Latest / Pearls and Prep / If We Don't Understand Autoreceptors, We Don't Understand Psychopharmacology

Transcript

If We Don't Understand Autoreceptors, We Don't Understand Psychopharmacology · Pearls and Prep

• 0:00
  Foreign.
• 0:05
  Welcome
• 0:05
  back,
• 0:05
  my
• 0:06
  friends,
• 0:06
  to
• 0:06
  another
• 0:06
  episode
• 0:07
  of
• 0:07
  Pearls
• 0:07
  and
• 0:08
  Prep.
• 0:08
  Npz.
• 0:09
  Here,
• 0:09
  your
• 0:09
  preceptor
• 0:10
  in
• 0:10
  your
• 0:10
  pocket,
• 0:11
  your
• 0:11
  go
• 0:11
  to
• 0:11
  place
• 0:11
  for
• 0:12
  pearls
• 0:12
  that
• 0:12
  prep
• 0:13
  you
• 0:13
  to
• 0:13
  practice.
• 0:14
  My
• 0:14
  friends,
• 0:14
  I'm
• 0:15
  going
• 0:15
  to
• 0:15
  go
• 0:15
  ahead
• 0:15
  and
• 0:16
  make
• 0:16
  a
• 0:16
  very
• 0:16
  bold
• 0:17
  claim.
• 0:17
  You
• 0:18
  ready
• 0:18
  for
• 0:18
  this
• 0:19
  very
• 0:19
  bold
• 0:19
  claim
• 0:20
  right
• 0:20
  here,
• 0:20
  right
• 0:21
  now.
• 0:22
  And
• 0:22
  that
• 0:22
  is
• 0:23
  we
• 0:23
  cannot
• 0:24
  understand
• 0:26
  medication
• 0:26
  management
• 0:26
  if
• 0:27
  we
• 0:27
  don't
• 0:27
  understand
• 0:28
  autoreceptors.
• 0:30
  I'm
• 0:30
  going
• 0:31
  to
• 0:31
  say
• 0:31
  it
• 0:31
  one
• 0:31
  more
• 0:31
  time,
• 0:32
  okay?
• 0:33
  We
• 0:34
  cannot
• 0:34
  understand
• 0:34
  medication
• 0:35
  management
• 0:35
  unless
• 0:36
  we
• 0:36
  understand
• 0:36
  autoreceptors.
• 0:38
  We
• 0:38
  can't
• 0:39
  understand
• 0:40
  the
• 0:41
  way
• 0:41
  these
• 0:42
  medications
• 0:42
  work,
• 0:43
  why
• 0:43
  they
• 0:43
  take
• 0:43
  time
• 0:44
  to
• 0:44
  work,
• 0:45
  why
• 0:45
  they
• 0:45
  sometimes
• 0:46
  don't
• 0:46
  work
• 0:46
  very
• 0:47
  well
• 0:47
  at
• 0:47
  all
• 0:47
  in
• 0:48
  specific
• 0:48
  people,
• 0:49
  why
• 0:49
  some
• 0:49
  medications
• 0:50
  work
• 0:50
  faster
• 0:50
  than
• 0:51
  others,
• 0:52
  why
• 0:53
  it's
• 0:53
  not
• 0:53
  as
• 0:53
  simple
• 0:53
  as
• 0:54
  just
• 0:54
  increasing
• 0:54
  neurotransmitters.
• 0:56
  Oh,
• 0:56
  no,
• 0:56
  no,
• 0:57
  no.
• 0:57
  When
• 0:57
  we
• 0:58
  demystify
• 0:58
  this
• 0:59
  through
• 1:00
  the
• 1:01
  autoreceptor
• 1:02
  discussion,
• 1:03
  we're
• 1:03
  going
• 1:03
  to
• 1:03
  have
• 1:04
  today,
• 1:04
  you're
• 1:04
  going
• 1:04
  to
• 1:04
  have
• 1:04
  a
• 1:04
  much
• 1:05
  better
• 1:05
  understanding
• 1:05
  of
• 1:06
  psychopharmacology,
• 1:07
  period.
• 1:07
  That
• 1:08
  includes
• 1:09
  SSRIs.
• 1:10
  It
• 1:10
  includes
• 1:10
  medications
• 1:11
  like
• 1:11
  Remeron
• 1:12
  and
• 1:12
  Velazidone,
• 1:13
  Trintellix,
• 1:15
  Clonidine,
• 1:16
  Guanfacine,
• 1:17
  you
• 1:17
  name
• 1:18
  it.
• 1:18
  These
• 1:19
  are
• 1:19
  very
• 1:19
  important
• 1:20
  concepts.
• 1:20
  And
• 1:21
  you
• 1:21
  will
• 1:22
  feel
• 1:22
  empowered
• 1:22
  by
• 1:22
  the
• 1:23
  end
• 1:23
  of
• 1:23
  this
• 1:23
  podcast
• 1:23
  that
• 1:24
  you
• 1:24
  know
• 1:24
  a
• 1:24
  little
• 1:24
  more
• 1:24
  about
• 1:24
  med
• 1:25
  management
• 1:25
  and
• 1:26
  you
• 1:26
  can
• 1:26
  explain
• 1:26
  things
• 1:27
  better
• 1:27
  to
• 1:27
  your
• 1:27
  patients.
• 1:29
  Now,
• 1:30
  what
• 1:30
  the
• 1:30
  heck
• 1:30
  is
• 1:30
  an
• 1:31
  autoreceptor?
• 1:32
  The.
• 1:33
  The
• 1:33
  word
• 1:33
  itself,
• 1:34
  the
• 1:34
  name
• 1:34
  itself
• 1:35
  is
• 1:35
  very
• 1:35
  off
• 1:35
  putting.
• 1:36
  It
• 1:37
  confused
• 1:37
  me
• 1:37
  a
• 1:37
  lot
• 1:37
  as
• 1:38
  a
• 1:38
  student.
• 1:39
  I
• 1:39
  won't
• 1:39
  go
• 1:39
  as
• 1:39
  far
• 1:40
  to
• 1:40
  say
• 1:40
  as
• 1:40
  it
• 1:41
  kept
• 1:41
  me
• 1:41
  up
• 1:41
  at
• 1:41
  night
• 1:42
  or
• 1:42
  that
• 1:42
  I
• 1:42
  had
• 1:43
  obsessional
• 1:43
  thoughts
• 1:43
  about
• 1:44
  it,
• 1:45
  but
• 1:45
  it
• 1:45
  was
• 1:46
  an
• 1:46
  annoying
• 1:47
  word
• 1:47
  that
• 1:47
  I
• 1:48
  felt
• 1:48
  I
• 1:48
  could
• 1:48
  never
• 1:49
  really
• 1:49
  grasp
• 1:49
  and
• 1:50
  understand.
• 1:50
  And
• 1:50
  at
• 1:51
  the
• 1:51
  end
• 1:51
  of
• 1:51
  the
• 1:51
  day,
• 1:51
  what
• 1:51
  makes
• 1:51
  it
• 1:52
  even
• 1:52
  more
• 1:52
  annoying
• 1:53
  is
• 1:53
  that
• 1:53
  it's
• 1:53
  really
• 1:54
  simple
• 1:54
  and
• 1:54
  it
• 1:54
  doesn't
• 1:54
  have
• 1:55
  to
• 1:55
  be
• 1:55
  annoying.
• 1:55
  Whoever
• 1:56
  named
• 1:57
  this
• 1:57
  receptor
• 1:58
  was
• 1:58
  not
• 1:59
  thinking
• 1:59
  very
• 1:59
  clearly
• 2:00
  and
• 2:01
  should
• 2:01
  have
• 2:01
  named
• 2:01
  it
• 2:01
  something
• 2:02
  different.
• 2:02
  And
• 2:02
  I
• 2:02
  think
• 2:03
  maybe
• 2:03
  we
• 2:04
  can
• 2:04
  all
• 2:04
  talk
• 2:04
  about
• 2:05
  that
• 2:05
  offline.
• 2:05
  What
• 2:06
  we
• 2:06
  would
• 2:06
  actually
• 2:06
  name
• 2:07
  this.
• 2:07
  I
• 2:08
  think
• 2:08
  just
• 2:08
  calling
• 2:08
  it
• 2:09
  like
• 2:09
  a
• 2:09
  thermoreceptor,
• 2:11
  as
• 2:11
  in
• 2:11
  thermostat,
• 2:12
  would
• 2:12
  have
• 2:12
  been
• 2:13
  way
• 2:13
  more
• 2:14
  intuitive
• 2:14
  and
• 2:15
  way
• 2:15
  more
• 2:15
  elegant.
