Latest / The Sober Creative Podcast / Episode 068 - What Alcohol Actually Does To Your Brain

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Episode 068 - What Alcohol Actually Does To Your Brain · The Sober Creative Podcast

• 0:00
  SPEAKER_01: Welcome everyone to The Sober Creative Podcast.
• 0:02
  SPEAKER_01: Every guest has done the same hard thing.
• 0:05
  SPEAKER_01: They've become honest about what was getting in the way.
• 0:08
  SPEAKER_01: Now they're creating from a space that's actually theirs.
• 0:10
  SPEAKER_01: I'm your host, Josh Woll, and today we're gonna go somewhere else.
• 0:15
  SPEAKER_01: Instead of one person's story of what they let go,
• 0:19
  SPEAKER_01: we're going into the biology underneath all of our stories.
• 0:22
  SPEAKER_01: Most of us, most of what I know about alcohol, I learned by living it.
• 0:28
  SPEAKER_01: I know what nine beers a day did to my sleep, my mornings, my work, and my sense of who I was.
• 0:36
  SPEAKER_01: What I've never had is the other half of that picture,
• 0:39
  SPEAKER_01: the part happening at the levels of receptors and stress hormones and inflammation
• 0:45
  SPEAKER_01: in a place I can't see and was never taught to look.
• 0:48
  SPEAKER_01: Today's guest has spent her career in that place.
• 0:52
  SPEAKER_01: Dr. A. Leslie Morrow is a John Andrews Distinguished Professor and Emerita in
• 0:59
  SPEAKER_01: the Department of Psychiatry and Pharmacology at the University of North Carolina
• 1:04
  SPEAKER_01: at Chapel Hill.
• 1:06
  SPEAKER_01: She earned her PhD in Neuroscience at UC San Diego in 1985,
• 1:11
  SPEAKER_01: completed her postdoctoral training at the National Institute of Mental Health,
• 1:16
  SPEAKER_01: and joined the faculty at UNC in 1990, where she stayed for 35 years.
• 1:22
  SPEAKER_01: In that time, she published more than 238 scientific articles,
• 1:27
  SPEAKER_01: Served 14 years on NIH study section and sat on the editorial boards
• 1:33
  SPEAKER_01: of psychopharmacology,
• 1:36
  SPEAKER_01: pharmacology logical reviews,
• 1:39
  SPEAKER_01: and alcohol clinical and experimental research, among others.
• 1:44
  SPEAKER_01: She was associate director of the Bowles Center for Alcohol Studies for 25 years,
• 1:49
  SPEAKER_01: and she trained 20 postdocs and eight graduate students who went on to careers
• 1:54
  SPEAKER_01: of their own.
• 1:56
  SPEAKER_01: Her work centers on GABA-A receptors and the body's own neurosteroids.
• 2:02
  SPEAKER_01: Allopregnanolone.
• 2:05
  SPEAKER_01: I was going to butcher that word.
• 2:07
  SPEAKER_00: Allopregnanolone.
• 2:09
  SPEAKER_01: Thank you.
• 2:09
  SPEAKER_01: In particular,
• 2:12
  SPEAKER_01: those discoveries led to clinical trials of alcohol use disorder and brexanolone
• 2:17
  SPEAKER_01: for depression.
• 2:24
  SPEAKER_01: And they point towards treatments for conditions we haven't figured out yet.
• 2:29
  SPEAKER_01: So I come into this one with a long list of questions.
• 2:32
  SPEAKER_01: What is actually happening in there after the first drink and after the thousandth?
• 2:38
  SPEAKER_01: Why the recovery takes so much longer than the hangover?
• 2:42
  SPEAKER_01: And why cutting back fails for so many people who are trying as hard as they know how?
• 2:47
  SPEAKER_01: And what she has come to understand about all of this after four decades of looking closely.
• 2:53
  SPEAKER_01: So Leslie, thanks for being here.
• 2:56
  SPEAKER_00: Well, Josh, thanks very much for inviting me.
• 2:59
  SPEAKER_00: I'm really delighted to be here.
• 3:01
  SPEAKER_00: And boy,
• 3:03
  SPEAKER_00: you've asked the really big questions,
• 3:06
  SPEAKER_00: the questions that I've worked on for a long, long time.
• 3:09
  SPEAKER_00: And I think that I'd like to start by saying, what's alcohol doing in there?
• 3:14
  SPEAKER_00: Well, that depends on the dose of alcohol.
• 3:19
  SPEAKER_00: So what's alcohol doing in there with one or two drinks?
• 3:23
  SPEAKER_00: It's very different than what alcohol is doing in there with four or six or nine drinks.
• 3:29
  SPEAKER_00: And so, you know,
• 3:33
  SPEAKER_00: over 40 years of studying these questions,
• 3:36
  SPEAKER_00: every couple of years, there's a new discovery about what's alcohol doing in there.
• 3:41
  SPEAKER_00: And then people find, okay, there's a new site of alcohol action.
• 3:47
  SPEAKER_00: If we block that site, can we help people with With alcohol drinking issues.
• 3:55
  SPEAKER_00: And, you know,
• 3:56
  SPEAKER_00: we haven't been very successful in finding treatments that were helpful
• 4:01
  SPEAKER_00: for people using that approach.
• 4:04
  SPEAKER_00: And so what I would like to kind of do is rather go through a lot
• 4:09
  SPEAKER_00: of technical science that may or may not be useful
• 4:15
  SPEAKER_00: to people is tell you what I think has been the most important discovery of And
• 4:24
  SPEAKER_00: that is that what a lifetime of excessive alcohol consumption does is causes a lot
• 4:31
  SPEAKER_00: of inflammation in the brain and in all the organs, in fact.
