Thank you. And again, it's our pleasure to have Dr. Shelly Greenfield with us here today. She is a professor. Oh, my notes just went away here. I'm sorry, you want me to get unstop my sharing? No, no, I just had to exit my full screen. Professor of psychiatry at Harvard Medical School and the Christine M. Trustee Endowed Chair of Psychiatry at McLean Hospital, where she's also the chief academic officer, past president of the academy or of us of AAAP. She has served as a PI and co-investigator on federally funded research focusing on treatment for substance use disorders, gender differences in substance use disorders and health services for substance use disorders, and has developed and tested a new manual-based group therapy for women with substance use disorders, which is called the Women's Recovery Group, or the manual is called Treating Women with Substance Use Disorders, the Women's Recovery Group Manual. And I could probably keep going on and on, but I will say also very importantly, as a psychiatrist, shares our enthusiasm for addiction psychiatrists to be prepared and ready to engage patients with psychotherapeutic modalities. So I will turn it over to you, Dr. Greenfield. Thanks so much. And thanks for the nice introduction. I really appreciate it. And thank you for inviting me to participate in this webinar. I'm very excited to be here. And I'm going to talk with you today, just as was stated, about gender differences in substance use disorders and talk to you about the Women's Recovery Group and its development, implementation, and dissemination. And I just wanted to mention, I don't have disclosures here. I do want to tell you that I am the author of this book that David just mentioned, Treating Women with Substance Use Disorders, the Women's Recovery Group Manual, for which I receive small royalties on an annual basis. And I want to just acknowledge the generous support from the National Institute on Drug Abuse that supported some of the work I'll tell you about today. So what I wanted to start with for all of you is just a reminder that this area of gender and sex differences in human health, overarchingly, is a relatively new field, which dates really back to 1990, when the Office of Research on Women's Health was first established at the NIH by Congress. And then in 1993, the NIH published its Revitalization Act and Guidelines, which said that women and minorities must be included in clinical trials that are federally funded. And it wasn't until 2015 that the NIH mandated that sex as a biological variable must be included in all human, vertebrate, and animal research. And I only point this out to you because for all human health research, we've sort of been in a process of catch-up, because it's really only been in this last 25 plus years that we've really been focused on gender differences, and specifically on women's health. With respect to women and addiction, though, we have known for many years that that women are affected by addiction, by substance use disorders, although really, for most of the centuries preceding, we thought of this as mainly a problem of men. However, that was true right up until the very end of the 20th century. But in the last decade of the 20th century, and now into the third decade of the 21st, what we've been seeing is this very precipitous narrowing of this gender gap in substance use disorders in the U.S. And so what I want to tell you about today are these recent epidemiologic trends, the narrowing of this gap. I'm going to tell you a little bit about alcohol, opioids, and cannabis. We're going to talk a little bit about risks for substance use disorders and treatment barriers for women. Then we're going to talk about this clinical treatment gap and the need for gender-specific intervention for women that can be implemented in routine clinical practice. And that's when I'm going to really tell you more about the Women's Recovery Group and how we went about developing it in stage one and stage two therapy development trials. I'm going to show you some of the qualitative data, and we're going to talk a little bit about what we thought was the mechanism of action and how we tried to figure that out. And then I'm going to tell you a little bit about some digital adaptations we're doing. So what we know is that before the COVID-19 pandemic, we knew that men, still the prevalence of substance use disorders was higher in males than females. But we knew that the gap had been narrowing. In 2019, there had already been an increase from 2019 to 2018 in substance use disorders for adult women age 18 and over. 7.2 million women over the age of 18 had a substance use disorder. Many of them had co-occurring other psychiatric disorders as well. And before the COVID-19 pandemic happened, we were seeing, and you can sort of see on my screen here, between 2013 and 2019, in 12 and over, 18 and over, just look at these for a moment, you can already see sort of that these bars are narrowed just in a six-year period of time, you know, between males and females. But what I want to show you is this. In the 12 to 17-year-old group, actually in 2013, there was no difference between boys and girls. And by 2019, girls had exceeded boys in this age group in terms of a past year substance use disorder for the first time ever since we've been gathering data. In fact, in 1990, we knew that the male-to-female prevalence of alcohol use disorders was 5 to 1. But by 10 years later, it already narrowed to 2.3 to 1. And by about 10 years after that, it narrowed even further to about 1.9 to 1. And looking at all these epidemiologic studies, we had seen that women born after World War II, so in the latter half of the 20th century, were having lower levels of abstaining from alcohol and higher levels of alcohol use disorders compared to the birth cohorts preceding World War II. And what we've seen is that this narrowing has just continued, so that between 2001 and 2012, there was a 16% increase in the proportion of women who drink alcohol, a 58% increase in women's high-risk drinking compared to 16%, and you all know what high-risk drinking is, I've just put it here, though, anywhere for you to take a look at. And then there was also an 84% increase in women's one-year prevalence of having an alcohol use disorder compared to an increase of 35% in men. If you look here at people 12 and older on the left-hand side of the screen, you can look at male and female alcohol use disorders, alcohol use and alcohol use disorders down here and up here, and you can kind of see that these gaps between 02 and 18, they're getting narrower. If you look at 12th graders, what you can see is the good news, which is that, in fact, people's past month drinking and past month episodes of getting drunk in 12th grade from the late 70s to 2018, look at how that's been declining, that's like the good news. Here, what you see, though, is that the gap has completely closed between girls and boys who are in 12th grade. So why do we worry about any of this stuff? Why does it matter? Well, I think you all know that there are many alcohol-related health risks through the lifespan, including liver disease, brain health and memory, cancer, which includes breast cancer for women, cardiovascular disease, multiple mental health consequences. And then what we notice for women, there's an increased risk with binge drinking and heavy drinking of violence and assault, of unintended pregnancies and of sexually transmitted infections. I want to just spend a moment on liver disease because I'm not sure if you are aware of these facts, but it's been very alarming to many different medical disciplines that in this young age group of 15 to 39, between the late 80s and like 2012, and this has only increased, there has been in this young age group, an increase in alcohol-related liver disease. You can sort of see this is for the whole population going up here, this middle green line, but you can see in females, the increase has been 240% versus 90% in males. So that's the gender difference that we were already seeing before the pandemic, and then the pandemic happened. And we knew that in April to June of 2020, compared with the same period in 2019 in the United States, the frequency of alcohol use increased 14% overall and 17% in women. Women had a 41% increase in heavy drinking days in that first year and a 39% increase in the short inventory of problem scale for alcohol. Interestingly, we also saw that there were some gender differences in self-reported alcohol consumption during the pandemic with people's self-reports of stress. And what you see here in both of these figures is that this heavy black line shows that as women were reporting COVID-related psychological distress, they had an increase in their alcohol consumption, whereas this correlation was not true for men. So one of the problems that we worry about in terms of this increasing rates of alcohol consumption, alcohol problems, and alcohol use disorders in women is a phenomenon known as telescoping. And if I were able to see all of you, what I would do is ask you to all raise your hand, have you heard of telescoping yet? Because it's like February of your fellowship year, and I'm hoping you've all heard this, but if you haven't, it's good for me to be able to talk to you a little bit about it because it's an important concept where women who drink, we know, progress more rapidly to serious alcohol-related physical and social consequences than their male counterparts. And what we mean by that is there's a shorter time between the landmarks of illness progression, so first use to first