13
LIVING SMARTER
Cognitive enhancement
Get rich without working! Lose weight by eating anything you want!! Get smarter by doing crossword puzzles or sudoku four times a week!!! (The companies that advertise these promises seem to be in cahoots with the companies that manufacture exclamation points.) We all like the sound of these promises, and Americans are especially drawn to these kinds of claims. We are a paradoxical culture of do-it-yourselfers, self-made millionaires, and people who still think they can get something for nothing.
There has been much media attention paid to the idea of “brain games for better aging.” Added to the old standbys like crosswords, KenKen, and sudoku are new Internet- or computer-based brain-training games. The important questions about these puzzles and games, both old and new, are: If I play brain games, will it make me less likely to lose my glasses? Will I drive more safely? Will my memory improve? In other words, will the skills and practice I gain transfer from one activity to others? Unfortunately, the answer for most of these is no. If you spend time doing sudoku, there is little evidence that you’ll get better at other things—all that happens is that you get better at doing sudoku. Several systematic reviews and meta-analyses have concluded that there is no convincing evidence that brain-training games enhance cognition beyond the realm of the game, nor do they fend off dementia.
Why do we think these games will lead to cognitive enhancement? In part because of aggressive advertising by Lumos Labs, the company that makes a brain-training game called Lumosity, which was found guilty of false advertising and fined $50 million. But they’re not the only culprits. A competing company, Neurocore, backed by US education secretary Betsy DeVos, was admonished by the National Advertising Review Board for making unsupported claims in their advertising. Collectively, these “brain-training” games may actually set you back because if you spend time doing them, that’s time you’re not doing the things that we know make a difference, such as outdoor exercise or spending time with others. (In addition, the phrase adopted by the manufacturers of these games, brain training, is misleading because very few studies have looked at actual brain changes in response to the training.)
The Association for Psychological Science (APS) published a paper in 2016 by a team of experts led by Daniel Simons, an experimental psychologist at the University of Illinois. The team analyzed 132 papers cited by these for-profit brain-training companies. The paper is very carefully prepared and documented. It reads something like an indictment from a federal prosecutor. Of the 132 papers, 21 were review papers that did not report any new data and therefore were redundant; 15 reported on data from only a single study; 36 lacked an adequate control group; 6 papers with a control group lacked random assignment; 5 other papers had similar reasons not to include them. Of the remaining 49 papers, 25 were reporting on the same six experiments. Many of those 49 were authored or co-authored by employees of the company whose products they were testing, and so they are not independent assessments of the products. If you are not an expert, it is easy to be bowled over by the sheer number of papers cited by these companies. But you know better now. Simons’ team found, as many others had, that brain-training games develop a particular, narrow set of skills and lead to improvement in those skills but not others, even others that would seem to be related. Simons and his colleagues concluded,
We found little compelling evidence that practicing cognitive tasks in brain-training products produces lasting cognitive benefits for real-world cognition. . . . If your hope is to stave off the cognitive losses that sometimes accompany aging or to enhance your performance at school or in your profession, you should be skeptical.
Consumers should also consider the comparative costs and benefits of engaging in a brain-training regimen. Time spent using brain-training software could be allocated to other activities or even other forms of “brain training” (e.g., physical exercise) that might have broader benefits for health and well-being.
These brain-training activities are fun. They present us with challenges and an opportunity to get better at something. I do crosswords and KenKen every day, but they don’t make me better at writing books or calculating a tip on a restaurant check—they are their own world, a world I enjoy and consider to be among my rewarding hobbies. I do them because they give me pleasure and challenge me mentally, not because I think they’ll make me better at other things.
Art Shimamura counsels:
You may be better off engaging in things that more closely resemble the kind of mental activities you enjoy or want to improve. Do you want to learn more from reading? Join a book club and discuss your thoughts with others. Do you want to be more attentive in daily activities? Practice the specific kinds of activities that demand such mental processes. Do you want to be creative? Learn a new musical piece, dance step, or dinner recipe. Explore new locations around your neighborhood.
Ethical Issues
Imagine a time, say, twenty-five years in the future, when bioengineers and genetic engineers have developed ways of enhancing our lungs and muscles, allowing more of us to run marathons, and to do so more easily. That would not have been their primary goal, at least not at first. These intrepid researchers, some of whom are probably at their lab benches right now, would be trying to find cures for lung cancer or sarcopenia (recall from Chapter 10, on movement and exercise, that sarcopenia is for muscle what osteoporosis is for bone). Somewhere along the line someone would realize that the technology they’ve developed can be used to enhance normal function, creating greater capacity than a person would typically have.
If an athlete with lung cancer received a treatment that eradicated it and brought them back to their own normal, would you allow them to compete in the Olympics? Why not? That seems no different than letting them take aspirin for a headache, having a bunion taken off their foot, or training in high-altitude thin air, all of which the International Olympic Committee allows. But what if that same lung treatment conferred an advantage when given to someone without cancer? That strikes many of us as unethical, tantamount to the use of steroids. We allow athletes to take steroids if it is a medical necessity, but not if it is purely for enhancement. Many of us share the feeling that sports competitions should follow well-defined rules that ensure fairness. The idiom level the playing field is, of course, a sports metaphor.
