Frontiers in Psychiatry,
Journal Year:
2023,
Volume and Issue:
14
Published: June 26, 2023
Background
Ketamine
and
psychedelics
have
abuse
liability.
They
can
also
induce
“transformative
experiences”
where
individuals
experience
enhanced
states
of
awareness.
This
awareness
lead
to
changes
in
preexisting
behavioral
patterns
which
could
be
beneficial
the
treatment
substance
use
disorders
(SUDs).
Preclinical
clinical
studies
suggest
that
ketamine
may
alter
markers
associated
with
synaptic
density,
these
underlie
effects
such
as
sensitization,
conditioned
place
preference,
drug
self-administration,
verbal
memory
performance.
In
this
scoping
review,
we
examined
measured
animals
humans
after
exposure
and/or
psychedelics.
Methods
A
systematic
search
was
conducted
following
PRISMA
guidelines,
through
PubMed,
EBSCO,
Scopus,
Web
Science,
based
on
a
published
protocol
(Open
Science
Framework,
DOI:
10.17605/OSF.IO/43FQ9
).
Both
vivo
vitro
were
included.
Studies
included:
dendritic
structural
changes,
PSD-95,
synapsin-1,
synaptophysin-1,
synaptotagmin-1,
SV2A.
Results
Eighty-four
included
final
analyses.
Seventy-one
treatment,
nine
psychedelics,
four
both.
Psychedelics
psilocybin/psilocin,
lysergic
acid
diethylamide,
N,N-dimethyltryptamine,
2,5-dimethoxy-4-iodoamphetamine,
ibogaine/noribogaine.
Mixed
findings
regarding
hippocampus
prefrontal
cortex
(PFC)
been
reported
when
administered
single
dose
under
basal
conditions.
Similar
mixed
seen
conditions
used
repeated
administration
ketamine.
However,
during
stressful
found
counteracted
stress-related
reductions
PFC.
Repeated
stress
hippocampus.
generally
increased
markers,
but
results
more
consistently
positive
for
certain
agents.
Conclusion
increase
Heterogeneous
relate
methodological
differences,
agents
(or
different
formulations
same
agent),
sex,
type
markers.
Future
address
seemingly
by
using
meta-analytical
approaches
or
study
designs
fully
consider
individual
differences.
European Archives of Psychiatry and Clinical Neuroscience,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Feb. 27, 2024
The
growing
interest
in
the
rapid
and
sustained
antidepressant
effects
of
dissociative
anesthetic
ketamine
classic
psychedelics,
such
as
psilocybin,
is
remarkable.
However,
both
psychedelics
are
known
to
induce
acute
mystical
experiences;
can
cause
symptoms
out-of-body
experience,
while
typically
bring
about
hallucinogenic
experiences,
like
a
profound
sense
unity
with
universe
or
nature.
role
these
experiences
enhancing
outcomes
for
patients
depression
currently
an
area
ongoing
investigation
debate.
Clinical
studies
have
shown
that
following
administration
(S)-ketamine
(esketamine)
not
directly
linked
their
properties.
In
contrast,
potential
(R)-ketamine
(arketamine),
thought
lack
side
effects,
has
yet
be
conclusively
proven
large-scale
clinical
trials.
Moreover,
although
activation
serotonin
5-HT
Neuropsychopharmacology,
Journal Year:
2024,
Volume and Issue:
49(4), P. 747 - 756
Published: Jan. 11, 2024
Major
depressive
disorder
(MDD)
is
one
of
the
most
disabling
psychiatric
disorders
in
world.
First-line
treatments
such
as
selective
serotonin
reuptake
inhibitors
(SSRIs)
still
have
many
limitations,
including
a
resistance
to
treatment
30%
patients
and
delayed
clinical
benefit
that
observed
only
after
several
weeks
treatment.
Increasing
evidence
indicates
acute
administration
psychedelic
agonists
5-HT
Chemical Reviews,
Journal Year:
2023,
Volume and Issue:
124(1), P. 124 - 163
Published: Nov. 30, 2023
Psychedelics
make
up
a
group
of
psychoactive
compounds
that
induce
hallucinogenic
effects
by
activating
the
serotonin
2A
receptor
(5-HT2AR).
Clinical
trials
have
demonstrated
traditional
psychedelic
substances
like
psilocybin
as
class
rapid-acting
and
long-lasting
antidepressants.
However,
there
is
pressing
need
for
rationally
designed
5-HT2AR
agonists
possess
optimal
pharmacological
profiles
in
order
to
fully
reveal
therapeutic
potential
these
identify
safer
drug
candidates
devoid
effects.
This
Perspective
provides
an
overview
structure–activity
relationships
existing
based
on
their
chemical
classifications
discusses
recent
advancements
understanding
molecular
pharmacology
at
structural
level.
