Friday, February 24, 2012

The Smart Drugs of Today, Scheduled Tomorrow

As neuroscientists unravel the mysteries of the brain, every so often their discoveries are met with controversy. One recent controversial discovery is the finding of cognitive-enhancing drugs, known as nootropics. Nootropics are drugs that improve mental functions such as cognition, memory, intelligence, motivation, and concentration, while also being neuroprotective. The most famous nootropic is piracetam, which has been shown to enhance both memory and creativity. The discovery of nootropics such as piracetam has caused an uproar in the academic community, especially after the drugs became popular among college students. The questions raised are whether it is fair that some college students use cognitive-enhancing nootropics to put themselves ahead of their peers, and if it is not fair then what should be done about it. Nootropics are the steroids of academia, and through an investigation as to why performance-enhancing drugs are banned in sports, we can better decide if nootropic use should be similarly regulated in educational institutions.

Anabolic Steroids & The Use of Performance Enhancing Drugs in Sports

Use of anabolic steroids may have occurred as early as ancient Greece. It is believed that the anabolic steroids they used were natural substances that promoted androgenic and anabolic effects. It was not until 1935 that anabolic steroids were isolated, identified, and synthesized. In that year, two researchers experimenting on dogs discovered that testosterone given under certain conditions increased muscle mass. Immediately afterward, the scientific community began examining the medicinal uses of anabolic steroids and discovered that anabolic steroids helped increase bone growth, stimulate one’s appetite, and increase muscle growth.

Today, the mechanism of action of anabolic steroids is well understood and is not a unique bodily interaction. Anabolic steroids are lipid-soluble hormones that can permeate through the cell and nuclear membrane. When the anabolic steroid enters the cytoplasm of the cell, it binds to an androgen receptor. From there the steroid-receptor compound diffuses into the nucleus of the cell, where it can either alter the expression of genes or activate processes that send signals to other parts of the cell.

By acting as a transcription factor, anabolic steroids have a notable effect on muscle mass. First, they increase the production of protein. Second, they block the effects of the stress hormone cortisol on muscle tissue. Cortisol is a glucocorticoid known for its catalytic effects; therefore, blocking its effects reduces catabolism of muscle and also greatly reduces muscle recovery time. Furthermore, anabolic steroids influence cellular differentiation by causing cells to develop into muscle cells rather than fat-storage cells.

Obviously one major argument for the scheduling of steroids are their numerous detrimental effects. Most of the negative side-effects are dose-dependent, and the most common side-effect is elevated blood pressure, especially prevalent in people with pre-existing hypertension. However, there are many other adverse side-effects that are also worth mentioning which help clarify why anabolic steroids are scheduled in the United States.

The most well-researched adverse side-effects are anabolic steroid interactions on serum lipoproteins and the cardiovascular system. Most investigations on the cardiovascular system have focused on how anabolic steroids increase risk factors for cardiovascular disease. Researchers have found that during anabolic steroid use total cholesterol tends to increase, while HDL-cholesterol demonstrates a marked decline. HDL is a lipoprotein that transports cholesterol and triglycerides throughout the bloodstream, and HDL is believed to have protective value against cardiovascular diseases such as ischemic stroke and myocardial infarction. Low concentrations of HDL have been shown to increase the risk for atherosclerotic diseases.

Furthermore, anabolic steroids have been shown to increase LDL-cholesterol. Similar to HDL, LDL is a lipoprotein that transports cholesterol and triglycerides in the blood stream. However unlike HDL, LDL particles have been shown to promote cardiovascular disease. Males have been found to have higher levels of LDL to begin with, and this factor coupled with anabolic steroid use greatly increases their risk for developing atherosclerotic diseases.

