On a sunny July day in Paris, 189 cyclists breathe a sigh of relief. Some are celebrating, some are disappointed, and some are just grateful that they can get some rest. It is the year 2005, and they have just completed all 21 days and 3,593 kms of the Tour de France. Grueling and brutal though it is, the Tour is among the world's premier sporting events, with cyclists competing for upwards of €2,000,000 in prize money and the eyes of over a billion viewers around the globe. More than anything, prestige is on the line. While it was a foregone conclusion that 6-time winner Lance Armstrong would finish in first, victors in any of the 21 stages would have their names etched into sports history.
Yet as soon as the race had concluded and the cyclists had flown home, investigations into the legitimacy of the final standings had been launched. Like all sports, cycling is plagued by a history of doping, the use of drugs which can enhance athletic performance. Faced with the intense pressures of competition, many athletes hope that banned performance-enhancing drugs (PEDs) will give them an edge over their fellow competitors. In the days leading up to the 2006 Tour de France, the second, third, fourth, and fifth place finishers from the previous year were disqualified for doping . Taking advantage of the rare opportunity, American Floyd Landis finished first, only to be stripped of the title in 2007 after a failed drug test. Lance Armstrong, the seven-time consecutive winner of the 1999-2005 Tours, was stripped of his titles in 2012 after years of doping allegations.
It is easy to understand why PED use is so common among athletes. With well-documented benefits and limited detriments, doping can lead to greater success in a high stakes, competitive environment. But for all its use among athletes, PED use among the general population remains relatively low. For the average person, the increased physical performance from PED use is not worth the high prices, detrimental side effects, and legal consequences. Instead, the average working person or student is held back by cognitive limitations, including concentration, memory, fatigue, and general intelligence.
But what if a drug existed that could remove these limitations, giving individuals a mental edge over others? Enter nootropics, a group of substances purported to improve cognitive function. Nootropics may seem far-fetched, but they are already commonly used around the world. One that you've likely heard of—caffeine—is used daily by 90% of American adults . Just as well known, but much more heavily regulated and abused, are the stimulants known as Adderall and Ritalin. These therapeutic drugs can only be used in certain circumstances when prescribed by a physician. While these nootropics are heavily-researched and appropriately regulated, there exists a separate realm of supposed nootropics with scarce research and, crucially, lack of regulation. Compared to the aforementioned nootropics with well-studied stimulating effects, these unregulated substances promise a range of cognitive improvements that have little scientific backing. Still, large online communities dedicated to reviewing, sharing, and selling these substances focus primarily on the benefits without noting the possible deleterious effects. While the popularity of certain stimulants like caffeine indicate that nootropics as a whole may one day be more prevalent, snake oil salesmen have already begun to populate the Internet, where they can peddle pseudoscientific gibberish and profit off of unregulated substances. Sold as supplements and powders online, these nootropics evade FDA regulation.
However, before understanding the status of other nootropics, it is essential to consider why certain drugs like caffeine and Adderall, among others, are widely accepted. Backed with extensive research investigating their mechanisms and efficacy, these drugs are better understood and more appropriately regulated than other nootropics. In the case of caffeine, its mechanisms of action had been identified and well-documented by 1987, when Dutch researchers linked the structures and effects of caffeine and adenosine (a compound that modulates neural activity) . A later study found that caffeine binds to a certain class of adenosine receptors, inhibiting the drowsiness-inducing effects of adenosine . In response, cells release a greater quantity of the neurotransmitters (neural signaling molecules) dopamine, norepinephrine, and glutamate . These neurotransmitters work in tandem to stimulate the central nervous system, increasing overall neural activity. In addition to the demonstrations of caffeine’s efficacy, other information pertinent to users has been documented. Even among chronic users who have developed tolerance, caffeine maintains residual stimulating effects—the result of its interaction with the adenosine receptors . While caffeine can cause minor anxiety and jitteriness, no severe physical or psychological effects have been observed [4, 6]. At the same time, moderate use of caffeine will not result in an overdose and the substance is not considered highly addictive . Thus, satisfactory knowledge of its efficacy, mechanisms, tolerance, side effects, and dosages makes caffeine’s relative lack of regulation by the FDA and other administrative bodies appropriate . But without an understanding of the aforementioned factors, it is impossible for any drug, including nootropics, to be properly evaluated.
