Distinguishing between Drug Addiction and Drug Dependence

I came across the following article in Vice in which the author warns about confusing drug addiction with drug dependence:

"It may seem like a trivial or academic distinction, but addiction is not dependence, and dependence is not necessarily a problem."

As an example, the author describes the following case:

"Chris from Houston" said he's taken opioid painkillers for six to seven years, allowing him to function, despite chronic pain, at what he called "a very labor intensive job." However, if he doesn't take his pills, Chris suffers withdrawal symptoms. Concerned, he asked whether this makes him "an addict."

The author goes on to conclude that

"Chris doesn't qualify, so long as his description of his situation is accurate. What he describes experiencing is physical dependence, a natural consequence of taking certain medications over time. Addiction, in contrast, consists of compulsive drug use despite negative consequences."

Not so fast. One has to be careful before concluding that the situation does not represent drug addiction. Indeed, what is the acid test for distinguishing between the two?

"Physical dependence occurs very frequently with repeated opioid exposure, but dissipates promptly after a few days of opioid tapering and discontinuation," explains Nora Volkow, director of the National Institute on Drug Abuse. "Addiction occurs only in those vulnerable and is a slow process that, once it has occurred, can take months and even years to overcome and requires persistent treatment."

In other words, it is extremely difficult to kick-the-habit if you are addicted; physical dependence dissipates by careful weaning from the drug.

There are two important points to make. First, one should reiterate the main point of the article which is that the vast majority of people who take opioid pain-killers regularly have developed physical dependence but are not addicted so that they could be weaned off by careful tapering of the dose. The key benchmarks are the dose and how fast the dose is increasing. Is the dose in a range that is considered safe? Without more details on dose, we do not know whether Chris is addicted or not.

Second, one should be careful about trying to draw a clear line between addiction and dependence; the boundary can be fuzzy. Indeed there is most likely a continuum from casual use to physical dependence to addiction. As mentioned above, a lot depends on the dose and how much that dose is increasing. If you are using a high dose that is increasing significantly, then you are probably either addicted or on your way to addiction. Most opioid pain-killers have a maximum daily dosage that should not be exceeded.

The Vice article author goes on to make an analogy that I did not like:

"In other words, if pain medications are making your life genuinely better and improving your ability to love and work, what you are experiencing if you have withdrawal symptoms is dependence, not addiction. People with diabetes, for instance, are dependent on—but not addicted to— insulin; people on certain antidepressants are dependent on them, but, again, not addicted."

One problem with opioids is tolerance; you need a higher and higher dose to get the same effect. Most patients with Type 1 diabetes, do not have insulin resistance, and so the insulin dose should not increase. It is a bad cycle for opioids in which a higher and higher dose creates more dependence and any interruption will result in withdrawal.

Tolerance arises through a process called adaptation, which is a property of most G-protein coupled receptor system including opioid receptors. A constant input (e.g. presence of opioids in the blood) leads to down-regulation of the receptor signaling through various mechanisms including receptor internalization from the cell surface (Figure 1). As a result, a greater input (dose) is needed to achieve the same amount of signaling (effect).

The second special problem with opioids is that they directly affect the reward (dopamine) center of your brain which is linked to addictive behavior. The same is not true for insulin or antidepressants.

In summary, I would argue that there is a continuum between drug addiction and drug dependence that depends on the dose and whether the dose is increasing or not. Opioids are particularly dangerous because they induce tolerance resulting in the need for a higher dose for the same physiologic effect, and because they affect dopamine-influenced reward-motivated behavior. Ultimately, whether you can be weaned off the drug is the ultimate test of addiction, and the higher the dose you are receiving the harder it will be.

Figure 1. Opioid receptors activate G-protein signaling molecules when they bind an opioid agonist molecule. Persistent signaling causes the down-regulation of the receptor that involves the inhibitory phosphorylation of the cytoplasmic loops (red circles labeled with a P), and the internalization of receptors into endocytic vesicles removing them from the surface of the cell. The adaptation occurs on multiple time scales from seconds to minutes to hours to days to weeks (Figure from http://pharmrev.aspetjournals.org/content/65/1/223).