• 2:16
  And
• 2:16
  it
• 2:16
  would've
• 2:16
  probably
• 2:17
  saved.
• 2:18
  I
• 2:18
  wouldn't.
• 2:18
  I
• 2:18
  won't
• 2:18
  go
• 2:18
  as
• 2:19
  far
• 2:19
  to
• 2:19
  say
• 2:19
  as
• 2:19
  it
• 2:19
  would
• 2:20
  have
• 2:20
  saved
• 2:20
  a
• 2:20
  lot
• 2:20
  of
• 2:20
  human
• 2:21
  life,
• 2:22
  because
• 2:22
  this
• 2:22
  is
• 2:22
  not
• 2:22
  a
• 2:22
  life
• 2:23
  or
• 2:23
  death
• 2:23
  situation.
• 2:25
  It's
• 2:25
  more
• 2:25
  semantics.
• 2:26
  But
• 2:26
  it
• 2:27
  would
• 2:27
  have
• 2:27
  definitely
• 2:28
  saved
• 2:29
  900
• 2:29
  million
• 2:30
  Google
• 2:30
  searches
• 2:31
  from
• 2:31
  students
• 2:32
  who
• 2:32
  have
• 2:32
  no
• 2:32
  clue
• 2:32
  what
• 2:33
  autoreceptors
• 2:34
  mean.
• 2:34
  And
• 2:34
  I
• 2:34
  was
• 2:35
  probably
• 2:35
  800
• 2:35
  million
• 2:36
  of
• 2:36
  those
• 2:36
  searches.
• 2:37
  So
• 2:38
  we
• 2:38
  should
• 2:38
  call
• 2:39
  them
• 2:39
  or
• 2:39
  think
• 2:39
  of
• 2:39
  them
• 2:40
  more
• 2:40
  as
• 2:40
  thermoreceptors.
• 2:41
  And
• 2:41
  the
• 2:42
  best
• 2:42
  way
• 2:42
  I
• 2:42
  can
• 2:42
  describe
• 2:42
  it
• 2:43
  is
• 2:43
  it's
• 2:43
  a
• 2:43
  receptor
• 2:44
  that
• 2:44
  sits
• 2:45
  in
• 2:46
  a
• 2:46
  neuron
• 2:47
  and
• 2:47
  it
• 2:47
  listens
• 2:47
  to
• 2:48
  that
• 2:48
  neuron
• 2:48
  and
• 2:49
  it
• 2:49
  compensates
• 2:50
  based
• 2:50
  on
• 2:50
  that
• 2:50
  neuron's
• 2:51
  activity.
• 2:51
  If
• 2:52
  that
• 2:52
  neuron,
• 2:52
  let's
• 2:53
  call
• 2:53
  a
• 2:53
  serotonin
• 2:54
  neuron,
• 2:54
  if,
• 2:55
  if
• 2:55
  that
• 2:55
  neuron
• 2:56
  is
• 2:56
  releasing
• 2:57
  too
• 2:57
  much
• 2:57
  serotonin,
• 2:58
  this
• 2:59
  autoreceptor,
• 3:00
  or
• 3:00
  as
• 3:00
  NPZ
• 3:01
  calls
• 3:01
  it,
• 3:01
  a
• 3:02
  thermoreceptor,
• 3:03
  this
• 3:03
  thermoreceptor
• 3:04
  is
• 3:05
  going
• 3:05
  to
• 3:06
  turn
• 3:06
  down
• 3:07
  the
• 3:07
  amount
• 3:08
  of
• 3:08
  serotonin
• 3:09
  release,
• 3:10
  it
• 3:10
  is
• 3:10
  going
• 3:11
  to
• 3:11
  compensate
• 3:11
  for
• 3:12
  that
• 3:12
  release
• 3:13
  of
• 3:13
  serotonin
• 3:14
  and
• 3:14
  it's
• 3:14
  going
• 3:15
  to
• 3:15
  lessen
• 3:16
  it.
• 3:16
  Sort
• 3:17
  of
• 3:17
  a
• 3:17
  homeostatic
• 3:18
  built
• 3:18
  in
• 3:19
  switch
• 3:20
  that
• 3:20
  keeps
• 3:21
  things
• 3:21
  even,
• 3:22
  right?
• 3:22
  And
• 3:23
  so
• 3:23
  that
• 3:23
  is
• 3:23
  my
• 3:24
  most
• 3:24
  elegant
• 3:24
  definition
• 3:25
  of
• 3:26
  an
• 3:26
  autoreceptor,
• 3:27
  as
• 3:27
  I
• 3:27
  deem
• 3:27
  thermoreceptor.
• 3:29
  And
• 3:29
  so
• 3:30
  it's
• 3:30
  homeostatic
• 3:31
  in
• 3:31
  a
• 3:31
  way.
• 3:31
  Okay.
• 3:32
  And
• 3:32
  I
• 3:32
  think
• 3:32
  that's
• 3:33
  really
• 3:33
  important.
• 3:34
  But
• 3:35
  what
• 3:35
  becomes
• 3:35
  more
• 3:36
  important
• 3:36
  is
• 3:36
  that
• 3:36
  like
• 3:37
  when
• 3:37
  you
• 3:37
  prescribe
• 3:37
  an
• 3:38
  SSRI
• 3:39
  now
• 3:39
  you're
• 3:39
  blocking
• 3:40
  the
• 3:40
  reuptake
• 3:41
  of
• 3:41
  serotonin,
• 3:42
  so
• 3:42
  you
• 3:42
  have
• 3:42
  so
• 3:42
  much
• 3:43
  more
• 3:43
  serotonin
• 3:44
  hanging
• 3:44
  out
• 3:44
  in
• 3:44
  the
• 3:44
  synapse,
• 3:45
  which
• 3:45
  is
• 3:45
  a
• 3:46
  great
• 3:46
  thing.
• 3:46
  And
• 3:46
  you
• 3:46
  might
• 3:46
  be
• 3:47
  so
• 3:47
  excited
• 3:47
  and
• 3:47
  you
• 3:47
  might
• 3:48
  say,
• 3:48
  oh
• 3:48
  my
• 3:48
  God,
• 3:48
  look,
• 3:48
  I'm
• 3:49
  going
• 3:49
  to
• 3:49
  do
• 3:49
  this,
• 3:49
  I'm
• 3:49
  going
• 3:49
  to
• 3:49
  prescribe
• 3:50
  Prozac,
• 3:50
  I'm
• 3:51
  going
• 3:51
  to
• 3:51
  prescribe
• 3:52
  Zoloft,
• 3:52
  and
• 3:53
  all
• 3:53
  of
• 3:53
  a
• 3:53
  sudden,
• 3:53
  more
• 3:54
  serotonin
• 3:54
  in
• 3:54
  the
• 3:55
  synapse.
• 3:55
  Let's
• 3:55
  have
• 3:55
  a
• 3:55
  party.
• 3:56
  But
• 3:56
  your
• 3:57
  autoreceptor
• 3:58
  is
• 3:58
  going.
• 4:00
  You
• 4:00
  didn't
• 4:01
  say
• 4:01
  the
• 4:01
  magic
• 4:01
  word.
• 4:03
  You
• 4:04
  didn't
• 4:04
  say
• 4:04
  the
• 4:04
  magic
• 4:04
  word.
• 4:05
  You
• 4:05
  remember
• 4:05
  that
• 4:05
  scene
• 4:06
  from
• 4:06
  Jurassic
• 4:06
  Park.
• 4:07
  Dennis
• 4:07
  Nedry,
• 4:08
  he
• 4:08
  shuts
• 4:08
  down
• 4:08
  the
• 4:08
  park
• 4:09
  and
• 4:09
  all
• 4:10
  the
• 4:10
  raptors
• 4:10
  get
• 4:10
  loose.
• 4:11
  Well,
• 4:11
  this
• 4:11
  is
• 4:12
  a
• 4:12
  little
• 4:12
  different,
• 4:12
  but
• 4:13
  it's
• 4:13
  also
• 4:13
  very
• 4:13
  similar
• 4:14
  in
• 4:15
  that
• 4:16
  at
• 4:16
  the
• 4:16
  end
• 4:17
  of
• 4:17
  the
• 4:17
  day,
• 4:18
  the
• 4:18
  autoreceptors,
• 4:19
  they're
• 4:19
  going,
• 4:19
  wait
• 4:20
  a
• 4:20
  minute,
• 4:20
  this
• 4:20
  is
• 4:20
  too
• 4:20
  much
• 4:21
  serotonin
• 4:21
  in
• 4:21
  the
• 4:22
  synapse.
