Trauma, PTSD, MDMA‑Assisted Therapy: Key Findings & Epigenetic Impact

Name: The brain on MDMA can go somewhere CBT has never been able to reach | Rachel Yehuda: Full Interview
Uploaded: 2026-04-10T13:01:17+00:00
Duration: 50 min 1 s
Channel: Big Think
Description: Summary and key takeaways on Trauma, PTSD, MDMA‑Assisted Therapy: Key Findings & Epigenetic Impact, covering The Nature of Trauma Stress fades when the source

Big Think

Apr 10, 2026

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50 min video

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YouTube video ID: cXjlNvw4fIk

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Stress fades when the source disappears, but trauma endures as a watershed event that continues to shape a person’s life long after the danger has passed. Roughly 70 % of the population experiences at least one potentially traumatic incident, and a quarter of people face multiple life‑threatening events. Most survivors do not develop post‑traumatic stress disorder (PTSD); the disorder emerges from how individuals interpret the event, the narratives they construct, and the cultural messages they receive.

Societal attitudes that blame survivors—such as asking “why didn’t you fight back?”—reinforce self‑blame and keep PTSD active. These messages embed a persistent sense of guilt, preventing the natural resolution of the trauma and turning a single incident into a lasting psychological scar.

MDMA‑Assisted Psychotherapy

MDMA differs from classic psychedelics because it preserves coherent introspection while dampening the fear response. During a session, MDMA lowers amygdala activity, allowing patients to revisit painful memories without being overwhelmed by terror or shame. This creates a therapeutic “telescope” that brings hidden layers of self‑blame and distorted narratives into clear view, much like a microscope reveals unseen cellular detail.

Clinical trials report about a 66 % reduction in PTSD symptoms when MDMA is paired with twelve structured psychotherapy sessions. The medication alone is not a passive cure; success hinges on the patient’s intention, the strength of the therapeutic alliance, and the willingness to confront difficult material. Each preparation session lasts 90 minutes, and the current FDA‑approved protocol includes three medication sessions embedded within the broader psychotherapy schedule.

Epigenetics and Intergenerational Impact

Trauma can leave epigenetic marks on stress‑responsive genes, such as those governing cortisol receptors. These modifications can linger through cell division, keeping the stress response primed even after the original threat has vanished. However, the marks are not immutable. Healing environments and effective treatment can reverse them, demonstrating that biology remains adaptable.

Intergenerational trauma is not a literal inheritance of memories but a biological and behavioral adaptation that may convey heightened vigilance or “wisdom.” When a parent receives successful PTSD treatment, the positive shift can cascade to the next generation, potentially erasing fear‑related epigenetic markers and improving resilience in offspring.

Mechanisms & Explanations

Trauma Persistence: Epigenetic changes to stress‑related genes prevent the shutdown of the stress response, sustaining hyper‑arousal.
MDMA Mechanism: By reducing amygdala activation, MDMA creates a safe window for exposure therapy, enabling fear extinction without retraumatization.
Fear Extinction: Repeated exposure to a trigger without negative outcome—illustrated by the cherry‑blossom/shock‑mouse study—can overwrite epigenetic fear markers.
Therapeutic “Telescope”: Psychedelics act as tools that magnify otherwise inaccessible layers of self‑judgment, allowing precise therapeutic work that ordinary consciousness cannot achieve.

Hard Facts at a Glance

70 % of people encounter at least one potentially traumatic event.
25 % experience multiple such events.
MDMA‑assisted therapy shows roughly a 66 % recovery rate for PTSD.
The FDA‑approved trial structure includes three medication sessions and twelve psychotherapy sessions, each preparation meeting lasting 90 minutes.

Key Voices

Researcher Rachel Yehuda has documented the biological imprint of trauma across generations, while Stan Groff coined the “telescope” analogy to describe how psychedelics expand therapeutic perception. Emory University’s work on fear extinction in mice provides a laboratory model for reversing epigenetic fear markers, and the FDA continues to oversee the pathway toward broader clinical use of MDMA‑assisted therapy.

Takeaways

Trauma is a watershed event that continues to affect individuals long after danger has passed, unlike temporary stress that ends when the stressor is removed.
About 70 % of people encounter at least one potentially traumatic event, yet only a minority develop PTSD, with personal narratives, cultural messages, and self‑blame shaping the disorder.
MDMA‑assisted psychotherapy produces roughly a 66 % reduction in PTSD symptoms, but it requires active participation, clear intention, and a supportive therapeutic setting across twelve psychotherapy sessions.
MDMA works by dampening amygdala activity, allowing patients to revisit traumatic memories without overwhelming fear, while classic psychedelics induce ego dissolution rather than coherent introspection.
Trauma can create epigenetic marks on stress‑responsive genes, but healing environments and successful treatment of parents can reverse these changes, offering potential benefits for future generations.

Frequently Asked Questions

How does MDMA facilitate trauma processing differently from classic psychedelics?

