From Our Neurons to Yours

Can brain science save addiction policy? | Keith Humphreys

• Wu Tsai Neurosciences Institute at Stanford University, Nicholas Weiler, Keith Humphreys • Season 7 • Episode 10

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If addiction is a disease of the brain, what does that mean for how we treat people—and how we write policy? In this wide-ranging conversation, Stanford addiction expert and policy advisor Keith Humphreys returns to the show to walk us through what neuroscience has taught us about substance use disorders and how that science intersects with law, public health, and politics.

From the biology of craving to the limits of autonomy, we explore the tension between compassion and accountability, and what truly effective treatment and prevention might look like.

Episode Highlights

  • Why addiction isn’t just a moral failure—and how brain science explains drug-seeking behavior
  • The biological pathways affected by opioids, alcohol, and stimulants—and why some drugs are harder to treat
  • What makes some people more vulnerable to addiction than others
  • Why effective addiction policy must account for impaired decision-making
  • How policy can—and can’t—respond to the science
  • The promise and limitations of brain stimulation, psychedelics, and medications like naloxone
  • Why prevention—especially for teens—is key to long-term change
  • What a more human, effective, and science-based future could look like

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Nicholas Weiler (00:11):

You're listening to From Our Neurons to Yours, the podcast from the Wu Tsai Neurosciences Institute at Stanford University, bringing you to the frontiers of brain science. Today we're going to explore one big, very complicated question.

(00:35):

If we accept that alcoholism and addiction are in fact diseases, neurological conditions, then what does that actually mean for how we treat people and how we shape policy? No one is better positioned to help us think through these thorny questions than today's guest.

(00:53):

He's one of the leading voices on addiction treatment and drug policy in the US, and he's advised policymakers at all levels, from local city officials all the way to the White House.

Keith Humphreys (01:04):

My name's Keith Humphreys. I'm the Esther Ting Memorial professor in the Department of Psychiatry, and a long-term affiliate of the Wu Tsai Neurosciences Institute.

Nicholas Weiler (01:12):

Keith Humphreys, it's so great to have you back on the show. You joined us one of our first episodes, I think episode five, and now we're on episode 55, I think.

(01:21):

So it's great to have you back and to talk more about the science of addiction and addiction policy.

Keith Humphreys (01:27):

Very glad to be here.

Nicholas Weiler (01:28):

So you have long been studying and advising leaders locally, regionally around the world on addiction policy. But you've also been closely affiliated with this Big Ideas in Neuroscience initiative, the NeuroChoice initiative here at Wu Tsai Neuro.

(01:45):

And the goal of that was to connect our basic understanding of the brain circuits of choice and decision-making to what we know about human psychology, all the way up to your area of expertise in policy. And how we actually implement change to help people with addiction in particular.

(02:05):

So this is a show about neuroscience, about the frontiers of brain science. And I want to understand how has brain science influenced our understanding of addiction and influenced how we think about addiction policy? But I'd love to start with the science.

(02:22):

What has neuroscience or psychiatry or psychology taught us over the past decade or so about what addiction is, and maybe new ways of thinking about treating people with addiction?

Keith Humphreys (02:37):

Addiction has been approached historically as sometimes as a sin or sometimes as bad behavior, and certainly as something inexplicable and maddening. From the outside, it makes no sense. Why does this person keep doing this thing that seems so destructive, despite all these consequences?

(02:53):

And neuroscience has given us both a set of findings, as well as a language, to help understand exactly why this person is doing that, and that it's not because it's sinful and not because they're a bad person. It's because of the effect of a certain class of molecules on the human brain.

(03:10):

Very simply, as has been well documented, we have a reward pathway mediated by dopamine, and it tells us all those things we need to know evolutionarily like you were cold and you got warm, that was great. Remember, do that the next time. And you were hungry and you ate and that was great, do that again next time.

(03:25):

But that pathway is extremely sensitive to drugs like cocaine, like heroin, like alcohol, which give it a false signal. By which I mean it tells us, it fools us that this was really, really important, more important than eating, more important than social relationships and all those things.

(03:44):

And that miseducation of the brain with repeated administrations, "I get that big reward. I start to anticipate a really big reward," is how people get in this state we call addiction. You can call it a disease if you like, or another way to think is it's just deeply maladaptive learning.

(04:00):

The person believes and acts as if a set of molecules that in fact are unnecessary and are doing damage to them, are in fact the most important thing that they need to continue consuming.

Nicholas Weiler (04:11):

It's an interesting point. Is there a difference between calling it a disease and calling it, I don't know, the world's worst bad habit?

Keith Humphreys (04:18):

Yeah. When people argue about disease, what I've concluded is they're never really arguing about the same thing. It's usually a proxy for something else, and so sometimes people say it's not a disease. I say, "Why do you think it's not a disease?" Because my husband drank and ruined our lives, and that's his fault and I'm mad at him. And we don't get mad at people for being sick.

(04:39):

And I always say like, "Well, let's separate those things out. If your husband stole your money and was a bad husband and walked out, you're going to be angry at him. That's perfectly fine to be angry at him. That is a separate question of whether he has an illness. It had effects on you, they're upsetting. It's natural that you would feel that way."