Now imagine also that in this near future, neurochemists have developed various ways of modifying our brains to enhance cognition. Collectively, these are called pharmaceutical cognitive enhancers, or PCEs. The initial motivation might be to restore lost function in people with cognitive impairment brought on by disease or injury. But then, the medicinal cat would be out of the bag. Would it be fair for otherwise healthy people to take them? This strikes many people as unfair. Okay. But if people who you are competing with are taking drugs—people within your own company vying for a promotion, workers at other companies plotting to overtake your market position—should you take the drugs also just to keep pace? Now, to up the ethical ante: What if cognitive enhancement taken by scientists could speed up finding a cure for cancer, or if taken by negotiators could solve the Palestinian-Israeli conflict—would that change the ethical calculus?
If you’re still feeling uncomfortable about cognitive enhancement, consider that we already alter our neurochemistry through caffeine and alcohol (not to mention Prozac). A neural implant may more efficiently stimulate the prefrontal cortex and brain stem the way that these drugs do, but with greater precision. A PCE or implant that can improve memory could allow you to remember crucial details such as whom to call for help, how to use the phone, and where you live. Will we accept an implanted memory restorer for people with Alzheimer’s? What about schoolchildren? Neuroscientist Michael Gazzaniga imagines one such possible conversation: “Honey, I know that we were saving this money for a vacation, but maybe we should get the twins neural chips instead. It is hard for them in school when so many of the other kids have them.” If this feels fundamentally different from previous generations buying glasses or hearing aids or paying for Ritalin, the difference is that glasses, hearing aids, and Ritalin (at least for those diagnosed with ADHD or related conditions) are treating something. Healthy students and corporate execs who take Ritalin, on the other hand, might be construed as cheats, trying to game the system.
And yet, why should we draw an artificially defined line between socially sanctioned drugs, such as caffeine, and pharmaceuticals, such as Ritalin? It is difficult to say, and ethicists disagree about where to draw the line.
In the case of aging adults, drawing the line requires subtlety and medical knowledge we don’t yet possess. Roughly one out of six adults over age sixty has mild cognitive impairment, a legitimate medical condition. We treat a whole range of maladies for individuals in this age group, from blood pressure to elevated cholesterol and arthritis. Why not treat mild cognitive impairment? Should diseases of the brain be so stigmatized that we don’t treat them? That attitude thrusts us backward a hundred years to when people with schizophrenia, Down syndrome, and autism were locked away in sanitariums. And then, as a step further, what about the other five in six adults who have not been diagnosed with mild cognitive impairment but might be developing cases of it, or have cases that are as yet undetected? Suppose you just feel like you’re losing it, only a little. Your memory and energy aren’t what they once were. Why can’t you have this enhancement, too?
Ethicists have begun to grapple with all of these issues, and some of the considerations raised so far include (1) unknown long-term effects and side effects of cognitive enhancement drugs and implants, (2) inequality of access to these technologies, (3) the possibility that some military or business organizations might force individuals to use them, and (4) whether the use of them constitutes cheating in competitive contexts (academics, business, military operations, diplomatic negotiations, sports).
The US Bioethics Commission issued a report in which they delineate these different uses as a way to frame the ethical discussion.
Neural modification can serve at least three purposes, to (1) maintain or improve neural health and cognitive function within typical or statistically normal ranges; (2) treat disease, deficiency, injury, impairment, or disorder (referred to as “neurological disorders”) to achieve or restore typical or statistically normal functioning; and (3) expand or augment function above typical or statistically normal ranges. In delineating these neural modification objectives, the Bioethics Commission is mindful that they are not always sharply distinguishable.
Point 1 is relevant to the discussion of older adults and mild cognitive impairment: Older adults may seek simply to maintain their neural health and cognitive function as it was when they were younger, to the best of their abilities. Whether that is deemed an ethical use or not isn’t clear-cut. The commission fell short of taking a position, but they were firm on one point: If such enhancements are available to some, they should be equally available to all. “We urged that policymakers ensure equitable access to beneficial neural enhancers. In our society, access to existing services and opportunities, such as education and nutrition, is not equal across individuals or groups.” The commission argues that these various enhancers should not be the exclusive province of those who are already the wealthiest and most successful, because this would serve only to enlarge the gaps in opportunity, a trans-societal problem. The wealthy already have better access to health care, legal representation, and social mobility.
Stimulants—Adderall, Modafinil, Pitolisant, Ritalin, Nicotine
Members of the US Bioethics Commission write:
Adderall and other stimulants are used off-label by individuals who desire to increase their competitive advantage by working longer hours with greater attentiveness while sleeping less. At every turn, we see headlines announcing “epidemic” amphetamine use by high-achieving students seeking top grades and standardized test scores.
There is no evidence that this condition has changed in the years since the commission issued this statement. Adults who are experiencing the effects of aging may find that stimulants, carefully used (and preferably under a doctor’s supervision), can make them feel younger, more energetic, and more alert. What we don’t know for sure is whether such medications have lasting, damaging effects.
