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I was flying across the country today and the program guide in the inflight magazine listed an action movie I’d been wanting to see. But it turned out that the movie was Dolphin Tale, the story of a dolphin that was injured and required her tail to be amputated because of infection. The story also focused on the people who helped her survive and named her Winter. I was disappointed and almost turned it off, but it caught my attention. I was crying by the time the movie ended. Just goes to show how what we want isn’t always the best thing for us.

To say the story is inspiring is an understatement, and what was most touching to me was the connection that human amputees had to Winter. I was struck by their bravery and Winter’s, and by the tenacity needed to get up every day and face the world without all of your parts.

Then I realized I meet such people every day because addiction is like an amputation. The patients I see in recovery get up everyday and face the world with a part of them missing.

Most people only see addiction from looking at behavior, but from talking to people with the illness I’ve long ago come to realize that the symptoms of the illness are independant of drug use. Most of my patients can identify the missing piece was missing long before the first drug, and they can all recall with great clarity the feeling of getting that back with their first use.

For them, recovery is getting up every day and voluntarily going without a part when they could readily go get a temporary prosthesis. True, the prothesis wouldn’t work for long, but it’s an amazing temptation when your brain knows what will make everything easier, even if only for a little while.

But recovering people aren’t, as they say, “a glum lot,” but actually quite at peace with the situation. There’s a line in the movie where one of the human amputees is depressed because he can no longer do the one thing he always wanted to do. Morgan Freeman’s character tells him, “Well, you’ll just have to pick something else to want to do. Luckily, there’s about a million things to choose from.”

That’s the attitude I see in successfully recovering people. They’re not depressed because of what they can’t do, but are grateful and glad to have the rest of the world to choose from.

A lot of peple will have difficulty seeing addiction as a disability or like an amputation. Many may feel offended that I’m likening people with addiction to people who have lost a leg through no fault of their own. Well, such is my experience, and this is my blog, so I guess you’ll just have to be angry. But, in case you have an open mind let me share with you some of the things I’ve heard from patients:

“I never knew what ‘have a nice day’ meant until I had my first cigarette.”

“My whole life, I knew I could never measure up to other people, and then somebody gave me a pain pill, and I felt normal for the first time.”

“I’d just sit there thinking of nothing and getting nothing done, paralyzed by my own brain. Then I found speed.”

“Nothing made any sense at all. I couldn’t concentrate. It was like everyone was speaking another language and they were all mad at me for not understanding. But when I drank I could understand them and respond to what they were saying.”

“The first time I felt part of the world around me was when I took my first Lortab.”

Most people get to be with other people, fit in, understand and feel part of the world around them. Most people can concentrate and remember and feel joy in daily living. But if there’s not enough dopamine tone in the midbrain, these things are missing. They’re not missing because the person wants them to be missing or because the person did something to make them go away. These things aren’t missing because the person is bad or weak or missing some element of character. These things are missing because of a deficit in the brain, a physical problem, a thing that is missing.

I forget sometimes what bravery and determination it takes for my patients to get up every day and face the world. I forget the fortitude it takes to redirect one’s brain to the parts of the world that are available and happliy focus on them. I’d still like to see that action movie, but I’m glad today that the universe had other plans.

Recently I had a conversation with a colleague who asked for a recommendation for a therapist for one of his patients with addiction who was having family problems. I responded by asking how vigorous of a recovery program she was working? His response was something like this, “Oh, she’s in recovery. But the problem is that some people have intraspsychic conflicts and interpersonal deficits that make it difficult for them to engage support networks.” That really didn’t answer my question, or maybe it did.

My colleague doesn’t see the difference between being in recovery from an illness and working an addiction recovery program. Yes she’s not using; yes, she’s attending her appointments; yes, she even goes to a few meetings; but she’s not working a recovery program.

Recovery, as the word is used in 12-step fellowships, means a great deal more than going to meetings and not using. It involves work and so is most spoken of as “working a recovery program.” Of course there are people who don’t work a program who consider themselves in recovery, but they are missing out on some of the best things recovery has to offer. So what is it to work a recovery program? We’ll take 12-step recovery as an example.

In 12-step recovery, it is the steps that are worked, not just once, but on a daily basis. We can break that down, and I have in other writings, so I won’t repeat it here. But what is important to reveiw is some of what happens when someone works the steps.

The first thing that generally happens is that the person stops trusting the thinking that got them into trouble. They start to uncenter themselves as the driving force in their life and start opening up to others. They start to gain friends and fellows whom they trust and with whom they gain trust by being honest on a consistent basis. They have many methods to deal with day to day feelings and start to trust the universe that things will work out now that they aren’t running the show. They stop being afraid of things and can face their challenges honestly.

