The Happiness Quest

Of all the prophecies in Aldous Huxley’s dystopian classic Brave New World, none is as conspicuous by its present-day absence as Soma, the State-produced happy pill that takes citizens on enjoyable, hangover-free holidays. Though mankind has experimented with euphoria-producing substances for millennia, a safe shortcut to psychological well-being has proven elusive and will likely remain so, despite the incalculable market potential for such a molecule.

After all, today’s drugs for depression (like Prozac, Zoloft and Paxil) and anxiety (like Xanax, Ativan and Valium) account for billions of dollars in annual sales. Yet these pills are only marginally effective for many patients and have a wide range of side effects. The lack of better mood enhancers doesn’t stem from a dearth of commercial potential, but rather from inadequate understanding of the brain.

Relief from depression is not the same as happiness, but it is a step in the right direction, notes British economist Richard Layard, author of Happiness: Lessons from a New Science (Penguin 2005). As a Labor member of the House of Lords, Layard fought for, and got, increased funding for mental health coverage, including cognitive behavioral therapy for depression. He says he is inspired by the 18th-century philosopher Jeremy Bentham, who posited government ought to focus on creating the greatest happiness for the greatest number.

“The basis for getting back to the Enlightenment view has been set by developments in science,” Layard says. Neuroscientists “have discovered the areas in the brain that correlate to feeling good or feeling bad, and can measure it. That means happiness is actually an objective phenomenon.”

Much of the research showing that happiness or depression correlate to measurable activity in specific regions of the brain originated in the lab of Richard J. Davidson, a pioneer in affective neuroscience and professor of psychiatry and psychology at the University of Wisconsin-Madison. One of his most startling discoveries has been that mindfulness meditation, a secular contemplative activity based on ancient Buddhist practices, not only improves mood but creates lasting structural change in the brain.

The flip side of employing silent contemplation to improve one’s emotional profile is a growing body of work showing the positive impact of exercise on the brain. Multiple studies have shown that daily vigorous aerobic exercise not only lifts mood but can be an effective treatment for attention deficit, anxiety, memory loss and addiction. While narcotics or antidepressant drugs typically boost one or two brain chemicals, like dopamine or serotonin, exercise increases the supply of many substances implicated in mood, and it does so without harmful side effects, except perhaps sore muscles.

What aerobic exercise and mindfulness meditation have in common is you have to work at them, every day and forever. It’s not like taking a pill, but the effects are potentially far more lasting. Both may in fact be addictive, in the sense that practitioners tend to increase the intensity of their workouts or the duration of their meditation over time and feel ill at ease when they stop.

A Brief History of Euphoria

Humans have been getting high for a very long time. According to the Drug Enforcement Administration, the earliest reference to opium growth and use is in 3400 B.C., when the opium poppy was cultivated in lower Mesopotamia (Southwest Asia). The Sumerians referred to it as “hul gil”: the “plant of joy.” The Sumerians soon passed it on to the Assyrians, who in turn passed it on to the Egyptians. As people learned of the power of opium, demand increased and many countries began to grow and process it, expanding its availability and lowering its cost. Opium cultivation spread along the Silk Road, from the Mediterranean through Asia and finally to China, where it was the catalyst for the Opium Wars of the mid-1800s.

Coca has been used as a medicine and stimulant for over 4,000 years in what is now Colombia, Peru and Bolivia. The drug was considered a safe stimulant and nerve tonic, but cocaine’s addictive and destructive properties became apparent within 30 years of its introduction as a pharmaceutical. Early in his career, Sigmund Freud was a vocal proponent of cocaine, taking it himself and promoting its use to patients. Cocaine use jumped in the 1970s, when it was touted as the champagne of drugs because it was expensive, high-status and said to have no serious consequences. Cocaine remains a huge business: Colombia produces an estimated $400 million of cocaine each week, the DEA says.

Of course, opium and coca derivatives have devastating effects on the individuals and communities that use them. Heroin and cocaine make the user “happy” for a time, but rapidly become addictive, and with continued use make users wretched and ill. Opiates and cocaine have different mechanisms of action, but both increase the concentration of dopamine, an important neurotransmitter, in the nucleus accumbens, known to laypeople as the “reward center” of the brain. Because the brain, like most organs, seeks homeostasis, it down-regulates its dopamine response, increasing the amount of drug a user needs to feel euphoria and leading to severe depression and other path-ologies when the drug is withdrawn.

“If you define happiness as euphoria, we have lots of happy drugs like cocaine,” says Stanley D. Glick, Ph.D., M.D. and director of the Center for Neuropharmacology & Neuroscience at Albany Medical College in New York. “But there are no drugs that have just one effect. Advertisements tell you the good effects first, then a whole host of negatives in the small print. Every drug works on multiple places in the nervous system, and it’s impossible to get one that just works on the one you want. That’s how the nervous system is structured.”

