Welcome, Professor Monti. Tell us about when you first arrived at Brown University.

50 years ago I saw an advertisement for a job at Brown as a project coordinator. Having just received my Ph.D., it looked like an interesting opportunity, so I took it and worked on a pharmacotherapy trial. I thought I was going to be around for a year doing that, and here I am 50 years later, not able to find a real job otherwise.

That must have been quite a study!

We were studying a group of psychiatric patients with a variety of diagnoses, and substance misuse was emerging as a theme in our work. A lot of studies involving psychiatric patients were eliminating people who had alcohol use disorders. They were looking at this as a nuisance variable. If they were, for example, studying depression, they didn't want to study people who were drinking because drinking would interfere with the study of depression. Well, when you do that, you eliminate vast chunks of the population.

We decided that they were throwing the baby out with the bathwater and we decided to focus in on the substance use, particularly alcohol, at that time. We began to forge a research program around alcohol, eventually, with people with alcohol use disorder. That's how it evolved.

Somebody else's nuisance variable turned out to be the thing that enamored us most and captured our attention. That led to a variety of pilot studies and ultimately, we approached the National Institute on Alcohol Abuse and Alcoholism for funding and received our first grant, to take a look at craving and alcohol use disorder (AUD).

Your work on craving turned out to be a major advancement.

Yes, we stumbled on what has become a major mechanism in the field. In order to measure craving as an endophenotype, if you will, we devised a phenomenon referred to as cue reactivity. We happened upon this quite serendipitously. I was doing coping skills training, which is what I had been writing about, and we were trying to make role-plays for people who had alcohol use disorder as realistic as possible. So we introduced a prompt of beverage alcohol in the role-play. So for example, if somebody was doing a role play of refusing a drink, we would hold up a glass to them and say, ‘Here, you take this drink, I'll grab myself another,’ and the participant, the person with alcohol use disorder, was supposed to come up with an effective way to refuse that drink.

Well, what we found is that we were getting a pretty big bang for our buck with the prop there. It was just a prop to make the thing more realistic, but it took us down the path toward this endophenotype measuring craving in the context of the cue reactivity. We did a number of studies showing that alcoholics, severe alcoholics, differed from people with minor drinking problems in terms of their reaction to the cues. And to this day, the phenomenon of craving as measured in the endophenotype of cue reactivity is being used. 

A few months ago in Science Magazine they were talking about the new magic bullet for diabetes, the popular drug Ozempic. It seems they’ve stumbled upon the fact that people who had diabetes, who were put on this drug, were not only losing weight, but were also reporting less interest in alcohol. And lo and behold, they're using our cue reactivity protocol to measure craving in people who are on or off Ozempic.

So it's gratifying that we uncovered this serendipitously almost 40 years ago now, and to this day it's being used in the scientific study of craving.

Fifty years ago, the popular view of alcohol dependence was very different than it is today.

The scene was shifting at that time, yes. (Alcohol use disorder) was initially seen, in the 1930s and 40s, as moral failure. We began getting some scientific bulk around the notion that it was a coping problem, and maybe a brain disease. To this day, it's still probably a combination of both, but clearly, at that time, we were emerging from where it was seen as moral failure, to more of a medical or psychiatric or psychological social problem, if you will.

But that former way of thinking contributed to stigma that still persists today.

People who suffer from a variety of addictive disorders are almost uniformly subject to stigma. Understanding this, not only from a social perspective, but from a clinical perspective, I think is very important. It is a disorder that is found largely in underserved populations. Certainly the wealthy are not immune to it, but for people who are underserved, who haven't been treated fairly and are under a great deal of stress, both psychological stress, pharmacological stress, that needs to be acknowledged when approaching their respective addictions. Not to do so misses the mark.

What role does abstinence play in thinking about addictive disorders?

For a long time,  Alcoholics Anonymous was totally against harm reduction—abstinence was the only way. And for the most part AA has maintained that stance.

They're a little bit more accepting now of pharmacological interventions. For a while, no drugs at all were allowed. But harm reduction is particularly useful for people who either cannot or are not willing to totally abstain.

In my work, and in the work that we do at the Center for Alcohol and Addiction Studies,  harm reduction seems to be the way to go with both young adult drinkers and adolescent drinkers because there's no way you're going to help a 13-year-old who is drinking alcohol profusely and getting into trouble over it, by preaching that he or she needs to not drink at all for the rest of their lives. 

