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A Therapeutic Trip: From Experience to Epigenome

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We are entering a new phase of understanding how our social environments affect our biology, particularly how they influence the genes involved in brain development and function. This knowledge helps us see how experiences like stress, trauma, and isolation can cause changes at the molecular level that may increase the risk of mental disorders. On the other hand, we’re also exploring how positive experiences induced by psychedelics, which create feelings of unity and insight, might lead to beneficial molecular changes.

Most mental health disorders, whether psychiatric, neurodevelopmental, or neurodegenerative, arise from both genetic and environmental factors. Recognizing this, research now combines studies of these exposures with molecular biology to better understand how our behaviors and environments can directly impact our genetic expression, shedding light on why some people are more vulnerable to mental health issues. This field, known as behavioral epigenetics, explores how our experiences can shape our genetic makeup and influence our brain health.

In this week’s episode of the Everything Epigenetics podcast, Dr. Candace Lewis shares her insights into epigenetics, discussing how early life stress can affect gene regulation and how attachment and societal influences shape our biology. The conversation then turns to psychedelics, with Candace outlining the history and ongoing research into their potential as a therapeutic tool for mental health disorders. She explains the mechanics of psychedelic-assisted therapy and the importance of understanding its broader context.

We then chat about the therapeutic possibilities of psychedelics and their role in epigenetics, and the importance of creating a safe environment for individuals to explore their emotions and experiences with psychedelics. Candace draws parallels between acute stress and the psychedelic state, suggesting that research into psychedelics could reveal important information about the epigenetic changes they induce. Lastly, Candace also mentions the Psychedelic Genome Project and the significance of collecting genetic and epigenetic data to advance the field.

Candace is currently the director of the BEAR Lab (Brain, Epigenetics, & Altered states Research) at Arizona State University aiming to acknowledge the harm caused by psychology and genetic sciences on minorly groups, increase diversity in training and study cohorts, and change policy to improve mental health for all.

In this podcast you’ll learn about:

– The Brain, Epigenetics, & Altered states Research (BEAR) lab
– Complex relationships between experiences that shape cognition, mood, and behavior
– How stress, trauma, and lack of connection may lead to molecular changes that increase risk for mental disorders.
– Candace’s editorial: What is up with psychedelics anyway?
– How epigenetics shed light on psychedelic therapy
– MDMA-assisted therapy
– DNA methylation of gene systems involved in addiction, cognition, stress, and immune function
– The glucocorticoid receptor gene (NR3C1)
– How DNA methylation is associated with MDMA-assisted therapy treatment response for severe PTSD
– The hypothalamic-Pituitary-Adrenal (HPA) Axis
– Similarities between the acute stress response and the psychedelic state
– The psychedelic Genome Project (PGP)

Transcript:

welcome to the everything epigenetics podcast where we discuss DNA regulation and the insights it can tell you about

your health I’m Hannah went and I’m the founder of everything epigenetics today

my guest is Dr Candace Lewis we have a very fun podcast for you

all today we really talk about Candace in the lab she runs called bear it

stands for brain epigenetics and altered state research at Arizona State University we really dive into what she

studies and talk about how this affects every aspect of life she not only looks

at everything at the cellular level but she also looks at everything at the physiological level and then the family

level and the societal level as well we talk about her editorial she wrote in 2023 called what is up with psychedelics

anyways we know that’s a new sexy hot topic nowadays we also talk about how genetics

sheds light on psychedelic therapy and we even break down one of her pilot

studies published in Frontiers in 2023 that suggest DNA methylation of the

glucocorticoid receptor Gene NR 3c1 is associated with MDMA assisted therapy

treatment response for severe PTSD we also talk about her psychedelic

Genome Project why it’s important and how you can get involved and we really

also discussed during the entirety of this call just all of the projects that she’s working on and what really excites

her we then end by talking about her research focusing more on social stress

exposures and how those experiences can shape Dynamic regulation of Gene systems

underlying cognitive emotional and Behavioral Health through development a little bit about my guest

today Dr Lewis grew up in rural Alaska where she was exposed to high rates of poverty mental illness violence and

addictions and those personal experiences that she went through really drove her commitment to revolutionize

mental health understanding treatment and even policy change to this end she earned a masters in counseling a PhD in

behavioral neuroscience and studied genomic science at a leading institution and studied psychedelic science at the

University of Zurich like I mentioned she’s at the be lab where she really focuses on three different things the

impact of early life social experiences on epigenetic regulation of Gene systems involved in mental health she even

studies the relationship between peripheral epigenetics and brain structure so function the microbiome

composition and even behavior and then number three which is my personal favorite as we dive into on the podcast

as well is the potential of psychedelic assisted therapy to reduce symptoms through psychological healing and

epigenetic alterations through her research she aims to to acknowledge the harm caused

by psychology and genetic Sciences on minority groups increasing diversity in training and study cohorts and really

pushing to change policy to improve health for all when not working Dr Lewis

enjoys family time with her three sons and wife going to festivals hiking running reading creative writing and

talking all things spirituality social justice and science now for my guest

Candace Lewis I hope you all enjoy welcome to the everything epigenetics

podcast Dr Lewis I’m so excited to have you here today thanks for being here of course I’m happy to be here yeah so

we’re just going to jump right into it you know you run the brain epigenetics and Altered States research lab or be