problematic use to a use disorder to treatment. And importantly, it happens at lower doses of alcohol consumed less frequently. We also have seen some evidence of this kind of telescoping course with stimulants, with opioids and nicotine, but the physiology is a little better worked out for alcohol. And I'm going to just tell you a little bit about this. So what's been demonstrated over the last 30 years are in multiple different studies that compared with men, women have less alcohol dehydrogenase in their gastric mucosa. And you all know that ADH is the beginning of first pass metabolism where the body has the first opportunity to begin to break down ethanol into its metabolic components. So what that means is if you have decreased first pass metabolism, females has greater absorption of ethanol directly into the circulatory system. Women have more adipose tissue and lower total body water. So it means that for each ounce of alcohol consumed, there's a higher blood alcohol concentration, which circulates in the body and actually is therefore all of the different organ systems that we are worried about are subject to higher levels of alcohol ounce pounds consumed. And so we have seen some of these similar findings. There's been some evidence for opioids, nicotine, and other stimulants that the same kind of telescoping course has been seen, but as I said, less well worked out physiologically. So with that, I'm going to segue out of alcohol and into opioids and just show you some of the epidemiologic trends that we've been seeing there. So I think you all know that opioid use disorder still in fact is the prevalence is higher in males and females as is overdose deaths by opioid poisonings in males. It's still higher prevalence rate in males and females, but importantly from the late, you know, from about 2000 to 2019 and then really increasing the percent in women has increased 640% versus 478% in men. So it's a steeper rate of increase, even though the absolute difference is still higher, as I said, in males and females. There are some other things that we've learned about sex and gender differences in opioids. This is from the large post study, the prescription opioid addiction treatment study, which showed that women are over the lifetime, are more likely to be prescribed opioids than men. Women report greater cravings for opioids and women report using opioids more frequently to cope with pain and negative affect more than do men. We also made a comparison between 2015 and 2019 from the National Survey on Drug Use and Health. And I just wanted to kind of show you some of this because this is 2015 to 2019. I want to show you first here that if you see this, but in these age groups, you know, it's not really a two to one difference. Like get over here to 35 to 49, this is past your opioid analgesic use disorder. This is pretty close. This age group, 50 to 64, this is pretty close too. And it's, you know, not, it's like probably two to one in 65 and over. But over here, just take a look at the 12 to 17 year olds where girls are twice as likely to have passed your opioid analgesic use disorder than are boys. So that's like a parallel to what I was showing you, right, with the alcohol. And that's kind of, I don't know, I think that's, that's pretty alarming actually. That's like a first time ever. So you're seeing first time ever things in this, first time ever. Okay. So then we get to this and what you see here again, look at this, this is opioid, sorry, analgesic use disorder. Again, it's not two to one here. It's very close. Misuse, very close. And here, opioid analgesic initiation, females greater than males. And then come over here to past your opioid analgesic misuse. Again, this is almost exactly equivalent for males and females. But again, look at that 12 to 17 year old age group. Past your opioid analgesic misuse, girls exceed boys 12 to 17 years old. And then we have some alarming trends in pregnant and postpartum women, which I think you probably have all heard of, but in case not, the mortality rates for recently pregnant women increased 4.4% annually. Like each year there was an increase between 2015 and 2019, mostly attributable to causes other than pregnancy specific complications, including drug and alcohol poisonings. And these rates were greater for recently pregnant women than for the total female population of childbearing age. We also unfortunately have seen these statistics with a rise in pregnancy associated mortality involving opioids that more than doubled in both the rate and the percent of all pregnancy associated deaths. This was reported in 2021. And then in the state of Massachusetts, there was a study done, this is already like 10 years ago, that showed that the overdose rates were lowest in the third trimester amongst all pregnant women who were delivering in Massachusetts, but they increased during the postpartum period with the highest rates seven to 12 months post-delivery, which really tells you about, this is a very vulnerable time for people and these rates escalate postpartum. The good news is all of you do know by this point in time in your fellowship year is that we can treat opioid use disorder in pregnancy. We should be treating it in pregnancy and that we treat it with medications for opioid use disorder, meaning buprenorphine and methadone. And I just wanted to tell you, you can go online to SAMHSA, you can download this really fantastic clinical guidance for treating pregnant and parenting women opioid use disorders. And it includes clinical fact sheets that you can download and you can share them with patients. And then there's this shared decision-making tool that I encourage you to look up by Connie Gill and Andre Jones that you can use to help patients figure out whether and make decisions with you about whether they wish to go on medications for opioid use disorder. And now I just have a couple of slides about cannabis. I just want to show you this. These are past year substance use disorders in 2019 amongst women 12 and older. And this shows you that there was a 13% increase from 2018 to 2019 amongst women who had a cannabis use disorder. These are the other rates here, but this is not alcohol, this is illicit drugs. But I just thought this was a pretty interesting statistic. And the other one that's pretty interesting is regarding the COVID-19 pandemic, where we saw in certain studies for adults in general, amongst those who were making non-medical use of cannabis prior to the pandemic, there was an increase in use patterns after the pandemic. We also saw in Northern California amongst pregnant women, same thing before COVID-19, pregnant women who said that they were using cannabis, this is pre-COVID, it went up during COVID. And so before the pandemic, the standardized rate of prenatal cannabis use was about 6.75% of pregnancies, but the rate increased to 8% of pregnancies during the pandemic. So why do we care about that? Well, we care about that because there is some evidence now that there are risks to the fetus exposed to cannabis. And there is this one study that came out from the ABCD trial, which if you don't know about ABCD, it's the trial that's looking at adolescent behavioral and cognitive development study. It's like an NIMH, NIDA, NIAAA study where it's a giant cohort. And what they found, which is concerning to many in this one published study here is that amongst kids who had been prenatally exposed to cannabis, what they found was that there were in mid-childhood latency, they were finding that there were more psychopathologic characteristics during middle childhood, even after they accounted for confounding variables. And so the endocannabinoid receptors come online in the fetus around six weeks of gestation. And so up till that point, there aren't endocannabinoid receptors in the fetus. After that point, there are. So there's some time in there, pretty soon, quickly to help people either before they're pregnant or when they get pregnant to kind of think about their substance use during pregnancy, especially a lot of women don't know that it's actually potentially harmful to the fetus if they are using cannabis. Finally, I just want to show you these data from, this is again, the National Survey on Drug Use and Health. This is something you can download. It's the intersection of gender, race, and ethnicity in the 2015 to 2019 data. I'm very enthusiastic about this report that SAMHSA published because we have basically not been able to access, I'm just kind of moving you guys around my screen. I see you in pictures and I'm moving you so I can see my slides a little bit better. Because what I want to show you is what happened here is that they started to, they showed us, we could either get data by race, ethnicity, or data by gender. We really had a hard time getting race, gender, ethnicity prior to this report. And then they gave us this report, and what we were able to start to see here is that when we were looking at substance use disorders in the past year among people 12 and older, you know, I was just telling you there's kind of like a 2 to 1, 1.9 to 1 kind of overarching, you know, general population. But what's really important here is that this actually varies by race and ethnicity. So, for example, the male to female ratios, as I calculated them here from the data, shows that for Hispanic or Latino identifying people, it's a 2 to 1 ratio, male to female. For black or African Americans, 1.9 to 1. Asian Americans and white Americans, about 1.7 to 1. For American Indians or Alaska Natives, 1.46 to 1. It narrows more for people