• 4:37
  SPEAKER_00: And that inflammation is interfering with the normal function of all those organs.
• 4:43
  SPEAKER_00: And that's why it's so hard to control oneself That's why there's so much craving.
• 4:52
  SPEAKER_00: Those changes actually make everything worse.
• 4:58
  SPEAKER_00: If you started out drinking because you were anxious or stressed,
• 5:03
  SPEAKER_00: well, those inflammatory changes just make you more anxious and more stressed.
• 5:09
  SPEAKER_00: If you start out drinking because you're experiencing pain,
• 5:13
  SPEAKER_00: physical pain, emotional pain, Well, all that drinking just makes that pain worse.
• 5:23
  SPEAKER_00: So basically, it's making all the triggers stronger.
• 5:27
  SPEAKER_00: How do we know this?
• 5:29
  SPEAKER_00: Okay.
• 5:30
  SPEAKER_00: Well, if we look at the brains of people who died of alcohol use disorder
• 5:36
  SPEAKER_00: and we study what's happening in their brain,
• 5:38
  SPEAKER_00: we see a lot of inflammatory cytokines and chemokines.
• 5:44
  SPEAKER_00: And these are basically danger molecules.
• 5:48
  SPEAKER_00: They're bad players that are interfering with normal function of all our organs,
• 5:54
  SPEAKER_00: including our brain.
• 5:57
  SPEAKER_00: And so this inflammation,
• 5:59
  SPEAKER_00: I think,
• 6:00
  SPEAKER_00: hasn't really been,
• 6:02
  SPEAKER_00: it's recognized now scientifically,
• 6:05
  SPEAKER_00: but I don't think that the general public is aware so much
• 6:09
  SPEAKER_00: of this research showing how important inflammation is
• 6:14
  SPEAKER_00: In driving alcohol use disorder and making it more difficult for people
• 6:19
  SPEAKER_00: to gain control over their drinking and manage their anxiety
• 6:27
  SPEAKER_00: and normalize their response to stress.
• 6:31
  SPEAKER_00: Okay.
• 6:32
  SPEAKER_00: So I want to talk about inflammation today.
• 6:35
  SPEAKER_00: But the other thing I wanted to say in kind of getting started as
• 6:40
  SPEAKER_00: to what is alcohol doing in there What alcohol is doing in there depends
• 6:47
  SPEAKER_00: on what you have going on in there when you start drinking.
• 6:52
  SPEAKER_00: Like if you're already really anxious,
• 6:57
  SPEAKER_00: if you're already stressed,
• 7:00
  SPEAKER_00: if you've already got a lot of pain,
• 7:04
  SPEAKER_00: if you've already got other things going on,
• 7:07
  SPEAKER_00: when you add alcohol, what it's doing is different.
• 7:12
  SPEAKER_00: Then if you start drinking without any of that stuff.
• 7:17
  SPEAKER_01: How so?
• 7:20
  SPEAKER_00: Well, that's because there's already been changes in the normal pathways.
• 7:26
  SPEAKER_00: There's already been changes in the normal way that the brain is working
• 7:31
  SPEAKER_00: and your other organs are working, by the way.
• 7:34
  SPEAKER_00: I mean, alcohol doesn't just act on the brain.
• 7:38
  SPEAKER_00: It acts on the whole body.
• 7:40
  SPEAKER_00: And has systemic effects that impact lots of things in many, many ways.
• 7:47
  SPEAKER_00: So it's a tiny, tiny molecule and it acts at many, many sites.
• 7:53
  SPEAKER_00: It acts at some sites at low doses, but at high doses, it's toxic.
• 8:00
  SPEAKER_00: And so if you add a toxin to a situation that's already working abnormally,
• 8:07
  SPEAKER_00: It's going to have different effects than if you add that toxin to
• 8:11
  SPEAKER_00: a physiology that's normal.
• 8:17
  SPEAKER_00: So what do we do about it, right?
• 8:19
  SPEAKER_00: Well,
• 8:19
  SPEAKER_00: what I love about this new knowledge about inflammation is that now we know
• 8:30
  SPEAKER_00: what is
• 8:30
  SPEAKER_00: the cause of the inflammation.
• 8:33
  SPEAKER_00: What are the cytokines and chemokines that are increased by alcohol?
• 8:37
  SPEAKER_00: Well, we've studied the human brain of people who were alcoholics or suffered
• 8:43
  SPEAKER_00: from alcohol use disorder during their life,
• 8:46
  SPEAKER_00: and we figured out what the problem players are.
• 8:50
  SPEAKER_00: And, you know, this is not the same inflammation as arthritis.
• 8:55
  SPEAKER_00: This is not the same inflammation as a headache, a common headache.
• 8:59
  SPEAKER_00: These are specific inflammatory pathways that are specific to alcohol.
• 9:05
  SPEAKER_01: Mm-hmm.
• 9:06
  SPEAKER_00: And so now that we know which ones are involved,
• 9:11
  SPEAKER_00: we can do things to maybe calm them down and bring them back to normal.
• 9:19
  SPEAKER_00: But the other good thing,
• 9:21
  SPEAKER_00: the other important thing is,
• 9:25
  SPEAKER_00: and this is where my work came in,
• 9:27
  SPEAKER_00: is that we have endogenous steroids in our body that already work
• 9:33
  SPEAKER_00: to keep those Those inflammatory pathways dampened and tempered and under control.
• 9:42
  SPEAKER_00: And those are the steroids that we talked about, pregnenolone and allopregnanolone.
