A Difficult Distinction

Why understanding the difference between dependence and addiction is critical to effective treatment


As the opioid crisis spread across America, the face of addiction changed. Ever since, it has become impossible to believe in the previous stereotype of the down-and-out street-drug addict. As the struggle with addiction moved into mainstream America, real estate agents, teachers, grocery store clerks, doctors, homemakers and students became the new faces of addiction. Never has it been more important to talk about addiction, but the words we need to use can often be the source of confusion, even within the medical community. It is helpful to understand these words before trying to make sense of the processes that lead to addiction and subsequently how effective treatment works. In the simplest sense, addiction is defined as compulsive substance use despite harmful consequences. But that definition falls short of explaining how addiction occurs and further still from suggesting how to treat it.

Let’s begin by looking at the changes that occur in the brain when it is exposed to opioids so we can begin to understand the complex mechanisms underlying addiction.

When the brain is exposed to opioids for the first time, the receptors in the cell membrane are activated and create a response, typically relief of pain, euphoria and energy. If the brain is exposed repetitively to opioids, those receptors begin to multiply, and the result is that to achieve the same response, one requires a higher dose of opioids. This is the first modification to the brain and is known as tolerance.

It is followed closely by dependence, which is defined by the physical withdrawal symptoms one experiences if opioids are ceased. This is often the first opportunity for confusion. It seems reasonable to believe that the withdrawal symptoms associated with dependence were the cause of addiction, but addiction is something different and much more complex.

To understand addiction, we must first understand something called the reward pathway. The reward pathway is a complicated connection of neurons in all our brains but not a specific anatomic location. We are born wired with these connections. They have evolved over a very long period of time to specifically motivate us to do the things that protect us and ensure the survival of our species.

The reward pathway uses the release of a specific neurotransmitter — dopamine — to direct our behavior. Dopamine, in a very basic sense, is responsible for creating euphoria. Every time you experience euphoria, you have engaged in a behavior that has some benefit to your own survival or the survival of the species. Sex, food, companionship and exercise all result in euphoria because over thousands of years these are the things that have correlated with an increased likelihood of survival. If these things did not feel good, we would be less inclined to do them and, subsequently, less likely to survive. The reward pathway does its best to encourage us to do the things in life that are good for us by creating a direct connection between euphoria and the things that benefit us.

This is the beginning of understanding how addiction occurs. When opioids create euphoria, they do so by releasing dopamine in a way that mimics the reward pathway, and slowly, we begin to believe that opioids are on the same list of things required for survival. In fact, the amount of dopamine released by opioids, and therefore the pleasure, is so high our brains begin to believe that not only are opioids life-sustaining but that they are actually more so than the other things the reward pathway directs us toward.

The way the brain comes to believe this is important for understanding addiction and equally important for understanding how effective treatment occurs. The process is most similar to how a memory is formed. Memories are formed in our minds by creating connections between neurons in a circuit. The more times that circuit is activated, the stronger and more long-lasting those connections and the resulting memory becomes.

In the same way, when one experiences euphoria from opioids over and over again, the brain develops a false belief that opioids are life-sustaining. Just like memories, the more times this happens and the  ore powerful the experience is, the stronger the belief becomes. It is hard to remember what you ate for lunch last month because it happened once and was probably a relatively unremarkable experience. The address of your childhood home is equally hard to forget because you thought of it many, many times over a long period of time. Similarly, the more times one uses an opioid and experiences euphoria from it, the more likely it becomes the reward pathway will begin to adopt the idea it is a life-sustaining part of existence.

The reward pathway works not only by creating euphoria to encourage us to engage in beneficial activities. It also has a mechanism that reminds us when those life-sustaining things are absent. This mechanism creates feelings called cravings. This is another common point of confusion because often cravings occur concurrently with physical withdrawal symptoms. The difference is that withdrawal symptoms are a function of the receptors in our brains that are responsible for dependence, while cravings are the psychologic symptoms created by the reward pathway.

Given time during abstinence, usually several days, the receptors in the brain will return to normal, and as they do, the physical withdrawal symptoms pass. But because cravings are not due to these receptors, they persist as long as the reward pathway continues to believe it is missing something vital for existence. Until the reward pathway ceases to believe opioids are life-sustaining, cravings continue.

“Withdrawal symptoms are to dependence what cravings are to addiction.”

Now that we understand that cravings originate from a false, subconscious belief, it follows that the cravings will fade as that belief changes. Furthermore, because that belief was created in the same way a memory forms, it makes sense that that belief and the cravings it creates will change over the same time period that a memory fades.

This begins to hint at one of the most important components of successful treatment: time. Nothing accelerates the process of a memory fading. Only time weakens memories. Conversely, it is very easy to revive a memory. All one needs to do is repeat the activity that created it in the first place.

Now we have almost enough pieces of the puzzle to understand how treatment can work and how it can fail. The final piece of the puzzle is the answer to the unavoidable question: How long do cravings last? The answer to that question is the same as the answer to the question of how long does it take for the reward pathway to change the false belief that opioids are life-sustaining?

Unfortunately, there is no one answer to this question for all people because every individual’s addiction is unique to their own life story. However, we can get closer to the answer by taking another look at memories.

It is unrealistic to think someone who has repetitively used a powerful opioid will forget they did or the euphoria it created. So, in this memory model of addiction, how can we ever expect anyone to cease

to crave heroin? The answer is that although some memories never fade completely away, they lose a certain emotional component. There are many kinds of memories; however, the memories that are most similar to the beliefs created by the reward pathway are the memories someone has for a romantic partner.