• 4:22
  We
• 4:23
  need
• 4:23
  to
• 4:23
  cool
• 4:23
  things
• 4:23
  down.
• 4:24
  We
• 4:24
  need
• 4:24
  to
• 4:24
  actually
• 4:24
  decrease
• 4:25
  the
• 4:25
  amount
• 4:26
  of
• 4:26
  serotonin
• 4:27
  firing.
• 4:27
  This
• 4:28
  is
• 4:28
  excessive.
• 4:28
  This
• 4:29
  is
• 4:29
  too
• 4:29
  much.
• 4:30
  Party's
• 4:30
  over
• 4:31
  and
• 4:32
  too
• 4:32
  bad.
• 4:33
  Think
• 4:33
  of
• 4:33
  it
• 4:33
  almost
• 4:33
  as
• 4:33
  a
• 4:34
  bouncer.
• 4:34
  The
• 4:34
  club
• 4:35
  is
• 4:35
  getting
• 4:35
  too
• 4:36
  lit,
• 4:36
  you
• 4:36
  know,
• 4:36
  serotonin
• 4:37
  too
• 4:38
  fast,
• 4:38
  coming
• 4:39
  in
• 4:39
  too,
• 4:39
  too
• 4:39
  much,
• 4:40
  too
• 4:40
  quickly,
• 4:41
  too
• 4:41
  hard.
• 4:41
  Maybe
• 4:42
  it's
• 4:42
  like
• 4:42
  a
• 4:42
  long
• 4:43
  line
• 4:44
  into
• 4:44
  a
• 4:44
  nightclub
• 4:45
  and
• 4:45
  there's
• 4:45
  just
• 4:45
  too
• 4:46
  many
• 4:46
  partiers
• 4:47
  and
• 4:47
  to
• 4:47
  the
• 4:47
  point
• 4:47
  where
• 4:47
  the
• 4:48
  party's
• 4:48
  getting
• 4:48
  really
• 4:48
  chaotic
• 4:49
  and
• 4:49
  nervous
• 4:49
  and
• 4:50
  scary
• 4:50
  and.
• 4:51
  And
• 4:51
  so
• 4:52
  the
• 4:52
  bouncers
• 4:52
  come
• 4:52
  in
• 4:54
  akin
• 4:55
  to
• 4:55
  an
• 4:55
  autoreceptor
• 4:56
  and
• 4:56
  go,
• 4:56
  wait
• 4:56
  a
• 4:56
  minute.
• 4:56
  Let's
• 4:57
  turn
• 4:57
  this
• 4:57
  down.
• 4:57
  This
• 4:58
  is
• 4:58
  a
• 4:58
  little
• 4:58
  too
• 4:58
  intense.
• 4:59
  We
• 4:59
  went
• 4:59
  from,
• 5:00
  like,
• 5:00
  smoky
• 5:01
  jazz
• 5:01
  club
• 5:01
  chill,
• 5:03
  okay.
• 5:04
  To
• 5:05
  it's
• 5:05
  a
• 5:05
  fricking
• 5:06
  rave
• 5:06
  in
• 5:06
  here
• 5:07
  too
• 5:07
  quickly.
• 5:07
  And
• 5:07
  so
• 5:07
  the
• 5:08
  autoreceptor
• 5:08
  comes
• 5:09
  in
• 5:09
  and
• 5:09
  kind
• 5:09
  of
• 5:10
  like
• 5:10
  a
• 5:10
  brake
• 5:10
  pedal,
• 5:11
  like
• 5:12
  a.
• 5:12
  Like
• 5:12
  a
• 5:12
  bouncer
• 5:13
  who
• 5:13
  doesn't
• 5:14
  want
• 5:14
  a
• 5:14
  party
• 5:14
  to
• 5:15
  get
• 5:15
  too
• 5:15
  fun
• 5:16
  kind
• 5:16
  of
• 5:16
  comes
• 5:16
  in
• 5:16
  there
• 5:16
  and
• 5:17
  slows
• 5:18
  things
• 5:18
  down.
• 5:18
  Less
• 5:19
  neuron
• 5:19
  firing,
• 5:19
  less
• 5:20
  neurotransmitter
• 5:21
  release,
• 5:21
  okay?
• 5:22
  The
• 5:22
  brain
• 5:22
  does
• 5:22
  not
• 5:23
  like
• 5:23
  sudden
• 5:23
  changes.
• 5:24
  So
• 5:24
  these
• 5:24
  autoreceptors
• 5:25
  are
• 5:25
  one
• 5:26
  of
• 5:26
  the
• 5:26
  most
• 5:26
  most
• 5:27
  important
• 5:27
  concepts
• 5:28
  in
• 5:28
  all
• 5:28
  of
• 5:28
  psychiatry
• 5:29
  because
• 5:29
  they
• 5:29
  kind
• 5:30
  of
• 5:30
  explain
• 5:30
  why
• 5:30
  SSRIs
• 5:31
  take
• 5:31
  so
• 5:31
  much
• 5:32
  time,
• 5:32
  right?
• 5:32
  If
• 5:32
  your
• 5:32
  patients
• 5:33
  ever
• 5:33
  asking,
• 5:34
  why
• 5:34
  do
• 5:34
  I
• 5:34
  have
• 5:34
  to
• 5:35
  wait
• 5:35
  weeks
• 5:35
  at
• 5:35
  a
• 5:35
  time?
• 5:36
  Or
• 5:36
  if
• 5:36
  you
• 5:36
  wanted
• 5:36
  to
• 5:36
  proactively
• 5:37
  explain
• 5:38
  why
• 5:38
  this
• 5:39
  takes
• 5:39
  time,
• 5:40
  one
• 5:40
  of
• 5:40
  the
• 5:40
  reasons
• 5:41
  is
• 5:41
  you
• 5:41
  have
• 5:41
  an
• 5:42
  autoreceptor
• 5:42
  on
• 5:43
  these
• 5:43
  neurons
• 5:43
  that
• 5:43
  is
• 5:44
  trying
• 5:44
  to
• 5:44
  keep
• 5:44
  things
• 5:45
  nice
• 5:45
  and
• 5:45
  smooth
• 5:45
  and
• 5:46
  calm
• 5:46
  and
• 5:46
  mitigate
• 5:47
  the
• 5:47
  amount
• 5:47
  of
• 5:48
  neuron
• 5:48
  firing
• 5:49
  and
• 5:50
  neurotransmitter
• 5:51
  release,
• 5:52
  okay?
• 5:52
  But
• 5:52
  eventually
• 5:53
  the
• 5:53
  bouncers
• 5:53
  get
• 5:54
  kind
• 5:54
  of
• 5:54
  tired
• 5:54
  and
• 5:54
  kind
• 5:55
  of
• 5:55
  bored,
• 5:55
  and
• 5:55
  they're
• 5:55
  like,
• 5:55
  well,
• 5:57
  I'm
• 5:57
  kind
• 5:57
  of
• 5:57
  used
• 5:57
  to
• 5:58
  this
• 5:58
  volume
• 5:58
  now.
• 5:59
  Yeah,
• 5:59
  the
• 5:59
  party's
• 5:59
  been
• 6:00
  kind
• 6:00
  of
• 6:00
  crazy.
• 6:00
  Sure.
• 6:01
  I
• 6:01
  kind
• 6:01
  of
• 6:01
  shut
• 6:02
  down
• 6:02
  the
• 6:02
  worst
• 6:02
  of
• 6:02
  it,
• 6:03
  but
• 6:03
  I'm
• 6:03
  kind
• 6:04
  of
• 6:04
  used
• 6:04
  to
• 6:04
  all
• 6:04
  this
• 6:04
  noise
• 6:05
  now.
• 6:06
  So
• 6:06
  the
• 6:06
  bouncers
• 6:07
  get
• 6:07
  kind
• 6:07
  of
• 6:07
  tired,
• 6:08
  and,
• 6:08
  you
• 6:09
  know,
• 6:09
  their
• 6:09
  muscles
• 6:09
  are
• 6:09
  sore.