identifying as two or more races, 1.3 to 9.1, and it's the closest here for Native Hawaiians or Pacific Islanders. So why do I think that that's important? You know, I think it's really important that we know about this in this intersectional way because it can really assist us in identifying specific barriers for specific populations and solutions for overcoming those barriers like access to care, stigma, and other kinds of things so that we can be, you know, culturally responsive and gender appropriate in our interventions. So that's why I think the reporting in this way is really helpful. And I do encourage you to go online and download that report. It's like ton as chock full of information, really important information. So what I want to do is recap where we are right now. What we know is that compared with men, women now initiate the use of substances at an earlier age than in previous generations at approximately the same age as their male counterparts. We know they have lower levels of abstaining, higher rates of use, misuse, and substance use disorders from recent birth cohorts. We know they advance more rapidly from first use to regular use to first treatment, the so-called telescoping course, and yet that happens using smaller quantities of substances, often for fewer years, and they can average more medical, psychiatric, and social consequences as a consequence of their use. So among the most reproducible research findings we have is this increased prevalence in women in the past three to four decades. There's this heightened vulnerability we see of women to adverse medical and social consequences, the telescoping course we just discussed, and then a treatment entry with fewer years of use, women have more medical, psychiatric, and adverse social consequences than their male counterparts. So now I want to turn my attention to these risk factors for women and what are particular risk factors. So I know by now you know for men and for women there are genetic factors that can form the biological basis significant for both, and I'm talking about like family history, for example. We know a primary parent or grandparent that can demonstrate some genetic vulnerability, and you all know that age of onset of initiation of use is a predictor for a higher risk to go on to have a substance use disorder in the lifespan, but particularly significant for women are heavy drinking or drug use by a significant other partner, a history of sexual violence or physical abuse or family violence, these co-occurring psychiatric disorders which tend to be higher in women than men like depression, anxiety, and PTSD, and then we know there are some special possible sex differences in stress responsivity. I just want to focus on these two risk factors here for a moment. I want to talk about trauma and abuse. Violence and trauma are prevalent among individuals with substance use disorder, males and females across the genders, but we do know that women are more likely to experience childhood sexual and physical abuse, and that is a potent predictor for girls and women of a potential risk for the development of a substance use disorder later in life. There's this demonstrated very strong relationship between abuse history, sexual abuse history, and substance use disorder onset. Given the emerging trends I've just been talking to you about for developing substance use disorders, are there gender differences and barriers to substance use treatment or treatment outcomes, and what about gender-specific treatment for women? We're going to head into the second part of the talk in a moment. First, what I really want to say to you because it's relevant is that there are specific barriers to treatment entry for women. They're less likely to be screened even now in primary mental health care. There's a lack of treatment services for pregnant and parenting women. There are economic barriers that disproportionately fall on women, like lack of insurance and other kinds of resources, trauma histories we just talked about. Social stigma and discrimination, we'll talk a little bit about that in a moment. All of our patients with substance use disorders suffer from social stigma and discrimination, but women actually bear a disproportionate barrier of a disproportionate amount of this, especially in their roles as mothers, parents. We also know that women have a higher risk for these co-occurring psychiatric disorders by populations such as mood, eating anxiety, and PTSD. These things can actually form barriers to their getting substance use disorder treatment. One thing that's really important to just make sure you know is that gender itself, though, however, is not a specific predictor of substance use disorder treatment outcomes. Rather, there are known predictors of treatment outcomes, and these can vary in their prevalence and severity or significance by gender. For example, the things we just talked about, co-occurring disorders, trauma histories, employment, educational attainment, social support, these things can vary by gender, and these predictors, therefore, can have a differential level of significance for men's and women's treatment outcomes and recoveries. This is especially true for co-occurring psychiatric disorders and histories of trauma, which disproportionately affect women and girls. Here's some interesting data. Yet, when we look across substance use treatment facilities that offer specifically tailored programs or groups by client type, 50% offer treatment for women, 52% co-occurring disorders, 42% trauma, only 28% offer any programming for sexual abuse, 28% for intimate partner violence, 24% for pregnancy. Even though we just talked about all these things that affect women and girls, look how low it is in terms of the proportion of what is offered in our treatment programs. So, moving into the women's recovery group portion of this talk, what we recognized quite a long time ago is that most women were going to receive treatment in mixed gender substance use treatment programs, and we recognized that there was a need for treatment that would be gender responsive for women with substance use disorders based on all this stuff that I just talked to you about. And so, we embarked on a program of research to develop an evidence-based group therapy designed for women with substance use disorders who are heterogeneous with respect to their substance disorder, meaning alcohol or drug or other, their co-occurring other psychiatric disorders, their trauma histories, meaning they have a trauma history or they don't, their partner and parenting status, meaning they do have kids, they don't have kids, they have a partner, they don't have a partner, their life stage, young adults, middle adults, older adults. So, that was the impetus for the women's recovery group study. And so, the women's recovery group, which I'm going to be telling you now much more about, was developed and tested in NIH NIDA-funded stage 1 and stage 2 psychotherapy development trials using what we call mixed methods, meaning quantitative and qualitative data outcomes. It's a 90-minute, 12-session, relapse prevention, skills-based group therapy. It's designed for women, heterogeneous, with respect to their substance use, alcohol and drugs, their co-occurring psychiatric disorders, and trauma histories, just as I said. The WRG has women-focused content and an all-women's group composition. It has structured sessions with a check-in, topic presentation, and open discussion, take-home messages, the assignment of a skill practice, and a checkout. I'm going to tell you more about that in a moment. And we have 14 topics that could either be all run, 14 in a row, which we do in real clinical practice, but for the purposes of our studies, we used 12 out of 14 for 12 sessions, and that those 12 sessions could be flexibly chosen. We've published quite a bit on the women's recovery group study. The stage 1 trial has 7 published peer-reviewed papers. The stage 2 trial has 5 published peer-reviewed papers. And then in 2016, we published the dissemination manual, which, what that really means is that we went from what was a research manual, research manual really was for the research trial, and it kind of came with me, you know, helping in the research study. The dissemination manual was published, it basically is meant to be like an off-the-shelf, you're a therapist, you can pluck this thing off the shelf, and you can actually use it and implement this group. There's quite a big difference between a dissemination manual that enables a therapist to actually implement this in real-world clinical practice than like a research manual where the developer is actually attending to it. In addition to this, it is disseminated now into clinical practice, and we've had like a number of adaptations to this. Justine Welsh, who's also a AAAP member, she actually adapted this to transitional-age women called the WRGYA. And then Barton and colleagues in the Puget Sound VA adapted this to women military vets. And that's also published, their outcomes. And then we've been working on a variety of research projects to develop this into some digital applications, and I'll tell you about that at the very end. So in a nutshell, what is the Women's Recovery Group? It's a professionally led, evidence-based, manualized treatment. It can accommodate women, typical and addiction treatment programs, who are heterogeneous, as I just explained, clinically and demographically. The content is gender responsive, based on the evidence on gender differences, much the same as the things I just presented to you. It