Never Enough: The Neuroscience and Experience of Addiction

by Judith Grisel

Worldwide, addiction may be the most formidable health problem, affecting about one in every five people over the age of fourteen. In purely financial terms, it costs more than five times as much as AIDS and twice as much as cancer. In the United States, this means that close to 10 percent of all health-care expenditures go toward prevention, diagnosis, and treatment of people suffering from addictive diseases, and the statistics are similarly frightening in most other Western cultures. Despite all this money and effort, successful recovery is no more likely than it was fifty years ago.

The drug provided physical relief and spiritual antidote for the persistent restlessness I’d been unable to identify or share.

Until the moment alcohol first filled my belly and brain, I hadn’t consciously recognized that I’d been just enduring, but that evening, as I leaned out the open window of my friend’s bedroom, gazing at the stars, I took what felt like my first truly deep breaths.

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.

George Koob, has said that there are two ways of becoming an alcoholic: either being born one or drinking a lot.

In other words, my response to being overwhelmed by the deep void was to leap into it.

The opposite of addiction, I have learned, is not sobriety but choice.

culvert

nadir

lorn

I’d finally reached the dead end where I felt I was incapable of living either with or without mind-altering substances. This bleak situation describes the condition of many, if not all, addicts and illustrates why relatively few recover.

The fundamental role of the brain is to be a contrast detector. As experiences are distinguished from monotony, they spark neurochemical changes in specific brain circuits, informing us of all we care to know: opportunities for food, drink, or sex; danger or pain; beauty and pleasure, for example.

Repeated administration of any drug that influences brain activity leads the brain to adapt in order to compensate for the changes associated with the drug.

Having a set point enables meaningful interpretation of a stream of ceaselessly changing input. Sustained feelings in either direction impede our ability to perceive and thus respond to new information, so the nervous system imposes transience.

When the brain is first exposed to a stimulus, the a process is unmitigated by compensatory brain mechanisms, and thus State A is experienced in full. However, as the b process is recruited, State A is dampened.

The hallmarks of addiction—tolerance, withdrawal, and craving—are captured in the consequences of the b process. Tolerance occurs because more drug is needed to produce an a process capable of overcoming a stronger and stronger b process. Withdrawal happens because the b process outlasts the drug’s effects.

In other words, the brain is so well organized to counteract perturbations that it uses its exceptional learning skills to anticipate disruptions, rather than wait for the changes themselves, and begins to dampen drug effects before the drug has even been delivered.

Suppose you enjoy a few drinks with friends at a neighborhood bar every Friday after work, as you have been doing for years. It turns out that the predictability of this routine leads to changes in your experience. First, the alcohol will have less effect on you in that particular place and time and with those particular friends than it would have elsewhere. If you changed plans and went instead to a party, you’d become more intoxicated with the same amount to drink.

One of my favorite moments was shortly after coming to consciousness in a new day and seeing for an instant the vast bleakness of life before me and then suddenly realizing—just as newlyweds might reach in excitement and hope for a spouse beside them in bed—that I could get high.

and more people now die of narcotic overdoses than automobile accidents.

In fact, pain has two primary purposes: the first is to teach us to avoid dangerous stimuli or situations, and the second is to encourage recuperation after failing the first lesson.

The bipolar practice of pitying addicts while at the same time greasing virtually every social interaction with an obscene amount and variety of booze seems heartless if not mindless. It’s also exclusionary—as if the only truly comfortable place for people who can’t handle their drink were under a bridge.

Moreover, because alcohol reduces anxiety, this drug will be more reinforcing to those who are naturally anxious than to those who are not, increasing the risk of regular drinking in such individuals. There is good evidence that those of us who are naturally inclined toward any of these predisposing states are more likely to abuse the “complementary” substance.

Over the years, a wealth of data from studies on twins had demonstrated that about 50–60 percent of the risk for alcoholism came from inherited factors.2 And those who have a positive family history for alcoholism are three to five times more likely to develop the disease than those without such a background,3 though the particular genes responsible remain largely unknown.