(04:55):

When people know that, then you can say, "Yeah. They had an illness, but also by the way, I'm mad." And they don't feel like, "I'm a bad person because I'm mad at someone who's sick." A lot of people then can let it go.

Nicholas Weiler (05:04):

Yeah.

Keith Humphreys (05:05):

The other point is about accountability. So some people when they hear disease, they think what is being said is, "Oh, so people can just drive drunk and wreck their cars, and snort cocaine and become aggressive and hurt people, and they just get a blank check because they have a disease."

(05:18):

I'm like, "No, we're all accountable for what we do. Our brains, our bodies and all that put certain limits on us. We have to do the best we can, but we're still accountable." So it doesn't mean the fact that it's a disease that someone who has an addiction can do as much harm as they want and none of us can even complain.

(05:35):

When you separate those out, then people are more willing to say, "Okay. Well, maybe there is something actually, fundamentally different about this person, about their brain and their body for me, such that things that are easy for me are hard for them. And effects drugs have on them, they don't have on me."

Nicholas Weiler (05:49):

To me, the definition of a disease in a way, sorry, this is actually coming to me in the moment, so it's probably a good chance of being wrong. It seems like maybe a useful definition of a disease is something that we would consider treating.

(06:02):

So we can see that there are particular circuits that you were alluding to in the brain, and we can see that there might be treatments that we could apply to help someone deal with this thing. So what have we learned about the biology of addiction over the past 10, 20 years that maybe we didn't know before?

Keith Humphreys (06:22):

We have pretty good specification now of where all the drugs we would get addicted bind in the brain, and that has been useful for treatments. So we know what a mu receptor is. We know opioids bond there, so that if I'm, let's say, addicted to fentanyl and I'm given naltrexone, that will bond at that site and block the rewarding effect of that drug.

(06:43):

Or if I'm given methadone or buprenorphine, which are opioid agonists, a full agonist to a partial agonist respectively, I will have reduced craving for that drug and then be less likely to take it. And then go to another level, if I am taking fentanyl, and as one of the effects of fentanyl is I'm experiencing is that my breathing is stopping.

(07:01):

We know that we can take naloxone, which goes to that side as a rapid-acting antagonist, which essentially dislodges the fentanyl and then lets me start breathing again. So that stuff we all have learned. We wouldn't be able to figure any of that out without neuroscience saying, "This is where it bonds. Therefore, that gives us a therapeutic target."

(07:18):

With other drugs, it's harder. Alcohol's hard. Alcohol goes everywhere in your body that water goes, so it does have stimulation of mu receptors, but it affects lots of other systems as well. We do have some medications for alcohol, but they aren't quite as potent as the ones we have for opioids. Stimulants are harder still.

(07:34):

Many, many smart people have worked very hard on trying to find a medication for stimulant use disorder and have not been able to do it. And if we get one, it may end up being something that is using entirely different technology. These emerging brain stimulation techniques, which we are doing at Stanford and Wu Tsai has been involved in.

Nicholas Weiler (07:52):

You mean things like transcranial magnetic stimulation, things like that?

Keith Humphreys (07:55):

Exactly. Yes, yeah. Which have proved for some disorders, particularly treatment-resistant depression, have been transformative and are now being tested for lots of different addictions, including for stimulants.

(08:06):

That might be a place where we're able to make some treatment progress there that we have not been able to make through the pharmacotherapy route.

Nicholas Weiler (08:13):

I'm really interested in continuing to discuss other sort of frontier therapies, things like psychedelics and so on.

(08:20):

But I also want to what do we know about the differences in the brain for someone who is susceptible to substance use disorder, let's say, particularly opioids?

(08:31):

And what do we know about what the abuse of those substances does to change the brain? Have we been able to parse those differences out very well?

Keith Humphreys (08:40):

Yeah, so there's a lot of science in this area. Let's start with genes. Are we all born with the same amount of propensity to consume different drugs? And we absolutely are not, and we know that from adoption studies, for example.

(08:52):

And that is both the subjective reaction we have to drugs. For example, sons of fathers who were addicted to alcohol have less body sway, which is something you can't even control consciously when administered alcohol.

Nicholas Weiler (09:06):

Body sway like instability?

Keith Humphreys (09:08):

How much you're moving when you start administering ethanol, we move a little bit. You can measure this with a seismometer. It's so small you can't see it, and you can't consciously fake it or restrain it, but you can tell who has a [inaudible 00:09:22] because they don't react as much. They also tend to have lighter hangovers, which you would think for a normal person would say, "Oh, I really overdid it last night. I'm not going to do that again."

(09:30):

But if you've got that resistance so you don't get that message of that was too much, you're like, "Maybe I'll do the same thing tonight." We also know there's big drug-liking differences between people. I've had a few injuries in my life, as most of us had, and I've had to take oral opioids a couple of times. And I find that experience so unpleasant, that I really basically go for the pain.

(09:51):

I'll just say, I remember I broke my wrist. It's like I took one, and just like, "Oh God, I feel depressed. My stomach feels all bound up. I'm just going to accept the pain from here on out." There are other people, who I've met clinically, who said, "The first time I took an opioid, it was like a hole in my chest that had been there my whole life filled up for the first time."