has this all-women's group composition to enhance the affiliation amongst group members. The idea is to minimize differences amongst group members, maximize similarities, and therefore increase affiliative bonding. It's a skills-based relapse prevention group. It has a structured session, which means it has a check-in, it has a check-out, it has a topic presentation, and an open discussion. There are skills practices that are handed out, which people do in between sessions. It balances content presentation and open discussion in an interactive format. And then there are what we call four levels of participation, a group theme, a central recovery rule, and 14 session topics that I'm going to tell you more about. But first, I want to tell you about the hypothesis. So what was our hypothesis regarding the mechanism of action? Well, what we said based on the data, which was 20 years ago, that there was going to be an all-women's group composition, which the data told us would increase group cohesiveness and affiliation, increase an open discussion amongst women of triggers and relapse prevention, thereby increasing comfort and support. Because it was an all-women's group, it would enable us to focus on women-focused group content, the education about the antecedents and the consequences of substance use that differentially affects women. Again, in similar ways to what I've presented to you, and that these two elements would synergize to enhance outcomes for women in the women's recovery group. So again, the structure is it's 90 minutes. We start with a brief check-in. Then there's a review of a skill practice from the last week. And also, what did we do last week? What's our last week's topic? A presentation of this week's session topic done by the group leader in an interactive way, then an open discussion about any relapse prevention-related topic, an open discussion by the participants. Then at the end, there's a review of the session's take-home message and the upcoming week's skill practice, which is passed out, and then a checkout. So the 14 session topics, these in blue font are the ones that I consider gender-specific. We talk about the effect of drugs and alcohol on women's health, managing mood, anxiety, and eating problems without using substances, violence and abuse, getting help, women and their partners, the effect on the recovery process, women as caretakers, can you take care of yourself while taking care of others, women's use of substances through the life cycle, substance use in women's reproductive health, the issue of disclosure to tell or not to tell, this takes on the issue of stigma. And then these in the black font are what I sometimes think of as bread and butter issues in relapse prevention, but they're infused with women-focused content, and they include things like what are obstacles to seeking treatment and getting into recovery? How do you manage triggers in high-risk situations? Using self-help groups to help yourself. Can I have fun and not use drugs or alcohol? Coping with stress and achieving a balance in your life. So what do I mean by four levels of participation? Well, when we're onboarding people into this group, we tell them there are four levels of participation, and you need to titrate your participation to your comfort level. The first is to attend. We want you to attend the groups. Unless you're intoxicated at the time, please come. Reflective listening. Please listen to what others are saying reflectively and think about what they're talking about. Then speaking. Contribute to the conversation. And then do the skills practice between sessions. And what we mean about this is titrate to comfort is participate at the level that you can do. But what we say is if you can participate at all four of these levels, you are probably more likely to get the most from this. What we have sometimes seen with people who are very shy or very introverted, they may start with attendance, and as they get used to being in a group, they may they're listening the whole time, but they may graduate into speaking. They may already be doing these skills practices in between sessions. Sometimes we have people who are doing these three things, but they haven't quite caught on to doing this, and then they get to that a little later down the line. But we try to tell people if you can do each of these things, you're going to get more from the group. The theme of the group is recovery means taking care of yourself, and the central recovery rule is recovery equals relapse prevention plus repair work, and I'm going to say more about those things. So recovery means taking care of yourself. When we do this live prior to the pandemic, we would post that group theme in the room where people sat. We actually hand it out basically to people when we're doing these groups virtually, which we did move to doing a lot of these groups virtually during the pandemic. And what does it mean? It means paying attention to your triggers, your urges, your cravings, planning to avoid high-risk situations, etc. I won't read through this whole thing, but this theme of taking care of yourself, self-care, the therapist comes back to this all the time throughout all the group sessions. And then the central recovery rule again is that recovery equals relapse prevention plus repair work, and that the group actually focuses on both. What do we mean? Relapse prevention is identifying your triggers and your high-risk situations, planning to avoid high-risk situations, developing coping skills to deal with non-avoidable situations, trying to create as best as you can a trigger-free environment, getting treatment. All those things are in the relapse prevention area. And then repair work, we think of as repairing damaged relationships, damage to yourself, learning to enjoy your life without using substances. And what we say is that women's recovery group sessions include both relapse prevention and repair work. And we kind of think about it a little bit like some of them focus a little more on relapse prevention. Some of them focus a little more on repair work. Some of them have a little bit of elements of both, but the whole group treatment is really doing both of these things and addressing both of these things. So just once again, as a recap, here's what the structure looks like in kind of an approximation of how many minutes we spend, depends on how large a group it is. But like the structured check-in, I'm going to show you what that is in a second, is about 15 minutes long. We spend about five minutes saying, oh, how was the skill practice for each of you? Did you do it? You know, what was it like? Oh yeah. And we remember last week we talked about X topic. Today, we're going to talk about this topic. Then there's an interactive presentation of the topic. And then the therapist segues into a discussion of the session topic of that week. Then at the end of that, the therapist helps to segue into a wrap-up and summarizes what the discussion was about. Then there's a reading of take-home messages for each of the topics. And then there's a handout of the skills practice. And the therapist briefly describes, here's the skills practice. This is what we're going to, what it's about. And then there's a structured checkout. And again, everything is tried to be done in as interactive a way as possible. So let me just show you what a check-in looks like. When we did it live, we have like a laminated sheet that people would pass around on a virtual thing. You know, people have it in front of them. It's been handed out to them as a handout. It can also be displayed on a screen. And it's like about two to three minutes per member. The therapist has to manage this so that it doesn't exceed time. And if somebody starts to say much more than the two minutes, the therapist says, let's defer that to our open discussion time. But each member answers three questions in a structured way. Did you have any cravings or urges to use? Did you use or if not, how were you able to remain sober? Did you do the skills practice? If so, what did you find do or find helpful? Most people can actually answer these things in about two, two and a half minutes. And the structured checkout, it's a single question. Members go around the room and answer, what will you do in the coming week to support your recovery? Then the therapist concludes the session by thanking everyone and wishing everyone a good week and saying she looks forward to seeing them next week. All right. So now I'm going to take you through the data and show you some of the results of some of the studies we've published. So the stage one trial was really focused on developing the therapy itself. The therapy, the treatment was developed in several steps and then it was tested in a small pilot study. And what we saw is that number one, we could implement it feasibly. It was acceptable to patients and participants, and it had a high participant satisfaction. And what we saw in this very small stage one pilot study, which we randomized women to the all women's women's recovery group or to a mixed gender control group, which was an evidence-based treatment called group drug counseling, a mixed gender group that was meant to be like group counseling, no gender related content, just a lot of relapse prevention and highly effective had been used in multiple other kinds of clinical trials. So we randomized people to those two. And what we saw was that there were equivalent reductions in substance use during the 12 weeks that treatment was ongoing, but we got a signal on this that there were sustained