Current Neuropharmacology,
Journal Year:
2023,
Volume and Issue:
22(3), P. 495 - 520
Published: Aug. 3, 2023
Background:
The
diathesis-stress
paradigm
and
the
cannabinoid-hypothesis
have
been
proposed
as
possible
pathophysiological
models
of
schizophrenia.
However,
they
historically
studied
independently
each
other.
Objective:
This
PRISMA
2020-compliant
systematic
review
aimed
at
reappraising
interplay
between
hypothalamic-pituitary-adrenal
(HPA)
axis
endocannabinoid
(eCB)
system
in
psychosis-
spectrum
disorder
risk
outcome.
Methods:
All
outcome
clinical
studies,
concomitantly
evaluating
two
systems
psychosis-spectrum
different
stages
illness,
were
gathered
from
electronic
databases
(Pubmed,
Web
Science,
Scopus),
discussed.
Results:
41
eligible
outputs
extracted,
focusing
on
least
a
biological
measure
(9
HPA-related
studies:
4
eCB-interventional,
1
HPA-interventional,
both
HPA-interventional
non-interventional,
3
non-interventional;
2
eCB-related
non-interventional),
environmental
measures
only
(29
eCB-
interventional,
28
genetic
(1
study:
non-interventional).
Independent
contributions
aberrancies
to
physiopathology
psychosis
confirmed.
Also,
concomitant
alterations
systems,
either
genetically
defined
(e.g.,
CNR1
variation),
biologically
determined
dysfunctional
HPA
or
signaling),
behaviorally
imputed
cannabis
use,
stress
exposure,
response),
consistently
reported
psychosis.
Further,
complex
biobehavioral
perturbation
was
revealed
not
within
use
affecting
eCB
tone,
exposure
axis),
but
also
across
THC
axis,
childhood
trauma
signaling).
Conclusion:
There
is
need
study
systems’
mechanistic
contribution
order
establish
more
refined
relevance.
Journal of Clinical Medicine,
Journal Year:
2021,
Volume and Issue:
10(24), P. 5852 - 5852
Published: Dec. 14, 2021
The
stress
response
is
a
well-defined
physiological
function
activated
frequently
by
life
events.
However,
sometimes
the
can
be
inappropriate,
excessive,
or
prolonged;
in
which
case,
it
hinder
rather
than
help
coping
with
stressor,
impair
normal
functioning,
and
increase
risk
of
somatic
mental
health
disorders.
There
need
for
more
effective
safe
pharmacological
treatment
that
dampen
maladaptive
responses.
endocannabinoid
system
one
main
regulators
response.
A
basal
tone
inhibits
response,
modulation
this
permits/curtails
an
active
chronic
deficiency
associated
pathological
complications
stress.
Cannabidiol
exogenous
cannabinoid
enhancer
could
useful
have
been
seven
double-blind
placebo
controlled
clinical
trials
CBD
on
combined
total
232
participants
partially
study
120
participants.
All
showed
was
significantly
reducing
non-inferior
to
pharmaceutical
comparators,
when
included.
trial
results
are
supported
established
mechanisms
action
(including
increased
N-arachidonylethanolamine
levels)
extensive
real-world
preclinical
evidence
effectiveness
treating
Current Neuropharmacology,
Journal Year:
2023,
Volume and Issue:
22(12), P. 2059 - 2078
Published: Sept. 13, 2023
:
Cannabis
has
shown
therapeutic
potential
in
mood
and
anxiety-related
pathologies.
However,
the
two
primary
constituents
of
cannabis,
cannabidiol
(CBD)
Δ-9-tetrahydrocannabinol
(THC)
produce
distinct
effects
on
molecular
pathways
neural
circuits
associated
with
affective
disorders.
Moreover,
it
been
proposed
that
combination
THC:
CBD
may
have
unique
synergistic
properties.
In
present
study,
a
1:100
ratio
edible
formulation
were
tested
behavioural,
neuronal
assays
for
anxiety
depressive-like
endophenotypes.
Adult
male
female
Sprague-Dawley
rats
stressed
14
days.
Then,
three
weeks,
open
field,
elevated
plus
maze,
light/dark
box,
social
interaction,
sucrose
preference,
forced
swim
test
performed
90
minutes
after
acute
consumption
(30
mg/kg),
THC
(0.3
or
THC:CBD.
After
behavioural
tests,
vivo,
electrophysiological
analyses
ventral
tegmental
area
prefrontal
cortex
(PFC).
Furthermore,
western-blot
experiments
examined
expression
biomarkers
disorders,
including
protein
kinase
B
(Akt),
glycogen
synthase
kinase-3
(GSK-3),
BDNF,
mTOR,
D1,
D2
receptor
nucleus
accumbens
(NAc)
PFC.Edible
THC:CBD
produces
significant
anxiolytic
antidepressant
only
rats.
most
cases,
had
stronger
than
either
phytochemical
alone.
These
are
alterations
Akt/GSK3
D2-R
NAc
BDNF
PFC.
reverses
chronic
stress-induced
PFC
activity.
findings
demonstrate
novel
formulations
stress-related
Current Neuropharmacology,
Journal Year:
2023,
Volume and Issue:
22(3), P. 495 - 520
Published: Aug. 3, 2023
Background:
The
diathesis-stress
paradigm
and
the
cannabinoid-hypothesis
have
been
proposed
as
possible
pathophysiological
models
of
schizophrenia.
However,
they
historically
studied
independently
each
other.
Objective:
This
PRISMA
2020-compliant
systematic
review
aimed
at
reappraising
interplay
between
hypothalamic-pituitary-adrenal
(HPA)
axis
endocannabinoid
(eCB)
system
in
psychosis-
spectrum
disorder
risk
outcome.
Methods:
All
outcome
clinical
studies,
concomitantly
evaluating
two
systems
psychosis-spectrum
different
stages
illness,
were
gathered
from
electronic
databases
(Pubmed,
Web
Science,
Scopus),
discussed.
Results:
41
eligible
outputs
extracted,
focusing
on
least
a
biological
measure
(9
HPA-related
studies:
4
eCB-interventional,
1
HPA-interventional,
both
HPA-interventional
non-interventional,
3
non-interventional;
2
eCB-related
non-interventional),
environmental
measures
only
(29
eCB-
interventional,
28
genetic
(1
study:
non-interventional).
Independent
contributions
aberrancies
to
physiopathology
psychosis
confirmed.
Also,
concomitant
alterations
systems,
either
genetically
defined
(e.g.,
CNR1
variation),
biologically
determined
dysfunctional
HPA
or
signaling),
behaviorally
imputed
cannabis
use,
stress
exposure,
response),
consistently
reported
psychosis.
Further,
complex
biobehavioral
perturbation
was
revealed
not
within
use
affecting
eCB
tone,
exposure
axis),
but
also
across
THC
axis,
childhood
trauma
signaling).
Conclusion:
There
is
need
study
systems’
mechanistic
contribution
order
establish
more
refined
relevance.
