Never Enough

Why do we keep chasing highs that inevitably bring pain? In Never Enough: The Neuroscience and Experience of Addiction, behavioral neuroscientist Judith Grisel explores this question with the precision of a scientist and the vulnerability of a recovering addict. She argues that addiction is not simply a moral failing or a matter of weak will—it’s a predictable outcome of how the brain learns, adapts, and strives to maintain equilibrium. The tragic irony, she shows, is that the same neural plasticity that allows us to grow and learn also fuels compulsive self-destruction.

Grisel contends that the brain’s incredible ability to adapt—its homeostasis—means we cannot ever achieve a lasting high. Every surge of pleasure creates an opposing response. Each rush of dopamine, every drop of fear or pain, is followed by the brain’s countermeasure. Over time, these adaptations become permanent, making addicts need their drug just to feel normal. “There will never be enough,” her friend Steve said after a binge—and that is the law of the brain itself.

The Core Argument: Addiction as a Natural Brain Process

The book’s central claim is revolutionary in its simplicity: addiction arises from normal brain functioning gone awry. The same systems that let us learn patterns, pursue rewards, and adapt to our environment are hijacked by substances that overactivate “pleasure circuits.” When these neural pathways are continually flooded with drugs, the brain recalibrates, suppressing sensitivity and creating a state of painful deprivation in their absence. The addict’s “need” is not imagined but rooted in altered physiology.

What You’ll Learn Inside

In this summary, you’ll explore how Grisel interweaves her life story with neuroscience. You’ll learn how addictive drugs manipulate neurotransmitters, especially dopamine, the molecule of anticipation and motivation; how the brain’s reward system (the mesolimbic pathway) evolved to promote survival but is now exploited by modern chemistry; and how homeostasis, the brain’s balancing act, ensures that emotional highs must breed lows.

Grisel introduces readers to foundational principles—what she calls the Three Laws of Psychopharmacology: all drugs act by changing what’s already happening in the brain; all drugs have side effects; and the brain adapts to every drug by counteracting its effect. These laws frame addiction not as exceptional behavior but as predictable biology.

Why It Matters—The Personal and Social Stakes

Grisel’s scientific explanations are grounded in raw autobiography. She describes being a teenager who felt alienated and restless until alcohol “made life bearable,” and later a twenty-something homeless addict who realized her endless pursuit was futile. These personal moments make the science resonate deeply: addiction isn’t “bad behavior” but the brain’s desperate attempt to restore balance.

The book also challenges how society sees addicts. Neuroscience, Grisel argues, should not strip away moral accountability or human empathy. Understanding the brain’s role gives us compassion, but not excuses—it illuminates the shared vulnerability of every human mind that seeks pleasure and relief from suffering.

From Molecules to Meaning

Grisel isn’t content to just map the damage. She asks what recovery looks like in a brain that forever remembers pleasure. Some substances can be physically removed from the body; the mental circuits, however, persist for decades. Only by creating new forms of reward—through connection, purpose, and compassion—can one rewrite those pathways. “The opposite of addiction isn’t sobriety,” she writes. “It’s choice.”

The Broader Vision

In her sweeping closing chapters, Grisel turns from neuroscience to philosophy and social critique, arguing that addiction flourishes in modern isolation. Drugs are both symptom and scapegoat of a world obsessed with comfort and avoidance of pain. Our brains, designed for interconnection and meaning, struggle in a culture of consumption—and turn inward toward chemical shortcuts. Fighting this epidemic requires transforming not just individuals but environments: fostering community, compassion, and depth of experience as antidotes to alienation.

“Addiction is a natural consequence of a normal brain doing its job in an abnormal world.”

Grisel’s insight reframes our understanding: the problem isn’t the capacity to seek pleasure, but how modern life floods that capacity without meaning. Her story and science combine to offer a nuanced, hopeful view—one that demands empathy, discipline, and a recognition that freedom lies not in getting high, but in learning to live fully awake.

Grisel begins with how pleasure is wired into the brain. In the 1950s, scientists James Olds and Peter Milner discovered the “reward center” when rats pressed levers to electrically stimulate their own brains. Those pulses released dopamine in a region called the nucleus accumbens—the hub of desire, motivation, and pleasure. The rats would ignore food, water, even sex, to keep pressing. In humans, addictive drugs stimulate the same circuitry, turning natural incentives like eating or love into secondary rewards beside the drug’s thrill.