improvements in substance use in the six months post-treatment phase that were greater amongst the women in the women's recovery group compared to the group drug counseling condition. And so it was a tiny trial, but it gave us the opportunity to move on to a larger trial. This one was published in 2007, and then the results from the larger trial were published in 2014. And what the stage two trial was, we had 156 participants, and the stage two trial was actually more of a stage two, stage three trial, meaning that it was both a stage two trial, larger, but also it was kind of an implementation trial. We basically did not get, didn't think we were going to get another bite at the apple here, and we wanted to make it so that if we had at least, if it was at least a non-inferiority, meaning it was equivalent, we wanted to make sure that it could be rolled out into real-world clinical practice. So we recruited 156 participants, 100 women, 56 men. We had two sites, one at McLean and one in Southeastern Mass and Fall River, two very different sites, a public clinic, you know, private non-profit. Women were randomized to the women's recovery group or to the standardized group drug counseling, and what we did was we wanted to be just like the way things are in any outpatient clinic, meaning open enrollment, rolling group, you know, groups just start and they roll, and people come in and out of the groups depending on when they're admitted into the outpatient clinic. We ran the groups in both sites for 24 months. They ran every week for 24 months with no stop in these two outpatient programs, and we asked would the outcomes of the WOG implemented in community-based practice be at least equivalent to the outcomes of the effective mixed-gender group drug counseling. We tried to have very few exclusion criteria. We wanted to make this as externally valid to the kinds of folks who come into the clinics, so you can see that on the AXIS-1, AXIS-2 based on DSM-IV at the time, you know, what we had were very high levels of major depressive disorder, generalized anxiety disorder, and PTSD, and also AXIS-2 disorders, and what we found in this larger trial was that all the women randomized to either the WOG or the GDC, everybody did better during the three months, and what we found was that people generally sustained their gains six months post. We didn't see a difference between the two groups, but we did demonstrate non-inferiority, meaning that you could have a gender-responsive component of care, and it would do at least as well as the mixed-gender effective group drug counseling, and so we concluded from the stage two trial that this was an effective group therapy for women who are heterogeneous with respect to all the characteristics I just mentioned to you, and that we could deliver it importantly in community treatment in a rolling group format as a gender-responsive component of mixed-gender treatment. So just to recap, in the stage one trial, we saw that during the six months post-treatment follow-up, the women in the women's recovery group demonstrated a pattern of continued reductions in their substance use six months after treatment, but the women in the mixed-gender group did not. I want you to hold that thought for a minute because I'm going to show you something really interesting in a sub-analysis from the stage two trial in a moment, because as I just mentioned, what we saw in the stage two trial was that when you put it into real-world community practice in the way that we were able to do for the study, it demonstrated comparable effectiveness to standard mixed-gender treatment, and that women in both conditions maintained their gain six months post-treatment, but I'm going to show you something really interesting about this in a couple of slides. So just hold that thought. I told you this was a mixed-method study, meaning that we did a lot of qualitative data analysis, and I want to show you some of that because it's very interesting. So we wanted to measure... So remember I showed you that hypothesis that we thought affiliation would potentially predict outcomes? So we actually looked at this question, does affiliation in group therapy for substance use disorders in the women's recovery group, does it matter whether the group is an all-women's or mixed-gender treatment? So the first study we wanted to see, is there a difference in affiliation amongst all-women's women's recovery group, mixed-gender group drug counseling? We asked, would there be greater affiliation among members as measured by verbal affiliative statements of empathy and support? We double-coded all group therapy tapes for eight categories of statements of empathy and support between the two groups, and we found that the number of affiliative statements of empathy and support made in the women's recovery group was 66% higher than was made in the mixed-gender group drug counseling condition. So we thought that was pretty interesting, that there was higher level of affiliation that we could tell by these mechanisms of verbal affiliative support. But what it didn't tell us was like, did that matter at all in terms of outcome? So we did this other study where we looked at whether or not in-session affiliation would predict women's substance use treatment outcomes. And this was a really interesting set of analyses my colleague Linda Valeri actually ran, recoded a lot of our data, and this very novel what she was able to do here. What she did was she measured the relationship for every single person, every woman who was in this study, and she measured the relationship between the frequency of the affiliative statements they were exposed to across all the groups they were in, and then the trajectory of their days of any substance use during the three months of treatment, and then six months post-treatment. What they found was that at the end of the treatment phase of three months, women who had experienced the highest level of verbal affiliative statements, greater than 65 affiliative statements on average, were found to have more reductions in substance use by about 1.75 days more than women who had the lowest level of affiliation. And interestingly, that effect persisted six months post-treatment and was moderated by the therapy group, meaning that the women enrolled in the single-gender women's recovery group benefited the most from higher levels of affiliative statements, especially six months post-treatment. So it's very interesting vis-a-vis our initial stage one trial. It also tells you something really important about group treatment. The more you could probably encourage any group therapy to have more affiliation and affiliative statements made on the part of the group members, the better off probably everybody is. But for women in particular, being in the single-gender women's recovery group in this study and being exposed to these higher levels of affiliation seemed to better predict six months post-treatment outcome. So now we want to tell you a little bit about another set of qualitative data analysis that we did, looking at people's experiences in single-gender versus mixed-gender substance abuse group therapy. So for the stage one trial, we did these semi-structured interviews. We completed these with 28 women enrolled. These interviews were transcribed, encoded, and now analyzed for themes. And we found that the women in the women's recovery group said that they focused on gender-relevant topics supporting their recovery compared to the women who are in the mixed-gender condition. The women in the women's recovery group more frequently endorsed feeling safe, embracing all aspects of themselves, having their needs met, and feeling intimacy, empathy, and honesty. We did the same thing for the larger trial, the women's recovery group, and we exit-interviewed as many people as we possibly could. But in this case, we had more women and we could exit-interview both women and men. And we could analyze women's and men's experiences in group therapy and then analyze that. And we had some interesting findings, I thought. We did a thematic analysis from the stage two trial for 77 women and 38 men. Again, we saw that the women in the group drug counseling condition rated the group gender composition as significantly less helpful to them than the women in the women's recovery group. And again, just like replicating the stage one trial, the women in the women's recovery group endorsed more feelings of safety, support, being themselves, opening up about important issues such as trauma, abuse, and important issues and relationships in their lives compared to the women in the mixed-gender condition. More of the men endorsed the benefit of mixed-gender groups than did the women. Interestingly, both women and men endorsed feelings of guilt and shame related to their substance use disorder, but only women discussed societal stigma and judgment, and that there's a harsher attitude toward women, especially in their roles as women and mothers. So, I want to just give you some of this qualitative feedback in the women's own words. I'm going to just read through some of these comments. So, from the stage one trial, one woman said, a lot of the information that was presented to me, I was very unaware of, in particular, women's health, what alcohol does to a woman's body. The education end of it was huge for me, really huge to the point that I was sharing it with my family and friends. I think the fact that it's all female, the fact that it's run by a female are essential because nobody ever talks about the issues being related to being a female, being a