• 9:49
  SPEAKER_00: So those steroids naturally control the inflammatory pathways,
• 9:56
  SPEAKER_00: but our steroids can get depleted
• 10:01
  SPEAKER_00: and those inflammatory pathways can get triggered Not just by alcohol but
• 10:07
  SPEAKER_00: by other toxins and by stress.
• 10:11
  SPEAKER_00: And when our stress system is depleted from chronic stress,
• 10:16
  SPEAKER_00: then all of our natural ability to fight those inflammatory pathways is depleted.
• 10:25
  SPEAKER_00: And so...
• 10:26
  SPEAKER_00: This gives us two ways to kind of approach this.
• 10:31
  SPEAKER_00: We can look for antagonists of the inflammatory molecules.
• 10:37
  SPEAKER_00: And we actually have discovered, not me,
• 10:41
  SPEAKER_00: when I say we,
• 10:43
  SPEAKER_00: I'm talking about the field of neuroscience,
• 10:46
  SPEAKER_00: has discovered some important things that might be helpful to people.
• 10:51
  SPEAKER_00: And the first one is exercise.
• 10:54
  SPEAKER_00: Exercise actually counters the effects of inflammation.
• 10:59
  SPEAKER_00: And we don't know exactly how it does that, but we know that it does.
• 11:06
  SPEAKER_00: So the work started out in animal models.
• 11:09
  SPEAKER_00: So we can take little rats,
• 11:11
  SPEAKER_00: we can make them dependent upon alcohol by feeding it to them for a period
• 11:17
  SPEAKER_00: of several weeks at doses that are appropriate, similar to what humans take.
• 11:25
  SPEAKER_00: And we can see that they develop the same inflammatory changes in their liver and
• 11:31
  SPEAKER_00: in their brain that we humans will exhibit.
• 11:37
  SPEAKER_00: And then we can give them the opportunity to exercise.
• 11:42
  SPEAKER_00: And we can exercise them before,
• 11:47
  SPEAKER_00: during the time they drink, or after we stop them from drinking.
• 11:53
  SPEAKER_00: And either way you do it,
• 11:55
  SPEAKER_00: exercise reduces those inflammatory molecules in their brain and in their liver.
• 12:03
  SPEAKER_00: So exercise is a really good thing.
• 12:06
  SPEAKER_00: And if people are struggling,
• 12:09
  SPEAKER_00: fighting the fight,
• 12:11
  SPEAKER_00: and just can't quite get past something that they're trying to get past,
• 12:18
  SPEAKER_00: adding exercise to your life can really make a tangible difference.
• 12:23
  SPEAKER_00: And so, you know, people might say, well, what do you mean exercise?
• 12:31
  SPEAKER_00: You know, well, you know, what I mean is whatever you enjoy.
• 12:36
  SPEAKER_00: It could be walking.
• 12:37
  SPEAKER_00: It could be yoga.
• 12:38
  SPEAKER_00: It could be pumping weights.
• 12:40
  SPEAKER_00: It could be whatever, whatever you enjoy.
• 12:43
  SPEAKER_00: Just make sure you do it more than four days a week, more than half of the days of the week.
• 12:50
  SPEAKER_00: Make sure you exercise.
• 12:52
  SPEAKER_00: And if you do that,
• 12:55
  SPEAKER_00: from what we've learned from animal studies,
• 12:57
  SPEAKER_00: this should decrease the inflammation in all your organs.
• 13:02
  SPEAKER_00: And this might help you to achieve what you're trying to achieve.
• 13:06
  SPEAKER_01: Okay.
• 13:07
  SPEAKER_01: Yeah.
• 13:08
  SPEAKER_01: It's a big, big practice for me.
• 13:11
  SPEAKER_01: I get a lot of the steps in and go to the gym.
• 13:14
  SPEAKER_01: Yeah.
• 13:15
  SPEAKER_00: Yeah.
• 13:15
  SPEAKER_00: Yeah, so the science is really strong behind this.
• 13:18
  SPEAKER_00: And this was not my work.
• 13:20
  SPEAKER_00: This is work of other people in the field.
• 13:22
  SPEAKER_00: But it's the really strong science.
• 13:25
  SPEAKER_00: And so I think this is something that a lot of people don't realize,
• 13:29
  SPEAKER_00: that there's really good science that suggests that this can be really helpful.
• 13:35
  SPEAKER_00: Okay.
• 13:36
  SPEAKER_00: All right.
• 13:36
  SPEAKER_00: So the particular pathways that alcohol activates are called toll-like receptor pathways.
• 13:46
  SPEAKER_00: And the toll-like receptor 4 pathway is the main one.
• 13:50
  SPEAKER_00: And that's because high doses of alcohol causes leaky gut.
• 13:56
  SPEAKER_00: And in our gut, we have endotoxin or lipopolysaccharide.
• 14:04
  SPEAKER_00: Everybody's got it in their gut.
• 14:07
  SPEAKER_00: And as long as it stays in your gut, it's okay.
• 14:10
  SPEAKER_00: But if it leaks out of your gut into your bloodstream,
• 14:14
  SPEAKER_00: It activates this toll-like receptor 4 pathway.
• 14:19
  SPEAKER_00: And that's really difficult to overcome because once that pathway is activated,
• 14:28
  SPEAKER_00: it reactivates itself.
• 14:30
  SPEAKER_00: It works in a feed-forward manner to keep things going.
• 14:36
  SPEAKER_00: So once you start that inflammatory process,
• 14:40
  SPEAKER_00: particularly in the brain, it's not easy to stop it.
• 14:44
  SPEAKER_00: Because the TLR4 pathway produces more molecules that reactivate itself
• 14:53
  SPEAKER_00: and activate other TLR pathways.
• 14:58
  SPEAKER_00: So that's why it's important to target this TLR4 pathway.