Adderall is one of a group of amphetamines, which are often taken “off label” (that is, in a nonapproved application) for cognitive enhancement. There are mixed results as to whether Adderall and other amphetamines actually enhance cognition; however, they are known to increase motivation, which is no small thing. On the flip side, there are a few reports that they impair creativity.
I’ve mentioned modafinil, a drug that is prescribed for jet lag or shifting your circadian rhythm. It does not stimulate the production of dopamine, but it binds to dopamine receptors in the brain and inhibits dopamine reuptake, causing whatever dopamine is already in the system to stay around longer, and it is also an adenosine receptor antagonist, like coffee, tea, and caffeine. Like Adderall, modafinil (originally sold under the brand names Provigil and Alertec) can increase motivation and promote wakefulness. Some healthy individuals who are not chronobiologically shifted have turned to it for cognitive enhancement. One systematic review found that modafinil consistently enhanced attention, executive functions, and learning, with few side effects. However, other reviews show mixed results including impairments, such as a reduction in creativity, and in another, it led to cognitive slowing with no increase in performance accuracy. Some use it when they have repetitive, boring work to do that doesn’t require creativity. Others report that it allows them to focus on a task but that the focus can be so narrow that it makes them inattentive to other things, causing them to be absentminded, misplace things, or not properly shift attention when an attentional shift is required. (A newer formulation of the drug is called armodafinil and is sold under the brand name Nuvigil; they have essentially the same effects.)
Pitolisant, currently available only in the United Kingdom and Europe (but scheduled for FDA approval in the United States), is a wakefulness- and alertness-promoting agent that acts as an H3 (histamine) receptor antagonist. Developed for narcoleptics, it has also been used off label for cognitive enhancement and alleviating depression.
Ritalin (generic name methylphenidate) is one of several available dopamine promoters, and it also enhances levels of norepinephrine. As we’ve seen, aging is typically accompanied by loss of dopamine receptor neurons in the brain, and it is believed that this is partly responsible for the cognitive decline we observe, including the finding that older adults are especially disadvantaged when fast and efficient processing in novel situations is required. College students have been taking Ritalin for fifty years to help them study and for general cognitive enhancement—in surveys, between 5 and 35 percent report having used it within the past year. This is not to say that changes in other neurotransmitters, such as serotonin, acetylcholine, or noradrenaline, don’t affect cognition, just that dopamine appears to, and dopamine promoters such as Ritalin serve as effective neuroenhancers.
To a neuroscientist, nicotine is in many ways the perfect drug for cognitive enhancement. It increases vigilance, attention, focus, memory, and creativity, and it refines motor skills, all without causing the jitters or stress that usually accompany stimulants—in fact, it tends to reduce stress. In particular, nicotine enhances attention by deactivating areas of the default mode, such as the posterior cingulate. It is being considered as a treatment for late-life depression and Parkinson’s disease and Alzheimer’s disease, where it is believed to have neuroprotective effects. Scientific American touted nicotine as the next smart drug.
The problem with nicotine is that the most common delivery systems, smoking and chewing, cause cancer. Even with other delivery systems, such as gum, patches, and the new mouth sprays, it is highly addictive. It can increase heart rate, blood pressure, and inflammation, it can cause nausea, and in rodents it promotes cancer growth. In large doses nicotine is a poison, an evolutionary adaptation in the leaves of the tobacco plants to prevent insects from eating it. Humans can tolerate it in small doses, however, and if you get the dose right, you might get the benefits without the drawbacks. To minimize the possibility of addiction, it’s best to use it occasionally, for focus and energy, and not for more than a few days in a row. And it’s important to use a low dose. If you want to experiment, try the gum or the mouth spray, and start out with the smallest dose possible. But caveat emptor. As of this writing, vaping tobacco is no better than smoking and may in fact be much worse.
There are dozens of other drugs linked to cognitive enhancement. One is tolcapone, a nonstimulant dopamine promoter that in a small number of studies has been shown to significantly improve information processing, attention, and memory. The problem is that it is highly toxic to the liver; after three patients in Europe died from liver injury attributed to tolcapone, it was withdrawn from the market. A drug that is chemically similar, entacapone, is easier on the liver but doesn’t cross the blood-brain barrier as well, and so doesn’t confer equivalent cognitive benefits. Then there’s pramipexole (Mirapex, Mirapexin, Sifrol), another dopamine promoter that researchers thought would enhance cognition but instead induced sleepiness and impaired learning in healthy people. I mention all these as cautionary tales of how a drug that can enhance one physiological system can wreak havoc on another. I’ve reported in this section those drugs that are relatively safe (at least for short- and medium-term use), compared to the dozens that have either been withdrawn from the market or are risky to other systems.
Dave Hamilton, co-founder of The Mac Observer, attended a “Cannabis and Parenting” meet-up at the SXSW festival recently. One woman spoke and shared the story of a teenage girl whose doctor put her on cannabis to deal with a medical condition. The doctor’s instructions to the girl were the salient point and apply to any medication or treatment: Watch yourself.
If your grades (or work) start to slip, we need to find a different treatment plan. Similarly, you need to stay socially engaged. If you find yourself withdrawing from the company of others and holing up in your room, your treatment plan needs to change.