I thought about that when my colleague told me that his patient had become depressed and non-functional after her husband left her, that she felt alone and was moving in with her father to be taken care of. I thought of the family difficulties that I’d seen handled by people in recovery and how they responded. I thought of situations like his patient’s that I’d seen in people in recovery. I thought of the bands of recovering women I know who support each other, and I couldn’t imagine how someone in recovery could be alone. I imagined what would happen to the women I knew in recovery if such a thing had happened.

They would have known from working the steps what was theirs and what was their husband’s and would not take his selfishness personally. They would express their feelings with their friends and would be surrounded by their recovery community. They would have worked the steps on their anger and their fear and found relief and peace. Of course they would still have feelings, but they’d have many tools and methods of dealing with them. They would not be helpless, alone, or unable to function.

So what about those that can’t get into a 12-step recovery program? When the symptoms of the illness prevent the person from engaging in 12-step recovery, we work with medications to aleviate those symptoms. Rather than decrease participation in recovery, I have found that correct application of medication increases participation in recovery. Once symptoms are relieved, we use cognitive approaches to help people change their point of view about the illness and the barriers they have to working a recovery program. Finally, for some, the 12-step approach is a barrier. They just won’t work that method. For them, we recommend other forms of recovery.

I’ve watched people get the same benefit from these other forms of recovery. What good recovery programs have in come is this: a reliance on taking life on its own terms rather than self will, a community without a hierarchy, a mentor who serves rather than bosses, honesty and confession, personal amends, helping others. If a recovery program has those things, the person working the program will likely get the same benefits.

Most of those benefits are spiritual. There is a calm that comes with acceptance of how the world works. When we are running the show, there’s a constant fear that we’ll mess up or that someone will figure out that we can’t do it. We’re alone and isolated, spending our energy to erect and maintain a false self that we present to the world. When we are working a recovery program, we can relax, because we aren’t running the show. We don’t have to be afraid of others or the universe. It doesn’t mean that we’ll get our way or that everything will work out well, just that we’ll stop making things worse. We find that the world isn’t nearly so scary when we aren’t at the wheel.

There are neurobiological benefits as well, especially for the person with addiction. When we are running the show and feeling isolated or afraid of being found out, we actually lose dopamine receptors. We feel less of our brain’s own dopamine. Working a recovery program literally makes us feel better. That’s why people in recovery don’t use drugs or compulsive behaviors; not because it’s wrong, but because they don’t need to. In addition, studies have shown a lot of other health benefits of a spiritual life from less brain loss with age to lower blood pressure.

As someone who treats addiction, I don’t think stopping drug use is sufficient as an endpoint. It’s a necessary beginning. The real endpoint isn’t a point or an end at all. The real goal of treatment is to create a person who is working a recovery program. Once that’s done, most other psychological treatment becomes unnecessary.

The SNP rs1799971 (also called A118G) is famous. Well, if you hangout with addiction doctors or genetics people it is. I promise.

It’s famous for being the mutation of the mu opioid receptor that is most closely associated with addiction, especially to opioids and alcohol. If you have the mutation you’re more likely to have increased cravings for alcohol and more likely to have alcohol or opioid dependence says the medical literature. A well known addiction medication, naltrexone, seems to work better for stopping drinking if you have the mutation. I’ve been looking at genetic testing results now for over a year and just haven’t found it helpful so I decided to take a quick statistical look. First, some background on the “research,” if we can call it that.

Every patient entering my treatment program is given the option of getting free genetic testing. None have turned it down. They all signed informed consent to have their data kept anonymously along with non-identifying clinical data and to allow it to be used in pooled anonymized analysis. A local IRB approved the use off this database as exempted.

The database consisted of 221 sequential admissions to a private for profit Intensive Outpatient Program level of care for addiction. The population is 62% male, >90% caucasian, and the average age is 35. While all subjects were admitted for treatment of addiction, they each identified a primary “drug” that was their Most Effective Reward (MER). The frequency of those drugs as MERs were: opioids 51%, alcohol 31%, cocaine 6%, cannabinoids 6%, amphetamines 5%, and the other one percent divided between overeating and co-dependency.

If rs1799971 is important in causing addiction we should see it more frequently in an addicted population than in a general population. Of course this isn’t a population of people with addiction, but rather a population of people with addiction seeking outpatient treatment. The frequency may be different in those not seeking treatment, but this is the population I have to work with.

The allele frequency at rs1799971 in a caucasian population is A84% and G16% where G is the risk allele for addiction. Rather than finding a higher frequency of G in our population, the frequencies were A90% and G10%. It doesn’t seem to fit. So I looked at the association of having G with most effective reward. I’d have expected that G would be over represented in people whose MER is opioids or alcohol.