Lab at Arizona State University and this is the first time we’ve ever chatted I know I reached out to you via email to

to get you on here so I know just very little about your story and and how you got into this field besides what’s on

your your beautiful Lab website so us off and and tell me more about yourself how you ended up in the bear lab tell me

a little bit more on what that Journey looks like wow so much so many years um

okay so I did not grow up thinking I was going to be an academic or a scientist

um you know I thought which a lot of kids in the 90s did I don’t know if they still do the scientists were like old

white dudes wearing lab coats playing with green fluids um and it was in undergrad that I

realized that I really love school and I just was working really hard I was working full-time while trying while you

know getting straight A’s and um I happened to come across this Fellowship called The Truman Fellowship which I

decided to apply for not really knowing what it was and it turns out that it is a highly competitive national

scholarship to go to grad school um after an arduous application Pro um process I got it and it’s so funny

because during the interview process they said do you want to get a master’s or a PhD and I was like I don’t know the difference is because that’s how much I

not prepped to go to graduate school and it was in graduate school that I really

kind of was exposed to um the idea of studying stress and the idea of studying

early life stress and the idea that there’s this whole science around understanding um how it affects us at

the biological level we’ve known for a long time that behaviors are associated with early life stress right there a

really large predictor for most psychiatric disorders um PTSD depression anxiety disorders substance use

disorders and uh that really called to me because I grew up in a chaotic home where I was

in and out of foster care and um and I we were also you know we lived in deep

poverty and we were in rural Alaska so I saw a lot of this around me in a lot of different ways I mean Alaska is like has

some of the highest rates per capita for a lot of these disorders um so I was in a lab I was

studying stress I was like find myself now and I’m I’m an academic I’m a PhD and it was my first year as a grad

student that I learned about epigenetics and it was just kind of just coming onto

the scene you know um it was just getting really big the field was exploding with the idea that epigenetics

are not just static Regulators of cellular differentiation but that at at least

some parts of the epigenome it is it can be responsive to early life experiences

and by responsive you know I mean that like it’s going to change it’s going to adapt in that those regulatory changes

stay consistent or are longterm and in effect they change Gene

transcription which changes um everything about the cellular makeup of

the brain which then the brain is what’s regulating all physiology and behavior so I was just like this is amazing my

mind was blown I fell in love immediately and like this is it and at the time I was studying addiction um at

an animal model of addiction and I was like you know so early life stress influences drug and take beh avior in

rodents we know that um so instead of you know instead of staying in this cortisol stress reactivity depression

findings that the field was really focused on I decided to look at is early life stress influencing epigenetic

regulation in brain regions associated with um with addiction and so that was

my graduate work and it was it was great you know like we really we really showed this this causal pathway between early

life stress altering epigenetic regulation in the nucleus thatum core and that being associated with the

animals different um methamphetamine intake Behavior we were also able to reverse those epigenetic changes and

showed a decrease in drug andtake Behavior so that was like my background that’s what started it all and I’ve been

doing it ever since yeah thanks for the introduction that’s that’s quite a story that you know the application of really

how understanding how stress affects our our body is something I’m personally super passionate about as well I’m just

like a naturally stressed out person like super anxious all of the time and really understanding like what I can do

to actually reverse that so I want to ask you one more question before we move on you mentioned that in the the mice

you were you know measuring the eptic patterns and you actually saw a reversal in that stress um in in those patterns

too so what caused that reversal well unfortunately it was a research method not anything that we can apply to

ourselves in life it was an in it was a viral after injection yeah brain region

but I want to say I want to say though because I think it’s so important right because I I find myself in these types of conversations because I study how you

know maternal care and all these things and all the moms in the audience and I’m a mom too so I get it they’re just like

oh my God I’m messing up my kid I’m messing up their gentics I’m like no no no no I really think that it would

behoove us to understand this new incredibly complex beautiful thing about

our brains that it’s like molecularly adapting to our environment that it’s a good thing so the way that I like to

kind of explain that to people is you know if you’re born human or primate or rat you’re you know and you’re you’re a

pup you’re developing and you’re born into into an environment that has low maternal care low resources high stress

um it would make sense and it is highly adaptive for your brain to be like okay

this is this is this is what I got and I need to be hypervigilant and it modulate gene expression for you to be able to

fight for and seek your needs and hypervigilant is like another word that we call anxiety

today gotcha yeah yeah go ahead keep going I just think that you know I think that

sometimes it’s important to see that um we have you know our current Western model of medical of mental health we

have these disorders and then we all think about them a lot you know people say all the time oh I have OCD well they

don’t really have a diagnosis of OCD but they see themselves in that description and um and a lot of times

people get caught up and what does that mean about my brain what does that mean about my genetics and what does that mean about my children um and I think

it’s just so important to always bring it back even though I studi the biology that the disorder is just a list of

behaviors it’s a list of behaviors that you self-reported at a time and maybe at

that time they made a lot of sense you’re not biologically you know stuck

here to a certain degree right it’s all Spectrum me yeah yeah so yeah you’re saying you know you can e and flow in

and out of kind of these um I don’t know if you want to call them then you know diagnoses or you know time of how you

were feeling right in terms of of those outcomes because yeah I mean I can even reflect back on myself and say hey I

felt more anxious you know during this time because of these things or you know my environment my behavior my

surroundings and so I think what I’m interpreting from what you’re saying Candace is more you know you’re you’re

in control right it’s how you’re feeling and and different things can can trigger that again that environment or that

behavior and maybe it’s not necessarily always a negative feeling too there’s maybe some positive connotation behind

that yeah I mean I think you know I think control is a tricky word to use um um especially when we start bringing

systemic issues however I guess yes the idea is sometimes anxiety makes a lot of sense

for what life’s throwing at us and sometimes being really sad makes a lot of sense for what life’s throwing at

us and um yeah and I’m just really interested in that throughout the lifespan right our brain um our brain is

adapting to that yeah I like that I’m gonna have to sit on that more and like actually you know do a lot of like self-reflection so

thank you that’s a that’s a really good you know introduction to this entire podcast um I want to dig a little bit

