What Are the Risks and Side Effects of Taking Nootropics?

If you are not using iodized salt or enriched flour, then you and your children need to take iodine supplements. Most once-a- day multivitamin pills contain plenty, but check the label because some don’t.

When and how often

Every morning or with a meal.

Vitamin B1 (Thiamine)

Used to treat alcoholics and sleep-apnea patients with memory loss, as it helps to rebuild neurons-particularly those in the mamillary bodies of the hypothalamus in the brain.

Will I feel anything?

Nope, but if you take an overdose, you may feel nausea.

Where to get it

Pork and yeast have the highest natural concentrations, but most of us get it from cereals (wheat, corn, rice, etc.) In pill form, you can find it in any supermarket or drugstore’s nutritional supplements aisle.

When and how often

Every morning or with a meal.

Piracetam and Friends

A memory enhancer. The racetams (“ra-see-tam”) are the first drugs to inspire the term Nootropic, and the trade-name for Piracetam is Nootropil. At the time of writing, their physical effect is believed to be similar to acetylcholinesterase inhibitors, meaning that it disables the action of an enzyme that deactivates a neurotransmitter called acetylcholine (see the next segment on Choline for more information). The judicial suppression of this enzyme can lead to greater memory retention and neural growth. Racetams now come in a large number of formulations, which although they vary at the molecular level, are all based on the same chemical theme and all have the same effect in different degrees. Those on the market are:

• Piracetam
  · Aniracetam
  · Oxiracetam
  · Pramiracetam

All are unregulated in the United States and sold over-the-counter as nutritional supplements. You’re unlikely to find them in nutrition stores like GNC or Vitamin World, but all variants are easily found for sale on the Internet.

The differences between the varieties come down to whether they are fat soluble or not, which affects how easily they cross the blood-brain barrier. To you, the matter is not of effectiveness but convenience. Piracetam is water soluble and extremely cheap ($20 buys a large tub of Piracetam powder, of about 500 doses worth, and which dissolves easily into any beverage), but Oxiracetam and Pramiracetam are fat soluble (add cream to your drink before you dissolve them, if you bought powered forms) and proportionately more effective. Whichever you chose you will get the same bang for the buck.

The racetams are also called cognitive enhancers, but this is a subjective term used when advertising them. Studies of the drug have only tested for and revealed improvements to memory.

Racetams are currently considered to be risk free, hence their unregulated status. There are no immediate negative side effects, and-at the time of writing-no studies have exposed any long-term negative side-effects. If you buy a tub of oxiracetam powder and take a teaspoonful, it’ll probably have the taste and texture of sugar. But buy it from a reputable source, and you won’t have been ripped-off. There is a patented method for manufacturing drugs in a form that resembles and tastes like sugar. Piracetam in powdered form tastes like nasty sugar, so try mixing it with chocolate milk or a citrus drink.

Will I feel anything?

You may experience a slight buzz 30 minutes to an hour after taking your first high dose (2,000mg of piracetam), but this will soon go away. If you take piracetam regularly, then this sensation will rarely ever return, even with higher doses. The real effect of the racetams is on learning.

Some users experience headaches while taking racetams, which can be eliminated by supplementing with Choline (described below).

Where to get it

I have purchased and used Piracetam from the following sources:

· Amazon.com
· Biogenesis Antiaging
· Bodybuilding.com
· Smart Powders
· Aniracetam from
· Amazon.com
· Biogenesis Antiaging
· Smart Powders

Oxiracetam from

· Amazon.com
· Smart Powders (best value: they offer quantity discounts if you buy 2 or more)

When and how often

Users have recommended taking a quadruple-dose 30 minutes before a study session, then taking regular doses every 2-4 hours afterwards. Piracetam’s suggested regular dose is 800mg (one pill, but check). I have not experienced any side-effects after doses of 3,200mg at one time, but remember that Aniracetam and other formulations are more potent and require lower dosages. The ‘racetam family haven’t been proven effective as a daily supplement, so their usage ought to be restricted to study sessions specifically.

Choline

A memory enhancer and the most basic of a class of substances called cholinergic. Choline is an essential nutrient that you get in your diet already, particularly from eggs, fish and chicken. Your body uses it in at least two places: cell membranes and the neurotransmitter acetylcholine.