In fact, just he opposite. Those with G were no more likely to have listed opioids as their MER (38% of Gs said opioid were MER while 54% of non-G subjects said another drug, p=.09). So I combined alcohol and opioids in a single class to see if G was associated with either rather than one or the other. Again, not as expected (72% of the G carriers said MER was opioids or alcohol while 85% of the non G carriers said the same, p=.09). In addition, I was not able to replicate the finding that G carriers had the paradoxical stimulating response to opioids most commonly seen in opioid dependent people. About 65% of both G and non-G carriers experienced getting energy from opioids (p=NS).

I have no doubt that people with opioid system mutations have a predisposition to addiction with MER of opioids or alcohol, but rs1799971 doesn’t appear to be the smoking gun. Of course there could be a lot of reasons why I don’t see the association. The population I’m looking at may be very different in some way from those where the association was seen.

This kind of work needs to be repeated in a more rigorous format of course, but with the increasing availability of GWAS genetic testing data, much more can be determined from multiple site studies than could have been done at much greater expense before in academic centers.

I’m going off topic a bit because of the Occupy Wall St (OWS) movement. They say they are 99% of the people who are overly affected by the 1% that hold most of the wealth, and have spawned a counter group referring to themselves as the 53%, the 53% of Americans that pay taxes. The second group seems to think that the first group is asking for handouts and suggests that if they want to occupy something, they should occupy a job. I think they are missing the point.

From what I’ve read, the OWS doesn’t seem to want handouts, but rather is arguing for change in a system that leads to such concentration of wealth. They don’t seem to be complaining about the wealth disparity as much as they are the power concentration that comes from the wealth. I think they would be happy to be in a level playing field with rich people, but are arguing about the playing field not being level. And while I think they may be right and are sort of aiming in the right direction, they haven’t identified the real underlying cause.

It’s not so much the greed of the banks or the greed of Wall St that has caused the problems, but rather it’s the fact that banks control the money supply. It may seem odd to talk about banks not controlling the money supply, but in the history of the country, except for brief periods, the money supply was controlled by the people until 1913 with the creation of the Federal Reserve Bank.

The Federal Reserve Bank seems to be able to create money out of nothing by loaning it to the government. The government then deposits this money in other banks which get the first use of it. These banks, that have a requirement set by the Federal Reserve to keep a certain amount of money in reserve against bad loans, can loan out about 10 times what they have in deposits. This increases the money supply several fold and inflates the economy. In times of inflation people make bad economic choices based on false assumptions. When these bad choices are concentrated by whims of culture they go to extremes and are referred to later as bubbles (tulip, south sea, and more lately, housing). But the source of the bubble is always the creation of more money than would have been created through normal economic means.

Most people don’t see inflation because it happens so slowly, but the bankers have a front row seat. I think that if all of us knew what they knew, we’d probably want big bonuses too. Because they see that the ultimate end of this is that the money they get is worthless, so their normal human reaction is to get as much as possible, as fast as possible, and buy with it things that will retain their value. And the rest of us have been okay with that as long as we’ve been able to get by. But the whole process of inflation has had dire consequences for our thinking and our culture.

While most of us don’t consciously notice it, I think we do at core. While we don’t have the resources to buy a house in the Hamptons, we do have the ability to choose a X-box rather than saving the money. And when the money is losing its value due to inflation, we, like the bankers, will buy things that will seem to hold their value. Inflation makes us all overvalue immediate reward; it has changed our culture.

So rather than the 53% looking at the OWS and saying, “Get a job,” I think we in the 53% need to look at ourselves and ask why we are willing to live with a system that gives the economic power of money creation to banks and bankers. If we got rid of fractional reserve banking and had a truly distributed system such as a free mint gold standard the power would rest with the people, all the people. We’d have a reason to save, and we’d invest our savings carefully. Our economy would grow as it did between 1870 and 1913, some of the greatest growth we’ve ever had.

If you know me, you know that I don’t believe that addiction is any more common now than it was in 1789 when the constitution was written. But if it is, the best possible reason is not a new drug or anything else that most people associate with addiction. If there is more addiction now then when the founders wrote the constitution it is more likely the normal effect on the midbrain reward system of a depreciating money supply. Not surprising that we wouldn’t notice it because everyone alive now has grown up since 1913 (the founding of the Federal Reserve Bank) and most since 1932 (when circulation of gold coin stopped) and even most since 1971 (when the dollar was completely removed from a gold standard). We don’t think of money and wealth in the same way as most of the world has for most of human history. It’s pretty to think that we’re right and they’re wrong, but not very likely.

I recently finished reading “Transcriptional and Epigenetic Mechanisms of Addiction” by Alfred J Robison and Eric J Nestler published in Nature Reviews: Neuroscience (vol12,Nov2011,pp623-637). Most of the issue is related to addiction and this is one of four featured papers on the subject. The article outlines the research done on the expression and repression of existing genetics in an individual animal because of chronic drug use. There’s the first problem. The article has a lot to do with the consequences of drug use, but little to do with addiction.