Dr. Gianoulakis and her colleagues showed that high-risk individuals have about half as much beta-endorphin in their blood as those at low genetic risk;4 Jan Froehlich and her colleagues then showed that these levels come largely from our parents.5 But most interesting to me was the fact that alcohol was able to remedy this natural deficit especially in those who inherit a high risk for excessive drinking and, at higher doses, produce a surfeit of the peptide.6

In fact, alcohol killed about twice as many people in 2016 as prescription opioids and heroin overdoses combined, and even this number would be almost three times higher if it included drunk-driving-related deaths.

The demand for benzos is higher than ever. Excessive anxiety is estimated to be the sixth leading cause of disability across the globe.

It might be a good time to ask, given our long and ardent relationship with this class of drugs despite their substantial liabilities, whether there is a better way to help those suffering with insomnia or anxiety. Or even to wonder how these conditions are so common as to be statistically normal—indeed they afflict at least one in three adults in the United States—yet still are considered abnormal behaviors.

contraindicated.

In moderate doses, caffeine may elevate mood and reduce symptoms of depression.

According to the World Health Organization, over 1.1 billion people smoke tobacco, and more than 7 million die each year from their addiction. Like every addict who dies gradually, it isn’t because they over-enjoyed a good thing. Instead, the misery imposed by an adapted brain makes quitting seem worse than dying.

On average, tobacco users lose fifteen years of life. Today, 5.7 percent of total health expenditures are spent treating smoking-related illnesses, and 12 percent of all adult deaths worldwide result from this habit. In fact, the total annual cost of smoking is almost 2 percent of global gross domestic product, which is also about 40 percent of what all the world’s governments spent on education.4 In total, nicotine addiction burdens the global economy with more than $1.4 trillion in health care and lost productivity each year.

For one, any drug that stimulates dopamine greases the rails for another.

monoamine

That I was easily able to find the room in Parkland speaks to the implicit kinship among users; the further away from social norms I traveled, the easier it was to connect with my kind, just as water flows to the lowest point.

Research in rats and primates indicates that moderate to high doses of MDMA damage nerve terminals, perhaps permanently.

example, primates given ecstasy twice a day for four days (eight total doses) show reductions in the number of serotonergic neurons seven years later.

The recent history of these drugs began with the isolation of mescaline in 1898 by the German chemist Arthur Heffter, who obtained peyote from a colleague in the United States.

Only 50 to 100 micrograms (0.00005 grams = 50 micrograms) of LSD, usually delivered through a paper tab that has been dosed with a small amount of liquid, will induce a trip that lasts for six to twelve hours.

the single exception to humans being the sole species to show any interest in volunteering to test psychedelics were nonhuman primates who—only when deprived of normal external stimulation, including social interactions—would sometimes prefer to sit alone in their cages and self-administer psychedelics, lost in what, I can only imagine.

I mean, that’s at least in part why I ingested chemical waste—it was a kind of desire to abbreviate myself….I wanted to be less, so I took more—simple as that. —Carrie Fisher, Wishful Drinking (2008)

The drive to alter experience is universal. We have been intentionally administering substances in order to alter psychological functioning as far back as we have written records (and likely before). For every advance in our understanding of how the brain works, we discover that there exists a natural product to exploit it.

For instance, khat is so popular in Yemen that its cultivation consumes an estimated 40 percent of the country’s water supply. One “daily bag” of khat requires an estimated 500 liters (130 U.S. gallons) of water to produce, which has lowered the water levels in the Sanaa basin.

kappa opioid agonist.

Salvinorin A has no other known activity across fifty other receptors, transporters, and ion channels, including the serotonin 2A receptor—the principal site of activity of classic psychedelics such as LSD and psilocybin.5 So far, so mysterious.

Every time I draw a clean breath, I’m like a fish out of water. —Narcotics Anonymous

My desperate evasions were just like those of millions of other people determined that they’d never be like a drunkard parent or a panhandling nomad; not one of us sees it coming.

But as I gradually came to terms with the fact that I didn’t use drugs as much as they used me, my thoughts turned to figuring out why on the way to fixing it.

The four are these: an inherited biological disposition, copious drug exposure, particularly during adolescence, and a catalyzing environment. It’s not necessary to have all four, but once some threshold is reached, it’s like breaching a dam—virtually impossible to rebuild. So, 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 first is that the more DNA one shares with an addict, the higher one’s risk. Typical siblings share 50 percent of their DNA, but identical twins share virtually all of it, and they are about twice as likely to have similar addiction histories.