Compendium 37 — Dopamine Nation: Finding Balance in the Age of Indulgence
“We’ve lost the ability to tolerate even minor forms of discomfort. We’re constantly seeking to distract ourselves from the present moment, to be entertained.” — Anna Lembke, MD
📖 Brief Overview
The neurotransmitter dopamine plays a crucial role in the brain's reward processing, with studies showing that it contributes more to the motivation for rewards than to the pleasure of receiving them. For a rat in a box, chocolate increases the release of dopamine by 55%, sex by 100%, nicotine by 150%, cocaine by 225%, and amphetamines, the active ingredient in speed, meth, MDMA, and Adderall (used to treat ADHD and narcolepsy) by 1000%. According to one study, abusing dopamine levels alters our ability to delay gratification, with addicts referring to their futures as only nine days long, compared to 4.7 years for the non-addicted participants.
Since the discovery of dopamine, neuroscientists have found that pleasure and pain are processed in overlapping brain regions and form opposite sides of the desired equilibrium (homeostasis). Repeated exposure to the same or similar pleasure stimulus diminishes pleasure's effects while pain increases in intensity, a process known as neuroadaptation. Tolerance arises when homeostasis is knocked out of alignment, causing the brain to enter a dopamine deficit state, where pain sensitivity elevates while the capacity to experience pleasure decreases. Correcting this balance between pleasure and pain has become more critical than ever, with modifiable behavioral factors accounting for 70% of global deaths.
To reach homeostasis, we can harness hormesis, a branch of science that shows administering small amounts of pain increases our resistance to it. Self-binding can help control pleasure by creating physical barriers between us and our drugs of choice, thus managing our exposure and, therefore, our behavior.
💡 Six Significant Ideas
1. What is Dopamine?
Scientists rely on dopamine as a kind of universal currency for measuring the addictive potential of any experience. The more dopamine in the brain’s reward pathway, the more addictive the experience.
The main functional cells of the brain are called neurons. They communicate with each other at synapses via electrical signals and neurotransmitters. Neurotransmitters are like baseballs. The pitcher is the presynaptic neuron. The catcher is the postsynaptic neuron. The space between pitcher and catcher is the synaptic cleft. Just as the ball is thrown between pitcher and catcher, neurotransmitters bridge the distance between neurons: chemical messengers regulating electrical signals in the brain. There are many important neurotransmitters, but let’s focus on dopamine.
Dopamine was first identified as a neurotransmitter in the human brain in 1957 by two scientists working independently: Arvid Carlsson and his team in Lund, Sweden, and Kathleen Montagu, based outside of London. Carlsson went on to win the Nobel Prize in Physiology or Medicine. Dopamine is not the only neurotransmitter involved in reward processing, but most neuroscientists agree it is among the most important. Dopamine may play a bigger role in the motivation to get a reward than the pleasure of the reward itself. Wanting more than liking. Genetically engineered mice unable to make dopamine will not seek out food, and will starve to death even when food is placed just inches from their mouth. Yet if food is put directly into their mouth, they will chew and eat the food, and seem to enjoy it.
This is not to say that high-dopamine substances literally contain dopamine. Rather, they trigger the release of dopamine in our brain’s reward pathway. For a rat in a box, chocolate increases the basal output of dopamine in the brain by 55 percent, sex by 100 percent, nicotine by 150 percent, and cocaine by 225 percent. Amphetamine, the active ingredient in the street drugs “speed,” “ice,” and “shabu” as well as in medications like Adderall that are used to treat attention deficit disorder, increases the release of dopamine by 1,000 percent. By this accounting, one hit off a meth pipe is equal to ten orgasms.
2. Pleasure and Pain Are Co-Located
In addition to the discovery of dopamine, neuroscientists have determined that pleasure and pain are processed in overlapping brain regions and work via an opponent-process mechanism. Another way to say this is that pleasure and pain work like a balance. Imagine our brains contain a balance—a scale with a fulcrum in the center. When nothing is on the balance, it’s level with the ground. When we experience pleasure, dopamine is released in our reward pathway and the balance tips to the side of pleasure. The more our balance tips, and the faster it tips, the more pleasure we feel.