MDMA reduces amygdala activity, keeping fear and shame low while preserving clear cognition, so patients can examine traumatic memories with compassion; classic psychedelics typically cause ego dissolution, which limits coherent therapeutic dialogue in the therapeutic session.

What evidence suggests that trauma‑related epigenetic changes can be reversed?

Research shows that epigenetic marks on stress‑responsive genes persist through cell division but are not permanent; healing environments and successful PTSD treatment in parents have been observed to erase these marks, indicating that recovery can alter biological inheritance.

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Full Transcript YouTube

Hi, I'm Rachel Yehuda and I study post-traumatic 
stress disorder and the effects of trauma,  
including intergenerational trauma. Chapter 
one, why trauma sticks? >> In graduate school,  
I studied the neuroscience of stress. Many people 
were studying that at the time, and post-traumatic  
stress disorder was a relatively new disorder. 
It was a very provocative and challenging concept  
because what the concept of post-traumatic stress 
disorder wanted you to understand was that the  
effects of stress were enduring. Stress theory at 
that time basically suggested that stress effects  
were temporary. They could be quite severe and 
serious at the time that you were undergoing  
a stressor. >> But that the natural way that the 
body had of dealing with stress was to recalibrate  
and achieve a kind of a homeostasis, kind of come 
back to itself. Whereas there was a lot to look  
at in terms of neuroscience in an organism that 
was under threat or that was undergoing stress.  
The idea that there was still something to see 
weeks, months, years, and even decades later was  
really interesting from the perspective of the 
neuroscience of stress. My current research is  
really about understanding long-term effects of 
stress and really entertaining the question of why  
we are so transformed when we undergo traumatic 
experiences and why the effects can linger for so  
long. We are looking at a variety of hormonal and 
molecular mechanisms to try to help us understand  
that. I'm also interested in treatment of PTSD 
and really what to do about the fact that so many  
people have effects of traumatic experiences 
that trouble them. They feel haunted by their  
traumatic experiences or they feel really stuck 
because of things that have happened to them in  
the past. So what's the best way to get unstuck 
and what's the best way to move forward following  
trauma exposure? So those are the things that my 
colleagues and I are studying. Why I've dedicated  
my career to studying the effects of trauma is 
because trauma exposure seems to be everywhere  
and increasingly the more we seem to be learning 
about the effects of trauma. In some ways the more  
stuck we're getting as a society. We see it as 
sort of an insurmountable burden or barrier when  
in fact there's always been stress and there's 
always been trauma. And truly there must also be  
a way to go forward in the face of trauma and use 
the lessons of trauma to really achieve resilience  
and post-traumatic growth. I think what's really 
helpful is to make the distinction between the  
experience of stress and the experience of 
trauma. So maybe what's useful is to talk  
about the difference between stress and trauma. 
We experience both. I'm pretty much a regular  
basis according to statistics. Many people see it 
as a kind of continuum with stress being maybe a  
less serious version of trauma and trauma sort 
of at the other end of the spectrum and that's  
not entirely wrong. A stressful event is something 
that is challenging to you in the moment. It could  
be a trouble at work, trouble in interpersonal 
relationships. It could be an illness or coping  
with really any of a number of things. When 
most people talk about a traumatic experience  
they're talking more in the order of life threat, 
interpersonal violence, childhood abuse, combat,  
being in a natural disaster. So clearly there 
is a range of challenging events with trauma  
being at the other end of the spectrum. But the 
differences go even deeper than that because when  
we talk about a stressful situation, once you 
remove the stressor or the thing that is giving  
you the symptoms and the angst or the challenge, 
usually you don't feel under the influence of the  
stressor anymore. You can relax and say things 
like, "Well that was stressful. I'm glad that's  
over now." I mean in fact when you used to go to a 
physician who used to tell you you were under too  
much stress, the solution to that problem was 
removing the stressor. But I think with trauma  
it's different because the effects of trauma 
can remain with you even after the event is  
in the rear view mirror. Even if there's no active 
threat, the person who perpetrated the violence is  
in prison, the war is over. You've fully recovered 
and rebuilt your house from the natural disaster.  
You can still feel the effects of that experience 
because it comes back to you. So the way that I  
like to think about a traumatic experience is 
an event that really divides your life. It's a  
watershed. And it's a event that will continue to 
be experienced by you in some way or continue to  
have some major presence in your life even though 
it is in the past. And that is just not true of  
stress when the solution to being under stress 
is to remove the threat. With trauma it's not  
quite as simple because some events really have a 
bigger power to transform us. I think what's also  
very important to understand when we're talking 
about traumatic events, I like to refer to them as  
potentially traumatic events, the kind of events 
that are capable of eliciting a post-traumatic  
stress disorder is that these events are way more 
common than we think. About 70% of people really  
around the world, but certainly in the United 
States, have experienced at least one of these  
potentially traumatic experiences in their 
lives and about 25% have experienced multiple  
life threatening or potentially life threatening 
events. When you look at the prevalence of PTSD  
compared to the prevalence of trauma exposure, 
what you begin to understand is that most people  
don't develop post-traumatic stress disorder when 
they're exposed to trauma. What's important about  
that is that trauma itself doesn't have the power 
to transform people. It's our responses to the  
trauma. But when you look at the statistics, you 
see that compared to the prevalence of trauma,  
which is quite high, the prevalence of 
post-traumatic stress disorder is quite  
a bit lower. The important thing about a traumatic 
event is really how you process it, what you think  
about it, why you think it happened. And you know 
what's really interesting about the prevalence of  
post-traumatic stress disorder is that it varies 
from nation to nation. They've done studies on  
this. And so sometimes that's linked to the 
fact that there are more trauma exposures in  
one country and war-torn countries versus other 
countries. But it's not simply that. Culture has a  
very important role in teaching us how we respond 
to traumatic events. We've done such a good job of  
validating the experience of trauma exposure and 
of letting people know that traumatic experiences  
can result in mental health symptoms, that it's 
not stigmatizing to develop symptoms of anxiety  
or depression or just to feel very incapacitated. 
Perhaps we've done too good a job on this concept  
because I think people automatically assume that 
if they're exposed to trauma, they're going to  
develop a mental health problem. And so what we 
need to do is really underscore the idea that  
trauma is something that is survivable and that we 
have tools to help people who have been exposed to  
trauma recalibrate and really work with what has 
happened so that they don't remain permanently  
stuck. Chapter two. How MDMA assisted therapy can 
break the loop. What's the thing about trauma is a  
prison, we're all kind of doomed because traumatic 
experiences are here to stay and we shouldn't view  
them as a prison. We should view them as simply 
an occurrence because that's what they are.  
And of course traumatic experiences are going to 
be very challenging and they have the power to  
be extremely disruptive and they have the power to 
produce a lot of mental health symptoms. But there  
are ways to also be resilient. There are ways to 
cope with trauma and there are ways to do amazing  
things not only despite the trauma but because of 
the trauma. When we talk about using psychedelic  
assisted psychotherapy to heal from trauma and 
to heal from post-traumatic stress disorder,  
what we're really trying to do is use the power 
of psychedelics to induce kind of an altered state  
to help people do the work of trauma-focused 
therapy that is often very hard to do when you're  
in an ordinary state of consciousness. The reason 
that it's so hard for people in the aftermath of  
a trauma is not only because something terrible 
has just happened but because they construct a  
narrative about why it happened and what they did 
wrong as a result of it happening. But a woman  
who's been exposed to interpersonal violence can 
get the impression that maybe if she would have  
fought harder or worked harder or didn't send 
certain signals into the stratosphere that she  
could have prevented this or that she was maybe 
too passive and didn't fight as hard as she could  
have. And this is really what's sustaining the 
post-traumatic stress disorder. It's not just  
that she was violated but that she disappointed 
herself in her own actions. Even something like  
9/11 which was 20 years ago, had a lot of people 
who were murdered whether trying to run and save  
themselves was the best course of action, 
maybe they should have gone back and maybe  
they should have helped other people struggling 
to get out of the burning building. So there's a  
lot of room after a traumatic exposure to kind 
of second-guess yourself. And what happens is  
that this narrative can be perpetuated every time 
you think about the traumatic event which can be  
very often. And you start to believe that the 
problem isn't only what happened but it's you.  
When you use conventional therapies to try to 
get at these, we call them "altered cognitive  
schemas" or "altered cognitions". When you try to 
use cognitive behavioral therapies to get people  
to look at some of these ideas, what happens is 
that they can get very, very distressed. And so  
many times they give up on the therapy and right 
now we have cognitive behavioral therapies for  
PTSD that can work quite well for people but also 
equally many people find that these therapies are  
just too emotionally draining or too distressing 
for them. A lot of trauma survivors with PTSD  
feel really alienated. They feel different. They 
try to avoid people. Sometimes it's because they  
don't want to hurt the ones that they love because 
they feel inside that they're very aggressive or  
they don't want to get really too close to someone 
that they were once close to because that person  
might start asking questions and the trauma 
survivor doesn't want to give them horrific  
details about what happened to them. Mostly out of 
protecting the person or out of this feeling that  
once a person understands what happened to them, 
they may not want to see them the same way. It's  
distancing and all the partner experiences is that 
they've lost their loved one in some fundamental  
way that sometimes they can't even name. MDMA 
is now undergoing kind of the last stage before  
FDA approval. And in phase two and phase three 
studies, MDMA has shown remarkable efficacy for  
reducing symptoms of PTSD and about two thirds of 
people that are treated report no longer having  
PTSD and also report feeling changed in a very 
positive direction. That's a very, very high  
rate of recovery for any kind of a treatment and 
that's why it's exciting. MDMA is not a classic  
psychedelic. It works very differently than 
say, psilocybin, which is commonly referred  
to as magic mushrooms or LSD or ayahuasca. Those 
experiences produce a much more dramatic out of  
body experience or mystical experience or even a 
sense that you might even have an ego dissolution,  
your sense of self and maybe blending into a 
larger cosmos. Those experiences can be very,  
very powerful. I think those kinds of psychedelics 
