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Points Bookshelf: “Never Enough” by Judith Grisel

Updated: Aug 29, 2023

Editor’s Note: Welcome to the first installment of the Points Bookshelf, in which we review books about drugs, alcohol, history–and maybe even a combination of all three. We open with a review of Judith Grisel’s new book “Never Enough: The Neuroscience and Experience of Addiction,” which was released last month. 

If you’re interested in reviewing a book for Points, get in touch! You can reach editor Emily Dufton at emily.dufton (a)

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I first heard Judith Grisel on Fresh Air. Her interview with Terry Gross was fascinating. She has a PhD in behavioral neuroscience and psychology from the University of Colorado, Boulder, and she spent a good part of her early life addicted to numerous substances, including alcohol, marijuana, cocaine, heroin, and more. Now drug-free for over thirty years, she is a professor of psychology at Bucknell University, in Lewisburg, Pennsylvania.

Her approach to the difficult subject of addiction is thus colored by all of her experiences. Because of her years as someone who had an unhealthy romance with numerous intoxicants (the title comes from a statement a friend made to her in a seedy hotel room in Miami as they snorted up as much cocaine as they physically could; there would “never be enough cocaine” for Grisel, her friend said, and when she realized the truth in this statement, it was a turning point in her life and career), she’s aware of the havoc addiction can wreak in individuals’, families’ and communities’ lives. As a neuroscientist and psychologist who has spent decades studying how the brain reacts to, and adapts to, intoxicant use, she’s also adept at explaining the biological and neurological underpinnings of this issue.

I was particularly drawn to her honesty. Though Grisel still struggles with the idea that she cannot reliably use substances socially (she could never have just one or two drinks, she writes; she would want the whole bottle, and then ask for another), she also uses her unique perspective to study addiction with an evenhanded approach. After I heard her on Fresh Air, I immediately pre-ordered the book.

To be honest, Never Enough wasn’t what I expected. Grisel’s story runs through the text, but this is far from a traditional “once upon a time I was an addict but now I’ve overcome the problem” memoir. Instead, Never Enough is an immensely scientific work, featuring diagrams of the brain, illustrations of the ethanol molecule, and charts depicting the brain’s process of tachyphylaxis, or “acute tolerance” (the “adaptive, compensatory changes that begin as soon as alcohol reaches the brain”).

I am far from a neuroscientist–the last biology class I took was in 11th grade–but I found Grisel’s book engaging and accessible. Never Enough is written in language I can understand, with an approach that translates the complex functionings of the brain into fun–and often frightening–reading.

Grisel opens with a bit of her backstory. When she first started drinking, at age 13, it was a remarkable release for a quiet, shy girl from Florida. As her inhibitions melted away, she wondered why everyone didn’t drink more, and more often. Soon her interest in alcohol expanded to the use of other, and nearly all, drugs. In each, she adored the liberating sense of oblivion they provided. As she writes in the introduction,

“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 (and missed opportunities) fill me with an overwhelming sense of desperation.” (6)

This is a pretty heavy perspective, though one that I imagine many people can relate to. It also makes for a strong foundation for the behavioral neuroscientist she was about to become.

At 23, Grisel attended rehab and stopped the use of all drugs. This has been difficult at times, including after she successfully defended her dissertation and couldn’t celebrate with champagne as was traditional in her department. But it launched a research topic and a career, the fruits of which can be seen in Never Enough.

Her first chapters outline the brain in relation to drug use: how it functions, the “laws of psychopharmacology,” and the bidirectional relationship between the brain and intoxicants. Her three laws of psychopharmacology are as follows:

1.) All drugs act by changing the rate of what is already going on.

2.) All drugs have side effects.

3.) The brain adapts to all drugs that affect it by counteracting the drug’s effects.

In short, this means that, neurologically, there is no free lunch. “If chemicals are used with regularity,” she writes, “the brain always adapts to compensate. The brain’s response to a drug is always to facilitate the opposite state” (32). This means that, with increased use, the comedown will always be harder, more painful, because the brain is trying to once again reach a state of homeostatis. The coffee drinker doesn’t drink coffee because she is tired; she is tired because she drinks so much coffee. Heroin blocks pain in a naive user, but if the user tries to stop, they will be in excrutiating pain.

Grisel calls the brain’s equal and opposite response to drug use the b process, and the more a person uses a substance, the more protracted and painful the b process will be. We can see this in the struggle people have to quit smoking, the pain of opioid withdrawal, and the irritation of someone trying to give up sugar, alcohol, marijuana or coffee. And these effects last far longer than the traditional “withdrawal period.” As Grisel explains, after giving up intoxicants, it took her one full year to stop missing alcohol, and 9 full years to stop missing marijuana. Neurologically, psychologically and emotionally, intoxicants make changes in the brain that last for a very long time.

Grisel then goes on to outline the effects of several specific substances on the brain. She spends a chapter apiece looking at THC, the active ingredient in cannabis; opiates; alcohol; tranquilizers; stimulants; psychedelics; and “other abused drugs,” including ephedra, phencyclidine, ketamine, salvia, spice, Xyrem, and inhalents. The effects of these substances on the brain, which Grisel outlines at length, were enough to give me pause. She calls alcohol a “pharmacological sledgehammer,” cocaine a “laser,” and marijuana a “bucket of red paint,” because it bathes neural processing so completely, and, most worrisome for a neuroscientist, in ways that researchers like her still don’t understand (52).

