[APPLAUSE]
[Dr. Nora Volkow Speaking]                                                 Good afternoon. It’s a pleasure. It’s
an honor. It’s a privilege for me to be
here with all of you and to celebrate all
of the fellows. And I want to thank the APA
and Dr. Summergrad for giving me the opportunity
to share this moment with you.
I devoted all of my life to study the effects
of drugs in the human brain. To try to understand
what is it that they do to our brains that
in some people that are vulnerable that leads
them to the complete loss of control with
severe catastrophic consequences.
But, before I actually go into that and what
I’ve learned I want to share with you. I
want to share a personal story that perhaps
can help you put it in perspective.
As Dr. Summergrad mentioned, I was born in
Mexico City, and many, many years ago, when
I was five or six years old, I remember having
dinner with my family, with my parents and
my three sisters, and there was a man that
came to deliver a telegraph to my mother.
I remember my mother crying after she read
the telegraph. I had never seen my mother
cry, and I wanted to console her. But she
did not want us to see her cry, and she left
the room and locked the door behind her. The
next morning, my father told us that the father
of my mother had died.
It was many, many years later, when I had
gone to medical school, when I had completed
my residency training in psychiatry, when
I had already been working for many years
in brain imaging to investigate what drugs
do to our brains and how we become addicted.
At the time when my mother was dying of cancer,
she called me and said, “Nora, I need to
tell you something I have never spoken to
you about.” And she told me that my grandfather,
her father, had been an alcoholic, and that
in his distress at not being able to control
his strong urges to drink alcohol, he had
killed himself.
And I was taken aback by this, because I never
knew my grandfather was an alcoholic and I
had always thought that he died from cardiac
complications. But I was also taken aback
by the fact that my mother had kept this a
secret from me, even though she knew that
my professional life was devoted to trying
to understand what drugs do to the brain.
She had heard me speak of addiction as a disease
of the brain. So I wondered how I had miscommunicated,
how could I have not made her realize, that
it was okay to speak about addiction.
And then as I think about these words I’ve
gone over many times in my brain, and I realize
that describing addiction as a brain disease,
describing addiction as a chronic brain disease,
is sort of a theoretical concept. Say that
you have two parents with a very sick child,
and they go to the hospital, and the doctor
says, “Your child is in a coma because he
has diabetes.” And he explains to them that
diabetes is a disease of the pancreas, a chronic
disease of the pancreas. This does not explain
why that child is so severely ill. What explains
it is the understanding that the cells in
the pancreas can no longer produce insulin,
and we need insulin in order to be able to
use glucose as an energy source, so without
it, the cells in our body are energy-deprived—which
explains why this child is so sick.
So when we speak of addiction as a chronic
disease of the brain, what does it mean? How
does it help us explain the devastating changes
in behavior of a person that’s addicted,
where even the most severe threat of punishment
is insufficient to have them stop taking drugs,
where they are willing to give up everything
they care for in order to take a drug? How
does “a dysfunction in the brain” help
us understand that?
Well to start with, we’ve known for many
years that all the drugs of abuse that produce
addiction, all of them, whether it’s legal
or illegal, all of them increase dopamine
in brain reward regions, activating them—and
that, in turn, motivates our actions. Which
explains why behaviors that are rewarding
have been used by nature in order to ensure
that we survive, as an individual, and as
a species. That is why food is so rewarding.
That’s why sex is rewarding so we can survive
and procreate. Drugs hijack that system.
So it made perfect sense that one of the first
theories regarding why a person that’s addicted
will take drugs was because in them their
brains was much more sensitive to the rewarding
effects of drugs. In other words, in them
the drugs will produce much larger increases
in dopamine than in a person that was not
addicted. Which will then explain their enhanced
motivation for taking the drug.
Except that the research shows that was not
the case. In fact, it showed that the opposite
appeared to be true, that people who are addicted
to drugs, showed much lower increases in dopamine
when they were given the drug, than those
who were not addicted. This was completely
counterintuitive. It was counterintuitive.
You’re addicted. The addicted person has
less increases in dopamine with a drug and
we are saying that the ability of drugs to
increase dopamine in reward regions is why
we take them?
So why would an addicted person even bother
to take the drug?
As counterintuitive as this may seem, it was
actually very consistent with what we had
started to learn about how the dopamine cells
in our brains responds to reward. This was
actually a very, very unexpected finding.
It was first reported by Wolfram Schultz,
who showed that in animals, when you give
an animal a reward, their dopamine cells fire,
but with repeated administration of that reward,
the dopamine cells stop firing to that reward.
But instead, fire when they get exposed to
the conditioned stimuli that predicts the
reward.
What is a conditioned stimuli? A conditioned
stimuli is that one that has been associated
by its temporal sequence or by its spatial
presence with the actual experience of the
reward, and this conditioned stimuli by itself
increases dopamine. When we increase dopamine
that activates the motivation and drive that
leads you to want to consume that particular
reward.
Now, things when we look at them scientifically
retrospectively can make a lot of sense and
when I think about this particular finding,
I just marvel at the extraordinary design
of nature. Why do I say this? I say this because
increasing dopamine in reward regions is what
motivates our behavior. What nature is aiming
for us to do is to ensure that we do the behaviors
that will allow us to survive. In the case
of food, to consume it. But it wants you to
be motivated to engage in the behaviors that
will allow you to get the food so you can
consume it.
So, by being conditioned, you will engage
that motivational system that is anticipating
to receive a reward so that you can ensure
to do the behaviors and procure the reward.