Dopamine: Not Just Pleasure, But Anticipation

While dopamine has often been labeled the “pleasure chemical,” Grisel clarifies that it actually signals the anticipation of pleasure—the buzz that leads us to act. This is why dopamine peaks when you expect a reward, not when you receive it. Cocaine, alcohol, and heroin hyperactivate this loop, flooding dopamine so powerfully that the brain begins to crave the feeling of anticipation itself. Over time, the nucleus accumbens dulls, requiring more drug for the same “promise” of pleasure.

The Twin Pathways of Desire and Motion

Grisel distinguishes two major dopamine circuits: the mesolimbic pathway (from the midbrain to the limbic system) governs emotional anticipation, while the nigrostriatal pathway (connecting the substantia nigra to the striatum) triggers movement—the physical impetus to act on desire. This is why drugs that elevate dopamine make users both euphoric and restless. When Parkinson’s disease destroys dopamine neurons in the second pathway, action freezes—an eerie reflection of addiction’s converse: desire without motion.

Hijacking Nature’s Design

The evolutionary role of dopamine was to ensure survival—to urge us toward food, sex, and safety. But artificial substances like cocaine or meth hijack that mechanism with precision. They act like floodlights rather than dawn’s slow glow, creating stimulation that’s far beyond what nature intended. Unlike natural rewards spaced across time, drugs deliver immediate, predictable jolts, training the brain to depend on certainty instead of curiosity. The result is what Grisel calls “addiction’s short circuit”: the brain learns that pleasure equals immediacy, not engagement.

The No-Free-Lunch Principle

Eventually the system collapses under its own excess. Dopamine receptors downregulate; the nucleus accumbens becomes mute. The brain builds tolerance—meaning it now expects the drug as baseline and produces withdrawal when it’s gone. “An addict doesn’t drink coffee because she’s tired,” Grisel writes. “She’s tired because she drinks coffee.” Pleasure becomes impossible without chemical aid. And in that grim economy, the brain repays every dopamine loan—with interest.

Relevance Beyond Addiction

Grisel’s account of dopamine speaks not only to drug users but to all of us. Smartphones, gambling, social media—they all exploit the same mesolimbic circuits, delivering rapid, predictable “newsworthy” stimuli. (Note: neuroscientist Anna Lembke’s Dopamine Nation echoes Grisel’s thesis, showing that modern overstimulation drives global anhedonia, or inability to feel joy.) Understanding dopamine’s anticipatory nature helps you see why craving, not pleasure, drives consumer culture—and why true satisfaction requires slowing the pace and diversifying what sparks reward.

What happens after the high? That’s where Grisel’s most haunting insight lies: the brain never stops adjusting. Using the opponent-process theory introduced by psychologist Richard Solomon, she explains that for every stimulus, the brain generates an opposing reaction to restore balance. Pleasure triggers a counterbalancing pain; relief summons tension. This process, vital for survival, becomes catastrophic in addiction because repeated use amplifies the opponent response until withdrawal far outweighs the high.

Homeostasis and Emotional Set Points

The nervous system’s job is to detect contrast—what’s new or meaningful—and then return to baseline. Grisel illustrates this through homeostasis: just as body temperature or heart rate stay stable, so too do emotions. Love may feel like soaring joy, but eventually the brain neutralizes it—unless separation occurs, triggering the mirror image of heartbreak. Similarly, repeated drug use lowers the emotional set point, creating chronic depression or anxiety when pleasure pathways are depleted.

The A–B Process: Tracing Addiction’s Arc

Grisel uses “A process” for the drug’s immediate effects and “B process” for the brain’s opposing adjustments. On first use, the A process (the rush) dominates. With repetition, the B process grows stronger and faster, dampening the highs and deepening the lows. Over time, addicts take drugs not for euphoria but to cancel withdrawal. This pattern explains tolerance, craving, and relapse as mathematically predictable outcomes of an adaptive brain.