Dave notes that “such smart, enlightened advice is for any of us on any treatment plan with any medication. Just because our doctors and WebMD say something is ‘right,’ we need to maintain that self-awareness of any residual effects on our lives as a whole.”
Memory and Attention Enhancement
Rivastigmine and Memantine
There is early and incomplete evidence that rivastigmine (brand name Exelon) can ease some of the symptoms of cognitive decline, including memory difficulties and disorientation. Rivastigmine enhances acetylcholine in the brain (it is a cholinergic agonist), but we still don’t understand its precise mechanism of action or why it has the therapeutic effects that it does. You may recall that acetylcholine is involved in sleep, and so rivastigmine may simply help patients to achieve a better night’s sleep, and that’s a big deal. But as we’ve seen, neurotransmitters are typically involved in a great number of activities, and acetylcholine is also associated with transmission among brain regions involved in attention, memory, and cognitive control. Rivastigmine has a long list of side effects, suffered by about two-thirds of users, and many discontinue its use. But the side effects appear to be reversible, and if you are suffering and high on Factor V (Openness to Experience) you might ask your doctor to let you try it and decide for yourself.
Similarly, there is early and incomplete evidence that memantine (brand name Namenda) might ease and reverse symptoms of mild cognitive impairment and mild neurocognitive disorders. Memantine blocks glutamate (it is a glutamatergic antagonist), and glutamate is associated with excitation of neural signaling. As with rivastigmine, we still don’t understand the mechanisms of action. Part of what might be going on is related to hyperexcitability that can occur in the hippocampus if too much glutamate is released, or if it is not absorbed quickly enough; either of these things could happen due to general age-related wearing out of cellular assemblies in the brain. When the hippocampus gets too much glutamate, a condition called glutamate-induced excitotoxicity, we have observed decreased neuronal regeneration and dendritic branching, and impairments to memory and learning.
In terms of the difference between rivastigmine and memantine, Carlos Quintana, a board-certified neurologist in San Francisco, uses the analogy of tuning in a car radio station. “Rivastigmine is like tuning in the frequency more precisely, and memantine is like turning up the gain. The two drugs work together very well and are often co-prescribed.” Indeed, a recent meta-analysis concluded that there is moderate evidence that combination therapy using the two drugs yields small improvements in cognition, mood, and behavior. The thing to keep in mind is that this small improvement represents a statistical average of people who see large improvements, people who see none, and people who get worse. You may very well experience greater than “small” improvements (but you may very well not). As before, if you’re feeling adventuresome, and your doctor has not diagnosed you with a condition that contraindicates it, you might try it as an experiment.
Hormones, Revisited
I’ve mentioned the role of hormones in physical and mental health, and in particular, how hormone replacement therapy can help with restoring sleep cycles. Some individuals are very sensitive to the hormonal balance in their bodies, and age-related declines of even a small amount of testosterone, estrogen, or progesterone can cause cognitive difficulties, particularly in memory and attention.
You’ll recall that senescence is the cumulative effect of things that happen to our bodies over time that may be harmful or cause difficulties for us. Cellular senescence is the specific case of our cells losing the ability to repair themselves and replicate. Much of what we recognize as the undesirable effects of aging is caused by cellular senescence—wrinkles, memory loss, and a lowered immune-system response. This is paralleled by a progressive decline in the ability of most organs to repair and recover from injury and disease. Many—perhaps most—older adults are living with chronic low-grade inflammation and decreased immune-system function. The majority of studies suggest that this inflammation is due to hormone deprivation (estrogen and testosterone).
Why some people age more successfully than others is clearly not a simple question. If the effects of aging are simply due to low-grade inflammation, everyone who took anti-inflammatories would stop aging. If it were just lack of hormones, hormone replacement therapy would solve the problem—but it doesn’t. Many driven, successful people I know in their seventies and beyond are taking prescription hormonal supplements, but many are not. There are, as with everything else, great individual differences. But for many, testosterone for men and estrogen for women can lead to increased mental clarity, ability to focus, and improved memory.
Cognitive Stimulation Therapy
Among nondrug treatments, cognitive stimulation therapy (CST) has the highest record of efficacy. Administered by a therapist or facilitator, CST strives to reorient individuals to their memories and current lives, as well as promote physical and social activity. The data on this are not particularly strong, because of a lack of rigorously controlled studies, but the preliminary picture is that cognitive stimulation therapy is responsible for significant improvements in cognitive function and self-reported quality of life, although it had no significant effect on self-sufficiency.
Other Treatments
The studies I’m about to review in this section are only preliminary. By a rigorous definition, none of them qualify as “medicine” because the evidence is still being gathered. Many of the findings are based on animal models and have yet to be verified in humans. To my knowledge, none of these treatments has been shown to be harmful; they should all be regarded as works in progress. The list of supplements for which manufacturers declare age-defying properties could take up more than a hundred pages. If it is not listed here, I know of no reliable evidence that it works. This includes things like DHEA, beta-carotene, vitamin E, selenium, ginseng, creatine, ginkgo, ginseng, and piracetam.
