Things I like to Blog About: Addiction and the Opponent Process Theory

Perhaps I should put a special category up for “things I like to blog about”. Or maybe just ‘basics’.
Sci’s been a little out of her bloggin’ groove lately, feelin’ her stuff is not up to snuff. But with THIS, Sci will get her groove back. And she will get it back with pictures. Pictures that are drawn in powerpoint so they don’t make your eyes bleed. I care.

So what is the opponent-process theory? The opponent-process theory (hereafter called the OP Theory) is one of the current theories we are using to understand addiction. Because, to be honest, we don’t really understand it. Oh sure, we know about initial rewarding effects, we know about withdrawal, we know about tolerance. But do we really KNOW what it is that makes people walk away from their families and homes and jobs and sell themselves for their next hit? A next hit that, oftentimes, they HATE and need at the same time? …nope. Still working on that.

But one of the theories out there to explain drug addiction and how it may work is the OP Theory.


Postulated in 1974 by Solomon, the OP Theory is actually one of motivation. The idea is that hedonic states, the ones that feel good, are modulated by mechanisms that reduce the intensity of the state. So euphoria might be countered by depression, for example. Unfortunately, the more positive feelings you feel, the more you become tolerant to them. And the more your central nervous system will seek to counter them with negative feelings. In the language of addiction, this corresponds roughly to drug affect and withdrawal states.
And though it sounds complicated (and reading any review of it in science-ese, you’d think it was complicated), all you need is a picture in your head. The picture is this:
OP Theory1.png
So what are you looking at here? The yellow arrow pointing up is going to represent positive drug effects: euphoria, energy, less-anxiety, pain relief, whatevs. The red arrow pointing down is negative drug effects: paranoia, nausea, anxiety, etc. And the two opposing loops are measures of relative drug effect.
The idea is this: every drug you take will elicit both positive and negative effects in your body. The positive effects are things like, say euphoric mood, while the negative effects are things like headache, nausea, depression, things like that. These positive and negative effects that you experience are the result of changes in the underlying neurobiology of your brain. So the original acute effects of a drug are opposed by your own neurobiology, as your brain strives to bring itself back toward homeostasis.
So, the first time you take a drug, it might look like this:
OP Theory2.png
The drug has pretty major positive effects at first, with reward neurons firing on all cylinders. The drug completely overwhelms the pleasure circuits, and the brain can’t muster enough negative effects of come back to homeostasis. The result: that feels REALLY GOOD.
OP Theory3.png
Of course, this effect doesn’t last. As you take the drug more and more, you begin to develop tolerance. The key is that tolerance tends to develop to the positive effects. The OP Theory states that it’s not that your body and brain are tolerant to the positive effects, rather, they are sensitizing to the negative effects. Because of this, your perception of the positive effects become blunted. So over time, you start to see something like this:
OP Theory4.png
The positive effects of the drug remain the same, while the negative ones increase. So now your perceiving drug effect looks more like this:
OP Theory5.png
Yeah, looks like that doesn’t feel as great. And this is more pernicious than it appears.
First of all, you’re going to have to take more drug to get the same initial euphoric effects you had before, because it will take more drug to overcome the negative effects.
Secondly, these negative effects tend to last LONGER than the positive effects of the drug. This is often the result of altered neurobiology. Your body is used to having the drug on board, and certain kinds of signals will get stronger, trying to be heard over the presence of the drug. As your body gets used to the presence drug, it comes to a new state of normalcy. For example, a person without a drug addiction might look like this at the baseline state:
OP Theory6.png
No more positive than negative. Feels like normalcy.
An addict, on the other hand, might look like this:
OP Theory7.png
Ouch.
For example, alcohol. It’s pretty well known that alcohol is a potent anxiolytic (I would imagine that if people didn’t have alcohol to relieve their anxiety, a good portion of the populace wouldn’t get laid at all). Unfortunately, the more alcohol you drink, the more your baseline levels of anxiety increase, especially if you were already pretty anxious to begin with. And those who are pretty anxious to begin with…tend to need a few drinks to relax. But when they stop drinking, the anxiety remains, and the alcohol withdrawal will actually make that anxiety STRONGER, driving an alcoholic toward relapse.
So your positive effects aren’t as great, and you need more drug to get high. Not only that, the negative effects of the drug and the withdrawal syndrome stick around, driving you to seek out the drug again, just to overcome your new negative state of homeostasis.
So basically, the idea of the OP Theory is one of limited reward. You don’t want to be feeling the massive effects of reward all the time, you need it to be balanced out by other things, like discomfort. This keeps you aware of the world around you and able to respond, instead of blissed out. So sex, for instance, will feel good, but not THAT good.
Drugs, on the other hand, hijack this system. They feel TOO good. Your body can’t achieve homeostasis. It has to drive negative signalling up a notch to counteract the drug. But the drug goes away, and the negative feeling stays. And the next things you know, you’re just STRESSED, you know, and all you really need is a drink…
There’s only one issues with the OP Theory: it’s probably wrong. But it’s wrong in the way that most of the theories we have about understanding the brain, and particularly about understanding things like motivation and reward, are wrong. It may not be entirely wrong, it may just be incomplete.
The important thing is, it’s not perfect. There are some drugs that have relatively limited negative effects, increases in which do not account for the tolerance to the positive effects (like cocaine). There are some drugs which have some pretty major negative effects (like alcohol), which don’t seem to have enough positive effects to make them appealing. Yet they are.
So, until we come up with a new theory, or find explanations for way to make exceptions fit, the OP Theory is a flawed one. But isn’t every theory a flawed theory? And it’s what we’ve got to go on right now. Give us a few years, and we’ll give you the next theory, until we finally get it right.