• 15:05
  SPEAKER_00: And right now we don't have any medications that specifically target this TLR4 pathway.
• 15:13
  SPEAKER_00: But scientists, of course, are working on this.
• 15:16
  SPEAKER_00: And in the course of doing this,
• 15:19
  SPEAKER_00: there's one group at UNC,
• 15:21
  SPEAKER_00: actually,
• 15:22
  SPEAKER_00: who have found that there is a naturally occurring antagonist of this TLR4 pathway
• 15:29
  SPEAKER_00: in licorice root.
• 15:33
  SPEAKER_00: It's called glycerisin, glycerisin glabra.
• 15:37
  SPEAKER_00: It's the component of licorice root.
• 15:41
  SPEAKER_00: And you can buy licorice root over the counter, you know, at your favorite online retailer.
• 15:50
  SPEAKER_00: You just want to make sure that it's independently tested and,
• 15:55
  SPEAKER_00: you know,
• 15:55
  SPEAKER_00: because there's a lot of supplements that are available to everyone
• 16:01
  SPEAKER_00: that are really not what they say they are.
• 16:04
  SPEAKER_00: So you want to make sure you're buying it from a quality source.
• 16:08
  SPEAKER_00: But glycerin blocks that TLR4 pathway.
• 16:13
  SPEAKER_01: So before you go,
• 16:17
  SPEAKER_01: can you simplify the pathways a bit more for me
• 16:20
  SPEAKER_01: so I can understand what they're doing?
• 16:23
  SPEAKER_00: Well, so the TLR4 pathway,
• 16:26
  SPEAKER_00: when it's activated,
• 16:28
  SPEAKER_00: it produces those inflammatory cytokines and chemokines that are the markers
• 16:35
  SPEAKER_00: of inflammation.
• 16:37
  SPEAKER_00: We call it inflammation.
• 16:39
  SPEAKER_00: Okay.
• 16:39
  SPEAKER_00: It's not that the brain is red and swollen.
• 16:42
  SPEAKER_00: You know,
• 16:43
  SPEAKER_00: it's that these,
• 16:44
  SPEAKER_00: it has these inflammatory markers that change its normal function and interfere
• 16:51
  SPEAKER_00: with everything it is supposed to be doing normally.
• 16:54
  SPEAKER_00: And they change so many things.
• 16:57
  SPEAKER_00: They change all the way that alcohol is acting.
• 17:00
  SPEAKER_00: They change the way all our normal neurotransmitters are acting.
• 17:05
  SPEAKER_00: And, and it, it, um,
• 17:09
  SPEAKER_00: It leads to extra anxiety, extra depression, extra pain, extra craving.
• 17:16
  SPEAKER_00: All of these things that we feel are all affected by these inflammatory mediators.
• 17:24
  SPEAKER_00: And so the TLR4 pathway is what produces those inflammatory mediators.
• 17:34
  SPEAKER_00: And alcohol activates that pathway.
• 17:38
  SPEAKER_00: So I don't think we want to get more technical than that.
• 17:41
  SPEAKER_00: I mean, I give you a lot more words, but I don't know that that would be helpful to you.
• 17:47
  SPEAKER_00: But what I'm trying to say is that glycerin has been shown to block that inflammatory pathway.
• 17:55
  SPEAKER_00: And in animal models of alcoholism, in mice and rats, glycerin helps with a lot of things.
• 18:03
  SPEAKER_00: It reduces drinking,
• 18:05
  SPEAKER_00: voluntary drinking,
• 18:07
  SPEAKER_00: In those animal models,
• 18:09
  SPEAKER_00: it blocks the inflammatory changes in the brain in those animal models.
• 18:14
  SPEAKER_00: It reduces anxiety-like behavior in those animal models.
• 18:19
  SPEAKER_00: And that compound,
• 18:21
  SPEAKER_00: which is a naturally occurring compound,
• 18:24
  SPEAKER_00: is about to start clinical trials in people.
• 18:31
  SPEAKER_00: Now, the thing is, pharmaceutical companies...
• 18:37
  SPEAKER_00: Play a really important role in the development of medications for human disease.
• 18:42
  SPEAKER_00: But naturally occurring compounds can't be patented.
• 18:47
  SPEAKER_00: So if they can't be patented,
• 18:49
  SPEAKER_00: the pharmaceutical company can't make enough money to pay for the costs of bringing
• 18:55
  SPEAKER_00: a compound through clinical trials and getting it approved for treatment.
• 19:01
  SPEAKER_00: So natural compounds are...
• 19:05
  SPEAKER_00: Not likely to be picked up by pharmaceutical companies and developed for treatments.
• 19:11
  SPEAKER_00: And that's just the nature of how pharmaceutical development occurs in our country.
• 19:19
  SPEAKER_00: And so this is a natural compound that might be a tool that might be helpful
• 19:27
  SPEAKER_00: to some people, something to keep in mind.
• 19:32
  SPEAKER_00: The other thing is,
• 19:34
  SPEAKER_00: To keep in mind is that, hey,
• 19:37
  SPEAKER_00: there's really smart people working on this problem and trying to find other ways
• 19:44
  SPEAKER_00: to help.
• 19:47
  SPEAKER_00: And so I think that that hopefully will give people hope that they can do something about this.
• 19:56
  SPEAKER_00: And then the last thing I want to tell you about if we have time
• 20:01
  SPEAKER_01: Yeah, yeah.
• 20:02
  SPEAKER_01: I have some questions for you.
• 20:03
  SPEAKER_00: Yeah.
