The Would-Be Wonder Drug
To convey the nature of, and the difference between, these two emotions of reward and contentment, and how these emotions have been hacked, I must first convince you that that these and other emotions are rooted in the workings of the brain. So let me now give you two examples of the power and scope of these three pathways on your emotional state, and how manipulating them either externally (using a drug) or internally (through a wayward passion) can take a simple positive emotion and turn it into a weapon of mass destruction. I offer you Exhibit A: rimonabant.
If it weren’t for reward or the promise of it, we’d all commit suicide due to deep and inconsolable misery. This hypothesis was put to the test a decade or so ago with the release in Europe of the anti-obesity drug rimonabant (Accomplia, Sanofi-Aventis). This medication looked extraordinarily promising right up to and through its approval for general use by the European Medicines Agency (the European equivalent of our FDA). The first endocannabinoid antagonist, rimonabant was the anti-marijuana drug. As it turns out, many of the brain pathways outlined above possess a receptor for tetrahydrocannabinol (THC), the active compound in marijuana. When THC binds to this receptor, known as the CB1 receptor, it heightens mood and alleviates anxiety, which partially explains why people become so giddy when they smoke pot; it also heightens the transduction of pleasure, which explains why so many pot smokers have sex after they partake; and it explains why people get the munchies afterward. Why would Mother Nature put a receptor for marijuana in our brains anyway? As it turns out, we make our own endogenous brain compound, called anandamide, which naturally binds to that CB1 receptor and which keeps us eating and renders most of us semi-functional in social groups, even if we’re not smoking pot. But in those who toke, anxiety is thrown to the wind along with every inhibition it suppresses, leaving plenty of room for pleasure.
Rimonabant blocks this CB1 “feel good–munchies receptor.” This drug was approved by the European Commission in 2006. As a weight-loss drug, it worked very well and mitigated the co-morbidities of obesity.1 The data were incontrovertible. Lots of people lost lots of weight. Their appetites went down and they stopped eating junk food. They lost all interest in food; it just didn’t provide pleasure anymore. In fact, they derived no pleasure from anything. Rather, their anxiety increased markedly. For five years prior to approval, rimonabant was all anyone in the obesity field could talk about. Rimonabant was going to be “da bomb.” And then it bombed: European post-marketing data showed that 21 percent of the people who took it became clinically depressed, and many of them committed suicide. Sure, you will lose weight if you don’t get pleasure from eating. But you also lose your motivation for any reward, which means you lose your motivation for life. Suffice it to say, it was rapidly withdrawn from the European market and the U.S. FDA never approved it.
What does the rimonabant lesson teach us? First, it clearly demonstrates that the biochemistry drives the behavior—and the emotions. Rimonabant, by blocking the CB1 receptor, led many into clinical depression, and led to suicide in a few. Anxiety is one of the chief antagonists to both reward and happiness. No wonder marijuana use has skyrocketed, to take the place of alcohol as the preferred method to reduce anxiety,2 leading to its legalization in many states. After all, which is more dangerous to society at large, marijuana or alcohol? Since most statehouses are now controlled by baby boomers, the switch is not surprising. Second, it shows us that reward-seeking behavior is a double-edged sword. It’s the factor that ensures the survival of the species, but it clearly doesn’t ensure the survival of any one individual. In fact, just the opposite. Stifle pleasure (with rimonabant) and we plunge into the depths of despair—yet too much pleasure, which we will learn in Part II, is the underpinning of the addiction response, and also can drive us to the depths of despair. You can think of reward as having a bell-shaped curve (see Chapter 3). There’s a sweet spot in the middle. Anywhere else on the curve and you play with fire. And third, it shows us that things that interfere with the normal functioning of the limbic system will increase your anxiety, which will secondarily reduce your pleasure; and when pleasure is reduced severely, it can cause depression and even suicide. No pleasure means no happiness. Pleasure is the straw that stirs the drink. Happiness is the drink. Anxiety melts the ice cubes. We all need reward, because reward keeps anxiety at bay . . . for a short time. Since the rimonabant debacle, Big Pharma has conducted many forays into blocking the endocannabinoid system, thus far all coming up empty. On the other side, medicinal marijuana dispensaries are popping up like weeds.
Not Feeling the Love?
Now let’s turn our attention to a set of emotions with which virtually everyone has some level of experience—a set of emotions that clearly parse the difference between the reward and contentment pathways, and how conflation of the two can get you into some serious hot water. I offer you Exhibit B: love.
“I love you, now let’s make love.” Two different statements, stemming from different biochemical reactions in the brain, with little in common except the word. Love is the harbinger and result of contentment; sex is driven by our need for reward.
