Source: Popular Science
Date: September 2005

The Quest for A Smart Pill

Will Drugs Make Us Smarter and Happier?

James Vlaho

June 6, 2025, 7:30 a.m. The alarm is going off, and I feel great. Thanks to Reposinex, I’ve had a full four hours of deep, restorative sleep. My head hit the pillow, and boom! I was right into slow-wave delta sleep. In the car, driving to work, I sip an Achieve latte. I love these things—they sensitize my dopamine receptors, shift my MAO levels, and send my noradrenaline levels soaring. I have no jitters, and my concentration is tack-sharp. Driving used to freak me out, actually. I was involved in a bad accident a few years back. Good thing the doctor prescribed that trauma blunter. I still remember the accident; it just doesn’t bug me anymore. I’m no longer one of those Human 1.0s—I’m a human with complete control of his brain chemistry.

June 6, 2005, 7:30 p.m. Ramez Naam has a queen and a six face-up on the green felt of the blackjack table. The dealer shows a six. The obviously correct strategy is for Naam to stay, but this is his first time gambling at a casino, and nothing is obvious to him. Naam is 32, with dark hair and a neatly trimmed goatee. He peers uncertainly at his hand through blue-rimmed glasses, then taps the table with his fingertips. The dealer flips a card: a jack. Naam is out. He’s blown through his $40 stack of chips in less than 10 minutes.

Designing software for Microsoft is Naam’s job; envisioning the future—one in which biotechnology would allow us to shatter natural evolutionary limits—is his calling. A senior member of futurist think tanks such as the Acceleration Studies Foundation and the Foresight Institute, he speaks regularly at technology trade shows and is the author of the provocative new book More Than Human: Embracing the Promise of Biological Enhancement. Like most overachievers, Naam doesn’t like to lose. In blackjack and in life, of course, many factors are beyond our control—we can’t choose what we’re dealt, from the card deck or the genetic one—and Naam argues that we should change the restrictive rules of the biological game. He asks: What if you could pop a pill to make you remember more, think faster, or become happier or higher-achieving? What if there were safe steroids for the brain? You could effectively stack the deck, and the payoff could be huge.

The prospect of drug-enabled superminds is not just a futurist’s fantasy. In the past 20 years, scientists—aided by advances in computing, brain imaging and genetic engineering—have made significant progress toward understanding the biochemical systems that regulate cognition and emotion. This knowledge has raised the possibility of manipulating those systems more powerfully and precisely than ever before. One prominent neuroscientist, Anjan Chatterjee, calls what’s coming the era of cosmetic neurology. “Prospecting for better brains may be the new gold rush,” he says.

Roman Casino, where I’ve met Naam, is Caesars Palace on a serious budget, located in a strip mall near Seattle rather than on the Strip in Vegas. Coming here was my idea. A casino—where quick thinking, a good memory and control of your emotions can pay—seemed like a fitting backdrop for getting an overview of the possibilities of enhancement drugs. After a fruitless go at the tables, Naam and I retreat to the bar and order rum-and-Cokes.

“We’ve been enhancing ourselves since the dawn of civilization,” he says. The latest drugs are, to be sure, considerably more complex than the caffeine and alcohol we’re sending toward our bloodstream at the moment. And the way new enhancement pills reach us is complex as well: A pharmaceutical company develops a medication to treat a recognized physical or mental illness; people gradually realize that the drug can help healthy users too; doctors prescribe the substance to patients “off label,” meaning for purposes other than the ones recognized by the Food and Drug Administration; and other people obtain it illegally. Thus, college students end up popping Ritalin to help them ace exams. Concert pianists take propranolol, a hypertension and angina medication, to ease preperformance jitters. And coffee addicts switch to Provigil, a sleep-disorder medication, for powerful, enduring, jitter-free stimulation.

Naam argues that we shouldn’t be limited to using bootlegs of therapeutic drugs (FDA rules prohibit the development of drugs just for enhancement). If companies could turn their attention directly to the task, he says, “in the next few decades, we could create new drugs to sculpt or alter any aspect of human behavior: infatuation, pair-bonding, empathy, appetite, spirituality, thrill-seeking, arousal, even sexual orientation.”

These drugs wouldn’t simply be nice to have, he and other enhancement advocates believe—they would enable a societal transformation every bit as significant as the one wrought by computers. To true believers like Naam, the issue with drugs of the future is about cognitive liberty, the right to do what we want with our minds. It is about a capitalistic fight for the neurocompetitive advantage: The country with the most drug-enhanced citizens wins. And it is an ideological war against bio-Luddites. Past technological revolutions have allowed us to master the world around us. The pharmaceutical one, he believes, will allow us to master the world within.