• 20:04
  SPEAKER_00: Well, what my work showed is that those naturally occurring steroids,
• 20:10
  SPEAKER_00: the ones that naturally protect us from inflammation,
• 20:14
  SPEAKER_00: they can get depleted with chronic stress,
• 20:17
  SPEAKER_00: and they also get depleted with chronic alcohol use.
• 20:23
  SPEAKER_00: And so we can replace that.
• 20:26
  SPEAKER_00: Just like people do hormone replacement therapy,
• 20:30
  SPEAKER_00: You know,
• 20:31
  SPEAKER_00: as an aging tool or in menopause in women,
• 20:35
  SPEAKER_00: we can replace some of these steroids that are anti-inflammatory.
• 20:40
  SPEAKER_00: And the one that we can replace is pregnenolone.
• 20:45
  SPEAKER_00: It is the grandfather or grandmother's steroid.
• 20:49
  SPEAKER_00: It's the precursor of the other protective steroids.
• 20:54
  SPEAKER_00: And itself is a blocker of the TLR4 pathway.
• 21:00
  SPEAKER_00: It blocks activation of the TLR4 pathway.
• 21:04
  SPEAKER_00: So if LPS leaks from the gut into the bloodstream and is trying to activate
• 21:10
  SPEAKER_00: the TLR4 pathway, pregnenolone can block that directly.
• 21:15
  SPEAKER_00: And pregnenolone is available over the counter.
• 21:20
  SPEAKER_00: Again, you want to look for a reputable place to get it.
• 21:24
  SPEAKER_00: It does not require a prescription and is a way
• 21:29
  SPEAKER_00: to bring Your natural endogenous steroids back up to the normal level
• 21:35
  SPEAKER_00: where they should be.
• 21:38
  SPEAKER_01: So when you were a kid and you went through high school and all that,
• 21:45
  SPEAKER_01: what drew you to pick this field of work?
• 21:50
  SPEAKER_00: Wow.
• 21:52
  SPEAKER_00: Well, so...
• 21:54
  SPEAKER_00: When I was a kid, I thought I didn't know that I would ever go in this direction.
• 22:01
  SPEAKER_00: But when I was in college, I had a professor that really got me excited about science.
• 22:10
  SPEAKER_00: And so as I went through college, I got really interested in neuroscience.
• 22:15
  SPEAKER_00: And so I started out working in a lab in college.
• 22:20
  SPEAKER_00: And then I applied to graduate school.
• 22:23
  SPEAKER_00: And when I got into graduate school,
• 22:25
  SPEAKER_00: I found a lab that was doing really exciting work on receptors.
• 22:30
  SPEAKER_00: And so I learned all about brain receptors and how to study them and so forth.
• 22:35
  SPEAKER_00: And then when I did my postdoctoral work at the NIH, I was studying the GABA receptors.
• 22:44
  SPEAKER_00: And that's when I started studying these endogenous neuroactive steroids.
• 22:50
  SPEAKER_00: Because when I was a postdoc,
• 22:51
  SPEAKER_00: We discovered that they were very potent activators of GABA receptors.
• 22:57
  SPEAKER_00: And that was very exciting because this was,
• 23:00
  SPEAKER_00: okay, we have an endogenous steroid that helps us relax.
• 23:05
  SPEAKER_00: We have an endogenous steroid that helps us sleep.
• 23:08
  SPEAKER_00: We have an endogenous steroid that protects our stress system.
• 23:14
  SPEAKER_00: And we did a lot of studies on How does this endogenous steroid work?
• 23:19
  SPEAKER_00: Why is it good for us?
• 23:21
  SPEAKER_00: Why is it important?
• 23:23
  SPEAKER_00: And that wasn't until the last eight or 10 years that my lab discovered
• 23:28
  SPEAKER_00: that these same endogenous steroids also block these inflammatory pathways.
• 23:36
  SPEAKER_00: And so now we go, oh my goodness, we have these endogenous steroids that have many actions.
• 23:45
  SPEAKER_00: They enhance GABAergic transmission.
• 23:47
  SPEAKER_00: Which makes us feel better,
• 23:49
  SPEAKER_00: calms us down,
• 23:50
  SPEAKER_00: helps us deal with stress, and helps us deal with inflammatory insults.
• 23:55
  SPEAKER_00: And they come from excess stress,
• 23:58
  SPEAKER_00: and they come from excess alcohol,
• 24:00
  SPEAKER_00: and they come from other toxins in our environment.
• 24:04
  SPEAKER_00: And there's more and more of them all the time that our bodies have to cope with.
• 24:11
  SPEAKER_00: So I came to kind of a curlicue way.
• 24:15
  SPEAKER_00: But it started out because I was interested in the brain, how the brain works.
• 24:21
  SPEAKER_00: And it's been really rewarding to actually learn some things now that can help people.
• 24:27
  SPEAKER_01: Why'd you pick alcohol?
• 24:33
  SPEAKER_00: Yeah.
• 24:34
  SPEAKER_00: Well, it's interesting,
• 24:37
  SPEAKER_00: you know,
• 24:37
  SPEAKER_00: working on GABA receptors and we discovered
• 24:41
  SPEAKER_00: that alcohol was also Activating GABA receptors.
• 24:47
  SPEAKER_00: And at the lower doses,
• 24:48
  SPEAKER_00: like the one or two drink doses, alcohol was enhancing GABAergic function.
• 24:55
  SPEAKER_00: And that's kind of what provides those first nice feelings of alcohol,
• 25:00
  SPEAKER_00: the kind of the, ah, that one feels with that first drink.
• 25:06
  SPEAKER_00: You know, that kind of a sense of relief.
• 25:09
  SPEAKER_01: Warm sensation that comes up.
• 25:11
  SPEAKER_00: Yeah, and that feeling of relief and kind of letting go and whatnot.