• 6:10
  There's
• 6:10
  only
• 6:10
  so
• 6:10
  much
• 6:11
  bouncing
• 6:11
  you
• 6:11
  can
• 6:11
  do
• 6:11
  of
• 6:12
  throwing
• 6:12
  people
• 6:12
  out
• 6:12
  of
• 6:12
  the
• 6:12
  club
• 6:13
  before
• 6:13
  you
• 6:13
  need
• 6:13
  a
• 6:13
  break.
• 6:14
  And
• 6:14
  so
• 6:14
  they
• 6:14
  get
• 6:14
  kind
• 6:15
  of
• 6:15
  lazy
• 6:15
  and
• 6:15
  tired,
• 6:16
  and
• 6:16
  they
• 6:16
  stop
• 6:17
  throwing
• 6:17
  people
• 6:17
  out
• 6:17
  of
• 6:18
  the
• 6:18
  club
• 6:18
  after
• 6:18
  a
• 6:18
  while.
• 6:19
  And
• 6:19
  lo
• 6:19
  and
• 6:19
  behold,
• 6:20
  here
• 6:20
  you
• 6:20
  have
• 6:20
  more
• 6:21
  people
• 6:21
  who
• 6:21
  are
• 6:22
  not
• 6:22
  getting
• 6:22
  bounced
• 6:23
  out
• 6:23
  of
• 6:23
  the
• 6:23
  club.
• 6:23
  That
• 6:23
  would
• 6:23
  be
• 6:24
  the
• 6:24
  serotonin
• 6:25
  reuptake
• 6:25
  inhibition,
• 6:26
  right?
• 6:26
  We're.
• 6:26
  We're
• 6:27
  prescribing
• 6:27
  an
• 6:28
  ssri,
• 6:28
  and
• 6:29
  less
• 6:29
  of
• 6:29
  that
• 6:30
  serotonin
• 6:30
  is
• 6:30
  being
• 6:31
  recycled
• 6:31
  back
• 6:31
  into
• 6:31
  the
• 6:32
  neuron.
• 6:32
  It's
• 6:32
  staying
• 6:32
  in
• 6:33
  the
• 6:33
  synapse.
• 6:33
  And.
• 6:34
  And
• 6:34
  that
• 6:34
  would
• 6:34
  be
• 6:34
  akin
• 6:35
  to
• 6:35
  people
• 6:36
  just
• 6:36
  partying
• 6:36
  on
• 6:37
  the
• 6:37
  dance
• 6:37
  floor.
• 6:37
  The
• 6:37
  bouncers
• 6:38
  aren't
• 6:38
  yanking
• 6:39
  them
• 6:39
  off
• 6:39
  anymore.
• 6:39
  They're
• 6:40
  kind
• 6:40
  of
• 6:40
  tired.
• 6:40
  They're
• 6:40
  used
• 6:40
  to
• 6:41
  the.
• 6:41
  The.
• 6:42
  The.
• 6:42
  The
• 6:42
  volume
• 6:43
  in
• 6:43
  the.
• 6:43
  In
• 6:43
  the
• 6:44
  whole
• 6:44
  place,
• 6:44
  and
• 6:44
  they
• 6:44
  kind
• 6:45
  of
• 6:45
  just
• 6:45
  let
• 6:45
  go.
• 6:46
  And
• 6:46
  so
• 6:46
  that's
• 6:46
  when
• 6:46
  the
• 6:47
  party
• 6:47
  actually
• 6:47
  starts.
• 6:48
  That's
• 6:48
  when
• 6:48
  you
• 6:49
  have
• 6:49
  serotonin
• 6:50
  in
• 6:50
  the
• 6:50
  synapse
• 6:50
  that
• 6:51
  has
• 6:51
  increased
• 6:51
  and
• 6:51
  you
• 6:52
  have
• 6:52
  meaningful
• 6:52
  therapeutic
• 6:53
  effects.
• 6:54
  And
• 6:54
  bam.
• 6:54
  Everybody's
• 6:55
  kind
• 6:55
  of
• 6:55
  happy,
• 6:56
  right?
• 6:56
  The
• 6:56
  bouncers
• 6:56
  kind
• 6:57
  of
• 6:57
  let
• 6:57
  loose,
• 6:57
  and
• 6:57
  they're
• 6:58
  cool,
• 6:58
  and
• 6:58
  the
• 6:59
  party
• 6:59
  Starts.
• 6:59
  That's
• 6:59
  the
• 7:00
  best
• 7:00
  way
• 7:00
  I
• 7:00
  can
• 7:00
  describe
• 7:01
  it.
• 7:01
  But
• 7:01
  that
• 7:01
  again
• 7:01
  is
• 7:02
  why
• 7:02
  you
• 7:02
  can
• 7:03
  have
• 7:03
  serotonin
• 7:04
  or
• 7:04
  SSRIs.
• 7:05
  I
• 7:05
  should
• 7:06
  say,
• 7:06
  take
• 7:06
  weeks.
• 7:07
  Okay.
• 7:08
  Um,
• 7:08
  which
• 7:08
  I
• 7:08
  find
• 7:08
  very
• 7:09
  interesting.
• 7:09
  Also,
• 7:10
  I'd
• 7:10
  like
• 7:10
  to
• 7:10
  make
• 7:11
  an
• 7:11
  important
• 7:11
  distinction
• 7:12
  that
• 7:12
  will
• 7:12
  help
• 7:12
  you
• 7:12
  think
• 7:12
  about
• 7:13
  your
• 7:13
  meds
• 7:13
  better
• 7:13
  and
• 7:13
  more
• 7:14
  clearly.
• 7:14
  We're,
• 7:15
  it's.
• 7:15
  Prozac
• 7:15
  is
• 7:16
  not
• 7:16
  a
• 7:16
  serotonin
• 7:17
  pill.
• 7:17
  It's
• 7:17
  not
• 7:17
  like
• 7:18
  vitamin
• 7:18
  D,
• 7:18
  where
• 7:18
  you
• 7:19
  take
• 7:19
  vitamin
• 7:19
  D
• 7:19
  and
• 7:19
  you
• 7:20
  have
• 7:20
  more
• 7:20
  vitamin
• 7:20
  D,
• 7:21
  right?
• 7:22
  This
• 7:22
  is
• 7:23
  serotonin.
• 7:23
  You're
• 7:24
  not
• 7:24
  giving
• 7:24
  someone
• 7:24
  serotonin.
• 7:25
  Not
• 7:25
  that
• 7:25
  I
• 7:25
  assumed
• 7:26
  any
• 7:26
  of
• 7:26
  you
• 7:26
  thought
• 7:27
  you
• 7:27
  were
• 7:27
  just
• 7:27
  handing
• 7:28
  someone
• 7:28
  a
• 7:28
  pill
• 7:28
  full
• 7:29
  of
• 7:29
  serotonin.
• 7:29
  But
• 7:30
  as
• 7:30
  you
• 7:30
  can
• 7:30
  see,
• 7:30
  the
• 7:30
  actual
• 7:31
  mechanism
• 7:31
  of
• 7:31
  action
• 7:32
  is
• 7:32
  a
• 7:32
  lot
• 7:32
  more
• 7:32
  elegant,
• 7:33
  it's
• 7:33
  a
• 7:33
  lot
• 7:33
  more
• 7:33
  intricate.
• 7:34
  We're
• 7:35
  blocking
• 7:35
  the
• 7:35
  reuptake
• 7:36
  of,
• 7:36
  of
• 7:37
  serotonin
• 7:37
  to
• 7:37
  keep
• 7:38
  it
• 7:38
  in
• 7:38
  the
• 7:38
  synapse
• 7:38
  longer.
• 7:39
  And
• 7:39
  of
• 7:40
  course
• 7:41
  that
• 7:41
  has
• 7:42
  a
• 7:42
  whole
• 7:43
  host
• 7:43
  of
• 7:43
  other
• 7:43
  effects
• 7:44
  because
• 7:45
  different
• 7:45
  receptors
• 7:46
  are
• 7:46
  getting
• 7:46
  activated
• 7:47
  when
• 7:48
  you
• 7:48
  have
• 7:48
  more
• 7:48
  serotonin
• 7:49
  in
• 7:49
  the
• 7:49
  synapse,
• 7:51
  right?
