A Neuroscientist Explores Addiction, the Brain, and Her Past

Judith Grisel shares her story and science in her book, ‘Never Enough’

ByBy the time Judith Grisel turned 23, it had been years since she had gone so much as a day “without a drink, pill, fix, or joint,” she says now. Homeless in South Florida, Grisel stole credit cards to feed her habit, got kicked out of three colleges, and ultimately began shooting cocaine. At one point, while doing cocaine with a Vietnam vet named Johnny, the man overdosed. His eyes rolled back in his head, and he began convulsing. Grisel’s response? “He probably won’t want his next bump,” she remembers.

As Grisel writes in her new book, Never Enough: The Neuroscience and Experience of Addiction, Johnny didn’t die that day. But decades later, of the three people in his apartment during that overdose, Grisel is the only one still alive.

Now a professor of psychology and neuroscience at Bucknell University in Pennsylvania, Grisel has been clean and sober for more than 30 years. Her turning point, she says, was the hope that her seemingly hopeless addiction could be solved with science—specifically through understanding the neuroscience of addiction.

OneZero caught up with Grisel and discussed whether addiction is a mental illness, if more psychoactive drugs should become legal, the promise of psychedelics, and more.

This interview has been edited and condensed for clarity.

OneZero: At the outset of the book, you refer to your struggles with addiction as a mental illness. Yet you also write that you made a “life-or-death choice” regarding whether you “could continue colluding with … [your] mental illness” or “find a different way to live.” There’s an argument to be made that addiction isn’t an illness as we understand it, because drug or alcohol use is a choice, unlike cancer, for instance. Is it fair to use the disease model for addiction?

Judith Grisel: I think we make a mistake, either way, going from one extreme to the other. In the past, addiction was considered a moral illness. Now, we hear individuals can’t do anything about it because it’s in the brain. One thing that’s clearly very different between addictions and cancer is that cancers are problems with cells, and addictions are problems with behavior—like obesity, or gambling, or even OCD [obsessive-compulsive disorder]. But behavior is complex, and I worry about the direction of a purely reductionist biological perspective and saying that we’re sort of automatons.

There has to be some middle ground, and where that’s easy for me to see is that we can manipulate behavior by manipulating the brain. We can also change the brain by changing behavior. So, behavior interventions for anything are often more efficacious than interventions based on neurochemicals or genes.

People are really caught up in this thing now about “Is it a disorder or a disease?” It doesn’t really matter to me what you call it because clearly it’s irrational behavior in the end.

You say that “the brain’s response to a drug is always to facilitate the opposite state; therefore, the only way for a regular user to feel normal is to take the drug.” What’s going on there?

That’s the heart of the matter. The first part is why does the brain adapt like this? Why not just let us mess around and enjoy it? I think the reason for that is the brain is always trying to detect contrast. Has something happened? Is it good? Bad?

For each drug, it kind of adapts in a different way. Sometimes it’s a simple thing, like the down-regulation of cannabinoid receptors, or in the case of Xanax, which interacts with these GABA receptors, those things are so malleable. They really change their structure and function in response to our experiences. Our experience could be a drug or alcohol or it could be stress. Those receptors are constantly trying to adjust to kind of compensate.

For alcohol, the drug does so many things. Every single one of those things that we look at adapt. It causes the system’s release of endorphins. Chronic alcoholics produce very little endorphins, if any. The body just stops making it. It also acts on those GABA receptors. Whatever alcohol does, or any drug, the opposite happens with chronic use.

So many heroin addicts, for instance, not only become physically addicted to the drug, but also the process of doing it. That is, the ritual of being dopesick, scoring, shooting up, etc.

Our brains are so competent they use not only the drug to predict the drug, but the environmental cues to predict the drug. It’s a kind of torture. Imagine your lover has been out of town for a while, and you’re going to meet at the airport. It’s both good and bad. Definitely arousing, definitely seductive, definitely kind of a craving state. Craving is to a point kind of fun. I think the paraphernalia, the bag in your pocket, all those things illicit a sort of anticipatory wide awake brain state. Pleasure and pain are so close that it’s hard sometimes to tell the difference. Now, in deep withdrawal, if you stop them at that point when they’re about to score, they’re about to use, and you hold off, that gets increasingly less and less pleasurable.

You write that the “solution [to addiction] isn’t coming in a pill.” You received some pushback on social media for discounting medication-assisted treatment (MAT) during a recent ‘Fresh Air interview. So, say the opioid addiction medication methadone does get abused, there are some studies that show it can still improve someone’s quality of life or save it.

