles in mass-market publications, most bemoaning the abuse of Adderall and Ritalin by college students as giving them an unfair advantage. After about a decade of this kind of chatter came the movie Limitless and suddenly nootropics became a topic of interest to a more mainstream audience.
Limitless is a movie about an experimental drug – – that gave users mental superpowers, tunnel vision, and a host of methamphetamine blackout inspired side-effects. It showed the main character transforming from a slacker to a prolific writer overnight simply by taking the pill. He then proceeds to become a stock market prodigy and eventually after some drama becomes a candidate for the US Senate. Many viewers were enchanted by the idea of genius in pill form and started scouring the internet for a similar remedy.
As a supplier of nootropics, I’ve fielded countless inquiries from people looking for the silver bullet that will turn them into a genius without effort. I hate to be the bearer of bad news, but such a product does not and can not ever exist, though with the bad news also comes the good: what does exist on the market does give the majority of users a significant benefit without any of the side-effects that Limitless used as a plot device. Before I get into any more detail on this, let me list some of the various categories of nootropics and how they function.
Choline: The mother of all nootropics is choline. Choline is a dietary nutrient found primarily in eggs, meat, seafood, and dairy products and over 90% of the population is in a state of deficiency. While the body can produce choline, it requires supplementation from dietary sources for optimal performance. Choline is used to build and repair cell walls since it is a rate limiting ingredient in the production of phospholipids. It is also a critical part of a neurotransmitter called acetylcholine, which is the primary neurotransmitter that cholinergic nootropics interact with. Acetylcholine (hereafter ACh) is critical for memory recording and retrieval, cognition, and plays a role in mood regulation. People deficient in choline will find that their memory capacity is poor, their cognition sluggish, and generally that they’re functioning in a fog. Choline can be supplemented in a number of ways, from Alpha-GPC products at the high priced and very effective end of the scale, to choline citrate at the midrange, to choline bitartrate at extremely low prices. Any and all nootropic regimens should focus on ensuring that choline levels are sufficient or they will not be effective.
Reversible acetylcholinesterase inhibitors: Acetylcholinesterase is an enzyme found in the synapses of neurons that mops up acetylcholine after signal transmission. Incidentally, irreversible acetylcholinesterase inhibitors are used as nerve gases since they will prevent a muscle from relaxing after a contraction signal is sent to it by keeping the contraction signal (ACh never is cleared from the synapse, so the signal is seen as constant). For nootropic purposes we look at reversible inhibitors that slightly increase the length of the neurotransmitter pulse. If you think in terms of the spark plug in a car engine, a reversible acetylcholinesterase inhibitor allows the spark to stay “sparky” for longer thereby ensuring a better rate of fuel burn (incidentally, this is something that many spark plug manufacturers strive to do through adjusting the shape of the plug tip). In terms of nootropic use, it gives the brain a better chance of interpreting signals and can enhance both cognition and memory I/O in a meaningful way. Unlike drugs that increase neurotransmitter production, these mimic that effect by letting the ACh you already have survive in the synaptic cleft longer. The two most common inhibitors are galantamine and huperzine A. Unfortunately, while you can get a moderate boost from taking these, the limiting factor is that if they were any more potent they could cause you injury (and overdosing on these is a very bad thing to do). These are best used with other cholinergic nootropics rather than by themselves.
Vasodilators and metabolic enhancers: Certain vasodilators and metabolic regulators specialize in increasing blood flow and ATP metabolism in the brain. Most of these are rather mild in their nootropic effects, though to people with certain medical conditions these can have a noticeable effect. Included in this group are Picamilon, Coenzyme q10, and Vinpocetine. Like with acetylcholinesterase inhibitors, overdosing is a real possibility so these are supplements you want to carefully manage the dosing of.
Stimulants: Caffeine, amphetamines, and nicotine all fall into this category. While caffeine’s effect is primarily limited to increasing alertness, the others exert their effects by increasing the amount of neurotransmitters in the neural synapses or by direct receptor stimulation. While this gives a noticeable temporary effect, it also causes a rebound at the end of dosing that decreases cognitive abilities and over time can permanently impair your mental faculties. All of these “supplements” by nature are addictive.