To get these individuals to reduce harm makes the most sense both clinically and empirically. We know that it works much better than trying to get kids to abstain. A number of clinical trials have taken a look at teenagers who are randomly assigned to various types of treatment, and a coping skills treatment that teaches harm reduction skills has emerged as the treatment of choice.

Pharmacotherapy is another form of harm reduction. Why is it so challenging to discover new drugs for treating AUD?

The pharmacotherapy of alcohol use disorder has suffered over these three or four decades. We haven't introduced a new drug that is effective in reducing alcohol craving since naltrexone. And we did some of those early naltrexone trials here at Brown. The problem with the pharmacotherapy of alcohol is that the effects are not great. People who are troubled by alcohol don't take the medicine. And drug companies are not motivated to put a lot of effort into drug discovery because the market is not there as it is with something like Ozempic. So we’ve relied on some of the standby formulas such as Naltrexone or Vivitrol, which is the injectable form of Naltrexone, in conjunction with behavioral therapy.

It’s in the behavioral realm that CAAS has distinguished itself.

We are probably the go-to place in the world for behavioral science around addictive disorders. What we've done in the School of Public Health over the past ten years is brought that to the forefront. We've recruited faculty with interests in this area. We probably have the largest group of faculty studying these problems anywhere in the country, certainly, and anywhere in the world as well. The School of Public Health has allowed us to do that by bringing in several people who were noted for their work and would be complementary to our work in craving and coping skills. 

Right now, the Center for Alcohol and Addiction Studies has over a dozen full professors collaborating with each other. This is very unique in the field. At most places you’ll find one or two people studying the same general phenomena. Here at Brown, we have people studying different aspects of the elephant, if you will, because addiction is multifaceted. You need social scientists, you need behavioral scientists, pharmacologists. And the only way you can do that is in the context of a large university. But very often in large universities, research intensive universities, people are siloed and they don't talk to each other. 

At a place like Brown, those silos don't exist for the most part. And I've been able to go to my colleagues in neuroscience and tell them about a neuroimaging study that we want to do and collaborate with them. Or go to my colleagues in microbiology and tell them that we're interested in studying fecal samples and we'll collaborate with them. I'm able to go to psychiatry, where I essentially grew up in the field and have lots of collaborations. 

As someone who has been at Brown for many decades now, how do you explain its unique collaborative culture?

Brown started out as a university-college, if you will; basically as an undergraduate college. When I was hired almost 50 years ago, they were just launching the medical school. There was a lot of hiring and so there weren't a lot of prima donnas at Brown. Everybody was relatively new. There were great people in the basic sciences, there were great, great people in the psychological sciences, and of course the arts in general were always very strong. I think because people began at around the same time, there wasn't the silo-like atmosphere that you might get at a very large state university or one of the Big Ten schools where there are very, very powerful medical schools.

I think over the past 10 years with the School of Public Health, the phenomenon is kind of similar. We did a lot of hiring; we brought people in to fill gaps that we knew we had if we were going to be launching a first-class school of public health. We were able to pick people who were collaborators and not silo villagers.

It’s unusual for faculty members to spend their entire careers at one institution yet, 50 years later, you haven’t left Brown. Why did you stay?

Every time I went to Brown with an idea, it was a very encouraging atmosphere. That's not to say there weren't serious tugs on my career over these years to go elsewhere, but a combination of personal, family reasons, and the fact that I was able to do what I wanted to do at Brown, is what kept us here in Providence, and not for one minute do I ever regret it.

We've built what I had a vision for. I didn't have the vision 50 years ago, I probably had the vision 30 years ago when I started to know better what was available at other places and what Brown was willing to do. And the emergence of the School of Public Health  provided another opportunity to broaden the perspective from the clinical level and the notion of intervention, to the possibilities for prevention, and on a much larger scale.

What do you see in the future of addiction studies?

I think it's going to be a combination of finding things that help with this endophenotype,  this craving phenomenon, on the one hand, and getting that under control—and it may take a pharmacological intervention to do that. But to think that that's going to be a magic bullet and that people are not going to need a psychosocial intervention along with it is very short sighted.

And so I think it's going to continue to be a partnership of both medicine, if you will, and psychology, or medicine and social science. I think that's true for other disorders as well, not only addictive disorders. I think, for example, the management of diabetes is not just a magic bullet kind of thing. It needs to be done in the context of social support and psychological support as well.