more deeper though into exactly what you’re studying um so yeah if you want to give your own explanation of you know

what is the Bayer lab which is an awesome acronym and what exactly are you studying now what are you most passionate about so I think about my

research in um two kind of parallel lines I like to look at the things that

are affecting us early in life that may be predisposes towards these behaviors that we call psychiatric symptoms so um

okay so that’s the one track what are the things that are happening to us that are potentially altering epigenetics of

genes that are involved in things like mood and cognition and stress physiology

right and these are the underlying pillars of the psychiatric disorders additionally I’m interested in um if

we’re so susceptible to these um to these hard experiences to

these experiences that are telling us you’re not that safe then is there then what’s the inverse what are the

experiences that we can be having that say like you are safe um and our and

does our epigenome respond to those as well so in that sense um I also am

interested in looking at psychedelic therapies and the idea that potentially um in a very similar way in which our

body responds to these moments that are screaming like you’re not safe so you should be responding and altering is it

possible that psych different Psy compounds are inducing a similar type state where your body is responding and

be like okay I actually am safe I can I should be modifying to adapt to that new found um

experience so but one thing I want to unpack about that quickly is because the semantics right we uh we always get back

in the semantics so trauma people ask me this a lot well what do you think trauma

is and I think that you know we have the ace lists right those 10 things or like

the yes or no you know and the DSM is still pretty pretty hardcore clinging to the idea that there has to be like a

threat to safety um whether perceived or even witnessed of someone else however I

like there’s so much data showing that it doesn’t have to be this really really strong what we would call trauma to

shape us so like what I mean by that you know have a lot of people they go to therapy and they’re depressed and maybe

they’re anxious and maybe they have a substance use issue and they’re like nothing happen me nothing happened to me I had a great childhood my parents were

married we had resources I was on the basketball team and so it’s confusing for them because they can’t check the

trauma um lists however I think that there’s so much more going on with like

attachment attachment and safety and if you look through the attachment field and you look at the

like long-term associations with disorganized or non-safe attachment while you’re

younger they look a lot like the same effects trauma go and you’re just by that too

you’re just talking about like different attachment Styles is that correct just to clarify well um that one even gets

really tricky because like there’s the science of attachment Styles and then there’s this like fake pseudo parenting

theory that came out a long time ago it’s like never put your baby down so that word gets really tricky to use to

people too I’m using the word attachment because I’m because I want it to Encompass so much more of childhood

experiences than just trauma but it’s you know I think that probably there’s a lot more layers to it so like emotional

availability is something that comes up which you know could be nested under attachment but really it’s the perception it’s the childhood perception

am I loved am I safe what are the conditions that I have to meet to earn those

things and then I think how far that child has to deviate from their authentic self to meet those

conditions is a is a very um it’s a experience that is very shaping

throughout childhood so I think what kind of ends up happening with a lot of these people who can’t check the trauma

box is you dig deeper and you’re like okay um yeah maybe maybe I really felt

that Mom and Dad didn’t love me unless I got all a so no I’m not talking about trauma

like at that moment right we’re not call call that trauma but I’m interested in the whole gamut because there’s so much

literature out there showing that those experiences shape us too those experiences can their lie anxiety

you know yeah a lot of high performers this you know right now I think we are seeing a world of like

everyone you know in a certain age bracket it’s like I’m so anxious and like I really think that there’s this

like generational reason of you know the expectations that we put on them to

school work Sports manners absolutely I think like I I think I fall in that category um

absolutely and uh it’s it’s interesting too so yeah you’re doing a lot of cool stuff at the bear be lab you know you’re

interested in what’s like happening to us to affect these disorders the experiences we’re having um you know

showing us that if we’re safe or not and and we’re really going to dig into that on the podcast today but I like that you

also mentioned hey it doesn’t have to be trauma it can be this like attachment it can be trying to fill fulfill this image

or I really like how you put even deviating from your authentic self so um

you know I’m sure yeah trauma you can talk about it in in many different ways or other things have happened to you and

I don’t know that I’ve even ever shared this on my podcast before either but you know grandmother passed away from

Alzheimer’s that was a really large event that happened in my family and not necessarily even myself going through it

but seeing like my mom go through it right and seeing how she grieved you never want to see people you love being

upset and hurt um my dad passed away at a super young age unexpectedly from a cardiac related event right so those I

would say you know maybe they fit in that traumatic kind of category but also I did just feel the need to perform like

I got straight A I played you know five sports year round and not because my parents were like you know you need to

get straight A you need to get straight A’s but I did feel this like untalked about like pressure right um whether it

was like definitively stated or or not um and you know that could be the underlying reason I I’m obviously you

know gonna gonna dig into that a little bit deeper as well but I thought it was was an interesting piece thank you for sharing all of that right and I and I

think that your example it so shines a light on why this is hard not a list of

10 things we can check yes to like you said maybe it was never even said to you

but it was felt right right and it just goes kind of unsaid and yeah you’re trying to meet these expect expectations

and it’s not necessarily the the truth but rather the story you’re you’re making up about it so yeah I I think

it’s just cool you’re you’re looking at all different um aspects not just like the ace um you know kind of check box or

or scores you’re really digging into almost like that social aspect of like the humans and us like actually

living uh which I think goes missed a lot of the times in in this type of research I I I constantly am reminding

people when I talk about my research that like I for the most part I’m never talking about an individual um I’m

talking kind of about a a system and systemic issues and cultural um you know

right because so here example I have a paper that looks at harsh parenting so

parents self-reported and it was it happened to be on moms we used Prim married caregiver and that cohort it was all moms um they self-reported when the

kids were 2 years old and it was things like you know screaming yelling um

threatening throwing spanking the type of things that you cannot to get your

children removed from for DF from Child Services um and then we looked at the

Children’s epigenetics when they were 8 years old parent self-report of harsh parenting was able to predict DNA

methylation of nr3 C1 the glucocorticoid receptor and other HPA genes so for a little bit

of background for to explain that system so the HBA system is the hypothalmic pituitary adrenal system it is the

system that that um is responsible for your cortisol response to stress and um

chronic levels of uh chronic high levels of cortisol has been well documented to

be associated with with many psychiatric and neurogenerative disorders actually and wreaks havoc on your immune system

like this is a well-known thing chronic cortisol is not a good thing and the um the Weaver 04 the big paper that made

the huge spash that looked at maternal care and rodents this was the gene that they really looked at um so we were a

you know and then after that a lot of the human studies followed up with these big trauma cohorts so um yeah the you

know the more than the trauma category cohorts and I wanted to follow that up with harsh parenting and we sound we

found that same relationship right yeah um and so I’m writing the discussion of this paper and

I stop and I think oh my gosh I sound like Freud I was like I can’t publish this I’m just I I’m saying everything’s

mom’s fault like it’s kind of like take home of the message moms no matter what you do you’re G to screw your kids up and stop yelling it’s like I yell at my

kids sometimes because life’s hard sometimes that’s the it happens you know what I mean so I like I can’t put

this out there um but I think it’s so important so what do I do so what I did is I dove into the literature of what

predicts harsh parent ing it’s a societal issue it’s not mom’s

fault okay so I was able to find all this research so like here here are some of the high hitters lack of sexual

education lack of uh birth control availability poverty marriages uh forced

marriages you know not not chosen marriages inequal distribution of Labor

not having paid paternal leave these are systemic

things that are all throughout America and it leads to very high levels of

stress for millions of us that are living paycheck to pay Jack did not have

access to sexual education yada yada yada and so I put that paragraph in there that is a very rare paragraph to

find in a molecular biology research paper but I think it is so important

last thing I was giving this talk I was giving that talk one time at an International Conference and I stopped in the middle of that slide and I looked

at them in the room and I go none of you understand what I’m talking about cuz none of them are

Americans they were all Western they’re all from a Western European country in all of their countries all of those

policy things that I just listed they don’t share those issues and I was just blown away

by yeah I study the family I study the individual and I study molecules and I’m a neuroscientist so I’m all about the

biology but I think for me and for my lab it’s so important to recognize how

the bigger picture is affecting all of our biology absolutely well said very well

said you’re looking at the entire picture I really I literally got like chills and goosebumps as you were going through that I’m like wow um yeah so

that actually was not a paper I I was like going to bring up pretty intentionally on the agenda today

because I I like got the paddle like I remember like my mom and dad like you know screaming yelling like I got

spanked when I like would get out of line and I have two younger sisters so it got better like they didn’t get you

know as much punishment as as I did Growing Up I’m I’m the oldest um and I was like you know what I don’t think I’m

going to bring that one up or ask about it because like I’m kind of embarrassed of like you know that like entire thing

and I don’t want people to think my mom’s a bad person because she’s not you know what I mean um but yeah I must have

even skipped through and obviously you know didn’t dive into all of the details there and like hit on that like one

paragraph because that is so important where you’re like okay I’m not going to blame the person for being that way I’m

going to ask like what why like why are they actually being that way um so

that’s huge thank you for explaining that and um you know like thanks for sharing and know your mom’s a wonderful

mom and um it’s even so in harsh parenting and a corporal punishment it

is it is a very tricky topic right now right it’s very tricky and what we’re finding is that these kind of like

negative long-term consequences then it’s mostly in white

kids and and people are having a hard time replicating it in African-American and Hispanic

cohorts and I think that one could you know go in for a long time to to kind of say why but to

me they um culturally they also have much higher levels of emotional availability with their

children so so kind of like kind of back to your experience and like you know witnessing death in your family um so

hard right it was so hard and getting spanked by your parents it could be so hard but all of these things that

children can be exposed those to the really important other side of that is not just the

exposure it’s what what’s the package yeah every everything together

everything together what are the resilience factors because if you know if I was not close to my parents at all

um and I feel like they didn’t know me and I was kind of scared of them and I got spanked like I could see how that

would be really horrible as opposed to if I’m like really close to my parents and I know that they are my everything and they have my back and and you know

all of that package and they SP me once in a while I was like I probably deserved it I was being a little brat I don’t know you know what I mean so this

just like again I like always want to bring it back to it’s just so much bigger than any one research paper can

ever actually explain it and the media so often finds these papers and it gets

really confusing exactly yeah the whole reason I have this podcast essentially is like to break this down and to talk about it

because again it’s so individualized too you can’t just point to like one General cohor or or kind of populationbased

study I mean of course when we go into the biology and the gluc cortico receptor elements and you know regulating cortisol and things like that

of course we can make you know more of those generalized statements but it really is so situational specific

because of how you’re interpreting things you’re interactions your relationship with self and and kind of

taking taking that deeper dive so thanks for for bringing up up that paper I want to switch gears now to Candace and and

really dive into psychedelics so that’s a big part of of research um super

excited to jump in you wrote an editorial in 2023 called what is up with psychedelics anyway and I think that’s a

perfect place to start so yeah what what’s up with psychedelics it’s you know the new sexy hot topic that that

everyone’s talking about so give us an introduction there what is up with psychedelics so I

think we all have like the general background narrative right um became popular in the 60s and like the hippies

use them in Woodstock and free love flowers and then they became schedule

one substances which means the federal government regards them as completely unsafe with no medical use whatsoever

even MDS cannot prescribe them um High rates High um danger of addiction so

that’s schedule one and then a lot of propaganda came out for a lot of decades right so like I love I love asking

people what have you heard so some of my favorites are okay so there’s the chromosomal split like there was some kind of paper back in the day about like

LSC is going to be like breaking open your chromosomes and then there was the uh if you take LC once it gets stuck in

your cerebral spinal fluid the rest of your life and every time you sneeze you’re going to trip um and then of course the big you’re going to think

you’re an orange and peel your skin off and you’re going to think you can fly and jump out the window so these this was it this was reiterated over and over

again for decades um and so research took a sharp um you know stopping point

and then they’ve kind of come back so the you know there was very there was three very small trials that came out of

UCLA John Hopkins and New York University I don’t even know how long ago now probably 15 20 years ago that

looked at treating depression and anxiety symptoms in cancer

patients using a psilocybin therapeutic protocol and the results were you know

really really great small small sample size so you can’t do so much about it at that point but it really was the jumping

off point for what we’re seeing now so what we’re seeing now is we have MDMA which is the active

component in ecstasy is currently under review by the FDA for a treatment for

PTSD so phase three trials have been completed the FDA will tell us there um their outcome in August s the cybin has

been given granted breakthrough breakthrough status um two separate times for treating depression and we’re

currently still seeing a lot of phase two Trials come out and um then there’s a lot of little oh and then also still

ayin for substance use disorders we’re in phase two trials right now as well um

and I realized I gave a talk a couple weeks ago and I had a question afterwards that was like so what happens

you know if they like stop taking the siloc cybin and they don’t feel good anymore and I was like oh no no no no

they’re not like taking soloc cyon and that really made me pause to like think about that I live in a bubble and maybe

everyone doesn’t understand this so much so when we say psychedelic assisted therapy in today’s modern world there

did used to be a couple different versions of it but right now like kind of the standard protocol that people are using is you you start a relationship

with your therapists typically there’s two of them you build rapport this is the same exact thing we do in standard therapy and during that process you’re

also choosing your intentions you’re choosing your targets that you want to be working on while the dosing session

happens that’s also very similar to standard therapeutic practices today that you set goals with your

therapists um and there’s preparation right so you’re told what to expect um

which really helps with a lot of people’s anxiety around going into a new experience that you know their whole life and their parents life were told

you know split their chromosones and so then you have your dosting session like you know you know

um and during that session you’re there’s a lot of being

invited to go inward into kind of seeing where you go yourself but your therapists are there to support you when

needed and then after that the different trials have different numbers one two or three trials um one two or three dosing

sessions in the different trials I’d say is most common and then you have integ ation where you like talk about what

insights you may have gained from those experiences so that’s kind of like the Psychedelic model right now it’s not

we’re not replacing ssris with um psilocybin and again this can be really confusing and I get why because as the

clinical trial uh psychic assisted therapy movement was growing so was micro doing but like most people realize

that the micro doing movement was not scientific it was blogs

but they all Rose to the same occasion so I can see how it’s very very easy to be very confused of like micro do things

the new depression treatment so I think like more more research will be done on micro doing we will we will find out

more uh but there there’s very little actual like controlled you know data on

it at the moment yeah yeah and you know psychedelics we’re going through this

like massive change right now I feel like in in the US they’re still legal in in some parts like organ I think in 2020

in Colorado in November of 2022 um but really it’s going to vary like depending on your your state the specific

substance you know it’s been decriminalized in in specific cities so we know this is a huge growing interest

and you know acceptance of these potential therapeutic benefits of psychedelics especially for conditions

uh that you know you’re looking into like depression PTSD um and anxiety and some cases they may be super helpful but

um yeah so the the legalities I think make it a little bit bit of a a wishy-washy even subject to to even talk

about so um yeah they’re they’re pushing them through these these trials um you know and then uh I think we’ll learn a

lot in in August with with MDMA being in in phase three yeah it’s funny my mom was visiting me a couple weeks ago and

she knows what kind of research I do but we never really talk about it it’s she’s like so tell me like it’s funny kind of the title of my editorial maybe I should

just send it to her what what’s up with psychedelics anyway I think is what she said to me she like well like what is it doing

why does it work like what what is this and I was like wow like and I kind of felt like I was put on the spot and was

and I kind of fumbled my way through explaining to her and I was like basically like this is my best like non-scientific way you know I like this

is not the way I’d say it in a paper but I maybe say it to a person

um they’re putting you in a state where therapy becomes much more accessible so

your cognitive capacities are not you know at your highest right like let’s like let just go ahead and name that no

one wants you to go driving a car when you’re tripping on mushrooms because your cognitive capacity is hard

impaired and some people might think well like well then how can you do therapy but in reality um it kind of

helps to be able to break free from the cognitive protections we have built

around our narrative our whole life you know so like whether it was

trauma or whether it was just the extreme pressure to perform a lot of us haven’t

actually sat in what that means to us and how it feels in our body we avoid it

avoid avoid avoid avoid so in that state maybe like your your you know cognitive

defenses are down a little bit and you have these profound feelings of safety

and unity and love for yourself and others so now all of a

sudden you feel safe enough in your body to go there wherever there is for you

right so I imagine in the beginning with these cancer patients there was the was

the real real exploring of of the fact that they’re about to

die yeah yeah I mean that makes sense and I I’ve never done the the uh psychedelic assisted therapy personally

myself I know a lot of people who have and they explain it as something where

you know it’s like you go to your your best friend or your closest friends and you’re able to give them advice right and tell them exactly what to do and

like you know feel the feelings and everything but like you would never take your own advice or even like talk to

yourself in that same kind Voice or that that same way so I think that’s an an interesting and unique perspective there