The first role has been found important for pregnant and post menopausal women since pregnancy, and low estrogen levels can drain the body’s choline reserves. Its second role in neurotransmitters is what makes it a possible nootropic since a 1975 study found that increased choline intake resulted in higher levels of acetylcholine in the brain, and acetylcholine is believed to be involved in the formation of memories.

Cholinergics cover a wider range of supplements that either act as a precursor to acetylcholine (an ingredient chemical needed to synthesize the neurotransmitter), or that modify the way your nervous system interacts with it. For example, an Acetylcholinesterase Inhibitor. Let’s break down that mouthful of words:

Acetylcholine is a neurotransmitter; it bridges the gap between synapses when they’re ready to “fire.”

Acetylcholinesterase is an enzyme that “cleans up” acetylcholine, removing it from the synapse to reset it. ie: it’s anti- acetylcholine.

An acetylcholinesterase inhibitor is a chemical that interferes with acetylcholinesterase, preventing it from cleaning up the synapse. ie: it’s anti-anti-acetylcholine.

Rosemary, sage and marijuana are acetylcholinesterase inhibitors. For that matter, so is nerve gas and some types of snake venom. Mild inhibitors such as Huperzine A are being used to treat Alzheimer’s disease, as it’s suspected that the inhibition of the neurotransmitter stimulates nerve growth-a little bit like how you need to tear down muscle with exercise to make the body grow it back stronger.

Choline and the Racetams

Some users of the racetam family of drugs experience headaches that can be relieved by taking a choline supplement, and there is also subjective reports that it potentiates racetams (makes them more effective).

Fish odor syndrome

If you chose to supplement with choline, don’t take too much of it or you’ll soon have an embarrassing body-odor problem. Choline is also a precursor to trimethylamine, the chemical produced by decomposing fish that give them their distinctive smell. Your body can break-down trimethylamine when you consume choline in normal quantities, but overdosing on choline can overwhelm this process.

Will I feel anything?

No, although choline can eliminate headaches caused by other nootropics such as piracetam.

Where to get it

Choline is naturally found at high concentrations in eggs. It’s also found in an emulsifier called lecithin, which can be derived from either soy or eggs. Many processed foods use lecithin to prevent the oils in emulsions like chocolate and peanut butter from separating. Another popular form of choline is Choline Bitartrate, which is cheap, or CDP Choline, which is more expensive but better quality.

· Any GNC or Vitamin World store
· Amazon.com
· Smart Powders

When and how often

No more than 500 milligrams, taken as either a daily supplement (watch out for fishy-BO) or at the same time as your first dose of Piracetam.

Creatine

An IQ booster. Creatine is already very popular with bodybuilders, and this makes it extremely easy and cheap to obtain. There are dozens of manufacturers, and it’s sold everywhere that dietary supplements are. It occurs naturally in your body and improves the supply of energy to your muscles. It has been found safe in doses of up to 20 grams per day, but there are known problems in those with kidney and liver disease, as well as those with diabetes or hypoglycemia.

Add to that its tendency to increase the production of formaldehyde with long-term use. Its popularity with bodybuilders comes from giving them the ability to do more in a workout, leading to an increase in muscle tissue.

Its nootropic effects come from its effect on the production of Adinosine Triphosphate-the chemical energy that drives cellular activity. This makes it a type of stimulant, and in studies, it was found to improve results in tests of fluid intelligence, which is the ability to find meaning in confusion, draw inferences, make symbolic connections, and solve problems. This is compared to crystalized intelligence, such as when you learn how to add or tie your shoelaces. These studies were performed on vegetarians to isolate the effects of the supplement with natural creatine in meat.

Creatine supplements come in two chemical forms: Creatine monophosphate and Creatine ethyl ester. The latter, CEE, is supposed to have higher absorption rates and half-life, but there haven’t been any studies that bear this as true. In fact, the addition of the ethyl group appears to hasten its breakdown and instability, meaning that you’re better off with the monophosphate variety.

Will I feel anything?

You may notice that you have more energy when you exercise 30 minutes after taking a dose of creatine. If you’re taking creating for nootropic effect, you should combine it with exercise such as walking or running to experience the stimulant effect.