18 Responses

  1. Pile O’ Crap

  2. great description, Sci!
    for a recent review of some of the neurochemical bases of some of the above-described effects:
    http://www.ncbi.nlm.nih.gov/pubmed/18154498

  3. Leigh: hehe, I read that as part of my prep for this post. 🙂 It’s great, but unfortunately I figured the neurochem would be a bit much.

  4. Nice post! Alcohol appears at first to be a curious exception; but the negative/positive argument ignores the temporal aspects of intoxication. The stimulant ‘feel good’ properties are much more evident on the ascending (BUZZ) part of the blood-ethanol relationship. Next time you drink socially, look at your watch every time you get a new drink. After the first drink, most ‘experienced’ drinkers will continue to consume at a defined rate — keeping them on the ascending limb and avoiding the ‘negative’ sedative properties. Notably, alcoholics become remarkably tolerant to the sedative properties, but then engage the withdrawal-related negative consequences. So, one specific component missing from the theory might be ‘temporal’ interactions between acute use and neurobiological alterations during the addiction process. Hard stuff to model…
    BTW — I don’t believe you can say that cocaine has limited negative effects. Most models just don’t bother to look for them.

  5. Tex: excellent points about alcohol. I also agree that cocaine has negative effects, but they aren’t really tested for. I have seen a model of OP where they extend the negative portion out temporally to represent the neurobiological changes occurring over repeated use, but it IS a tough thing to model.

  6. From my understanding as you presented it here, the OP Theory seems to imply that the CNS actively works to counteract the rush of the drug to maintain a homeostatic emotional state.
    Doesn’t tolerance+withdrawl+neuron damage+variant of learned helplessness account just fine for this anhedonic state? I don’t see why we need to tack on some additional hypothesis that the CNS is somehow actively increasing negative states to counteract the high.
    Additionally, even if the OP Theory is in some way correct it doesn’t fully explain why drug addicts keep taking the drug even though it doesn’t get them as high any more. In my opinion, a more interesting and hopefully explanatory avenue here is research how drugs usurp the dopamine pathways responsible for awareness, saliency, and working memory. With this perspective we are dealing more with the extraordinary power of drugs to create potent cues — cues which are so potent that they maintain their power long past tolerance and self-hatred sets in.

  7. Colin: the tolerance withdrawal stuff are the phenomenons that the OP Theory is trying to explain. Basically it’s an overarching theory of addiction that takes those into account. According to OP, the tolerance to positive effects is partially due to the increase in withdrawal and the neurobiological changes producing negative effects. It’s a way to explain the presence of the anhedonic state and how that contributes to further drug taking.
    The idea that addicts will continue to take the drug because they are now using it to counter the anhedonic effects they have when the drug is not on board. It may not be as pleasant as it once was to be drunk, but being drunk still feels SO much better than how you now feel sober, because being sober now feels awful.
    Keep in mind that the OP Theory is an overarching theory, taking into account things like the dopamine pathway and reward system changes, cue salience, and tolerance and withdrawal to produce an overall picture of how drug addiction occurs. Kind of a way to tying it up in a neat little package.