can and should be tried in PTSD. They might be  
very interesting. But they're different because 
while you're having those kind of experiences,  
it's hard to do psychotherapy. It's hard to be 
coherent in a sentence. A lot of the healing  
work with those kind of classic psychedelics are 
occurring really after in integration, which is  
usually very short in clinical trials, but ideally 
the material that is brought up in that kind of a  
session can be talked about for a long time in 
therapy. With MDMA, this is just psychotherapy.  
A lot of the therapeutic work is being done in the 
session while you're in the altered state because  
you can be coherent because you are not having 
an ego dissolution experience. Those people,  
but not all, experience a sense of pleasure. It's 
called ecstasy. It gives your body a good feeling  
sometimes. Some people during the session can also 
report feeling not so good. Sometimes people say,  
"I don't know why they call this ecstasy," but 
that's because they're also re-experiencing  
very difficult memories. But being in a 
situation where you feel calm and serene  
can have different effects in different people, 
but being in a state where you're not so worried  
about getting agitated can be very helpful for 
processing traumatic memories. So for example,  
a woman who's been exposed to interpersonal 
violence as an adult or even a child may be able  
to look past the self-flame and the disappointment 
that she feels in herself to really seeing that  
really she was always with really the responses 
that she made at the time with the ones that  
were most conducive to keeping her alive. But 
instead of just understanding this intellectually,  
which is what happens in cognitive behavioral 
therapy, she feels it as a truth. She sees it  
in a different and more powerful way and she sees 
it in a way that is also infused with compassion  
for herself and similarly a combat veteran might 
also be able to understand that the monster that  
he feels that is now inside of him is actually a 
monster he can let go of because that part of him  
that was aggressive saved him in a situation where 
it was life or death and also was brought about  
by the need to provide service to keep others 
alive, which is an extraordinary thing that  
combat veterans certainly in the United States and 
also around the world often do voluntarily. Being  
in a state that is induced by a psychedelic such 
as MDMA may enhance your empathy for yourself,  
your introspection, your ability to see things 
differently and also make you feel part of the  
world. The idea of the cognitive behavioral 
therapies has always been really correct. The  
idea is to kind of go back there and correct 
some of the faulty assumptions that you have  
about yourself in the world as a result of the 
traumatic experiences. Why they didn't work as  
well as we had hoped they would work for as 
many people as we had hoped they would work  
for is because some of the things that happened 
to people are really horrible. And so going back  
and trying to discuss this in an ordinary state 
of consciousness is just too much for people.  
So a lot of times I'm certainly aware of this 
people engage in cognitive behavioral therapy  
and they talk about a trauma but it isn't the 
trauma because they just can't bear to go into  
something so deeply distressing and so many people 
have had aspects of a traumatic experience that  
they can talk about but that they hold something 
back. In our society unfortunately we have given  
some people the message. Perhaps unintentionally 
or unwittingly that if they would have only done  
something different during a traumatic experience 
it wouldn't have happened. They might have been  
able to prevent it. I remember my mother telling 
me that when the Holocaust survivors came  
from Europe to Israel after the war a lot of 
people asked them why they went like lamps to  
the slaughter. And there were so many of you 
that were so few of the Nazis like how did you  
let this happen? Obviously that's really not the 
right thing to say to a trauma survivor. What it  
does though is it makes you wonder well why did 
I go to a lamp to slaughter? The influence of a  
psychedelic you may really understand that you had 
absolutely no choice with all those machine guns  
firing at you and aimed at your loved one and if 
you didn't march they would die. So we create a  
lot of narratives in our society sometimes that 
suggest to people that they have choices during  
a trauma that they may not have. Plus which we 
don't often understand that the biologic reality  
of the fight or flight response is really to try 
to preserve one's life. You're not really stepping  
through this cognitive process at the time of a 
trauma you're just trying to survive. I think part  
of the reason that we sometimes do second-guess 
trauma survivors is because of our own  
difficulty hearing traumatic material and in fact 
the reason it's important for people with severe  
PTSD to go and seek therapy is because you do have 
to be trained to kind of not have these reactions  
to somebody's trauma to listen non-judgmentally 
and with extraordinary empathy and compassion for  
someone as they're telling their tale. What most 
people find when they really go into a deep state  
where they have empathy and when they are in the 
presence of therapists that can help them process  
the traumatic experience is that they actually 
were heroes. That they survived something that  
was designed to kill them or hurt them. And that 
they did so as best as could be expected in the  
time and that the reason they did so is because 
life is worth living. And that now they can kind  
of take some of that and try to regain that will 
to live without worrying that they may be horribly  
defective not only because of what the trauma did 
but because of the because of who they were that  
they weren't able to overcome the experience of 
adversity. So in part there's a cultural message  
and a societal message here that we need to really 
let trauma survivors know that we understand how  
difficult it was and really embrace their survival 
and adaptation. But sometimes we live in a society  
that's pretty judgmental and so that can add fuel 