Where to get it

· Any GNC or Vitamin World store
· Amazon.com
· BodyBuilding.com
· Smart Powders

When and how often

Creatine is a supplement that can be taken daily. Take two 750mg capsules two to three times per day.

Sulbutiamine

Is a stimulant as well as a memory enhancer. It’s a chemical variant of vitamin B1, and the crucial difference is that it can cross the blood-brain barrier better than conventional B1 (thiamine). The B- family of vitamins tend to be stimulants because of their role in the metabolism of stored energy, and the more sensitive you are to stimulants such as caffeine, the more sensitive you’re likely to be to the B vitamins, including Sulbutiamine.

It’s sold over-the-counter in powder form. It’s better to get it in pill form, if you can, for it has a bitter taste and is hard to mix with drinks without making them taste nasty.

Note: The nutritional supplement company Fast 400 has been selling Sulbutiamine as Sulbutiamine, apparently a typo that they haven’t fixed. It is the same substance, however.

Will I feel anything?

You might feel more energetic, especially if you combine it with light exercise. If you take a dose higher than 500mg, you may experience nausea or upset stomach.

Where to get it

I’ve noticed an increasing trend to pull pure Sulbutiamine off the market and retail it as a cocktail instead. The following are where I’ve purchased pure Sulbutiamine in the past, and Your Results May Vary.

· Amazon.Com
· Bodybuilding.com (now only seems to be available in “energy pill” cocktails)
· Smart Powders

When and how often

As needed for a stimulant.

Centrophenoxine (Meclofenoxate)

A memory enhancer first used to treat Alzheimer’s disease and senile dementia in the elderly. There’s been a rush to raid the Alzheimer medicine cabinet, lately, in the hopes that what will make the senile keep their memory will make the healthy get even smarter, Centrophenoxine is the poster child of this movement. The chemical itself is a compound made from one naturally occurring substance-dimethylaminoethanol (DMAE)-and one synthetic, which is parachlorophenoxyacetate (PCPA). Exactly how it improves memory isn’t known, but there are two leads: 1) it’s a precursor to the neurotransmitter acetylcholine and may increase levels of it in the brain, and 2) it removes lipofuscin deposits in the brain and skin.

Lipofuscin on the skin leads to “liver spots”, while its build-up in the brain is suspected to be behind the “plaques” that are observed in brain tissue samples taken from Alzheimer’s patients. The theory for Alzheimer’s is that the lipofuscin clogs ion channels on the surface of nerve cells, preventing the movement of potassium through these channels and degrading memory and cognition in the process.

Centrophenoxine gave the author mild nausea when it was taken on an empty stomach, but not when taken with food. Avoid it completely if you suffer from high blood pressure or epilepsy. It’s available over-the-counter from nutritional stores, but usually only those on the Internet. Like with the racetams and Sulbutiamine, I have not seen it in main-street nutrition stores.

Will I feel anything?

Nope.

Where to get it

· Bodybuilding.com (best value, when they have it in stock)
· Biogenesis Antiaging

When and how often

Centrophenoxine’s benefit comes from preventative maintenance. Take 250 to 500mg per day in the morning with breakfast.

Modafinil (Provigil / Alertec / Modalert)

Modafinil was first prescribed to narcoleptics to help them stay awake during the day and then used by the Navy and Air Force to help pilots stay alerted on long missions. Modafinil keeps you awake and alert, has an effectiveness that spans up to 8 hours, increases the capacity of your working memory, and is the closest thing you can get to the fictional NZT-48 from the movie Limitless. It remains prescription-only in the United States, and any US resident would need to either obtain a prescription from a doctor or purchase it from a foreign supplier.

Modafinil increases the level of dopamine in the brain and is therefore potentially addictive. I will go out on a limb to say I’ve not developed an addiction to it, in spite of taking it frequently, but this is only my experience. Do not take Modafinil if you have cirrhosis of the liver or heart disease, and do not mix it with alcohol.

Because this list is given in order of increasing risk, I’ll point out that Modafinil is our turning point between unregulated “nutritional supplements” and drugs that are powerful enough to stay behind the counter. From Modafinil and onwards in this list, you will not want to take these if you are pregnant, breastfeeding, or have not received a physical exam from a doctor in the past year.