The
encouraging
clinical
outcomes
psychedelics
depression
treatment
sparked
discovery
endeavors
aimed
developing
novel
with
improved
subtype
selectivity
signaling
bias
properties,
which
could
serve
potentially
nonhallucinogenic
These
efforts
can
be
significantly
expedited
through
utilization
structure-based
methods
functional
selectivity-directed
screening.
ACS Pharmacology & Translational Science,
Journal Year:
2023,
Volume and Issue:
6(8), P. 1221 - 1231
Published: Aug. 2, 2023
While
correlations
between
drug-induced
cortisol
elevation,
self-reported
anxiety,
and
treatment
outcomes
have
been
reported
for
human
studies
during
psilocybin-assisted
psychotherapy,
the
mechanistic
relationship
psychedelic-associated
alterations
in
plasma
glucocorticoid
responses
time
course
of
anxious
responsiveness
remains
unclear.
Using
rodents,
both
time-bound
manipulation
concentrations
assessment
anxiety-like
behaviors
can
be
achieved.
Here,
3
mg/kg
IP
psilocybin
was
found
to
anxiolytic-like
effects
C57BL/6
male
mice
at
4
h
after
treatment.
These
were
not
altered
by
pretreatment
with
a
5-HT2A
antagonist
but
blunted
receptor
or
suppression
psilocybin-induced
corticosterone
elevations.
Anxiolytic-like
also
observed
following
nonpsychedelic
agonist
lisuride
dose
causing
similar
increase
glucocorticoids
as
that
seen
psilocybin,
well
stress-induced
(via
repeated
injection)
release
alone.
Psilocybin's
persisted
7
days
administration.
The
long-term
anxiolytic
lost
when
administered
animals
ongoing
chronic
elevations
concentrations.
Overall,
these
experiments
indicate
acute,
resolvable
drives
postacute
its
abolished
presence
chronically
elevated
Journal of Anesthesia and Translational Medicine,
Journal Year:
2024,
Volume and Issue:
3(3), P. 65 - 75
Published: July 11, 2024
Ketamine,
a
dissociative
anesthetic,
is
widely
utilized
in
both
human
and
veterinary
anesthesia.
Its
(S)-enantiomer,
esketamine,
similarly
employed
for
anesthesia
analgesia.
The
anesthetic
effects
of
ketamine
esketamine
arise
from
their
antagonism
the
N-methyl-D-aspartate
receptor
(NMDAR).
In
field
psychiatry,
rapid-acting
antidepressant
properties
severe
depression
have
generated
significant
interest,
resulting
its
increased
off-label
usage
United
States
(U.S.).
2019,
nasal
spray
received
approval
use
U.S.
Europe.
However,
concerns
emerged
regarding
potential
adverse
effects,
including
long-term
efficacy,
addiction
risks,
suicide
risk
clinical
settings.
contrast,
arketamine,
(R)-enantiomer
ketamine,
exhibits
superior
longer-lasting
rodent
models
depression,
with
fewer
side
compared
to
esketamine.
Nevertheless,
research
on
efficacy
safety
arketamine
patients
remains
limited.
This
article
provides
concise
exploration
historical
two
enantiomers
while
also
delving
into
future
directions
application
these
fields.
European Journal of Neuroscience,
Journal Year:
2024,
Volume and Issue:
60(2), P. 4063 - 4077
Published: May 21, 2024
Abstract
Psychoactive
substances
obtained
from
botanicals
have
been
applied
for
a
wide
variety
of
purposes
in
the
rituals
different
cultures
thousands
years.
Classical
psychedelics
N,N′‐dimethyltryptamine,
psilocybin,
mescaline
and
various
lysergamides
cause
specific
alterations
perception,
emotion
cognition
by
acting
through
serotonin
5‐HT
2A
receptor
activation.
Lysergic
acid
diethylamide,
first
famous
breakthrough
field,
was
discovered
chance
Albert
Hoffman
Zurich
Sandoz
laboratory
1943,
studies
on
its
psychoactive
effects
began
to
take
place
literature.
Studies
this
area
were
blocked
after
legislation
controlling
use
research
psychedelic
drugs
came
into
force
1967,
but
since
1990s,
it
has
started
be
matter
scientific
curiosity
again
groups.
In
particular,
with
crucial
reports
psychotherapy‐assisted
psilocybin
applications
life‐threatening
cancer‐related
anxiety
depression,
new
avenues
opened
treatment
psychiatric
diseases
such
as
treatment‐resistant
depression
substance
addictions.
An
increasing
number
show
that
very
promising
potential
neuropsychiatric
where
desired
efficiency
cannot
achieved
conventional
methods.
context,
we
discuss
therapy,
encompassing
historical
development,
therapeutic
effects—especially
trauma
disorders
disorders—within
framework
ethical
considerations.