I need to be more careful. I think to help someone get off heroin, it might be useful. Although, I’ve also heard from people who say they wished they had never taken it. They subsequently try to get off it, and it deepens the addiction. But I don’t want to minimize the fact that people are dying and suffering from their addictions.

I really value the opportunity to not be dependent on a drug. I think that we’re kind of ignoring the cost because of the short-term expediency. I understand that’s an important thing, but I think that the long-term costs are being minimized or ignored. Those are costs to both the individual and their communities.

There is something about human ability to choose that I think is so precious and should be preserved. In the long run, what I would like is everybody to have as much choice as they can. Having choice is sort of the high point of our species.

In regards to choice, are you in favor of more drugs being legal?

Yeah. I think that does go with my view. One, alcohol and nicotine are unbelievably damaging and they’re legal, so it seems irrational to cut it off there. Also, we have a history of making drugs illegal when they’re not used by the powerful. If they’re not, then they’re going to be illegal, so we put [users] in jail. I think legislation has been used to keep people down.

The other reason, which is maybe more pragmatic, is it doesn’t work. Where did we ever get this idea that you could legislate right action? Fear doesn’t work. Look at all the prisons that are full. I guess it gives the politicians something to do, but it doesn’t have a real impact.

Take marijuana. I do think it can be misused. I like the argument that it should be legal, but not for profit because I do think that if we really wanted to enhance people’s lives, we would take away the for-profit industry for addictive drugs, including alcohol and tobacco.

Would you go far to say things like heroin should be legal?

I have mixed feelings. I don’t think it works to make it illegal, so if I had to pick, I would say yes. Maybe everything should be legal and we should spend a lot more time, effort, and money on education. The ideal place for me would be where people knew the risks and could choose. I think that making it illegal almost increases the chances of people who were already on the margins, like an adolescent, or people who don’t have good jobs and stuff. I think that we need education.

Look at injection sites. Now, the fact people are against having clean sites for people to inject, I can’t understand that, as if we’re going to teach them a lesson by letting them catch AIDS or get infections. There’s no evidence that works and not worth shunning the risks involved.

Speaking of risk, you say that the “most depressing chapter” in your book is the one on stimulants like cocaine and the psychoactive drug MDMA. Could you talk a little bit why you wrote that?

I think my experience with those drugs—I still have a feeling of doom when I think about them. It kind of reminds me of what you were saying about the opioid addicts going through the whole rigmarole to get ready to use. It’s an awful push-pull that they create.

With MDMA, that’s a drug most people wouldn’t use every day. Nevertheless, there is evidence that even trying it a few times can cause permanent damage, right?

There is evidence. One thing I think I may want to say more clearly, that I probably didn’t connect in the book, is everything we do changes our brain, and a lot of those changes are kind of permanent. So, the choices, the behaviors we engage in, the things that we read, the food that we eat, the exercise we do, those things and the drugs we take, are all changing our brain.

Just when we say that it changes your brain, it makes it sound like the brain would have been static and now we’ve messed it all up. But what the data suggests is that MDMA is causing changes that are probably more permanent than the changes from opiates, or THC, or maybe even alcohol. Those changes are probably permanent, are going to cause depression, lack of attention, and anxiety. I think those disorders are already epidemics, so we probably don’t want to do anything to increase those.

I tell my students, my own kids, these are the drugs I would not do. At the very bottom of the list would be MDMA and methamphetamine. Cocaine probably would be above that for me because it doesn’t get into the cells, so it might not be quite as a long-lasting problem. Of course, it depends on the dose and it depends on the amount. Then everything up from there. I think alcohol, for instance, is worse than THC, and I think psychedelics cause probably the least amount of harm.

Opiates are somewhere in the middle. Because, like THC, they mimic natural compounds like endorphins, they are not as bad as MDMA or coke (both of those exploit natural processes but not through a normal mechanism). In fact, your brain would adapt but not be damaged, after decades of opiate abuse—in sharp contrast to alcohol. On the other hand, narcotics (that is, opiates) are of course terrible for your life.

In your book, you’re actually fairly optimistic about psychedelics. Are you excited about some of the studies and research on say, psilocybin?

I think it’s exciting. There’s many things different about that class of drugs. They’re wildly potent, like 100 or 1,000 times more potent than anything else we’ve talked about. They work in a targeted way, at a specific receptor. They’re not self-administered by non-human animals. And they don’t release dopamine in the brain region called the nucleus accumbens. For those reasons, I don’t think they’re addictive in the classic sense. Of course, though, people can get addicted to placebos. We are weird.