to the fire when combat veterans returned home  
from the Vietnam War. I think one of the biggest 
contributors to their ongoing symptoms and their  
subsequent readjustment was being called baby 
killers. That is a great example of how to not  
help somebody get over combat trauma. So thinking 
people for their service and understanding the  
absolutely impossible situation that somebody is 
in is more appropriate to helping combat survivors  
heal because it reminds them that they were 
doing a mission perhaps in an extraordinary cost.  
One of the ways that I like to think about how a 
psychedelic assists the psychotherapy process is  
really based on a quote from Stan Groff which 
says that psychedelic is to the brain what the  
telescope is to astronomy or the microscope is 
to biology just allows you to go deeper and see  
things that perhaps you couldn't ordinarily see. 
And I think that's exactly why these compounds  
have so much potential and particularly MDMA 
for PTSD because it allows you to get past this  
initial layer that you can't see which is how did 
I let this happen or how could this have happened  
to me and go to that next layer that perhaps is 
more microscopic which is because I couldn't do  
anything else because I had no other options and 
it also developed that sense of self-compassion  
that allows you to understand that you don't 
need to be punished or punish yourself because  
you didn't live up to your own expectations 
for how you should have behaved. I think the  
most important thing to let people know about 
psychedelic assisted psychotherapy if you're using  
it for the purpose of healing for mental health 
symptoms is that intention is very important.  
It's not only intention it's the desire to go 
deeper than you've been able to go. On some level  
you have to have this sense that I know I need to 
be going deeper I just can't it's too upsetting  
it's too traumatic it's too difficult and really 
using the medicine for what it is there to do  
which is help you see that thing that you can't 
see with your naked eye and really wanting to see  
it. The MDMA or any psychedelic really won't have 
healing properties if you're afraid to have the  
experience or if you're reluctant about it it's 
like saying well look through the telescope but  
I'm also going to put my hand on the back of the 
telescope because I'm really kind of afraid of  
what I might see. There are ways to be avoidant 
even using a psychedelic assisted psychotherapy.  
It's very important to not give people the 
impression that there's a passive cure. You lie  
down there on the bed you take MDMA you swallow it 
with some water and magical things start to happen  
in terms of processing trauma. That isn't what the 
therapy is about. Ideally therapists who really  
know how to work with trauma in an ordinary state 
can use those tools and techniques to help you do  
the work of pushing forward while you are in the 
state induced by MDMA and really kind of help you  
supercharge the psychotherapy. The way that this 
is being rolled out for PTSD is more medicalized.  
It is that's not to say that people won't have 
good experiences with psychedelics that are taken  
outside of their context. People really show 
a range of different experiences ranging from  
this saved my life to I'm not doing that again 
that was pretty bad. Psychedelics are really  
interesting that way so much of how they're 
going to work has to do with where you are,  
who you're with, what your intention is and 
also probably your internal biochemistry  
so there's no way to really predict it. Even 
though this treatment has been found to work in  
two thirds of people with PTSD there's this other 
third. So everyone that tries this treatment has  
to understand that people respond very differently 
to different kind of medications and to make sure  
that you're working with somebody really ethical 
and can respect your boundaries. Anyone that is  
in an altered state of consciousness is more 
vulnerable and so you really want to make sure  
you're working with people of the highest not only 
therapeutic skill but ethical standards. What's  
fascinating about psychedelics is that the same 
person can have remarkably different responses  
in different settings. When we talk about MDMA 
assisted psychotherapy for PTSD we're talking  
about a process where there's readiness where we 
prepare people to work with the medicine. We talk  
a lot about what the experience will be like and 
what they want to get out of it and what some of  
the stuck points have been. What their hopes are 
for getting past those stuck points. There are 390  
minute sessions to do that. Not to mention that 
these are patients you might have known and have  
tried to work with for a long time before the 
MDMA assisted psychotherapy and they need work  
during the session, any work after the session and 
the way that the MDMA assisted psychotherapy is  
structured right now there are going to be three 
medicine sessions. So you have three very long  
days to kind of get where you need to go and 
hopefully you can make great strides with it  
but for anyone that thinks this is a quick fix. 
That's a perception that needs to be corrected  
because the way that it's being rolled out right 
now with clinical trials with the FDA is a three  
month experience with 12 psychotherapy sessions 
in addition to the medication sessions. It's a  
commitment that somebody is making towards their 
own healing and working in a very non passive way  
to try to really understand what it is they saw 
so that they can make something out of it and  
tackle their lives in a different way. When 
people hear this kind of stuff about how great  
MDMA assisted psychotherapy is or psychedelics, 
there are psychedelic experiences in general and  
they have a natural curiosity to want to try it 
or they want to see if they can learn more about  
themselves. I mean that's a very natural reaction. 
It's important to understand that not everybody  
responds the same way. It's important to adjust 
one's expectations of this and really be in the  
hands of somebody that is very trusted. Different 
states in the United States are experimenting  
with different levels of decriminalization and 
