Loss, but not absence, of control – How choice and addiction are related

In a recent post the notion that “loss of control” is an addiction myth was raised by our contributing author, Christopher Russell, a thoughtful graduate student studying substance abuse in the U.K. Though I obviously personally believe in control- and choice-relevant neurological mechanisms playing a part in addiction, this conversation is a common one both within and outside of the drug abuse field. Therefore, I welcome the discussion onto our pages. I’d like to start out by reviewing some of the more abstract differences between my view and the one expressed by Christopher and follow those with some evidence to support my view and refute the evidence brought forth by him.

Addiction conceptualization – Philosophical and logical differences and misinterpretations

One of the first issues I take with the argument against control as a major factor in drug addiction is the interpretation of the phrase “loss of control” as meaning absence, rather than a reduction, in control over addiction and addictive behavior. Clearly though, one of the definitions of loss is a “decrease in amount, magnitude, or degree” (from Merriam-Webster.com) and not the destruction of something. Science is an exercise in probabilities so when scientists say “loss”, they mean a decrease and not a complete absence in the same way that findings showing that smoking cigarettes causes cancer do not mean that if an individual smokes cigarettes they will inevitably develop cancerous tumors. Similarly, the word “can’t” colloquially means having a low probability of success and not the complete inability to succeed. Intervention that improve the probability of quitting smoking (like bupropion or quitlines for smoking) success are therefore said to cause improvements in the capacity for quitting.

Next, Christopher wants scientists to identify the source of “will” in the brain but I suggest that “will” itself is simply a term he has given a behavioral outcome – the ability to make a choice that falls in line with expectations. In actuality, “will” is more commonly used as a reference to motivation, which while measurable, isn’t really the aspect of addiction involved in cognitive control. Instead, what we’re talking about is “capacity” to make a choice. The issue is a significant, not semantic one, since the argument most neuroscientists make about drug abuse is that addicts suffer a reduced capacity to make appropriate behavioral choices, especially as they pertain to engaging in the addictive behavior of interest. If someone is attempting to get into a car but repeatedly fails, we say they can’t get in the car (capacity), not that they don’t want to (will). Saying that they simply “don’t” get in the car doesn’t get at either capacity or will but instead is simply descriptive. I don’t believe that science is, or should be, merely descriptive but instead that it allows us to form conclusions based on available information.

That there is a segment of individuals who develop compulsive behavioral patterns tied to alcohol and drug use and who attempt to stop but fail is, to my mind, evidence that those individuals have a difficulty (capacity) in stopping their drug use. Their motivation (will) to quit is an aspect that has been shown to be associated with their probability of success but the two are by no means synonymous. It is important to note, and understand, that the attribution for the performance should not fall squarely on the shoulders of the individuals. We humans are so prone to making that mistake that it has a name, “The fundamental attribution error,” and indeed, individuals who show compulsive, addictive, behavior do so because of neuropharmacological, environmental, and social reasons in addition to the complex interactions between them all. But no one is disputing that and in fact, the article used by Christopher to point out the notion of a “tipping point” in addiction directly points out that fact in the next paragraph (Page 4), which he chose not to reference or acknowledge.

“Of course, addiction is not that simple. Addiction is not just a brain disease. It is a brain disease for which the social contexts in which it has both developed and is expressed are critically important… The implications are obvious. If we understand addiction as a prototypical psychobiological illness, with critical biological, behavioral, and social-context components, our treatment strategies must include biological, behavioral, and social-context elements.” (Lashner, 1997)

Lastly, Christopher’s philosophical musings are interesting, but they seem to stray away from trying to find an explanation for behavior and instead simply deconstruct evidence. In a personal communication I explained that while most addiction researchers understand that addiction, like most other mental health disorders is composed of a continuum of control ranging from absolute control over behavior to no control whatsoever (with most people fitting somewhere in the middle and few if any at the extreme ends), categorization is a necessary evil of clinical treatment. The same is true for every quantitative measure from height (Dwarfism is sometimes defined as adults who are shorter than 4’10”) to weight (BMI greater than 30 kg/m²). I think it’s equally as tough to argue that someone with a BMI of 29.5 is distinctly different from an individual with a BMI of 30 as it is to argue that there is no utility in the classification. Well, the same applies for drug addiction, although some people categorically object to classification and believe it has no utility or justification.