In my experience, psychedelics can be helpful in the sense that they can provide the ability to step out of oneself. Still, I don’t think, “Oh, everybody should go out and do this.” But we have so much suffering and self-absorption, really, that it might be worth experiencing these things. And there’s no evidence of brain damage.

The big side effects are terrible trips, where you really can exacerbate or bring on psychosis, if you’re at risk. And that’s real. You can also experience flashbacks. And we don’t really understand the flashback, but we are starting to. Maybe it has to do with how potent the stuff is, and you never actually get rid of any drug you take, except for alcohol. I mean, you’re always removing just a percentage of what’s left. So it could be that these few molecules of, say, LSD are still floating around. You just activate one receptor or something. But we don’t understand how that happens. It’s hard to study in the lab.

Are there certain drugs that affect women and men differently?

Oh yes. All the opiates. Probably all drugs really. Here’s a not-so-fun story: When I was in grad school, we used only male subjects in every study in all the labs I was in. And if you look at all the studies from the 1980s and ’90s, it’s almost always white male rats or mice.

The rationale is really nutty because it was sort of two contradictory things. One argument was that men and women are the same, so male is sort of the defaults for humanity. And then the second argument was that women are too variable because of their modulating hormones, which just totally contradicts the first one.

At any rate, binge-drinking, for instance, is probably motivated for different reasons in men and women. I just was reading a paper today on the downregulation of cannabinoid receptors, and it may differ in males and females. It may be more extreme in females. This is a 2019 paper. Cocaine also differs in the intensity and the rate of addiction development. It’s higher in females.

So, in general, women have used at lower frequencies, but when they do use, they develop problems more quickly and they become addicted more quickly. They seem to be more sensitive. The reasons—the molecular and cellular reasons for that—are just beginning to get uncovered. There’s probably 10 years of research and maybe 200 papers on it, which is nothing.

Is there such thing as an addictive personality?

We know about half the risk for developing an addiction is genetic and half is environmental. In those cases, we don’t know the precise causes of that. Even though we’ve known that addiction runs in families, and we know it’s carried in our DNA somehow, we don’t have many specific genes. There are a few. There’s a good one for nicotine dependence. There’s one for opiates. So there’s a few, but if you take all the genetic variants, all the genetic influences on addiction, we’ve only explained a very small percentage of it. Like less than five percent of it, and actually the biggest one is metabolism of alcohol in the liver.

It’s the same with the environment. There’s all this environmental influence, but we don’t have any idea what most of it is. Of the genetic influences, personality factors, which are largely genetic, you’re born with certain tendencies and they’re basically stable throughout your life, things like high novelty seeking and low harm avoidance. This is another reason, going back to legislation, that people who are prone to addiction are those very people who are least likely to be swayed by the threat of punishment. So if you say to 10 kids, “You’re going to get in trouble for this,” the three who don’t care are also the three who are likely to become addicts or get in trouble.

Addicts are often seen—and identify—as addicts for life, even when it’s been years since they used. Do you think there’s value in always referring to oneself that way, and do you still refer to yourself as an addict or recovering addict?

Yeah, I do refer to myself as a recovering addict. It’s a descriptor like I’m married, I’m a mother, or I’m a scientist. It’s a part of who I am, because those experiences shaped so much of my life. It’s been 32, almost 33, years since I’ve used, and every once in a while, I still have a big urge to do so. It’ll come out of the blue. A certain kind of weather and I’ll really like a margarita. And people say, “Judith, do you want just a glass of wine?” No! Do you know what I want? A whole bottle of scotch!

Would you encourage people who have struggled with addiction to do abstinence only? For instance, if I was a former heroin addict, would you say I probably shouldn’t try to be a social drinker?

The evidence is in the favor of abstinence. Most people just can’t moderate. Now, most people don’t stay abstinent either, but it seems to be more helpful in the long run. It would be terrific if you could find a bunch of people who suddenly became social users, but there’s not a bunch of those people. There’s a few that maybe grow out of it, but not a lot. That’s not a great thing.

I guess I’m for reducing harm. I think less is better than more, if you’re like me. The thing that I like about abstinence, and it’s sort of paradoxical, but I feel more free. I guess because I recognized that I wasn’t really able to limit myself.

I don’t think I’m any more of a moderate person than I was. But what I now enjoy is my peace of mind and personal freedom. And that’s all contingent on not having this constant wrestling match with addictive drugs every day.

A writer. Not based in Brooklyn. Recent bylines with Vox, Vanity Fair, Harvard Magazine, MIT’s Undark, VICE and Playboy.

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