legalization. So I suspect that we will have a lot  
more information about the effects of psychedelics 
in the general population. When you think about  
psychotherapy, that was initially meant for people 
that had serious mental health issues and a lot  
of people go for psychotherapy even if they don't 
have a mental health disorder. We may see after we  
have enough experience with psychedelic assisted 
psychotherapy in clinical populations. That might  
be a very natural transition that it might be 
particularly helpful and maybe easier in some ways  
for people that don't have as intransigent 
mental health symptoms. Obviously want  
to understand themselves better. So it's an 
exciting time to see what the future brings.  
Chapter 3, healing can echo across generations. 
One of the dilemmas that people had when they  
first heard about the diagnosis of PTSD or thought 
about the enduring effects of trauma is how can an  
event in the past continue to exert symptoms, 
continue to exert biologic effects? Why can we  
measure the blood or the brain in people that have 
post-traumatic stress disorder and see differences  
even though the event is passed? When we look 
at some of the hormonal changes that we see in  
people that have post-traumatic stress disorder, 
you don't really see the kind of things that you  
would see in someone that is undergoing stress. 
And one of the biggest examples of that is that  
people with post-traumatic stress disorder have 
lower cortisol levels. Cortisol is a hormone that  
is released by the adrenals during stress. It is 
designed to help you cope with the fight or flight  
challenge. We think that lower levels of cortisol 
are part of why the stress response doesn't fully  
shut off and continues to live on in some 
ways. But it wasn't until we began looking  
at epigenetic mechanisms or molecular mechanisms 
for the stress hormone receptors that we began  
to understand that perhaps one of the things 
that are allowing kind of the enduring effects  
of trauma are changes that are actually made 
into how those receptors work in the long run.  
So that in response to a very big traumatic 
event earlier on, there can actually be molecular  
changes and epigenetic changes that can change the 
way that the stress receptor genes function and  
really in some way keep alive a stress response. 
Many people have misconceptions about epigenetics.  
Epigenetics refers to the study of how genes 
are regulated. A lot of epigenetic mechanisms  
occur during development and help really with the 
complex choreography of which genes are firing at  
any given time. It explains something very real 
about why things just don't go back to normal.  
When epigenetic mark, once it's on the DNA, it 
survives cell division so that the daughter cells  
that are formed when the cell replicates itself 
through the process of mitosis and also meiosis,  
which is the process of making sperm and egg. The 
epigenetic mark is robust and it can survive cell  
division. A lot of excitement occurred a few 
decades ago when people began to understand  
that experience can also influence epigenetics. 
Now people talk a lot about how trauma influences  
epigenetics, but trauma is just another example 
of an environmental influence that can have a  
profound effect. The experience of treatment is 
also an environmental experience that can have  
profound effects and some of the work that we have 
done in the last decade has really demonstrated  
an improved response to treatment even to 
psychotherapy. When it comes to understanding  
issues like, well, how does psychedelics work? 
Why do they produce, if they do, a long lasting,  
enduring and transformative response? Many people 
who are treated with MDMA-assisted psychotherapy  
for PTSD actually say, "I feel really different 
now about my PTSD symptoms." First of all,  
they have far fewer PTSD symptoms. They also 
feel more self-compassionate and they also feel  
ready to kind of take the next step in life. 
They feel transformed. The word "transformed"  
could have also been used to describe how they 
felt when they had their traumatic experience  
to begin with. I'm not the same person that I 
used to be. And probably epigenetic mechanisms  
will be very important in helping us understand 
both the kind of transformative and enduring  
changes that occurred following trauma exposure 
and the ones that are associated with deep  
healing. It's not about a good event or a bad 
event. It's just about experience and the impact  
that experience can potentially have in regulating 
stress-responsive genes. Well, one of the really  
interesting things about epigenetics of PTSD and 
the epigenetics of recovery from trauma is that  
we found changes in the same region of the same 
stress-related gene in both situations. That there  
are epigenetic changes that on stress-related 
genes that might explain enduring effects and  
might also explain why we're more sensitized 
to our environments. And that somehow when  
people are successfully treated with PTSD, that 
you see some of those epigenetic changes again  
on those same genes, but in a reverse direction. 
So it's important to understand about epigenetics,  
and this is that you're not stuck just because 
there's an epigenetic change. If a certain  
region of a certain gene is responsive to the 
environment, then make healing environments so  
that we can transform in positive directions 
and I think to me that's really the message.  
I think it's really important to not take the 
epigenetics too literally and try to tie little  
regions on little marks on genes to specific 
behaviors. Certainly when people start talking  
about intergenerational epigenetic effects, we're 
not carrying trauma with us. These changes are not  
necessarily responsible for all the behaviors, but 
they're present. And their presence is probably  
a way to really allow the experience to stick 
with us for some reason. I'd like to think that  
epigenetics provides a mechanism for adaptation. 
Traumatic experiences really in essence provide  
a way of learning. Sometimes we don't like the 
lesson, but a traumatic event may teach us that  
certain situations are dangerous. And we want to 
have a way of really recollecting that and really  