• 7:51
  And
• 7:52
  that
• 7:52
  causes
• 7:53
  nausea
• 7:53
  in
• 7:53
  some
• 7:54
  people,
• 7:54
  that
• 7:54
  makes
• 7:54
  them
• 7:54
  more
• 7:55
  anxious
• 7:55
  because
• 7:56
  5ht2a
• 7:57
  is
• 7:57
  being
• 7:57
  activated.
• 7:58
  So
• 7:58
  people
• 7:58
  feel
• 7:58
  a
• 7:59
  little
• 7:59
  more
• 7:59
  ruminative
• 7:59
  and
• 7:59
  anxious.
• 8:00
  Maybe
• 8:00
  they
• 8:00
  have
• 8:01
  insomnia.
• 8:01
  5
• 8:02
  HT2C
• 8:03
  is
• 8:03
  activated
• 8:03
  by,
• 8:04
  uh,
• 8:04
  the
• 8:05
  increased
• 8:05
  serotonin
• 8:06
  in
• 8:06
  the
• 8:06
  synapse,
• 8:06
  which
• 8:06
  can
• 8:07
  make
• 8:07
  people
• 8:07
  have
• 8:07
  less
• 8:07
  of
• 8:07
  a
• 8:08
  libido
• 8:09
  or
• 8:09
  less
• 8:09
  of
• 8:09
  a
• 8:10
  sexual
• 8:10
  desire.
• 8:10
  That's
• 8:11
  5ht
• 8:11
  2c.
• 8:12
  Right?
• 8:13
  And
• 8:13
  again,
• 8:14
  the
• 8:14
  autoreceptor's
• 8:15
  kind
• 8:15
  of
• 8:16
  doing
• 8:16
  its
• 8:16
  thing
• 8:16
  and
• 8:17
  it's
• 8:17
  reversing
• 8:18
  a
• 8:18
  lot
• 8:18
  of
• 8:18
  your
• 8:19
  progress,
• 8:19
  cuz
• 8:19
  it's
• 8:20
  freaked
• 8:20
  out
• 8:20
  that
• 8:20
  there's
• 8:21
  too
• 8:21
  much
• 8:21
  serotonin,
• 8:22
  the
• 8:22
  party's
• 8:22
  getting
• 8:22
  too
• 8:23
  hot,
• 8:23
  and
• 8:23
  so
• 8:23
  they're
• 8:24
  yanking
• 8:24
  people
• 8:24
  out
• 8:24
  of
• 8:25
  the
• 8:25
  club.
• 8:25
  And
• 8:25
  that's
• 8:25
  why
• 8:25
  you're
• 8:25
  not
• 8:26
  having
• 8:26
  a
• 8:26
  lot
• 8:26
  of
• 8:26
  fun
• 8:27
  until
• 8:27
  those
• 8:27
  bouncers
• 8:28
  get
• 8:28
  tired
• 8:28
  four
• 8:28
  to
• 8:29
  six
• 8:29
  weeks
• 8:29
  later.
• 8:30
  And
• 8:30
  at
• 8:30
  that
• 8:30
  point
• 8:30
  you
• 8:31
  need
• 8:31
  to
• 8:31
  ask
• 8:31
  yourself,
• 8:31
  are
• 8:32
  we
• 8:32
  doing
• 8:32
  what
• 8:32
  we
• 8:32
  need
• 8:32
  to
• 8:33
  do?
• 8:33
  Is
• 8:33
  this
• 8:33
  good?
• 8:35
  And
• 8:35
  some
• 8:35
  patients
• 8:35
  might
• 8:36
  say
• 8:36
  no,
• 8:37
  they
• 8:37
  don't
• 8:37
  feel
• 8:37
  anything,
• 8:38
  they
• 8:38
  don't
• 8:38
  feel
• 8:38
  good.
• 8:39
  Things
• 8:39
  aren't
• 8:39
  working
• 8:40
  out
• 8:40
  on
• 8:41
  the
• 8:41
  Prozac
• 8:41
  or
• 8:41
  the
• 8:42
  Zoloft.
• 8:42
  And
• 8:42
  genetically
• 8:43
  those
• 8:43
  folks
• 8:43
  could
• 8:44
  actually
• 8:44
  have
• 8:44
  really
• 8:44
  strong
• 8:45
  bouncers,
• 8:45
  right?
• 8:46
  Maybe
• 8:46
  they
• 8:46
  have
• 8:46
  20
• 8:47
  bouncers
• 8:47
  instead
• 8:48
  of
• 8:48
  five
• 8:48
  bouncers.
• 8:49
  And
• 8:49
  those
• 8:49
  bouncers
• 8:50
  have
• 8:50
  extra
• 8:50
  big
• 8:50
  muscles,
• 8:51
  right?
• 8:51
  These
• 8:51
  are
• 8:51
  kind
• 8:51
  of
• 8:52
  the
• 8:52
  genetic
• 8:52
  precursors
• 8:53
  that.
• 8:59
  Mitigate
• 8:59
  the
• 8:59
  amount
• 9:00
  of
• 9:01
  serotonin
• 9:02
  even
• 9:02
  more
• 9:03
  aggressively
• 9:03
  because
• 9:03
  there's
• 9:04
  more
• 9:04
  of
• 9:05
  them,
• 9:05
  more
• 9:05
  autoreceptors
• 9:06
  or
• 9:06
  they're
• 9:06
  more
• 9:06
  sensitive,
• 9:07
  kind
• 9:07
  of
• 9:07
  like
• 9:08
  a
• 9:08
  super
• 9:08
  sensitive
• 9:08
  smoke
• 9:09
  alarm
• 9:09
  that
• 9:09
  goes
• 9:09
  off
• 9:10
  and
• 9:10
  shuts
• 9:10
  down
• 9:11
  that
• 9:11
  party
• 9:11
  even
• 9:11
  harder
• 9:12
  more
• 9:12
  often.
• 9:13
  That,
• 9:13
  of
• 9:13
  course,
• 9:13
  can
• 9:13
  happen
• 9:14
  genetically.
• 9:15
  So,
• 9:15
  you
• 9:16
  know,
• 9:16
  that's
• 9:16
  a
• 9:16
  big
• 9:16
  deal
• 9:17
  because
• 9:17
  that
• 9:17
  might
• 9:17
  explain
• 9:18
  why
• 9:18
  some
• 9:18
  of
• 9:18
  your
• 9:18
  patients
• 9:19
  are
• 9:19
  not
• 9:20
  getting
• 9:20
  a
• 9:21
  lot
• 9:21
  better.
• 9:22
  Okay.
• 9:22
  They
• 9:22
  have
• 9:23
  increased
• 9:23
  autoreceptor
• 9:24
  expression.
• 9:24
  Okay.
• 10:20
  That's
• 10:20
  stronger
• 10:21
  serotonin
• 10:22
  inhibition
• 10:22
  across
• 10:23
  the
• 10:23
  board,
• 10:23
  reduced
• 10:23
  serotonin
• 10:24
  neuron
• 10:25
  firing.
• 10:25
  Okay.
• 10:26
  Some
• 10:26
  people
• 10:26
  are
• 10:26
  born
• 10:27
  with
• 10:27
  that
• 10:27
  extreme
• 10:27
  sensitivity
• 10:28
  or
• 10:28
  those
• 10:28
  extreme
• 10:29
  smoke
• 10:29
  detectors
• 10:30
  or
• 10:30
  the
• 10:31
  extremely
• 10:31
  strong
• 10:32
  bouncers
• 10:33
  that
• 10:33
  have
• 10:33
  a
• 10:33
  very
• 10:33
  low
• 10:34
  tolerance
• 10:34
  for
• 10:34
  extra
• 10:35
  noise.
• 10:35
  Okay?
• 10:36
  So
• 10:37
  even
• 10:37
  a
• 10:37
  small
• 10:37
  amount
• 10:38
  of
• 10:38
  serotonin
• 10:39
  can.
• 10:39
  Can
• 10:40
  make
• 10:40
  that
• 10:40
  bouncer
• 10:41
  just.
• 10:41
  Just
• 10:42
  kick
• 10:42
  down
• 10:42
  the
• 10:42
  door
• 10:43
  and
• 10:43
  shut
• 10:44
  everything
• 10:44
  down.
• 10:44
  And
• 10:45
  they
• 10:45
  might
• 10:45
  respond
• 10:45
  poorly
• 10:46
  to
• 10:46
  SSRIs.
• 10:47
  They
• 10:47
  might
• 10:47
  need
• 10:47
  longer
• 10:48
  treatment.