Amoeba engage in asexual reproduction. They don’t need a limbic brain system. They don’t even need a brain. But mammals do, and they can’t do it alone. They not only need a partner, they get off on it. Friction in and of itself is not necessarily a pleasurable experience, but throw in a few sex hormones and you can generate quite a party. And that’s why mammals have genital nerves that transmit what would otherwise be an unwelcome sensory annoyance anywhere else on the body as exciting foreplay instead. Even male rats engage in foreplay before copulation and their eventual intromission (the rat version of ejaculation). But this happens only under the influence of the male hormone testosterone. No testosterone, no interest. And female rats arch their backs to attention (known as lordosis) to allow for copulation whenever their flanks are stroked, but only under the influence of the female hormone estrogen. It’s the same with humans, minus the lordosis. Think about it. Why in the world would post-pubescent young adults otherwise endure the pain of possible rejection, the idle chitchat, the overpriced bar bill, the smelly pheromones, and the bad breath, if there wasn’t a really top-notch reward at the end of it? There had better be a big payout. All because of testosterone and estrogen. Before sex hormones kick in at puberty, it’s all cooties. And then it’s all angst. Again, the biochemistry always comes first.
Love has been around for all of human history, hasn’t it? Maybe not . . . as Tina Turner admonished us back in 1984, “What’s love but a secondhand emotion?”—suggesting that it has hardly been a primary endpoint. While this sentiment may not garner me a top spot in the romantic bastion of chick lit, it really is all about the biochemistry.
One of the seminal problems parsing the pathways of love is yet another etymological problem. The Inuit have fifty-six names for snow, but we have only one. Similarly, the Greeks had three words for love, which relate more closely to the biochemistry than our one word. Eros is the intense infatuation you feel for your partner at the beginning of the relationship, often tied up in sexuality, and based on testosterone, estrogen, and suspension of reality. It’s a hot mix of increased dopamine in the reward pathway, but with a reduction of serotonin in the happiness pathway.3 Biochemically, it resembles a transient obsession. Philia is the more “chill” love you feel toward friends, family members—the love (and frustration) you feel toward your parents and your long-term spouse. The mediator of love between a mother and her children is a different hormone called oxytocin and works through a different emotional pathway unrelated to the three delineated in this chapter.4 Animal studies where oxytocin is either genetically knocked out or pharmacologically inhibited demonstrate that an otherwise caring mother becomes completely disinterested in her offspring, often to the point of allowing them to starve to death.5 We will see in Chapter 14 how this pathway can be compromised by dopamine, even in humans. A
nd finally, agape is the love one feels for God, but when hijacked by dopamine, resultant zealotry can lay waste to entire peoples in the name of religion (see Chapter 16).6 So is love an emotion? Or is it just the outward manifestation of some wayward biochemistry? Ultimately there’s no difference.
Using new imaging techniques like PET scanning, we can now peer into the brains of people who are in love, i.e., infatuated. In this state, dopamine charges like a bull into the china shop of the PFC, that part of the brain that’s supposed to keep you on an even keel, so they become impulsive and aggressive (see Chapter 4).7 At the same time, serotonin levels fall, reducing any feelings of contentment that might modulate their angst. People suffering from infatuation exhibit anxiety, stress, and obtrusive thinking—the emotions and the behaviors of obsessive-compulsive disorder, a psychiatric condition associated with low serotonin levels.8
Love Letters
Now some of you are likely saying, Wait, it’s the relationship, the meaningful connection to a member of the opposite (or same) sex, that makes the process worth it, and which drives the behavior. Obviously, you’ve never been on a Tinder date. If you ever thought pleasure and happiness were the same, sex will teach you otherwise. Sex brings reward to a relationship (dopamine) and can mature into contentment (serotonin) if you’re lucky. But contentment doesn’t drive survival of the species or evolution. Reward does. We don’t know if love is uniquely human. We can’t tell if rats are happy. We don’t even know if primates are happy. We do know they’re social. We know they congregate, and we know they have alpha males and subordinates, which is a manifestation of their degree of response to hierarchical stress. We know they demonstrate empathy, which suggests they do have emotions. But we don’t really know if they’re happy or what makes them happy. Nope, it’s reward that drives the primary DNA directive, the survival of the species. Yet the contentment of being in a mutual relationship is a bonus, albeit achievable only for some of us mortals. Consider yourself lucky if you have access to this dividend. Studies of married couples show that the contentment derived from the commitment of an interpersonal union generates added individual benefit: people within such unions tend to live longer and develop fewer diseases than those who have never married (odds risk ratio 2.59) or those who are previously divorced (odds risk 3.10).9 Because it’s actually about the feeling of social connection that comes with marriage. Those with positive social connections and affiliation are happier, and they live longer because of it.
Still, it’s hard to dig out and parse the differences between “love” and “in love” from our human history or literature. Did Adam love Eve? I suppose before she ate the apple, you could make a rudimentary case. After all, ignorance is bliss. But afterward? No love lost there. You might try tracing the first literary exhibition of love to Homer’s Iliad, which hinges on the love between Paris and Helen—although a more careful reading suggests otherwise. After all, Helen was already married, and the only reason Paris was enamored with her was because Aphrodite promised him the most beautiful woman in the realm. Sounds like Paris was suffering from a good case of infatuation rather than love.
Most writers conflate infatuation (or desire) with love on purpose. Infatuation is dopamine, the revving of the reward system, the motivation; it’s the phenomenon we are drawn to, in part because we can all identify: we’ve all been there at least once. Infatuation is a big seller, the stock and trade of all those romance novels, and the underlying appeal of Fifty Shades of Grey (2011), which has one more kink going for it.