Racetams: This is my personal favorite in terms of nootropic use due to the general effectiveness and tested safety of the chemicals. Generally speaking, the nootropic effects gained are of the same general type that is seen in amphetamines, though the mechanism that they use to achieve their effect is quite different, longer lasting, and without a rebound to subnormal neural efficiency. While amphetamines flood your synaptic clefts with excess neurotransmitters to get the job done, racetams will lightly bond to the receptors temporarily changing their shape and making them more effective at utilizing the neurotransmitters you already have through allosteric regulation. The beauty of this system is that nothing is irreversibly changed in your body: as easily as it bound to the receptor, the racetam molecule can detach unchanged either to enhance a different receptor or be excreted. Furthermore, since the body isn’t breaking down or processing the racetam molecule, there are no worries about breakdown byproducts or metabolites causing undesired effects in the system. In the end, you have a potent nootropic effect without the side-effect profiles or safety hazards of other agents such as amphetamines. Since the unique shape of each racetam makes it more likely to bind to certain subsets of neuroreceptors, racetams are often stacked together with great results.
This group has a number of different chemicals each with varying effects. To give a quick breakdown, here is a list:
Piracetam: This is the most common, the best studied, and the most cost effective of the racetams. It can dramatically enhance general cognition, memory I/O, and linguistic skills. Being water soluble, it has a long half life in the system, but can take up to 6 weeks of daily dosing before full effects are apparent. Typical dosing is 2-5g per day.
Oxiracetam: Another water soluble racetam, this can take up to two weeks for full effects to be apparent. Unlike the other racetams there is very little memory enhancement, though there are none that enhance spatial reasoning and logic nearly as much. Many also experience a moderate mental stimulant effect. Typical dosing is 1-2g per day.
Aniracetam: A fat soluble racetam, meaning it is fast acting. Unfortunately, this also means it is fast to exit the system, with typical effectiveness in the 6-7 hour range at typical dosing levels. Of all the racetams this has the greatest effect on memory I/O and creativity. Uniquely, it also exerts a mild anxiolytic effect making it sought after by those seeking stress relief. Typical dosing is 500-800mg every 6-7 hours.
Pramiracetam: Another fat soluble racetam, it gives good general cognitive and memory enhancement, but uniquely it has a focusing and motivating effect that many compare to stimulants. Many people use this as an “as-needed” study aid for cram sessions, exams, or writing papers in much the same way people will use amphetamines. Unfortunately, this is also the most expensive racetam on a per-dose basis. Typical dosing is 200-600mg every 7-8 hours.
Noopept: This is the newest entry to the racetam lineup, and is wildly different in structure when compared to the others. For the longest time it was imported in OTC form from Russia, but in the recent past has become available in bulk. The effects are quite unique, as well, since while it has some of the features from all the other racetams, it has no stand-out feature that sets it above the rest. This is the only racetam that has a reachable overdose level, and since dosing is 20-30mg every 7-8 hours unless you have a precise milligram scale or pre-dosed capsules it is quite feasible to get yourself into to trouble with this. Unlike the other racetams this does require a small level of metabolism before it goes active in the body.
Where to Start?
Common to nearly all the racetams is a very bitter taste that is nearly impossible to wash away. For this reason many opt to either buy their powders pre-encapsulated or purchase a capsule machine and do it themselves. Side-effects from racetams are usually limited to headaches if you are choline deficient, and increased urine odor since they are filtered by your kidneys.
I’m often asked what I recommend for someone wanting to give them a try. For nearly everyone the best start is the most basic: Piracetam with a choline supplement if needed. No other nootropic is as cost-effective or has had as much clinical safety testing to back it up.
The one caveat with racetams: from a wealth of anecdotes about a third of the population is non-responsive or only mildly responsive to one or more types, and about a third are high responders that can experience spectacular results. This is based on your individual brain chemistry and can’t be overcome regardless of dosing. It is vanishingly rare to be a low or non-responder to all types.