• 10:48
  They
• 10:48
  might
• 10:49
  benefit
• 10:49
  from
• 10:49
  non
• 10:49
  traditional
• 10:50
  strategies
• 10:51
  down
• 10:51
  the
• 10:52
  road
• 10:52
  if
• 10:52
  you
• 10:52
  find
• 10:52
  their
• 10:52
  treatment
• 10:53
  resistant.
• 10:53
  Now
• 10:53
  we're
• 10:54
  talking
• 10:54
  ketamine,
• 10:54
  which
• 10:54
  sort
• 10:55
  of
• 10:55
  bypasses
• 10:55
  all
• 10:55
  of
• 10:56
  this
• 10:56
  entirely
• 10:57
  through
• 10:57
  a
• 10:57
  whole
• 10:57
  different
• 10:57
  mechanism.
• 10:58
  We'll
• 10:58
  talk
• 10:58
  about
• 10:59
  later.
• 10:59
  We've
• 10:59
  touched
• 11:00
  on
• 11:00
  it
• 11:00
  in
• 11:00
  previous
• 11:00
  episodes.
• 11:01
  So,
• 11:02
  yes,
• 11:02
  we
• 11:03
  have
• 11:03
  seen
• 11:03
  in
• 11:03
  animal
• 11:04
  models
• 11:04
  that
• 11:05
  some
• 11:05
  people
• 11:05
  have
• 11:06
  more
• 11:06
  of
• 11:06
  those
• 11:06
  serotonin
• 11:07
  autoreceptors.
• 11:08
  They
• 11:08
  have
• 11:08
  excessive
• 11:08
  amounts
• 11:09
  to
• 11:09
  too
• 11:09
  many
• 11:09
  bouncers.
• 11:10
  Well,
• 11:10
  you're
• 11:10
  not
• 11:10
  going
• 11:10
  to
• 11:11
  have
• 11:11
  a
• 11:11
  really
• 11:11
  fun
• 11:11
  nightclub
• 11:12
  when
• 11:12
  you
• 11:12
  have
• 11:12
  too
• 11:13
  many
• 11:13
  bouncers.
• 11:13
  That's
• 11:14
  not
• 11:14
  going
• 11:14
  to
• 11:14
  be
• 11:14
  fun,
• 11:14
  okay.
• 11:15
  And
• 11:15
  so
• 11:15
  they
• 11:15
  tend
• 11:16
  to
• 11:16
  have
• 11:16
  more
• 11:16
  SSRI
• 11:17
  resistance,
• 11:17
  more
• 11:17
  depressive
• 11:18
  like
• 11:19
  behavior.
• 11:19
  Okay,
• 11:20
  so
• 11:21
  that
• 11:21
  explains
• 11:22
  a
• 11:22
  lot
• 11:22
  of
• 11:23
  this,
• 11:23
  right?
• 11:23
  We
• 11:24
  talked
• 11:24
  about
• 11:24
  why,
• 11:24
  how
• 11:25
  SSRIs
• 11:25
  take
• 11:26
  some
• 11:26
  time
• 11:26
  for
• 11:26
  a
• 11:26
  reason.
• 11:27
  Because
• 11:27
  this
• 11:27
  is
• 11:27
  sort
• 11:27
  of
• 11:27
  this
• 11:28
  homeostatic.
• 11:28
  Whoa,
• 11:29
  whoa,
• 11:29
  whoa.
• 11:29
  Too
• 11:29
  much
• 11:29
  serotonin.
• 11:30
  Let's
• 11:31
  not
• 11:31
  do
• 11:31
  this
• 11:32
  kind
• 11:32
  of
• 11:32
  thing
• 11:33
  now.
• 11:34
  This
• 11:34
  is
• 11:34
  where
• 11:34
  things
• 11:35
  get
• 11:35
  interesting.
• 11:35
  And
• 11:36
  you
• 11:36
  all
• 11:36
  know
• 11:36
  how
• 11:36
  much
• 11:37
  I
• 11:37
  absolutely
• 11:38
  love.
• 11:40
  We
• 11:40
  won't
• 11:40
  do
• 11:40
  a
• 11:40
  super
• 11:41
  deep
• 11:41
  dive
• 11:41
  into
• 11:41
  how
• 11:41
  great
• 11:42
  Remeron
• 11:42
  can
• 11:42
  be
• 11:43
  for
• 11:43
  the
• 11:43
  right
• 11:43
  patient.
• 11:44
  But
• 11:44
  Remeron
• 11:45
  is
• 11:45
  really
• 11:45
  interesting
• 11:46
  because
• 11:47
  what
• 11:47
  it
• 11:47
  does
• 11:48
  here
• 11:48
  is
• 11:48
  it
• 11:48
  rips
• 11:49
  that
• 11:49
  autoreceptor
• 11:50
  out
• 11:51
  directly,
• 11:51
  okay?
• 11:52
  It
• 11:52
  does
• 11:53
  not
• 11:53
  block
• 11:54
  the
• 11:54
  reuptake
• 11:55
  of
• 11:55
  serotonin
• 11:55
  like
• 11:56
  Prozac,
• 11:56
  Zoloft,
• 11:57
  Lexapro
• 11:57
  or
• 11:57
  Celexa.
• 11:58
  No,
• 11:59
  no,
• 11:59
  no.
• 11:59
  It
• 12:00
  actually
• 12:01
  directly
• 12:01
  blocks
• 12:02
  presynaptic
• 12:03
  alpha
• 12:03
  2
• 12:04
  adrenergic
• 12:04
  autoreceptors.
• 12:06
  It
• 12:06
  is
• 12:06
  exactly
• 12:06
  like
• 12:07
  yanking
• 12:08
  the
• 12:08
  smoke
• 12:08
  detector
• 12:09
  out
• 12:09
  of
• 12:09
  the.
• 12:09
  Out
• 12:09
  of
• 12:10
  the
• 12:10
  wall
• 12:10
  completely
• 12:10
  so
• 12:11
  it
• 12:11
  never
• 12:11
  gets
• 12:11
  to
• 12:12
  beep
• 12:12
  or
• 12:12
  alarm.
• 12:13
  It's
• 12:13
  like
• 12:14
  yanking
• 12:14
  the
• 12:14
  bouncers
• 12:15
  out
• 12:15
  and
• 12:15
  say,
• 12:15
  go
• 12:15
  home,
• 12:16
  you're
• 12:16
  fired
• 12:16
  without
• 12:17
  pay.
• 12:17
  Never
• 12:17
  come
• 12:17
  back
• 12:18
  here.
• 12:18
  And
• 12:19
  so
• 12:19
  you
• 12:19
  have
• 12:20
  less
• 12:20
  inhibition.
• 12:21
  So
• 12:21
  when
• 12:21
  the
• 12:21
  serotonin
• 12:22
  is
• 12:22
  normally
• 12:23
  expressed
• 12:24
  and
• 12:24
  released
• 12:24
  in
• 12:24
  your
• 12:25
  neurons,
• 12:25
  just
• 12:26
  normal
• 12:26
  serotonergic
• 12:27
  activity,
• 12:28
  it's
• 12:28
  no
• 12:28
  longer
• 12:28
  being
• 12:29
  inhibited.
• 12:29
  By
• 12:30
  that
• 12:30
  break
• 12:30
  by
• 12:31
  the
• 12:31
  autoreceptor.
• 12:32
  And
• 12:32
  mirtazapine
• 12:33
  or
• 12:33
  Remeron
• 12:34
  directly
• 12:34
  blocks
• 12:35
  that
• 12:35
  presynaptic
• 12:36
  alpha
• 12:36
  2
• 12:36
  adrenergic
• 12:37
  autoreceptor.
• 12:38
  And
• 12:38
  so
• 12:39
  instead
• 12:39
  of
• 12:39
  waiting
• 12:40
  weeks
• 12:40
  for
• 12:41
  everything
• 12:41
  to
• 12:41
  desensitize
• 12:42
  like
• 12:42
  you
• 12:42
  did
• 12:42
  with
• 12:42
  SSRIs
• 12:43
  and
• 12:44
  the
• 12:44
  autoreceptor
• 12:45
  that
• 12:45
  was
• 12:45
  there,
• 12:45
  well,
• 12:45
  we
• 12:45
  just.
• 12:46
  We
• 12:46
  just
• 12:46
  yanked
• 12:47
  the
• 12:47
  smoke
• 12:47
  detector
• 12:48
  out,
• 12:48
  so
• 12:48
  less
• 12:49
  inhibition.
