Is CBD an Endocannabinoid Reuptake Inhibitor?

0
5


Transcript


Project

CBD
:


Welcome
to
another
edition
of

Cannabis
Conversations
.
I’m
Martin
Lee
with
Project

CBD
,
and
today
we’re
going
to
be
speaking
with
Matt
Elmes.
Matt
is
the
director
of
new
product
development
at

CannaCraft
,
a
major

cannabis

company
in
California.
Matt
heads
up
the
science
team
there,
and
CannaCraft
has
been
a
supporter
of
Project

CBD

for
several
years.
Matt
holds
a
PhD
in
molecular
and
cellular
biology
from
the
State
University
of
New
York
at
Stony
Brook,
where
he
also
did
his
post-doc
work.
And
much
of
that
work
focused
on

the
endocannabinoid
system
.
And
that’s
what
we’re
going
to
talk
about
today.


Let’s
roll
back
the
clock
for
a
moment
to
the
1990s

the
decade
of
the
brain.
There
were
several
discoveries
about
the

endocannabinoid
system

and
certain
components
that
comprise
what
scientists
would
refer
to
now
as
the
“canonical

cannabinoid

system”

the
cannabinoid
receptors
in
the
brain
and
the
body,

CB1

and

CB2
,
and
also
the
endocannabinoids
that
bind
to
these
receptors.
And
then
there
was
the
identification
of
certain
proteins
that
were
involved
in
the
biosynthesis
and
the
breakdown
of
these
endocannabinoids.
Your
group
at
Stony
Brook,
Matt,
added
a
whole
other
dimension
to
understanding
the
endocannabinoid
system.
You
were
involved
in
the
discovery
of
what’s
known
as
“transport
molecules.”
Maybe
you
could
explain
what
a
transport
molecule
is
and
what
it
has
to
do
with
the
endocannabinoid
system.


Elmes:

The
transfer
molecules
we’re
talking
about
are
the
fatty
acid
binding
proteins,
or
I’ll
call
them
the

FABP
s.
First
they
have
a
canonical
role
in
transporting
fatty
acids
throughout
the
body,
and
that’s
why
they
got
their
name.
However,
my
group
at
Stony
Brook,
particularly
my
mentors
Dale
Deutsch
and
Martin
Kaczocha,
led
the
discovery
that
these
molecules
are
also
transporting
the
endocannabinoids

namely
2-AG
(2-arachidonoylglycerol)
or

anandamide
.


Project

CBD
:


Why
would
they
need
to
be
transported?
Why
don’t
they
just
sort
of
go
in
the
blood,
wherever
they
need
to
go?


Elmes:

That’s
because
endocannabinoids,
and
cannabinoids
in
general,
are
highly
lipophilic,
so
they
are
like
oil
in
water.
They
will
sequester
to
the
oil
phase
and
stay
away
from
water.
Now
remember,
all
the
cells
in
our
body
are
essentially
a
bubble
of
oil
where
the
water
is
in
the
inside,
that’s
the
cytoplasm.
So,
we
knew
the
endocannabinoids
are
made
on
the
outside
of
the
cell
[membrane] and
they’ll
stick
to
that
lipid
layer.
However,
the
enzyme
that
breaks
them
[the
cannabinoids] down,
particularly
we’re
talking
about
the
anandamide
breakdown
enzyme
which
is
known
as
fatty
acid
amide
hydrolase
or

FAAH


that’s
found
on
the
endoplasmic
reticulum.


Project

CBD
:

So
that’s
inside
the
cell.


Elmes:

Essentially
in
the
middle
of
that
bubble
of
oil.
We
knew
the
endocannabinoids
somehow
got
from
the
outside
to
the
inside,
but
no
one
ever
knew
what
that
process
actually
was,
and
how
that
happened.
There
were
a
lot
of
theories
out
there

So
about
10
years
ago,
our
group
found
that
the

FABP
s
in
the
brain,
the
few
specific
isoforms
that
are
found
in
the
brain,
essentially
pick
up
those
endocannabinoids
from
the
outside
of
the
cell,
carry
them
inside
the
cell,
and
pass
it
off
to
that
enzyme
[FAAH] or
other
areas
too.
Because
these
endocannabinoids
are
also
interacting
with
nuclear
receptors
such
as
the

PPAR

receptors.
So,
they’re
essentially
a
shuttle
protein,
they’re
picking
up
cannabinoids
and
transporting
them
all
throughout
the
cell.


Project

CBD
:


So
these
transport
molecules,
these
fatty
acid
binding
proteins
you
referred
to,
what
do
the
phytocannabinoids,

CBD

and

THC
,
if
anything,
what
do
they
have
to
do
with
this?