Nicholas Weiler (10:09):

Wow.

Keith Humphreys (10:09):

This just is not a story about I must be a good person and they're a bad person, it's just that there's just the roll of the dice. There's the genes and probably also experiences we have, which we don't understand very well. The interplay of when things get activated based on life experiences we have and early exposures we have, and things like that.

(10:26):

So we know people don't come to this with the same sort of risk. So I say it to people so they can understand, the family member like, "Why does he keep doing this?" It's like, "Well, I don't have any trouble not using meth. You don't use meth, but for you, that's like maybe lifting a one-pound weight. And for your mom, it's like lifting a 50-pound weight.

(10:43):

"And it's not that she can't do it, but she's doing something that's a lot harder for her than you." On the adaptations things, there's very interesting things about the relative value of different rewards. Obviously, we all are evolved to pursue certain natural rewards, things like food and sex, and warmth, safety and love, which has kept Homo sapiens alive.

(11:05):

As people repeatedly administer these drugs, which is giving them remember this massive dopamine spike beyond what anything else does, those other rewards start to gray out for people and they don't seem as appealing anymore. This is one of the tough things in early recovery. I've stopped taking the drugs, so I've stopped taking this thing that gives me this great sense of feeling.

(11:24):

But I don't feel that excited about cuddling my kids right now, and I used to enjoy a sunny day and I just feel kind of grayed out.

Nicholas Weiler (11:30):

And nothing else compares.

Keith Humphreys (11:31):

Yeah, so it's very tempting to say, "I'm going to go back." Now, fortunately, particularly if you're young, that brain is still pretty plastic. That is something that returns to people over time, but that period is really difficult. And there's a very eminent neuroscientist named George Koob, who runs the National Institute on Alcohol Abuse and Alcoholism.

(11:48):

He has this term he calls Hyperkatifeia, which is about an emotional grayness. It's not the same as depression. But he thinks with repeated exposures to alcohol over and over and over, there's adaptations in the extended amygdala, which produce what he calls an anti-reward system. So if you're just going to think about how this would mean is as Hyperkatifeia sets in, let's say, how good I feel just to be alive goes in a 1 to 10.

(12:12):

And I'm the kind of person who wakes up as a six and I have a few drinks, I go 7, 8, 9. And so I keep doing that, doing that, doing that, well, over time, I adapt to it such that I don't wake up as a six anymore. I wake up as a three or a four. And I need those two or three drinks to get back to six where I started in the first place, because of this grayness has set in.

(12:32):

And you can just see how that would build on itself. If I drop down to a one or two, I'm going to have to drink more because I can't stand this emotional, gray, unrewarding existence.

Nicholas Weiler (12:44):

We've talked a few times on the show about the brain circuitry of decision-making. We talked with Neir Eshel about dopamine and decision circuits. One of the repeating themes here is just trying to understand the ways in which the interplay of our genetics and our environment and our past all program our decision-making circuitry.

(13:09):

So one of the things that's so interesting academically and difficult I imagine policy-wise about addiction, is it's this blend of past decisions you've made, biological susceptibility, the impact of this external thing. These highly refined drugs that didn't use to exist on the brain circuits.

(13:30):

And now you're trying to design policy for people whose ability to make decisions has been impaired. Would you agree with that framing like that's a central challenge here?

Keith Humphreys (13:40):

Absolutely, and a lot of policy is explicitly designed as if that weren't the case. So for example, I say I'm addicted to alcohol and I drink and drive a lot, and I've been arrested my first time, my second time, my third time. It'd be very common for a judge or someone to say, "If you do this again, someday we're going to catch you again. Then maybe you'll have a trial and then maybe then you'll get sent to prison."

(14:06):

And that would make a lot of sense if I had a very long-term time orientation and a balance assessments of risk and rewards in my life, I think ahead and all that, and that's exactly not where I am. I'm addicted to alcohol. I have a very short-term time orientation. I don't value distant, probabilistic costs. I value immediate rewards, and so they're speaking another language to me, and then shouldn't be surprised that I show up in the court again.

(14:30):

And the kinds of programs that work do the complete reverse. Those are the ones where they say, "You're going to be monitored for your drinking every single day, twice a day. And the second you drink, there will be a consequence of some sort. It won't be severe, but something will happen not in the future, but right now, not possibly, but immediately."

(14:48):

And those programs dramatically change the behavior of people who have been arrested over and over for drinking and driving, in a way counting on distant threats that would motivate a well-functioning certified public accountant don't.

Nicholas Weiler (15:00):

It's so interesting. That immediately reminds me of parenting seminars I've gone tom about the need to if you're trying to encourage certain behaviors or eliminate problematic behaviors, that consistency and immediacy is so critical for kids. Because they don't have the same orientation to the future that we try to have as adults.

(15:22):

We don't always have it as adults either. Which brings me to this question about is the solution to or is the approach to policy around addiction, does it require a certain level of what you might call paternalism? Are we saying that people with addiction have to lose some of their independence or their ability to make their own decisions? How do you think about that, I guess?

Keith Humphreys (15:45):

Yeah. I would say they already have, in that they are, by definition, they're repeatedly engaging in a behavior that is causing damage to themselves and people they care about despite destructive consequences. And it's like, "Well, that tells you there's something compromising their decision-making to begin with."

(16:03):

So if we just say, "Well, the important thing is we just need to honor their autonomy and let them do whatever they want to do continually," their odds are very good they'll keep doing that. And so you do end up intervening more than you would in a condition that like asthma, say, that didn't change how else people think and change their judgment.

(16:22):

The other issue with addiction is there's what an economist would call negative externalities that don't exist again for asthma or high blood pressure. In that there are other people who quite legitimately would like to say, "I'd like to drive down the road and not be struck by a car. I would like my mom to not spend all our grocery money on drugs. I would like my father not to be drunk and violent and those kinds of things."

(16:45):

And that puts some pressure sensibly on communities, on families and ultimately on policy to say, "We can't just count on this person to eventually figure it out. We have to act in some way." Particularly when someone is threatening public safety, that does end up being a paternalistic intervention. There's a whole class of interventions that are shorthanded, therapeutic jurisprudence where the law is involved because someone has done something illegal.

(17:11):

But the goal of the law is not to punish but to rehabilitate. And so they'll say, "Keith, you're addicted to meth and you shoved down a woman and grabbed her phone, and ran off with it and we caught you, and normally that's assault and theft. Normally, we could send you into a jail for that. But we are willing and she is willing to give you a shot, which is you can stay out of jail if you enroll in this drug court.

(17:34):

"And you're going to be monitored and you may not like being monitored, but on the other hand, you don't have to serve this jail term. If you complete treatment, we'll expunge the arrest and all will be well." That is basically a paternalistic offer, that at the same time when for many people is life-changingly good.

Nicholas Weiler (17:51):

So as I mentioned, you advise policymakers around the world on drug policy, so we're very honored to have you here giving us your insights.

(17:59):

In your view, how much is our growing scientific knowledge helping us tackle some of these social challenges?

(18:06):

And how much is it more on the social and policy side that we've got the tools, we just need to figure out how to implement them?

Keith Humphreys (18:13):

Yeah, so here's the thing how policy is different than other parts of science. Let's say you ran a regression model with 20 different variables that predicted will someone become addicted to something? And you have big, explanatory effects for their age and their genes and their race. And a smaller explanatory effect for the quality of housing in their neighborhood, just making this up.

(18:39):

But in policy, you would say, "Well, that's a lot of variance explained, but there is no policy that changes people's genes or their age or their race." So even though the housing policy explains this variance, it's the changeable variance through policy, and so I'm interested in that. So let's talk about housing policy and that's different than we just think aside.

(19:01):

We're very interested to know what are all the contributors? But a lot of contributors are like sunlight makes people happier mood that this is our sun and we got it. I can tell you to go outside more, but I can't turn it on or off so that's not that useful. And so that can be helpful with some of these policymakers to let them know what can and can't be controlled and where to invest and not to invest.

(19:24):

I do a lot of work with attorneys generals and people who interact with addicted people, police officers, police chiefs. But even a lot of people who interact within the health context, they're not really beyond the kind of metaphorical level going to understand what a synapse is, or what neural adaptation is. But they can understand that this person has become different through this use over and over again.

(19:47):

And therefore, the normal thing you might do with somebody else is just not going to work. And tell them this is what it's like to be that person. This seems like the most important thing in the world to them, way more important. It seems crazy and rational to you, but to them it seems perfectly rational. They don't have their big, temporal discounters, meaning they're interested in sooner, smaller awards, not longer, later ones.

(20:09):

So whatever you do has to think about that time perspective. They come with significant risk for harm to themselves every single day. They can overdose, they can go into withdrawal and all that. So whatever systems you interact with, has to have a potential for a crisis response because you're going to be dealing with people in crisis response, all those things. And they can get that stuff.

(20:30):

The other thing is, this may seem silly, but why Alan Leshner was so successful as the National Institute on Drug Abuse director in persuading Congress particularly to invest in treatment and understand the role of neuroscience and addiction. Science had talked about this a long time. It's not as if we didn't know the brain was implicated.

(20:48):

And I know Alan pretty well, it's like, "Why was Alan so persuasive?" He says, "Because Alan had pictures." If a scientist talks, "Well, there's the brain and the brain changes." But Alan would hold up these things like, "Look, this is a PET scan. Do you see this level of activity in this person's brain, and you don't see it over here? That's because they've used meth for a long time."

(21:09):

And those pictures people can get. You don't have to be a genius to see, "Wait a minute, that person doesn't look the same. I don't even know what all those chemicals are. I don't know what a ligand is. I don't know what D2 is, but I know what looks the same and looks different." And I think there's no doubt that has made a difference to policymakers and also to the public, who has seen more and more of those images too.

Nicholas Weiler (21:30):

So I'm looping back to this philosophical question we've talked about we can see genetics of whether someone is liable to become addicted to certain substances or not. We've talked about changes in the brain that are caused by those substances, basically overriding the normal decision-making circuits.

(21:49):

And an increasing recognition that that's the case and that you can't treat someone who's addicted to a substance, or presumably to something like gambling or something like that as well. I don't know if we want to get into that sidetrack.