Nutritional supplements: There are a wide variety of nutritional supplements that can enhance brain functioning—particularly in the deficient—such as Sulbutiamine (vitamin B1). I could write a novel on this subject, though it is best summed up simply: a balanced healthy diet goes a long way toward improving brain function, and these are best used to fill any deficiencies.
No one Talks About this Stuff!
By now you’re probably asking yourself why you’ve never heard of any of this before, and why it isn’t available at your local health food store. First of all, some of it it: choline, huperzine A, coenzyme q10, and a number of other supplements are out there, though it is rare to see them marketed as nootropics. This isn’t a matter of safety or honesty in labeling so much as politics and big government in action. While there has been a healthy market for many nootropics for decades (after all, piracetam was developed in the 60s), it has never hit the mainstream because it is seen as cheating. While some see it as unlocking their full natural potential, others see the use of nootropics as no different than steroid use in athletics, giving the user an unfair advantage over those that don’t. Unlike in athletics, academics isn’t necessarily a zero sum game. While in a race there is necessarily a winner and a loser, nobody in academics is held back if another student is better able to retain their information. Unlike cheating scenarios that can earn a student academic recognition for material they did not or could not pick up, nootropics enhance a students ability to gain and retain new knowledge. While I would hate to find out that my physician had used crib cards to make it through medical school and then cheated on his licensing exams, I would have no problem trusting one that used nootropics to maximize their learning potential. Unless you are looking from the perspective of the government, there is never any downside to greater intelligence and recall.
That argument aside, the primary reason that you don’t see these products in mainstream production and retail is government regulation. I primarily deal with regulation in the US, though am familiar with the laws in other countries and in most the reasons for a lack of availability are the same. In many nations these are considered to be prescription medications, but unregulated for possession (this is typically the case for the race tams and sometimes some of the others). In the US, some are considered food supplements and are unregulated. Some are considered nutritional supplements and are regulated only in the manner of their production. Some are considered orphan drugs and while there is no law against possession or use, it becomes stickier when it comes to their sales. Then again, there is always the option to This not only saves you money, but it allows you to avoid any potential difficulties that may arise with you own country’s policy regarding prescription medication. Choosing to order online is the smart way to go, especially if you know there are cheaper alternatives out there. If you are sick and you need medication, there’s no reason not to look into this method of producing medicine. Even if you can afford your medication with no problems, why would you spend the extra money when it’s not necessary?
In the US, racetams and certain other nootropics can only be sold as research chemicals, not for human consumption. Despite this fact, many companies still market their wares as supplements on various merchant sites such as Amazon and Ebay and as the FDA shuts one down two more pop up. Other companies have relabeled their products as research chemicals in an effort to sidestep the FDA’s jurisdiction. On the customer’s side, it is completely legal to order and possess any amount of racetams if ordered domestically, and up to a three month supply (as defined by Customs) if ordered from overseas. Should anyone desire to spend millions of dollars to apply for OTC drug status for any of the racetams these limitations could be lifted, though since none are patentable the limitations would be lifted for everyone with no way to recoup your costs. It isn’t surprising that nobody is willing to be the one footing the bill.
In Canada, Great Britain, and Australia the situation is a bit different. In all three countries racetams are considered to be prescription drugs. The problem is that they can’t be sold legally in-country since none have proper coding for the medications in their health systems. The only legal way to acquire racetams in these countries is to import them, and you are again limited to a three month supply. Australian customs in particular is known for hassling people about import (technically Piracetam is scheduled, so in rare instances they may request proof of a prescription), though if the products are properly labeled they usually get through.
As with any supplement routine it is best to talk to your health care provider first to ensure that there is no conflict with existing medications or conditions. It is safe to say that the majority of people can improve their academic ability and possibly even their quality of life from a rather modest nootropic regimen. While the idea of enhancing ones intelligence through the equivalent of taking your daily vitamins seems shocking to some, it is a definite possibility for those inclined to try to reach their full potential.
John Holcomb –