• 12:50
  And
• 12:50
  that
• 12:50
  is
• 12:50
  theoretically
• 12:51
  why
• 12:52
  Remeron
• 12:53
  may
• 12:53
  work
• 12:53
  a
• 12:53
  little
• 12:54
  bit
• 12:54
  faster.
• 12:55
  Um,
• 12:55
  it.
• 12:55
  It's.
• 12:55
  It's
• 12:56
  pretty
• 12:56
  fascinating,
• 12:56
  right?
• 12:57
  So,
• 12:57
  again,
• 12:57
  please
• 12:58
  appreciate
• 12:58
  the
• 12:58
  fact
• 12:58
  that
• 12:59
  Remeron
• 13:00
  does
• 13:00
  not
• 13:00
  add
• 13:01
  neurotransmitters
• 13:02
  into
• 13:02
  the
• 13:02
  brain.
• 13:02
  You're
• 13:03
  not
• 13:03
  giving
• 13:03
  someone
• 13:03
  a
• 13:03
  pill
• 13:04
  with
• 13:04
  neurotransmitters
• 13:05
  in
• 13:05
  it,
• 13:05
  okay?
• 13:06
  That
• 13:06
  is
• 13:07
  fundamentally
• 13:07
  not
• 13:07
  at
• 13:08
  all
• 13:08
  what
• 13:08
  we
• 13:08
  do.
• 13:09
  And
• 13:09
  instead,
• 13:10
  it
• 13:10
  removes
• 13:11
  the
• 13:11
  inhibitory
• 13:12
  signals
• 13:12
  that
• 13:12
  normally
• 13:13
  suppress
• 13:13
  neurotransmitter
• 13:15
  release.
• 13:15
  And
• 13:15
  you
• 13:15
  can
• 13:15
  imagine,
• 13:16
  as
• 13:16
  you
• 13:16
  know
• 13:16
  about
• 13:16
  Remeron,
• 13:17
  its
• 13:17
  affinity
• 13:18
  for
• 13:18
  norepinephrine,
• 13:19
  its
• 13:19
  affinity
• 13:20
  for
• 13:20
  serotonin.
• 13:21
  So,
• 13:21
  yes,
• 13:21
  there
• 13:21
  are
• 13:21
  actual
• 13:22
  autoreceptors
• 13:23
  on
• 13:23
  norepinephrine
• 13:24
  neurons.
• 13:25
  And
• 13:26
  normally
• 13:27
  those
• 13:27
  autoreceptors
• 13:28
  tell
• 13:28
  those
• 13:28
  norepinephrine
• 13:29
  neurons,
• 13:30
  hey,
• 13:30
  enough
• 13:30
  norepinephrine.
• 13:31
  Slow
• 13:32
  down.
• 13:32
  But
• 13:33
  Remeron,
• 13:33
  again,
• 13:33
  yanks.
• 13:34
  That
• 13:34
  blocks
• 13:35
  these
• 13:35
  receptors,
• 13:35
  essentially
• 13:36
  yanks
• 13:36
  out.
• 13:36
  The
• 13:36
  bouncer
• 13:37
  says,
• 13:37
  stop
• 13:38
  cooling
• 13:38
  off
• 13:38
  this
• 13:38
  party.
• 13:39
  And
• 13:39
  so
• 13:39
  all
• 13:40
  the
• 13:40
  people
• 13:40
  in
• 13:40
  line
• 13:40
  that
• 13:41
  are
• 13:41
  due
• 13:41
  to
• 13:41
  get
• 13:42
  into
• 13:42
  the
• 13:42
  club,
• 13:42
  they
• 13:42
  get
• 13:42
  into
• 13:43
  the
• 13:43
  club.
• 13:43
  They're
• 13:43
  not
• 13:43
  being
• 13:44
  bounced
• 13:44
  out,
• 13:45
  right?
• 13:45
  You
• 13:45
  didn't
• 13:46
  add
• 13:46
  people
• 13:46
  in
• 13:47
  the
• 13:47
  club.
• 13:47
  Like,
• 13:48
  in
• 13:48
  other
• 13:48
  words,
• 13:48
  you're
• 13:48
  not
• 13:48
  adding
• 13:49
  serotonin
• 13:49
  and
• 13:49
  norepinephrine
• 13:50
  artificially
• 13:51
  through
• 13:51
  your
• 13:51
  pillow.
• 13:52
  You're
• 13:52
  actually
• 13:53
  just
• 13:53
  allowing
• 13:54
  the
• 13:54
  people
• 13:54
  in
• 13:54
  line
• 13:55
  to
• 13:55
  get
• 13:55
  there
• 13:55
  and
• 13:55
  party
• 13:56
  and
• 13:56
  whip
• 13:57
  out
• 13:57
  their
• 13:57
  glow
• 13:57
  sticks
• 13:58
  and
• 13:58
  have
• 13:59
  a
• 13:59
  great
• 13:59
  time
• 14:00
  and
• 14:00
  not
• 14:01
  yank
• 14:01
  them
• 14:01
  out.
• 14:01
  Right?
• 14:02
  So
• 14:02
  you're
• 14:02
  removing
• 14:02
  the
• 14:03
  inhibition,
• 14:03
  the
• 14:03
  big
• 14:04
  muscly
• 14:04
  bouncers.
• 14:05
  And
• 14:05
  I
• 14:05
  think
• 14:05
  that's
• 14:05
  a
• 14:06
  really
• 14:06
  cool
• 14:06
  thing.
• 14:07
  Now,
• 14:08
  not
• 14:08
  to
• 14:08
  get
• 14:08
  too
• 14:08
  nitty
• 14:09
  gritty,
• 14:09
  but
• 14:10
  those
• 14:11
  same
• 14:11
  norepinephrine
• 14:12
  neurons
• 14:12
  that
• 14:13
  you're
• 14:13
  targeting
• 14:13
  with
• 14:13
  Rembron
• 14:14
  can
• 14:14
  also
• 14:14
  suppress
• 14:15
  serotonin
• 14:15
  neurons
• 14:16
  through
• 14:17
  those
• 14:17
  same
• 14:18
  autoreceptors.
• 14:19
  They're
• 14:19
  heteroreceptors.
• 14:20
  Okay?
• 14:20
  One
• 14:21
  mnemonic
• 14:21
  for
• 14:21
  me
• 14:21
  is
• 14:22
  I
• 14:22
  think
• 14:22
  heterosexual.
• 14:23
  Okay?
• 14:23
  I
• 14:23
  think
• 14:24
  almost,
• 14:24
  maybe
• 14:24
  even
• 14:24
  I'll
• 14:25
  think
• 14:25
  bisexual.
• 14:26
  Right?
• 14:27
  And
• 14:27
  what.
• 14:28
  What
• 14:28
  I
• 14:28
  mean
• 14:28
  by
• 14:28
  that
• 14:28
  is
• 14:29
  that
• 14:29
  these
• 14:29
  norepinephrine
• 14:30
  neurons,
• 14:31
  when
• 14:31
  we're
• 14:31
  talk
• 14:31
  heteroreceptors,
• 14:32
  we're
• 14:32
  talking
• 14:33
  about
• 14:33
  the
• 14:33
  fact
• 14:34
  that
• 14:34
  they
• 14:34
  have
• 14:34
  influence
• 14:35
  over
• 14:35
  more
• 14:35
  than
• 14:36
  just
• 14:36
  the
• 14:36
  ne.
• 14:36
  Norepinephrine
• 14:37
  receptor,
• 14:37
  and
• 14:38
  it's
• 14:38
  also
• 14:38
  the
• 14:38
  Serotonin
• 14:39
  receptors.
• 14:41
  So
• 14:41
  again,
• 14:41
  we're
• 14:42
  not
• 14:42
  blocking
• 14:42
  sirt.
• 14:43
  We're
• 14:43
  also
• 14:44
  doing
• 14:44
  the
• 14:44
  same
• 14:44
  thing
• 14:45
  with
• 14:46
  Remeron
• 14:46
  as
• 14:46
  it
• 14:46
  relates
• 14:47
  to
• 14:47
  serotonin
• 14:48
  neurons,
• 14:48
  okay?
• 14:49
  Where
• 14:49
  we're
• 14:50
  stopping
• 14:50
  the
• 14:50
  inhibition,
• 14:51
  we're
• 14:51
  yanking
• 14:52
  the
• 14:52
  bouncers
• 14:53
  out
• 14:53
  of
• 14:53
  the
• 14:53
  nightclub,
• 14:54
  saying,
• 14:54
  hey,
• 14:55
  now
• 14:55
  you
• 14:55
  get
• 14:55
  to
• 14:55
  party.
