In this piece, Hackie Reitman, M.D., interviews Bankole A. Johnson, DSc, MD, MBChB, MPhil, FRCPsych, DFAPA, Dip-ABAM, Dip-ABDA, FACFEI, who heads the Brain Science Research Consortium Unit (BSRCU) at the University of Maryland School of Medicine, and is one of the world’s leading authorities on the subject of addiction. He is a leading neuroscientist and a pioneer in the development of medications for the treatment of alcohol abuse. Professor Johnson discusses the ties between addiction and neurodiversity, what he hopes the future holds for treatment methods, and his experiences on the HBO documentary series, “Addiction.”
HACKIE REITMAN, MD (HR): Professor Johnson, do you see addiction as a neurodiversity with different wiring in the brain?
BANKOLE JOHNSON, DSc, MD, MPhil, FRCPsych (BJ): It’s a disease of the brain. It’s a disease that has a core in the central areas in the brain associated with both impulse control and decision-making. And once somebody becomes addicted, those circuits that are involved in decision-making and impulse control get corrupted. Therefore, the person is unable to make good decisions.
HR: So your approach to change is that circuitry is pharmacological?
BJ: Yes, pharmacological, and using two aspects: either general pharmacology or pharmacogenetics.
HR: Does that work hand-in-hand, or completely separate, from any behavioral approaches? Are they both necessary? Or do you feel it’s more weighted toward the pharmacological approach?
BJ: We always pair the pharmacological approach with behavioral components to our treatment, because you do need to be able to have people comply with treatment, and come in and continue to see you — which is not possible by simply handing somebody a pill. Over the last 25 years, there’s been a tremendous amount of research on the amount of behavioral treatment needed for patients with alcohol dependence. And the bottom line is that most of the psychological treatment needed is actually quite low. Currently, in the NIAAA studies that we do, we pair the psychological and behavioral treatments. Psychological treatments in clinical trials are now provided by computers in the last set of studies. They’re not performed by humans anymore. And, the response rate is about the same.
HR: When I was in Boston University School of Medicine — back in the 1970s — we had a biochemistry professor who used to talk to us all the time about Serotonin, and how it “makes you feel good, and why you should eat a lot of bananas!” And when I was reading up on you, even though I’m just an orthopedic surgeon, it’s all Greek to me – but do some of the pathways involve the Serotonin pathways?
BJ: Some of them involve Serotonin. The circuits involved are primarily of the orbital frontal cortex. The orbital frontal cortex has about 100 different neurotransmitters, so it’s all important. Building it is important, but so are multiple co-modulators of orbital frontal cortex function.
HR: What inspired you to get into all of this?
BJ: I unfortunately was teased while I was at Oxford, looking for a doctoral. I had been told that no one who would be produced by Oxford would find the cure for alcohol dependence, and this was my mission. So, this became my doctoral piece. Of course, I did get my doctorate, but I didn’t cure alcoholism. But, I learned a lot along the way.
HR: Now I was reading that you received the highest degree you can get in all of the British Empire – with a science degree in Glasgow.
BJ: The doctoral science degree is higher than a PhD. It’s basically a degree awarded by the Senate of the University. And usually, what happens is you have to demonstrate PhD-level expertise in more than one area. My areas are neuroscience, neuropsychopharmacology, and molecular genetics. So, it basically means, I suppose, that you have a great deal of expertise about some of it, *Laughs*
HR: *Laughs* You’re very modest. Can you tell us a bit about your upbringing? You were born in Nigeria?
BJ: I was born in Nigeria, but my father left shortly after to work in England. Between the ages of 1 and 5, I actually was (there), in pre-K and kindergarten. And then I went back for my – what would be an American first grade in Nigeria – to about 15. Just before I turned 16, I went off to France to study languages, and then I went to medical school just before my 17th birthday. So, of course, I’ve been in the profession a very long time, even though I might not appear to be 70 years old. But I have the same amount of time in the field.