Environmental Cues and Learned Craving

Because the brain learns context, cues linked to drug use—friends, places, smells—trigger the B process automatically. Grisel recounts how recovering alcoholics relapse merely entering their old bar or hearing a familiar song. The “b process” begins in anticipation, creating craving that can last decades. To counteract this, modern therapies expose addicts to their triggers without the drug (cue extinction). Slowly, the associations weaken, but the shadow remains—a reminder that memory itself is biological addiction.

Pain as the Flip Side of Pleasure

Socrates observed that pain and pleasure “grow from one head.” Grisel resurrects that truth with neuroscience. The same neural mechanisms that make us feel bliss also make us suffer when overused. “Who goes up, must come down,” she writes, echoing Newton. Understanding this paradox helps you see addiction’s perverse logic: each dose is an attempt to escape the very discomfort the previous dose caused. Recovery therefore means learning to endure tension and sadness—to live with contrast rather than seek constant balance.

Grisel explores addiction through its diverse agents—alcohol, cannabis, opioids, tranquilizers, stimulants, and psychedelics—each revealing different weaknesses in the brain’s design. Rather than just catalog drugs, she shows how each exploits specific neurotransmitters and circuits. Her approach blends memoir with molecular biology, making readers feel the science from the inside out.

Cannabis and the Floodlight Effect

Marijuana, she explains, acts like “a bucket of red paint”—nonselective, splashing activity across the brain via CB1 receptors. Natural cannabinoids like anandamide help mark meaningful experiences. THC overwhelms them, making everything feel significant. Grisel recalls scouring beaches for shells in ecstatic wonder. But when everything is highlighted, nothing stands out. Chronic use downregulates CB1 receptors, dulling all experience and creating amotivational states. Abstinence reverses this—she describes noticing fall foliage as if for the first time months after quitting.

Opiates and the Dual Chemistry of Pain

Opiates mimic endorphins, nature’s morphine. Initially, they produce tranquility and bliss. But the body evolves “anti-opiates”—compounds like dynorphin—that create pain to restore balance. The result is a see-saw between euphoria and agony. Research she recounts shows rats releasing endorphins at the mere sight of danger and anti-opiates at safety cues. This biological system explains why addicts suffer terribly in withdrawal and why some countries, like China, attempt cures by severing these circuits surgically.

Alcohol: The Universal Sedative

Alcohol, “the neurological sledgehammer,” slows the entire brain. It enhances GABA (calming) and inhibits glutamate (exciting), tricking the brain into relaxation—until adaptations reverse these effects and produce anxiety, seizures, and malaise. Women metabolize alcohol differently, progressing faster to damage. The contrast between celebration and sedation fascinates Grisel: a society that toasts joy by dulling sensitivity. Her central warning—that every drunk high deepens the low—rings true in both personal and public contexts.

Tranquilizers and Manufactured Calm

From Valium to Xanax, sedatives act on the same GABA receptors as alcohol. Initially revolutionary “little helpers,” they now contribute to dependency epidemics. Grisel explains that benzodiazepines rewire receptor subunits, producing swift tolerance. They promise sleep but ultimately cause insomnia by flattening natural rhythms. Over decades, pharmaceutical cycles repeat: new formulations marketed as “safe” only to reveal identical flaws. Her advice is pragmatic—treat anxiety through life changes, not chemistry, or the chemistry will worsen it.

Stimulants and the Mirage of Energy

Cocaine, meth, and amphetamines block monoamine reuptake—dopamine, norepinephrine, serotonin—creating manic bursts of confidence and focus. Sensitization replaces tolerance: users grow jittery, paranoid, desperate. Cocaine’s short half-life drives compulsive binges. Meth’s long half-life burns the brain’s dopamine neurons. Grisel’s own relapse stories and those of friends show addiction’s tragic symmetry: stimulant highs that fuel obsessive lows, each use simultaneously energizing and emptying the soul.

Psychedelics and the Possibility of Healing

Not all mind-altering substances destroy. LSD, psilocybin, and DMT, acting on serotonin 2A receptors, seem non-addictive and even therapeutic. Hofmann’s “medicine for the soul,” Grisel says, might reveal what other drugs hide: consciousness itself. Modern studies show these can relieve depression and end-of-life anxiety by rewiring connectivity, increasing “global plasticity.” Yet she cautions that mystical experiences can’t substitute for growth—they must catalyze meaning, not evade it. Psychedelics may embody the paradox of addiction reversed: instead of narrowing perception to one craving, they expand it to everything.

