Never Enough: The Neuroscience and Experience of Addiction

by Judith Grisel

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

all addictive drugs are addictive precisely because they share the ability to stimulate the mesolimbic dopamine system.

most research suggests that the psychedelic LSD does not stimulate the mesolimbic pathway. From this and related evidence, the majority of addiction researchers would argue that LSD is not an addictive drug.

We now also understand that the opposite of pleasure is not depression but anhedonia, the inability to experience pleasure. Of course, depression and anhedonia are not mutually exclusive, because many depressed individuals also have difficulty experiencing pleasure. But in general, the mesolimbic pathway conveys a transient good time, not a stable sense of hopefulness that would truly serve as an antidote to depression.

All drugs act by changing the rate of what is already going on. All drugs have side effects. The brain adapts to all drugs that affect it by counteracting the drug’s effects.

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.

The brain’s response to a drug is always to facilitate the opposite state; therefore, the only way for any regular user to feel normal is to take the drug.

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.

For some drugs, such as antidepressants, adaptation is actually the therapeutic point. Developing tolerance to selective serotonin reuptake inhibitors (SSRIs) may help to change a pathological affective “set point” so that being depressed is no longer the patient’s normal state.

I’ve been clean for more than thirty years, and I’m still not really interested in moderation. Often people ask whether I don’t wish I might have a glass of wine or a hit off a joint, but I don’t want just one glass or a light buzz; I want the whole bottle, the bag, and then some more of each. The Grateful Dead argued that “too much of everything is just enough,” but as it turned out for Jerry Garcia, and I’d bet is the case for many of us, too much is still not enough. In other words, if by chance someone does develop a pill to cure my addictive nature, I’d take two and use every day.

So, if you smoke weed, remember that infrequent and intermittent use is the best way to prevent downregulation and its unfortunate effects: tolerance, dependence, and a loss of interest in the unenhanced world.

Moreover, simply snipping a pair of cranial nerves could quickly render someone blind, deaf, or anosmic—the pathways are relatively simple, discrete, and well characterized. Pain is processed redundantly and diffusely, and there is simply no surgical intervention to relieve chronic pain (as many medical doctors and their patients know too well). Instead, pain recruits overlapping pathways and circuits throughout the body and brain and, along with a rich neurochemistry of opioids and anti-opiates, portends the critical nature of pain for our survival.

Recently, however, methadone has been used in younger and younger addicts. This is especially tragic, if not unethical, from both a neurobiological and a social perspective. Because methadone is such a long-lasting opiate, when prescribed with the clinical goal of keeping the brain soaked in the stuff to stave off withdrawal, it produces an immense addiction. This drug is even harder to kick than heroin; the latter is hell, but for a relatively short time. Therefore, to prescribe a drug like this to people barely out of their teens is to condone “maintenance” that is in some ways a life sentence akin to housing the mentally ill in the back wards of state institutions: they’ll be less trouble for the rest of us, but unlikely to have much of a life.

Suboxone is a combination of a Narcan-like drug and an opiate drug called buprenorphine. Buprenorphine doesn’t have much street appeal for the same reason it’s a good choice here: although it occupies the same places in the brain as opiate drugs, it doesn’t do as good a job and therefore it is much less rewarding than its abused counterparts. However, the effects are potent enough to reduce symptoms of withdrawal, including craving, and to allow addicts to sleep. It’s less stigmatizing than methadone, but even more important, under a doctor’s supervision, it won’t make the addiction stronger. For someone motivated to get clean, this could provide a sound start. If the dose is tapered over time, it’s likely to afford the best shot at a life free from opiate addiction.

For example, by the 1970s, Valium was the single most prescribed brand of medicine in the United States, used by about one in five women. It was also the cause of more emergency room visits than all illicit drugs combined. Though overdose from Valium is virtually impossible, withdrawal symptoms are anything but banal; combined with tolerance and craving, these drugs are highly addictive. Nonetheless, in 1980, 2.6 billion pills were dispensed, which is almost one hundred doses per person.

Phenobarbital is currently the most widely prescribed antiepileptic drug in the world, aptly dubbed “king of the barbiturates.”

More recently, Michael Jackson succumbed to a massive dose of Propofol, which his private doctor administered to help him sleep. The very short-acting anesthetic doesn’t share the barbiturate structure, but acts in a similar fashion. It’s a very good anesthetic because it has a really fast onset and short half-life, but like all these drugs, as well as the rest of Mr. Jackson’s pharmacological strategies, doses need to escalate as tolerance develops, making the therapeutic window grow narrower and the risk of accidental overdose grow greater over time.

Speaking of which, both inventors of barbiturates, the chemists Fischer and von Mering, died of overdose after years of dependence.

Barbiturates are still used for surgical anesthesia, as well as in the treatment of epilepsy, and to help reduce intracranial pressure following traumatic brain injury. However, in the 1960s another class of sedative-hypnotics, also GABAA agonists, was introduced—benzodiazepines—and these were purported to be much safer and less addictive than their predecessors. Not surprisingly, those claims were overstated. Millions of people are now hooked on benzos, but on the bright side it’s not possible to overdose from them alone, so the market is likely to stay strong.

On average, tobacco users lose fifteen years of life.

The United Nations Office on Drugs and Crime indicates that meth is one of the most popular synthetic drugs worldwide, with at least thirty-seven million users—about twice the number of either cocaine or heroin (with about seventeen million users each).

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.