The same connection between a drug’s base of scientific knowledge and its usage and regulation can be seen with the drug Adderall, a mix of two amphetamines (stimulants). Used primarily as a treatment for attention-deficit/hyperactivity disorder (ADHD), the stimulant is known for its abuse among students as a cognitive performance enhancer. To perform both of these functions, Adderall blocks dopamine and norepinephrine reuptake—keeping the neurotransmitters active—and also stimulates dopamine release. This results in higher concentrations of these neurotransmitters in the prefrontal cortex, the brain region responsible for our ability to focus . Studies have also suggested that the amphetamines present within Adderall can result in moderate improvements in delayed recall performance . Unlike caffeine, however, Adderall has a high potential for abuse, accompanied by potentially serious cardiovascular risks that result from improper dosage . Like with caffeine, Adderall’s efficacy, mechanisms, tolerance, side effects, and dosages are well known, allowing administrative bodies to make appropriate regulatory decisions. When balancing its medical applications with its risk for abuse and addiction, Adderall is classified, along with other amphetamines, as a Schedule II Controlled Substance, with greater scrutiny by the DEA, FDA, and other legislative bodies. Even though Adderall may be occasionally abused, these regulations allow physicians to make informed decisions about prescriptions and prevent abuse among the greater population.
Most common drugs follow the same general pattern from their initial production to their broader distribution. In the face of scientific scrutiny, these drugs demonstrate their efficacy in treating a disorder or improving a certain function. As further research reveals ideal doses, potential addiction, and possible deleterious effects, these substances become more regulated. Some, like caffeine, are determined to be relatively harmless and face little regulation. Other drugs which can have a high risk of abuse and other negative effects, like Adderall, face much greater regulation and are held behind prescriptions. Through the interaction between research and regulation, drugs are appropriately monitored to ensure that they do not cause public harm. In most cases, administrative bodies collaborate to “schedule” these drugs, placing them into distinct categories depending on their potential for abuse. When drugs are scheduled, both customers and regulators are better informed about the dangers a drug could present. Many nootropics gaining traction today, however, exist outside of this realm. An overwhelming scientific consensus on the usage of these substances simply does not exist. Because these substances have not yet been scheduled, nootropics can be sold as dietary supplements, as long as their sellers do not make completely outrageous claims about unproven health benefits.
Online sellers, like Nootropics Depot, tend to follow these general rules of conduct. Selling different pills, tablets, and powders, the seller is careful to not overstate the possible beneficial effects, lest they incur legal consequences. On their store page, all substances are labelled as dietary supplements, and descriptions of their functions are hedged with inconclusive statements like "may support … brain health" and "reported health benefits" . But if a simple visit to a website like Nootropics Depot provides inconclusive evidence about which substances are more effective, how do prospective buyers choose which nootropic to buy? For many, the answer lies in online forums like the subreddit r/Nootropics. A fast-growing community with over 240,000 members, anonymous users discuss their own experiences and suggestions about the function and use of all kinds of nootropics. When interested users ask for recommendations for their first nootropics, power users respond with their suggested substances, dosages, and a handy link to existing “research.” Posts singing praises about certain nootropics are particularly popular. In these posts, users often attribute life-changing benefits to their nootropic use. As an example, a recent post, with over 400 upvotes and a 97% upvote-to-downvote ratio, was titled “I thank life every day for L-Theanine and this sub” . Of course, these users are usually well-intentioned. But as a whole, the incomplete—and often contrasting—information presented on these forums can have dangerous effects.
The life cycle of tianeptine, a former r/Nootropics favorite, demonstrates the effect that these forums can have on substance use and abuse. Shown in some studies to be an effective antidepressant, tianeptine is unscheduled in the United States . Before 2015, tianeptine was a favorite for users on r/Nootropics. On a daily basis, posts praised the miraculous effects of tianeptine on treating social anxiety and depression while reporting minimal or nonexistent negative side effects [14,15]. Other posts shared websites on which new tianeptine-based products were being sold [16,17]. Occasionally, a user would even post a “legitimate” study suggesting that tianeptine had other functions, like improving working memory . According to r/Nootropics, tianeptine was a safe, legal, and effective nootropic.
However, largely ignored on the subreddit was existing evidence that tianeptine’s mechanism of action could lead to dependence and addiction [13, 19, 20, 21]. These negative properties would come to light when, in 2015, Texan Colby Patrick Brennan died from an apparent overdose from tianeptine purchased from the popular online outlet Powder City. The subsequent lawsuit, accusing Powder City of failing to label their product with instructions and warnings, resulted in a monetary settlement of an unspecified amount . Over the course of a year, Powder City would pull tianeptine from their website and would eventually shut down operations entirely [23, 24]. On a broader scale, the National Poison Data System (NPDS) reported a drastic increase in tianeptine exposure calls in 2014-2017, the same period in which tianeptine reached its peak r/Nootropics popularity. While the NPDS received only 11 tianeptine-related calls from 2000 to 2013, they received 207 tianeptine calls from 2014 to 2017 . Since then, the state of Michigan classified it as a Schedule II Controlled Substance, effectively banning tianeptine in 2018 . In March 2020, Italy became the first European country to ban tianeptine altogether . In r/Nootropics, tianeptine is now rarely discussed and seemingly forgotten altogether. But because r/Nootropics is still plagued by misinformation, it is not difficult to imagine that some new trendy substances, as with tianeptine, are being presented to users dishonestly.