This is exactly why people that are addicted
to drugs have the enhanced motivation to take
them because they have been conditioned. They
have been conditioned to the place where they
take drugs. They have been conditioned to
the dealer that sells them their drugs, to
the friends with whom they get high. They
have been conditioned to the emotional state
that precedes the anticipation of getting
that drug. This drives their behavior.
But addiction does not end there in the reward
motivation conditioning system. Drugs, by
their chemical nature, activate dopaminergic
pathways and the repeated administration of
these drugs triggers neural adaptations
on those pathways rendering them much less
sensitive to normal physiological stimuli.
But the dopamine pathways are not limited
as I say to reward and motivation. In fact,
in psychiatry for many years we already knew
that the dopamine system was fundamental in
the function of the prefrontal areas of the
brain.
In studies, first of all, by work in part
by Dr. Patricia Goldman-Rakic, we’re actually
trying to understand the role of dopamine
in Schizophrenia and was able to document
that it is indispensible for the proper function
of the prefrontal areas in our brains that
enable us to exert executive function, self-control,
self-regulation, working memory, decision-making,
and judgment. More recent work has shown that
disrupted dopaminergic signaling into the
prefrontal cortex helps us explain the impulsivity
in patients that suffer from Attention Deficit
Hyperactivity Disorder.
We have also learned, in part by research
in other psychiatric diseases, that the dopamine
system is also extraordinarily important in
regulating the function of limbic areas of
the brain, such as the amygdala and the hippocampus,
that are processing emotions, that are processing
our reaction to stressful stimuli. We have
known of their involvement in Schizophrenia,
and more recently we have also come to recognize
their fundamental role in Post Traumatic Stress
Disorder, where again, just as in addiction,
dopamine enables that conditioning. Conditioning
in this case to a negative stimuli in contrast
to conditioning to a rewarding stimuli. All
of these pathways get disrupted by the repeated
administration of drugs.
So what is the clinical significance?
Dopamine enables us to regulate our behavioral
choices, our ability to change our behavior
when the environment changes so that we can
optimize our actions to sustain effort, to
resist immediate rewards, to delay gratification,
to be able to conceive a goal for our future,
and to carry it through. Drugs disrupt that.
But these networks that are disrupted by drugs
do not belong uniquely to addiction. As I
already mentioned, they contribute to the
psychopathology of multiple psychiatric diseases.
I mentioned Schizophrenia, ADHD, Post Traumatic
Stress Disorder, among others. Which of course
gives us an explanation about why these individuals
with mental illness are more vulnerable to
taking drugs. Because the dopamine enhances
the effects of drugs, this will temporarily
relieve some of the symptoms. The problem
is that with repeated administration it will
downregulate their function, exacerbating
the clinical presentations of the patients.
It also highlights to us as we think of addiction
as a disease of multiple networks being disrupted,
that our therapeutic approaches should follow
a multi-prong strategy. We should aim to enhance
the motivation for other non-drug behaviors
in addicted people so that they have alternative
actions. We should aim to strengthen prefrontal
cortical circuits so that they can exert cognitive
control over their desires, their emotions,
so that they can predict situations where
they may be at greater danger of taking drugs
and avoid them. Interventions to decrease
the strength of condition stimuli; to decrease
the enhanced sensitivity to stressors, to
improve their negative emotions, so we can
help them and prevent them from relapsing.
I think a lot and I go back a lot to that
conversation with my mother, and I always
of course wonder what did I miss. I missed.
Of course I failed because she kept the story
of her father a secret from me. But I also
realize that her shame or her fear, was not
just because my grandfather had been an alcoholic,
but because he had committed suicide. He had
committed suicide out of hopelessness and
helplessness at the inability to control the
strong urges to drink, and then relapse, and
the inability to stop taking the alcohol,
and then relapse again, and again, and again,
until there was one last moment of self-hatred,
and he killed himself.
This should have not happened. But, it’s
too late. My grandfather had died. My mother
died thirty five years later*… and it’s the past.
It’s my story and I live with it. But I
wanted to share it with you so that this does
not happen to our future patients. So that
this does not happen to our current patients.
We psychiatrists have an obligation to treat
substance use disorders in our patients. Whether
they are by themselves, or as they frequently
emerge comorbid with other mental illnesses,
you can treat substance use disorders, and
in so doing, you will improve the outcomes
of the patients, for the substance use disorder,
but also the other comorbid psychiatric disease.
You will decrease the suffering in the families
and the health care system will win.
All of the averted cost associated with adverse
medical consequences, averted cost associated
with accidents, averted cost from criminal
behavior… if we in psychiatry embrace addiction
as a chronic disease of the brain, where the
pathology is the disruption of the areas of
the circuits that enables us to exert free
will. That enables us to exert free determinations.
Drugs disrupt these circuits.
The person that is addicted does not choose
to be addicted; it’s not a choice to take
the drug. Many times they take it and they’ll
say it’s not even pleasurable. “I just
cannot control it.” Or they’ll say, “I
have to take the drug because the distress
of not having the drug is so difficult to
bear.”
If we embrace the concept of addiction as
a chronic disease where drugs have disrupted
the most fundamental circuits, that enable
us to do something that we take for granted—make
a decision and follow it through—we will
be able to decrease the stigma, not just in
the lay public, but in the health care system,
among providers and insurers. So that patients
with mental illness do not have to go through
obstacles to obtain the evidence-based treatments,
so that they don’t have to feel that shame,
they don’t have to feel inferior, and perhaps
we will be able to feel empathy for a patient
suffering from a disease we call addiction.
Thank you very much.
[APPLAUSE]