um so it’s really yeah about peeling back those layers and and feeling safe which you know this is a a fun maybe

exercise too think of like the last time you just like sat with yourself like you were on your phone you didn’t have some

type of I was goingon to say stimulus but like stimuli around you whether it it’s a screen a TV um you know when the

last time you actually said like am I happy or you know what am I doing today how does that make me feel I think we’re

so disconnected with ourself even without the Psychedelic therapy um that there are so many things that we can do

beforehand and you know personally I just got um uh I I just got went through

a transcendental meditation program and got certified there and you know even waking up doing you know 23 minutes in

the morning 23 minutes at night and just sitting without nothing and just having my mind run free and be able to you know

transcend and relax like I really do think it’s made a world of difference in my you know anxiety per se um or kind of

how I’m feeling yes I couldn’t agree more and I want to add to it that for a lot of

people they have never felt safe not once in their life and that’s

why I’m so interested in early life trauma early life stress early life experiences because you know in the

first few years of our life our brain is building like it’s not preset it’s preset in in the ways that we are human

right our our human brains are going to build pretty similarly however it is responding to our experiences and so kind of going

back to those early examples like maybe maybe you weren’t safe and so your you know your brain and your physiology kind

of built up around that knowing um and so I think for a lot of

these meditation Traditions spiritual traditions and even Psychotherapy Traditions which are highly similar if

anyone ever chose to sit down and actually study it all um for me personally it was always very

lonely um to like be studying the spiritual traditions and be constantly um referred to like well you can feel

your inner Love by you know like it’s like a mother’s love ouch ouch for all

of those who never felt it you know and in therapy there’s this expectation that our patients are

they’re reaching for something right like we want like what are your goals oh to feel better oh you know not hate

myself uh whatever they’re reaching for something that they’ve maybe never felt so I think that there’s this whole

other level for um the Psychedelic experience that it and I can this is

something that I can say from my personal experience it provided me the first taste of what safety even feels

like and there was no chance that me as an individual could have reached that

state without being shown what that state was yeah that makes sense absolutely I have

a um I have an adopted son and he’s such a supernova he’s so amazing uh we got him at five he had a lot of trauma and I

can already see the same things in him like I I can already see that like he is 10 now and he’s gotten so much love and

safety and you know just you know he has gotten from our F from his you know his

second family all of the things um but he didn’t have them the first 5 years

and I can can still see how his uh his physiology it’s you know it’s stressed

it’s not relaxed and it’s because it was built that way yeah yeah interesting

it’s it’s interesting too how you’re able to like yeah look at you know your son that way and you know really pair it

up with the the research and everything that you’re studying I mean it’s like a an example right in front of you and and

someone who I’m sure you you love dearly so absolutely I’m you know yeah definitely want to to go down the the

Psychedelic assist therapy at at one point in my life we’ll see if it’s you know within the next year within the next five or so but um I’m excited when

the time comes for sure so to get back to the biology a little bit because I feel like yes this is your epics podcast and I keep taking it to all these other

plac good which is the Crux of what I do right like I it can be yeah like I am at

this like molecular level but I go out and it’s it’s fun for me and sometimes challenging because in a room of

psychologists and I can speak their language and they’re just like I don’t know what you’re talking about with molecules and then I try to talk to the room of biologist just about B you know

about molecules and they’re like I don’t know what you’re talking about what is attachment so that’s the seat I sit in

um okay so the biology here’s we don’t know we don’t know what we don’t know

what is happening at the biological level that makes the epigenome or makes these uh dnmts and methyl transferases

like why are they changing like what is the signal that you know the methylation on your nr3 C1 Gene is like whoop we

need to change this up we don’t know uh there’s still so much we don’t know um

so what I find very interesting is the similarities between acute stress and a

psychedelic state so this is what I mean by it so the psychological level they’re both really highly Salient right like

when if you know you get in a car wreck and when that memory is like in there um

and for the Psychedelic experience all the older you know the older data from John Hopkins it’s like 97% of people

said it was the top f one the top five experiences of their whole life so you have this really

Salient impactful psychological State okay neurochemically you have increased

levels of Serotonin dopamine cortisol glutamate stress does the same thing

we’re increasing levels of those physiologically you have increased heart rate increased blood pressure in um um

and a couple others might be forgetting the physiological level right so when we take out the idea of okay was that

traumatic or was it healing the state can be very is very

similar and I wonder if there’s something about and this is not there’s no data to back this up this is me you know talking about my ideas as

scientists um I’m just wondering if there’s a clue there because we don’t know why when why the epome response or

experiences I’m wondering if there’s some Clues because they’re so similar on the outside of you can have an acute

traumatic experience and your behavior changes right right that is what we refer to is like well this person came

back from war and now they have PTSD what having PTSD means is behavior so

they had experiences that changed their behavior then if we look at the Psychedelic literature and all of the

the nonscientific stories people say I had this experience and I

changed so to me there it’s possible that there that we could use the

Psychedelic model to understand more about what is the biology

underlying our EP our epome responding to our changes in a way that shape

Downstream physiology and behavior yeah yeah and so yeah you know

you’re seeing that the same exact process if you’re not assigning anything to them you’re seeing the same thing

essentially so you have this experience and then it’s changing the behavior it’s changing the outcome and you know you you notice those difference like you

mentioned with the NR 3c1 um gluc cortic cord receptor um Gene and now you have this this theory

of you know what can that tell us is there a way that you imagine actually like measuring that and diving into that

like I feel like it’s like yeah how how do you even go P that how how do you like study that hanana the amount of

ideas I have for studies I don’t have the time or money

to do them all and really even the expertise I think a lot about cell culture being a lot of the um about