Vitamin B12
Vitamin B12 (cobalamin), found in meat, poultry, eggs, milk, and fish, is necessary for the production of myelin in the brain and is involved in the metabolism of every cell in the body. Vegans are prone to B12 deficiency and are advised to take supplements. As we age, our stomachs produce less gastric acid, reducing the body’s ability to absorb vitamin B12 that’s found in food, and so B12 deficiency is more common among older adults.
Much B12 research has been driven by the homocysteine hypothesis. Homocysteine is a potentially toxic amino acid, and elevated levels of it are associated with cognitive impairment, Alzheimer’s disease, dementia, and cardiovascular disease. We believe that it increases oxidative stress and increases damage to DNA and that its neurotoxicity leads to cell death. B12 (along with B6 and folate) is responsible for recycling homocysteine, thereby keeping its levels in check; insufficient amounts of B12 are therefore believed responsible for a toxic buildup of homocysteine.
Vitamin B12 deficiency is associated with cognitive decline, and older individuals with higher B12 levels generally perform better on cognitive tests. Of course, the mere fact that deficient levels of B12 are correlated with cognitive deficits does not mean that B12 supplementation will correct that. Indeed, a 2003 Cochrane review showed no association between B12 supplementation and improvements in cognitive function. Although a 2017 review demonstrated that B12 was indeed effective at lowering homocysteine levels, that alone did not translate to measurable cognitive improvements.
On the other hand, a different meta-analysis found B12 supplementation led to significant memory improvement, and another found that it slowed the rate of brain atrophy associated with dementia and mild cognitive impairment, with the strongest effect being in those with higher homocysteine levels to begin with.
Anecdotally, many doctors and patients claim that B12 supplementation increases energy and lifts depressed mood. Taking B12 supplementation does not cause any harm as far as we know, provided that your blood plasma levels don’t exceed recommended maximums, and there is a possibility that it may be neuroprotective as we age by promoting myelination.
Neuroshroom
Bob Weir, a founding member of the Grateful Dead (age seventy-two), has been taking a commercially available formulation of dried mushroom extracts called Neuroshroom. He started, he says, because “a medical doctor friend of mine who lives near me in Mill Valley, who is also a shaman, suggested I try them. They contain a neurotrophic growth factor. The effect is subtle but I feel like it makes my day a little bit lighter and my focus a little bit better.”
Mushrooms are a mixture of proteins, unsaturated fatty acids, carbohydrates, and a variety of trace elements. One of the active ingredients in the Neuroshroom mix is Hericium erinaceus polysaccharides (HEP). It increases levels of acetylcholine in the brain (the same system that rivastigmine affects), which is normally secreted in great quantities during stage 4 sleep (as we saw in Chapter 11, on sleep). The dreamy quality we associate with sleep, or being in certain altered states, is mediated by this neurochemical. HEP rapidly increases gene expression of neural growth factor in the hippocampus, the seat of memory. This could simultaneously improve the storage of new memories and the retrieval of old ones—even old memories that you thought were long gone.
HEP also has neuroprotective and neuroregenerative qualities, allowing for the repair of damaged nerves and the growth of new ones. In one study it improved overall cognitive performance and was even effective in people up to age eighty who are suffering from mild cognitive impairment. There’s also some evidence that it improves immune-system function and can form a natural immunological resistance to cancer. Some studies have shown that it reduces depression and anxiety.
Another ingredient in the mushrooms Weir takes is Cordyceps militaris, which has been shown to eradicate fatigue and boost energy levels. A third ingredient is Ganoderma lucidum, which has been shown to reduce fatigue in breast cancer patients. It appears to have neuroprotective effects on the hippocampus and promotes cognitive function in mouse models of Alzheimer’s disease. It also has anti-inflammatory properties and reduces oxidative stress. A 2019 study examined nearly seven hundred adults aged sixty and over in Singapore and found that participants who consumed more than two portions of mushrooms a week reduced their odds of having mild cognitive impairment by 50 percent, and this was independent of age, gender, education, cigarette smoking, alcohol consumption, hypertension, diabetes, heart disease, stroke, physical activities, and social activities.
Bacopa
Bacopa monnieri, water hyssop, is a plant native to southern and eastern India, Australia, Europe, Africa, Asia, and South and North America, including parts of the southeastern United States. There is emerging evidence that it can improve higher-order cognitive processes such as learning and memory and, in particular, has a significant effect on retaining new information, even among older adults. It appears that it does this by regulating tryptophan hydroxylase and serotonin transporter expression. Capsule formulations of the extract are available, and traditional Indian cooking uses it as an ingredient in food. It is fat soluble so should be taken with a meal. It takes time to work—don’t expect a noticeable effect before twelve weeks.
The treatments mentioned in this section, such as Neuroshrooms and bacopa, and the omega-3 fatty acids mentioned in Chapter 9, on diet, are foods, of course, not “medication.” What exactly is the distinction between diets and medicine, given that the food we consume can also affect our health in a similar way to pills or medication? It isn’t clear. To some degree, diet and food choices are a form of medicine. (Perhaps my grandmother was right about the chicken soup.)