…I don’t want to be trying to treat the most highly motivated, non-impulsive, well-supported alcohol dependent person who is going to do better anyway. I want to be able to treat the ambivalent, weak-willed person who doesn’t really want treatment, who really can’t be convinced they have anything. That’s the person I really want to focus my treatment on, because they’re the most vulnerable.
HR: What is the biggest single thing that you can tell our audience about addiction or alcoholism that the public, the average Joe, doesn’t get? Whether they be in the United States or Nigeria or England?
BJ: I have 10 myths of alcohol dependence that I believe the general public has. I do a free course for our community members –it’s called the Mini-Med School, and usually these are older adults, who don’t have a chance to go to medical school, but are interested in learning about medicine. I give them these 10 myths, and they tend to be pretty surprised. One of the interesting things about alcohol dependence is that alcohol itself is actually a weakly-addictive drug. If it was powerfully addictive, 80% or 90% of the planet would be addicted to alcohol. So it’s a weakly-addictive drug. Strangely, alcohol has no receptors in the brain. That means the brain has to decode it another way. We know that about 60% of alcohol dependence is inherited and about 40% of it is acquired. That doesn’t mean that the 40% is not important, but it does mean that if you don’t have a pharmacological treatment of any kind, then you really are struggling. You’re working on the 40% of the disease, which is not particularly effective. So, the other interesting piece of information is that alcohol dependence has a very high spontaneous remission rate. That means that, of any given four patients with alcohol dependence, one of them will recover spontaneously in one year.
So, if you are offering a placebo treatment, and you decided to set up a tent and invent some kind of treatment for alcohol dependence, you will be successful 25% of the time, irrespective of the value of your treatment. That’s why I think some people get misled, because they will say, “Well, I went for this type of treatment or to this type of group or this type of self-help and my Uncle Johnny got better.” But Uncle Johnny might be one of that 25%, and the key to what we’re trying to achieve with alcohol dependence is not to get 25% of people better. It’s to get everybody better. Which is a far more difficult challenge.
Therefore, one of the issues that you have with treating alcohol dependence is you have to be wary. Though some people can recover on their own, others have a genetic make-up that makes it very difficult for them to recover on their own. That’s part of the work that we did with the Serotonin blocker and with the pharmacogenetics of alcohol. Some people have this genetic pattern, which is very, very interesting indeed. Especially the one in the Serotonin system. The Serotonin system is the oldest monoamine in the brain; it really is one of our ancestral genes. So, if you look at rates of the polymorphism of Serotonin, you can actually use those ancestral markers. For example, as people moved out of Africa and into Europe, they retained a high degree of these polymorphic genes, but as they moved into Asia, etc., they began to lose these polymorphic genes. So, you can actually see that the rate of alcohol dependence is very low in many parts of Asia and, in other parts of Asia and some parts of Japan, the rates are incredibly low. You can think of alcohol as almost like a relationship between your genes and your environment, and some people are more prone than others to this combination.
HR: That makes a lot of sense. What was it like for you working on that HBO documentary, Addiction?
BJ: There’s some notes, it’s too bad, that didn’t appear in the program. The HBO producers that came to see me said, “Doc, you seem to have a great rate of success when it comes to treating patients with alcohol dependence. And maybe it’s because you select your patients deliberately to get a good response. What we’re going to do is interview, at random, patients who are coming into your clinic, and select for you the patients you are going to treat in the documentary.” So, I had no hand in selecting the patients. In fact, one patient selected – the young guy with a guitar – lived about 40 miles away, and they used to send a car for him and bring him to the clinic. And I said, “I only needed to see him for 15 minutes a week.” They said, “15 minutes, doc?!” I said, “15 minutes. That’s it. And I need to give him his treatment and he will get better.” And the older guy, too, 15 minutes. And they found this guy who didn’t really want treatment, who was skeptical, and brought him to the clinic all of the time. I didn’t have any other contact with him but, in a few minutes, I saw him and I gave him his meds and explained things to him. So that was actually not part of the subtext of the story in the HBO commercials, and the HBO movie, but they really tested me. *Laughter* Had they not have gotten better, I would have been in trouble. But I always said to the producers, which could have been my downfall, is that I don’t want to be trying to treat the most highly motivated, non-impulsive, well-supported alcohol-dependent person, who is going to do better anyway. I want to be able to treat the ambivalent, weak-willed person who doesn’t really want treatment, who really can’t be convinced that they have anything. That’s the person I really want to focus my treatment on, because they’re the most vulnerable.