In the penultimate section, Grisel traces why some people are more vulnerable than others. “Why me?” she asks—why do some walk away from drugs untouched while others ruin their lives? Her answer fuses genetics, epigenetics, and experience: biology loads the gun, environment pulls the trigger, and exposure decides how many shots are fired.

Inherited Risk

Addiction runs in families not by moral contagion but through shared DNA. Twins and adoption studies show that 50–60% of risk is inherited. Yet scientists cannot find a single “addiction gene.” Instead, dozens of small variations—affecting dopamine sensitivity, serotonin metabolism, or anxiety—interact. The total effect resembles a deck of red and black cards: risk and protection mixed in each hand. Genes merely set predispositions; they do not dictate destiny.

Epigenetics and Generational Echoes

Grisel highlights new findings that trauma, stress, and drug use can imprint chemical markers on DNA passed to offspring. Studies on rats show parents exposed to THC or stress produce addicted, anxious descendants. Human research links Holocaust trauma or famine to generational stress sensitivity. She speculates her own family’s history of loneliness and criticism may have left similar molecular scars, priming her for alienation long before her first drink. (Note: This view aligns with Bruce Lipton’s work in The Biology of Belief.)

Adolescence: The Gateway Phase

The teenage brain, rich in plasticity but poor in impulse control, is the perfect storm. The prefrontal cortex—the seat of reasoning and restraint—is still developing, while reward systems surge with dopamine. Drugs profoundly remodel this architecture. Early use of marijuana or alcohol can permanently lower motivation and impair cognition, explaining why initiation before twenty-one multiplies addiction risk fourfold. Grisel remembers starting at thirteen and watching peers mature while she stagnated—a neurobiological time stamp of risk.

Personality and Environment

Finally, temperament matters. Thrill seekers with high dopamine tone and low harm avoidance—people drawn to risk and bored by routine—are statistically most vulnerable. Combine that with environments saturated in stress or scarcity, and addiction thrives. Native American communities devastated by colonization, she writes, suffer not from biology but from despair: “Few of us spend time on reservations. There’s nothing else to do but drink.” This insight reframes addiction as systemic, not individual—a mirror for a world that breeds escapism.

The book concludes by turning neuroscience outward—to culture, policy, and hope. Despite monumental advances in brain science, Grisel admits the rates of addiction are rising. The cure will not come from molecules or surgery but from meaning, connection, and compassion.

Why Science Alone Can’t Save Us

Grisel recounts her days as a researcher during the Human Genome Project, when scientists thought mapping DNA would solve behavioral diseases. Instead, it revealed complexity—we have fewer genes than potatoes. Addiction, like consciousness, emerges from interaction, not code. Neuroscience can explain mechanism but not motivation. It can tell us why we crave but not why we suffer.

The Myth of Control

Policies treating addicts as threats—whether Duterte’s killings or punitive U.S. laws—fail because they attack behavior, not cause. You can’t legislate away pain or desire. As she notes, “removing the drive to get high is as likely as removing our desire to explore.” True healing lies in expanding freedom, not restricting it. Autonomy and purpose—not coercion—lead to recovery.

Addiction as Isolation

Grisel links addiction to modern alienation: technology, consumerism, and the erosion of community. Humans evolved to seek meaning through connection, yet today’s culture floods reward circuits with empty stimulation. Drugs, screens, and shopping fill the void temporarily, but deepen loneliness. Her prescription echoes Gabor Maté’s In the Realm of Hungry Ghosts: addiction is not about substances but the hunger for belonging.

Healing Through Compassion and Choice

Holding her father’s hand at dinner was her turning point—not a punishment, not a lecture, but love. Neuroscience confirms that empathy and safe relationships restructure the brain more effectively than chemicals. Recovery, then, means building contexts of connection—families, communities, and societies that validate pain rather than deny it. Choice, not abstinence, is the opposite of addiction. Grisel’s story closes in humility and hope: “Because it could be any of us, and because it is many of us, we must reach for each other.”