being the model that potentially I’m going to need to kind of dive into the these Realms of my questions I I currently do not have a cell culture set

up in my lab but um but yeah I think I think there’s just still so many

questions about the epome so for example in all of my research I can I keep consistently coming across these openc

cpg sites do you know what these are should I give some background on that yeah let’s give some background on open open in the in the DNA mation world we

have really cute uh jargon so we have our Islands which are cpg sites cpg

sites are just like the location in which we primarily study methyl groups even though it’s not the only place to

happen and um these islands are defined by being around the promoter of a gene

which just means it’s the start of the Gene and if you block the start of the gene you’re going to decrease that Gene

from happening so if you look into the epigenetic literature you know around

exposures and psychiatric behavior and like this whole new like neuroepigenetics field

the vast majority of them are only looking at Islands like the vast majority of them because the biological

consequence of methyl groups there is is pretty well understood if you have

methyl groups you’re blocking transcription you’re decreasing Gene um Gene products however um there are cpg

sites across the whole Gene and there are cpg sites in between genes and um and my data keep showing

them be very important um um but I’m looking at their association with phenotype so there’s so many steps in

between what I’m looking at that I can’t tell you like what is what is methylation um at a cpg site in the

third intron doing and I keep I keep reading and I keep trying to read more and more and more and I can’t find a

whole lot out there um so a lot some cancer cancer is where I go to a lot Cancer’s been looking at epics for a lot

longer than neuroscientists have um and it’s a cleaner tissue type and they get to look at their tissue so cancer

epigenetics they get to cut the cancer out and they get to compare it to the non-cancerous tissue right I rarely get

to cut brains out um so it’s a whole another it is a whole another podcast to start talking about the peripheral

epigenome and why it’s related but I would love to sometime um so anyways so

we don’t know so like there’s some evidence that they’re change that they can be changing transcription levels as well methylation across a gene and then

there’s also evidence that they could be changing the iso form so they could be changing uh what part of the gene is

transcribed which then down the road changes the makeup of the protein which down the road changes the function of

the protein which is how we change Behavior like and I think that’s

something I try to drive home for people so much of like I’m over here talking about genes and I’m over here talking

about behavior um everything about your output your behavior is

coming from brain and that’s all proteins baby we talk about receptors and

Transporters and you know dritic Arbiter and like um yeah those are all changes in gene transcription those are you know

those are proteins yeah just there’s so many unknowns even at the cellular level of

like what are we measuring what does this mean yeah I like the the cute little jargon you you use there um which

is yeah so true um but is is that still like a huge area of of interest for you is really diving into the epigenetics

like do you think like most of the answers lie there I mean I know there are a lot of um the entire central dogma

that you need to get through to see the phenotypic outwards expression and then the behavior so there’s a lot of steps and I understand you have to use them

all together to really start to hypothesize as to you know why is this this happening um but do you think the

epigenome holds more of those answers like what’s your your thought there yes

yeah is your question do I want to run a center where I have 10 different people with expertise doing the studies I want them to do

yes yeah I need people yeah I need cell I need cell culture I need U more anal

we do we do animal research in our lab as well which is really great because get brain tissue but even then um even

then we’re still we’re still talking about if you if you get a brain chunk say I want to look we’re looking at different cell types um it’s still very

all so complicated so yes I want to look at the whole picture and yes I think epigenome is holding a lot of

information that we don’t know like a lot a lot a lot I think about a lot I think about a lot about like the genetics and how much when we started

the Human Genome Project we there was a lot of people that were so convinced we

were about to solve all of it and it turns out we only have more questions

like now we know the human genome and we’ve learned a lot and we’re still we’re more confused about the CLX us and

I think I think a lot about Evolution I think a lot about like the um you know

like we all get it we all get the idea we’ve all been taught like uh um a difference came out in a genome and

somehow that difference was advantageous and and boom thousands of years and now more people have and then and the other

one went away and I’ve personally have always found that theory lacking in like really that’s the only thing that

happened so I’m was gonna you know I I think that we’re gonna find out a lot more about that you know think I think

there’s a lot of answers there that we’re all I think it’s gonna take like way outside of my lifetime to answer them all yeah yeah I use that example a

lot with the Human Genome Project and you know how we thought we were gonna like solve all the diseases and cure cancer and you know everything would be

fine um and then we’re like okay cool we have this information but it’s very very limited and like what else is there

there has to be other reasons and other why so I usually compare epigenetics to you know the Human Genome Project it

used to cost like millions of dollars to sequence your genome it used to take like so long and now you know it’s under

$100 it’s less than 24 hours and I think epigenetics like understanding your EPO

especially being able to retest after certain experiences which change those behaviors to start to see those

differentiated methylated regions and those patterns is really what we need and that’s harder to do obviously in the brain because we need brain tissue so

you can just see how those those complexities add add up but nonetheless I think a really good thought experiment

yeah and I will have some papers coming out um soon that you’ll be able to I’ll follow up on me on where we are looking

at neuroimaging metrics so brain structure and looking at DNA methylation of genes highly expressed in those brain

structures but we’re looking at DNA methylation for bual cells and we are showing that they are highly predictive

in certain age brackets yeah so it’s like yeah I’m really excited to uh to to read some of those

those papers so um we’ll definitely have to have another conversation and I I like the peripheral genome example you

gave earlier too so this will this will be the the first of many um and you know I know we’re getting to the end um here

as well Candace I I want to point out I know you have the um pgp or the Psychedelic Genome Project um can you

give our listeners a little bit more information on on what that is like why that’s important can people get involved um in your work yeah wow um so the pgp

we want to collect samples biological samples from clinical trials and or

people using at home and or people in Oregon and soon to be Washington and Colorado that are going to clinics and