Benzodiazepines, a class of sedatives that includes Xanax and Ativan, are among the most commonly prescribed drugs, and are used to treat anxiety, insomnia, agitation, seizures, muscle spasms, and alcohol withdrawal, and as a premedication for medical or dental procedures. But these drugs also have a potent short-term euphoric effect and are among the most frequently abused prescription medicines. They work by enhancing the effect of a neurotransmitter known as gamma-aminobutyric acid (GABA), which is the same mechanism triggered by alcohol. Indeed, psychiatrists sometimes refer to Xanax as “an extremely dry martini.” Benzodiazepine addiction is common, and withdrawal has been described in the medical literature as more difficult and dangerous than kicking heroin.

Today’s antidepressants do not produce euphoria and are not “addictive” in the conventional sense of that word. But they usually take a few weeks to work, don’t work in everybody, and may require a long, gradual withdrawal period to avoid unpleasant effects. Though they are known to boost the amount of the neurotransmitter serotonin in the brain, no one knows exactly how they work, which has hindered the search for better antidepressants with fewer side effects.

“Almost everything we have today is just an iteration of drugs discovered in the ’50s by accident,” says Steven Paul, former director of the National Institute of Mental Health, now a partner with Third Rock Ventures. “In 1993, when I left the N.I.H. and went to Lilly, there was great excitement about these drugs. They were the most commercially successful drugs of all time, even including the statins. Why was that? They weren’t that great. They do work somewhat. And the alternatives are definitely not great. If you could come up with something that’s just 20 percent better than Prozac or Cymbalta, it would be a blockbuster times 10. But right now, you see a lot of big companies getting out of this area.”

The Mindful Way To Mood Enhancement

FDA officials say evaluating drugs for depression is complicated because it is a relapsing and remitting disease, meaning that it comes and goes, even without treatment. Ketamine is particularly problematic because it has become a popular party drug, taken for its hallucinatory effects. But what if there were another modality to treat drug-resistant depression, one with no side effects, that did not require regulatory approval? There is.

In a series of trials initiated in the United Kingdom and since duplicated at many sites, patients who had failed multiple rounds of different antidepressants responded to mindfulness-based cognitive therapy (MBCT). A group intervention that lasts eight weeks, MBCT draws upon cognitive behavioral therapy, which teaches patients to replace “errors” in thinking, such as overgeneralizing, magnifying negatives and “catastrophizing” with more realistic and effective thoughts. It also employs mindfulness-based stress reduction, a meditation program developed by Jon Kabat-Zinn at the University of Massachusetts Medical School.

MBCT is not a cure, and is best begun when depression is in remission, as its developers, Mark Williams, John Teasdale, Zindel Segal and Kabat-Zinn, caution in The Mindful Way Through Depression (Guilford 2007). But none of the drugs available today or currently under development are cures either, and unlike them, mindfulness can be practiced for life without side effects. And while antidepressant drugs do nothing to elevate mood in people who are not clinically depressed, mindfulness can provide an emotional lift to anyone.

In The Emotional Life of Your Brain (Hudson Street Press 2012), Professor Davidson of the University of Wisconsin-Madison and Sharon Begley describe how each of us has an emotional style, which determines how we respond to the pleasures and vicissitudes of life. This style has six components, each of which exists along a continuum: resilience, outlook, social intuition, self-awareness, sensitivity to context, and attention. Davidson suggests that we can adjust each of these emotional components up or down through mindfulness work and conscious effort, despite whatever genetic tendencies we may have toward happiness or melancholy, social skill or shyness. Using technology such as functional magnetic resonance imaging (fMRI), Davidson has documented changes in brain activity from these interventions.

These changes are promoted by “neurally-inspired behavioral interventions,” says Davidson. “These are behavioral interventions that can potentially produce more specific effects than any medication can. Meditation, as well as any other kind of experience that can change behavior, has to change the brain. These changes are both functional and structural. The implication of this work is we can take some responsibility and potentially push the brain in more positive directions.”

Were such results confined to Davidson’s lab, they would still be remarkable. But together with the work of Kabat-Zinn and Daniel Goleman, author of Emotional Intelligence, Davidson’s studies inspired a young Google engineer, Chade-Meng Tan, to develop a program to improve emotional intelligence there. As Meng writes in Search Inside Yourself (Harper One 2012): “Essentially, because emotion has such a strong physiological component, we cannot develop emotional intelligence unless we operate at the level of physiology. That is why we direct our mindfulness there.” So successful has Search Inside Yourself been at Google that Meng and his colleagues now offer it broadly, in a traveling series of classes.