Anabolic steroids also have numerous side effects on both the male and female reproductive system. In males, application of anabolic steroids leads to supra-physiological concentrations of testosterone derivatives leading to a decrease of luteinizing hormone and follicle stimulation hormone. In bodybuilding, where high dosages are typically used, the prolonged use of anabolic steroids leads to hypogonadotropic hypogonadism, characterized by decreased functional activity of the gonads that results in lower amounts of testosterone. The consequences of hypogonadotropic hypogonadism include: poor libido, fatigue, erectile dysfunction, and high cholesterol.

Similarly in females, anabolic steroid use is associated with decreased levels of estrogen and progesterone and an increase in the amount of circulating androgens inhibiting the production and release of luteinizing hormone and follicle stimulation hormone. Lower levels of luteinizing and follicle stimulation hormones inhibit follicle formation, ovulation, and cause irregularities in a woman’s menstrual cycle. Often the menstrual cycle is characterized by a prolongation of the follicular phase and a shortening of the luteal phase.

Another noteworthy side-effect is the increase of aggression, coined as “roid rage.” A 2005 review determined that there is a correlation between anabolic steroid use and increased aggressiveness. Furthermore, a 2007 study on a nationally representative sample of young adult males in the United States found an association between lifetime and past-year self-reported anabolic-androgenic steroid use and involvement in violent acts. Compared with individuals who did not use steroids, young adult males who used anabolic steroids reported greater involvement in violent behaviors. In addition, a 2006 study of two pairs of identical twins, in which one twin used anabolic steroids and the other did not, found that the steroid-using twin exhibited high levels of aggressiveness, hostility, anxiety, and paranoid ideation not found in the control group twin.

Although there are an overwhelming number of adverse side-effects coupled with steroid use, to fully understand why steroids are scheduled in the United States it is important to examine the different realms where steroids are banned. Currently it is illegal to possess steroids without a prescription, and steroid usage is also forbidden in athletic competitions. We will see that there are different reasons for scheduling in these two realms, and both reasons will shine light as to what should be done for nootropics in academia and personal use.

First, I would like to call attention to steroid use and scheduling in athletic competitions. The use of anabolic steroids as performance enhancing drugs began in 1954 among Olympic weightlifters. In 1956, Methandrostenolone was first marketed in the United States, which helped initiate the rise of anabolic steroids in America.

At first, only world-class athletes in high-strength sports such as weight lifting abused anabolic steroids. Unfortunately, the science behind anabolic steroids was not well understood in the 1960s, and athletes and trainers developed extremely high dose steroid regimens. Often the methods had no scientific backing and were passed along by word of mouth from one trainer to another.

The scientific community and athletic community responded to the growing use of anabolic steroids by stating that there was no evidence that steroids caused muscle growth or improved performance. They also claimed that large amounts would lead to dramatic toxic adverse effects in all users. Yet there were little to no scientific studies backing these claims at the time and athletes recognized this. Athletes and trainers discredited scientists because scientists’ claims went against the athletes’ personal experience with anabolic steroids. Also, athletes did not notice any of their colleagues having detrimental effects due to steroid-usage, which further increased distrust of scientific sources. Although the scientific claims were unwarranted, today we know the truth behind their claims. However, since the athletes discredited scientific information, anabolic steroid abuse spread to other sports and athletic levels.

Today, anabolic steroids are banned by all major sporting bodies. The World Anti-Doping Agency (WADA) maintains the list of performance-enhancing substances banned from use by many major sports bodies; this list includes all anabolic agents. The WADA was created though a collective initiative led by the International Olympic Committee and aims at providing equal opportunities for all athletes. Punishments for being found using anabolic steroids can include being banned from the sporting event, paying hundreds of thousands of dollars in fines, and possibly spending years in prison. It may be obvious to some as to why performance-enhancing drug use is considered cheating, but in actuality the argument is more complex than it appears.