we just want a pre and a post saliva sample and then to fill out um some

common questionnaires after your experience so the idea is we want to look at these Baseline epigenetics and

genetic predictors of how did it go for you did you take cbon did you have

Adverse Events you know how did you feel afterwards and then we can kind of start

to um untangle are there genetic are there genetic profiles that we can say

hey this is not a good psychedelic therapy for you there’s a lot of evidence that people that have similar genetic profiles they’re having a lot of

adverse responses right now we just exclude people from trials that if you have any family history of psychosis you

just can’t be in here and so that’s an example like well we could be doing that in a much more modern way and then maybe

you know maybe you do have a family history of psychosis but the genetics suggests that you’re not going to have an Adverse Events and then we want to

look at these prepost like you were saying before the power of the longitudinal model with epigenetics is we can see if um your psychedelic

exposure is related to a change in epigenetics that uh that explains the

change in behavior that you had so the reason but so so basically I just describes like a pretty standard idea

for like a genetic and epigenetic study of exposure however what makes the ggp so different is because we want all the

samples to come to one place so you know we are sitting on about 50 less than

that 40 Years of genetic research and Psychiatry where it was just like it’s a mess because everyone’s doing a genetic

study here they’re doing a genetic study here they’re doing a genetic study here the the samples get processed differently the timelines are different

their behavior data that they’re collecting is different and so now we’ve real and we need big sample sizes for

genomic science so now with the psychiatric world you know like we’re trying to like we’re trying to bring it

all together like let’s everyone share our data let’s everyone put our genetics in the same database let’s see what we can do and that’s great and with

psychedelics we have the opportunity to not have to reverse engineer the issue

we can just prevent it by let’s all join together let’s all psychedelic

researches around the world collect the samples and send them to the same place for processing which is just really gold

standard scientific method yeah for sure yeah I know I I’m definitely going to get involved and and

you know look into that and and submit some data submit my samples I’m even going to do eventually when I do the

Psychedelic uh assistant therapy do like my epome before and after um on you know an epic Ray or something too so i’ would

be super interested in looking at uh the the NR 3c1 gene on on just kind of an N1

level too so I I’ll get back to you on that and share some some data there I love that you’re saying that and of course I know you’re going to but I have

to since you know it’s hard with the N of one Hannah I don’t I don’t want to

set you up for disappointment in either direction yes UND understood completely

give you the group level results perfect let’s do that let’s do that we we’ll we’ll look at both of them

um well awesome now we we covered so many amazing like areas in in this topic it just excites me all over again this

is exactly why why I do this anyways um we’re coming to the close here um one

question I always ask everyone at the end um if you could be any animal in the world what would you be and why well

because life is dynamic and I’m Dynamic and Mya it’s a dynamic that has changed over the

years I like it so you’ve thought about this oh yeah um so when I was younger I was a bald eagle Fierce and strong right

Independence um now and then I went for a long time with a quala bear nickname because I hug with all

Limbs and uh now we’re going to go with

Hannah does everyone always have an answer no no some people like it some people like struggle to answer it yeah

some people are like I know right away but you’re like going through this like evolutionary process so I like this too I don’t think everyone anyone has like

done this because you know you know how my mind works now okay so my answer

right now for right now in this time of my life I’m gonna say is I believe in tools like a toolbox and my goal in life

right now is to have all the tools or not have all of them is to know which ones I’m good at and know which ones I need to get better at so that any given

situation I can pull out the tool that works for that situation so with that being said I guess I’m going to go with

chillion oh I like it I don’t know I wasn’t like expecting anything but I was like I’m I’m I like pride myself in

being authentic and it’s not that tools don’t make you unauthentic tools I think make you help

help you be even more of who you are because you’re choosing how to respond to every situation right right I like it yeah

that’s a good answer that’s a deep answer I like it yeah um cool well we’ve come to the end of this um awesome

podcast interview so for listeners who want to connect with you you know where can they find you how can researchers connect with you um can they reach out

you you can find the be laab email at our um we areth bear.org

um we will be H pushing a very heavy recruitment effort for pgp samples um by

both clinical trials and individuals whether they’re going to a clinic in

organ of their own accord or um at home users however we haven’t started that recruitment process yet um so just keep

a lookout on our website if you’re interested in that cool well I am so excited to get

this episode out um thanks everyone for listening to us at everything EP genics podcast we’ll be linking all of the

research um in the bear lab links below that candus mentioned and remember you have control over your epigenetics so

tune in next time to learn more thanks so much

About this Guest Expert

Dr. Candace Lewis
Dr. Lewis grew up in rural Alaska where she was exposed to high rates of poverty, mental illness, violence, and addictions. These personal experiences drove her commitment to revolutionize mental health understanding, treatment, and policy change. To this end, she earned a Masters in Counseling, a PhD in Behavioral Neuroscience, studied genomic science at a leading institution, and studied psychedelic science at the University of Zurich. She is currently the director of the BEAR Lab (Brain, Epigenetics, & Altered states Research) at Arizona State University. Her lab’s research focuses on 1) the impact of early life social experiences on epigenetic regulation of gene systems involved in mental health; 2) the relationships between peripheral epigenetics and brain structure, function, microbiome composition, and behavior; and 3) the potential of psychedelic-assisted therapy to reduce symptoms through psychological healing and epigenetic alterations. Through her research, she aims to acknowledge the harm caused by psychology and genetic sciences on minority groups, increase diversity in training and study cohorts, and change policy to improve mental health for all. When not working, Dr. Lewis enjoys family time with her three sons and wife, going to festivals, hiking, running, reading, creative writing, and talking all things spirituality, social justice, and science.

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