Revisiting the 1960s
Recreational Drugs
Many members of the Woodstock generation took drugs in an effort to expand their consciousness, for spiritual enlightenment, to feel closer to nature, or just for fun. The hallucinogenics (aka psychedelics), such as peyote, mescaline, LSD, and psilocybin, were most closely associated with these uses, whereas cocaine, amphetamines, barbiturates, and quaaludes were associated less with mind expansion and more with mood modification, energy-state manipulation, or just experimentation (“Hey, man—try this”). The problem is that all of these get lumped into a single category of “drugs” and yet they are very different substances with dramatically different effects, both biologically and psychologically.
For current members of the Woodstock generation, now in their sixties and seventies, judicious ingestion of hallucinogenics can, for some, be cognitively and emotionally enhancing. Physicist Leonard Mlodinow reports that experiences with cannabis can enhance an ability he calls “elastic thinking.”
There are certain talents that can help us, qualities of thought. . . . For example, the capacity to let go of comfortable ideas and become accustomed to ambiguity and contradiction; the capability to rise above conventional mind-sets and to reframe the questions we ask . . . to overcome the neural and psychological barriers that can impede us.
And the effects of cannabis are most pronounced on those who are less creative to begin with. In other words, it acts as a perception, creativity, and insight equalizer.
Psilocybin users report having “mystical experiences” and terminal cancer patients have found it helpful in reducing the anxiety about their impending deaths. A single dose of the drug in older adults caused a lasting, positive change in Factor V of personality—Openness to Experience. Science writer Michael Pollan’s book How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression, and Transcendence explores a kind of resonant echo of some of the more idealistic goals for the use of psychedelics that drew many to them in the 1960s.
I got intensely curious about the experiences of people I was interviewing—stone-cold atheists telling me they’d had a profound spiritual journey, and people who’d been terrified of death completely losing their fear. It was clear there was so much more to learn about these extraordinary molecules—at the level of neuroscience, but also at the level of personal experience.
This led Pollan to experiment with them himself, and in the book, he describes these recent experiences as a sixty-year-old taking hallucinogenics for the first time, which he says improved his life. He emphasizes the importance of having a guide to help you prepare for the experiences, and an integrator to help you process them—in Pollan’s case, the integrator was his wife. Pollan summarizes:
The journeys have shown me what the Buddhists try to tell us but I have never really understood: that there is more to consciousness than the ego, as we would see if it would just shut up.
Psychedelics also helped him feel more open, more patient, and more connected to nature. In effect, it seems to me, they helped him to hit the reset button, to stop taking mundane things in his life for granted, and to approach the world and his life in it more like a younger person would. If you are interested in learning more about these, Pollan’s book is a good place to start, and there is a nonprofit informational website, Erowid.org, that provides information about plant-based psychoactives.
I want to be careful here and point out that these are powerful drugs and they are not without risks, especially for people who may have psychiatric problems. (Then again, everything we take has risks.) David Nutt, a neuropsychopharmacologist at Imperial College London, calls hallucinogenics “among the safest drugs we know of.” Nevertheless, if you have latent tendencies toward mental disorders, drugs can put you over the edge, sometimes to the point of no return. This is what may have happened to Brian Wilson, the creative genius behind the Beach Boys, who ended up with schizoaffective disorder. In another case, an artist who took powerful drugs for many years (who shall remain unnamed due to privacy considerations) suffers from paranoid delusions, thinking that CIA agents are living in the basement of their home, and delusional parasitosis, thinking that thousands of microscopic bugs are under their skin, and that snakes inhabit every bed in the house. In the latter case, these delusions have not interfered with creativity or productivity, and the artist refuses to acknowledge that these delusions are products of the mind.
My own observations of people who have taken LSD multiple times have caused me to believe that there is a more or less fixed number of times that you can take it with no ill effects, and that this number is unique to each person and their own psychological makeup. The problem is that you don’t have any way of knowing what that number is. For some people it may be only a handful of times; for others it could be one hundred. I know many people who took multiple LSD trips and were fine, until one day, suddenly, they weren’t. By the time you’re sixty or seventy, though, you probably know yourself pretty well. You know if you’ve heard voices in your head or had manic-depressive episodes, paralyzing self-doubt, or suicidal thoughts. If you have had any of these, drug experimentation is probably not for you.
Microdosing
I have been spending time in Silicon Valley since I first attended Stanford there as a student in 1974. I still go back regularly to give talks, meet with colleagues at Google, or visit friends. It has always been odd, but recently it has gotten weirder. There was a casual, laid-back quality to it in the 1970s that has morphed into an intense desire everyone seems to have to outperform everyone around them in every domain possible. You see it in the frenetic way people drive, or in the tech workers eating in restaurants while manipulating two or three smartphones at once. Silicon Valley these days is full of people in their twenties and thirties who are looking for anything they can do to gain a competitive edge.
So it was no surprise to me when Forbes published an article in 2015 (following a report in Rolling Stone) that twentysomethings in Silicon Valley had started taking psychedelics in microdoses to enhance creativity and productivity. (In The Good Fight, Diane Lockhart, played by Christine Baranski, experiments with microdosing psilocybin.)