  8. I saw a presentation at a conference that touched on this model in rats, by way of microinjections to the brain. Some of their results seemed to provide support for the OP model: slight differences in the spatial location of the administration contributed more or less to euphoria vs. dysphoria (implying two different systems at work, in two slightly different places in the brain).

  9. sure, some of the neurochemical effects are complicated. but they address a lot of what your commenters criticized… and you’re not afraid of complicated stuff.🙂

  10. Nicely explained.
    And, as leigh said, the neurochemical explanations are complicated, but they address the criticisms – and you’re not afraid of complicated stuff. Don’t be afraid to go out on some limbs here. You did a good job with this; I think you can with the more complex explanations as well… Maybe one drug at a time?

  11. Sigh…you people, being all hard on poor Sci and giving her so much WORK to do.🙂 I’ll see what I can do. Might have to by neurotransmitter system, rather than by drug. More reading is a must.

  12. Great post.
    IMO the biggest problem with the theory as stated is that it leaves out the time frames of various effects. Any drug can (potentially) have several effects, each with its own time frame. Not only that, the body’s attempts to adjust the homeostasis can also have various time frames.
    Thus, for instance, the response to heroin use for several hours at a time might involve a steady-state change to receptor balances that lasts for weeks, reducing the effect during use, while producing an opposite effect after it wears off. AFAIK something like this could explain both withdrawal symptoms and the need for increased dosages to get the same effect.
    Now, add in the effect of endomorphins, and perhaps you’ve got an explanation for things like chocolate addiction.

  13. I like the graphs that mean nothing at all, but perhaps you could have found a better way to visually represent the challenging mental concept of positive drug effects outweighing negative ones.

  14. Check out some of Koob reviews for some more informative figures and more specifics.
    Interesting post. The temporal component of this process is (I thought) fairly well defined. In the sense that for alcohol exposure, you don’t see protracted negative affective states until you have prolonged alcohol exposure. It is emergent only after long term exposure. These adaptations may be similar to acute withdrawal (hangover?). In fact some data suggests that acute withdrawal recruits the same systems (lets borrow a page from Dr. Koob and call them ‘stress systems’), but it is transient in nature.
    I think the psychostimulant field doesn’t pay this much heed…but there are similar neurochemical alterations following extended cocaine exposure. More-over, some data from Dr. Koob’s lab shows that blocking CRF, can reduce cocaine self-admin in these models, suggesting that the same ‘stress’ system that is engaged with alcohol, is engaged with cocaine.

  15. It bears noting, that I am not related or connected to the Koob lab in any sense. It is just that he has some of the easiest to remember examples.

  16. jamie: Sci should point out that the graphs you see above are a big challenge to her artistic skills. Trust me, you don’t want to see anything more involved.
    Pinus: Hehe. I have read a LOT of Koob in my time, never fear. I have to say that I think the psychostimulant field is beginning to pay more attention to Koob’s idea of allostatic states, especially after finding of hypodopaminergic functioning in cocaine addicts, implying increased reward thresholds…
    Aw hell…wait on the next post.

  17. I have seen this effect many times at work. I spend some 50 hours a week dealing with drug and alcohol addiction at Narconon Vista Bay alcohol treatment centers and this diagram calls it on the money. Its tough to get over drug problems but it is possible. All it requires is the willingness to do so. WE have helped over a 1000 graduates and that helps 10 people around them. Just take a moment to realize what harm you are doing to your body and get some help before you hit the tail end of those examples, I promise you its no fun. i have been there and done that.

  18. I have to say that I think the psychostimulant field is beginning to pay more attention to Koob’s idea of allostatic states, especially after finding of hypodopaminergic functioning in cocaine addicts, implying increased reward thresholds…
    Really quite a fascinating story about the conduct of science, personality conflict, turf defending and above all else the streetlight problem.
    A cynical person might suggest that the psychostimulant field had all the data available to everyone else all along. What has apparently changed is who gets what fraction of the NIDA ear at present versus times past. One might also point to the massive failure in the eggs-in-one-basket attempt to design agonist therapy for cocaine dependence as another key factor which finally kicked people out of their theoretical rut.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

%d bloggers like this: