Dialogues in Clinical Neuroscience,
Journal Year:
2020,
Volume and Issue:
22(3), P. 207 - 222
Published: Sept. 30, 2020
The
endocannabinoid
system
(ECS)
is
a
highly
versatile
signaling
within
the
nervous
system.
Despite
its
widespread
localization,
functions
context
of
distinct
neural
processes
are
very
well
discernable
and
specific.
This
remarkable,
question
remains
as
to
how
such
specificity
achieved.
One
key
player
in
ECS
cannabinoid
type
1
receptor
(CB1),
G
protein–coupled
characterized
by
complexity
cell-specific
expression,
cellular
subcellular
adaptable
regulation
intracellular
cascades.
CB1
receptors
involved
different
synaptic
plasticity
brain's
bioenergetics
context-specific
manner.
CB2
also
important
several
neurons,
glial
cells,
immune
cells
brain.
As
polymorphisms
components,
external
impacts
stress
metabolic
challenges,
can
both
lead
dysregulated
activity
subsequently
possible
neuropsychiatric
disorders,
pharmacological
intervention
targeting
promising
therapeutic
approach.
Understanding
neurobiology
depth
will
aid
optimal
design
interventions,
minimizing
unwanted
side
effects.
Cellular and Molecular Life Sciences,
Journal Year:
2016,
Volume and Issue:
73(23), P. 4449 - 4470
Published: July 11, 2016
The
CB2
receptor
is
the
peripheral
for
cannabinoids.
It
mainly
expressed
in
immune
tissues,
highlighting
possibility
that
endocannabinoid
system
has
an
immunomodulatory
role.
In
this
respect,
was
shown
to
modulate
cell
functions,
both
cellulo
and
animal
models
of
inflammatory
diseases.
regard,
numerous
studies
have
reported
mice
lacking
exacerbated
phenotype.
This
suggests
therapeutic
strategies
aiming
at
modulating
signaling
could
be
promising
treatment
various
conditions.
Herein,
we
review
pharmacology
receptor,
its
expression
pattern,
pathways
induced
by
activation.
We
next
examine
regulation
functions
evidence
obtained
from
primary
human
cells,
immortalized
lines,
inflammation.
Finally,
discuss
possible
therapies
targeting
questions
remain
addressed
determine
whether
a
potential
target
treat
disease.
Physiological Reviews,
Journal Year:
2016,
Volume and Issue:
96(4), P. 1593 - 1659
Published: Sept. 15, 2016
Apart
from
having
been
used
and
misused
for
at
least
four
millennia
for,
among
others,
recreational
medicinal
purposes,
the
cannabis
plant
its
most
peculiar
chemical
components,
cannabinoids
(phytocannabinoids),
have
merit
to
led
humanity
discover
one
of
intriguing
pleiotropic
endogenous
signaling
systems,
endocannabinoid
system
(ECS).
This
review
article
aims
describe
critically
discuss,
in
comprehensive
possible
manner,
multifaceted
aspects
1)
pharmacology
potential
impact
on
mammalian
physiology
all
major
phytocannabinoids,
not
only
famous
Δ
9
-tetrahydrocannabinol,
2)
adaptive
pro-homeostatic
physiological,
or
maladaptive
pathological,
roles
ECS
cells,
tissues,
organs.
In
doing
so,
we
respected
chronological
order
milestones
millennial
route
medicinal/recreational
beyond,
as
it
is
now
clear
that
some
early
steps
this
long
path,
which
were
originally
neglected,
are
becoming
important
again.
The
emerging
picture
rather
complex,
but
still
supports
belief
more
discoveries
human
physiology,
new
therapies,
might
come
future
knowledge
field.
Cell,
Journal Year:
2019,
Volume and Issue:
176(3), P. 459 - 467.e13
Published: Jan. 1, 2019
The
cannabinoid
receptor
CB2
is
predominately
expressed
in
the
immune
system,
and
selective
modulation
of
without
psychoactivity
CB1
has
therapeutic
potential
inflammatory,
fibrotic,
neurodegenerative
diseases.
Here,
we
report
crystal
structure
human
complex
with
a
rationally
designed
antagonist,
AM10257,
at
2.8
Å
resolution.
CB2-AM10257
reveals
distinctly
different
binding
pose
compared
CB1.
However,
extracellular
portion
antagonist-bound
shares
high
degree
conformational
similarity
agonist-bound
CB1,
which
led
to
discovery
AM10257's
unexpected
opposing
functional
profile
antagonism
versus
agonism.
Further
structural
analysis
using
mutagenesis
studies
molecular
docking
revealed
basis
their
function
selectivity
for
Additional
analyses
our
antagonist
agonist
pairs
provide
important
insight
into
activation
mechanism
CB2.
present
findings
should
facilitate
rational
drug
design
toward
precise
endocannabinoid
system.
Frontiers in Cellular Neuroscience,
Journal Year:
2017,
Volume and Issue:
10
Published: Jan. 3, 2017
The
identification
and
cloning
of
the
two
major
cannabinoid
(CB¬1
CB2)
receptors
together
with
discovery
their
endogenous
ligands
in
late
80s
early
90s,
resulted
a
effort
aimed
at
understanding
mechanisms
physiological
roles
endocannabinoid
system
(ECS).
Due
to
its
expression
localization
central
nervous
(CNS),
CB1
receptor
(endocannabinoids)
enzymes
involved
synthesis
degradation,
has
been
implicated
multiple
pathophysiological
events
ranging
from
memory
deficits
neurodegenerative
disorders
among
others.
In
this
review,
we
will
provide
general
overview
emphasis
on
health
disease.
We
describe
our
current
complex
aspects
signaling
trafficking,
including
non-canonical
pathways
such
as
those
mediated
by
β-arrestins
within
context
functional
selectivity
ligand
bias.
Finally,
highlight
some
which
have
implicated.
Significant
knowledge
achieved
over
last
30
years.
However,
much
more
research
is
still
needed
fully
understand
system,
particularly
vivo,
unlock
true
potential
source
therapeutic
targets.
Cannabis and Cannabinoid Research,
Journal Year:
2017,
Volume and Issue:
2(1), P. 48 - 60
Published: Jan. 1, 2017
An
agonist
that
acts
through
a
single
receptor
can
activate
numerous
signaling
pathways.
Recent
studies
have
suggested
different
ligands
differentially
these
pathways
by
stabilizing
limited
range
of
conformations,
which
in
turn
preferentially
drive
downstream
cascades.
This
concept,
termed
"biased
signaling"
represents
an
exciting
therapeutic
opportunity
to
target
specific
elicit
only
desired
effects,
while
avoiding
undesired
effects
mediated
The
cannabinoid
receptors
CB1
and
CB2
each
multiple
pathways,
evidence
is
emerging
for
bias
within
review
will
summarize
the
current
biased
subtypes
CB2.
