condition that’s probably going to
affect everyone in this room either
directly or indirectly depending on the
personal experiences we have in our
lives of addiction or the experiences
that one of our loved ones has with
addiction we can come up with all sorts
of different rationalizations to explain
why addictive behaviors take place okay
so we can think of addiction as a bad
habit so something that we’ve fallen
into due to circumstances in our lives
beyond our control may be addiction is
just a personal choice is addiction may
be a moral failing is to do to some sort
of intrinsic personality flaw well
recently we’ve been thinking about
addiction in terms of it being a disease
state now I’m a neuroscientist I’ve been
studying the neurobiology of addiction
for almost 20 years now I’ve come to
appreciate the importance of how we
conceptualize addiction because it
really addresses how we approach the
issue of addiction in terms of our
research and in terms of how we treat
people that are suffering from addiction
now the disease model of addiction is
probably one that everyone in this room
is familiar with it sort of thinks of
addiction as being an organic brain
state sort of akin to what we think of
typical brain disease diseases like
Parkinson’s or Alzheimer’s it’s also
suggesting that addiction should be
thought of as a permanent state of brain
pathology the idea that once an addict
always an addict sort of encapsulates
this idea that addiction might be best
represented as a disease state but I’m
gonna argue today that this is probably
not the best way for us to be
approaching addiction or to be thinking
about addiction and I’m going to suggest
that there’s an alternative way to think
of addiction more as a disorder of
reward and memory pathways in your brain
now some of the implications of this
model of addiction suggest that
addiction is rather a plastic series of
brain adaptation it’s a dynamic process
in the brain rather than a permanent
state of brain pathology it’s something
that we can reverse and finally decide
that addiction might be controlled by
specific molecular mechanisms in the
brain that can actually take you from a
healthy non-addicted state to an
addicted state okay so the well-known
addiction cycle all drugs of abuse begin
by producing very strong rewarding
effects in my field of a my field of
study we look at the rewarding effects
and the addictive properties of opiate
class drugs so this includes drugs like
heroin morphine and more recently
prescription narcotics and we’ve had a
tsunami of addictions related to drugs
like vicodin percocet oxycodone costing
us billions of dollars not to mention
the horrendous social cost associated
with addiction to these substances
now if we take these drugs over an
extended period of time
what happens is we start developing
adaptations in our brain changes in the
brain happened in terms of our neural
chemistry the molecular substrates
controlling these pathways and even
structural differences in various brain
regions finally we develop psychological
and physiological dependence on the drug
after a period of exposure to the drug
of abuse now this is especially true
with opium class drugs we have this very
strong physiological dependence syndrome
that develops with opiate class drugs
now once the drug is taken away from us
we almost inevitably are going to go
through a period of withdrawal and
that’s accompanied by these very strong
feelings of craving you’ve got to get
this drug back into your system to
alleviate those feelings of withdrawal
that you’re experiencing now finally
sort of the fourth part of this chain
and we argue is actually extremely
important and one that’s been under
looked for a long time is the importance
of memory induced relapse so if I were
to inject myself with heroin right now
and experience these profound rewarding
effects and then I forgot about it in 20
minutes
chances are I’m not gonna become
addicted what happens when we experience
the rewarding effects of a drug of abuse
our brain forms associations between
those effects of the drug and all of the
environmental cues so for example
someone that was addicted to heroin and
has been clean for 10 even 15 years
walking down the street they see some
sort of – in their environment that re
triggers those addiction memories and
they fall right back into relapse so you
can see when we look at it in terms of
this chain of events to effectively
treat addiction we need to break at
least one of these links so in a
nutshell we can sort of think of
addiction as being importantly
controlled by reward systems in the
brain and memory systems in the brain
now in terms of explaining addiction
based on many years of animal-based
research and clinical research as well
there were two sort of general theories
of addiction that were sort of popular
at the time when I began this sort of
research about 15 20 years ago one set
of theories were the dopamine reward
theories and this was based on the idea
that almost every single drug of abuse
activates dopamine neurons you get this
release of dopamine in the brain so
logically we thought that ok drugs would
use activate dopamine so that’s why I
become addicted we activate our dopamine
system and that’s why we keep taking
drugs now on the other side of the
spectrum theories sort of focus more on
the darker side of the addiction process
withdrawal and these sorts of theories
suggested that the reason we keep taking
drugs of abuse is because we go through
the draw and we need to seek out those
drugs in our environment to alleviate
those unpleasant feelings of withdrawal
that we’re experiencing so when you
think about these theories for a second
you sort of realize that there’s some
obvious problems with both of them in
terms of dopamine well as the years went
by we realized that dopamine is not as
simple as we thought dopamine tomorrow
more complicated so for example dopamine
is activated even during unpleasant
experiences the other problem
theory is that it does a good job
explaining why we take drugs in the
first place but we know that when we
continue taking drugs of abuse they’re
rewarding effects tend to decline over
time even the dopamine response can
sometimes get lower and lower so how
does it account for why we continue
taking drugs of abuse for years and
years and years now on the other side of
the equation
withdrawal based theories do a good job
of explaining why we fall into a relapse
to addiction but they don’t do such a
good job of explaining why we started
taking drugs with use in the first place
so an obvious question is
is there some sort of link between the
brain mechanisms that control these
early rewarding effects of drugs and
these later effects of withdrawal and I
want to present this idea of an
addiction switch that can essentially
serve as a a mechanism to account for
the transition from the healthy
non-addictive brain state to the
addictive bracelet we know that
addiction fundamentally changes the
brain I talked about a couple of those
changes they have been at the molecular
level or chemical level structural level
and more importantly looking beyond the
brain addiction fundamentally changes
the cell it changes your personality
changes your cognition it changes your
behavior and anyone who has watched a
loved one go through the horrible
effects of addiction one of the things
that stands out in your mind is you
remember how much that person’s
personality and their behavior changes
while the while they’re under the
influence of the drugs of abuse now in
terms of opiates one of the most
addictive drugs that are potentially
available we knew a couple important
things about opiates that suggested that
there might be some sort of switching
mechanism going on between these we knew
that in the naive state so before you
became addicted to opiates the effects
of opiates could be mediated through a
dopamine independent pathway so you
don’t need dopamine to experience the
rewarding effects of opiates when you’re
first starting out taking the drugs
obviously in the naive state there’s an
absence of withdrawal mechanisms in the
brain there’s a very minimal amount of
molecular changes that are taking place
but then we looked at the effects of
opiates in the addicted State and we saw
a profound difference so first of all we
noticed that the rewarding effects of
opiates once you’re addicted opiates
activate the dopamine system so you need
to have a switch to a dopamine system
there is very strong feelings of
withdrawal and craving there’s obviously
profound molecular alterations and
various brand reward pathways that are
very important so the question that was
posed when I actually began looking at
this question about about 15 years ago
back
University of Toronto was whether or not
we can find this elusive hypothetical
switching mechanism in the brain that
controls this transition from a
non-addictive state to an addicted state
so without going through the minutia and
the years of research that led to these
conclusions what we were able to find
was that when we focus on an area of the
brain called the ventral tegmental area
neuro Anonymous like coming up with
these unpronounceable words but we’re
just going to call it the VTA for the
sake of simplicity this is an area in
the middle part of your brain sort of
the base your brain and it contains the
dopamine system and it’s very important
for drugs of abuse because almost all
drugs of abuse produce their effects
through the VTA so in a very simplified
explanation of this what we found was
that gaba-a receptors which is a type of
inhibitory receptor located in that area
of the brain was actually able to serve
as a molecular switching mechanism
between a non addicted state and in it
an addicted state so normally you can
think of the GABA a receptor as
controlling the bio electrical
properties of a neuron they control
whether a neuron is on or off and
remarkably what we found was that in the
non addicted state the gob a receptor
acted normally it produced inhibitory
signals to the neuron it shut down
neurons but once we looked at an
addicted brain the function of GABA a
receptor switched to an excitatory State
so essentially we’re looking at a
mechanism that controls reward signaling
for a non-addictive grant award pathway
versus a system that is switched on in
the addicted state and transfers reward
signals through an addiction brain
reward pathway so that’s great we found
this hypothetical switching mechanism in