In a relationship, one might feel deep, powerful, passionate feelings, even love for someone. Think of these feelings as similar to those that one might develop for an opioid. When a relationship ends, there are proportionally powerful feelings of loss and yearning for the other person. One might even crave the other person. Although it is unlikely that person will ever be completely forgotten, over time, those feelings of loss lose their emotional component. Over time, it becomes possible to remember that person without also experiencing such intense feelings.

The same process occurs with the belief the reward pathway forms toward opioids. Once someone has been addicted to opioids, they are unlikely to forget their experiences, but the cravings are comparable to the intense emotions we feel when a relationship ends. Using the example of a relationship breakup, we can begin to answer the question of how long it takes for the false belief that opioids are life-sustaining to fade.

Here it is: When a relationship ends, it usually takes about half the time one was in that relationship before the memory of the other person is no longer so emotionally intense that we crave them. Extending that analogy, it takes a period of abstinence that is about half the time someone was actively addicted for the belief that opioids are life-sustaining to fade and cravings to become tolerable.

Now we have all the pieces of the puzzle, but before we try to put this puzzle together, let us summarize what we have covered.

When the brain is exposed to opioids repetitively, the opioid receptors in the brain change first, creating a tolerance to opioids and then dependence. During the same period of repetitive use, the euphoria one experiences allows the reward pathway to create the false belief that opioids are life-sustaining. In the absence of opioids, physical withdrawal symptoms will occur until the receptors in the brain return to normal. Cravings will persist until the reward pathway no longer believes opioids are vital for existence. Physical withdrawal symptoms typically last for days, while cravings last for a much longer time, perhaps years.

Armed with this information, we can now begin to understand how different treatment models succeed or fail.

One of the first mistakes is to believe that treating dependence is treating addiction. Many addicts believe if they can simply get through the withdrawal symptoms they will be free of addiction. Treating dependence is challenging but actually very simple: Remove opioids and endure the withdrawal symptoms. This is commonly referred to as detox. Eventually, the receptors in the brain go back to a normal state and physical symptoms resolve.

The problem with detox is that nothing has been done to address the reward pathway’s belief that there is something missing, and although physical symptoms pass, cravings remain. Those cravings are initially so intense that even in the absence of physical withdrawal symptoms, relapse is common, if not the rule.

This is an exercise in opposing the forces of the reward pathway. One should expect to be no more successful with this approach than they would be resisting any other thing the reward pathway encourages us to do. Abstaining from sex, food or companionship is likely to be as successful, which is to say, not that likely. Detoxing alone does not allow enough time to pass for the belief to fade. A treatment plan that does not address cravings is likely to enter a cycle of detox and relapse.

The main approach to controlling cravings is opioid replacement therapy. This method employs the use of opioid medications such as buprenorphine and methadone. In this method, someone ceases to use the drug to which they are addicted, but rather than entering withdrawal and also experiencing cravings, they begin opioid medications. The dose of these medications is precisely adjusted to stimulate the receptors in the brain just enough to remove cravings and withdrawal symptoms but not enough to create euphoria. If this balance can be struck, the false belief the reward pathway created that opioids were life-sustaining is not reinforced because euphoria is not experienced. In this way, one can live without the crippling cravings and withdrawal symptoms that might otherwise make it impossible to resist opioids.

If this state can be maintained for an extended period of time, gradually the reward pathway begins to lose the false belief that opioids are vital for existence. The longer this is maintained, the lower one’s vulnerability to relapse becomes. This also creates the time during which one can participate in counseling and other forms of therapy such as group meetings.

During this time, the other elements of one’s life that were damaged by addiction can be addressed. People can repair relationships, seek jobs, tend to health issues and improve finances. As time passes in this state, vulnerability to relapse decreases such that eventually tapering off replacement medication can be considered.

At this point in treatment, nothing has been done to address dependence, so transitioning to lower doses and ultimately off these medications invariably requires experiencing withdrawal symptoms. The difference to detox is that when the withdrawal symptoms pass, there should be little to no cravings. The vulnerability to relapse will never entirely disappear. In fact, few things increase vulnerability more than believing that one has transcended beyond it.

However, rather than discussing relapse, it might be more useful to simply consider the concept of vulnerability to addiction. In this sense, everyone has a certain risk, even those who have never used opioids. There are things within us and surrounding us that raise or lower our vulnerability to addiction. This is true of people who have never tried opioids as well as those who have, though, in general, people who have been addicted to opioids will always have a certain element of vulnerability beyond those who have not. Even the most effective treatment will never eliminate that vulnerability to use opioids. Effective treatment can hope to clear the path to a life where cravings have faded and are no longer overwhelming, but humility and hard work are the currency of successful, lifelong sobriety.

Addiction is a complicated topic, with roots in biology, psychology and sociology. Words such as dependence, addiction, withdrawal, cravings and detox can quickly confuse the conversation, but we owe it to those who suffer in the grip of this disease to understand how addiction is created, and even more so, how it is treated.

With this knowledge, whether we grapple with addiction personally or struggle to reach out to a loved one, we can do so with the advantage of understanding its origins. We can find compassion for ourselves and others by realizing how this disease evolves in people who look just like us. We can abandon previous stereotypes and look beyond the confusing behaviors created by addiction to the see the person struggling with a disease, even if it is ourselves.

Dr. Alexander Lapidus graduated from the University of California, Santa Cruz in 1990 with a degree in molecular, cellular and developmental biology. He completed medical school at University of California, Davis in 2000, followed by a residency in emergency medicine at Oregon Health & Science University. He has practiced emergency medicine for 16 years in the Portland area. Through his experience practicing emergency medicine, he met countless patients struggling with addiction and became dedicated to serving them. Lapidus has worked in addiction medicine for over five years and believes that a successful approach to addiction involves a balance of appropriate medications, introspection, counseling and personal growth.


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