The neuroscience of psychedelic drugs, music and nostalgia

At various points over the past 20 years,

I've studied two fundamental
human experiences

that have taught me
an awful lot about emotion,

and that may hold the keys
to a revolution in psychiatry.

The first is how we experience music.

The second is how we experience
psychedelic drugs

such as LSD and magic mushrooms,

or psilocybin,

which is the active component
in magic mushrooms.

You may be wondering what these two things
have in common outside of Woodstock.

After all, music is not
a physical substance.

It can be described as a limited set
of vibrations in the air

that can be detected by your ear.

And music may seem to have more to do
with aesthetics than with biology

or chemistry.

Psychedelic drugs, on the other hand,
are physical substances.

They are chemical compounds
that you can ingest

that directly interact
with brain chemistry

and change your experience of the world.

This change is temporary,

but the effects of this change
can alter the course of your life.

But let's face it:

psychedelics have the potential

to trigger unexpected
and potentially dangerous effects.

So what could these two very different
things possibly have in common?

I've found that music and psychedelics
can impact our well-being

in powerful and complementary ways.

Music can have a direct
impact on our emotions,

with measurable impacts on the brain;

psychedelic drugs,
under the right circumstances,

may have therapeutic effects.

These effects can be manifest in patterns

that we can study
and document with brain scans.

And together, and leveraged
in a purposeful fashion,

music and psychedelics may have
an even greater healing impact

on patients.

What's more, these effects can be manifest
in healthier and happier lives

and more integrated personalities.

I began my journey into the mental
health benefits of music

long before I ever intended
to make such a journey.

For roughly half of my life,
I've been a musician,

having played in community orchestras,

community theaters,

wedding bands, a salsa-merengue band.

I was a member of a string band
in Philadelphia for many years.

And for the better part
of my formative years,

I was the drummer
in a Weezer-Nirvana cover band

that morphed into a hardcore punk band.

(Laughter)

That's right.

Drummer in a punk band.

But it wasn't until I really began
my career in psychology and neuroscience

that I began to also appreciate
how widely and how deeply we as a species,

both implicitly and explicitly,

use music as a tool to try
to regulate our emotions

and to heal.

And for some of us, music keeps us going.

For others, music isn't quite enough.

For me, this led to some
fascinating questions.

I began to use music as a tool
to study emotion and memory in the brain.

My first scientific study was focused
on music-evoked nostalgia.

Nostalgia's a rich and bittersweet emotion

that is intimately tied up
with our autobiographical memories.

We can often encounter nostalgia
in unexpected places.

You may have had the experience
of driving down the highway,

turning on the radio

or firing up your favorite music
recommendation service,

and you hear a song
you haven't heard in ages,

and you get immediately
transported back in time

and dumped into this immersive memory --

something you haven't
thought about in ages

but was very meaningful to you --

maybe wedding day or senior prom

or the birth of your first child

or the death of a loved one.

Music can serve as a powerful context cue

for deeply meaningful and intensely vivid
nostalgic memories such as these.

Nostalgia, in a sense,
is deeply woven into our sense of self.

Who are we at our most authentic selves?

By connecting us
with our emotional histories,

nostalgia can help us
to stave off sadness, loneliness,

existential threat

and even the imminence of death

and the approaching horizon
of our lives as we age.

To try to get a better understanding
of how music may tap into nostalgia

and what that may be doing in the brain,

I began to work with computational
models of music cognition.

I applied these models
to interrogate brain activity

that was recorded
while people were listening

to nostalgia-evoking
and nonnostalgia-evoking music.

And importantly,
at least to a brain geek like me,

I found that nostalgia was able
to recruit a wide network of brain regions

involved in multiple levels
of different cognitive processes.

Whereas nonnostalgic music
could recruit brain regions

such as Heschl's gyrus,

involved in basic auditory processing,

or Broca's area,

which is involved in processing
grammar and syntax

not only in language but also in music,

nostalgia was able to recruit
these brain regions and more.

Brain regions such as the substantia nigra
involved in reward processing

or the anterior insula involved
in the visceral experience of emotion

or brain regions
in the inferior frontal gyrus

that are involved
in autobiographical memories.

Nostalgia was also able to recruit
a wide network of brain regions

in prefrontal, frontal, cingulate,
insular, parietal, occipital

and subcortical brain regions

that span nearly all
of our cognitive faculties.

This may explain why nostalgia
can have such an outsized impact on us.

But as powerful as it is in the moment,

the salve of music-evoked
nostalgia eventually fades.

Nostalgia may be more of a Band-Aid,

less of an antibiotic

and typically far from a surgical
intervention for our emotional health.

Music can draw out nostalgia

and music and nostalgia
can move our feelings,

but how do we make these feelings stick?

After studying the nostalgic brain,

I joined a team
at Johns Hopkins University

that was studying the effects
of psychedelic drugs,

and I quickly began to learn how deeply
a piece of music could impact a person

during a psychedelic experience.

I was previously vexed by the difficulty
in predicting precisely

what musical stimulus would evoke
precisely what response

within a given individual.

A song that evokes nostalgia in one person
could just as easily evoke disinterest

or disgust in another person.

I began to learn how deeply most music
seemed to impact most people

during psychedelic experiences.

Since at least the late '50s,

the value of using music to help people

to navigate psychedelic
experiences was clear.

We continue this tradition
in our modern research,

asking volunteers to listen to music

during the course
of a psychedelic therapy session,

and despite most people being
mostly naive to the music that we play

before they get into the sessions,

after these sessions,

our volunteers practically
beg us for the playlists.

And some of them report
returning to the songs

that were most impactful to them
during their psychedelic experience

weeks, months and even many years
after the experience.