Microdosing is just taking small amounts of substances, such as LSD, that are believed to be below the threshold of any noticeable effect, typically 5 to 10 percent of a normal dose. An ideal dose is “when you feel good, you’re working effectively, and you’ve forgotten that you’ve taken anything.” Many of the reported beneficial effects associated with regular doses of hallucinogens are reported for microdoses of them but, understandably, in more controllable and less spectacular form. Users report enhancements of creativity, reductions in fear and anxiety, and lifting of mood. Microdosers scored lower on measures of dysfunctional attitudes and negative emotionality and higher on measures of wisdom, open-mindedness, and creativity, as well as a reduced incidence of suicide. Regular low doses of THC, the active ingredient in cannabis, were found to reverse memory deficits and restore cognitive function in old mice, a promising avenue for future human experiments.
Devices
Earlier, I mentioned neural implants. As futuristic and crazy as they sound, they already exist. Cochlear implants are surgically implanted in people who are born deaf and whose hearing deficit is due to problems in the inner ear, inside a snail-shaped structure called the cochlea. When you hear any kind of sound, your eardrum wiggles in and out with the frequency of the sound. The cochlea translates this in-and-out motion into electrical signals that it transmits to the auditory cortex. They have been in use since the first one was implanted at Stanford University in 1964, and today there are an estimated six hundred thousand people who have them worldwide.
Other forms of neural implants have been in use to control epilepsy, treat Parkinson’s, and lift clinical depression. The downside to them is that they are invasive—they require surgically opening the skull and implanting something in your brain (and really, is there anything more invasive than that?). But as robotic surgery becomes more refined, and more commonplace, we may soon see the sorts of implants that seemed fanciful in the past—memory enhancement by stimulating hippocampal pathways (or more intriguingly, by stimulating selectively those emotional pathways that facilitate memory storage and retrieval), or attentional networks in the prefrontal cortex, insular cortex, and anterior cingulate.
As I am writing this, a paper was just published in Nature Communications by a team at the University of Pennsylvania led by Michael Kahana. They developed a neural implant that increased memory encoding and recall of newly presented information, a possible first step toward alleviating the most devastating symptoms of Alzheimer’s disease and dementia. An innovative feature of their implant is that it doesn’t fire all the time—it studies neural firing patterns in the brains of implantees and sends electrical signals only when the brain appears to be having trouble encoding new information, and it remains dormant the rest of the time. (In this way it resembles a pacemaker for the heart.)
“We all have good days and bad days, times when we’re foggy, or when we’re sharp,” said Kahana. “We found that jostling the system when it’s in a low-functioning state can jump it to a high-functioning one.” Kahana thinks that future research could preferentially target the retrieval of old, forgotten memories as well.
Bionics
Bionic products can enhance our sensory receptors, delivering information to us that we might not otherwise receive. They can allow us to do things with our bodies that we couldn’t do before, and through embodied cognition, this could enhance our mental lives. Bionics are becoming increasingly sophisticated and people’s attitudes toward them are changing. The technology, driven in part by the need to serve war veterans with amputations, has allowed us to provide functionality. We’ve now seen Olympic runners using prosthetic legs. One recipient of a prosthetic hand skydives, chops vegetables, and can even use chopsticks, and an experimental “sensory” hand is allowing another amputee to feel the shape and composition of objects for the first time since his amputation.
Samantha Payne, COO of Open Bionics, a prosthetics company, says that the commercialization of this technology is just around the corner. “All we need is smaller motors, better batteries; once the components advance, the products will come to market. . . . I feel there has been a huge cultural shift. We’ve found a very distinct gap between younger amputees and those aged forty and older. The older ones wanted a bionic hand as close to real skin as possible. The younger generation all want highly personalized hands. We’ve moved from a society that valued conformity to one that celebrates individuality. People are more willing to experiment with their body. It’s wide open.”
Brain implants are being used to help quadriplegics type or move paralyzed limbs with their minds. One twenty-four-year-old broke his neck in an accident and hadn’t been able to move for six years. A neural implant now lets him move his previously paralyzed right arm enough that he can play video games. Imagine a neurosurgeon whose hands are too shaky to operate but who can think about what he wants to do while a robot does it.
Zoltan Istvan is a controversial figure who self-identifies as part of the transhumanist movement, a group of individuals who seek to augment the human body and mind with implants as a way to greatly enhance human intellect, achievement, and physiology; some see it as a road to immortality. So far followers have not done much beyond radio-frequency chip implants that allow them to unlock doors and start cars, a skull implant to allow listening to music wirelessly (the neurojack, the writer Sandy Pearlman once called it), and magnetic implants that allow people a sixth sense to know when metal is nearby. Another enthusiast, Neil Harbisson, had an antenna installed in his head that allows him to hear color waves, sensing colors he wouldn’t normally experience, such as infrared and ultraviolet. He also has a Bluetooth implant in his head. “I can either connect to devices that are near me,” he says, “or I can connect to the internet. So I can actually connect to anywhere in the world.”
