The
first
purpose
of
the
present
dissertation
was
to
apply
a
high
throughput
assay
systematically
screen
library
food
and
drug
administration
(FDA)-approved
drugs
as
potential
ligands
for
cannabinoid
receptor
2
(CB2).
A
cell-based,
homogenous
time
resolved
fluorescence
(HTRF)
method
measuring
changes
in
intracellular
cAMP
levels
validated
found
be
suitable
testing
that
may
act
on
CB2.
Among
640
FDA-approved
screened,
raloxifene,
used
treat/prevent
post-menopausal
osteoporosis,
identified
novel
CB2
inverse
agonist.
reporting
these
results
demonstrated
by
acting
CB2,
raloxifene
enhances
forskolin-stimulated
accumulation
concentration-dependent
manner.
Furthermore,
data
showed
competes
concentration-dependently
specific
[3H]CP-55,940
binding
In
addition,
pretreatment
caused
rightward
shift
concentration-response
curves
agonists
CP-55,940,
HU-210,
WIN55,212-2.
Raloxifene
antagonism
is
vi
most
likely
competitive
nature,
shifts
were
parallel
not
associated
with
any
efficacy
discovery
an
agonist
suggests
it
might
possible
repurpose
this
therapeutic
indications
which
target.
identifying
also
provides
important
mechanisms
actions
explain
known
effects
raloxifene.
second
current
study
investigate
ability
third-generation
selective
estrogen
modulators
(SERMs)
bazedoxifene
lasofoxifene
bind
receptor.
We
have
identified,
time,
target
lasofoxifene.
Our
able
compete
enhanced
accumulation.
parallel,
WIN55,212-2
without
altering
indicates
bazedoxifene-
lasofoxifene-induced
nature.
SERMs
can
potentially
repurposed
SERMs.
third
structure-activity
relationships
fatty
acid
amides
activating
desensitizing
G
protein-coupled
119,
promising
both
type
diabetes
obesity.
Using
detailed
potency
analyses,
degree
saturation
acyl
chain
charged
head
groups
profound
compounds
activate
119.
pretreatments
119
desensitize
degrees
desensitization
correlate
well
their
fourth
use
fragment-based
approach,
categorical-SAR
(cat-SAR),
model
GPR119.
are
GPR119
confirmed
experimentally
agonists,
four
distinct
cat-SAR
models
developed.
leave-one
out
validation
routine,
best
had
overall
concordance
99
%,
sensitivity
specificity
100
%.
from
in-depth
fragment
analysis
several
consistent
previously
reported
relationship
(SAR)
analyses.
Overall,
while
development
highly
predictive
rapidly
prospective
applicability
domain
must
taken
into
consideration.
Moreover,
demonstrating
report
expert
system
ligands,
many
agents.
Pharmaceuticals,
Journal Year:
2025,
Volume and Issue:
18(2), P. 148 - 148
Published: Jan. 23, 2025
Background/Objectives:
Current
inflammatory
bowel
disease
(IBD)
treatments
focus
on
symptomatic
relief,
highlighting
the
need
for
innovative
approaches.
Dysregulation
of
cannabinoid
1
(CB1)
receptor,
part
endocannabinoid
system,
is
linked
to
colitis.
While
tetrahydrocannabinol
(THC)
alleviates
colitis
via
CB1
activation,
its
psychotropic
effects
limit
clinical
use.
ZCZ011,
a
CB1R
allosteric
modulator,
and
cannabidiol
(CBD),
non-psychoactive
cannabinoid,
offer
alternatives.
This
study
investigated
combining
sub-therapeutic
THC
doses
with
ZCZ011
or
CBD
in
murine
model
dextran
sodium
sulphate
(DSS)-induced
Methods:
Acute
was
induced
4%
DSS
7
days,
followed
by
3
days
water.
Chronic
modelled
over
24
alternating
concentrations.
The
combination
2.5
mg/kg
20
10
evaluated.
Key
markers
were
assessed
determine
efficacy
safety,
including
activity
index
(DAI),
inflammation,
cytokine
levels,
GLP-1,
organ
health.
Results:
DSS-induced
resulted
increased
DAI
scores,
cytokines,
inflammation
dysregulation
GLP-1
ammonia.
at
significantly
improved
but
ineffective
5
mg/kg.
alone
showed
transient
effects.