As yet, few side effects are known that would threaten your health. But since 1998, the FDA has seen several cases of dermatologic (skin) reactions to Modafinil, some severe enough to require hospitalization. I have only experienced mild headaches and stomach discomfort, however.

Modafinil is broken down by the liver enzyme CYP 3A4, and 3A4 itself is inhibited by the naturally occurring chemicals found in grapefruit juice. Doctors who prescribe Modafinil, therefore, warn their patients against drinking grapefruit juice while they’re on the medication (and as it happens, many other drugs are broken down by 3A4 and are similarly affected). Given that Modafinil has low overdose potential, the author tried deliberately taking it with grapefruit juice but did not perceive a change in effect.

Modafinil can promote wakefulness without the jitters of caffeine, and under the right conditions can let you stay awake for 48-hours without feeling excessively sleepy. But taking it doesn’t mean you’ll suddenly be fatigue-free and spend the next two days wide awake; Modafinil-used as a nootropic-helps those who already have a good sleep pattern. The author was not able to dispatch sleep by popping a few pills, but he was able to perform and concentrate superbly under its influence for hours at a time.

Take about 100mg for every 100lbs of body weight, anything less and you won’t feel much of a difference. If you take the right dose then in about an hour you’ll start to feel a subtle buzz, like someone swapped the battery in your brain with one that has a higher voltage. Take the first dose in the morning, and-if necessary-a second dose in the afternoon. While some have used it to pull all-nighters, you can’t use it to eliminate sleep-there’s no drug which can do that. Nor should you take it every day for nootropic use, because your body will adjust and require higher doses to get the same effect. My practice is to use it no more than once a week on a day that I’ve set aside for an important project.

If you want to take it for nootropic effect, then don’t take it when you feel tired, because while it will lift you out of your stupor, it will just be an expensive way to get the same effect as a nap and a cup of coffee.

Modafinil is far and away the superior alertness drug, but it is expensive. A 30x100mg package of Provigil will cost around US$175, while the licensed brand Alertec is at least $140. The author has recently tried a cheaper generic brand called Modalert with excellent results, at $130 for 80 x 200mg. This brand is manufactured in India, and it does not use the same formulation as Provigil-a difference that affects the rate at which it’s absorbed into the bloodstream. As such, slightly higher doses are required for the same effect. Beware of firms that advertise prices significantly lower than the above, because you will probably not get the real thing. Since Modafinil is in extremely high demand, with would-be-superheroes willing to get it from almost anywhere, there are a lot of scam operations in business trying to take your money and sell you sugar. The author has purchased from the sources listed below and can vouch for them.

Domestic generic modafinil should become available in 2012, but this is only after generic drug makers contested Cephalon’s patents that cover both modafinil itself and its formulation as a drug. It may not go truly generic until 2015.

Adrafinil (Olmifon) and other formulations Adrafinil is Modafinil lite, but specifically, a prodrug that your body will metabolize into Modafinil in vivo. It’s both cheaper than Modafinil and unregulated in the United States, but you have to take a much larger dosage to get the same effect. Being unregulated doesn’t mean it’s available over-the-counter at your local drugstore, though; you’ll still need to order it over the Internet.

Adrafinil is also harder on your liver than Modafinil is since your liver has to convert it into Modafinil before it can have an effect. In my experience, Adrafinil is disappointing: you can take a huge dose, feel the little effect, and wonder if your eyes are going to turn yellow as a consequence.

Cephalon has also introduced a similar drug called Nuvigil (Armodafinil), which is the right-hand enantiomer of Modafinil- another way of saying it’s Modafinil’s sister, or what you get when the molecule is flipped back-to-front like a mirror image.

Many drugs fit into this class called stereoisomers, where the drug molecule comes in “left hand” and “right hand” shapes. Sometimes the two enantiomers have the same physiological effect in the body, and when the patent is due to expire on the “left hand” version the Pharmacy company patents and begins selling the right-hand version. The popular heartburn medicine Prilosec (Omeprazole), for example, has an identically functioning twin sister called Nexium (Esomeprazole), but while you can now get generic Omeprazole OTC, Nexium is still a patented drug sold by prescription.

And this is what Armodafinil is. So far it seems to have the same effect as Modafinil, but the looming 2012 availability of generic Modafinil has spurred Cephalon to market Armodafinil (Nuvigil) as a “better” version for a broader range of ailments (including bipolar disorder and schizophrenia).