(22:01):

You can't necessarily just assume that they've got the same level of autonomy, the same level of decision-making rationality, whatever you want to call it, as someone who's not. We had Rob Sapolsky on the show a couple of months ago, and he would say that none of us have autonomy.

(22:16):

That we're all just essentially biological machines that are driven by everything that's happened to us in the past, and to our ancestors through our genetics and our environments and so on. I don't know that we need to go that far, but addiction seems like it gives us this case of we really see a decline in decision-making and autonomy.

(22:34):

And that challenges, as you've pointed out, our normal approach to how we help people with disease and how we treat people who commit offenses against society. So you've been writing a lot recently about the experiment in drug policy all along the West Coast from Vancouver to California of basically decriminalizing many forms of drug use and possession.

(22:58):

And that's been rolled back a lot in recent years as people have been very dissatisfied with the level of disorder that they've seen. So to merge these streams, where's the response that respects people's dignity as individuals, but also protects the rest of society and helps people get treatment?

Keith Humphreys (23:18):

Right, that's really the issue. And so the period you're referring to, so 2020, 2024, at least a certain amount of both policymakers and the activist community forgot that people who don't use drugs matter, which was strange for me. Because most of my career, I've been spent saying, "People who are addicted are human, they have rights, they have needs."

(23:39):

And this was the shift to the other direction, which is whatever immediately served that person. They want to use drugs, they want to use them wherever they want to use them, they want to sell them wherever they want to use them, they should be allowed to do that. Kind of forgot that most people don't use drugs and they're trying to raise families, and get to work and they need to have safe communities.

(23:56):

And these things were all falling apart around them. It is a human, social process where we decide these things and there are trade-offs no matter what. First off, people enjoy using substances. There's a certain amount of pleasure debate involved. There's the risk for addiction, which is destructive. There's how much do you want law enforcement involved or not?

(24:17):

Law enforcement can make things better, law enforcement can make things worse. How do you balance the splits within families, where one person has an addiction and feels everything is fine? And the other person is losing their mind in fear and worry for this person that they love. And people will frequently say, "There's a simple solution, we just do this and then that."

(24:37):

And I'm always the person who says, "It's more complicated than that," which may be unsatisfying emotionally, but it is more complicated than that. We should have a really well-developed treatment system, which most of the country we do not have. Such that addiction is as normal a part of the healthcare system's business as heart disease or as cancer.

(24:58):

It would just be as normal for me to go to my doctor and say, "I have this funny feeling in my chest when I exercise." I'm worried to say, "Those pills you gave me for my twisted ankle, I can't stop taking them and I've started buying them on the street." It should be as normal and be handled the same way, so that's about how people are trained.

(25:15):

It's also about the attitudes that staff have to recognize addiction is a legitimate health problem. And then the thing I've worked on a lot when I was in government, especially in the Obama administration, is it requires adequate financing. Insurance companies have to play ball, and Medicaid and Medicare have to play ball.

(25:33):

Just like if I developed a heart murmur, I would get something from my health insurance that, likewise, if I got in trouble with my opioid medication or my benzodiazepine medication that there would be coverage. You have to do all those things. Even when we do all of them, we're still going to have this reality that there are plenty of people who do not want to seek treatment because this is the state they're in.

(25:56):

And drug use feels rewarding in the short term, and some of them are going to do things that threaten public safety. And so there will be some public pushback, some people get pushed towards treatment. Now, many of people's lives have been saved, but whenever you have vulnerable people that are being pushed by the state to do something, there is potential for harm from the push.

(26:16):

And we certainly see that and sometimes confrontations between law enforcement, for example, and people who are out on the street intoxicated. And sometimes those end horribly because they're mishandled by the police, or they're just really hard situations and they can't be handled well.

(26:31):

And you want as little of that as possible, but there will be some of it, because people very baldly said, "When people are intoxicated and/or addicted, they do a lot of things they wouldn't otherwise do. And some of those things are really dangerous." And then while we're doing all this, we have to remember that we can't just respond to the imminent crisis.

(26:50):

People are addicted now, and I've done this obviously my whole life, I've focused on addiction, so obviously I think it's really important. But in an ideal world, we would be investing a lot more in prevention. Because I try to help people, we all try to help people, but so much better for a person not to get addicted in the first place.

(27:07):

And we know from neuroscience and from developmental psychology when to invest, which is while brains are developing. This is almost all being initiated when people are teenagers. We don't want dare, but we want really good. And there are some really good, developmentally informed interventions that not only help kids avoid drugs.

(27:27):

But also help them learn how to connect with other people, develop global management skills around stress, around planning, help them find prosocial adult role models, all those things. And when kids get those things, they're not only less likely to use substances, they're more likely to finish school.

(27:42):

They're less likely to drop out and have a kid at age 15, they're more likely to end up in college, all those things. So you want to keep making that investment. Because otherwise, if you just start with our policies about addiction, you're just hanging out waiting for people, you'd do that forever.

Nicholas Weiler (27:56):

Yeah, that's a great point. I was certainly falling into that when I was thinking about this conversation. What's the neuroscience? What's the policy? I was very much thinking about for people who are already addicted. So you mentioned a few things, programs for teens and adolescents.