Many researchers in CAAS are using new tech in the alcohol space, such as wearable devices that monitor subjects. How is research on substance use disorders enabled by this kind of technology?

At the Center for Alcohol and Addiction Studies we have been studying so-called ecological momentary assessment (EMA), which is measuring, in real-time, in the real world, what's going on. We've developed EMA programs, ecological momentary assessment programs, that have enabled us to take a look, for example, at what teenagers do, how they respond to the subjective effects of alcohol in the real world. 

Of course we can't provide teenagers with alcohol in the lab. But if you can take a look at their blood alcohol levels in the field, where we know they're drinking, and have them monitor the subjective reaction to the alcohol—how they feel, how comfortable they feel, how anxious they feel, how depressed they feel—and get good measures of their blood alcohol level—and you can with these technologies—it's every bit as good, if not better, than measuring these things in the laboratory. 

That’s an example of technology that I get very excited about. We’ve brought in people who have this expertise. I'm currently collaborating with a postdoctoral fellow on a grant. We're going to bring the role-playing that I mentioned up to the 21st century by introducing virtual reality into the role plays so that the alcohol-troubled person can actually see themselves in their own personal situation through virtual reality technology. We're hoping to do a pilot study. So those are two examples of, I think, the path forward.

You must have taught and mentored hundreds of students in your time at Brown.

Frequently students come to me because they have had a personal experience with  addiction, whether it be alcoholism or some other form of addiction, in their personal lives. Not necessarily their own abuse of substances, but perhaps a parent or a grandparent or a relative. Eight times out of ten when students come to me for that reason it’s because they want to understand more; they want to protect or to help with the solution of the problem. 

We've sent several of these students on to graduate school and medical school, and I'm very proud of the fact that some of them are now in very responsible positions not only in academia, but in government as well. I think that in training the next generation of researchers is where I've had my biggest impact. 

Tell us about the CAAS postdoctoral programs.

We have a large training program funded by the National Institute on Drug Abuse that I instituted at Brown and ran for a while. It brings in people who already have their M.D. or Ph.D. for up to three years of postdoctoral training. These people are launching their careers. Many of them are now staffing addiction centers around the country. One of our former postdocs runs the intramural program at the National Institute on Drug Abuse. So we have trained many members of the academic and government workforce in addictive disorders here at Brown. 

The COVID-19 pandemic impacted almost all areas of life. What effect did it have on people’s substance use?

There's no doubt that drinking in particular, but drinking and smoking, were up during the pandemic, and significantly up. And there were scientific studies to nail that down. So the pandemic did have an effect on substance use. People who didn't have problems before were at home drinking. And it was interesting because sales in liquor stores were up, rather than drinking in public places, because people were not going to bars and restaurants so much.

But I do think public health got a positive shot in the arm with the pandemic as well. I think people became very aware of the need for attention to public health. Say what you will about management of the pandemic, but I think the net effect was a positive effect on the public's perception of public health.

How did it impact your research program?

We were challenged during the pandemic to keep the research going, to keep the academic enterprise going. With respect to the research, we had to pivot to doing things remotely, and so we did a lot of treatment by video conferencing, we did a lot of experimental procedures remotely, and to this day, that provides an opportunity.

For example, I'm involved in a study now that is taking a look at patients who are HIV positive who drink heavily. We have been conducting this kind of work in the greater New England area, particularly Providence and Boston, for a number of years. Through the pandemic we were forced to go beyond our boundaries when we couldn’t bring people into the lab. We found we could do things remotely with blood alcohol levels that they mail back to us.

We're now doing research in some of the hotspots around the country for HIV, like Miami and Los Angeles. And we're doing work that's based here at Brown with participants that are in a variety of places around the country. The pandemic forced us to think outside the box and that's been a positive effect. 

The pandemic ended up changing the way faculty teach students as well.

Thanks to Zoom, our training program has collaborated with a number of training programs around the country. My lectures are Zoomed to Albany and Louisiana and their lectures are Zoomed to our post docs.

As part of our COBRI grant, which is known at Brown as the CADRE, the Center for Addiction and Disease Risk Exacerbation, we bring in distinguished scientists four or six times a year. Rather than halt that during COVID, we turned to Zoom.

COVID got us to think a little bit out of the box. It broadened our perspective and I think the byproduct of that has been better science.