We live in a world where people attempt to settle differences with insane wars and acts of terror. We foul our nest with an array of pollutants. We succumb to preventable diseases. We struggle to feed a growing global population. We clearly need to be smarter! If only there were a pill to boost our brainpower! A pill to allow us to learn things more quickly and actually remember what we learned. A pill to allow us to focus on whatever task is at hand without permitting our mind to drift. A pill for a better functioning brain. A “smart drug.” A “nootropic.”
“Nootropics” are chemicals that improve mental function in some way. The term was coined in 1972 from the Greek words for “mind” and “turn,” by Corneliu Giurgea, a Romanian-born pharmaceutical researcher who was working for the Belgian drug manufacturer UCB. Giurgea was trained both in psychology and chemistry and had an interest in drugs that would improve cognition, that is, those that would “turn the mind” in the right direction. In the 1960s while tackling the problem of motion sickness he investigated gamma-aminobutanoic acid (GABA), one of the many neurotransmitters nerve cells use to communicate with each other. GABA cannot be taken by mouth because it does not cross the blood-brain barrier, so Giurgea focused on synthesizing analogues that could be administered orally.
He came up with “piracetam,” a compound that did not help with motion sickness but did reduce nerve cell excitability, a property that proved to be useful in the treatment of myoclonus, the sudden, involuntary twitching of muscles, commonly in the arms or legs. But Giurgea also found that the drug improved cognition, leading to piracetam being commonly described as the “first synthetic nootropic.” It hit the market in Europe as “Nootropil,” a name obviously chosen to imply a nootropic effect. The stated indication was for the treatment of myoclonus, but once a drug is approved for sale, physicians can prescribe it as they see fit and piracetam soon developed an “off-label” use as a brain function enhancer. It also stimulated research into analogues, particularly in the old Soviet Union, with phenylpiracetam hitting the market as an anxiety-reducing and memory-enhancing agent. The Russians also developed phenibut, another GABA analogue that was used by cosmonauts to reduce stress and improve focus during space missions.
Describing piracetam as the first synthetic nootropic is not exactly correct. That distinction should go to amphetamine, also first synthesized by a Romanian chemist. Lazar Edeleanu made the compound in 1887, although its effects on the mind were not recognized at the time. By the Second World War, though, both the Allies and the Germans were using amphetamine for its performance-enhancing effects with pilots commonly popping the pills to stay alert during missions. Today, amphetamine is the active ingredient in Adderall, a medication used to treat attention deficit hyperactivity disorder (ADHD). It is also used and abused by students studying for exams because of its ability to increase focus.
Long before the advent of synthetic chemistry, many natural substances had developed a reputation as “brain enhancers.” The most widely used such substance is caffeine, which can certainly wake up a brain. But it doesn’t make you smarter. Olive leaf extracts have long been used, prompted by the biblical passage found in Ezekiel 47:12: "The fruit thereof shall be for meat, and the leaf thereof for medicine." Research on rats indicates that oleuropein, a compound found in olive leaves, may actually have an effect on cognitive function. When researchers treated rats with oleuropein, the usual cognitive dysfunction induced by administering colchicine directly into the brain did not occur. How do you know if a rat is cognitively dysfunctional? It has more difficulty in learning to find its way through a maze. So if your rats are having memory problems, you might think of treating them with a dose of olive leaf extract.
The herb bacopa monnieri was used by Ayurvedic physicians in India 1500 years ago to improve intellect, and gotu kola was recommended for memory enhancement. Traditional Chinese Medicine (TCM) has a number of brain-boosting herbs, with ginkgo biloba leading the way. In South America, maca root and yerba mate tea have a long-standing reputation as focus enhancers. Cocaine was once promoted by Sigmund Freud as a cognitive enhancer. Not a wise choice. All of these, save for cocaine, are available today as supplements and are often hyped as natural nootropics but the evidence for any significant effect is scanty.
Today, the most talked about nootropic is modafinil, trade name Provigil. The drug was developed in France in the 1980s as a treatment for narcolepsy and is now used for sleep and shift work disorders, but it is often used off-label as a cognitive enhancer. U.S. Air Force physicians prescribe it to pilots for fatigue management and the drug is available to the crew of the International Space Station to optimize performance while fatigued. Like any drug, modafinil can have side effects that range from nervousness and insomnia to anxiety and a potentially very serious rash. Modafinil received a boost for its much hyped nootropic effect from the movie “Limitless” since the fictional drug “NZT” in the film was thought to be modelled on modafinil. In Limitless the drug endows the hero with extreme mental prowess, far beyond anything achievable by nootropics.
When Dr. Corneliu Giurgea was asked back in the 1960s why he was so interested in drugs that would improve mental function, he replied that “man is not going to wait passively for millions of years before evolution offers him a better brain.”  So far, despite a great deal of research focused on prospective brain-enhancing drugs, we are still waiting for that better brain as evidenced by goings on in the world.