Elmes:

It’s
actually
where
my
whole
PhD
project
came
in
at
Stony
Brook.
So,
as
I
mentioned,
my
mentor
had
discovered
this
class
of
proteins
being
responsible
for
endocannabinoid
transport.
Phytocannabinoids
are
sort
of
a
similar
size,
they’re
also
very
lipophilic,
so
they
have
to
overcome
that
same
barrier
of
how
to
cross
these
aqueous
layers
in
the
body.
I
focused
on
[the
thesis
that] maybe

FABP
s
are
also
transporting

THC

and

CBD

or
other
phytocannabinoids.
We
did
some
testing.
I
found
that
in
vitro
these
things
are
actually
binding.

The

FABP
s
have
an
affinity
for

THC

and

CBD
.
Then
we
did
that
a
step
further,
and
showed
that
this
is
actually
happening
in
the
body.

THC

and

CBD

can
compete
for
anandamide
uptake.


Project

CBD
:


What
does
that
mean?
What
are
the
implications
of
that?
If
the
endogenous
cannabinoids,
like
anandamide
and
2-AG
that
you
mentioned,
they’re
hopping
on
these
transport
molecules
and
getting
through
the
cell
and
doing
their
thing,
what
does
it
mean
then
that

CBD

and

THC

can
do
the
same
thing,
on
the
same
fatty
acid
binding
proteins?


Elmes:

I
think
there’s
potential
that
they
are
modulating
the
endocannabinoid
tone
in
their
own
right.
But
again,
as
I
mentioned,

FABP
s
are
picking
up
the
endocannabinoid
anandamide
to
be
broken
down.
So,
if
we
block
that
transport
step,
there’s
going
to
be
less
anandamide
broken
down,
and
hence
more
anandamide
in
your
body
that’s
able
to
signal
and
hit
cannabinoid
receptors.


Project

CBD
:


And
what
would
be
the
implication
of
that,
for
example,
of
an
enhanced
signaling
from
the
endocannabinoids?


Elmes:

Exactly.
So
now
if
we
have

CBD
,
say,
competing
with
anandamide
for
binding
to
that
protein,
less
anandamide
is
going
to
be
able
to
bind
and
get
broken
down.
So,
the
fact
that

CBD

is
around
and
present
might
actually
lead
to
an
increased
levels
of
anandamide
and
increased
endocannabinoid
signaling.


Project

CBD
:


So
that
would
have
potentially
significant
health
benefits.


Elmes:

Certainly.
So
this
is
all
very
new
work.
And
we
are
still
learning
more
about
what
this
is
doing
and
how
this
is
interacting
between
the
phytocannabinoid
and
the
endocannabinoid
systems.
But
I
certainly
think
there
is
potential,
strong
potential,
for

CBD
,
a
partial
mechanism
of
action
for

CBD
,
to
be
modulating
the
endocannabinoid
tone
by
decreasing
the
rate
of
anandamide
breakdown
in
the
brain.


Project

CBD
:


So,
in
essence,
the
implication
would
be
that

CBD

boosts
our
own
endocannabinoid
signaling,
which
might
be
sort
of
like
a
natural
high,
you
might
say.


Elmes:

Yes.
Again,
we
are
still
working
some
of
the
pieces
out
and
we
can’t
definitively
say
this
for
sure.
But
I
think
it’s
certainly
a
partial
mechanism
of
action.


Project

CBD
:


One
of
the
knocks
on
cannabis
use
medicinally
is
that

okay
you
smoke
a
joint
or
you
eat
an
edible,
you
swallow
a
gel
cap
or
something,
take
a
tincture

it
has
a
global
effect.
It
affects
receptors
all
over
the
body
and
brain.
Whereas,
if
you’ve
got
a
problem
in
one
place,
what
do
you
need
all
the
rest
of
it
going
on?
What
about
the
fatty
acid
binding
proteins?
Is
it
still
the
same
problem
here,
if

CBD

or

THC

or
some
other

maybe
a
synthetic

ligand


was
targeting
these
fatty
acid
binding
proteins,
would
you
still
have
the
same
global
effect
and
would
that
be
a
detriment
as
far
as
a
pharmaceutical
company
or
pharmaceutical
development
was
concerned?


Elmes:

That’s
a
great
point,
Martin.
And

FAAH

inhibitors
have
been
developed
in
the
past.
Now
again,
that’s
the
enzyme
that
breaks
down
anandamide.


Project

CBD
:


So
that
would
also
be
kind
of
a
global
thing.
It
would
break
down
everywhere.