Somehow, these songs
can turn into touchstones

that can rekindle the most powerful
and impactful and insightful experiences

that people encountered
during their psychedelic sessions.

Of course, I had to know
what was going on here.

I began to deploy
my batteries of questionnaires

and my carefully crafted experiments

and my big, fancy MRI machines

to try to determine
just what could be happening

during these experiences

that could explain the depth
of impact that people were encountering.

At a basic psychological level,

my colleagues and I determined that,

for instance, LSD can increase
positive emotions

that are uniquely encountered
during music listening.

This may have relevance just by itself
for healthy individuals,

as well as people suffering from mood
and substance-use disorders.

But what was happening in the brain?

Earlier we learned that the entire brain
listens to nostalgic music.

When applying computational models
of music cognition

to interrogate brain activity
that was recorded during music listening

under the effects of LSD,

we found that the entire brain
was listening to music

and psychedelics were turning up the gain.

Where nostalgia could recruit
brain regions involved in language,

memory and emotion,

psychedelics were recruiting
these brain regions

at least twice as strongly.

Brain regions such as the thalamus,

that's involved in basic
sensory processing

or the medial prefrontal cortex

and the posterior singular cortex,

which can be involved in memory
and emotion and mental imagery.

These brain regions were recruited
up to four times as strongly

during the effects of LSD
than without LSD.

Psychedelics turn the knob up to 11.

Sensory information
is more richly experienced in the brain;

emotions, memories
and mental imagery are supercharged,

and it may be the wholesale
and strong recruitment

of a wide range of brain regions
during these experiences

that is the necessary key
to unlocking change

that sets these drugs
and these experiences apart from others.

And the effects can be long-lasting.

In a study of healthy individuals,

I demonstrated that a single
high dose of psilocybin

could reduce negative affect in volunteers
for at least a week after psilocybin,

and increase positive affect

for at least a month
after a single high dose of psilocybin.

The reduction in negative affect

that we observed after
psilocybin administration

was accompanied by a reduction,
one week after psilocybin,

in the response of a primitive
brain region called the amygdala

to emotional stimuli.

In a separate study in patients
with major depressive disorder,

not only did we observe a substantial
decrease in depression severity

in most of our patients
after two doses of psilocybin,

but we also observed a reduction
in the amygdala response

to negative affective
stimuli, specifically,

one week after psilocybin.

This reduction in amygdala response

was associated with an enduring
reduction in depression severity

for at least three months
after psilocybin administration,

but frankly, we're still counting.

So what does this all mean?

It means that music
and psychedelics may be able

to alter the entire brain
for a period of time,

and that may lead to a change
in neural circuitry

that may be stuck in patterns
of negative emotional bias.

This may be able to give people
a period of relief

from the grip and the claws
of negative emotion.

And that may be just enough to give
someone access to new perspectives

on their selves and their lives

and begin on the road to healing
from years of depression.

These drugs are early
in stages of research,

but they're now being researched
for a wide range of medical indications.

There's evidence growing

that psychedelics may be effective
in helping to treat mood disorders

such as major depressive disorder,

treatment-resistant depression

and the depression and anxiety

that accompany a late-stage
cancer diagnosis.

There's also evidence accumulating
that psychedelics may be effective

in helping to treat a wide range
of substance-use disorders,

including smoking, drinking
and cocaine use.

Additional studies
are either being planned

or are already underway

to determine whether psychedelics
may be effective in treating

an even wider range
of intractable disorders

such as OCD, PTSD,

opioid-use disorder and anorexia.

At this point it might be reasonable
to take a step back

and say, "Are psychedelics
being sold as a panacea?"

And if so, we should
be rightfully skeptical.

Why should we expect such a small family
of compounds to be so effective

in treating such a wide range
of disparate disorders?

Here's a perspective we might consider.

Some of these disorders
share a common thread.

At some level,

mood disorders and substance-use disorders
involve negative affect

and a disconnection
from our most authentic selves.

Psychedelics may break that mold.

Psychedelics and music
may represent a one-two punch

that can operate on psychological
neural processes such as negative affect

that cut across and contribute
to multiple disorders.

It may be that targeting
such transdiagnostic processes

is what's necessary to really help people

to develop the resources
that they need to begin to recover

from years of depression
and substance use.

They say you never get a second chance
to make a first impression,

and that may be true
for psychedelic drugs.

After all, no matter
how much data come out

for the potential of therapeutic
effects of these drugs,

there are still some who are stuck
on the stigma from the '60s and '70s:

myths of the wildly addictive
properties of these drugs

or myths of genetic abnormalities

or birth defects after
being exposed to these drugs,

or fears that people
are going to lose their minds

and go insane --

or maybe even most pervasive

is the sense that these effects
are necessarily real

and that they're a necessary outcome
of having been exposed to these compounds.

It may be time to change
our thinking on that point.

No one should expect psychedelic
drugs to work for everyone.

No one should expect psychedelic
drugs to work for everything.

They're powerful compounds

that need to be administered
under carefully controlled circumstances.

And there are almost certainly
people in this world

for whom psychedelics
are incredibly dangerous.

But ...

antibiotics administered to the wrong
person under the wrong conditions

can be incredibly dangerous, if not worse.

But administered to the right person
under the right conditions,

antibiotics save lives.

Administered to the right people
under the right conditions,

psychedelic drugs may save lives.

It can often feel like it's impossible
to heal our hearts and our minds

and to grow,

but I truly believe that we all have
the resources within ourselves

to do just that.

The challenge is often identifying
and connecting with those resources,

and it may be that psychedelics
and music can help people

to do just that.

Together, psychedelics and music
may be able to open our minds to change

and direct that change,

reconnect us with our most
authentic selves

and allow us access to the things

that really allow us to make
meaning in this world

and reconnect

with our most authentic selves.

Thank you.

(Applause)