11:15 a.m. Five projects, 10 deadlines, an uncountable number of engineering calculations. And I’m on top of it all. Since I started taking a cognitive enhancer, I don’t seem to forget a thing. And my mind runs so much faster. My boss doesn’t appreciate all I do, of course, but that doesn’t irritate me. Emoticeuticals—gotta love ’em. Zen-like calm, but I still feel the important stuff. If I did somehow get ticked and reached for a cigarette—my crutch from way back when—it wouldn’t do any good. Nicotine vaccination. No point in ever taking a drag again.

The road to Naam’s pharma-utopia may begin here: on a slide, under a microscope, where two slices of rat hippocampus are being stimulated by electrodes. The neurons in slice one have been treated with a type of drug known as an ampakine, while those in slice two have not. A computer records the levels of electrochemical signaling within each slice. The experiment looks low-tech, like something out of my seventh-grade science class, but it has far-reaching implications: Ampakines may prove to be the world’s most powerful cognitive-enhancing, memory-boosting drugs.

I squint through the microscope for a few seconds, making out pale gray cell bodies surrounded by tangles of stringy dendrites, and then head down a hall to the office of Gary Lynch. A neuroscientist at the University of California at Irvine, Lynch made a series of discoveries in the late 1980s and early 1990s about memory and the ways in which it might be manipulated chemically. In 1987 he co-founded a biotech company called Cortex Pharmaceuticals, which has been working since 1993 to bring an ampakine drug to market.

Lynch is waiting for me behind his desk. Sixty-one years old, he looks like a curly-haired version of Martin Short, complete with broad upper lip, grin full of teeth, and eyes glinting with private mischief. After a few preliminaries, he launches into his favorite subject—memory—and quickly gains oratorical traction. “If these drugs do what I do expect them to do, which is to improve cognition, the social implications could be astounding,” he says. “So much of our society is built around the idea of people thinking they’re smart or dumb—maybe you’d have people taking the pills and saying, ’I should be a professor at Harvard instead of doing this daily grind.’ ”

Cortex isn’t alone in the quest to boost cranial capacity. About 40 other companies, including behemoths such as Eli Lilly and GlaxoSmithKline, are pursuing what many consider the holy grail of pharmacology, a pill to boost sagging memory—Viagra for the brain. The profit potential is enormous. Some 4.5 million Americans suffer from Alzheimer’s disease, which currently has only marginally helpful drug therapies; at least four million are afflicted with mild cognitive impairment, a precursor to Alzheimer’s; and more than 10 million have age-associated memory impairment, which means their memories are far below average for their age. And, as is the case with drugs like Provigil, there’s an off-label market as well. “Companies won’t tell you this, but they are really gunning for the market of non-impaired people—the 44-year-old salesman trying to remember the names of his customers,” James McGaugh, another U.C. Irvine neuroscientist, has said.

Cortex is attempting to improve cognition by tinkering with the brain’s intricate system of electrochemical communication. To convey information, neurons release various types of neurotransmitter molecules, which bind to complementary receptor sites on adjoining neurons. Successful “docking” signals the neuron to open a channel that allows positive ions to flow inside, thus charging the cell. Ampakines crank up the volume of this neuronal conversation. They bond to the ampa receptor, which receives the neurotransmitter glutamate, causing the channel to stay open longer, allowing a stronger electrical charge to build.

“You can take a rat’s brain, stimulate one cortical region, and measure the electrical signal from another,” Lynch says. “Wash in an ampakine, and the signal is bigger.” Better signaling is thought to provide a cognitive boost, particularly in older brains with withering neurons. Aging baseball players have trouble hitting in part because they can’t process visual information as quickly, Lynch says. “Nothing is going to change that fact. But with an ampakine, maybe you could hit a curveball.”

Also intriguing to Lynch is the effect of ampakines on memory. When one neuron signals another, the connection between them becomes stronger. The frequency and strength of signaling helps determine how long the connection—known as potentiation—will endure. A link lasting for days or years is called long-term potentiation (LTP), and LTP is the fundamental biological mechanism of memory. Ampakines enhance LTP. Extending the amount of time that glutamate bonds to the ampa receptors triggers the opening of the neighboring NMDA receptors (another docking site for glutamate). They, in turn, admit calcium into the neuron, which signals the cell to establish LTP.