HR: You’re a real champion of the underdog.
BJ: Anybody can treat someone who is highly motivated. You just tell them to stop. I’ve had patients who were extremely highly motivated, and they obviously have a lot of family support – some of them have very good reasons, and they say, “What should I do, Doc?” And I say, “Stop drinking.” And that’s the end of the treatment. I don’t have to do anything else. They’re highly motivated. But anyone can treat a patient like that. It doesn’t require any skill of any kind. Just tell them to stop.
HR: That’s common sense, and yet we don’t think like that. The summer I was an NIH cancer fellow when I was in medical school, what was interesting to me is what percentage of anything has to get better for it to be deemed effective. I forget what the number was, 28% of anything. I don’t know what the numbers are nowadays, with any kind of study, how many will get better by the placebo. What are the rates and numbers that are thrown around now for efficacy?
BJ: The spontaneous remission rate is about 25%, and the typical placebo rate is running 25% to 30% in most clinical studies, and so if you’re giving a drug, the drug has to fall above this very high placebo rate. Sometimes, when people look and read these studies and say, “Well, the drug is not powerfully effective,”— the reason why it looks like that is because the placebo response, itself, is actually quite significant. For example, if you had end-stage pancreatic cancer, you only have to get a few people better to show a big difference – probably only 1% or 2%. Alcohol studies have to be larger because the spontaneous rates are very high. Plus, people go through phases of drinking and not drinking, so you need to have enough people to account for that variable in time. You know, the peak age of drinking and alcohol dependence is not 45, it’s about 19. A lot of people who drink are in between 19 and their early 20s, but do not continue to drink later on in their life. So, it’s not truly the case that once an alcoholic, always an alcoholic. For some people that’s true. But not for all people, and not for the majority of people.
Many people look at alcohol dependence as a chronic relapsing disorder. But I’ve actually started terming it differently. It’s not chronic and relapsing, it’s acute and relapsing. Because it’s only when it’s acute do people get in touch with you. So people can go for years without drinking, and there’s nothing happening at that moment of time, but then they have an acute relapsing disorder, which is a different type of treatment. Which means that you could, at some point in time, develop cognitive treatment. If you can work out which person is going to relapse next, you might be able to intervene earlier and provide preventative treatment at that point in time, and not have to waste medicine – just give them the medications at that targeted time. And this is a very important concept in research going forward, because no one likes adjusting between medications every single day.
HR: When I was in my third year of medical school, on my Clinical Rotation on Internal Medicine at the big VA hospital in Boston, everybody had Alcoholic Liver Disease. I mean they were just lined up. And chronic, chronic, chronic. And I wonder, first of all, what the new veterans are like compared to the old veterans, and I wonder what their make-up was and what kind of pre-selected group they were to be hospitalized with liver failure.
BJ: The genetics haven’t changed very much. They probably haven’t changed in thousands of years. But alcohol dependence, especially with post-traumatic stress disorder, is now more readily recognized among veterans. In fact, we were just about to launch a study to look at that. There is increasing concern about the rates [of alcoholism among veterans], but the rates are probably no different than what they were before. We may just be more aware to recognize it. Also, we’ve been engaged in more conflicts and more wars, and therefore we have more patients. So the underlying genetics are not changing, but the numbers are changing due to exposure.
HR: What about the gut-brain effect, with the microflora in your gut affecting the neuroplasticity and rewiring in your brain? What roles do diet and nutrition and the micro-biome play in your clinical picture of alcoholism?