Now for the evidence – “Choice” and “control” are not the same as “will”

Some people quit, even without help – Christopher and a number of the people he cites in support (Peele, Alexander), suggest that because some people do stop using that it can’t be said that there is a problem with any individuals’ capacity to stop. The problem with that argument is that it supposes that everyone is the same, a fact that is simply false. As an example I would like to suggest that we compare cognitive control with physical control and use Huntington’s Disease (HD or Huntington’s Chorea) as an example.

HD patients suffer mental dementia but the physical symptoms of the disease, an inability to control their physical movement resulting in flailing limbs often referred to as the Huntington Dance, are almost always the first noticeable symptoms. Nevertheless, HD sufferers experience a number of debilitating symptoms that originate in brain dysfunction (specifically destruction of striatum neurons, the substantia nigra, and hippocampus) and that alter their ability (capacity) to control their movements and affect their memory and executive function leading to problems in planning and higher order thought processes. So, while it is true that most people can control their arm movements, here is an example of individuals who progressively become worse and worse at doing so due to a neurophramacological disorder. There is currently no cure for HD but some medications that help treat it no doubt restore some of the capacity of these patients to control their movements. If a cure is found it would be difficult to say, as Christopher suggests of addiction, that the cure does not affect the capacity of HD patients to control what they once could not. I chose HD for its physiological set of symptoms but a similar example could easily be constructed for schizophrenia and a number of other mental health disorders (including ADHD and drug addiction). Importantly, cognitive control is a function of brain activity, activity that can become compromised as the set of experiment I will discuss next show.

An experiment conducted at UCLA (1) has shown that cocaine administrations reduced animals’ ability to change their behavior when environmental conditions called for it. Even more meaningful was the finding that once animals are exposed to daily doses of drugs, the way their learning systems function is altered even when the drugs themselves are no longer on board and even when the learning has nothing to do with drugs per se.

In the experiment, conducted by Dr. David Jentsch and colleagues, monkeys were given either a single dose (less than the equivalent of a tenth of a gram for a 150lb human) or repeated doses (1/8 to 1/4 of a gram equivalent once daily for 14 days) of cocaine. The task involved learning an initial association between the location of food in one of three boxes and then learning that the location of the food has changed. We call this task reversal learning since animals have to unlearn an established relationship to learn a new one.

Obviously, the animals want the food, and so the appropriate response once the location is changed is to stop picking the old location and move on to the new one that now holds the coveted food. This sort of thing happens all the time in life and indeed, during addiction it seems that people have trouble adjusting their behavior when taking drugs is no longer rewarding and is, in fact, even troublesome (as in leading to jail, family breakups, etc.).

In the experiment, animals exposed to cocaine had trouble (when compared to control animals that got an injection of saline water) learning to reverse their selection when tested 20 minutes after getting the drug, which is not surprising but still an example of how drug administration can causally affect an individual’s ability to make appropriate choices. As pointed above, the most interesting finding had to do with the animals that got a dose of cocaine every day for 14 days. Even after a full week of being off the drug, these animals showed an interesting effect that persisted for a month – while their ability to learn that initial food-box association, they had significant trouble changing their selection once the conditions changed. Remember, this effect was present with no cocaine in their system and with learning conditions that had nothing whatsoever to do with cocaine.

If that’s not direct evidence that having drugs in your system can alter the way your brain makes choices, I don’t know what is.

Another study conducted by Calu and colleagues with rats found similar (or even more pronounced) reversal learning problems after training the animals to take cocaine for themselves, clarifying that it is the taking of cocaine and not the method that causes the impairments.

Another entire set of studies has shown that stimuli (also known as cues or triggers) that have become associated with drugs can bring back long-forgotten drug-seeking behavior once they are reintroduced. This was shown in that Calu paper I mentioned above and in so many other articles that it would be wasteful to go through all the evidence here. Importantly, this evidence shows that drug associated cues direct behavior towards drug seeking in a way that biases behavior regardless of any underlying will. My own research has shown that animals who respond greatly to drugs (nicotine in our case) likely learn to integrate more of these triggers than animals who show a reduced response, indicating once again that these animals bias  their behavioral selection towards drug-seeking more than usual. While we have more studies to conduct, we believe that genetic differences relevant to dopamine and possibly other neurotransmitters important for learning (like Glutamate) are responsible for this effect.

