20 Apr 2023

By Sarah Crespi, Paul Voosen 

Jackie Oberst, assistant editor for the Custom Publishing office, interviews Friedman Brain Institute Director Eric Nestler and Director of Drug Discovery Paul Kenny, two experts on addiction from the Icahn School of Medicine at Mount Sinai. This segment is sponsored by the Icahn School of Medicine at Mount Sinai.

This week’s episode was produced with help from Podigy.


0:24:46.1 SC: Custom publishing assistant editor Jacquie Oberst chats with Eric Nestler and Paul Kenny, two experts on addiction about the latest research in the field.


0:25:18.8 Jacquie Oberst: Hello to our podcast listeners and welcome to the custom sponsored interview from the Science AAAS Custom Publishing Office. I’m brought to you by the Icahn School of Medicine at Mount Sinai. My name is Jacquie Oberst and I’m assistant editor for custom publishing at Science. Whether it’s a problem with alcohol, opioids, cocaine, or any other substance, addiction or substance use disorder is a chronic mental health condition that kills hundreds of thousands of Americans every year and impacts millions of lives.

0:25:45.4 JO: Addictions can destroy marriages, friendships, and careers and threaten a person’s basic health and safety. It is a medical problem that needs medical solutions. Today I’m very pleased to welcome two renowned experts on addiction. They are co-authors with several colleagues on an upcoming article about the science of addiction in a neuroscience supplement of science that will come out in June. Dr. Eric Nestler, who is the Nash family, professor of neuroscience, director of the Friedman Brain Institute, Dean for Academic Affairs at the Icahn School of Medicine at Mount Sinai and chief officer of the Mount Sinai Health System.

0:26:19.3 JO: His laboratory studies the molecular mechanisms of drug addiction and depression in animal models. We also have Dr. Paul Kenny, who is the Ward Coleman’s professor and chair of the Nash Family Department of Neuroscience, as well as the director of the Drug Discovery Institute at the Icahn School of Medicine at Mount Sinai. His multidisciplinary research involves the study of behavioral paradigms, physiological analyses, and the molecular underpinnings of neuro behavioral disorders such as schizophrenia and drug addiction. Eric and Paul, thank you so much for taking the time to talk with me today. Eric, I’d like to orient our listeners to the topic. How do researchers define addiction?

0:26:55.2 Eric Nestler: Researchers define addiction the same way clinicians do, and this is one of the major gaps in our knowledge. Addiction like all psychiatric syndromes can only be diagnosed by talking to a person or their family members and finding out what types of abnormal behaviors they exhibit. No blood tests, no genetic test, no brain scan can be used to diagnose addiction.

0:27:19.1 JO: Paul, could you please also weigh in?

0:27:21.7 Paul Kenny: Well, addiction’s a very tricky word. I think the way that Addictionologists would define addiction is a compulsive behavior that persists despite clear evidence suggesting that the behavior should stop and the behavior is directed towards obtaining drug of abuse.

0:27:35.1 JO: And now I’d like to focus on why this is an important issue. What is the impact that addiction has on society?

0:27:42.8 PK: On society? Addiction has a devastating consequence. I think we all know about the opioid epidemic that’s gripped the US over the past maybe 10 years. It’s a leading cause of premature death here in the United States and elsewhere in the world. And it’s not just death that is a negative consequence of illicit drug use. The impact really on every aspect of life and society is marked.

0:28:01.6 JO: Eric, are addiction related deaths on the rise. If so, why?

0:28:06.2 EN: Yeah, so we’ve seen an epidemic of addiction related deaths and I really want to underscore this. Before the pandemic, it was reported that about 70,000 Americans died every year of a drug overdose. And the vast majority of that being unintentional, these are not people who were looking to hurt or harm themselves. These are people who die accidentally by taking too much drug. That number has increased dramatically since the pandemic. So the last data available would suggest that 100,000 Americans die each year now from drug overdose. And I’d like to put that in some perspective. I was a teenager, young adult during the Vietnam War era. My generation was defined by that war. 58,000 American combat troops died during a 15 year course of that war. And my generation was torn up over it. Yet here we are in the United States today, losing 100,000 Americans every year because of addiction and we don’t seem to be able to marshal the resources to address it.

0:29:13.5 JO: Paul, your opinion on this please.

0:29:17.2 PK: There’s many reasons for an increased instances of death that we’re seeing. One of the major reasons is related to just the excessive amounts of opioids are consumed in the United States. The greatest quantities of opioid drugs are by far consumed in the United States or does the magnitude above opioid consumption in other parts of the world. But it’s not just opioids. We’re seeing a real clear spike in the use of other illicit drugs like psychomotor stimulants, cocaine, of course, being the example of that. Amphetamine, methamphetamine use is also on the increase and those drugs have devastating consequences as well.

0:29:48.7 JO: Eric, what do we know about the science of addiction that we didn’t know five years ago?