Examining the issue from the most basic standpoint, one may argue that the use of performance enhancing drugs gives users an unfair advantage. But how is this advantage unfair? This unfair advantage cannot be due to monetary issues, i.e. it gives the rich an unfair advantage because they can afford to purchase the performance-enhancing drug while the poor cannot. If this were the case, then the WADA would be obligated to ban new sporting equipment that increases the user’s performance. For example, new material technologies in the construction of swimsuits have been shown to increase the speed, buoyancy, and lower the endurance required for swimmers. An excellent instance of this is Speedo who claims that their newest swimsuit design reduces passive drag by 16.6% compared to competitor models. Yet what comes alongside the increase of performance is an extreme price tag. Olympic swimsuit models easily surpass ten thousand dollars, and the latest designs by Speedo are restricted to only certain athletes.

Analyzing why it is legal for some world-class athletes to have access to far better equipment, but unethical for world-class athletes to use performance-enhancing drugs brings a level complexity to the issue that may not be immediately realized. One belief we can hold is that it is unethical that some world-class athletes have access to better equipment. Most people would argue that the point of athletic competitions is to see which individual can push themselves harder than the other competitors in a fair environment. It is not a fair environment if one athlete has access to better equipment than his competitors. This creates an athletic competition based on technology, rather than determination and skill. If in fact it is an unfair environment, athletic competitions such as the Olympics should be obligated to reduce this competitive advantage. One possible way of reducing this advantage would be banning restrictive technology ties, where only certain athletes are allowed to use a company’s newest equipment technologies. While there are other alternative solutions, I will instead move on to another possible belief we may hold in terms of equipment and performance-enhancing drugs.

This is the belief that it is fair that some athletes are allowed to use better equipment than other competitors. Yet what follows from this belief is that performance-enhancing drugs should not be banned from athletic competitions based on availability or the sheer fact that it gives some competitors an unfair advantage. Coinciding with this belief, steroids and other performance enhancing drugs cannot be banned because only some athletes—probably the richer athletes—can afford or have easier access to the substances, because if this were the case then allowing some athletes to have access to better equipment should be prohibited too. Furthermore, to hold this belief would mean that you should also believe that steroids and other performance-enhancing drugs should not be banned solely because they give those athletes a competitive edge. If we claim that it is fair that some athletes have a competitive edge due to equipment, then if all things are the same it should be fair that some athletes have a competitive edge due to drugs. There must be another difference between performance-enhancing equipment and performance-enhancing drugs that lead us to ban only the latter.

As we have discussed, there are many adverse side-effects with anabolic steroids and other performance-enhancing drugs. Anabolic steroids have been now shown to elevate blood pressure, cause an increased risk of cardiovascular disease, and have extremely damaging effects on testosterone levels. We now may be compelled to say that the use of performance-enhancing tools should be permitted as long as they are not antagonistically pleiotropic—i.e. the performance-enhancing tool does not have adverse side-effects. This argument seems to make sense; most people would believe that it is not fair for an athlete to sacrifice his body so that he can do better in an athletic competition. Not only would most people argue that it is not fair, but most people would assert it to be unethical, claiming athletics would be transformed into a masochistic competition where those who do best are those willing to sacrifice the most. WADA claim that this is why they have been established, and this is the core reason as to why performance-enhancing drugs are banned from professional sports. Because the beneficial gain of performance is too greatly outweighed by the alleged health threat of performance-enhancing drugs, the organization regulates what substances can be used in competitions in order to provide equal opportunity for all athletes.

Now that we know the reasoning behind why performance-enhancing drugs are banned, let us imagine a drug that does not have adverse effects or at least no known adverse effects. Would the WADA be obligated to keep this drug unregulated? If they abide by their mission statement that they want to provide equal opportunity for all athletes by regulating substances with alleged health threats, it seems that they should not regulate this drug. The fact that it increases performance is no reason to ban such a drug. If that were the case, they should not allow athletes to use equipment that gives them a competitive edge. Furthermore, it cannot be regulated for the same reason as steroids because it lacks detrimental effects. If a drug had performance-enhancing effects, yet lacked detrimental side effects, the WADA would be obligated to keep the drug unregulated, or at least until adverse side effects were discovered.