While we can’t do these kinds of experiments with people (research approval committee’s just won’t let you give drugs to people who haven’t used them before), there is quite a bit of evidence showing an association between trouble in reversal learning and chronic drug use in humans (see citation 3 for example) as well as research showing very different brain activity among addicted individuals to drug-associated versus non-drug cues (like seeing a crack pipe versus a building). All this evidence suggests that drug users are different in the way they learn generally, and more specifically about drugs, than individuals not addicted to drugs. When it comes to genetics, we know quite a bit about the  association between substance abuse and specific genes, especially when it comes to dopamine function. As expected, genetic variation in dopamine receptor subtypes important in learning about rewards (D4 and D2) has been revealed to exist between addicts and non addicts. Without getting into the techniques and analysis methods involved in these genetic studies, their sheer number and the relationship between substance abuse and other impulse disorders points to a direct relationship between drug use disorders (and possibly other addictive disorders) and a reduced capacity to exert behavioral control. Less capacity for control is what researchers have found sets addict apart from non-addicts.

Summary, conclusions, and final thoughts

The toyota Prius is slow but efficientIn closing, there are undoubtedly imperfections about the ways we diagnose addiction (drug addiction and others). It would probably be nice if we could figure out a way to incorporate what we know about the continuous nature of the disorder with the need for clinical delineation of who requires addiction treatment and who doesn’t. Addiction researchers are far from the only ones who wonder about this question though (the same issues are relevant for schizophrenia, depression, and nearly every mental health disorder) and I am certain that better and better solutions will emerge.

However, the discussion of stigma in this context needs to allow us to discuss the reality of addiction without having to resort to blaming and counter-blaming. If I describe the Toyota Prius as being slow but incredibly efficient I am no more stigmatizing than if I describe a Ferrari as being incredibly fact but wasteful in terms of fuel. The same applies, or should apply, to health and mental health diagnoses – Just because an individual is less able to exert cognitive control over impulses should not by definition call into question their standing as a human being. We are complex machines and by improving our understanding of the nuts and bolts that make us function we can only, in my opinion, improve our ability to make the best use of our capabilities while understanding our relative strengths and weaknesses. Any other way of looking at it seems to me to be either wishful (I can do anything if I want it badly enough) or defeatist (I will never be anything because I’m not good at X) and neither seem like good options to me.

Citations:

1) Jentsch, Olausson, De La Garza, and Tylor (2002): Impairments of Reversal Learning and Response Perseveration after Repeated, Intermittent Cocaine Administrations to Monkeys. Neuropsychopharmacology, Volume 26, Issue 2, Pages 183-190

2) Calu et al (2007) Withdrawal from cocaine self-administration produces long-lasting deficits in orbitofrontal-dependent reversal learning in rats. Learning & Memory, 14, 325-328.

3) Some evidence in humans from Trevor Robbins’ group: Reversal deficits in current chronic cocaine users.

Is marijuana addictive? You can bet your heroin on that!

marijuana“Is marijuana addictive?” seems to be the ultimate question for many people. In fact, when discussing addiction, it is rare that the addiction potential for marijuana doesn’t come up.

Some basic points about marijuana:

The active ingredient in marijuana, THC, binds to cannabinoid receptors in the brain (CB1 and CB2). Since it is a partial agonist, it activates these receptors, though not to their full capacity. The fact that cannabinoid receptors modulate mood, sleep, and appetite is why you get the munchies and feel content and why many people use it to help with sleep.

But how is marijuana addictive? What’s the link to heroin?

What most people don’t know is that there is quite a bit of interaction between the cannabinoid receptor system (especially CB1 receptors) and the opioid receptor system in the brain. In fact, research has shown that without the activation of the µ opioid receptor, THC is no longer rewarding.

If the fact that marijuana activates the same receptor system as opiates (like heroin, morphine, oxycontin, etc.) surprises you, you should read on.

