#4 The difference that makes a difference: Craving

What really makes the difference between the addict and the non-addict is the suffering involved with addiction. For the addict, the most immediately conscious aspect of addiction is craving. This isn’t just a matter of really wanting something. Craving is the most powerful motivational force the brain can marshal. How strong is it? When an addict reports craving, the same neural processes are active in her brain that are active in a person with obsessive-compulsive disorder who is experiencing a compulsion (Koob & Le Moal, 2001). This is the primary source of an addict’s suffering.

In order to understand how craving works, we need to look at how it’s produced. Today, I’ll explore the neurochemistry behind stress, and how stress is related to craving. You know that an addictive substance or behavior (which I’ll just call “drug” from now on) makes the midbrain mark it as highly salient to survival, and rewards its use. It’s easy to see how reward-seeking motivates drug use, but how does that transition to dependence?

Enough with the carrot; time for the stick: 

Once the midbrain ranks a drug highest on the list of survival activities, it’s not enough just to reward/reinforce use of the drug anymore. The dopamine surges involved with using the drug are so high, nothing else comes close to producing that powerful message anymore. In fact, your midbrain interprets the “high” of the drug as being the new set-point against which all other activities are measured. It has to devote the lion’s share of its activity to reinforcing use the drug, which means other activities can’t be reinforced as highly. The addict begins to experience anhedonia, meaning “without pleasure,” a state in which nothing produces as much of a reward as the drug.

This is because the midbrain has begun to interpret lack of the drug as threatening to survival. It’s no longer just that the drug is pleasant; it’s that not using the drug becomes unpleasant. More brain systems have to be recruited, which motivates more drug use. This is where stress comes in.

The baseline functioning of your body’s systems tends toward what is called homeostasis. Homeostasis means both: 1) the basic set of parameters necessary for an organism to survive, like a certain blood pressure, internal temperature, and so forth, and, 2) the self-regulating process that keeps an organism’s functioning within those limits. For the most part, your organs are self-regulating. They know what their normal set-point is, and can correct minor problems locally in order to maintain that stability. When something is seriously out of whack, however, more of the body’s systems have to be recruited to maintain homeostasis.

Normally, when there’s an immediate environmental stressor, the Captain routes control of all systems to the bridge. Err… the brain’s stress system (CRF) takes over executive control through the release of neuropeptides that signal the release of adrenaline, cortisol, and so on. It shuts down appetite, increases blood pressure, heightens attention, decreases immunity responses, etc., in an effort to respond to the stressor. After the stressor goes away, the CRF relinquishes power and lets the organs take over their individual functions once again. This isn’t a bad thing, in and of itself. You should probably initiate red alert and pay attention if, say, a bear is munching on your arm. You can see how appetite and other activities might need to go on the back burner a bit while you discuss things with the bear. But you can also see how prolonged periods of stress would actually kill you.

In the case of addiction, lack of the drug prompts a continual red alert. The stress system declares martial law and takes over executive functioning pretty much all the time. This requires a significant outlay of resources. In this way, the body moves out of homeostasis and enters allostasis. Allostasis is the condition in which constant or chronic stress obliterates all the body’s normal set-points for homeostasis, and stress becomes The New Normal.


Now that the stress system is in charge, there is very little margin left for responding to novel stressors. You can’t afford to put a lot of energy into activities that don’t involve the drug. All your systems are recruited and pressed into the labor of maintaining allostasis, and you experience serious deficits in organ functioning and stress response. Hell, even your midbrain gives up trying to reward you for anything, including using the drug. It’s not even fun anymore. But you still remember it as being being better than expected.

This is how craving develops. We’ve said that all your systems are recruited in response to chronic stress and allostasis. Remember the frontal cortex? The one that gives a fuck about your future and does all your planning, who knows when to say when? The one who’s supposed to be in charge around here? In addiction, you become hypofrontal, which means the frontal cortex stops being in charge altogether, and is hijacked into giving all its fucks only about the drug. On a cellular level, in allostasis, the frontal cortex has to direct all its energies toward procuring the drug, planning for it, thinking about the next time you’ll have it, wondering if there will be enough when you get there. This transitions to obsession. You also have to hide the preoccupation and obsession. Everything you do that isn’t using the drug becomes “not-using,” a thing you do until you can get the drug again. This right here is craving, and it never goes away.

The addict cannot choose not to crave. When an addict stops using, at first there may be physical withdrawal symptoms that signal the body’s distress in absence of the drug, to varying degrees. But long after the physical withdrawal symptoms fade, craving continues. The neural pathway that associates the drug with survival is indelible. This is why I think there is plenty of reason to say that addiction is not, in itself, a choice. It starts in the midbrain, which has nothing to do with moral reasoning, damages the frontal cortex’s ability to make choices, and, years after an addict stops using, the physiology of addiction is still there in the form of craving.

I’ve said that drugs feel different to some people. Well, it’s also true that the world feels different to some people. Individual and genetic differences in how the brain interprets and handles stress make some people physically more vulnerable to addiction. I’m not talking about one’s attitude toward life here. I’m not talking about being weak in the face of stress. I’m talking about the brain’s physical chemical reaction to stressors, reactions that occur outside of conscious interpretation and which are inaccessible to rational control.

Some differences between addicts and non-addicts in terms of stress are down to genetic vulnerability, as we discussed in an earlier post. Some people’s stress systems don’t relinquish control after a stressor is gone for a much longer time than for others. This is true for many people with anxiety disorders, and anxiety is often linked with addiction. Environmental factors also make a difference: Living in dangerous conditions for a long time, certain types of prenatal stress, and things like PTSD can change the body’s set-points such that a person is forever and fundamentally altered with regard to the processing of stress. The connections between addiction and other disorders like anxiety and depression—both of which are states involving some degree of allostasis and anhedonia—also make more sense when you look at how we handle stress. So, you can see there are differences between addicts, as well.

All of this leads me to conclude that addiction is far better characterized as a disease than as a moral choice. On the disease model, addiction would be defined as a defect of the midbrain—a “stress-induced hedonic dysregulation” resulting in loss of control, craving, and persistent drug use despite negative consequences (McCauley, 2009). If this is true, it has serious consequences and challenges for the way we approach the treatment of addiction. What kinds of choices does the addict have, and how do we marshal those choices in order to aid the addict? These are the most important questions to be answered in addiction science.

*Edit: I’ve cleaned up some mistakes here regarding how reward is not the same as reinforcement. I also originally referred to negative reinforcement as if it were the same thing as punishment. That’s not the correct technical terminology, and I appreciate Ann Locasio’s correction.


Koob, G.F. and Le Moal, M. (2001). Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology 24:97-129. http://www.nature.com/npp/journal/v24/n2/abs/1395603a.html

McCauley, K. (2009). Pleasure Unwoven. Film. The Institute for Addiction Study.

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