Fortunately for our thought experiment, there are performance-enhancing drugs with no known adverse side effects. One excellent example is phenylpiracetam. Phenylpiracetam was developed in Russia and goes by the trade-name of Phenotropil. Phenylpiracetam is believed to be a nootropic—cognitive enhancer—but has also been shown to increase tolerance to cold and stress. Although there are no scientific studies showing adverse side effects, the WADA banned phenylpiracetam because of its ability to provide users increased physical stamina and improved tolerance to cold. As a result of the ban, Russian biathlon Olympic silver medalist Olga Pyleva in the 2006 Winter Olympics was disqualified and banned from attending events for two years following a positive drug test.

Now what does this say about performance-enhancement in professional sports? Maybe performance-enhancement drugs are banned because they are something you ingest and affect your body directly, while performance-enhancing equipment is used as a tool and indirectly interacts with your body. But what follows from this is the question of why are some substances we ingest banned and others are not. For example, caffeine is a stimulant that is not regulated by the WADA, yet the stimulant amphetamine is regulated. We cannot say that this regulation is based on adverse side-effects because caffeine and amphetamine have similar detrimental effects when abused. Furthermore, the regulation of phenylpiracetam suggests that adverse side-effects are not the key reason as to why performance-enhancing drugs are banned in the first place. Some may bring up an argument of naturality, i.e. drugs that are naturally found and naturally consumed should be permitted as long as they have no major detrimental effects. Through my own research I believe this is the best explanation of WADA regulation policy. The WADA will not ban substances that are found in nature, commonly used, and that lack detrimental effects. However, it is important to note that these substances are not considered to be drugs; rather, in these cases we use the term supplement instead.

The difference between a drug and a supplement is that a supplement is a chemical or variety of chemicals that supplement one’s diet and provide nutrients, such as vitamins, minerals, fiber, fatty acids, or amino acids, which may be missing or may not be consumed in sufficient quantities in a person’s diet. However, the term supplement is used very loosely. The steroid hormone DHEA and pineal hormone melatonin are both marketed as dietary supplements even though they are not naturally consumed, thus causing confusion as to what should be labeled a drug and what should be labeled a supplement.

Ultimately, it seems that the WADA’s regulation policies are that all performance-enhancing drugs are banned, regardless of whether they have been shown to have adverse side effects. The only types of drugs that are not banned are those considered to be supplements. Yet, there is still confusion as to what is considered a drug and what is considered a supplement. The WADA regulation policies lead to the conclusion that performance-enhancing drugs are banned because of their nature as something ingestible and not traditionally used in man’s diet. When you look at the issue this way, it really makes their reasoning seem extremely fragile, especially when performance-enhancing equipment is permitted to be used by some athletes and other athletes are limited to using outdated, inferior technology. The fact that something is ingestible and not traditionally used in man’s diet do not seem like good reasons for the banning of all performance-enhancing drugs, yet these were the rules constructed by the WADA that all major sporting bodies abide by.

Now that we have analyzed why anabolic steroids and other performance-enhancing drugs have been banned from professional sporting leagues, it is also important to analyze why these drugs are scheduled in the United States. The U.S. Congress considered placing anabolic steroids under the Controlled Substances Act following the controversy over Ben Johnson’s victory at the 1988 Summer Olympics in Seoul. The American Medical Association, Drug Enforcement Administration, Food and Drug Administration, and the National Institute on Drug Abuse all opposed listing anabolic steroids as controlled substances while the U.S. Congress deliberated. The organizations cited that anabolic steroids do no lead to physical or psychological dependence, which is a requirement for scheduling under the Controlled Substance Act. Regardless, anabolic steroids were added to Schedule III of the Controlled Substances Act in the Anabolic Steroid Control Act of 1990. The act defined anabolic steroids as any drug or hormonal substance chemically and pharmacologically related to testosterone that promotes muscle growth.