caretaker, being a single mom, or being a career person in a man's world. In the stage two trial, a woman said, I didn't think it would make a difference to me, but it really did. I just feel a little more open with women. Another said, surprisingly, I like the fact that it was all women. Remember, everybody was randomized. They had no choice. So, some people were not necessarily endorsing that they wanted to be in an all women's group. This woman said, talking about different struggles that are gender specific, I think would not have happened in a mixed gender group. It would have been more about the alcohol itself, less about the reasons why. I think it's easier to be frank and more open than I would be in a mixed group. The past, physical abuse, I wouldn't talk about those things in a mixed group. Another person said, I think there's a difference in the male-female experiences with addiction. There are different reasons, different circumstances, and psychologically different needs that men and women have. I think women support each other. We listen. It's a safer place to be to just have all women. And another said, I think it's a societal perception that women who drink are just bad sloppy people. Men who drink are out to have a good time. And another said, I think it's easier for women to get sucked down by their illness because it's more of a negative for women in society, the way we are looked at. So now I just want to move on and just show you a few slides about some new research we're doing on digital adaptations of the Women's Recovery Group. And this is being led by Dr. Dawn Sugarman, a research psychologist at McLean Hospital, whose program of research is to develop sustainable strategies for integrating gender-responsive components of care for women with substance use disorders. And what she's been working on is taking the psycho-ed components of the Women's Recovery Group and putting these into digital modules. I want to tell you about two studies that she's done. So first of all, this should look familiar to you about the Women's Recovery Group and what the digital applications are, is to focus on the women-focused group content and to develop modules that are relevant for women with substance use disorders. The first study that Dr. Sugarman did was to adapt five of the topics of the Women's Recovery Group to a web-based format. And this was published in the Journal of Women's Health in 2020. And these are the five modules that Dr. Sugarman adapted. And in a pilot phase, she tested three of these with 30 women who were in a mixed-gender inpatient setting. And then in the pilot phase, she utilized five of these modules for 60 people who are in mixed-gender inpatient, outpatient, and partial, multiple levels of care. These women, again, had multiple co-occurring other psychiatric disorders, as shown here. The inpatient digital adaptation interface is much better now. So what I'm showing you is a very rudimentary old interface, but I just wanted you to take a look at this. What happens is a person has a web-based program that's displayed on any mobile device, like an iPad, for example. And when they click onto it, it looks something like, and the screen is much better now, but welcome for this topic you're going to learn about, X, Y, and Z. Have you or someone you know ever struggled with a mood, anxiety, or eating problem, et cetera? And as I said, the interface is way better now because we've been working on it for a while. The results of this study were very encouraging. With the pilot study, the whole five modules took an average of just 41 minutes on an iPad, and people rated it as easy to use, visually appealing, and that the gender-specific information was helpful. So it indicated a high level of satisfaction, and importantly, the result did not differ by the level of care, inpatient, partial, or outpatient. So it's a 40-minute module that you're sitting in a busy inpatient service, or you're in an outpatient department. You've got an iPad, 40 minutes, and you're going through these five topics, and the women rated that the most relevant to the recovery was the link between substance use problems, other mental health problems, especially depression, especially anxiety, and the effects of substance use on self-care. Qualitatively, and I think you'll recognize, it's very similar to the in-person group. Just learning all of this information is crucial for all women. I was unaware of a lot of it. I feel like the survey was right on and explained my problem as a woman with addiction to the T. It's really helpful to see the information in this way. In groups, it's great to be able to discuss these things with other people, but it's easy to miss something. So having it all laid out on an iPad like this was really helpful to remember everything and also see it visually appealing. So finally, the last study was one that Dr. Sugarman did for young women who might have substance problems who were receiving care at McLean for another co-occurring disorder. In other words, they were coming into the hospital for residential inpatient care for a mood problem, PTSD, an eating disorder, an anxiety problem, or some mix of those. These young women did not necessarily identify with having a substance problem, but their clinicians referred them because the clinicians thought that maybe they could benefit. And so Dr. Sugarman first interviewed 15 women, 18 to 25, and their primary diagnoses were depression, anxiety, trauma, PTSD, eating disorders, and BPD. And what these women said, she showed them the modules as they were, and these young women said, you have to increase the interactivity, we need more coping skills practices, please add information on navigating peer relationships, and also we'd like some more information on menstrual cycle and its relationship to substance use and craving. So the modules were all modified according to these participants' suggestions. And then Dr. Sugarman administered this to 44 women in that age range. You can sort of see that they had, these were the different treatment foci that they had. And overall, most of the women, you know, getting up to a little more than 80% were either very satisfied or mostly satisfied with the program. But what was really interesting to us, in addition to that, was that in this like 45-minute intervention, when a lot of these folks didn't even identify with having a problem, from pre to post-intervention, the participants' ratings significantly increased in their interest in making changes to their substance use and their willingness to make changes to their substance use. And again, I just stress, a few of them thought they had a substance problem, many of them did not. And we just thought this was an interesting signal to be followed up in future studies. So I'm going to wrap up now. And first, I just want to say some guiding principles when you're evaluating women's substance use disorders. You all know to always ask about the full range of substances. I think it's also important, given the neglect women often have of their own bodies, is to consider making a referral for a full medical evaluation, including a reproductive health assessment. It's really important to think about assessing for the full range of co-occurring psychiatric disorders, given the high prevalence, and think through some of the potential motivators and rewards for substance use disorder treatment, according to some of the things I just kind of laid out for you. But also, importantly, some of the gender-specific potential obstacles for recovery for women, which can include partner alcohol and drug use, these co-occurring other psychiatric disorders, shame, but also stigma, and then family legal unemployment obstacles, which can be very high for women. I think also, given the high levels of intimate partner violence, domestic violence, doing a kind of safety risk for women to see if they are safe in their home environment, figuring out the best ways to understand whether there have been some past histories of trauma, and then considering how to help people around any risky behaviors that they might have for HIV and other sexually transmitted infections, which can be disproportionately high at this point, amongst women. So, when you are treating women with substance use disorders, please consider using women-focused and gender-responsive approaches. And what I mean by that is integrating the conceptual and empirical evidence of the things I just was talking to you about, about these gender differences and antecedents and consequences of addiction and the treatment process, especially considerations around the need to treat these other co-occurring psychiatric disorders and considerations around trauma exposure and all the associated physical and mental health needs that that can create. I think addressing the central role that relationships play in women's addiction and recovery, especially with children, with intimate partners, these things are very important in women's addiction processes and also in their recovery, and it may include providing appropriate and necessary adjunctive services. So, now I'm going to wrap up and conclude. So, what I hope you've gotten from this talk is that we've seen this narrowing gender gap and the prevalence of substance use disorders, where women born in the last five decades have lower rates of abstinence and higher rates of substance use. Women have a telescoping course of addiction. There are very important considerations by gender and race and ethnicity. Treatment outcomes we know can be enhanced by programs that can provide services and