Will I feel anything?

Yes, you will. Oh boy, will you notice it? First time users will feel significantly more alert, like “my mind is a laser beam” alert. Some notice its effect in retrospect after they realize they’ve just consumed a few books and papers in one afternoon.

About 2-3 hours after taking a dose of Modafinil you will also notice a change in the odor of your urine-somewhat like the odor after eating asparagus. This is normal and caused by the sulphur metabolites of the drug when your body breaks it down.

However, if you take it too frequently (every day), then the effect will diminish until you don’t notice or benefit from it anymore.

Where to get it

Your doctor, by prescription. It’s prescribed for Shift-Work Sleep Disorder, so you may qualify if you work nights.

MyModafinilDR.com – Probably the best place to obtain Modafinil without a prescription. The company is based in the US, but the product ships from Mumbai, India. The brand they carry is ModAlert, which is significantly cheaper than Alertec or Provigil. I received my order from this company 7 days after placing it, and the product appears to be genuine. MyModafinil claims that they will re-ship any order that gets confiscated by Customs.

Biogenesis Antiaging – A South-African company that sells Provigil and Alertect brands without a prescription and will ship to the US, although it’ll take a couple of weeks. So far, none of my shipments (4 and counting) has been stopped at the border, but Biogenesis claims that they will reship it at least once if it gets confiscated.

When and how often

Not more than twice a week in doses of 200mg or less. I have tried taking big doses (400mg at once, and 200mg in the morning followed by 200mg at noon) without any substantial effect. If you want to march for 48 hours, then you need to take a bodyweight-appropriate dosage every 18 hours. Moda is for when you need it. It’s not a supplement. Your body will get used to it, and then the next “wake-me-up” dosage will just cost you more.

Nicotine

Windows and Linux were written by geeks chugging Pepsi and Mountain Dew, but the Saturn V and the Lunar Lander were designed by engineers puffing on cigarettes. Nicotine is a stimulant that can increase concentration. To insects, it’s poison (the tobacco plant produced it because it killed herbivorous bugs).

It can be absorbed through the lungs by smoking tobacco, or it can be absorbed through the skin by chewing nicotine gum (most of the nicotine is absorbed through the cheeks and tongue, just as with chewing tobacco) or by wearing a nicotine patch.

The effects of smoking on your health are well discussed outside of this article, so Ill focus on its mental effects: Nicotine can cross the blood-brain barrier very easily-about seven seconds from the first puff-and binds to nicotinic acetylcholine receptors on nerve cells. One consequence of this is the increase of dopamine in the brain that brings about a sensation called a “buzz”. It induces the liver into releasing glucose, providing a sense of increased energy, and it stimulates the adrenal gland into producing epinephrine (adrenaline).

Then there is the major metabolite of nicotine called cotinine, which is being investigated under the speculation that it has an effect on cognition, too.

Acetylcholine is the neurotransmitter that activates skeletal muscle cells, making them flex. But because of a single amino- cid difference between brain-cell acetylcholine receptors and muscle-cell receptors, nicotine will activate brain cells without activating muscle cells. That’s a difference between life and death, for if it did activate muscle-cell acetylcholine receptors, then nicotine would kill with a mechanism similar to the way nerve gas works. Now you know how tobacco plants deploy their insecticide: insects don’t have this difference, and the nicotine in tobacco plants kills them.

With cigarettes, you’ll have a choice of regular or mentholated. The addition of menthol increases the half-life of nicotine in the bloodstream because it inhibits the oxidization and glucose breakdown of the drug by the enzyme CYP 2B6, similar to the way the components of grapefruit juice inhibit CYP 3A4 and extend the half-life of modafinil.

Besides cigarettes, there are now chewing gums, patches, and battery-powered false cigarettes that deliver nicotine via steam, but these are not like a “Get Out Of Cancer Free” card.

My experience with cigarettes is that they do not contribute much towards mental powers, not enough to justify their use. I entertained the thought that the “buzz” could be beneficial for rare-once-a-year problems that require intense concentration to crack-, but there doesn’t seem to be any advantage over a good night’s sleep followed by a fresh cup of coffee.

Will I feel anything?