But before any of these far-out-sounding devices become commonplace, a real revolution is under way for diagnostics. Many of us already carry around or wear devices that track our movements and heart rate, and these communicate with smartphones to create an exercise record. In the coming five years, other wearables—patches, sensor-lined shirts, bracelets, and, yes, tiny implants, will be able to collect data that signal whether your blood sugar levels are off, whether you’re dehydrated, or whether you’re about to experience a seizure or migraine. The technology exists for these already. Serena Williams has been seen in ads wearing a patch manufactured by Gatorade that reads levels of chloride in sweat to indicate total electrolyte loss, an indicator of dehydration.
Meditation
A great number of claims have been made for meditation, and if you don’t meditate yourself, its adherents can seem annoyingly zealous about it. Meditation is not going to cure cancer or reverse Alzheimer’s disease or Parkinson’s disease. It’s not going to bring you fame beyond your wildest dreams. But as part of a healthy lifestyle, it can help to make your brain more effective and more efficient.
I asked the Dalai Lama, “In the future, suppose that you’re eighty-five years old, ninety years old, and you feel that your memory is getting bad. It could happen. Would you take a drug from a doctor that would help your memory improve?”
He replied, “I don’t know. I feel the training of mind through meditation is really what helps the sharpening of mind. And that is also helpful, you see, for keeping memory strong.” It also helps him to stay mindful of what is most important to him and to tame his own impulses. He continues . . .
I love to talk. I usually tell people one of my weaknesses is once my mouth opens blah blah blah blah blah, like that. So the time gets always from me. I think the main source of my strength is that I’m a Buddhist monk. Every day is filled with praying and thinking; my body, speech, and mind are dedicated to the well-being of others. Not just in this life, but as long as space remains, as long as sentient beings remain, I will remain to serve. So that really gives me inner strength, and I dedicate that strength. A mental life so full of enthusiasm also has a beneficial effect on the body.
He has worked closely with neuroscientists to better understand the brain basis of this. Meditation involves maintaining attention on your immediate experience in the moment and in the world, and away from distractions such as self-referential thinking and mind wandering. It helps to train you to avoid thinking about something other than what you’re currently doing, taming the default mode network that I mentioned earlier. Meditation reduces activity within the default mode network and increases connectivity between it and regions of the brain that are implicated in cognitive control—that is, controlling our thoughts: the dorsal anterior cingulate and dorsolateral prefrontal cortices. The result is that meditation simultaneously turns down the default mode’s pull on our attention, while streamlining and honing the network. Increased connectivity between the prefrontal region and the default areas also has an anti-inflammatory effect by reducing cytokines.
Neuroscientist Richard Davidson from the University of Wisconsin–Madison has found that monks show greater gamma waves during compassion meditation. Gammas are the signature of neuronal activity that knits together far-flung brain circuits. They underlie higher-level mental activity, such as consciousness. The mechanism is that gamma waves cause synchronization of neurons, and the resulting unity of firing leads to a unity of consciousness. Imagine the beautiful, mystical symmetry: An activity that can make us feel one with the universe is that which makes our billions of neurons fire as one.
Long-term meditators show structural changes in the brain as well, including increases in cortical thickness, hippocampal gray-matter density, and the size of the hippocampus. Additional changes are enlargement of the insula, somatomotor areas, orbitofrontal cortex, parts of the prefrontal cortex that help in paying attention and in self-awareness, and regions of the cingulate cortex instrumental in self-regulation and staying focused.
Even brief meditation reduces fatigue and anxiety and increases visuospatial processing, working memory, and executive functioning, and in many cases these benefits persist even after meditation practice is stopped. Meditators show lower levels of cortisol following a stressful task and decreased inflammation, not just during meditation, but day-to-day, and the benefits show up after as little as four weeks (or thirty hours) of mindfulness practice.
Davidson also showed that meditation may drive benefits at the level of genes. After an eight-hour day of practice, a group of long-term meditators (with about six thousand lifetime hours of practice) showed a significant downregulation of inflammatory genes. This decrease, if sustained over a lifetime, might help fight diseases with onsets marked by chronic low-grade inflammation—cardiovascular disorders, arthritis, diabetes, Alzheimer’s disease, and cancer. A handful of other pilot studies support the finding that meditation seems to have epigenetic effects. Loneliness triggers higher levels of pro-inflammatory genes; meditation can both lower those levels and decrease feelings of loneliness, as the Dalai Lama found when he meditates on how he is just one of 7 billion people on the planet (recall his remarks about this in Chapter 1, on individual differences). Mindfulness meditation is also associated with increased telomerase. In people with mild cognitive impairment and early-stage Alzheimer’s, meditation has been shown to slow or reverse cognitive decline, reduce stress, and increase quality of life, along with the neuroplastic changes I just described.
I’ve come to see a future in which we can plan ahead to fend off some of the adverse effects of aging; a future in which we can harness what we know about neuroplasticity to write our own upcoming chapters the way we want them to unfold; a future in which a combination of medical developments and healthy lifestyle choices can temper or reverse the effects of cognitive decline, depression, and loss of energy that we have for too long assumed were a nonnegotiable part of the aging process. That future is to a large degree already here for those who are willing to harness it.