There’s one problem with mindfulness meditation, which generally starts with focusing your undivided attention on your breathing. It’s really hard to do, as this author has discovered firsthand. Left to its own devices, the mind goes everywhere at once.

“That’s where most people typically start,” Davidson tells me. “And it’s great that you actually noticed that your mind is all over the place. That is actually the first step of awareness. It’s important to start with very short periods of practice, even as short as two minutes, and do that a few times a day, and gradually the mind will begin to settle. I believe that will take time. The notion of asking people to sit for half an hour the first time is wrong. Two minutes is much more doable and doesn’t set them up to fail.”

Running to Happiness

Exercise, it seems, is the cure for all ills. So many books and articles now tout exercise as the prevention or treatment for so many diseases that it’s hard to hear the signal for the noise. But it turns out that aerobic exercise is indeed one of the most empirically well-documented methods to increase neuroplasticity, the ability of the brain to change in sustainable ways. Whether that change will necessarily be for the better is open to question, but a growing body of evidence suggests that in regard to mood, the answer is positive. The improvement is often immediate.

Much of the writing about exercise comes from authors with rather scant medical credentials, but an exception is Spark: The Revolutionary New Science of Exercise and the Brain, by John J. Ratey, M.D. (Hachette 2008). Ratey, an avid runner, is also a practicing clinical psychiatrist and professor at Harvard Medical School.

Ratey’s premise is that exercise’s feel-good effect is much more profound than burning off stress or boosting endorphins, the chemicals behind the so-called runner’s high. “The real reason we feel so good when we get our blood pumping is that it makes the brain function at its best,” he writes. “In my view, this benefit of physical activity is far more important — and fascinating — than what it does for the body. Building muscles and conditioning the heart and lungs are essentially side effects. I often tell my patients that the point of exercise is to build and condition the brain.”

Most of human evolution took place during the hunter-gatherer period, where daily movement was crucial to acquiring sustenance and escaping predators, but today’s world of technology, and easy access to calories encourages sedentary behavior.

Much as our doctors encourage us to exercise, it’s easier not to, and most people don’t. This idleness is a disruption of our nature, Ratey argues, and poses a threat to our survival. In addition to the epidemics of obesity, diabetes and heart disease, inactivity is killing our brains, he writes, literally shriveling them.

Like Davidson, Ratey has done the lab work to prove his thesis, though in his case he is more often measuring physical evidence, like the presence of chemical neurotransmitters or the size of brain components, in research animals, rather than monitoring electrical activity in human brains. Yet his findings are equally remarkable. “It turns out that moving our muscles produces proteins that travel through the bloodstream and into the brain, where they play pivotal roles in the mechanisms of our highest thought processes,” he writes.

Outside the lab, as a practicing psychiatrist, Ratey works with patients suffering from anxiety, depression, attention-deficit disorder and age-related memory loss. In each of these pathologies, he has used an exercise regimen to bring significant relief, even after prescription drugs have failed. Moreover, he has been able to document specific molecules that modulate symptoms. One of them is atrial natriuretic peptide, or ANP, which is secreted by heart muscles during exercise, travels through the blood-brain barrier and dampens the sympathetic nervous system’s response to alleviate anxiety.

Keep in mind that Ratey’s exercise prescription is not the gentle walking recommended by government health advocates in the vain hope of getting dedicated couch potatoes on their feet. He’s talking about serious sustained aerobic activity. That means running, cycling or working out at a level that raises the heartbeat to 70 to 85 percent of its maximum rate, for 20 to 30 minutes at a time, every day of the week.

The good news is that while it may be hard to get started, such a workout rapidly becomes a habit. Is aerobic exercise addictive? Maybe so, if the growing popularity of distance running and hyper-intense workout programs like CrossFit is any indication. But for most of us, daily vigorous exercise does nothing but good, and again, in this author’s experience, it will make you happier.

Mixing Modalities for Best Outcomes

There are of course many people who meditate and exercise with equal devotion, and it is easy to imagine that they enjoy a particularly serene equanimity. Positive psychology, the discipline of learned optimism popularized by University of Pennsylvania psychologist Martin Seligman, makes no claim of changing brain activity, structure or chemical balance, but surely its recommended conscious acts of generosity and gratitude are compatible with and complementary to a mindfulness practice. Might true happiness be found mixing up all of these non-pharmaceutical medicines?

“One of the intriguing possibilities is, if you increase plasticity through exercise, it may only be beneficial if we accompany that plasticity with positive mental behavior,” says Professor Davidson. “If you engage in aerobic activity and do it at the same time that you’re filling your mind with positive thoughts, that may be especially beneficial. But that has never been tested. It’s pure speculation.”