the brain but remember that I said that
addiction is more than reward we also
need to experience memory we’re talking
memory is a very critical component of
addiction so for example as I mentioned
before we need to form these associate
memories in our brain in order to
continue that addiction cycle and we
next look at an area of the brain called
the basal lateral amygdala and then
another one of these unpronounceable
terms we’re just going to call it the
VLA now this is an area of the brain
located in your temporal lobes and it’s
extremely important for your ability to
form associative memories between the
effects of drugs of abuse and their
related environmental cues so we looked
at this region of the brain called the
PLA to see if this might serve as a
memory switch between the non addicted
state and what we found was that in the
non addicted brain the ability to form
opiate addiction reward memories
depended on a receptor substrate called
the d1 and it modulated a downstream
molecule we’re just gonna call it earth
so a non dependent drug naive molecular
mechanism in the BL a controlling
addiction memories in the naive state we
looked at the addicted brain and what we
found was that there was a switch
between this d1 receptor mechanism to a
completely different brain reward
mechanism for the formation of addiction
memories and now we were dealing with a
system that relied on a type of receptor
called the d2 receptor and an entirely
different molecular downstream signaling
pathway both cam kinase 2 so again just
like in terms of processing the
rewarding effects of drugs of abuse when
we look at the difference between the
addictive state and a non-addictive
state the ability to form drug addiction
memories is also under the control of a
discrete switching mechanism and the
really cool thing about this is that we
were able to target those molecules in
the amygdala and switch the brain back
and forth from an addicted state to a
non addicted state so this is really
exciting because to suggest that instead
of thinking of addiction as this chronic
permanent irreversible state we can
actually go into these brain areas we
can target these molecular pathways and
we can actually switch the brain from a
non-addictive state to an addicted state
and back and forth so this really calls
into the question the need for us to do
a new paradigm for conceptualizing
what’s really going on in addiction we
know that in the non dependence state
we’re dealing with an entirely different
set of molecular and neuroanatomical
mechanisms that control how you perceive
the rewarding effects of a drug like
heroin for example but once you become
addicted to that drug something switches
in your brain there’s a switch two
entirely separate molecular and neuronal
systems in the brain that control how
you perceive that rewarding effective
drugs of abuse so this is really
thinking of addiction much more in terms
of a plastic dynamic process that allows
us to go back and forth between these
different states so where do we go from
here I think one of the most important
questions to ask let’s go back to the
beginning and address the issue of
whether or not the disease model of
addiction has really served us well and
I’m going to argue that no it hasn’t
really been an effective model for us in
terms of our ability to understand
what’s going on in the brain and more
importantly in terms of developing
effective treatments for addiction
because remember after many decades and
many thousands and thousands of research
papers from all sorts of disciplines we
have yet to develop a truly effective
treatment for dealing with the
devastating effects of addiction the
problem with the disease model of
addiction is twofold
the first problem is that it doesn’t
take into account these dynamic
processes that are happening in your
brain as you go from a non-addictive
state to an addictive state because I
said at the outset we think of diseases
as these sort of permanent static
processes as opposed to these more
dynamics switching mechanisms that go on
in the brain the second problem is that
when we use a disease model of addiction
whether we’re talking about forming
questions for our research or developing
more effective cycle therapies for
treating addiction we tend to focus more
on the effects of addiction we focus on
the symptoms of a dish instead of the
underlying causes of addiction now
having said that I think that there’s
enough evidence out there it’s Jess
that a better way of thinking of
addictions are that we’re dealing with
an altered but reversible state of the
brain it’s controlled by a series of
molecular mechanisms that control the
switch of a non-addictive state an
addicted state and as I said before
what’s most exciting about this that
allows us to go into the brain target
these molecular pathways and potentially
develop more effective pharmacal
therapeutics or more effective
psychotherapeutic approaches to dealing
with addiction by appreciating some of
these dynamic mechanisms so as I said at
the outset one of the important things
about addiction in terms of
understanding how it processes the
rewarding effects of drugs of abuse is
this idea that we can identify a switch
and ultimately turn off the effects of addiction in the brain