(28:11):

What is the gamut of where we currently are in policy? From what you've been talking about in the Pacific Northwest with basically no enforcement, all the way to zero tolerance if you're public disorder, you get thrown in jail. Between what seems like the sweet spot and are there places where that's actually happening?

Keith Humphreys (28:33):

Yeah. I think that the region that we live in has made a lot of readjustments, San Jose, San Francisco, and I've worked with both of those cities.

(28:42):

I'm trying to get away from a more celebratory culture around substance use. Literally, we had billboards that glamorized fentanyl use put up in San Francisco.

Nicholas Weiler (28:51):

I remember seeing that and it was head spinning.

Keith Humphreys (28:54):

Almost unbelievable. Yeah, right. And that kind of stuff matters. We think about there's prevention in terms of programs, things you run in school, but there's also this surround of what advertising do you allow? How many liquor stores are there relative to grocery stores? Do you card people? Are doctors prescribing carelessly or are they being careful?

(29:13):

So we have levers and all those things, and that is another area where I think we've had a lot of improvement. The opioid crisis we have now really did start with very, very loose prescribing, 400% per capita increase in about a decade. So that we were five, 10 times any other developed country in terms of how many opioids we were pumping out, and also a lot of benzodiazepines.

(29:35):

So I think that's been something the country has done a good job on. I've been working with the board of supervisors and the mayor's office in San Francisco, and I'm very pleased at the moves they're making trying to find this sensible balance to all these different things, in a libertarian city and a progressive city that at the same time, where many people are fed up with disorder all at once.

(29:57):

So you have a mix of impulses of people wanting the state to be more invasive and less invasive, and so on. So and a good thing, what are some of the good things? One is trying to recognize that housing is obviously important. We have lots of homeless people, but there's a subset of people who really need housing that is recovery focused.

(30:16):

So I can go into that, say, straight out of maybe I've gone through a yearlong program at the Salvation Army, or at St. Anthony's Foundation where I'm a volunteer on the board. And I know that I won't be exposed to all the cues and all the role modeling behaviors, that we know from both behavioral work and from neuroscience work, will trigger intense desire for me to use and make it more likely for me to relapse.

(30:39):

So realizing that is important. Housing first is important, but also some housing needs to have a standard to keep people healthy, figuring that out. I'm impressed with the way the city has said they're going to continue to do harm reduction to stop the damage of drugs for those who continue to use them. But that their North Star, they have now officially said, is recovery.

(31:01):

So yes, of course, we want to keep people alive. I carry naloxone. When I go to them, I always have naloxone with me. I've done a lot to actually disseminate that amazing medication out there in the world.

Nicholas Weiler (31:12):

And that can immediately rescue someone from an overdose.

Keith Humphreys (31:16):

Yeah, that's right. Fast-acting opioid antagonist. So when we take an opioid, it basically has three classes of effect. It slows down certain bodily functions like breathing, it heals pain and it produces euphoria. And naloxone goes in there, when it does that, all three of those effects reverse.

(31:34):

So the person who is not breathing, not always, but usually because the opioids knocked out of the receptor, will then have the restoration of their breathing. So that's all great. But to say the goal for the city should not be, "I want to give you this naloxone today, in the hopes of giving it to you again tomorrow."

(31:51):

And the next day, or for that matter, two or three times a day. That's not good enough any more than a policy where our cardiac policy was, we have those shock paddles. And if EFT sees somebody have a heart attack, they shock them once, get in their car and drive away. They wouldn't do that, they would say, "Oh my God, you got a really serious problem. We need to get you to the hospital. We need to get you get you in cardiac rehab."

(32:11):

This has been a frightening experience, but it is an opportunity to change your life. So to say that that is the goal and give that message to everybody working in the city, that we believe that is possible. It's an optimistic statement about people who are addicted. It's a humanizing statement. And it's also just a statement about what we can achieve as a great city, that we can do more than just manage this problem for the next 24 hours.

(32:36):

We can achieve something greater. We can get more of our fellow citizens into a situation where they're healthy and they're fulfilled, and they're connected to their families. And they're being productive and contributing in a way that they're not able to do right now.

Nicholas Weiler (32:51):

I think that that really nicely conveys the usefulness of the disease model as a way of saying, "What can we do in education? What can we do in prevention?" With cardiac, we can talk about better diets, exercise, we can talk about prevention, we can have imaging.

(33:07):

We can have prediction of who's susceptible, and then we can identify people who are in the early stages or starting to suffer from problems and get them into treatment. There is still this challenge, of course, that if you hear that you've got heart disease, you're going to be pretty motivated to do something about it.

(33:25):

Whereas there's often this problem with addiction. I love what you said before about the place where it's important to destigmatize or make it easier for people to be open about it, is for someone to be able to go to their doctor and say, "Hey, I'm struggling with this. I'd like to get treatment."

(33:40):

But I think sometimes that's challenging if someone enjoys it, is not yet motivated to get treatment. I was reading about the California CARE Court. I don't know if that's something you'd want to talk about a little bit. You can maybe describe what it is exactly, but to me, it seemed like a potential sweet spot between autonomy, people doing what they want, and public safety.

