The Hallmarks of Addiction
Intro to the Hallmarks of Addiction
The word “Overdose” was again in the news when Cory Monteith, Finn from the hit show “Glee,” died on July 14, 2013. He joined the ranks of Amy Winehouse, Janice Joplin, and Jimmy Hendrix--a group of extremely talented people who fell for drug use and died from their addiction. The public often repeated one statement when reflecting on their deaths:
“I just don’t understand why he felt he had to do that.”
Statements like this sum up the mystery of addiction, a mystery that compels many of us to further study the phenomenon. At its heart, the statement holds two ideas: “I don’t understand” and “he was driven by a feeling.” These two feelings are deeply rooted in the biology of the disease.
Addiction behavior is driven by powerful feelings. Ironically, our attempts to rationally understand and empathize with people suffering mental illnesses are inevitably flawed because illness affects the reasoning and empathic skills of the sufferer. The disease of addiction changes the brain, and those without addicted brains find it very difficult to understand the actions produced a brain in the addicted state.
Author’s Note
Before we begin I’d like to take a moment to address the issue of terminology in addiction. As our understanding of this disease changes, so do the words we use to describe it. As a person who has lost the battle with substances, I call myself an addict. To many this can be an offensive word, to me it is an attempt to reclaim and redefine the word. I wear this word as a badge. To me it carries all the negative connotations surrounding addiction and at the same time I use it to show a fundamental principle of biology. Mechanisms are never good or bad; they are situationally dependent. The things that have make me an addict also grant me many benefits. My anxiety is the source of my drive. A combination of my altered anxiety and reward make me hypersensitive to certain emotions in others. The list of benefits is long...as is the list of cost.
Most current terminology favors terms like “Alcohol Use Disorder,” a thing a person has and not a thing that pers IS. These terms focus on the substance and a behavior as opposed to a description of a person, an “addict.” The distinction of substance (or behavior) is likely to be important in the future. People addicted to different substances are likely going to have many similarities, but the biological effects of the substances are also likely to cause unique changes to a person’s biology.
It is likely that addiction causes permanent brain changes and thus there is debate about whether someone who has become addicted and is now in prolonged abstinence is still technically addicted. For now, I will attempt to use the terms “in active addiction” and “in recovery” or “with prolonged abstinence” to help distinguish the symptoms. Similarly the people that I know use the term abstinence to describe someone who has gone some time without an abused substance. Those that are seeking medical, psychological, and even spiritual treatment to remain in abstinence are termed “in recovery.”
Like all things that are changing in this world, the best thing that a person attempting to understand a complex biology can do is ask questions rather than assume nomenclature. If you approach a situation with a question, I believe it is the best that you can do. Let’s move on to a description of addiction now.
Hallmarks
As I mentioned above, every person in the full state of addiction has different things happening in their brains. Many of these were happening before a person used drugs; some are simply a part of a person’s basic biology. There are the direct affects of a substance (or behavior) on the brain. These are generally characterized by short term changes. Most people are familiar with the idea that there is a dopamine release in the brain in response to drugs. There are also long term changes that can happen to the structure of the cells in the brains.
Each of these are going to differ by people, length of use and the type of drug. For example, some people have anxiety or impulse issues before they ever do drugs. Each is going to differ by drug. For example, alcohol and cocaine attack different and specific molecules in the brain.
However, there seem to be some strong similarities in people who display prolonged addiction behavior. As an homage to one of my favorite papers of all time, “The Hallmarks of Cancer” I am going to term these similarities, the “Hallmarks of Addiction.”
Hallmark 1: Reward
The repeated return to an addictive substance despite negative consequences is a hallmark of addiction behavior, and it helps to separate active addiction from other disorders like it. For example, having sex, drinking water, and eating highly palatable foods all activate the same pathway that taking cocaine and heroin do. However, most people won’t risk their lives for a brownie. The reward pathway, sometimes called the mesolimbic reward pathway, is a bundle of neurons that travel from the Ventral Tagmental Area (VTA) to the Nucleus Acumbens (NAc). Some neurons continue to the PreFrontal Cortex (PFC) (Ikemoto & Bonci, 2013). When activated, some of the reward pathway neurons release dopamine in the Nucleus Acumbens, and that constitutes part of the good feeling you get when you eat a brownie. In fact, anything that causes an increase of dopamine in the NAc will make you feel good. Because it feels good, you are likely to engage in the same behavior again. This is called positive feedback and is probably the most recognizable aspect of addiction. However, reward is only a small piece of this disease. It is complicated and contains many other major parts or hallmarks.
Hallmark 2: Tolerance
Tolerance is another hallmark of addiction. Through a variety of mechanisms, the brain can reduce the effect of addictive substances on the reward pathway. This means that someone’s second high will never be quite as intense as the first. Attempts at re-attaining the original high lead to increased amounts of and more frequent drug use. Ironically, as those in active addiction try harder to reclaim their initial high (pleasure, euphoria, bliss, peacefulness), another very powerful feeling begins to manifest itself. This feeling is the opposite of a high and is termed withdrawal.
Hallmark 3: Withdrawal
Addiction behavior is too complicated to be explained as the attempt to reclaim a high, specifically the lengths a person will take to seek the object of an addiction despite repeated negative consequences (incarceration, divorce, hospitalization). This happens as drug use moves in a trajectory from intermittent and acute to chronic. As a person in active addiction proceeds into withdrawal, the “dark side of addiction” begins to develop. The “dark side” is composed of feelings of anxiety, stress, and dread. These feelings increase over time until they replace the normal state of emotion. A person in acute withdrawal will feel this way all the time, and he or she will try hard to escape these negative emotions. This is called negative reinforcement, or behavior driven by the removal of a negative feeling. Part of this negative feeling is depression of the reward pathway, but there are also pathways built specifically for stress. Among them are the Kappa Opioid-receptor/dynorphin pathway and two other stress pathways, the hypothalamic-pituitary-adrenal axis and the brain aversive system, that both respond to the hormone Corticotropin Releasing Factor (CRF). The HPA axis is involved in early addiction, and the aversive systems become active in long-term withdrawal. In the end, both negative and positive enforcement can powerfully drive behavior; they just do it in slightly different ways (G. Koob & Kreek, 2007). It is also this hallmark that helps to separate addictions from other disorders like it. Addiction is a disorder of positive reinforcement, impulse, negative reinforcement, and compulsion.
Hallmark 4: The Things We Can’t Explain
Incentive Salience
The old models of addiction involve “high” seeking behavior and low willpower. These old models neither adequately explained the disease, nor did they suggest effective treatment. The addition of the compulsive aspect goes a long way in explaining the powerful motivation people have to seek addictive substances, but it still isn’t enough. The lethality of addiction disorders is terrifying to watch. Rats will seek addictive substances above all else--above food, above water--and in the end, they value the addictive substance more than they value their own lives. Incentive salience is a term that refers to the perceived magnitude of a reinforcing stimulus; it basically allows you to rank how important things are (Spanagel & Weiss, 1999). In addiction, the incentive salience is said to be redirected to the drug. The problem is that it is redirected from goals like trying to stay alive (G. F. Koob & Volkow, 2010). Again, ironically, this redirection of goals, setting the addictive substance to the highest properties, is likely related to one the brain’s most powerful features. It is a type of learning (Kalivas, Volkow, & Seamans, 2005).