other programming specific to women's needs, like co-occurring disorders, trauma, child care. We also talked about the Women's Recovery Group, which is a manual-based, single-gender recovery group with women-focused content that can enhance treatment outcomes, and we know it can be integrated and delivered directly into community-based substance use treatment programs. I've also talked to you a little bit about the digital adaptations that are promising to extend gender-specific treatment to women with substance use disorders. And I just do want to mention that I had just a team of many, many, many, many people through the years. These are a lot of the co-investigators and consultants and group therapists and research study staff that helped, as well as the funding from NIDA. And these are some of my great, amazing people who have worked on this through the years. And with that, I'm actually going to stop sharing my screen, I think, and open this up. Great. Thank you so much, Dr. Greenfield. So much great kind of background and useful information, and also kind of the development of this very well-received and effective group model, which is great. So we have a couple of questions, and you're kind of on such a roll, I didn't jump in with some of these, figured we can come back to them. That's great. One was just kind of going all the way back to the beginning with some of the data on gender differences. I think one of the learners wanted just clarification on women in the age group, whether it was 14% of the women having a cannabis use disorder, or maybe that was the percentage of women who had used cannabis have a use disorder. I think it's actually amongst those with an illicit use disorder, 14.8% of them had a cannabis use disorder. Got it. Okay. I'll be happy to maybe open it up. I'm scanning it. I'm just gonna say one other housekeeping item. Please feel free to raise your hand if you'd like to ask the question, and we can have you ask the question that way as well as put it in the question and answer box. Can I just, just one clarification. I'm sorry about that when I said ED. ED is eating disorders. So that's what ED meant in that slide. I think somebody asked me that. I'm sorry not to have seen that. It's mood anxiety and eating disorders. So sorry about that. So I just want to clarify that. And do you want me to, people could ask these out loud or I could just repeat that question. And then like, you know, somebody asked how about recovery time for women? Do you think, is there any gender-based differences? That's such an interesting question. And I don't know if the person who asked it is still online. I'm kind of curious if they don't mind unmuting themselves to, yeah, hi, how are you? How are you? I'm good, how are you? Good. Could you just explain, it would be great for me if you could just tell me just a little bit more about your thinking about that question. So I make sure that I'm trying to answer it in the, you know, in the best possible way. Yeah, so like you, when you were explaining your presentation that what we understand that, you know, now because of a lot of opioid use and other substances, we see not much difference in gender bias, right? So how about the recovery pattern for especially for women? Do you see any difference in recovery time period for women compared to men? That's such a fantastic question. And I'll tell you how I'm gonna answer that because I don't know that, I don't know that we've seen, here's what I would say about it. I think when we see people get into treatment, so for example, for opioid use disorder, when we see people be able to access, let's say medications for opioid use disorder and be, you know, adequately treated for opioid use disorder with medications, I actually don't think there have been, we have not seen gender differences in their recovery. What we have seen are differences in people's ability to access that care. And that's especially been true for pregnant and parenting women with opioid use disorder. So I think the way I would answer that based on the data that I'm aware of is that it's sometimes the access issue, getting two medications for opioid use disorder and getting on them that can be differentiated by a whole host of factors, one of which can be gender and can be pregnancy, can be pregnant, a parenting status. But once people are on them, the data doesn't show that there's gender differences in their, you know, overarching recovery or outcomes. So that's the way I can answer that question. I'm not sure I would be able to parse it any further than that based on the studies and the data. Does that help answer? Yeah, thank you so much. Thank you. Yeah, thank you for the question. That's a great question. Thank you. And then someone asked me, is there any data on differences in rates of severity of complication of alcohol withdrawal between men and women? That's a great question too. I don't know if this, if you're still on, do you wanna, would you like to like unmute yourself and just tell me specifically? Yeah, I'll give permission as well, yeah. Yeah. Yeah, hi there. Hi, I was thinking about what you had mentioned earlier in the lecture about the rates of absorption of alcohol in men versus women. And I'm working towards using more of a like benzo sparing protocol, but I'm wondering if I should actually be accounting more for those, you know, the differences between men and women and how they're digesting alcohol and being a little more conservative in women and making sure that they're safe through this process. That is a fantastic question. It's a really good question. I'm just trying to think about data that I've seen about differences in, you know, I'm just not even sure that's really good data on that, what you're asking, you know, in terms of like withdrawal protocols and whether or not they have been analyzed. You remember the very beginning of my slide about playing catch up on these things about gender differences and, you know, I'm not really sure that the studies that have really looked at that have actually published data to say whether or not those things have been different in terms of withdrawal outcomes and withdrawal protocol outcomes based on gender. I'm not really sure we have a great database about that. So I think actually, I mean, if Chris or David has any other information that I'm not thinking about, I'd love to hear it, but I am not remembering or recalling. So what I would say to you is, I think that's a really good question. If you have any appetite for studying that question, I would encourage you to do that because I think even if you publish a case series, you'd probably be contributing to literature, but I think your concerns are very well taken actually. And I actually will keep an eye out for that. I will tell you that we just did an article on access to treatment, engagement in treatment for women with alcohol use disorders, looking at very recent literature. And I didn't see anything about withdrawal protocols in that literature. What we did find though, is that not shockingly, in general, women were often not screened as frequently as were men, and nor were they offered treatment as frequently as men across the studies that we could find. So there's a huge gap in the literature here in something that we think we know a lot about already. So thank you, Hilary, for the question, and I'm sorry I can't do a better job in answering it, but I think your approach of being like thoughtful about making sure that women are really covered well is a good one. Yeah, I'm not aware of any specific data on that. I can say anecdotally that I have seen more complicated withdrawals in the women that I'm treating for withdrawal management. But also to piggyback off that question, something that I had, was when we're talking about the telescoping phenomenon, you had mentioned some physiologic reasons why it can happen from a physiologic standpoint, but do you think that there might be a psychological or neurobiological component to the telescoping phenomenon for women? Well, one thing, so just on the physiology, the thing that I didn't really mention, because it's less well-studied, but it's one of these things that, it's one of these things that, you know, people talk a fair amount about is sort of the estrogenic component of the telescoping course and how alcohol and estrogen actually interact with each other. We actually just took a look at that literature, and I'll tell you that literature is one big mess and doesn't really help that much, but it is another part of this story that it's not that well worked out in terms of the telescoping course. So that's just part one. I talked a lot about the alcohol dehydrogenase story and the body composition story in terms of adipose and total body water, because those things are kind of really been just there, they're out there, it's pretty clear. Estrogen story is still murkier. Now you're talking about neurobiology, you know, in terms of, I'm thinking that you're thinking about like sort of like the effect of alcohol in the brain in terms of neurobiologic circuitry. I think- Like, is there different activity in the amount of dopamine that's released that creates the dysfunctional pathways? I don't think that, you know, I was curious to know if, or could there be psychological contributions as well? So I don't think there's psychological contributions to the telescoping part of this. I think there's a lot of socio, I mean, one thing I didn't show you, there's a lot of sociocultural environmental influences right now on why there is a huge uptick in the United States on