Ampakines have an additional, related benefit: They trigger the production of brain-derived neurotrophic factor (BDNF), which many researchers suspect will lead to the creation of more receptor sites. In other words, the drug doesn’t just make the neurons listen longer, it also builds new ears. In rats, Lynch has been able to reverse memory decline using single injections of an ampakine, giving middle-aged animals memory abilities nearly equivalent to those of young ones. Maybe, Lynch speculates, ampakines will have the same regenerative effect in humans. “Can we make it go from the winter of the brain to the spring?” he asks.

Cortex has begun to gauge the efficacy of its drugs on people; earlier this year, the company tested CX717, its lead drug candidate, in a trial of 16 sleep-deprived British men. Fueled by ampakines, the impaired subjects showed improvements on a battery of cognitive tests. Three more trials, all in the U.S., are scheduled for this year: one for Alzheimer’s patients, one for adult sufferers of attention-deficit hyperactivity disorder, and another for sleep-deprived men, this one funded by the Defense Advanced Research Projects Agency. Soldiers and pilots are often sleep-deprived during missions, and the military is keenly interested in finding cognitive boosters that work better than today’s amphetamines.

Other companies, manipulating different neurochemical pathways, have also reported promising results in animals and are planning human trials. Both Memory Pharmaceuticals, co-founded by Nobel Prize–winning neuroscientist Eric Kandel, and Helicon Therapeutics, founded by neuroscientist Tim Tully, have developed drugs that improve the memories of rodents. “Memory enhancers could become ’lifestyle’ drugs,” Tully says, “to be used by anyone interest

ed in learning a language, in playing a musical instrument, or in studying for an exam.”But the drug researchers are cautious. The pharmaceutical industry is littered with would-be wonder drugs that didn’t make the leap from animals to people. Cortex has learned that some of its most potent ampakine formulations, those that best influence LTP formation, can also cause seizures in rats. Even if ampakines are safe, their primary benefit—making memory stronger—may also be a liability. Remembering is important, but so is forgetting; otherwise the brain would become swamped with trivia. “I’m not at all clear what is going to happen when you take a drug that makes it harder to get rid of the things you’ve encoded,” Lynch says.

Overall, though, he is an optimist. Gazing at a poster of the brain on his office wall, Lynch remarks that a thought is essentially an ad hoc network of communicating neurons. Ampa- kines, by improving that communication, would allow a larger network—and a larger thought?—to be formed. “I should say that the best implication of ampakines is that we make everybody go home happy when they’re 50—fully powered sexually, memory back, age slipping off like a cloak,” he says. “But actually, personally, I wonder: Will you be able to think things that you can’t think right now? Ultimately we’d find out the limits of being human and go beyond them.” 5:50 p.m. I’m driving home, and Senator Davidson is on the radio. I support this psychopharm-disclosure bill she’s pushing. Shouldn’t we have the right to know if our elected leaders are taking empathogens and avarice-reducers like they’re supposed to? My wife is working late tonight; I’m with the kids. I love them, but sometimes my patience wears thin. With the advanced beta-blocker I take, though, a tantrum doesn’t set me off. Before bed, we say prayers. Truthfully, I never used to believe. But one little white entheogen pill and I feel—I don’t know, a presence. It’s comforting.

Smarts, of course, don’t guarantee happiness. In the pro- enhancement manifesto The Hedonistic Imperative, transhumanist philosopher David Pearce calls for liberation from our natural biochemistry—the “sick psycho-chemical ghetto bequeathed by our genetic past”—and the beginning of an era of “paradise engineering.” With the help of drugs, he writes, we’ll be able to chemically crank our dopaminergic systems so that “undiluted existential happiness will infuse every second of waking and dreaming existence.”

Sounds great. Sounds familiar, too. Similar if slightly more modest claims circulated two decades ago about Prozac, Paxil and other selective serotonin reuptake inhibitor (SSRI) antidepressants. The drugs are indeed effective and popular. Still, most Americans don’t use them. Their side effects—jitteriness, fuzzy thinking and diminished sex drive—are one reason they haven’t been widely adopted as enhancers, says Samuel Barondes, a psychiatrist at the University of California at San Francisco and author of Better Than Prozac: Creating the Next Generation of Psychiatric Drugs. “The public’s desire for a pure, selective-acting wonder drug remains.”

For much of the 20th century, drug development relied on luck—usually in the form of a serendipitous discovery that a known substance had additional positive effects. Miltown, the first blockbuster psychiatric drug, launched in the 1950s, was originally an antibiotic; Prozac, created in 1972, was a descendant of a common over-the-counter antihistamine.