Despite the American Medical Association, Drug Enforcement Administration, Food and Drug Administration, and the National Institute on Drug Abuse’s protests, it appears the U.S. Congress went out of their way to schedule anabolic steroids as a publicity move. One key criteria of scheduling a substance is that it has physical or psychological dependence, which is something that anabolic steroids lack. Moreover, the controversy that followed Ben Johnson’s victory severely hurt the credibility of United States athletics. In response, the United States added anabolic steroids to Schedule III of the Controlled Substances Act to improve their tarnished image. Although what prompted this action may not be the best of reasons, especially when considering the detrimental health effects of improperly using anabolic steroids, it is probably in the best interest of the public that steroids were scheduled.

Now how should the U.S. Congress respond to other performance-enhancing drugs that may or may not have detrimental health effects? If they are to use the same reasoning as the original scheduling of steroids, then it seems that we are obligated to schedule these drugs too. Unsurprisingly, most of the performance-enhancing drugs are scheduled, but many have good reasons for their scheduling including narcotics, amphetamines, and growth hormones. However, there are a good number of WADA banned performance-enhancing drugs that are not scheduled in the United States. One such example are beta-blockers. Beta-blockers are beta-adrenergic antagonists that diminish the effects of epinephrine and other stress hormones. They have been banned in a number competitive sports for their ability to control social anxiety (stage fright) and reduce tremors. Regardless, the United States have not and do not plan to schedule beta-blockers at this time. This shows that the United States scheduling of performance-enhancing drugs is set at a higher standard than the banning of performance-enhancing drugs in athletic competitions.

Nootropics in Academia and the United States

Analogous to steroids in athletics, nootropics can be considered the performance-enhancing drugs of academia. The most famous nootropic is piracetam which is a cyclic derivative of GABA. As previously stated, piracetam has been found to enhance both memory and creativity in college students. Although its mechanism of action is not fully understood, it is thought to be a positive allosteric modulator of the AMPA receptor. Piracetam acts on ion channels leading to non-specific increased neuron excitability, while lacking inhibitory effects on synaptic action. Furthermore, piracetam improves the function of the neurotransmitter acetylcholine by acting on muscarinic cholinergic receptors and NMDA glutamate receptors, which are both involved in the learning and memory process.

However, unlike steroids and myriad other performance-enhancing drugs, piracetam and all other drugs termed “nootropics” are neuroprotective and extremely nontoxic. In a 1999 study using a high-dose regime of piracetam for treatment of acute stroke, no adverse effects were found in any of the patients. Furthermore, in another 1999 experiment that used piracetam for the treatment of cortical myoclonus, none of the patients experienced serious adverse side-effects even though they had dosages of up to 24 grams daily. Not only has piracetam been shown to have little adverse side-effects, but a 2001 study of piracetam on rat cortex suggested piracetam was even neuroprotective.

Now that we have a firm understanding of nootropics and performance-enhancing drugs in sports, how should we respond to nootropics in the realm of academics? If we are to say that nootropics are the performance-enhancing drugs of academics, then should they be banned like performance-enhancing drugs are banned in sports? First we should recognize that similar to athletics, college and other education institutions are a competition. Each and every student is competing against one another for higher grades. Those who perform the best on tests, write the best essays, and complete all assignments are those that receive the highest grades. Higher grades lead to better job opportunities, acceptance into other professional programs, and quite simply the opportunity to make more money. Some students may deny that this is their motive, yet they are not the norm. Although educational institutions portray themselves as a place where knowledge flourishes, in actuality these places often promote a competition of intellect and memorization.

Furthermore, like how an athletic competition has rules to provide structure and maintain fairness and legitimacy, educational institutions have rules for similar purposes. For example, plagiarism and cheating are two forms of academic dishonesty that every single educational institution has strict policies against. By establishing these policies, the institution provides fairness for its students and grades that accurately represent the student’s knowledge of a subject. Punishment for cheating and plagiarism are extremely severe and include failure on the assignment, failure in the class, or possible expulsion. Examples of cheating include any use of external assistance during an examination. One argument against nootropics is that it is an external tool providing the user increased memory capability during examinations. And in fact, it does seem that the nootropics users are given an advantage over their peers. Yet even if we rule this advantage to be unfair, we should not restrict the individual’s intellectual capabilities just because they are using a drug. Even though they consumed a drug does not discredit the fact that they themselves acquired the knowledge of what they were studying.

