Nolan Williams, MD | Mental Healthcare Innovations Summit 2023

Nolan Williams, MD | Mental Healthcare Innovations Summit 2023

thanks for having me appreciate the intro um can everybody hear me is there a doctor in the house all right um all right so hopefully there’s I think there’s probably at least one or two physicians in here um and so you all know that if I start having chest pain up here on stage right you’re going to have a certain number of tests alth The Limited and treatments although very limited that you can provide to me right here on stage right but what are you going to really do you’re going to call 911 and you’re going to get me to the emergency room right where there are going to be more tests and more treatments right they’re going to be able to you may be able to check my pulse here you may have some aspirin but when you get uh get me to the emergency room they’re going to have an EKG machine they’re going to have a cardiac CT and if I’m in if I’m truly having a heart attack then they’re gonna they’re not going to discharge me from the ER they’re going to admit me to the ICU where I’m going to get more tests and treatments right like that’s that’s how um you know most of medicine works right so they’re going to bring me up to the cath lab or they’re going to pull the clot out they’re going to stent stin that uh artery or whatever whatever the problem ends up being but in Psychiatry it’s different right how does it go in psychiatry so in Psychiatry the patient comes into the outpatient uh psychiatrist’s office and says I’ve been thinking about ending my life I’ve been researching uh ways to do it right and so what does the psychiatrist do politely steps out of the room calls the police the police come they uh handcuff uh the patient put them in the back of a squad car and drive them to the emergency room where once they they too get to that emergency room and then they’re strip searched and placed in a hall bed waiting for um a psych uh bed you a psych unit right and then when they get up there they’re told we don’t have any additional treatments for you beyond what was available as an outpatient and they’re told also they have to go in front of a judge and uh plea their case of why they want to leave the hospital earlier and that they’re safe to leave and then the patient realizes that they’re stuck in the psych unit and unlike the rest of medicine in Psychiatry as you escalate the Acuity of care you on average and there you know I can we can get into details but on average you lose treatment options and there are no tests right everybody on the same page with that one and what’s even more striking is that your suicide risk at discharges triple what it was um for the rest of your life life right so the highest risk period for a mood disorder patient is after the first admission to the psych unit and so we’ve been very interested in trying to challenge that problem right and solve that problem and that’s the problem of matching the Acuity level of the problem with a treatment that can work in the same time scale right which is very different than how we have been dealing with psychiatric illness mental health struggles right we have largely thought about uh treatments that work over the course of months right to get well and so you know we’ve been trying to challenge that um that particular issue and the first way that we’ve done it I came up here a little bit earlier trying to make sure this video would work so I think we’re going to get it to work is with neuromodulation and so we’ve been very interested in this idea of being able to do personalized Network mapping of uh Network nodes that are involved with mood regulation in this case the dors lateral prefrontal cortex and its inhibitory connection to an area called the subgenual anterior singulate cortex and so um TMS transcranial magnetic stimulation has been around for some time since the 90s is an experimental therapeutic but in the 90s when this was developed it was developed using ruler measurements that provided average skull positions right so you’re stimulating in the same skull spot in everybody but you’re stimulating in a different brain spot in each person because you’re not personalizing based off of their brain Network Anatomy you’re personalizing based off of their skull position and in many cases you’re going to miss the stimulation Target because you’re effectively doing it blindly does that make sense and so that’s the way that this has been done uh over the last 20 years it’s like signing up for heart surgery with an average chest circumference how many of you would want to do that right and so what we um have looked at is this idea that each network uh Topography is different in each patient and so can we Network map each patient and then have a personalized brain based uh Target for stimulation in each patient and in that case we can use in this case a TMS coil to engage the Target and we do that using Faraday’s law right this idea that if you induce current in electrically conducting substances you can uh I’m sorry if you pulse magnets in electrically conducting substances you can induce current and like moris code we can do it with a signal that can be interpreted by the receiver in this case it’s the brain with the hippocampal slice physiology patterning that is the memory signal of the brain we can do that um over very short periods of time and have developed something we we called San or Stanford accelerated intelligent neur modulation therapy that’s able to apply an entire six week course of uh conventional uh TMs over a single day so we personalize the position in the brain and then we’re able to apply um stimulation based off of the Native rhythms of the brain and we do it based off of something called space learning theory how many of you used uh note cards to study in college right you write out about 60 of them and then look at them over and over again right that’s actually space learning theory right so we can actually emulate that with an external stimulator and turn that brain region back on and kind of retrain it to learn how to keep that brain region on and so we’re able to utilize learning principles and then exogenously send signals into the brain to be able to get the brain out of these um these high-risk States and so we’re able to in this case as I said earlier apply six weeks of stimulation in a single day or in the case of what we’ve um you know what we’ve done is a clinical protocol applied five times that so we’re able to give large amounts of stimulation over very short periods of time and that’s actually the sort of time period that we’re working off of for an impatient psychiatric admission the average length of stay is about 7.4 days so if we can get people well a day to get in give them a day to leave 5 days and we can get folks well um that’s uh that’s