But here’s the important thing about the balance: It wants to remain level, that is, in equilibrium. It does not want to be tipped for very long to one side or another. Hence, every time the balance tips toward pleasure, powerful self-regulating mechanisms kick into action to bring it level again. These self-regulating mechanisms do not require conscious thought or an act of will. They just happen, like a reflex. I tend to imagine this self-regulating system as little gremlins hopping on the pain side of the balance to counteract the weight on the pleasure side. The gremlins represent the work of homeostasis: the tendency of any living system to maintain physiologic equilibrium. Once the balance is level, it keeps going, tipping an equal and opposite amount to the side of pain.
In the 1970s, social scientists Richard Solomon and John Corbit called this reciprocal relationship between pleasure and pain the opponent-process theory: “Any prolonged or repeated departures from hedonic or affective neutrality . . . have a cost.” That cost is an “after-reaction” that is opposite in value to the stimulus. Or as the old saying goes, What goes up must come down.
In real life, pleasure and pain are more complex than the workings of a balance. What’s pleasurable for one person may not be for another. Each person has their “drug of choice. Pleasure and pain can occur simultaneously. For example, we can experience both pleasure and pain when eating spicy food. Not everyone starts out with a level balance: Those with depression, anxiety, and chronic pain start with a balance tipped to the side of pain, which may explain why people with psychiatric disorders are more vulnerable to addiction. Our sensory perception of pain (and pleasure) is heavily influenced by the meaning we ascribe to it.
3. Anticipation and Craving
The pleasure-pain balance is triggered not only by reexposure to the drug itself but also by exposure to cues associated with drug use. In Alcoholics Anonymous, the catchphrase to describe this phenomenon is people, places, and things. In the world of neuroscience, this is called cue-dependent learning, also known as classical (Pavlovian) conditioning. Ivan Pavlov, who won the Nobel Prize in Physiology or Medicine in 1904, demonstrated that dogs reflexively salivate when presented with a slab of meat. When the presentation of meat is consistently paired with the sound of a buzzer, the dogs salivate when they hear the buzzer, even if no meat is immediately forthcoming. The interpretation is that the dogs have learned to associate the slab of meat, a natural reward, with the buzzer, a conditioned cue. What’s happening in the brain? By inserting a detection probe into a rat’s brain, neuroscientists can demonstrate that dopamine is released in the brain in response to the conditioned cue (e.g., a buzzer, metronome, light) well before the reward itself is ingested (e.g., cocaine injection). The pre-reward dopamine spike in response to the conditioned cue explains the anticipatory pleasure we experience when we know good things are coming.
Right after the conditioned cue, brain dopamine firing decreases not just to baseline levels (the brain has a tonic level of dopamine firing even in the absence of rewards), but below baseline levels. This transient dopamine mini-deficit state is what motivates us to seek out our reward. Dopamine levels below baseline drive craving. Craving translates into purposeful activity to obtain the drug. My colleague Rob Malenka, an esteemed neuroscientist, once said to me that “the measure of how addicted a laboratory animal is comes down to how hard that animal is willing to work to obtain its drug—by pressing a lever, navigating a maze, climbing up a chute.” I’ve found the same to be true for humans. Not to mention that the entire cycle of anticipation and craving can occur outside the threshold of conscious awareness. Once we get the anticipated reward, brain dopamine firing increases well above tonic baseline. But if the reward we anticipated doesn’t materialize, dopamine levels fall well below baseline. Which is to say, if we get the expected reward, we get an even bigger spike. If we don’t get the expected reward, we experience an even bigger plunge.
4. Neuroadaptation: Too Many Pleasures Reduce the Capacity for Pain, While too Little Pain Increases the Threshold for Pleasure
We’ve all experienced craving in the aftermath of pleasure. Whether it’s reaching for a second potato chip or clicking the link for another round of video games, it’s natural to want to re-create those good feelings or try not to let them fade away. The simple solution is to keep eating, or playing, or watching, or reading. But there’s a problem with that. With repeated exposure to the same or similar pleasure stimulus, the initial deviation to the side of pleasure gets weaker and shorter and the after-response to the side of pain gets stronger and longer, a process scientists call neuroadaptation. That is, with repetition, our gremlins get bigger, faster, and more numerous, and we need more of our drug of choice to get the same effect. Needing more of a substance to feel pleasure, or experiencing less pleasure at a given dose, is called tolerance. Tolerance is an important factor in the development of addiction. With prolonged, heavy drug use, the pleasure-pain balance eventually gets weighted to the side of pain. Our hedonic (pleasure) set point changes as our capacity to experience pleasure goes down and our vulnerability to pain goes up. You might think of this as the gremlins camped out on the pain side of the balance, inflatable mattresses and portable barbecues in tow.