BJ: We’ve been working on some interesting experiments. I don’t know the full results yet. But there’s a huge potential that we may be able to uncover specific microbiome or microbiome agents that do cross, in some way, the blood-brain barrier. Or, do you provide some kind of signaling mechanism to control alcohol intake? A lot of our neurotransmitters, like Serotonin, are not actually in our brain. They’re in our gut. And we have, probably for decades, ignored that fact and said, “Well, if it’s in your gut, there’s no way it can get into your brain, because your brain is not connected to your gut in any way.” So, we didn’t take it very seriously. But now we know there are signaling molecules that are probably getting into the brain in some way. And there are various techniques that we have now at the University of Maryland School of Medicine (UMSOM) that we think we can use to actually open up parts of the blood-brain barrier effectively, and maybe even use nanotechnology to influence different expressions and brain patterns with microbiota.
HR: Do you relate that to the autoimmune or the inflammatory process?
BJ: It absolutely is part of the neuro-inflammatory process. And the neuro-inflammatory process is really a big part of brain research at the moment. The Brain Science Research Consortium Unit (BSRCU), which I head, from the University of Maryland School of Medicine, includes 9 Departments and Centers, and is focusing on neuroinflammation. And the reason is that inflammation seems to be the basis of a lot of neuropsychiatric disorders. One of the intriguing things that has become obvious in the last three years is that a lot of the drugs that seem to work in treating alcoholism also have the effect of reducing neuro-inflammation. And so, neuro-inflammation seems to be very important in changing the expressed appreciation of alcohol in the human brain.
…as we have become more holistic in the last 10 years, we are now beginning to understand that there are important and powerful interactions between behavior, diet, nutrition, brain function, gene expression… It’s far more complicated than we ever thought it possibly could be.
HR: There are so many studies now of various neurodiversities—whether it be Parkinsonism, autism, Alzheimer’s—that are finding that a good workout and a good exercise regimen can greatly affect the wiring in the brain. Have you found that so for addiction?
BJ: About 15 years ago, I had a conversation with a chap who had presented to me some experiments in rats that had been drinking and that he put on an exercise regimen, and these rats got quite a good deal better, and they reduced the drinking dramatically. I didn’t know whether to leave the experiment with some amusement or skepticism. He wanted to do this in humans, but he was about 15 years ahead of his time. I thought to myself, “How could I possibly get an NIH grant to study people just exercising to help them get better from alcoholism ?” We didn’t do that study but it’s clear, and becoming even clearer, that exercise is associated with the release of multiple important neurotransmitters and neurochemicals, and might have an effect on drinking and even drug-taking. We don’t have anything truly definitive yet, but it certainly does not hurt to exercise and do physical fitness while you have an alcohol or drug problem. It seems to help but we don’t know exactly why. We don’t know all of the neurotransmitters involved and how they actually work to produce this effect.
But this is all part of the turn of the century in medicine, and the splitting off, if you like, of behavioral vs. pharmacological and genetic, etc. I think it didn’t do the field a lot of service, assuming that these are all sort of different types of modality. And, as we have become more holistic in the last 10 years, we are now beginning to understand that there are important and powerful interactions between behavior, diet, nutrition, brain function, and gene expression… It’s far more complicated than we ever thought it possibly could be. And that is part of the rich variety of treatments. I’m hoping that when I pass on the baton to my students, in a couple of decades, their treatment regiments will be far more sophisticated and far more algorithmic than what we have now.
HR: That is the big takeaway from this conversation. What you just said summarized how we have to look at our brains, and how things are indeed multi-factorial and commonsensical, too. Now with all of the great work that you’re doing, tell us more about being at the University of Maryland School of Medicine.