Love, on the other hand, is boring. It’s not bad—it’s just not a page-turner. Oh, yeah, sure, I know, you’re going to throw Erich Segal’s Love Story (1970) in my face and tell me that love sells just as well as infatuation. And I’m going to shoot that dead duck down by telling you that virtually every prizewinning novel where love is the basis of the relationship ends up with one of the lovers six feet under. Go ahead, pick your poison. Romeo did. How about Larry McMurtry’s Terms of Endearment (1975)? Emma gets breast cancer. How about John Green’s The Fault in Our Stars (2012)? Gus’s poison is chemotherapy for his osteogenic sarcoma. Or if one of them doesn’t die, then one partner is in some tragic accident and is paralyzed, like in the film An Affair to Remember (1957). Nope, you’re going to have to work much harder. Infatuation sells because infatuation is reward gone wrong, while long-term love equates with contentment, and requires the protagonist to get killed or maimed to sell books or movie tickets. The stage production of Into the Woods (1989) showed us all that “happily ever after” isn’t so happy after all.
Perhaps this quote from Louis de Bernières’s novel Captain Corelli’s Mandolin (1994) best explains the difference between “love” versus “in love”: “Love is not breathlessness, it is not excitement, it is not the promulgation of promises of eternal passion, it is not the desire to mate every second minute of the day . . . that is just being ‘in love’ which any fool can do. Love itself is what is left over when being in love has burned away, and this is both an art and a fortunate accident.”
Addicted to Love?
Robert Palmer posited in his 1986 video, “Might as well face it, you’re addicted to love.”10 Hey, at least 30 million YouTube viewers bought it (those five backup brunettes could addict anyone). OK, if infatuation is mediated by dopamine, then could love actually be addictive? Brian Earp, a neuroethicist at Oxford, also parsed this question by describing these two separate kinds of love. First is what Earp called “acute love,” the feeling that characterizes being in love, which is intensely emotional—in other words infatuation, or in the words of romance novels, desire11—and which leads to alterations in brain chemistry that resembles drug addiction, almost assuredly due to dopamine. And of course, as a kind of addiction, being in love can have severe adverse consequences, just as in true drug addiction.12 We read in the newspapers of the consequences of rages of passion. The second form of love is what Earp calls a “mature” love and which allows for social growth and cognitive learning,13 most likely driven by serotonin. Thus love itself, the contentment that truly defines the emotion, is not addicting.
Perhaps marriage is the most obvious institutional example of the achievement of personal happiness today. Yet the role of love in marriage is a relatively new occurrence. Historian Stephanie Coontz states that marriage grew out of convenience to document legitimacy of offspring, obtain the most powerful in-laws to make family alliances, and expand the family labor workforce. After all, even today in some societies, marriages are still arranged by the matchmaker. As Tevye remarks on life in 1905 Russia in the Broadway production of Fiddler on the Roof (1964): “Love? That’s a new fashion.” Marriage today isn’t even about marriage but the wedding. When girls envision marriage from a young age, they think about the big day. The ring and the dress. The stress of seating charts and picking the right photographer. The bridesmaids, the DJ, the hot chafing dishes, and the open bar. That’s marketing designed for your dopamine system, not serotonin, and not even necessarily directed at the bride. Not enough thought is given to what happens after the credit cards are maxed out and the flowers that match the dresses have wilted. The rock? That’s the reward for the effort, not the long-term happiness.
The differences between infatuation and love are but one example of the general dichotomies between reward and contentment. First is the experience of the motivation, of the pursuit; this is often followed by the heightening of visceral reward in the attainment of physical and sexual responses, often followed by a consummation of the entire reward experience in the form of sexual release. Ultimately over time is built a level of contentment and bliss that comes from the social and spiritual connection.
Two different neurotransmitters (dopamine versus serotonin), two different brain areas of residence (the ventral tegmental area versus the dorsal raphe nuclei), two different targets of action (the nucleus accumbens versus the cerebral cortex), two different sets of receptors, and two different regulato
ry systems. But each influences the other, in ways that can reduce both pleasure and happiness. When taken to their extreme, these two pathways can take you to the highest mountain or the lowest valley—addiction, depression, and just plain misery. The science in Parts II and III says so.
PART II
Reward—The Agony of Ecstasy
3.
Desire and Dopamine, Pleasure and Opioids
Contrary to the theme song from the musical Carnival (1960), love does not make the world go round. Rather, Cabaret (1966) got it right: money makes the world go round. Because money buys prestige and power and sex and big toys. All of these boil down to the same thing: reward. Regardless of the species, the motivation to attain reward (eat, fight, mate) remains virtually intact and unchanged throughout evolution. It makes sense that reward is a pretty strong and unflagging driver of emotion. There are myriad rewards out there, many shaped by culture, religion, and/or reality TV. However, the underlying, unflagging, and omnipresent truth is the drive to attain it. The impetus to get out of bed is generally a quest for reward, whether it’s going to work in order to pay the electric bill, or entering the fiery gates of Mordor to destroy the One Ring. For me, it’s two cups of coffee.
The Hacking of the American Mind Page 4