The primary assumption of the article, and of most of the work done in the field today, relates to the chronicity of addiction. As the authors say, “This persistence suggests that drugs induce long-lasting changes in the brain that underlie addiction behaviors.” It never seems to occur to them that perhaps the human illness of addiction is chronic because it isn’t caused by drugs and, in fact, is there before the drugs. If that is the case, we’d never expect it to go away just because the drugs do.

One of the reasons that this does not occur to them is that none of the work is done in humans. The work is done on animal models of addiction rather than humans with the actual illness. Now to be fair, this is as good as it gets. We could never do this work on people. But the fact that the work is done on a model of the illness in other species should suggest to most people that caution is advised when suggesting the focus of treatments and public policy.

Another, related assumption of the article and the field refers to the epigenetic changes seen after prolonged drug use. Again, the authors, “…such adaptations are one of the main processes by which drugs induce highly stable changes in the brain that mediate the addicted phenotype.” There is a subtle difference in this assumption and one that goes to the heart of how we define addiction in our society. The authors refer to addiction as a state that one can be in. Given that the world defines addiction as DSM substance dependence, such a rationale is reasonable. The state of active addiction can stop, when the person stops. However, the illness, without treatment, can and does continue with symptoms which put the person at a great risk of relapse into active use.

What amazes me, beyond the brilliant science contained in the paper and the work behind it, is the lengths that people in the field go to in order to protect the assumptions. Another quote, “Nevertheless, drug relapse can occur after decades of abstinence, a timescale dwarfing even phosphorylated dFOSB’s prolonged turnover rate. It is possible that dFOSB remains stably linked to individual gene promoters for long periods of time or induces long lasting changes to the chromatin structure of individual genes to influence relapse behavior long after total cellular levels of the protein have returned to baseline. These possibilities remain to be investigated in future experiments.” So what they are saying is that there is this “long standing” change brought about by chronic drug use that they think is the reason the illness is chronic. However, the illness is so chronic that it dwarfs the amount of time for which the change is stable. Rather than say, “Well, that can’t be why it’s chronic then,” they say, perhaps it’s even more stable than we think though there’s no evidence for it now. Perhaps future studies will show it. And how much money are we going to spend on the future studies when Occam’s razor suggests we ought to be looking elsewhere.

To be fair, there is no doubt that drugs effect how our genes are expressed. The work behind the paper is brilliant and, I think, will have a lot to offer the human condition. But the work really speaks to the fact that the environment changes gene expression, and drugs are just one example that environment. Limiting the data to drugs does tell us what happens to normal mammal midbrains if they chronically take drugs. The problem is that most other research shows that, left to their own devices, normal mammals won’t take drugs chronically. So rather than look at the changes that come from chronic drug exposure, we should be looking at what changes are necessary to get mammals willing to take drugs in the first place. Then we’ll begin to understand human addiction.

There are three other reviews in this issue of Nature Reviews: Neuroscience. I’ll start working on the next one.

On August 15th, ASAM published their new definition of Addiction, and on August 16th Maia Szalavitz, a health writer for Time, published an online critique of it. That was quick, she must be a fast reader.

Her first point is that while the intention of the new definition is, in part, to decrease stigma, calling something a brain disease is a bad way to do it. As evidence she sights a 2010 study in the American Journal of Psychiatry by Pescosolido, et al, entitled, “A Disease Like Any Other?” The study examined the difference in attitudes toward Major Depression, Schizophrenia, and Alcohol Dependence between 1996 and 2006 with regard to the public’s acceptance of these as neurobiological disorders and associated stigma. She points out that:

“While the percentage of people who said they believed alcoholism was a brain disorder increased from 38% to 47%, that shift was not linked with a decrease in stigma. In fact, over the same time period, the percentage of people who said they thought alcoholism was linked with “bad character” also increased significantly, from 49% to 65%.”

Ms Szalavitz misses the internal inconsistency in the data that stems from the “old” definition of addiction. Until ASAM’s new definition, every biological explanation of addiction as a whole or divided up into parts as addictions considered the etiology of the illness to be the drug which was used. Only such a definition could lead us to an increased understanding of something as a disease of bad character. What is missing in her critique is an examination of the real difference in the new definition: the word primary.

What ASAM’s definition says, at least by my reading, is that addiction is a primary change in brain function leading to symptoms which leads to the characteristic behavioral manifestations. This is utterly new. Addiction is not caused by using drugs; there is no mistake made by a weak person of bad character which caused the illness. This concept is so new, so different from what the public has been taught to believe that any past examination of beliefs about addiction would hardly be relevant.

