Never Enough

Never Enough Plot Summary

Introduction

At twenty-two, I found myself in a cheap motel room in Deerfield Beach, Florida, having just been on the receiving end of a drug deal gone wrong. My friend and I were using up a stash of cocaine that was meant for someone else when he made a comment that would haunt me for years: "There will never be enough cocaine for us." Though his words hit me like a revelation, they seemed irrelevant at the time. I was already deep in the throes of addiction, using not to get high anymore but simply to escape reality. Death didn't seem like such a big deal compared to the emptiness I felt. Addiction today is epidemic and catastrophic. In the United States, about 16 percent of the population aged twelve and older meet criteria for a substance use disorder, and worldwide, addiction affects about one in every five people over fourteen. Each day, ten thousand people around the globe die from substance abuse. The terrible truth for those who love mind-altering chemicals is that with regular use, the brain always adapts to compensate. An addict doesn't drink coffee because she's tired; she's tired because she drinks coffee. Regular drinkers don't have cocktails to relax after a rough day; their day is filled with tension because they drink. This adaptation turns out to be the driving force behind substance use and abuse: there will never be enough drug, because the brain's capacity to learn and adapt is basically infinite.

Chapter 1: Descent into Darkness: My Path to Addiction

The first time I got drunk at thirteen, I felt like Eve must have after tasting the apple. The drug provided physical relief and spiritual antidote for a persistent restlessness I'd been unable to identify or share. An abrupt shift of perspective coincident with guzzling half a gallon of wine in my friend's basement somehow made me feel sure that both life and I were going to be all right. At the same time, it seemed to deliver, on a satin pillow, the key to all my blooming angst. Abruptly relieved from an existence both harsh and lackluster, I had finally discovered ease. So I began with enthusiasm, even determination. From the start, I consumed as much and as often as I could—literally through most of seventh grade, because school afforded the best opportunities for freedom from parental oversight. Drinking before, during, and when I could after school, I seemed to possess an admirable innate tolerance. I was almost never sick or hungover and appeared presentable despite what would surely be deemed legal intoxication. As far back as I can remember, I felt hemmed in, frustrated by imposed limits and my own limitations. Longing for other, for something else, is at the core of my experience of self. Even today, below the persona of nurturing friend, committed partner, determined scientist, and adoring parent is a heartbreaking desire to embrace oblivion. From what or to where I seek escape, I really can't say; I just know that the constraints of space, time, circumstances, obligations, choices fill me with an overwhelming sense of desperation. The next ten years were characterized by a simple philosophy and practice: I sought any opportunity to use mind-altering drugs and paid any cost. My actions only made sense in terms of that guiding principle; virtually every moment was shaped by an orientation toward escaping sober awareness. For all this pharmacological conjuring, I traded myself away a piece at a time. Many of the experiences I had during this formative time are completely lost to memory, but of those I can recall, some were amusing or fantastic, like the evening just before final exams when I initiated a road trip from St. Louis to Nashville. Others were embarrassing or dangerous, like navigating my grandparents' Suburban with my head out the window because the streetlight seemed so much more informative than the dash or road signage. But the majority are painful. The science behind this trajectory is illuminating. Drugs of abuse hijack the brain's reward system, triggering the release of dopamine in the nucleus accumbens—the so-called "pleasure center." This initial flood of dopamine feels wonderful, but our brains quickly adapt by developing tolerance. As tolerance builds, we need more of the substance to achieve the same effect. Eventually, the brain adapts so completely that the drug no longer produces pleasure but merely staves off the misery of withdrawal. This is why addicts continue using despite devastating consequences: they're no longer chasing a high but fleeing the lows that come with abstinence.

Chapter 2: The Neural Mechanisms: How Drugs Hijack the Brain

I was squeaky clean despite a fairly ardent love of coffee. Like most consumers, I drink coffee because I appreciate the arousing effects of caffeine, which acts in the brain by speeding up a part of the nervous system involved in arousal. Before I became a devotee, I suppose I opened my eyes in the morning and felt pretty much awake. It would have taken a few minutes to become fully alert, but my nervous system, entrained to circadian rhythms, would kick in its own arousing mechanisms as an effective way to begin the day. No longer is this the case. I now need coffee to feel normal in the morning, and it would take something like a locomotive coming through the bedroom for me to feel aroused without it. This change in my behavior reflects the states of tolerance and dependence. The terrible truth for all those who love mind-altering chemicals is that if the chemicals are used with regularity, the brain always adapts to compensate. All drugs act by changing the rate of what is already going on. They all have side effects. And the brain adapts to all drugs that affect it by counteracting the drug's effects. These three laws of psychopharmacology apply universally. When any drug has an effect, it's due to the drug's chemical actions on brain structures. For most drugs of abuse, we know precisely which structures are modified, and this gives us a really good start to understanding how they make us feel the way they do. Cocaine blocks a protein that recycles dopamine, and because dopamine hangs around longer than usual, we feel euphoric and energized. For alcohol, the targets are not as clear, acting throughout the brain to influence a multitude of targets. The mesolimbic dopamine pathway is central to all addiction. This circuit, running from the midbrain to the nucleus accumbens, signals the anticipation of pleasure when activated. What's fascinating is that dopamine doesn't exactly signal pleasure itself but rather the anticipation of pleasure—the anxious, lip-smacking foretaste of something important just around the corner. All addictive drugs, regardless of their specific mechanisms, stimulate this pathway, creating a powerful motivation to seek and consume more of the substance. The brain's response to drugs is bidirectional. Not only do drugs act on the brain, but the brain responds to the effects of drugs. With repeated administration, the brain adapts to compensate for the changes associated with the drug, leading to tolerance and dependence. This means the only way for a regular user to feel normal is to take the drug, with getting high becoming increasingly short-lived, if it occurs at all.