Going forward, drug development will become less depen-dent on chance. Studies of genetically modified lab animals are revealing valuable information about the genetic and biochemical mechanisms underlying mood. At the University of Colorado, behavioral geneticist John DeFries selectively bred dozens of generations of mice until he had a dark-haired strain that was 30 times as brave as an albino one, as mea-sured by fearfulness tests. The gene variants governing mouse anxiety may turn out to be different than the human ones, but DeFries’s discoveries will probably shed light on genetic contributions to human fear—and may lead to new drug targets.

The completion of the Human Genome Project in 2003 and the rapidly decreasing cost of tools to collect and analyze DNA samples are also aiding drug development. By examining the gene variants that distinguish a depressed man from his happy brother, for instance, researchers may be able to create a more effective mood-elevating drug. Maybe. This burgeoning field, known as psychiatric genetics, is controversial. Any given aspect of personality, behavior or mood is influenced by the interplay of multiple genes—often a dozen or more—as well as environmental factors.

Nevertheless, futurists hail these genetic advances; some drug developers do as well, though more cautiously. In 2001 Emory University neurobiologist Larry Young genetically engineered a line of male prairie voles to have extra receptors for the hormone vasopressin. The manipulated voles formed bonds with females more quickly than normal voles and didn’t need to have sex before doing so. Futurists wonder: Will this knowledge pave the way for a drug to domesticate wayward men? Dean Hamer, chief of gene structure and regulation at the National Cancer Institute, has found that people with a variation of the VMAT2 gene, which affects the transport of the neurochemical monoamine, are more likely to report having transcendent spiritual experiences. Futurists wonder: A pill to make you believe in God?

And finally, happiness itself. Studies of twins have indicated that our fundamental dispositions may be 40 to 50 percent rooted in genetics. Futurist James Hughes writes in Citizen Cyborg: Why Democratic Societies Must Respond to the Redesigned Human of the Future that “the heritability of happiness . . . suggests that there could be future drugs and gene therapies that jack our happiness set-point to its maximum without negative side effects.”

June 7, 2025, 8 p.m. I’m out at dinner with my wife, and things couldn’t be better. Hard to believe we were so close to divorce. All that tiresome couples counseling. Then, simple oxytocin therapy. In a few sessions, it was as if we were dating again—such great chemistry. Right now, we’re on our third bottle of Connect—serotonin levels up, corticosteroid levels down. Sure, you can have an intimate conversation without this stuff, but it’s so much easier with it. We’ll go dancing later. Not naturally my thing, but I can pop some Steppinex—it makes me feel ecstatic. Before driving home, I’ll take an AntiStep and instantly be sober. Let’s say the optimists are right, and we’re able to create powerful new enhancement drugs. Should we? To many people, the answer is clear: absolutely not. Social critic Francis Fukuyama, author of Our Posthuman Future, presents a disquieting vision of a pharma-enhanced population. “Stolid people can become vivacious; introspective ones extroverted; you can adopt one personality on Wednesday and another for the weekend,” he writes. Fukuyama worries that the qualities that make us essen-tially human would be lost.

Biomedical philosopher Leon Kass, who recently chaired President Bush’s Council on Bioethics, writes that “in those areas of human life in which excellence has until now been achieved only by discipline and effort, the attainment of those achievements by means of drugs . . . looks to be ’cheating.’” Enhancement, in his view, is wrong because it is unfair. And unnatural: “All of our encounters with the world . . . would be mediated, filtered, and altered.” More than human, in his view, is no longer human at all. Back at the casino, Naam and I decide to have another go at the tables. He watches closely, soaking up information from the dealer and other players. Soon he’s hitting when he should hit, staying when he should stay, and doubling down. He goes up $120 before pushing back from the table, smiling and flipping the dealer a tip. Seldom is learning so rapid. Still, if Naam had been on a cognitive enhancer, maybe he would have learned even faster and lost less money up-front. Would that be unnatural? Unfair?

“I think it’s unfair that Michael Jordan was born with better basketball genes than me,” he says. “If somebody has a disposition toward being smarter or having a better memory than me, then maybe drugs could help even that out.” Naam also disagrees that enhancement drugs are unnatural. “The urge to better ourselves has been a force in history as far back as we can see,” he says as we head for the door. “Embracing the quest to improve ourselves doesn’t call our hu-manity into question—it reaffirms it.”

James Vlahos wrote about the riskiness of everyday life in July’s Popular Science.

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