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When people speak about addiction it is common to think about alcoholism. There is good reason for this. Alcoholism has been the most studied problem in addiction. Alcoholics Anonymous was the first mutual help organization for addiction to come to the fore. Finally, alcohol’s being legal has lent alcoholism more “social acceptability” than addiction involving illegal drugs.

I say this reference to alcoholism is common, but it is also unfortunate. The focus on alcoholism distorts the picture of addiction in more than one way. To understand this it is first important to understand what we mean when we say alcoholism. As with all things with names, the use of the names conjures in the listener’s mind a picture that they expect to see associated with that name.

The picture conjured by alcoholism is not a picture of the disease of addiction. Rather it is a mosaic of elements of the illness, elements of the drug effects of alcohol and epiphenomena of both. For example we could consider the “look” of an alcoholic.

When people think of a “beer belly” or a big red nose they are thinking of specific drug effects of alcohol. Alcohol’s effects on the liver, circulation and blood cell morphology are unique to that drug. But these drug effects are not the disease of addition or even markers for the disease.

Indeed, many alcoholics lack these signs. In any case these body changes are unimportant to the alcoholic and are rarely noticed by them unless pointed out by others. These changes are not central phenomena of people with addiction using alcohol; they are epiphenomena that are unique to that drug.

There are other epiphenomena that we confuse as central themes. The violence of alcoholics is a good example. The violence causing drug effects of alcohol on some people are not generalizable to all addicts, all drug users or even all alcoholics. And yet this picture of violence is generalized to those others in the belief it is a central issue.

Several social issues will arise with alcohol that have long been unique to it for a variety of scientific and social reasons. The primary one is that alcohol is legal, common, and socially acceptable to a certain degree. Many law-abiding people drink and gather together to drink at parties. Because it is common and often seen, alcohol will often be seen as the single cause of complex social problems such as divorce and children born out of wedlock. One can tell when another has been drinking often just by smell. A scientific example is the clear correlation between blood alcohol level and impairment coupled with technology that can noninvasively measure this level. Because this is true of alcohol we generalize it to all drugs even though such technology is not available.

One far-reaching effect of seeing the problem of alcoholism as the core chemical presentation of addiction, and all its epiphenomena together as a whole illness, is the research is done on alcoholism that is mistaken for research on addition. I suggest that when social scientists say they are studying the disease of alcoholism they are studying the problem of alcoholism.

So what is the central core of the problem of addiction as expressed with alcohol? The same as with any other drug or behavior. Writings from both the lab and the personal experiences of alcoholics suggest a two-fold answer. First, in an alcoholic who takes a drink, the ability to not take a second drink becomes a greatly diminished or is erased entirely. Second is that when an alcoholic tries not to drink an obsession develops which generally leads to failure of abstinence.

Others may say, “What about using alcohol in spite of adverse consequences? ” Isn’t that a core criterion for alcoholism in the DSM IV? Is it really a core phenomenon or is it an epiphenomenon seen in most people because most people have consequences. Consider a king who has unlimited resources and whom no one will oppose. If he has no consequences yet cannot control his intake and cannot abstain is he not an alcoholic?

Others will say, “What about tolerance? ” Isn’t that a criterion as well? Yes it is but one generally limited to sedative hypnotics and opioids.

“Well, what of withdrawal? That’s got to be central to alcoholism and addiction.” One would think, but the issue is far from what it appears. If one lets a drug habituated rat self-administer small amounts of drug directly to the brain’s reward center it will do this almost to the exclusion of all else. Now what if you suddenly cut off the supply of drug, say heroin or alcohol, after several weeks. Wouldn’t one expect withdrawal? Yet, it does not occur. However if you put the catheter in another part of the brain, the PAG, you would find there is no drug taking behavior. The animal will not self administer drug to that area. However if you administered it to that area everyday for a few weeks and suddenly stopped, the animal would go into withdrawal in spite of never having enjoyed the drug. So is withdrawal a central core part of addiction or an epiphenomenon stemming from the fact that human drug addicts don’t administer drugs with micropipettes directly to individual parts of their brains?

What of the other criteria? I think that failure to fulfill role obligations could be a consequence of either compulsive use or continuing obsession. Spending a great deal of time thinking about or using the drug, also both. Broken limits, clearly compulsive use. Failed attempts to quit, clearly continuing obsession.

If we accept that these two core phenomenon and these alone represent addiction without the complication of epiphenomena, then we should be able to find a biology common to all people with addiction that explains both of these phenomena. It is that biological explanation which is the main thrust of this blog. And once we know the biology, the drug doesn’t matter. Using food, gambling, sex, spending, heroin, cocaine, alcohol or anything else in the disease of addiction is still the disease of addiction. The biology of addiction is still the biology of addiction, and the treatment of addiction is still the treatment of addiction. We won’t solve the problem of addiction in our society while we focus on one drug or another.

I recently attended the Pain and Addiction day-long course at the annual meeting of the American Society of Addiction Medicine (ASAM). There I heard a lecture by a respected colleague arguing against allowing recovering physicians to work on the medication buprenorphine, a partial opioid agonist used in treating opioid dependence. His argument had three significant points.

First, that data from recovering physician programs showed that there is a low rate of positive urine tests out to 5 years using only behavioral methods and the medication is not likely necessary. Second, that recent research by Messinis et al showed that patients on buprenorphine were more impaired than those on naltrexone, a complete opioid blocker. And finally, that the data is clear that smoking increases the risk of relapse and both nicotine and buprenorphine cause dopamine release from the Ventral Tegmental Area and therefore buprenorphine can be assumed to increase relapse.

What is of even greater note is that he did the whole lecture with aplomb, humor, and a light touch of sarcasm so that the listener was adroitly pulled into his worldview without much chance for critical thought. I’ll take these points one by one.