Chapter 3: Adaptation: When Brain Chemistry Fights Back

On the last day of his life, shortly before being forced to drink poison, Socrates engaged in a final dialogue with his students. After a prison guard removed his chains, Socrates noted, "How singular is the thing called pleasure, and how curiously related to pain, which might be thought to be the opposite of it...he who pursues either of them is generally compelled to take the other. They are two, and yet they grow together out of one head or stem." This philosophical observation astutely predicted what scientists would later discover: moving between opposite biological states enables our bodies to maintain stability in the face of disruption. In the 1970s, researchers Richard Solomon and John Corbit proposed the "opponent-process theory," suggesting that any stimulus that alters brain functioning to affect the way we feel will elicit a response by the brain that is exactly opposite to the effect of the stimulus. As Newton might succinctly put it: who goes up, must come down. According to Solomon and Corbit, the brain responds to any stimulus by counteracting those feelings to return to homeostasis. The theory posits two processes: the a process, which is the direct neural response to the stimulus (like the euphoria from a drug), and the b process, which is the brain's response to the a process (like the crash or withdrawal after the drug wears off). When the brain is first exposed to a stimulus, the a process is unmitigated by compensatory brain mechanisms, and thus the full effect is experienced. However, as the b process is recruited, the experience is dampened. Repeated encounters with the stimulus result in faster, bigger, and longer-lasting b processes that are better able to maintain homeostasis in the face of disruption. This adaptation explains why the drug comes to function mainly to stave off withdrawal and craving rather than to produce pleasure. It also explains why the states of withdrawal and craving from any drug are always exactly opposite to the drug's effects: if a drug makes you feel relaxed, withdrawal will manifest as anxiety; if it helps you wake up, you'll experience lethargy during withdrawal. Understanding this adaptation is crucial to understanding addiction. The hallmarks of addiction—tolerance, withdrawal, and craving—are all consequences of this b process. Tolerance develops because more of the drug is needed to overcome an increasingly stronger b process. Withdrawal happens because the b process outlasts the drug's effects. And craving occurs because any environmental signal associated with the drug can trigger a b process that can only be relieved by using again.

Chapter 4: Substance Profiles: How Different Drugs Affect Us

From the moment I drank the wine in my friend's basement until I got clean and sober, I didn't turn down a single opportunity to use any drug. People often ask about a "drug of choice." To me this is an ambiguous concept. I, and hordes of people like me, will use virtually anything, depending on circumstances. In truth I'd choose them all, sometimes serially and sometimes all at once; I wasn't picky. But if the question were stated this way: "You're going to a desert island to live out the rest of your life and can only take one substance, what would it be?" Without hesitation, I'd choose a limitless supply of weed. Lysergic acid diethylamide, or LSD, compared with its natural analogs, psilocybin, N,N-dimethyltryptamine (DMT), and mescaline, differs most in its potency. LSD is one of the most potent psychoactive compounds we know and is effective at about two hundred times lower concentrations than the next strongest. The first time I tripped, and every time after, was like opening a door into a much more vast and mysterious existence than the one I usually inhabited. Twenty or thirty minutes after I put a tab under my tongue, chewed a peyote button, or ate magic mushrooms, a delicious feeling of invitation, crumbling boundaries, and mind-bending joy would begin to bubble up from deep inside me. Opiates deliver heartbreak like no other drug class, initially providing a sense of security and well-being that soon transmutes into something like being stranded on a barren moonscape without oxygen. In the beginning, opiates are an ideal other. As they beckon graciously, it feels entirely natural to respond with trust and gratitude. Unlike stimulants, or even alcohol, the subjective effects of these drugs seem almost perfectly subtle as they bestow utter contentment. At first the relationship is fun and easy, polishing up cloudy afternoons that might otherwise be irksome and muting broken edges of disappointment. The consequences of regular use are severe. Opiate tolerance is mind-bogglingly robust. Addicts can administer upwards of 150 times the dose that would be lethal to naive users and, even so, just feel "right" but not really high. In laboratory studies, it takes fully tolerant animals a "drug holiday" of nearly six days in order to regain just half of the intrinsic sensitivity to morphine that will get them high. In contrast, the half-life associated with the return of sensitivity to nicotine is about half an hour, and complete recovery occurs when doses are separated by only three hours. Despite these varied drugs affecting the brain in different ways, they all ultimately hijack the same pleasure pathways, and they all trigger the same opponent processes. The brain adapts to each one, ensuring that what begins as pleasure eventually becomes an endless, futile chase. As tolerance grows, users find themselves taking more and more just to feel normal, never again achieving the high they remember from their first experiences.