• 25:17
  SPEAKER_00: A lot of that has to do with those effects on GABA receptors.
• 25:24
  SPEAKER_00: So then I realized that my work on GABA receptors was really,
• 25:30
  SPEAKER_00: really relevant to this problem of alcohol use disorder.
• 25:34
  SPEAKER_00: And so...
• 25:36
  SPEAKER_00: That's how I kind of got interested in alcohol use disorders because I realized
• 25:42
  SPEAKER_00: that my basic research on the brain was really relevant to this disorder.
• 25:48
  SPEAKER_00: And part of it was an interest in doing something good to help people.
• 25:53
  SPEAKER_00: But part of it was also just practical.
• 25:55
  SPEAKER_00: I mean, I had to get my research funded.
• 25:58
  SPEAKER_00: I had to write grants to the NIH to get funding for my research.
• 26:03
  SPEAKER_00: And the National Institute of Alcohol Abuse and Alcoholism,
• 26:06
  SPEAKER_00: Was very interested in my work because they also saw the relevance to the problem
• 26:12
  SPEAKER_00: of alcohol use disorder.
• 26:13
  SPEAKER_00: And so that kind of,
• 26:16
  SPEAKER_00: that practical consideration of who will fund me basically turned me into
• 26:22
  SPEAKER_00: an alcohol researcher.
• 26:25
  SPEAKER_00: And so...
• 26:29
  SPEAKER_00: But then,
• 26:29
  SPEAKER_00: you know,
• 26:30
  SPEAKER_00: as you start to become an alcohol researcher,
• 26:32
  SPEAKER_00: you realize more and more people around you struggle with this problem.
• 26:38
  SPEAKER_00: And I suddenly became aware of the people in my family who had struggled
• 26:43
  SPEAKER_00: with this problem, you know?
• 26:46
  SPEAKER_00: And almost everybody has people in their family who have struggled with this problem
• 26:52
  SPEAKER_00: at one level or another.
• 26:53
  SPEAKER_00: I mean, it is so pervasive.
• 26:57
  SPEAKER_00: It's probably...
• 26:58
  SPEAKER_00: The biggest public health problem in the world,
• 27:01
  SPEAKER_00: and yet our National Institute of Health,
• 27:05
  SPEAKER_00: it's the smallest institute with the smallest budget.
• 27:10
  SPEAKER_01: Is that intentional by the alcohol industry?
• 27:16
  SPEAKER_00: Who knows?
• 27:17
  SPEAKER_00: Who knows?
• 27:18
  SPEAKER_00: I think it has to do with the fact that for a long time,
• 27:21
  SPEAKER_00: people thought of this as a moral problem,
• 27:24
  SPEAKER_00: not as a real biological problem.
• 27:28
  SPEAKER_00: And there's still people who look at it that way, unfortunately.
• 27:34
  SPEAKER_00: But I think as a scientist,
• 27:37
  SPEAKER_00: it's become really, really clear that
• 27:43
  SPEAKER_00: it's definitely a biological issue.
• 27:46
  SPEAKER_00: And so with more research and better understanding,
• 27:50
  SPEAKER_00: we should be able to develop tools that will help more people
• 27:54
  SPEAKER_00: to overcome their issues.
• 27:57
  SPEAKER_00: And it's entangled with a lot of other things.
• 28:04
  SPEAKER_00: Everything is connected.
• 28:08
  SPEAKER_00: But anyway,
• 28:09
  SPEAKER_00: I really feel like this inflammation discovery,
• 28:12
  SPEAKER_00: which was not my lab's discovery,
• 28:14
  SPEAKER_00: it was other labs in the field who discovered this,
• 28:17
  SPEAKER_00: is really key because controlling inflammation can have a major impact
• 28:25
  SPEAKER_00: and This is something that can be helpful to people to understand and to address.
• 28:31
  SPEAKER_00: And so I hope that the people that watch your podcast can think about that and think
• 28:39
  SPEAKER_00: about whether maybe they want to add things to their life like exercise
• 28:45
  SPEAKER_00: or supplements that can fight that inflammation and see if it helps them,
• 28:51
  SPEAKER_00: see if it makes them better.
• 28:53
  SPEAKER_01: Yeah,
• 28:54
  SPEAKER_01: that's what I feel like was so interesting what you said earlier in the conversation
• 28:58
  SPEAKER_01: that,
• 28:59
  SPEAKER_01: you know,
• 29:01
  SPEAKER_01: it doesn't really matter the amount,
• 29:04
  SPEAKER_01: you know,
• 29:04
  SPEAKER_01: of alcohol that you have is that it's going to affect your inflammation
• 29:10
  SPEAKER_01: in your body one way or another.
• 29:12
  SPEAKER_01: And so...
• 29:15
  SPEAKER_01: Like if someone was just to have two or three per week that's still affecting
• 29:21
  SPEAKER_01: the inflammation,
• 29:22
  SPEAKER_01: how long does it take for...
• 29:24
  SPEAKER_01: Because like what you said was really interesting too in that when you have alcohol,
• 29:30
  SPEAKER_01: it's changing things within your system.
• 29:33
  SPEAKER_01: And so does it eventually change back when you don't have alcohol for
• 29:40
  SPEAKER_01: a certain length or does your system stay a certain way for...
• 29:45
  SPEAKER_01: A long period of time.
• 29:47
  SPEAKER_00: Well, it's really hard to get rid of that inflammation.
• 29:51
  SPEAKER_00: It's really hard.
• 29:55
  SPEAKER_00: Once it starts, it can stay your whole life.
• 29:58
  SPEAKER_00: I mean, in the postmortem brain of human alcoholics,
• 30:01
  SPEAKER_00: those inflammatory markers were at really high levels.