The opioid system in turn activates the dopamine reward pathway I’ve discussed in numerous other posts (look here for a start). This is the mechanisms that is assumed to underlie the rewarding, and many of the addictive, properties of essentially all drugs of abuse.

But we’re not done!

Without the activation of the CB1 receptors, it seems that opiates, alcohol, nicotine, and perhaps stimulants (like methamphetamine) lose their rewarding properties. This would mean that drug reward depends much more heavily on the cannabinoid receptor system than had been previously thought. Since this is the main target for THC, it stands to reason that the same would go for marijuana.

So what?! Why is marijuana addictive?

Since there’s a close connection between the targets of THC and the addictive properties of many other drugs, it seems to me that arguing against an addictive potential for marijuana is silly.

Of course, some will read this as my saying that marijuana is always addictive and very dangerous. They would be wrong. My point is that marijuana can not be considered as having no potential for addiction.

As I’ve pointed out many times before, the proportion of drug users that become addicted, or dependent, on drugs is relatively small (10%-15%). This is true for almost all drugs – What I’m saying is that it is likely also true for marijuana (here is a discussion of physical versus psychological addiction and their bogus distinction).

Citation:

Ghozland, Matthes, Simonin, Filliol, L. Kieffer, and Maldonado (2002). Motivational Effects of Cannabinoids Are Mediated by μ-Opioid and κ-Opioid Receptors. Journal of Neuroscience, 22, 1146-1154.

Obesity, drug addiction, and dopamine

Eating junk-food can be addictive, and apparently, it causes brain changes that look eerily similar to drug addiction. That’s the message not only from the rapidly fattening waistlines of Americans everywhere, but also from the Johnson and Kenny labs at the Scripps Institute.

Food and drug addiction

The idea that obesity is caused by a compulsive pattern of eating, and that there could be a similarity between such compulsive eating and drug addiction isn’t super new. In fact, Dr. Volkow from NIDA seemed to make research into this association her goal when taking  the helm of the addiction research kingdom.

When you think about it, the notion isn’t far-fetched: Drug addicts continue to take drugs, in increasing amounts, even though they’d often like to stop (at some point) and in the face of negative consequences and the common loss of other important life functions (like family, work, etc.). Obese individuals are quite the same, eating more and more food regardless of their desire to adopt a healthier diet and in-spite of ridicule, low self-esteem, and decreased functioning that often accompanies extreme weight gain.

The research by Johnson and Kenny examined whether exposure to the kind of high-fat, super high-calorie foods that floods the junk-food market are responsible for creating food-addicts in a similar way to drugs that alter the brain in ways that make stopping more difficult.

Dopamine, reward, and junk-food

The study took three groups of rats and gave them either the regular chow diet lab animals are used to or the worse kind of birthday party food: bacon, sausage, cheesecake, pound cake, frosting and chocolate. You can imagine the party going on in the rat cages that got to eat that! Of the two groups that got to eat the crazy-fat food, one had unlimited access while the other got to binge for only one hour a day.

The bottom line: Only the rats that got unlimited access to the fat-party food developed compulsive eating habits that resulted in roughly twice the weight gain of the other two groups and the ability to continue eating even in the face of signals for punishment (a light that they were trained to associate with shocks).

When the researchers looked deeper, they found that the brains of these rats suffered a significant reduction in the density of a specific kind of dopamine receptor (D2) in a brain part known as the striatum, the same kind of reduction common in drug addicted people and obese individuals. This receptor type is often thought to be important for regulation of impulses, both physical and otherwise. It therefore makes sense that losing this type of function would cause uncontrollable eating or drug taking.

Are drug- and food-addictions the same?

While this research isn’t saying that compulsive eating, or obesity, are the same as drug addiction, it does strongly suggest that there are common mechanisms in both. More importantly, it reveals a common process that unfolds when over-exposure to the reward, in this case food, occurs. This tells us that there can likely be common pathways to these different addictive disorders, though whether any specific person ended up a food- or drug-addict because of this kind of process is still an open question. I wonder if we’ll see something like this with sex addiction soon…

Citation:

Johnson and Kenny (2010) Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nature neuroscience, 13, 635-641.