However,
either
alleviated
markers,
restored
colon
integrity
reestablished
homeostasis.
also
maintained
favourable
haematological
biochemical
profiles,
notable
reduction
colitis-induced
elevated
ammonia
levels.
Conclusions:
demonstrates
synergistic
potential
low-dose
combined
as
novel,
effective
safer
therapeutic
strategy
ulcerative
Journal of Clinical Medicine,
Journal Year:
2025,
Volume and Issue:
14(8), P. 2851 - 2851
Published: April 21, 2025
The
endocannabinoid
system
is
a
complex
communication
involved
in
maintaining
homeostasis
various
physiological
processes,
including
metabolism,
immune
response,
pain
modulation,
and
neuroprotection.
Endocannabinoids,
mainly
anandamide
2-arachidonoylglycerol,
are
natural
ligands
of
the
cannabinoid
receptors
CB1
CB2,
which
widely
distributed
throughout
central
nervous
peripheral
tissues.
Their
biosynthesis,
degradation,
interaction
with
other
signaling
pathways
play
crucial
roles
both
health
disease.
This
article
provides
comprehensive
overview
pathological
endocannabinoids,
discusses
their
potential
as
therapeutic
targets,
highlights
recent
advances
endocannabinoid-based
treatments.
Frontiers in Nutrition,
Journal Year:
2024,
Volume and Issue:
11
Published: June 24, 2024
The
prevalence
of
obesity
has
increased
dramatically
worldwide
and
become
a
critical
public
health
priority.
Obesity
is
associated
with
many
co-morbid
conditions,
including
hypertension,
diabetes,
cardiovascular
disease.
Although
the
physiology
complex,
healthy
diet
sufficient
exercise
are
two
elements
known
to
be
combating
this
condition.
Years
research
on
Mediterranean
diet,
which
high
in
fresh
fruits
vegetables,
nuts,
fish,
olive
oil,
have
demonstrated
reduction
numerous
non-communicable
chronic
diseases
diet.
There
strong
evidence
support
an
anti-inflammatory
effect
inflammation
key
driver
obesity.
Changes
alter
gut
microbiota
intricately
intertwined
human
physiology,
as
microbiota-derived
metabolites
play
role
biological
pathways
throughout
body.
This
review
will
summarize
recent
published
studies
that
examine
potential
metabolites,
short-chain
fatty
acids,
bile
trimethylamine-N-oxide,
lipopolysaccharide,
modulating
after
consumption
Mediterranean-like
These
modulate
through
NOD-like
receptor
family
pyrin
domain-containing
3
(NLRP3)
inflammasome,
toll-like
4
signaling,
macrophage
driven
effects
adipocytes,
among
other
mechanisms.
Case Reports in Psychiatry,
Journal Year:
2025,
Volume and Issue:
2025(1)
Published: Jan. 1, 2025
Background:
Rastafarianism
maintains
that
cannabis
is
a
sacred
element
of
the
religious
practice,
and
followers
religion
traditionally
engage
cautiously
with
western
medicine.
This
case
involves
Mr.
I,
72-year-old
Rastafari
male
acute
myelogenous
leukemia
(AML)
hepatic
decompensation,
who
developed
delirium
psychotic
features
which
were
initially
managed
quetiapine.
His
family
expressed
concerns
psychotropic
medications
requested
using
dronabinol,
synthetic
cannabinoid,
to
manage
his
symptoms
considering
spiritual
significance
cannabinoids
in
culture.
The
psychiatry
team's
dissenting
recommendations
regarding
dronabinol
was
met
resistance,
voiced
they
felt
their
beliefs
not
being
respected
considered
bringing
own
marijuana
products.
Following
an
ethics
consultation,
compromise
reached
trial
low-dose
dronabinol.
However,
I's
worsened,
prompting
discontinuation
management
olanzapine.
Discussion:
exemplifies
complexities
clinical
care
when
conflict
medical
necessity.
We
discuss
limited
indications
for
potential
adverse
effects
on
delirium's
behavioral
symptoms.
Concerns
about
fungal
sensitization
from
cannabinoid
products
context
immunosuppressive
chemotherapy
dysfunction
are
also
explored.
Moreover,
we
emphasize
importance
cultural
sensitivity
individuals
view
as
therapeutic.