However, this analysis shows that there is a difference in how we view users of performance-enhancing drugs and users of cognitive-enhancing nootropics. Although cognition is increased through the use of drugs, the scholar is still praised for their academic accomplishments. But when an athlete’s athletic performance is increased via drugs many claim that what the athlete accomplished is solely due to the drug and not of the athlete’s own ability. Is our praising the nootropics-using scholar a mistake or is it a mistake to discredit the steroid-using athlete’s abilities? In both cases, the individual’s performance is increased via a drug. There should be no difference in how we distinguish accomplishment in academia and sports, unless the rules governing the realms of academia and sports are vastly different from one another.

One way to show that the rules governing these two areas are different would be to say that academia is a not a competitive environment analogous to sports. The purpose of academics and educational institutions is to raise the level of understanding of the world. With this interpretation it would seem we that we should utilize anything non-detrimental that may help us decipher the world around us, such as nootropics. Unfortunately, it is very difficult to say that there is no competition in educational institutions, especially when students compete against one another to determine class curves and class rankings. The multiple ways of examining academia and educational institutions reflect the complexity of regulating cognitive-enhancing nootropics.

Also what may combat the idea that we should promote the use of nootropics is the light that this will shine upon academia. When we analyzed the use performance-enhancing drugs in sports, one issue focused on was the message that the use of drugs casts onto sports. If world-class athletes are required to use performance-enhancing drugs to keep up with their competitors, it alters the meaning of sports altogether. Victorious athletes will no longer represent a master of physical exertion and skill; rather, they become masochists willing to sacrifice their body to be at an athletic advantage over their opponents. Similarly, this argument can translate to academics. As students begin to use nootropics, test scores will go up and class curves will become more and more difficult. Consequently, the typical non-drug using student will be at a disadvantageous position. Instead of improving education, this transition would ultimately move academics further from its goal of promoting an information rich environment, and it would transform into a stressful environment where one must take cognitive-enhancing drugs to thrive.

Even though this analysis of whether to ban cognitive-enhancing nootropics in academia has proven to have no clear-cut answer, the U.S. Congress would be committing a disservice by scheduling the substance altogether. As previously discussed, the United States uses a higher standard for the scheduling of substances than what is used in sporting leagues. In the Controlled Substances Act there are five different Schedules. Each Schedule requires that the substance has a potential for abuse and that its use may lead to psychological or physical dependence. Regardless of whether nootropics create an unfair atmosphere in academia, if the nootropics in question do not meet both scheduling criteria the U.S. Congress should not add it to the Controlled Substances Act.

Although controversial and not well understood at this time, nootropics are the future. One day we may have biological technologies that can make us vastly smarter by merely swallowing a pill, yet I expect that this technology will be met with great controversy. This in depth examination of nootropics has shown that there are both reasons to regulate its use in academia and reasons for it to be left alone. The complexity of the issue coincides with the complexity of the purpose of educational institutions and whether or not schools or a place of competition or a place where knowledge thrives. Realistically, academia is a combination of both, and because of this the decision to regulate nootropics will never be black and white. Regardless of whether nootropics are ever banned from academia, they should not be scheduled in the United States unless it is discovered they have a potential for abuse and lead to psychological or physical dependence.


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  1. Nootropics are drugs that improve mental functions such as cognition, memory, intelligence, motivation, and concentration, while also being neuroprotective.

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  2. Hello! I am from Chile, last year bought Cerebrrin and noopept (Russian) on Ebay ... they got no problems by mail, the bad is that they are not at all miraculous, have no side effect (maybe I should up the dose), on pharmacies Hill has sold Actibrain."