very effective as a um as a solution to a problem that you can then discharge the patient out to and it deals with a lot of the health economics issues that uh that folks have largely had to um to deal with as far as long like this day for patients that are mental health patients in a psych unit and so with that we were able to um achieve remission rates that were strikingly high higher than conventional uh stimulation approaches uh this led to FDA clearance this led to sorry breakthrough it led to breakthrough status FDA clearance and then um it will be paid for um by Medicare in 2024 on psych units so um most of that data uh came out of the work that we did here at Stanford and um from philanthropists that supported uh the research so um you know folks can’t have real impact in these problems uh from giving which is great um I don’t know why this thing doesn’t want to advance my slides let’s see there we go okay um next part of the T so I was going to give some uh give a talk on some of our um psychedelic data but it’s under embargo uh with a journal uh and I’m not not so interested in making them upset so if there any journalists in the room this is under embargo can we agree to not not uh publish this all right great um great so we’ve been very interested in in uh a phenomenon that’s been going on for the last five years where veterans have been leaving the United States and going out to other countries particularly to Mexico to take psychedelics for mental health struggles um and in the case of special um operations veterans so Army Rangers Navy Seals those sorts of um Fighters that those groups have actually gone to to Mexico to take um ibigan which is a um root bark extract of an African tree from the um Central West African country of gaban um it’s an obscure psychedelic it’s not a it’s not a party drug it’s something that’s used um as a Sacrament in those countries and these folks would go down to to Mexico and come back and you know when when I talk to them tell me that they had um had a dramatic Improvement in their symptomatology um the buti which your buiti and Gabon if you’ve you’ve taken I you know iboga rotar that group would take this as a Sacrament group for group cohesion for for various symptoms and uh it’s been going on for centuries and that’s these are the the buti taking uh the root bark and what’s interesting is is that they describe as do the veterans describe this psychological phenomenon where they have these autobiographical replaying of earlier life memories where they see traumatic events they’re able to see it from a third-party perspective play that information back and forth and be able to um re-evaluate that information like they’re a third- party um you know participant in this they’re not they’re not experiencing it as self uh which which I thought was really interesting and the first thing that popped into my mind if uh as a you know as a a a uh child of the 90s or whatever is this Minority Report movie where Tom Cruz was able to to see the same sort of thing right you can play back and forth um you know past memories and have some some level of control over them and this is what uh most of our veterans describe they were able to see their trauma again this is what the buti um describe and so you know we were tasked to um evaluate uh a number of symptoms um related to uh you know you War trauma um and uh we didn’t know exactly why these guys were going down there so we did this very broad look at why folks were going down to Mexico so we looked at PTSD scores which you can see a range uh looked at depression scores anxiety scores and we were quite surprised at what we saw which was very dramatic improvements in PTSD and for a lot of folks they were able to hold it out to the month um you know so so really striking I actually told my postto to delete the code and rerun this because I didn’t buy it the first time I saw it um anxiety improvements as well as well as depression score improvements so re really striking um you know after one dose of ibigin the um primary alkaloid of this iboga root bark and uh this is disability um scores from traumatic brain injury on the uh hudas which is the World Health Health Organization disability scale for traumatic brain injury um this is another way of looking at it and I added a few how how are we doing on time I can do a few more we’re good okay um this is moral injury so folks who are um who did something that they you know kind of had to do accidentally did on the battlefield they don’t necessarily um you know have a hard time kind of dealing with like they accidentally left their bodyy on the battlefield they accidentally shot a civilian instead of the enemy and so reduction in those symptoms reduction in suicidal thinking um increases in executive functioning in key kind of executive functioning areas that are involved in kind of frontal circuitry like Flex cognitive flexibility cognitive inhibition processing speed we saw volume increases in key emotion regulation areas like the left insula the frontal pole as well as white matter volume whole brain white matter volume increases um what’s interesting some one of my posts get really interested in this idea of accelerated uh brain aging and the idea of this machine learning algorithm that can you know get your brain age right um and so um not everybody’s brain age and their chronological age is the same but um the machine learning algorithm has been trained to on hundreds of thousands of brains so it’s able to basically get a good sense of of that brain age um we saw a reduction in um overall brain age at the one month Mark which is interesting you know we fed some of our sham TMS data into this with the same time points there was like no change um so we’re going to look into that as well as uh increases in cerebral blood flow and key emotion regulation areas I talked about earlier the insula amigdala singulate and some of those blood flow changes were correlated with improvements in the disability score particularly the insula which is an interoceptive organ it’s um related to uh to kind of sensing your body in 3D space uh and that was uh even the subscales were correlated uh as well as uh changes in brain connectivity so how the brain is connected uh to itself um so yeah so we’re we’re really interested in trying to you know work on and develop and find Rapid acting treatments for neuros psychiatric illness um we’re trying to solve some of these problems of how do you how do you have a a treatment that matches the Acuity level and um you know appreciate the ability to share uh some of this with you so thank you thanks for the great talk um couple questions actually um so TMS has been around uh since the 80s I think um and uh so I just wanted to ask you a broader question about like why it’s not more common in terms of like why it’s not is