Neuroscientist Nora Volkow and colleagues have shown that heavy, prolonged consumption of high-dopamine substances eventually leads to a dopamine deficit state. Volkow examined dopamine transmission in the brains of healthy controls compared to people addicted to a variety of drugs two weeks after they stopped using. The brain images are striking. In the brain pictures of healthy controls, a kidney-bean-shaped area of the brain associated with reward and motivation lights up bright red, indicating high levels of dopamine neurotransmitter activity. In the pictures of people with addiction who stopped using two weeks prior, the same kidney-bean-shaped region of the brain contains little or no red, indicating little or no dopamine transmission. As Dr. Volkow and her colleagues wrote, “The decreases in DA D2 receptors in the drug abusers, coupled to the decreases in DA release, would result in a decreased sensitivity of reward circuits to stimulation by natural rewards.” Once this happens, nothing feels good anymore.
The paradox is that hedonism, the pursuit of pleasure for its own sake, leads to anhedonia, which is the inability to enjoy pleasure of any kind.
Science teaches us that every pleasure exacts a price, and the pain that follows is longer lasting and more intense than the pleasure that gave rise to it. With prolonged and repeated exposure to pleasurable stimuli, our capacity to tolerate pain decreases, and our threshold for experiencing pleasure increases. By imprinting instant and permanent memory, we are unable to forget the lessons of pleasure and pain even when we want to: hippocampal tattoos to last a lifetime. The phylogenetically uber-ancient neurological machinery for processing pleasure and pain has remained largely intact throughout evolution and across species. It is perfectly adapted for a world of scarcity. Without pleasure we wouldn’t eat, drink, or reproduce. Without pain we wouldn’t protect ourselves from injury and death. By raising our neural set point with repeated pleasures, we become endless strivers, never satisfied with what we have, always looking for more.
5. Lack of Self-Care or Mental Illness?
Seventy percent of world global deaths are attributable to modifiable behavioral risk factors like smoking, physical inactivity, and diet. The leading global risks for mortality are high blood pressure (13 percent), tobacco use (9 percent), high blood sugar (6 percent), physical inactivity (6 percent), and obesity (5 percent). In 2013, an estimated 2.1 billion adults were overweight, compared with 857 million in 1980. There are now more people worldwide, except in parts of sub-Saharan Africa and Asia, who are obese than who are underweight.
Princeton economists Anne Case and Angus Deaton have shown that middle-aged white Americans without a college degree are dying younger than their parents, grandparents, and great-grandparents. The top three leading causes of death in this group are drug overdoses, alcohol-related liver disease, and suicides. Case and Deaton have aptly called this phenomenon “deaths of despair."
Greater than one in ten Americans (110 people per 1,000) takes an antidepressant, followed by Iceland (106/1,000), Australia (89/1,000), Canada (86/1,000), Denmark (85/1,000), Sweden (79/1,000), and Portugal (78/1,000). Among twenty-five countries, Korea was last (13/1,000).
Prescriptions of stimulants (Adderall, Ritalin) in the United States doubled between 2006 and 2016, including in children younger than five years old. In 2011, two-thirds of American children diagnosed with ADD were prescribed a stimulant.
Prescriptions for sedative medications like benzodiazepines (Xanax, Klonopin, Valium), also addictive, are on the rise, perhaps to compensate for all those stimulants we’re taking. Between 1996 and 2013 in the United States, the number of adults who filled a benzodiazepine prescription increased by 67 percent, from 8.1 million to 13.5 million people. In 2012, enough opioids were prescribed for every American to have a bottle of pills, and opioid overdoses killed more Americans than guns or car accidents.
[Lembke's patient] David: “From 2008 to 2018, I was taking up to thirty milligrams of Adderall a day, fifty milligrams of Ambien a day, and three to six milligrams of Ativan a day. I thought, I have anxiety and ADHD and I need this to function.” David attributed fatigue and inattentiveness to a mental illness rather than to sleep deprivation and overstimulation, a logic he used to justify continued use of pills. I’ve seen a similar paradox in many of my patients over the years: They use drugs, prescribed or otherwise, to compensate for a basic lack of self-care, then attribute the costs to a mental illness, thus necessitating the need for more drugs. Hence poisons become vitamins.”
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