BJ: The University of Maryland School of Medicine is led by Dean E. Albert Reece, and he has charged me to be the head of the Brain Science Research Consortium Unit (BSRCU), which brings together multiple Departments. It brings together a group of individuals who are interested in the downstream pathobiological processes involved in the expression of a host of disorders. This entails traumatic brain injury, neurosurgery, neurology, pharmacology, physiology, and certain technologies like radiology and neuroradiology, and also focused ultrasound. Now, we’re adding computerized computation to our group. The idea here is to be able to bring a great number of neuroscientists together on this problem of brain inflammation, as it is associated with neuropsychiatric disorders: Parkinson’s, Alzheimer’s disease – most of the brain disorders that we look at have an impact. Say you’re walking down the street, and somebody punches you in the face. You’re not going to be happy about that. A few months later, you may be depressed and you may say, “Well, I don’t want to walk down that street or go down that place.” If you talk to most psychiatrists, they will probably say, “Obviously you feel unhappy because you’ve had a traumatic experience, you know, you had a psychological problem, and therefore need to talk about it.”
What we’re learning is that some people respond that way, and some people don’t get scared at all. And it might well be that the degree of neuroinflammation that was caused by that head injury—if that had been treated at that time or reduced, that that person might not have developed depression, and may not even be fearful of going back to that place. It’s a very different way of thinking that, yes, there’s the behavioral component that produced the injury. But actually, it’s possible to intervene on a pharmacological level to stop the sustained neuropsychiatric damage. I think that this is a good way of looking at the complexity of neuroinflammation.
And, of course, as a surgeon, you know that a lot of people who come into hospitals, who’ve had traumatic brain injuries and who were in a coma and their brains were swollen – the degree of neuroinflammation has a huge effect on their recovery, not just the recovery of the neuronal capacity, but also their psychological recovery. Trying to reduce the inflammation is important, but it’s still a bit of a dark art trying to reduce the neuroinflammation after a head injury. One of the things that we’re trying to do is to see how we can reduce that kind of neuroinflammation and that will work with car accidents, concussion symptoms. Reducing the amount of brain inflammation is really very important.
HR: What else is happening at your University?
BJ: I’m a Professor of many different Departments. I wear different hats. I’ve just become a Professor of Neurology. And it keeps me young, being the head of the Brain Science Research Consortium Unit (BSRCU), because I have to be able to think like a neurosurgeon; I have to be able to think like a neurologist, be able to think like a psychiatrist, and also like your basic scientist. I have to bring people together who have different views and try to work out what it is that connects them so that they can work well together and do some great research. It’s great to be working with such wonderful people and such great minds. It’s one of the true pleasures. I have a friend who says, “Bankole, you should go into private practice because you would have so many patients, and you wouldn’t have to work so hard,” and I say, “Well if I did that, I might not learn anything every day.” One of the joys of my work is that I learn something new usually almost every day. I would miss that terribly.
HR: What does your wife think of all this?
BJ: My wife is a fantastic sounding board for some of the ideas, because she has a medical background, and so I can ask her stuff like, “Does this make sense or does this sound like science fiction to you?” One of the things I told her about a couple of weeks ago is that we know so much about neuroinflammation about the brain, and that in 10 or 15 years, it will be possible to make an artificial brain simulation of neuroinflammation. I asked her whether that was science fiction. She said it sounded pretty way out. I said to her, “When I was a medical student, I never thought I would be doing something like this. I didn’t think about printing an artificial brain. But it is going to be possible for us to be able to do things like that.”
HR: That’ll be a nice thriller when that happens.
BJ: It would be a nice thriller, but I would probably be worn down by the amount of hard work to bring it to fruition. *Laughter*
For information about the HBO Addiction project, for which Professor Bankole Johnson was a contributing expert, visit: www.hbo.com/addiction
To find out more about Professor Bankole Johnson and the work he is doing with the Brain Science Research Consortium Unit (BSRCU), visit: medschool.umaryland.edu/bsrcu
For BSRCU’s newsletters, click here.
For the psychiatry department at the University of Maryland School of Medicine, visit: medschool.umaryland.edu/psychiatry