• 30:06
  SPEAKER_00: And the levels of the inflammation correlated with their lifetime use of alcohol.
• 30:12
  SPEAKER_00: So the more alcohol you drink, the more inflammation you're gonna have.
• 30:17
  SPEAKER_00: If you only drink one or two,
• 30:19
  SPEAKER_00: a few drinks a week,
• 30:21
  SPEAKER_00: but you already have underlying inflammation,
• 30:26
  SPEAKER_00: well, it's just gonna perpetuate that inflammation, okay?
• 30:31
  SPEAKER_00: If you don't have any inflammation and you only drink two or three drinks a week,
• 30:36
  SPEAKER_00: then you might be fine.
• 30:38
  SPEAKER_00: But if you can tamp down that inflammation,
• 30:42
  SPEAKER_00: Then you can basically block one of the things that's preventing you
• 30:49
  SPEAKER_00: from being healthy.
• 30:53
  SPEAKER_00: And so, you know, these are some things that people can add to their toolbox.
• 31:01
  SPEAKER_01: Yeah, yeah.
• 31:03
  SPEAKER_01: That's the thing, you know, with it is it's like it works.
• 31:08
  SPEAKER_01: It works in ways that people...
• 31:11
  SPEAKER_01: And so it's like we need these other tools in place to be able to, yeah, to work with all that.
• 31:17
  SPEAKER_01: Yeah.
• 31:37
  SPEAKER_00: Yeah,
• 31:38
  SPEAKER_00: and it's not like if you want to take pregnenolone to increase your neurosteroids,
• 31:44
  SPEAKER_00: you don't have to take it for the rest of your life.
• 31:48
  SPEAKER_00: You know, you can take it for two months.
• 31:51
  SPEAKER_00: And if you block the inflammation you already have,
• 31:58
  SPEAKER_00: then you might not need to take it again for a couple of years,
• 32:02
  SPEAKER_00: you know, unless that inflammation comes back for some reason.
• 32:06
  SPEAKER_00: Like you had a really bad binge period that made it come back.
• 32:11
  SPEAKER_00: Or maybe a really bad stressful period that made it come back.
• 32:15
  SPEAKER_00: Or maybe exposure to some toxins somewhere that made it come back.
• 32:21
  SPEAKER_00: So it's not like you have to
• 32:26
  SPEAKER_00: take these things for your whole life.
• 32:31
  SPEAKER_00: And exercise.
• 32:32
  SPEAKER_00: Exercise can be so beneficial and helpful.
• 32:35
  SPEAKER_00: And it can be preventative and protective.
• 32:39
  SPEAKER_00: And so maybe you have one bender and you're beating yourself up because you did that.
• 32:48
  SPEAKER_00: Well, instead of that, just increase your exercise for the next few weeks.
• 32:53
  SPEAKER_00: You know,
• 32:53
  SPEAKER_00: counter the effects of that bender
• 32:56
  SPEAKER_00: by doing something that's reducing your inflammation rather than increasing it.
• 33:01
  SPEAKER_00: And so turn it into a positive.
• 33:04
  SPEAKER_00: You know, is another way of doing it.
• 33:08
  SPEAKER_01: That was like when I stopped drinking,
• 33:10
  SPEAKER_01: that was my reason because I wanted to progress in my fitness
• 33:15
  SPEAKER_01: and I felt like I couldn't.
• 33:16
  SPEAKER_01: So, I mean, I almost was like, you know, I wasn't climbing.
• 33:20
  SPEAKER_01: You know,
• 33:21
  SPEAKER_01: if I was climbing and then I'd drink,
• 33:22
  SPEAKER_01: you know, bring me back down and then I'd try and climb again.
• 33:26
  SPEAKER_01: And so it was just, yeah, yeah, this has been really fascinating.
• 33:31
  SPEAKER_01: Thank you.
• 33:32
  SPEAKER_00: Yeah, absolutely.
• 33:33
  SPEAKER_00: My pleasure.
• 33:34
  SPEAKER_01: So like the, when, when you have the hangover the next day, is that the effects from that?
• 33:42
  SPEAKER_01: Is that from inflammation?
• 33:43
  SPEAKER_00: Um, well, it may or may not be.
• 33:49
  SPEAKER_00: Um, some of that is just the,
• 33:52
  SPEAKER_00: the immediate changes that alcohol cover that causes can explain a hangover
• 33:58
  SPEAKER_00: the next day.
• 33:59
  SPEAKER_00: Um,
• 34:00
  SPEAKER_00: It's more the long persistent changes that are still there after the hangover's gone
• 34:07
  SPEAKER_00: that are more likely to be caused by the inflammation.
• 34:12
  SPEAKER_01: What are some of those that you can list out?
• 34:17
  SPEAKER_00: Well, the brain fog,
• 34:19
  SPEAKER_00: the anxiety,
• 34:21
  SPEAKER_00: the enhanced sensitivity to pain,
• 34:24
  SPEAKER_00: the difficulty focusing, you know, those kinds of things.
• 34:31
  SPEAKER_01: Those can last a week.
• 34:33
  SPEAKER_00: Can last a really long time.
• 34:35
  SPEAKER_00: Yeah.
• 34:36
  SPEAKER_00: And basically when you feel like you're living with those things
• 34:40
  SPEAKER_00: and they just don't ever leave you,
• 34:42
  SPEAKER_00: to me that's a sign that you have inflammation that you need to address.
• 34:47
  SPEAKER_00: And then you'll be much better able to change your behavior the way you want to.
• 34:54
  SPEAKER_00: Okay.
• 34:55
  SPEAKER_01: So short list of combating inflammation.