Ms Szalavitz’s second point is that the word “chronic” in the definition is just wrong. As evidence she sites a study by Dawson et al in Addiction in 2005 that examined a natural history of DSM-IV alcohol dependence. Again, what she misses is the essential point. DSM defines alcohol dependence on a set a behaviors rather than as a biological disorder; it assumes no active illness if behavior changes, and does not consider drug switching in the definition. So in DSM, an alcohol dependent person who meets three of the seven criteria in a 12 month period modifies his drinking by increasing his use of pot (or overeating, or cigarettes or any other source of increased midbrain dopamine tone) no longer meets criteria for active alcohol dependence and would have been categorized in Dawson’s study as in non-abstinent recovery. What ASAM says is chronic is not the behavior, but the illness.

What ASAM’s definition gives us is a bottom up biologically based view much more like other illnesses than the behaviorally based view of DSM that has confused the public (and the press) into understanding addiction as a self caused “disease.” What seems to upset Ms Szalavitz is that ASAM is using words in it’s new definition that don’t fit her old definition.

Here’s her final example: the word spiritual. I take her point, “When trying to convince doctors and the general public that a condition is a genuine disease, I would argue that it’s probably best to leave God out of it.” However, as most people associate recovery from addiction with 12-step recovery, some concept of how the neurobiological fits with the spiritual may actually help with the acceptance of the definition. I won’t say more here as I have already written enough on this in a previous blog post in May of 2010.

Ms Svalavitz ends with, “Like depression, addiction is a real medical disorder that affects the brain. But if we want to reduce the stigma associated with it, emphasizing recovery and resilience is probably more useful than focusing on definitions of brain disease. To increase the use of effective and non-stigmatizing care, let’s stick to the empirical evidence, not the ineffable.” ASAM’s definition is based on far more empirical evidence of neurbiology than any previous definition. While I agree that focusing on recovery is important, the mistreatment, misunderstanding, and mis-application of treatment principles that have stood in the way of the recovery of so many is so pervasive in our field that ASAM would have been negligent not to step up and, using the latest scientific findings, give us a new view that offers a great improvement in treatment options.

I was amused to hear from the computer support person that my problem was a PICNIC. What’s a PICNIC? “Problem in chair, not in computer.”

Genetic studies have a similar problem. Let call it PIPNIG, Problem in phenotype, not in genotype.

Let’s say that we are going to do a study looking for the genetics of depression. The first problem will be the diagnosis of depression. The American Psychiatric Association has a definition by criteria for the diagnosis in DSM IV, but most people in America use the word to mean something different. Well that’s so obvious that no one would use a question such as “Have you ever had depression?” for a genetic study. Perhaps they’d tighten that up by saying, “Have you ever been treated by a physician for depression?”

That won’t be a whole lot better. Most cases of “depression” are treated by physicians who aren’t psychiatrists and who aren’t fluent in the diagnostic criteria in DSM. In addition to that anti-depressants are used for a variety of symptoms and syndromes and patients aren’t always clear about what they are being treated for. So people taking Prozac for pre-menstrual dysphoric disorder may very well think they are being treated for depression when they learn the medicine is an anti-depressant. I hear this response from patients all the time.

So it’s probably already obvious that it’s going to be a bigger problem to get information on psychiatric illnesses than, let’s say, gall stones. I mean, there either were gall stones or not. I know, there are still some confounders, but it’s a lot clearer than depression.

So we’ll have to move away from single question screening for phenotype. Maybe we should use the criteria themselves? Good idea. Should we use DSM IV? Or the Research Diagnostic Criteria? Or the ICD-10 criteria? Or perhaps some of the other many criteria invented to define the illness. And while we’re on the subject of the illness, should we use the criteria for major depression or dysthymia. reactive depression or atypical depression?

People have developed elaborate researcher given sets of questions to answer who has what. Even then, these are questions that are mostly behavioral or not biologically based, so that what we’ve really got is a group of man-made “phenotypes.” It’s so bad that if someone’s genetic research validated the current constructs, I’d have a tough time believing they didn’t make up the data. A genetic study that showed no association to these man-made constructs would be believable.

The bottom line is that the broken bone of mental illness has been missing all along. If you break your leg, you can take an X ray and see it’s broken. If there’s a problem with your brain, mostly we’ve been relying on seeing evidence in your behavior. So our definitions are behavioral and not, largely, biological. So if genetic studies don’t have great results with psychiatric illness, there’s a good reason: PIPNIG.

So what’s the solution? Stop using psychiatric diagnoses in genetic studies. Instead use actual biological phenotype. It won’t get us the holy grail answers the first time out but it will define and help us segregate the actual biological issues and eventually clarify the core of the problem. What are some of these? There are lab tests, but if we’re going to limit ourselves to self reports in order to get a lot of research done quickly we’re going to have to pass those up.