it just an accessibility issue or you know it’s been shown to have benefits and a lot of other conditions as well um across a broad range and so there’s a lot of interest for me personally for using this but what do you think is kind of held TMS back in sort of the broad scale um that’s question one uh and then I guess I’ll start there great yeah and thanks for that question it’s a good one um a lot of people have asked that question over time so um one issue is um how many of you would feel comfortable telling your boss that you need to take the next six weeks off or more take an hour and a half or two hours out of work and drive somewhere and do this and come back and Bank hours you know and so that’s the first one is the the timing of it right it’s you basically have to if you’re a working person you basically have to have that conver most people have to have that conversation with their uh with their boss right and so um that’s tricky um the second one is the number needed to treat so with conventional TMS the number needed to treat to remission is about six and so um you know the the odds of of getting to kind of full resolution of symptoms is um is not as good as kind of what we’re seeing with these more um you know matured uh technologies that we’ve been working on um and then uh and then it’s really a it’s kind of a conceptualization of mental illness problem right I think this year and the last year um there’s been a shift away from this kind of idea of chemical imbalance and kind of the frame that um had been set for what is the issue to uh an open question right with with some of us thinking about this um as a circuitry problem um and uh and I think that’s like all-encompassing right I think there’s lots of reasons why everybody here um can think about it as a circuitry problem even if your conceptualization is metabolic or diet or whatever it all ultimately goes into these brain circuits and um you know I think that as we shift into that concept new conceptualization this goes from being kind of weird and off like what is this doing like mixing the the chemical imbalance around I mean like people don’t have like a way of kind of thinking about it to oh we’re engaging a brain circuit that’s having an issue that’s having kind of a misfiring or kind of a Miss signaling problem right and if you can shift that thinking then it aligns more uh with with what the the treatment is and then more people are likely to do it and so you know my suspicion is that um by 2030 and the the data looks like this if you look at the Trends by 2030 there’ll be a lot more folks using TMS um and uh it’s just a matter of um of taking the time for for all those things to get sorted out finding a schedule that can you can get it done in a week without having to go um you know go and tell anybody you just take a vacation week and doing it and having you know greater efficacy and being able to um you know change the the the frame of why people think about what you know what they think about mental illness so thank you for that response would love to connect with you you more also about um how to sort of implement that as a primary care uh position and how to kind of refer afterwards um so my second question is um sort of about the description of ibugan and the effect sounds very similar to MDMA um which I’m more familiar with the literature on that or and I know that there’s plans or it sounds like there’s a chance that it’ll be legalized in 2024 uh from what I understand um how would you compare ibugan to MDMA in terms of of um side effect profile or just like overall efficacy things like that yeah no that’s a great question um so um with MDMA it’s MDMA assisted Psychotherapy that’s the data as you know that that’s out there and um and there’s not like an oblig you know with with I there’s almost this obligatory slideshow of effects that people end up encountering right where they they’re the the drug just for whatever reason seems to drive people into this phenomenon that’s really stereo yped across people with MDMA it’s more of a Psychotherapy um you know drug Psychotherapy kind of synergy effect and people will reencounter that trauma but the drug isn’t necessarily driving people into that experience every time right and so I think the difference is that with MDMA it’s an empathogen right so they’re having a almost a kind of a positive experience towards this with um with ibigan it’s uh it produces kind of a neutral state where you’re able to kind of kind of coldly look at it and be able to experience it and understand it without without your own context being brought in at least that’s the way that people have described it and that’s the studies of the phenomenology so far um you know there’s a cardiac risk to both of them part what I didn’t get into with um with what we were doing is we were actually giving people like cardioprotectant dose magnesium right before they were able to before they got the iban to kind of take take away some of the the risk of of inducing an arhythmia there’s there’s a uh arhythmia risk with MDMA although less than ibigan for sure um and so um you know both of those you’re going to have to have that in the back of your mind but um but yeah I you know I think MDMA is as a as a treatment that’s going to likely as you said get approved in hopefully in 2024 um is going to be important because it’s going to light the way for a lot of these other um these other you know meds to come these you know psychedelic sort of medications to come out and uh and be um go through the FDA process so yeah thanks incredible thank you so much appreciate it

Nolan Williams, MD, is an Associate Professor within the Department of Psychiatry and Behavioral Sciences and Director of the Stanford Brain Stimulation Lab. He has a broad background in clinical neuroscience and is triple board-certified in general neurology, general psychiatry, as well as behavioral neurology & neuropsychiatry. Themes of his work include examining the use of spaced learning theory in the application of neurostimulation techniques, development and mechanistic understanding of rapid-acting antidepressants, and identifying objective biomarkers that predict neuromodulation responses in treatment-resistant neuropsychiatric conditions. His work has resulted in an FDA clearance for the world’s first non-invasive, rapid-acting neuromodulation approach for treatment-resistant depression.

The Mental Healthcare Innovations Summit at Stanford Medicine brings together creators and action-oriented leaders across research, policy, government, funding, and mental health advocacy to build a cross-sector community and drive forward the powerful existing and emerging innovations in mental health to collectively reimagine what it is like to give and receive mental healthcare.

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