• 34:59
  SPEAKER_01: Exercise.
• 35:01
  SPEAKER_00: Exercise, Pregnenolone.
• 35:04
  SPEAKER_01: Is that, so is this the licorice?
• 35:07
  SPEAKER_00: No, no, licorice root is glycerin and licorice root.
• 35:11
  SPEAKER_01: Was that the third one?
• 35:13
  SPEAKER_00: That's the third one, those three.
• 35:15
  SPEAKER_01: What's the, wait, what was the second one?
• 35:19
  SPEAKER_00: Pregnenolone.
• 35:21
  SPEAKER_01: Is that taken as like a pill, like a supplement?
• 35:24
  SPEAKER_00: It's a pill, it's a supplement.
• 35:26
  SPEAKER_01: Okay, okay.
• 35:26
  SPEAKER_00: Yeah.
• 35:27
  SPEAKER_01: Okay.
• 35:29
  SPEAKER_00: 300 milligrams a day.
• 35:31
  SPEAKER_00: And if you find that it
• 35:33
  SPEAKER_00: was really helpful and you want to continue for longer,
• 35:36
  SPEAKER_00: probably after that 100 is enough.
• 35:38
  SPEAKER_00: But
• 36:01
  SPEAKER_00: But that 300 is the dose that has in the clinical trials was shown
• 36:06
  SPEAKER_00: to normalize your stress responses,
• 36:09
  SPEAKER_00: reduce stress-induced craving, reduce alcohol craving, and reduce alcohol intake.
• 36:16
  SPEAKER_00: In the clinical trials,
• 36:17
  SPEAKER_00: that was the dose reported by the group at Yale that did this studies with
• 36:25
  SPEAKER_00: about 300 people.
• 36:28
  SPEAKER_00: And it was just eight weeks of treatment.
• 36:31
  SPEAKER_00: Okay.
• 36:32
  SPEAKER_00: And then glycerin, it's about 400 milligrams a day.
• 36:39
  SPEAKER_00: And I don't know how long you have to take it,
• 36:42
  SPEAKER_00: but I don't think it could hurt you unless you have high blood pressure.
• 36:49
  SPEAKER_00: If you have high blood pressure, you need to make sure it's not changing your blood pressure.
• 36:54
  SPEAKER_00: But at that dose of 400 milligrams a day, it shouldn't affect blood pressure in most people.
• 37:01
  SPEAKER_00: But you have to pay attention to that.
• 37:05
  SPEAKER_01: Well, thank you so much for all this.
• 37:08
  SPEAKER_01: It's been so fascinating.
• 37:09
  SPEAKER_01: And if anybody here that's with us,
• 37:12
  SPEAKER_01: if you have any questions, feel free to pop them in the chat.
• 37:19
  SPEAKER_01: Leslie, do you want to let us know?
• 37:21
  SPEAKER_01: So what's next on the horizon for you?
• 37:24
  SPEAKER_01: Well, I'm retired now.
• 37:28
  SPEAKER_00: So I guess I'm really just going to be working on legacy things.
• 37:32
  SPEAKER_00: I want to get
• 37:35
  SPEAKER_00: our research out there to the public more because I think it can help people.
• 37:42
  SPEAKER_00: And, you know,
• 37:43
  SPEAKER_00: the drug companies aren't going to do this for us
• 37:46
  SPEAKER_00: because they can't make enough money to do this for us.
• 37:50
  SPEAKER_00: So I think that,
• 37:52
  SPEAKER_00: you know,
• 37:52
  SPEAKER_00: What I need to do now is work on the legacy of my work and the work of my colleagues
• 37:58
  SPEAKER_00: to the general public to help more people.
• 38:01
  SPEAKER_01: Well, I appreciate this opportunity to be able to share your work.
• 38:06
  SPEAKER_01: I mean, my eyes got wide when,
• 38:10
  SPEAKER_01: you know, you told me about inflammation can stay in your brain for your whole life.
• 38:15
  SPEAKER_00: That's... Oh, absolutely.
• 38:17
  SPEAKER_01: That's big.
• 38:18
  SPEAKER_00: It is big.
• 38:20
  SPEAKER_00: It is big.
• 38:21
  SPEAKER_01: That is really big, yeah.
• 38:23
  SPEAKER_00: And it plays a big role in other mental health disorders also.
• 38:29
  SPEAKER_01: Yeah.
• 38:30
  SPEAKER_00: Inflammation is really big in depression.
• 38:32
  SPEAKER_00: A lot of people who drink have depression.
• 38:35
  SPEAKER_00: A lot of people who drink, drink because they feel depressed.
• 38:39
  SPEAKER_01: That was totally me.
• 38:41
  SPEAKER_00: You know?
• 38:42
  SPEAKER_01: So, yeah.
• 38:44
  SPEAKER_00: Inflammation is a big part of that.
• 38:47
  SPEAKER_00: And by the way, it's the same pathway.
• 38:49
  SPEAKER_01: Mm-hmm.
• 38:51
  SPEAKER_01: Dr. Morrow, thank you.
• 38:55
  SPEAKER_00: Well, you're very welcome.
• 38:57
  SPEAKER_00: Have a great day.
• 38:58
  SPEAKER_00: And, you know, any questions, send it to me on Substack.
• 39:04
  SPEAKER_01: That sounds great.
• 39:05
  SPEAKER_01: All right.
• 39:05
  SPEAKER_01: Thanks, everyone, for joining us.
• 39:07
  SPEAKER_00: Have a good weekend.
• 39:08
  SPEAKER_00: Take care.
• 39:09
  SPEAKER_00: Okay.
• 39:09
  SPEAKER_00: Bye-bye.