Here are some examples of what we could ask:

1. If you are a woman, if you have ever been pregnant, if you feel you had chronic problems with low mood before pregnancy, did you notice that your mood was better when pregnant? [this measures for increased dopamine release with increased estrogen of pregnancy]

2. If you have ever been in an automobile accident in which you thought you would be killed or badly hurt, did you have sleep disturbance afterwards, and, if so, for how many days? [this is a proxy for the biological increase in autonomic sensitivity following trauma] [you could substitute any trauma or ask about many and combine for a trauma score - such as the Childhood Trauma Experiences Scale that Bess David and I developed] [you would want to ask about age of the trauma as well]

3. Have you ever been spoken to in such a shaming manner that you felt you’d never be happy again. [this is a proxy for the propensity for dopamine receptors to decrease in density when we are made to feel less than] [this may be a risk factor for early drug use]

I could keep going, but I think you get the point. We can take what we want to study and find in it the biological kernel and ask only about that. Hopefully, then, we won’t have a PIPNIG.

If you see addiction as an illness, and you want a monitoring system in place to make sure that the illness is contained as part of a larger treatment program, you probably want better drug testing than you have.

There are several questions to ask:

1. How often to test

2. What to test for

3. What method to use for screening

4. When to confirm and what to confirm for

But there is a larger question that underlies all of these and is the reason that any testing is done at all. That question is, “Has the patient used any substances since the last test?” We want to know if the patient is abstinent, if the usage, and that part of the illness, has been contained. We want to know that because there are certain parts of treatment that are appropriate for someone who is abstinent that are a waste of time if they aren’t. And there are certain interventions that are important if someone isn’t abstinent that are not only a waste of time, but actually hurtful, if the patient is.

So we really don’t want to know positive or negative answers unless they answer the larger question. A positive on a point of care (POC) cup for THC isn’t important unless it answers the question of whether or not the patient used since last tested. I’ve never seen a lab that actually caters to treaters of addiction in order to be able to give us a fast, accurate, reasoned answer to the big question. And when you think about it, it’s not a question a lab is designed to answer.

They want to answer the little questions, “Did he have more than 50ng of THC per ml in the sample you put in the cup?” or “How many ng of THC per ml was in the sample you sent?” A lab is a technical place and they want to answer technical questions. But clinicians don’t treat test tubes and we want answers that are important to the treatment we’re doing.

In a perfect world, we would test everyone everyday with a perfect confirmation analyzer we had in the clinic and get immediate and perfectly accurate results immediately. Oh, and it would be free also. So much for a perfect world.

So what we have now is a set of compromises because of the inability to get to that perfect goal and we come up with different compromises based on our setting (clinic, doctor’s office, inpatient, forensic, etc), the cost, our need for accuracy, our or our patients’ ability to pay, and our ability to wait. So before we can answer those four questions above we need to know these important factors.

I’ll give you my factors, but they are just mine. Yours will be different if you work in a different setting. My patients largely have insurance so can pay for testing. They are in an Intensive Outpatient Program (IOP) so they are seen frequently. They have jobs and resources so that they can afford drugs and have the freedom to go get them in between sessions if the disease is not contained. They may be on medications that need to be monitored to be sure the patient is taking them correctly. We track our patients’ progress through treatment with a numerical system so that we know what intervention to do when, so it’s important for us to know on a daily basis that the disease is contained or not; therefore we need the answers fast. Our goal is to prevent more expensive inpatient admissions so, some added cost for drug testing is acceptable. We need accurate answers on not only drug levels but corrected drug levels for state of hydration so that we can see if someone’s level is falling or rising.

So here’s what we’ve come up with. Because we need answers fast we use POC testing for as many things as we can. It’s not very accurate so we have to confirm our positive results. The problem is that the negatives aren’t always accurate either (especially for methadone, opiates, and benzos) so if we’re suspicious we have to send the entire panel off for confirmation. We’d love to confirm every test everyday, but can’t because of cost so we only do negatives when we’re suspicious. We test three times a week at first, though we’d like to test everyday but the cost is prohibitive, and lower to twice a week and then weekly as the patient stabilizes. If there is a positive we go back to three times a week and taper according to the person’s stability. We confirm our POC testing for the entire panel one time at first (to ensure that negatives are really negatives before using POC routinely) and then for suspicion, because we’ve had cases where people have been using something that POC testing can’t test for (like Z drugs or Soma). If on first test we find something like that we follow with lowest level of testing available to monitor for that. When we send things to the lab we always get validity testing to measure an accurate creatinine. That’s for comparing inter-test levels of drugs. For instance if we test someone a second time and the level went up, does it mean they used or are dehydrated the second time? With creatinine corrected values we can tell.

What I want is to find a lab that will come and pick up my samples after group and drive them overnight to the lab so that they can be tested first thing in the AM. I want the answer to the question before I see the patient again the next day. Otherwise I won’t be able to do the best intervention the next day. I want the lab to do the testing with accurate measures so we don’t need to keep confirming negatives and only confirm positives. I want that right away as well. This is going to cost, but it will save in other ways. Because I get the answer fast, treatment will go better and faster. I understand that in other treatment programs that say the same thing to each person everyday, it doesn’t matter, but to us it does. If I don’t have to use POC for fast results I can skip that step and use more accurate screening with the lab’s machine, thereby saving the necessity for confirming negatives. And when I get the answer from the lab, I want the answer to my question, not the answer to theirs.