Chapter 5: Recovery Dynamics: The Struggle to Reclaim Control

About six months after my bottom in that Deerfield Beach motel, through a series of circumstances rather than personal insight or strength of character, I was clean and sober for the first time in years, and therefore not quite so numb. I saw that I had a life-or-death choice. I could continue colluding with my mental illness as it inexorably consumed me, or I could find a different way to live. In my experience, very few faced with those possibilities choose life, and I first went with the majority. The cost of abstinence seemed too high: Without drugs, what would there be to live for anyway? In just ten years, my sources for solace had totally betrayed me, carving out a canyon deep and unlivable. Drugs were destroying every aspect of my life, yet my days revolved around self-administering until I passed out. By the time I turned twenty-three, it had been years since I'd gone even twenty-four hours without a drink, pill, fix, or joint. Though the fun and excitement were long gone, I also could not wrap my head around having a disease that necessitated a lifetime of abstinence. Eventually, two factors motivated my desire to recover. First, I began to wonder just a wee bit about what it would be like to live in the relatively uncharted territory of sobriety. I'd been scraping around the basement floor for so long it seemed as if it might at least be interesting to explore another place. I thought of myself as courageous, and it was equal parts courage and curiosity that contributed to the decision to give abstinence a try. My second motivation was a decision to find a cure for addiction by becoming a neuroscientist. My life had changed 180 degrees after getting clean. Not only did I have a shiny new Ph.D., but I was able to look people in the eye and feed my respectable habits without committing crimes. I'd wake up every morning feeling clean and rested, knowing where I was and more or less what my day would hold—a state so precious that everyone should be so fortunate. But being clean and sober for more than thirty years hasn't enabled me to "clear" my addiction. I've been able to stay a safe distance from my disease, but don't think for a minute that I've been cured. The craving doesn't disappear completely with time. My disease isn't caused by a virus or a drug, but instead abides in the way my brain responds to pharmacological treats—enthusiastically and profoundly. To this day, the surest way to get me to do something is to tell me not to. I'm not proud of my oppositional bias, but it seems to be a core part of my nature. I was probably grounded for half of my early adolescence, but during the rest of the time I made up for it. Recovery requires not just abstinence but a complete reorientation to life. It means learning to face feelings that drugs once numbed, developing healthy coping strategies, building supportive relationships, and finding meaning beyond the chemical escape. The brain can heal, but it takes time. Neuroplasticity—the brain's ability to rewire itself—works in our favor during recovery, allowing new neural pathways to form that support sobriety rather than addiction.

Chapter 6: Environmental Factors: Why Some People Become Addicts

In graduate school, I had my perspective enlarged when I took a course on Native American history and culture and chose to write my final paper on the very high rates of alcoholism in this group. At the time, I shared the dominant view that Native Americans possessed a faulty gene or enzyme or some other aspect of brain circuitry that was responsible for decimating the indigenous population. I figured I'd spend some time in the library perusing the literature and summarize the causes for an easy A. Native Americans happen to have the highest rate of alcohol use disorders of all ethnic groups in the United States, blighting entire communities in incalculable ways. For example, on some reservations close to half of children are born with fetal alcohol poisoning, and rates of addiction are similarly through the roof. I launched into research databases and catalogs full of naive enthusiasm that soon turned to wonder and then to disbelief. Not only was I frustrated by a dearth of good review papers, but there was not much to review. Despite loads of studies investigating genes, neurochemicals and structures, brain wave patterns, and liver enzymes, no unfortunate constitutional factor was found that renders Native Americans more susceptible to alcoholism. As I confronted my own assumptions, I realized how incredibly convenient a biological explanation for Native addiction rates would be for the rest of us. If we could attribute the epidemic of alcoholism and fetal alcohol effects on reservations to something about "them," we wouldn't have to ask about our complicity in the systematic denigration of their cultures, the theft of land and other resources, or realize that being exiled with little hope for personal growth or community prosperity might drive anyone to drink. There are four primary reasons people develop addictions: an inherited biological disposition, copious drug exposure (particularly during adolescence), a catalyzing environment, and epigenetic factors—experiences of our ancestors that affect our genes. It's not necessary to have all four, but once some threshold is reached, it's like breaching a dam—virtually impossible to rebuild. With enough exposure to any addictive drug, any one of us will develop the hallmarks of addiction: tolerance, dependence, and craving. But if the biological predisposition is very high, or use starts during adolescence, or certain risk factors are present, less exposure will do the trick. The environmental factors that pave the way for addiction include family stress, childhood abuse or neglect, environments with few positive role models, or a general lack of opportunity. Women, in particular, are likely to abuse substances in an attempt to self-medicate traumatic experiences such as sexual or physical abuse. Economic status, family stability, religiosity, and education have also been identified as aspects of our environment that can contribute to, or protect from, a tendency toward disordered use.