Keith Humphreys (34:00):

Yeah. So CARE Courts, as well as other similar kinds of initiatives the state has passed recently, are efforts to first off, face the fact that what we're doing now isn't working. We have a very large population of people who are addicted, people who are overdosing.

(34:17):

And that population overlaps heavily with people who have mental health problems and don't have anywhere to live, or at least some of their lives are out on the street. And so CARE Courts are funding in a system that is in the spirit of therapeutic jurisprudence. So let's say somebody who I'm out there on a cold day, I don't have any shoes on.

(34:38):

There's reasons to be worried about me, or maybe I am creating reasons to worry other people. I'm standing in a farmer's market screaming at people and grabbing them, and all that, where you say, "Okay, this person is not in a state to take care of themselves. So it is our job now to do that with legal warrant to help them because they have schizophrenia and they're addicted."

(34:59):

And the CARE Courts would allow, this will be done by counties as everything in California is, allow them to do that to say, "Okay, Keith will be under the supervision of this court. He's going to get a month long of risperidone for his schizophrenia. He's going to get counseling for his alcohol or whatever," that kind of thing.

(35:17):

And the idea of that is that it will bring me to a state where I can do something I can't do at the moment, which is make good decisions about my future. That's the hope. Anyone who has worked in this area will say, "Aren't there challenges with getting a legal system and healthcare system to work together? Well, aren't those big boxes?"

(35:36):

Yeah, there are challenges. Aren't there risks that if you aren't really careful to make sure you're protecting people's human rights and their dignities, that somebody could be harmed? Yes, that is also a risk. So it has to be done extremely thoughtfully, and it has to be done in a spirit of partnership between the legal system and the health system.

(35:56):

And my guess will be because we do everything at the county level in California, we will see some counties do this very well and some counties do it less well. And so my hope would be that in the long term, and I do talk to counties a lot, is the ones who are doing well, will be asked to help the ones who are not doing well. And share, "Why are you able to pull this off and we aren't?"

Nicholas Weiler (36:17):

Well, the last big topic I wanted to ask you about, given what we've talked about, what the neuroscience has taught us, what new treatments are available. I'm sure there's much more than we've actually had a chance to cover. This balance between individual autonomy and society coming in and saying, "No, you can't. You need to get help."

(36:35):

If you had the opportunity to stand up a major research and policy effort, either nationally or just here in California, what would your priorities be? And coming back to our earlier theme, how much of it would be scientific, making sure we've got better treatments, and how much of it would be purely policy?

Keith Humphreys (36:53):

I'm 59 years old, so I'm aware I only have so many mountains left, and so I've been actually thinking about what would be the big thing? So on the science side, the therapeutic progress in this domain is really much slower than what my colleagues in oncology, cardiology have experienced. Now, everything with the brain is tough, I think everybody knows that.

(37:16):

So having a network of people pulling together what right now I see in my promising therapeutic leads, with fundamentally new kind of therapeutic leads. Which are the glucagon-like peptide-1 agonists like Ozempic and Mounjaro, which seem to be having some effects in these opportunistic studies.

(37:36):

And maybe even across all kinds of drugs that would be remarkable, because most of these things, they only work for one. That's one. Second one are the brain stimulation techniques that are coming forward, and then the third one is potentially the psychedelics. My guess is I'm less optimistic about that, but I don't want to presume because there are some interesting findings in that space.

(37:55):

So if I had to look to a lot of resources, I think I would just find a science collaborative where I wouldn't even be doing the trials. I would get everyone who is together to say, "This is a really hard problem. A lot of people are dying. These are three exciting options. What if we all worked together and shared all our data as a collaborative?"

(38:11):

Rather than doing the normal thing of everybody works in their part of the forest and hoards the information they have, so that's what I'd like to see on the science side. On the policy side, we're in a tough environment right now candidly. What we were doing in the Obama administration around addiction was trying to unify the financing of care so that it would become normal, for lack of a better word.

(38:37):

In other words, often what's happened is historically there'll be a little set-aside, a block grant for substance use disorder, and then the whole healthcare system. And the whole healthcare system wouldn't even know what this block grant was. And when people are paid differently, they can't really work together.

(38:49):

And so our view was like so when you expand Medicaid, which we did, and you build these health exchanges where people can buy insurance. Addiction care, substance use care, it becomes a standard healthcare benefit, and then the system knows how to handle that.

Nicholas Weiler (39:04):

Right.

Keith Humphreys (39:05):

And it worked. 62 million people got improved coverage for the care of substance use disorders through those laws. Meaning either they had no insurance and then they got insurance, or they had insurance but it had a bad benefit. And then the rules about parity, which say that the benefits have to be comparable across mental health, substance use and other disorders, upgraded the benefits they had.

(39:28):

So if they ended up in that terrible situation of they get a call from college and your daughter has just shown up in the ER again with a drug problem. And they opened up their insurance, it wouldn't be you're entitled to one brief consultation in six months, but you would actually get the care that your daughter needs.

(39:46):

And this is all under threat at this moment, but that to me, like finishing that revolution, getting everybody else who doesn't have private care and doesn't have Medicaid care. And there's one more thing on this, is the last time I testified to Congress, I pitched this along with some other people.