Will I get that? Maybe one day. There’s a big shake up in our space because of parity, a new biological view of addiction, a more medically managed approach. We probably need to start from the bottom up because most labs available to us now started as monitors for pain management programs. Insurance companies have to start seeing their whole cost of the illness rather than looking only at treatment. Society has to embrace this illness as an illness rather than something blameworthy so the emphasis can leave “catching” and go to monitoring. We’ll need better informatics so that we can take advantage of the improved information flow and it will result in better treatment. I think we have a better treatment program, but currently our drug testing is holding us back. Others are probably holding back from improving treatment because the drug testing to support it isn’t available. Hopefully, that will change soon.

GWAS stands for Genome Wide Association Study. In a GWAS we’d take two groups, one that has an illness and one who doesn’t and then look across the entire genome in a shotgun type of way to see what genetic polymorphisms are associated with that illness. As you can imagine, we’d need a large number of people in both groups. For illnesses where there is no theory as to why they occur or no known pathophysiology to aim at, it’s a great way to get started.

For those who don’t have a biological definition of addiction or for those who use DSM’s behavioral approach to diagnosis, it sounds like a good idea. Too bad the disease of addiction didn’t read the DSM.

I’ve looked at the genome wide testing of over 200 people in the last year or so and, among other things, I looked at some SNPs (single nucleotide polymorphisms) that the addiction literature said were important because of findings in previous large, respected GWAS studies. There were 4 genes implicated in those studies, but the studies weren’t really on addiction. They used diagnoses such as alcohol dependence, cocaine dependence or nicotine dependence. The bottom line is that I’ve stopped looking at those SNPs because after the first 150 people I looked at there were no differences between those with and without addiction and no differences by the most commonly used drug in those with addiction. I’ll tell you more reasons in a bit.

Now those who laud GWAS studies for addiction will say that I was too hasty. “Only a hundred people? Those studies had thousands of people. How can you make any determination after only 100 people?” Because I practice medicine on one person at a time and will never see 10,000 patients in my lifetime. Things that are only seen in high-powered studies may be of interest to academics but they aren’t of interest to my patients. There are a few more reasons why I’m not looking for arcane one in 10,000 associations.

Addiction is a terminal, chronic, incurable illness with population prevalence of about 10 to 20% and is the ultimate cause behind the top 5 leading causes of death of Americans. Anything that important and that common has to have important factors that don’t need 10,000 people to see. Also, none of the studies were actually studies of an illness called addiction; they studied things like alcohol dependence. Let’s just take a minute to look at alcohol dependence and what GWAS studies measure.

To have the diagnosis of alcohol dependence you have to have three out of 7 alcohol related behavioral criteria in a single 12-month period. You can have them because your opioid receptor doesn’t work well and alcohol works to boost the signal. You can have them because your dopamine receptor doesn’t work well and alcohol works to boost dopamine release. You can have them because you’re being beaten at home and alcohol helps to tune out the pain. You can have them because you feel anxious and obsessive and alcohol helps you to calm down. You can have them because there used to be a good reason for you to drink too much, but even though the reason is gone now, you can’t stop because of the withdrawal symptoms. I can keep going with another couple of dozen reasons, but I think you get the point. The group that meets the criteria for alcohol dependence is biologically heterogeneous to such an extent that they don’t even all have the disease of addiction. And those that do, probably have it for multiple reasons.

So those that laud GWAS studies are now saying, “That’s my point. The population is so heterogeneous that you need a large sample to find the multiple factors.” That would be true if we didn’t have actual biological targets for the disease. If you read DSM, we don’t. If you understand addiction as a biological illness, we do. And if you look at the targets that derive from such an understanding, you don’t need 10,000 people in your sample.

For instance we saw in our first 40 patients a marker for deciding who needs a particular medication and had a good model of markers for that medication within the first 100 patients. That was based on understanding how that medication actually works in addiction and testing it. We found in our first 100, a marker for those that can’t take a certain other medication without a protective agent first. That’s because we had an understanding of how that medication works.

If I’ve stopped looking at the result of GWAS studies, what should we do instead? The first thing is to define addiction in a biological, not behavioral, sense. Then look for the actual biological factors that exist in the model and test them multiple times in populations only large enough to power the study. This will not lead us to a gene for addiction, but nothing else will either. There isn’t one SNP for cystic fibrosis, there are at least 30. There isn’t one gene for diabetes, but several. It will be the same for addiction.