0:29:54.3 EN: So several areas of advances have been made. First, we now understand what it is about a chemical substance that makes it able to cause addiction in a vulnerable person. Drugs of abuse all share the ability to act on the brain’s reward pathways. Reward pathways are parts of the brain that are very old from an evolutionary point of view, and they develop to regulate an individual’s responses to rewards in the environment. Our behavior is shaped by rewards, the availability of food and water, sex, social interaction, and our actions are being continually refined in response to these cues in the environment. When a person takes a drug of abuse, a person has the experience as if they’ve had the most rewarding experience possible without actually having something useful happening to them. No food, no drink associated with it. The power and persistence of these actions of drugs on the brain reward circuitry, triggers chemical changes in the brain that basically corrupt the brain’s ability to analyze rewards.

0:31:01.9 EN: Now an individual who’s addicted is not rewarded by natural things, things that most of us are rewarded by, but instead require the sledgehammer effects of a drug of abuse in order to feel that natural reward. And that is one of the reasons why people with addictions are driven so strongly to take drugs because this is the only way for their brains for themselves to feel normal. In addition to identifying parts of the brain that regulate these responses to drugs of abuse, we’ve also begun to understand the chemical changes that drugs produce in those brain regions to cause an addiction. And for that, much of the effort has focused on molecular biology, changes in the ability of certain genes within nerve cells in these brain reward regions to make their protein products. And somehow these changes in gene expression, as we would call it, drive addiction behavior.

0:31:57.5 JO: Paul, your thoughts please.

0:32:00.5 PK: We now are in a position where we can apply really nice tools to understand the most fundamental actions of drugs abuse in the brain, you know, the molecular cellular circuit level, also even the underlying genetics. What kinds of gene variants are we born with that may influence the likelihood that you’ll use drugs, if you use them that it’ll go off and develop a habit and the difficulty that you will have quitting.

0:32:20.0 JO: So applications, Eric, what are the most promising directions in current and future research and treatments?

0:32:26.7 EN: There are some medications that can be quite effective. So in the case of opioid addiction, we are fortunate to have treatments like methadone and buprenorphine. The brand name for buprenorphine with a co-medication is called Suboxone and methadone and suboxone can be extremely effective. And I’d urge your listeners to check out a Hulu series called Dope Sick, which was really an excellent depiction, first, of what opioid addiction can be like, how it can attack anybody regardless of their station in life. But it also depicted quite nicely that when people are given the right kinds of treatments like Suboxone, they can really do quite well and begin to recover toward a normal life.

0:33:09.6 JO: Paul, your opinion on this, please.

0:33:11.8 PK: For the most promising trends in the treatment of drug addictions is the fact that we’re now actually seeing compounds advance through the pre-clinical development pipeline and inter-human clinical trials. And without those types of data, of course we won’t identify new therapeutic. Also, without those kind of data, we won’t know if we’re moving the right direction, using the right tools, and thinking the right way. So we need those types of human experiments, if you will, to help guide the pre-clinical drug development and the likelihood that we can generate not just one therapeutic, but a whole armory of therapeutics that can address what is a very complex syndrome of behavioral abnormality.

0:33:44.1 JO: Behavioral therapies can be effective interventions for substance use disorders. Paul, what do we now know about the biological mechanisms of action of behavioral therapies?

0:33:54.0 PK: Really surprisingly little. I think that’s an area of research in our field that really would benefit from a lot more attention. You’re absolutely right. In fact, even the most effective therapeutic is about as effective as a behavioral intervention. And the best way currently of treating someone who’s suffering from substance use disorder is a therapeutic and kind of compound that’s beneficial, Buprenorphine being an example, and behavioral therapy combined. Why that is the case? We really don’t know. If I had to guess, I would suggest that something around the fact that humans are social animals and that social rewards are so critically important for us as a species. And that the reward circuitries that are co-opted by drugs abuse is some of the great leads that are likely involved in social reward-related behaviors.

0:34:33.9 JO: Eric, your thoughts please?

0:34:36.9 EN: Behavioral therapies are the mainstay for addiction treatment. For the majority of people, behavioral therapies are what are available and they’re effective in some people over time. But again, with very high rates of relapse, an 80% chance of relapse within a year of abstinence, a person would go back to behavioral treatment. And the cycle continues again and again, and what you hear from so many patients and family members is that a loved one has been in treatment repeatedly and still as at high risk of relapse. So to keep hope because there is always hope and eventually actually most people do kick the habit.

0:35:14.8 JO: Eric and Paul, it’s been a real pleasure having this opportunity. Thank you both for joining us. Our thanks to the Icahn School of Medicine at Mount Sinai for sponsoring this interview. This podcast has been edited and condensed for length by Erika Berg, director and senior editor of Custom Publishing and me Jacquie Oberst. Thank you for listening.