alcohol intake, binge drinking, you know, and alcohol related consequences for women and girls. We can talk about that for a moment. So I think in terms of how women get started, the quantities that women are actually drinking, that is, there's a lot of sociocultural dimensions there and probably psychological dimensions as well in terms of some women, like men too, you know, may have co-occurring other anxiety, depression related problems who may be using that, using it to cope with stress, et cetera. So that's that part of it. In terms of like the telescoping course, that's a really interesting question. You know, there is some data that would show that, you know, for cocaine, for example, you know, Regina Sinha has done a fair amount of work on cocaine and stress responsivity amongst people who develop cocaine use disorder and that there are big differences by sex differences and stress responsivity. And they actually have hypothesized that some of that actually is related to the course, you know, that men and women may experience in terms of sex differences. I have not seen that work replicated with alcohol, but I would imagine that it would not be surprising if there are some differences there, you know, in terms of stress responsivity for those who have kind of passed across the threshold where they're already have developed, you know, an alcohol use disorder. So that is possible. You know, what is seen is like a kind of almost like a lowering of a stress responsive threshold with cocaine use disorder may very well be the same in alcohol use disorder and therefore hypothesized increase in use. So that is possible. And I think that, you know, this is really, these are really fruitful areas for additional kinds of research, you know, the things that, as I said, that are the best worked out are the alcohol dehydrogenase story, the body composition story, something around estradiol and interactivity between alcohol and estrogen. But your point about what are the neurobiologic correlates here that could actually be facilitated? I think it's a great, great set of questions. I do want to say this one other thing because I didn't show you these slides, but we have seen just a very, very intense increase in direct marketing of alcohol related beverages to women in the last 15 to 20 years. And year over year, the numbers of products, beverage products that are basically, you know, all targeting and focused on women has been very, very high in year over year as every year of that increases, we have actually seen an increase in women's drinking and also women's binge drinking over time. So the CDC was already like putting out in 2010, like alerts that they were worried about this as a rising rates and epidemic in women. It's only increased. And I have my colleague Dawn Sugarman and I, we have like a lot of these slides which would just blow your mind about these products and the marketing toward women. And, you know, marketing is pretty, marketing is a reflection of social changes, but it also can drive social changes as you know. And we saw this with tobacco in the United States in the 20th century. And I believe we are seeing this with drinking and women in the 21st. So I know that's not exact answer to your question, but there you have it. I think I have some more questions. Bruxadi, yeah. So yes, there are some good, people are very excited about Bruxadi. And there are some, there is definitely some work that's been done in the MOMS trial right now with Bruxadi. This is one of the CTN trials. I think that people are very optimistic about Bruxadi because it just gives a little bit more of an opportunity for, you know, the periodicity of using injectables, you know, weekly to monthly. And so I think we're pretty optimistic actually about Bruxadi in general for pregnant women with opioid use disorder, but in general for opioid use disorder more. It just, it's another excellent possible tool now and treatment for people with opioid use disorder, inclusive of women and pregnant women with opioid use disorder. I think there's also, let me see. Opioid and polycystic ovary withdrawal is somewhat more difficult for women than men and alcoholism may be fairly similar between women and men. You know, I love this, I do love this train of thought here in the chat, you know, about clinicians who are scared to treat pregnant patients with MOUD that can limit access. I think that's a very good point that's being made here by Dave. I think we're really hopeful that the MOMS trial, which is, so the MOMS trial just, so you know that there are these, there was the MOTHER trial, now there's the MOMS trial. You know, the MOTHER trial was the one that Andre Jones led, which was the multi-cycle clinical trial, and the point of that trial was to show that you could use buprenorphine as well as methadone to treat pregnant women with opioid use disorder. And what they were mostly focused on in the MOTHER trial was to show what the neonatal outcome would be, right? So they were looking at days in the hospital and they were looking at, you know, NOWS, you know, neonatal opioid withdrawal syndrome. And what they showed in the MOTHER trial, that's a New England Journal article, I think in 2010, was that the babies, when they were born, they had a, you know, a shorter time, you know, in the NICUs when they were given buprenorphine. And there was the first of its kind. Now the national, the NIDA clinical trials network is doing the MOMS trial. The MOMS trial is a multi-cycle clinical trial. And what's really interesting about this trial, which I think it's going to be fantastic in terms of the information that we get, is it's a first of its kind. It's for pregnant women with opioid use disorder. It's randomized to two different preparations, sublingual buprenorphine versus injectable buprenorphine. It's to look at, you know, the way that it's all metabolized but it also for pregnant women. But the very innovative thing with protocol is that it's going to look at moms and babies outcomes going forward for 12 to 24 months. It's very rare, number one, for any randomized clinical trial to look at both maternal and neonatal and child outcomes. And there's never been a study that's gone out 12 to 24 months for moms and babies, believe it or not. It's because it's expensive to do. So there's going to be a tremendous amount of great data. And I'm really hoping that it helps with what you've just said about people, you know, people being worried about treating women. And that's why I wanted to show you that downloadable thing from SAMHSA I showed you on the slide, plus Connie Gill and Andre Jones, their guide to, you know, talking to patients about medications for opioid use disorder, pregnant women. It's great guide and very helpful for people who want to have those conversations. Then regarding all I'm going to say about the very amazingly excellent points all the way through here about withdrawal protocols and males and females, I would just say that, you know, we all have sort of some anecdotal experience here. I think this is, again, you're raising a topic that would be very worth some research. I mean, it would be really worth whether you do a case series or just want to encourage all of you who are here, you fellows, you know, this is like great. You know, you've just raised areas where there was a gap in our knowledge. This is right for do a scoping review, do a systematic review, you know, or think about taking on a case series or doing something a little bit more systematic to study these things. Because I think, you know, we could use a little bit more data actually so that when these questions get asked, we have something to say, you know, that's a little bit more evidence-based, even though we can put our heads together and talk about what we've actually seen in our own practices, which is always good when we're trying to help each other clinically, but it helps the field a lot if we can produce some additional data. And I'll just say one other thing I need to conclude. Part of the reason that I actually developed the Women's Recovery Group was that I was doing gender differences work in outcomes, treatment outcomes for men and women, which at the time in the early 2000s, there wasn't any data, believe it or not. And as I started presenting some of that, people started asking me questions. Well, what about gender-specific treatment for women? And I kept saying, well, there isn't any data about that. There isn't any data about that. There isn't any data about that. And by the time I'd said it for the 10th time, I thought, oh, I should do a study. And that's actually how I got started with the Women's Recovery Group. It was like noticing a data gap and trying to produce something that would help us figure out those things. And I think that that's, when you're seeing these clinical gaps where there's something not known, it's a great opportunity to try to study it in whatever ways you have available to you. Well, thank you again, Dr. Greenfield. I feel smarter for having been a part in this session. So I'm grateful for that. And thank you everybody for your attention. And just as a reminder, next month, we have Stephen Hayes talking about ACT. Good talk. Thanks again, Dr. Greenfield. Thanks everyone for joining. Thanks for inviting me. I appreciate it. Thanks a lot. Good night.

Dr. Shelly Greenfield

Dr. John F. Kelly

Women's Recovery Group

WRG

gender-responsive treatment

substance use disorders

relapse prevention group therapy

gender-specific factors

trauma

co-occurring disorders

gender-responsive approaches

digital adaptations