acting on that so that we don't find ourselves in 
harm's way as often, or if we do, we can mount a  
response. When people talk about intergenerational 
transmission of trauma, which I'd really like to  
correct, it's not intergenerational transmission 
of trauma, it's the idea that people in a  
subsequent generation may feel the effects of 
a trauma in a first generation. Maybe that is  
a way of kind of transmitting a lesson to the 
next generation about how to cope or about a  
potential dangerous situation or scenario. So the 
idea is that really it's a type of wisdom. I just  
want to correct this idea that trauma is inherited 
or trauma sticks with us for generations. That's  
not what the science says. What the science says 
is that there are epigenetic marks in the adult  
children of trauma survivors in the same location 
as in the trauma survivors. And so there are a lot  
of questions that we could ask about why that 
might be so and how did those marks get there.  
But what's inescapable is that many people feel 
that it's not just the genes that they inherited,  
it's the experiences that the parents have 
also had, whether they be personal or cultural  
experiences that are very shaping and determine 
much of who they are. We have to start thinking  
about epigenetics also in terms of what it 
tells us about adaptation and resilience.  
What lessons do we take forward that can help us 
cope with adversity should we have to experience  
something the way our prior generation did. 
Our work was done primarily in the adult  
children of Holocaust survivors, and many of 
them feel very hyper vigilant as if somebody  
is trying to hurt them or chasing after them 
for no reason other than who they are. That's  
a trauma they're parent-experienced. And so 
this hyper vigilance may not serve them in a  
world where nobody is chasing after them. But once 
there's anti-Semitism, again, and they notice it,  
they might be more attuned to it. And being 
more attuned to anti-Semitism might end up  
being something that is adaptive if that is indeed 
what is happening in society. There are biologic  
mechanisms to keep the effects of experience 
alive from one generation to the next. We don't  
know if they're memories, we don't really know 
what form they take, but we know that it is kind  
of a biologic possibility, and this has opened 
up a lot of questions and a lot of potential  
excitement. For many people, it just means that 
what I feel is real, and that's good too. We  
really are very affected by cultural and societal 
and personal experiences of previous generation or  
generations. Really does form a tremendous 
amount of our identity, and it forms the  
basis of how we do respond to adversity when it 
occurs from a cultural and societal perspective.  
But what it might also mean is that responding 
to mass casualty and mass trauma and big traumas  
in our society may not be only a mental health 
problem, but it might be a problem of creating  
resilient and healing societies so that we have a 
mechanism for positive transformation and change,  
and we can use the power of culture and society 
to help each other cope from adversity rather  
than kind of use it to make us feel more isolated 
and stigmatized like we let people down by the  
fact that trauma occurred or how we responded to 
it. The legacy that we have most often from our  
parents and prior generations is that whatever 
they went through, they survived, and that's  
why we exist. We're here because someone survived 
trauma. And then the question is what's the next  
step beyond survival? It's restoring, repairing, 
achieving resilience, achieving growth and really  
understanding how to go forward despite being 
exposed to trauma. It's beyond just surviving  
to living. How do we then do that? One of 
the benefits of having a complete healing,  
which I think is possible with psychedelic 
assisted psychotherapy because it's not about  
just dampening symptoms. It's not about just 
giving a medication so that you can sleep better  
or that you no longer feel depressed or anxious or 
hyper-vigilant. It's really about going deep and  
correcting and changing this narrative that you 
got stuck in that is some version of how bad you  
are and how deserving you were of this trauma. But 
now you're having a different narrative about how  
you actually survived, did the best you could, and 
you have not only a more compassion for yourself,  
but you feel that you can take your rightful 
place in society, that you are part of the world,  
you are part of the earth. And having that legacy 
can be profound from animal research is that, and  
this is not our work, this is work that was done 
at Emory University, if you subject a male mouse  
to a cherry blossom and then shock the mouth, that 
mouse can develop a fear of that cherry blossom.  
That fear of the cherry blossom is associated 
with epigenetic changes in brain and sperm,  
and if that mouse is mated, that mouse's male 
offspring will also have the same changes in  
the epigenetic, in brain and sperm, but will also, 
inexplicably, be afraid of cherry blossoms, even  
though you didn't have to shock that offspring in 
order to be afraid. And that is a really powerful  
demonstration of what we're talking about, when 
we're talking about behavioral epigenetics and  
the kind of things that can be passed. But if 
you use fear extinction on that male mouse,  
that you continue to expose the cherry blossom 
to that mouse that is now afraid of the cherry  
blossom, such that he now becomes sensitized and 
says, "Okay, I guess a cherry blossom doesn't  
mean I'm going to be shocked," and then make the 
mouse. That offspring doesn't have the epigenetic  
changes in the brain and sperm. So this is a very 
profound example of what we're trying to achieve  
here. By trying to understand the epigenetics 
of what occurs in healing, generally and also in  
response to psychedelic assisted psychotherapy, 
we're just wondering whether that can kind of  
restore a certain biological equilibrium. The 
real beneficiaries of successful PTSD treatment  
are the next generation in some very real way. Not 
necessarily only because of epigenetic changes,  
but because a change in their parent is going 
to make a gigantic difference in their lives.  