(40:02):

That funnily enough, we're usually pretty good with seniors in the United States for giving them health insurance. They're the first group we tend to think of, and Medicare came first and all that. But parity, this concept that the benefits should be comparable is it's now in CHIP, which is for kids, it's in the Medicaid expansion, it's in insurance plans sold on the exchanges.

(40:24):

The insurance, big companies, small employers, medium employers, all buy all get parity. Medicare Advantage doesn't, which is a huge part of the Medicare program. And deaths in the last 20 years, Chelsea Shover and I did a study here showing that all of those deaths among older Americans are up 400%. People think old people don't use drugs.

(40:45):

They do. They get a lot of polypharmacy through medicine. But also the boomers used a lot of drugs that carried those habits in. And so what we were testifying about is why not have Medicare have the same protection, which it doesn't have? Because that's 60-odd, more than that, over 60 million people, but making that standard.

(41:04):

So throughout life, no matter what insurer was carrying you. If you ever got in that situation, you had substance use or related mental health problem, you could know that you could go to the healthcare system, and get the same benefits you would if you had any other serious health problem.

Nicholas Weiler (41:20):

Well, I know that we're close to time now. This has been very illuminating for me. I'd love to ask you, Keith, you mentioned some of these ideas that we're in a challenging time for addiction policy right now.

(41:33):

I know this could be a whole conversation on its own. Could you briefly just tell us what you see as the big challenge right now? What's on your mind that makes this even more challenging than usual given the current political climate?

Keith Humphreys (41:45):

Yeah. Well, this is we're recording this in the middle of June. Currently, the Congress is debating pretty substantial cuts to Medicaid and different estimates. How many people would lose their Medicaid insurance, 8 million, 10 million? Then there's also subsidies on the health exchanges that help lower income people buy insurance that are being cut.

(42:08):

I have the Congressional Budget Office telling me, "When you throw those in, then you're going to get maybe 15 million people, maybe 20 million people." Some of those people are going to have substance use disorders. And when we were expanding all that, that was one of our arguments was if you want to take care of this population, smoking problems, drinking, drugs.

(42:26):

They happen in all classes, but they're disproportionately among lower income people. So if you want to take good care and keep people, you have to cover this stuff. This will also affect disproportionately lower income people. And so I know that a lot of them will have the need for substance use disorder care.

(42:44):

And if this goes through as written, millions of them will not be able to get it. So that is not something I would be doing, as I said before, I'd be going in the opposite direction. So that's what I meant it's a challenging time. The bill's not signed as we're talking, and there are lots of people pushing on this, but I'm worried about what's going to happen.

Nicholas Weiler (43:02):

All right. Well, just to close this out, what's your hope for the policy revolution you'd like to see in 20 years?

(43:10):

Paint me a one or two-minute picture of where we're at.

Keith Humphreys (43:13):

We would think of addiction as a chronic disease. Now here's an analogy that may be a good one is depression. So when I was young, we didn't talk about depression. If you had depression, you did not discuss it. And now, celebrities talk about their depression. We have tens of millions of people taking SSRIs.

(43:35):

People mention it at parties, "Oh, have you tried Prozac? I'm on Celexa." Primary care doctors screen and treat depression every single day. It has become the now. I don't mean that in a negative way, I mean that in a good way. It's okay to have that particular psychiatric problem and the system responds to that in a way that was unthinkable, unthinkable when I was young.

(43:59):

I would like to see it be that way around addiction. That it would be just no stranger to a doctor, no stranger to an insurer, no stranger to a hospital. For them to say, "This person's here because they've got an addiction. They belong here, just like the person with depression belongs here, just like we all agree, the person with cancer belongs here."

(44:18):

That's what I'd like to see, and then the system would manage it like any other chronic disease. And with the models we have, it'd make a lot of sense for any other condition that can't be resolved in an appointment or with one prescription that's not acute. But is a chronic problem that requires follow-up and coordination and work by the patient, work by the system. That's what I'd like to see.

Nicholas Weiler (44:40):

Well, thank you so much, Keith, for coming back on the show. This has been a really eye-opening conversation for me.

(44:46):

It's given me a lot to think about, and I hope it's given our listeners a lot to think about as well.

Keith Humphreys (44:49):

Really appreciate the chance to talk with you.

Nicholas Weiler (44:53):

Thanks again so much to our guest, Keith Humphreys. He's the Esther Ting Memorial professor in the Department of Psychiatry and Behavioral Sciences at Stanford Medicine, and he created and co-directs the Stanford Network on Addiction Policy. To read more about his work and the issues we discussed, check out the links in the show notes.

(45:12):

If you're enjoying the show, please subscribe and share with your friends. It helps us grow as a show and bring more listeners to the frontiers of Neuroscience. We'd also love to hear from you. Tell us what you love or what's not working for you about the show in a comment on your favorite podcast platform, or send us an email at neuronspodcast@stanford.edu.

(45:32):

We are listening and we really value your feedback. From Our Neurons to Yours is produced by Michael Osborne at 14th Street Studios, with sound design by Morgan Honaker. I'm Nicholas Weiler, until next time.