Chapter 7: The Path Forward: New Approaches to Addiction Treatment

The majority of addicts die as a result of their insane behavior and wreak havoc on the way. But there are millions of happy and successful people who were once as bad off as, or worse off than, I was, and these millions of examples offer a path based in freedom rather than control. Though many, like me, only begin to turn around when we run out of options, ultimately recovery is a process of expansion, not restriction. I understand firsthand the despair that grows as drugs come to make our choices for us, deciding whom we will be with and what we will do. This gloomy cell of repetition occupied by every addict, despite variation in periodicity, strips us of our most precious commodity, the freedom to choose. This is why I'm not against drugs or drug use, but am so thoroughly opposed to addiction: it strips us of our precious freedom. And this is also why it makes no more sense to cure addiction by imposing permanent or semipermanent limits on our range of choices than it does to teach compassion through corporal punishment. So, what might be an ideal cure? First, an easily administered formulation that would obviate withdrawal and craving, removing the biological necessity for a swift relapse. This is important because most daily users can't make it through the first hours of withdrawal without succumbing to an insatiable drive. And this is the easy part of our panacea; it's been done with Suboxone for opiate addicts, with Chantix for smokers, and with benzos for alcoholics, to a lesser degree. In each of these cases, the treatment is only effective when coupled with a slow reduction in dose and ample social support. Because stimulant users don't usually crave in the first few days after a binge, it seems as if we should be home free. But detoxing is only the beginning. The playing field of our neurobiology is not even, but especially because actions can and do alter our brain's structure and function, we probably have much more influence over the conditions of our lives, and the lives of others, than we realize or utilize. There will always be some of us who are more or less liable to find drugs a handy lever, but we are all positioned somewhere on the same scale. Increased incidence of addiction reflects a tipping of this scale, weighted by the burdens of loneliness; anxiety about the future; isolation despite our social media connections; the incoherence of institutionalized greed and selfishness; and a social structure that seems to devalue empathy and connection. Facing addiction requires a commitment to acknowledge the problem, to look at it deeply rather than away from it, and then to reach out to each other with our minds, hearts, and actions, connecting with those who need our help or those whose help we need. To be living on earth today is like being in a lifeboat with every other person on the planet; it's both inhumane and impractical to turn our backs. We are really all in this together.

Summary

The core truth at the heart of addiction is deceptively simple: there will never be enough of what doesn't satisfy. Our brains are designed to adapt to whatever substances we repeatedly introduce, ensuring that what once brought pleasure eventually brings only relief from discomfort. This neurological reality underlies all addiction, whether to alcohol, opiates, stimulants, or any other mind-altering substance. The brain's remarkable plasticity—its ability to change in response to experience—is both the source of addiction's power and, potentially, the path to recovery. What makes addiction so insidious is that it hijacks the very circuits designed to help us survive and thrive. When we repeatedly flood these circuits with artificial stimulation, they adapt by becoming less responsive, requiring more and more of the substance just to feel normal. This process explains why addiction is so difficult to overcome through willpower alone. It's not a moral failing but a profound rewiring of the brain's reward and regulatory systems. Yet this same neuroplasticity offers hope: with time, abstinence, and supportive environments, the brain can heal and establish new patterns. Recovery doesn't mean returning to a pre-addiction state, but rather building a new relationship with oneself and the world—one that doesn't require chemical escape. The true freedom lies not in perfect control but in the daily choice to face life's challenges with courage, connection, and compassion rather than numbing ourselves to both pain and joy.

About Author

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Judith Grisel

JUDITH GRISEL, Ph.D., is a behavioral neuroscientist and a professor of psychology at Bucknell University. She has been awarded more than a million dollars in federal funding to pursue research on the causes of drug abuse. Her work focuses on what in the brain predisposes people to addiction, and her most recent paper revealed a genetic risk for alcoholism in women.

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