Yes, nicotine will give you a noticeable buzz, and this is the primary reason for smoking cigarettes. This buzz will wane if you become a regular user until you don’t experience it anymore.

Where to get it

· Tobacconists, drugstores, supermarkets

• Nicorette Gum at Amazon.com, for those who are quitting cigarettes

When and how often

In general “never” is how often because of its addictiveness, additives, and nature as a carcinogen. Outside of that, nicotine’s value as a stimulant appears to work best when you are working on a difficult problem that matters. This is strictly Your Judgement, Your Risk.

Desmopressin

This turns on the tape-recorder in your brain. It’s also the most dangerous nootropic in the list because it interferes with homeostasis. Desmopressin is a synthetic analogue to the natural hormone vasopressin, which not only acts as a vasoconstrictor (shrinking the diameter of blood vessels) but also affects the hypothalamus and vastly improves memory formation.

For nootropic use, you need the nasal spray as to absorb the drug through the nasal membrane closest to the brain. Its effect is almost instantaneous, and its users tend to take it immediately before lectures, conferences, and study periods. The effect can last for several hours and tends to leave one with a stronger recollection of the material studied while under its influence.

Do not take Desmopressin if you have high blood pressure. You may recall at the beginning of this article that I said these drugs would be listed in order of increasing risk. We’re now at the end of the list and-if you pardon my language-you do not want to fuck with Desmo. I even placed it after smoking since it can kill you much faster and with fewer doses. Here’s the deal:

A vasoconstrictor will increase your blood pressure. It will make your kidneys retain water, so another effect of Desmopressin is to reduce urine production (Desmopressin is commonly prescribed to prevent Bedwetting).

Part of your body’s homeostasis mechanism is to regulate blood water content by removing it-via the kidneys-into the bladder Having too much water in your bloodstream can lead to electrolyte imbalance, and in severe cases, this is called hyponatremia, or “water poisoning.” Hyponatremia is difficult to treat. If your doctors cannot control the rebalancing of your electrolytes, you may experience central pontine myelinolysis-nerve damage to the central pons area of the brain stem, which regulates autonomic functions such as breathing. Heart failure is also possible.

Use Desmopressin irresponsibly, and you’ll enjoy the rest of your life in an iron lung unless you die before they can hook you up to one. If you remember the “Hold your wee for a Wi” contest held by a radio station, where a woman held her bladder for so long she died, know that she died of hyponatremia-the same malady that can be caused by the wrongful use of this drug.

If you were to take Desmopressin, then you must avoid heavy exercise and the excessive consumption of liquids for at least 6 hours afterwards. Do not drink sports drinks such as Gatorade or Powerade. Drink only when thirsty and only until you’re no longer thirsty.

Desmopressin costs about $25 for a nasal spray bottle containing enough liquid for 6-7 doses and is available over the Internet without a prescription from suppliers such as Biogenesis Antiaging. For nootropic use, hold your breath while you administer about 2 squirts per nostril, then breathe in through your nose. You may experience a runny nose and sneezing, but this is normal and will go away. The author has also experienced a mild buzz immediately after use that diminished after a few minutes.

Desmopressin should not be used more than once a week. It isn’t a supplement, and it won’t make you smarter. It’s what you would take before you have to study and memorize material that doesn’t lend itself to memorization easily, such as a lecture.

In many ways, this drug is the opposite of alcohol. Booze makes you pee and forget things, while Desmopressin restricts urine production and makes you remember everything, and the mechanisms for each are strikingly similar. Alcohol is a vasodilator: it makes your blood vessels expand and encourages the kidneys to remove more water from your blood. But you would be a fool- perhaps a dead fool-if you were to mix the both in hopes to get the fuzz of alcohol without the side-effects.

Will I feel anything?

Unlikely, its effect is on learning and memory retention. However, if you took it and then guzzled lots of sports drinks then you’ll soon experience a headache, nausea, confusion, lethargy and other symptoms. If you experience any of those symptoms, then call an ambulance and hope they know how to treat water poisoning.

Where to get it

Biogenesis Antiaging

When and how often

Immediately before studying or attending a lecture. Never more than once a week. Never before heavy exercise. Never before drinking alcohol or lots of fluids. This is not a nutritional supplement, it is a drug, and it’s dangerous.