First, that the medication isn’t necessary. The data presented showed that 82% of the addicted physicians being monitored had maintained abstinence as measured by the urine testing for over 5 years. This is a great accomplishment. However, there were no symptoms of addiction measured. There were no measures of family satisfaction or how well the person was working. There was no neurocognitive testing to see if the physicians were living with lowered midbrain dopamine tone. The only measure was not a measure of illness recovery, but of behavioral change. Even with behavior, there was no measure of gambling, compulsive sex or any other behavior commonly exchanged for drug when someone with untreated addiction cannot get the drug. Negative urine testing is a common endpoint in substance dependence research, but we’ll have to find another one to follow the disease of addiction.

Secondly, he quoted Messinis et al’s article in Human Psychopharmacology: Clinical and Experimental in 2009, “Neuropsychological functioning in buprenorphine maintained patients versus abstinent heroin abusers on naltrexone hydrochloride therapy” as stating that buprenorphine maintained patients did worse than patients on naltrexone. In fact, to quote Messinis et al, “There were no significant differences in any of the cognitive meausres between the BMP [buprenorphine group] and the FHAN [naltrexone group] groups or between FHAN group and controls.” The difference found was between the control group, a group that doesn’t have addiction, and the buprenorphine patients. The groups were not randomized to treatment arms and there may very well have been a difference in illness severity between the naltrexone and buprenorphine arms. Further, the dose of buprenorphine may have been too low, as I have seem neurocognitive performance increase in my patients when placed on buprenorphine and dosed correctly.

Lastly, he equated nicotine use in cigarettes to taking suboxone as prescribed. To conflate the two is a cute conceit, but a logical error. Nicotine raises dopamine release from the Ventral Tegmental Area when pulsed, which is why smokers smoke rather than use nicotine patches to get dopamine. Buprenorphine doesn’t cause pulsed release of dopamine, but rather a tonic release of dopamine, which is what we want in a low dopamine addicted person. A better comparison at the nicotine receptor would have been varenicline, a new anti-smoking medication that is a partial agonist at the nicotine receptor just like buprenorphine is a partial agonist at its receptor. Both medications cause tonic release of dopamine. If my colleague would like to object to varenicline in recovering physicians, he would be logically consistent.

Unfortunately, most people making public policy decisions still don’t see addiction as an actual biological illness, and even most physicians in public policy roles don’t give the illness the same respect as other biological illnesses. I wish this was just an illness that required behavioral change, because that would be easy. One day, hopefully, enough people will read enough research and accept the illness for what it is in nature and not what they think it should be.

© Howard C Wetsman MD FASAM

While most people without the disease of addiction can understand why someone would take something that made them feel better, few can understand why anyone would continue to use a substance once the pleasure is gone and only bad effects are left. The concept of compulsive use, use which seems to overpower the individual’s desire to not use, has always been both a core feature of addiction and a great mystery. In fact, when people with addiction are asked why they, for instance, drink past the 4th or the 5th drink when they get no additional reward but greater and greater impairment, most can just shrug their shoulders and say they have no idea. Like any symptom of an illness, compulsive use must have a pathophysiology, and that pathophysiology must be understood before the symptom can be addressed medically.

The home of the compulsive use pathology is the brain’s midbrain reward system. This system exists in mammals to discriminate important objects, events, and behaviors from the background of everyday life.The reward system does this by associating the object with the primary reward produced when the neurotransmitter dopamine is released at the Nucleus Accumbens. But this dopamine spike at the Nucleus Accumbens alone is not enough to explain compulsive use.

There is a positive feedback loop within the reward system consisting of the Ventral Tegmental Area that makes and sends dopamine to the Nucleus Accumbens and the Accumbens itself which makes and sends endorphin to the Ventral Tegmental Area. This is a positive feedback loop in that the stimulation of each promotes the stimulation of the other. Under normal circumstances, this feedback loop allows normally rewarding things to be rewarding.

This positive feedback loop, however, is also responsible in large part for the compulsive use seen in addiction. A large stimulus, like a drug, will cause a larger than normal release on one part of the feedback loop spinning the system up faster and to greater heights. The resulting dopamine spike can be measured in the lab and has given science great insight into compulsive use. Because this spike is beyond the limits expected by normal biology it exhausts what dopamine is ready for release, and the level then crashes.

It has been shown in lab animals that there is a dopamine level above which they do not seek drug. The crash that follows the peak is what precipitates that next use. Additionally one can measure a proxy for strength of craving by putting obstacles between the animal and the drug and seeing at what dopamine level the animal is willing to go through what obstacle. There is a line below which no matter what the obstacle, the animal will not stop until it gets to the drug.

So one can imagine, superimposed on this output spike from the Nucleus Accumbens, two horizontal lines.One is above the baseline, above which the animal feels fine and will not seek drug. The other is below the baseline, below which the animal will use regardless of what it takes. At some point between these horizontal lines is where the animal will use again if drug is freely available.

So it is the crash that causes the compulsive use regardless of whether the peak goes above the 1st line or not. In fact as the use continues there is less and less dopamine left for stimulation, so each resulting peak is lower than the one before it. After enough use, the peak is not even as high as the original baseline. At this point, the drug ceases to cause a rewarding feeling yet the animal, or the person, continues to use.

This biology may very well explain what William Silkworth MD called, in 1935, an allergy; that is, an abnormal reaction to alcohol, that does not occur in normal people. Silkworth said that only in alcoholics did taking one drink precipitate craving for the second. While this phenomenon may be explained by the biology described above it does not explain the other core feature of addition: why the person who knows he has this abnormal reaction ever takes the 1st drink. I’ll cover that another time.

© Howard C Wetsman MD FASAM