Elmes:

Exactly.
And
the

FAAH

you
find
in
the
brain
is
also
the

FAAH

in
the
liver,
the

FAAH

in
the
kidney,
the

FAAH

everywhere
in
the
body.
Now,
the

FABP
s
are
10
different
isoforms
found
in
mammals.
So,
in
humans
there
are
10
different
types
of

FABP
s,
and
they
have
tissue-specific
expression
patterns.
The
one
you
find
in
the
brain,
it
might
not
be
expressed
in
the
liver
or
any
other
part
of
the
body.
So,
what
our
group
started
doing,
and
we’re
in
the
process
of
doing,
is
developing
these
endocannabinoid
transport
inhibitor
compounds.
And
we’re
still
in
the
pre-clinical
drug
development
phase,
but
pushing
it
along.
We’re
trying
to
target
just
the

FABP

isoforms
that
are
found
in
the
peripheral
nervous
system
and
in
the
brain.
That
would
have
anti-inflammatory
and
anti-pain
effects
by
modulating
our
own
endocannabinoid
system.


Project

CBD
:


But
also
very
specific
effect,
because
if
there
are
these
different

FABP
s
in
different
parts
of
the
body
and
the
brain,
by
hitting
one
of
them
and
not
the
other
is
you
could
have
a
very
specific
effect
unlike


Elmes:

Exactly
right.
So
that’s
why
we’re
trying
to
target
just
those
few
isoforms
that
are
found
in
the
brain.
We
can
have
this
anti-pain
effect
without
shutting
down
our

FAAH

enzyme
in
the
liver

where
we
need
that
enzyme
to
process
other
phyto-functions
in
the
body.
It
gives
us
a
bit
of
more
finesse
in
a
precise
way
of
targeting
just
where
you
want
it
to
be
targeted,
just
to
modulate
the
endocannabinoid
system
in
these
specific
parts
of
the
body.


Project

CBD
:


That’s
something
I
would
presume
pharmaceutical
companies
might
be
interested
in,
as
part
of
their
drug
development.


Elmes:

Certainly.
We
had
some

IT

around
this
whole
idea
and
some
of
our
early
chemical
compounds
at
Stony
Brook.
A
company
called
Artelo
Biosciences,
it’s
a
small
biotech
company,
had
licensed
these
patents
from
us
and
they
actually
had
funded
my
post-doctoral
work
doing
some
preclinical
drug
development
toward
these
endocannabinoid
modulating
drugs.
There’s
certainly
interest.
And
we’re
trying
to
push
this
into
Phase
1
clinical
trials
to
learn
more
about
how
these
are
working.


Project

CBD
:


Last
question:
What
is
it
like
to
go
from
this
setting
in
academia,
where
you’re
working
at
a
high-powered
lab
doing
this
hard
science
[with
a] testing
program
for
drug
development

what
is
it
like
going
from
that
environment
into
the
cannabis
industry,
the
heart
of
it
in
California,
at
CannaCraft
where
you’re
focusing
presumably
on
product
development,
but
different
sort
of
work.
What’s
the
transition
been
like
for
you?


Elmes:

Well,
I
don’t
want
to
say
the
stress
goes
away!
There’s
certainly
a
lot
of
that.
But
the
work’s
very
interesting.
The
pay
is
certainly
better,
I’ll
say
that
much.
So
I
think
my
transition
might
have
been
a
bit
easier
because
I’m
moving
from
sort
of
a
hard
science
lab
into
an

R&D

environment,
where
your
scientific
knowledge
is
still
valued
and
we’re
still
doing
experiments
and
things
like
that.
But
there’s
less
of
a
focus,
obviously,
on
grant
writing
and
where
to
find
that
next
grant
money
that
keeps
funding
your
research
and
funding
your
own
payroll.
Now
it’s
more
about
making
the
best
quality
product
we
possibly
can

and
ultimately
money
of
course.
But
the
goals
are
a
bit
different.
It’s
more
of
a
typical
8:30
to
5:30
weekdays,
whereas
in
my
old
lab
it
was
also
weekends,
nights,
you
never
stop
thinking
about
it.
You
can
kind
of
turn
it
off
when
it’s
more
of
a
9
to
5
job.
But
so
far,
I’ve
been
loving
it.
It’s
been
great.


Project

CBD
:


Thank
you
very
much,
Matt
Elmes
for
sharing
your
perspective.
This
has
been
another
edition
of
Cannabis
Conversations.


(This
transcript
has
been
slightly
edited
for
linguistic
clarity)



Copyright,
Project

CBD
.
May
not
be
reprinted
without

permission
.


LEAVE A REPLY

Please enter your comment!
Please enter your name here

19 − 5 =