Grisel offers two major arguments in her book. The first is that “what goes up, must come down.” As explained above, the brain seeks to achieve stasis, which means that whenever it gets high, a downward spiral is around the corner. With many substances, especially opioids, the high quickly disappears and, since the b process lasts so much longer than the a process (the high), that means that many addicts are quickly forced to take the drug to simply feel “normal”–to negate, or at least hold off, the painful b process for just a bit longer. When this point is reached, it will take the brain even longer to adapt once again to statis, for a complete balance to be achieved. (Though, Grisel kindly notes, this is not impossible–the brain’s plasticity and ability to adapt to change never stops, even in advanced age–so there is always a chance for successful rehabilitation.)

But her other argument is even more important, and, given the current conversations surrounding drug use in the United States today, perhaps controversial. She argues that, if a substance affects the nucleus accumbens (the region of the brain associated with processing rewarding and reinforcing stimuli), it has the potential to be addictive. This applies to the usual suspects like heroin, coke and alcohol, but also to chocolate, hot sauce, sex, gambling, and marijuana. She is not quite Alex Berenson in Tell Your Children, arguing that marijuana is leading us all down the path to murdering our grandmothers, but she makes it very clear that cannabis has real, and potentially addictive and damaging, effects. Those arguing for legalization by suggesting that alcohol and nicotine are more damaging than THC would do well to read Grisel’s work; this may not be the most neurologically viable argument after all.

She makes a few other points that I imagine would disturb those in the legalization community. She makes it very clear that intoxicant use is best done after the age of 25, when the brain reaches “neural adulthood” and the potential for addiction plummets. (Thus, legalizing access to nicotine for 18-years-olds in the US and cannabis for 18- and 19-year-olds in the Canada is, in Grisel’s view, a bad idea; even the current drinking at, at 21, is too young.) She also addresses the “gateway effect.” “A growing body of research documents enhanced drug-taking and drug-seeking behavior in humans and animals following adolescent exposure to substances including cannabis,” Grisel writes, though she should note that her own early exposure, to alcohol at age 13, was also an example of this same effect (191).

My few other critiques of her work are that many of her chapters end abruptly, often when I felt like she was just getting rolling, and that some of her writing gets a bit silly. (See page 193, where she concludes a discussion of the problem between adolescent thrill-seeking behavior and higher rates of addiction with adolescent intoxicant use by declaring, “What a pickle!”) She also never goes into depth about her own process of recovery. She briefly mentions a “rehab” of some sort, but we never get any details on it. Instead, she lets us know that, though she still finds herself longing for intoxicant use, she successfully stopped using everything but caffeine over thirty years ago and has never looked back. This is remarkable, since relapse is so very common in the realm of addiction, and I felt it deserved a longer explanation.

Her conclusion is perhaps the most depressing part of the book. Researchers in America have been studying addiction for almost a century (see Nancy Campbell’s excellent book Discovering Addiction for more on that story), but, as Grisel points out, we still know very little about how, and why, addiction develops in certain individuals. We have moved from describing addiction as a moral failing, to a brain disease, to a learning disorder, but that still doesn’t quite completely define the problem. “Underlying all this uncertainty is the reality that we still have no objective measure to use for addiction,” she writes. “We’ve used ‘addict’ or ‘alcoholic’ and then ‘drug dependent’; now we talk about having a drug use disorder. Changing names or diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders might provide some with an illusion of progress, but I think it just makes it more clear how little we truly understand” (202).

Grisel ultimately blames addiction on larger cultural and social factors. Like Johann Hari, who concludes in Chasing the Scream that addiction is really an issue of the lack of connection, Grisel sees our society’s incredibly high rates of addiction and substance abuse as the result of the following factors:

  1. “More than ever before in our evolutionary history, we possess a keen awareness of widespread tragedy and suffering in the world. This is a painful context in which our attempts to avert and deny the burden of consciousness have grown more and more desperate and widespread” (214). In other words, life is more depressing than ever, and more people than ever want to escape.

  2. There are “rapid technological advances in drug potency and delivery,” which make it easier to access and use increasingly potent substances (think fentanyl rather than heroin, or 90% THC vape cartridges rather than homegrown flower) (214). And, as she notes, the more often we use the drug, and the more potent it is, the more likely the chance for addiction.

  3. Finally, one of the biggest changes is that “solitary drug taking” is now more common, as opposed to drug use as a “culturally endorsed ritual” (215). The “tendency to use alone is an index of abuse,” Grisel writes, and using alone, at one’s whim, is more likely to result in addiction than when drug use was limited to larger cultural practices (think of ayahuasca ceremonies in South America).

Grisel doesn’t offer any solutions to the problems of drug abuse (she calls finding the cure for addiction the “holy grail”), but her work is still of extreme import and use. Never Enough is an accessible primer on the effects of drugs on the brain, written by a pedigreed, experienced neuroscientist who has struggled with addiction herself. For its minor flaws, Never Enough is a useful, fascinating addition to the canon of books on drugs and drug use, and Grisel’s is another voice telling us that we have many more social and cultural problems to solve first if we ever want to truly confront, and transform, the problem of drug addiction in our world.


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