So many people think that one of the mechanisms 
of how psychedelic assisted psychotherapy can  
help us process trauma is that it reduces the 
fear involved in approaching traumatic memories.  
And that can allow, once you don't have the fear 
of talking about the trauma, that can allow for  
new mechanisms in a way that this can facilitate 
a fear extinction if you think the problem is the  
fear. And there are studies that have also shown 
that MDMA specifically can dampen down some of the  
activity in the amygdala that occurs when a trauma 
survivor is exposed to a traumatic reminder or a  
script of their trauma. That is definitely one 
of the mechanisms that might be at play here.  
But it's really important to understand that fear 
is only one component of why people have enduring  
post-traumatic stress symptoms and overemphasizing 
the link between fear and PTSD is, I think, leads  
us to focus really on things like extinguishing 
a fear response without delving into why there  
is such an over-consolidated fear response 
to begin with and why there might be such an  
over-consolidated fear response might have to 
do with guilt and might have to do with shame  
and self-blame and all of the other kinds of 
narratives. One of the things I really like  
about the MDMA-assisted psychotherapy approach 
is that it's not directed. That the therapists  
are trained to follow the patient's process, to 
go where the patient goes. The patient might not  
go to "I'm scared." The patient might go to "I'm 
bad and always have been" and then go leapfrog  
straight over the event that was discussed 
in preparation to something that happened  
in childhood. We don't fully understand why we 
respond to events the way we do. When a person is  
exposed to a traumatic event in adulthood, they've 
already lived a life and there might be a lot of  
events from their past that are contributing to 
why they think that something that happened was  
their fault. And they may identify one of those 
early events and that has to be corrected in  
some profound way or a person needs to develop 
a large sense of empathy for that five-year-old,  
for example, or that six-year-old that maybe 
didn't get something that they should have  
gotten or maybe has been harboring some sort of 
a secret inside. Again, we don't all respond to  
trauma with PTSD. That's very important. It means 
that it's not just the exposure alone that put us  
here. The kind of the beauty of the psychedelic 
assisted psychotherapy experience is that it keeps  
it open. And I think some of the limitations 
of the current cognitive behavioral approaches  
have been this narrowing on. We're going to talk 
about this trauma. We're going to focus on what  
happened to you that you believe is the focus of 
your symptoms. Without understanding that, you  
know what? It could be something before. It could 
also be something that happened after the trauma.  
Someone spoke to a veteran who told me anything 
that happened to him in war paled by comparison  
to the systemic racism that he experienced when 
he came back from war. It pales in comparison  
to the sense that even after I served my country 
dispensable, I am not worthy and I am lesser. And  
so I think that what we have to understand is that 
there are factors before that contributed to how  
you're going to respond to a trauma in the moment. 
There are factors after the traumatic event that  
are equally as important and they have to do with 
how we're treated by our loved ones, by society  
at large, and how we treat ourselves. So it's 
just this whole long chain. And when you have an  
experience with psychedelics, the whole thing is 
open. If you're with trained people, they're not  
going to shift your focus and call it avoidance 
if you don't stick with the traumatic experience  
that we've agreed is the source of your problem. 
You may be open to identifying the kind of things  
that are really impeding your recovery or the 
kind of things that you really can't get past.  
And so a lot of the time, if we're in abusive or 
traumatic environments after we sustain a trauma,  
that just makes it a lot harder. And so sometimes 
with a psychedelic assisted psychotherapy,  
you're more able to broadly understand what in the 
here and now needs to be changed, even though it  
doesn't have to do with a then and there. And so 
what kind of change can I make to improve my here  
and now so that I can recover from the trauma. 
And the other aspect is really that we're not  
just looking to neutralize something negative. 
We're trying to learn from a traumatic experience.  
And for many people that heal successfully, what 
that looks like is them taking everything that  
they learned about what it is to be exposed to 
trauma and helping the next person who is exposed  
to trauma. This is what I should have gotten. 
This is what I want to give you. This is what I  
wish somebody would have taught me and to teach 
them to be self-compassionate so that we create  
a more healing society. What I hope viewers take 
away from this is that there's hope. I've talked  
to so many trauma survivors with PTSD or maybe 
even other mental health conditions who really  
feel that because the trauma happened and because 
we can't erase the fact that the trauma happened,  
they're just going to be stuck and unless somehow 
we can go back in the past and change the course  
of history, they're going to be in the state 
that they're in forever. And I think what this  
kind of public education message is all about 
is letting people know that there are so many  
ways to begin to deal with even the most severe 
PTSD cases and that if you're watching this and  
you or someone that you know or love is struggling 
because a traumatic experience occurred to them,  
trauma and PTSD are things that the mental 
health community has made great advances  
in. And psychedelic medicine in particular 
really offers a lot of hope for people who  
have not benefited from more traditional forms of 
psychotherapy or medicine. [music] Want to support  
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Apr 30, 2026

MDMA‑Assisted Psychotherapy

Epigenetics and Intergenerational Impact

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