Balancing
ethical,
evidence-based
medicine
through
thorough
discussion
risks
benefits
essential
optimal
decision-making
such
ethical
dilemmas.
Psychopharmacology,
Journal Year:
2024,
Volume and Issue:
241(6), P. 1111 - 1124
Published: May 4, 2024
Abstract
Rationale
Evidence
on
the
effect
of
dopamine
D1-like
and
D2-like
receptor
antagonists
licking
microstructure
forced
swimming
response
led
us
to
suggest
that
(i)
receptors
plays
a
role
in
activating
reward-directed
responses
(ii)
level
activation
is
reboosted
based
process
evaluation
efficacy
requiring
receptors.
A
main
piece
evidence
support
this
hypothesis
observation
antagonist
raclopride
induces
within-session
decrement
burst
number
occurring
after
contact
with
reward.
The
few
published
studies
detailed
analysis
time-course
measure
were
conducted
our
laboratory.
Objectives
aim
review
recapitulate
discuss
as
behavioural
substrate
for
study
mechanisms
governing
ingestion,
related
processes,
its
relevance
drug
effects
ingestion.
Conclusions
gathered
so
far
suggests
provides
an
important
might
provide
decisive
drugs
However,
further
from
independent
sources
necessary
validate
use
proposed
interpretation
measure.
Heliyon,
Journal Year:
2024,
Volume and Issue:
10(10), P. e31197 - e31197
Published: May 1, 2024
Electroacupuncture
(EA)
is
an
effective
alternative
for
the
treatment
of
functional
dyspepsia
(FD).
It
reduces
low-grade
duodenal
inflammation
and
improves
symptoms
FD
by
downregulating
expression
NF-κB
p65
NLRP3,
but
its
mechanism
needs
to
be
elucidated.
To
examine
regulatory
effect
electroacupuncture
on
intestinal
flora
p65/NLRP3
pyroptosis
pathway
in
rats.
The
rat
model
was
established
via
multi-factor
stress
intervention
two
weeks.
rats
were
randomly
divided
into
NC
group,
NF-kB
inhibitor
group
(NF-κB
BAY
11–7082
administered),
EA
+
group.
After
14
days
treatment,
sacrificed,
protein
mRNA
levels
p65,
IκB,
NLRP3
duodenum
evaluated
Western
blotting
assays
real-time
fluorescent
quantitative
PCR.
Illumina
MiSeq
sequencing
platform
used
analyze
V4
region
16S
rRNA
gene
predict
genes.
concentration
short-chain
fatty
acids
(SCFAs)
feces
assessed
metabolomics.
can
decrease
promote
gastrointestinal
motility
This
mediated
inhibition
pathway,
increase
alpha
beta
diversity
gut
microbiota
duodenum,
abundance
beneficial
bacteria
at
phylum
genus
levels,
content
SCFAs.
protective
against
might
involve
multiple
hierarchy
pathways.
may
remodel
inhibiting
thereby
improving
Diseases of the Esophagus,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 3, 2024
Cannabis
use
is
becoming
increasingly
common,
both
for
recreational
and
medical
purposes.
However,
there
a
paucity
of
data
regarding
cannabis
in
the
context
eosinophilic
esophagitis
(EoE).
We
aimed
to
determine
impact
on
presentation
treatment
response
EoE.
To
this
end,
we
conducted
retrospective
cohort
study
at
large
academic
center
newly
diagnosed
EoE
patients
age
≥
12
years.
Self-reported
status,
baseline
characteristics,
topical
corticosteroids
dietary
therapy
were
extracted.
Bivariate
multivariable
analyses
used
compare
users
non-users
time
diagnosis
assess
response.
Of
983
patients,
80
reported
using
cannabis,
with
majority
reporting
daily
administration
by
inhalation.
Baseline
symptoms
peak
eosinophil
count
similar
between
non-users;
less
likely
have
endoscopic
findings
exudates,
edema,
stricture,
lower
total
Endoscopic
Reference
Score.
On
analysis,
younger
age,
male
sex,
non-White
race,
psychiatric
independently
associated
history
stricture
was
non-use.
Post-treatment
symptom
histologic
responses
though
higher
odds
post-treatment
inflammatory
features
use.
In
conclusion,
despite
presenting
milder
initial
findings,
exhibited
greater
after
treatment,
highlighting
potential
negative
influence
management.