Here’s an example of a study that someone could do right now if they happen to have a large genetic dataset. Ask everyone in the dataset one question, “When you took your first opioid pain medication of your life, did it give you energy?” That’s a specific biological factor that is likely genetic. Now look at the SNPs you have for the opioid receptors and the prodynorphin gene, and if you want, add the dopamine reward system and the liver enzymes that break down opioids. Select only as big a subset of your dataset that you need to power a large effect size , because the factor has a large effect size. In this case about 10% of the population gets energy from opioids and their experience is not even close to the response of the other 90% of the population who get a little nauseated and take a nap. Any SNPs stand out as being associated with energy on first taking opioids? Now repeat the study on the other parts of your dataset to confirm it. If you have a dataset of 10,000 individuals and did this ten times you’d have the most confirmed finding in science history.

This is the kind of work that is going to become very available and bump us ahead in our scientific understanding. As more and more people get genome wide testing for themselves, either direct from the companies offering them or through their doctor, the more people will be available to participate in this kind of research. And when I say participate, I mean participate. While we ask them, for instance, what the response to their first opioid is we may also want to ask them what other things they think may be biologically related to their addiction. For instance, “Of the other people you know with addiction, what traits did you have in common with them before your first use of any drug?” To be honest, so much addiction research has been done without being informed by the experience of those with the disease, that academic research has really lost its way. Now that ASAM has defined addiction in a biological sense, and future researchers will research the validity of the definition, we will start to actually have research on addiction. It’s about time.

We really want to be in charge. We really want to make decisions with our minds and have them be good ones. Even when we do things that are ineffective or downright stupid, we really want to say that we made the decision, that we were in charge. We worship the mind we make decisions with and we abhor anyone who tells us that something about our decisions or choices is determined by biology.

I see this all the time in addicted patients. Perhaps it’s just that they are socialized in a society that is so focused on choice that they can’t accept that the disease is biological. Almost everyone I’ve met who came to treatment came to stop a behavior that they considered was a choice. Very few understood the actual biological nature of the unified illness until they were taught it. Most, when taught, saw it right away, but some fight the idea, holding on to the end to the idea that they make the choices and are in charge.

I read a study recently that illustrates the principle here even though it has nothing to do with addiction. Scientists at the University of Toronto (1) showed pictures of men’s faces to heterosexual women at various points in their ovulation cycle. Half the pictures were of self identified gay men and half were of self-identified heterosexual men. They asked the women to pick which were the pictures of the heterosexual men.

A couple of points are illustrative. First, universally, all the women thought they did terrible at picking out the heterosexual men. No matter how close they were to ovulating or not, they felt that no one could do this. They couldn’t consciously find differences and, therefore, believed they couldn’t do it. The second point is that the closer the women were to ovulation the better they were at picking out the heterosexual men, an ability that fell off rapidly after ovulation.

Remember, these weren’t videos. There were no pheromones. There was no sound. They couldn’t interact with the men. The only thing they could do was look at facial photos.

Consciously, they had no idea that they could tell any difference. The part of the brain that they are aware of cannot do this, and so they didn’t think it was possible. It didn’t matter if the women wanted children or not. It had nothing to do with their wishes or their choices.

I’m going to leave aside all the other aspects of this study and just go over what it may mean for addiction. Obviously the study needs to be replicated, but assuming the findings are real, this tells us something important.

First, our brain is active in areas we aren’t aware of. It’s making choices and judgments we aren’t privy to. There’s activity there that we can’t monitor or control with our cortex. If it can happen in this aspect of a woman’s brain it can happen in the reward center where addiction is active.

Second, our brains aren’t “hardwired” the way we think. There are, of course, genetic limits, but even those may be modified or compensated for by other behaviors. Our brains just aren’t as steady as we thought, they are plastic and changeable, and not necessarily the way we’d pick or chose them to be. It’s not just women who have cycles and not all cycles are monthly. Circadian cycles, annual cycles, multi-year cycles all exist, and, in addition, there’s aging. We can’t necessarily rely on our brain to be the same as it was yesterday, no matter how much we want it to be so.

So back to people with addiction. What do you do if you can’t trust your brain to make decisions or even to monitor decisions? There are several things that successfully recovering addicts have found over the years. First, don’t do it alone. A loving community of other recovering people can see things you can’t. Second, you can’t change yourself by thinking differently; you have to change your thinking by behaving differently. You just can’t decide that this time the drink won’t set you off; you have to not take the first drink. Also, you can’t pick and choose which drugs are safe and which aren’t. Your reward system has already decided and you weren’t invited to the meeting. Finally, you can’t direct your recovery yourself. You may come up with a brilliant plan based on all the best information, but if your cortex isn’t running the show, it’s not likely that your plan will work.

So how much is determined? Not everything, but a lot more than we thought and a lot more than we are comfortable with.

1. Rule, NO, et al. Mating Interest Improves Women’s Accuracy in Judging Male Sexual Orientation. Psychological Science June 2011. Online before print 10.1177/0956797611412394