Regardless of the disastrous consequences of their actions, it is hard to blame those who post and comment on r/Nootropics. After all, they are just discussing a hobby. At worst, they simply do not understand the risks of promoting these substances. But over time, eager salesmen have discovered the value of these online communities and have begun aggressively marketing their products to them. The once-innocent discussion is now often directed by those with financial interests in nootropics. According to the moderators on r/Nootropics, a distributor named Oriveda made repeated attempts to astroturf the subreddit, posting “fake reviews and company propaganda [on] the subreddit using [certain] accounts" . The moderators also alleged that Oriveda deceptively marketed on other forums, including one named Nootropedia. As a result, these accounts were banned and posts mentioning Oriveda are now automatically deleted. While these allegations may be true, they could not be officially confirmed. Regardless, it is not as if r/Nootropics is now free from so-called astroturfing. In fact, “fake reviews and company propaganda” are commonplace within the subreddit. One of the r/Nootropics moderators is the owner of the retailer Nootropics Depot. This user, along with others associated with retailers, are frequently involved in discussion, subtly advertising their products .
This problem is prevalent not only on Reddit, but across the entire Internet. On YouTube, there are thousands of videos centered around “reviewing” nootropics. But in order to entice the thousands or even millions of views that these videos often receive, these creators are usually more interested in intriguing thumbnails and superlative content than honest reviews. In one video with more than 500,000 views, a man describes the "laserlike focus" he experiences as he uses the drug Modafinil . In the video’s description box, he provides a link to a website where supposed cognitive enhancers, among other supplements, are for sale. For the influencer, this additional link is financially motivated. While some influencers own a piece of the companies they promote, others can receive commissions from the purchases of their viewers. Nootropics Depot, for instance, offers a program where affiliates can earn an 8% commission on all sales . In recent years, nootropics have even begun to pierce the upper echelons of popular Internet content. One place where they are often discussed - The Joe Rogan Experience.
The Joe Rogan Experience, Joe Rogan’s eponymous variety podcast, is the most listened-to podcast in the United States . In May of 2020, Spotify and Joe Rogan struck an exclusive licensing deal for the podcast and its millions of listeners valued at more than $100 million . In these podcasts, the nootropic mix Alpha Brain is both a frequent sponsor and a popular topic of conversation. In one episode, Joe Rogan and director Judd Apatow talk about how Alpha Brain "completely works" . Rogan is, of course, a shareholder in Onnit, the company that manufactures Alpha Brain. Citing the credibility of the drug, Rogan distinguishes Alpha Brain from other nootropics by claiming that it is backed by “double-blind placebo-controlled studies” . In reality, the one study on Alpha Brain is funded by Onnit, has a small sample size, is not peer reviewed and demonstrates minimal overall effectiveness .
All of this is not to say that nootropics have no place in modern society. On the contrary, the continual growth in the popularity of this category of drugs indicates that the use of nootropics may eventually become more mainstream. The widespread discussion on nootropics in popular media, including Joe Rogan’s podcast, indicates that this process is already occurring. Yet as nootropic consumption has increased, regulatory processes have lagged behind. Without any change, ignorant drug abuse, like with tianeptine, is bound to continue, causing dangerous side effects and overdoses. For this reason, it is essential that the “miracle drug” narrative surrounding nootropics changes. In the US, there is now a unique opportunity for the government and its citizens to prevent the widespread abuse of nootropics before they become commonplace. As the study of nootropics continues, several simple steps can help curtail the rampant abuse of existing nootropics. For one, social media forums which host discussion of nootropics must be more vigilant in promoting safe use. On r/Nootropics, despite all the subreddit’s flaws, this change has been evident. A beginner’s guide suggests exercise, sunlight, sleep, and a good diet, before giving suggestions for research and safe usage. Sites like Facebook, Twitter, and YouTube already have drug policies, and should reevaluate how nootropics fit these existing guidelines. Greater public health education is also necessary, especially in school environments where students are at a high risk for abuse. Lastly, the government should step in with active, flexible policy that allows rapid response to new threats.
It is not as if nootropics are entirely harmful. As research on nootropics continues, their use can possibly increase human productivity. Yet if these drugs are treated as an advantageous shortcut to the top, they will be abused in the same ways that athletes abuse performance-enhancing drugs. When the long-term side effects of most nootropics are still unknown, this attitude may lead many to jeopardize their own health in exchange for minimal benefits. If nootropics are to benefit society, they must be cautiously approached and carefully regulated.
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