• 14:55
  Now
• 14:56
  you
• 14:56
  get
• 14:56
  to
• 14:56
  do
• 14:56
  your
• 14:56
  thing,
• 14:57
  okay?
• 14:58
  And
• 14:58
  that's
• 14:58
  really
• 14:58
  cool.
• 14:59
  So
• 14:59
  I
• 15:00
  really
• 15:00
  love
• 15:00
  that.
• 15:01
  And
• 15:01
  it's
• 15:02
  one
• 15:02
  of
• 15:02
  the
• 15:02
  many
• 15:02
  reasons
• 15:03
  I
• 15:03
  really
• 15:03
  dig
• 15:03
  Remeron.
• 15:05
  Now
• 15:05
  you
• 15:05
  have
• 15:05
  this
• 15:06
  other
• 15:06
  mechanism
• 15:07
  that's
• 15:07
  pretty
• 15:07
  elegant
• 15:08
  and
• 15:08
  pretty
• 15:09
  neat.
• 15:09
  You
• 15:09
  have
• 15:09
  this
• 15:10
  with
• 15:10
  velazadone,
• 15:12
  okay?
• 15:12
  You
• 15:13
  have
• 15:13
  this
• 15:13
  with
• 15:15
  trintellics
• 15:15
  where
• 15:16
  you
• 15:16
  have
• 15:16
  a
• 15:17
  built
• 15:17
  in
• 15:17
  autoreceptor
• 15:18
  modulation,
• 15:19
  okay?
• 15:20
  And
• 15:20
  so
• 15:21
  they
• 15:21
  do
• 15:21
  something
• 15:21
  that's
• 15:22
  a
• 15:22
  little.
• 15:24
  It's.
• 15:25
  It's
• 15:25
  a
• 15:25
  little
• 15:25
  more
• 15:25
  simple
• 15:26
  than
• 15:26
  SSRI
• 15:27
  blockade,
• 15:27
  okay?
• 15:29
  Yes,
• 15:29
  Velazidone
• 15:31
  blocks
• 15:31
  the
• 15:31
  reuptake
• 15:32
  of
• 15:32
  serotonin,
• 15:33
  but
• 15:33
  it
• 15:33
  also
• 15:33
  partially
• 15:34
  agonizes
• 15:35
  the
• 15:35
  5ht1a
• 15:36
  receptor,
• 15:37
  okay?
• 15:38
  That
• 15:38
  5ht1a
• 15:39
  presynaptic
• 15:40
  receptor
• 15:41
  is
• 15:41
  the
• 15:42
  autoreceptor
• 15:42
  we're
• 15:43
  talking
• 15:43
  about
• 15:43
  here
• 15:43
  on
• 15:43
  serotonergic
• 15:44
  neurons,
• 15:44
  okay?
• 15:45
  So
• 15:46
  instead
• 15:46
  of
• 15:46
  it
• 15:46
  being
• 15:47
  fully
• 15:47
  activated,
• 15:48
  like
• 15:48
  when
• 15:48
  we
• 15:48
  gave
• 15:49
  Prozac,
• 15:49
  when
• 15:50
  we
• 15:50
  gave
• 15:50
  Zoloft,
• 15:51
  right?
• 15:51
  And
• 15:51
  the
• 15:51
  neurons
• 15:52
  freaking
• 15:52
  out
• 15:52
  and
• 15:52
  the
• 15:53
  autoreceptor,
• 15:54
  or
• 15:54
  as
• 15:54
  I
• 15:54
  call
• 15:55
  it,
• 15:55
  the
• 15:55
  thermoreceptor,
• 15:56
  instead
• 15:56
  of
• 15:56
  it
• 15:57
  freaking
• 15:57
  out
• 15:57
  and
• 15:57
  just
• 15:58
  stopping
• 15:59
  the
• 15:59
  release
• 15:59
  of
• 16:00
  serotonin,
• 16:01
  the
• 16:01
  excess
• 16:01
  release
• 16:01
  and
• 16:02
  modifying
• 16:03
  it
• 16:03
  homeostatically,
• 16:04
  instead
• 16:04
  of
• 16:04
  doing
• 16:04
  that,
• 16:05
  Velazidone
• 16:06
  and
• 16:06
  trintellix,
• 16:07
  they
• 16:07
  will
• 16:07
  partially
• 16:08
  agonize
• 16:08
  that.
• 16:10
  That
• 16:10
  autoreceptor,
• 16:11
  okay?
• 16:12
  Which
• 16:12
  is
• 16:12
  pretty
• 16:13
  neat,
• 16:13
  right?
• 16:13
  So
• 16:13
  we're
• 16:13
  not
• 16:14
  like
• 16:14
  flooding
• 16:14
  it
• 16:14
  with
• 16:15
  so
• 16:15
  much
• 16:15
  that
• 16:15
  it
• 16:15
  overreacts
• 16:16
  and
• 16:16
  shuts
• 16:16
  down
• 16:16
  the
• 16:16
  party
• 16:17
  or
• 16:17
  just
• 16:18
  sort
• 16:18
  of
• 16:18
  gently
• 16:20
  partially
• 16:20
  agonizing
• 16:21
  it,
• 16:21
  okay?
• 16:22
  So
• 16:22
  it's.
• 16:23
  Instead
• 16:23
  of
• 16:23
  full
• 16:23
  activation,
• 16:24
  it
• 16:25
  produces
• 16:26
  a
• 16:26
  bit
• 16:26
  of
• 16:26
  a
• 16:26
  weaker
• 16:27
  signal.
• 16:27
  So
• 16:28
  that
• 16:28
  smoke
• 16:28
  detector
• 16:29
  still
• 16:29
  works,
• 16:29
  but
• 16:29
  it's
• 16:29
  a
• 16:29
  little
• 16:30
  quieter.
• 16:30
  Okay.
• 16:31
  And
• 16:31
  that
• 16:31
  might.
• 16:32
  That
• 16:32
  might
• 16:32
  quiet
• 16:33
  some
• 16:33
  of
• 16:33
  the
• 16:33
  resistance
• 16:34
  because
• 16:34
  you're
• 16:34
  not
• 16:34
  agitating
• 16:35
  the
• 16:35
  bouncer
• 16:35
  as
• 16:36
  much.
• 16:36
  It's
• 16:37
  not
• 16:37
  this
• 16:37
  rave
• 16:38
  in
• 16:38
  the
• 16:38
  nightclub,
• 16:38
  but
• 16:39
  you're
• 16:39
  starting
• 16:39
  to
• 16:39
  dance.
• 16:40
  Like
• 16:40
  you're,
• 16:40
  you
• 16:41
  know,
• 16:41
  you're
• 16:41
  not
• 16:41
  going
• 16:41
  in
• 16:41
  there
• 16:41
  like
• 16:42
  a
• 16:42
  zombie
• 16:42
  and
• 16:42
  not
• 16:42
  talking,
• 16:43
  but
• 16:44
  you're
• 16:44
  dancing
• 16:44
  a
• 16:44
  little
• 16:44
  bit.
• 16:45
  Not
• 16:45
  to
• 16:45
  make
• 16:46
  the
• 16:46
  bouncer
• 16:46
  overreact
• 16:47
  and
• 16:47
  yank
• 16:47
  everybody
• 16:48
  out
• 16:48
  of
• 16:48
  the
• 16:48
  club,
• 16:48
  but
• 16:48
  just
• 16:49
  enough
• 16:49
  so
• 16:49
  that
• 16:50
  the
• 16:50
  bouncer
• 16:50
  kind
• 16:50
  of
• 16:51
  chills
• 16:51
  there
• 16:51
  and
• 16:51
  doesn't
• 16:52
  overreact
• 16:52
  and
• 16:52
  yank
• 16:53
  everybody
• 16:53
  out
• 16:54
  of
• 16:54
  the
• 16:54
  club.
• 16:54
  Okay?
• 16:55
  Some
• 16:55
  evidence
• 16:56
  that
• 16:56
  those
• 16:56
  two
• 16:57
  medications
• 16:57
  work
• 16:57
  a
• 16:58
  little
• 16:58
  faster.
• 16:59
  Not
• 16:59
  Ketamine
• 16:59
  fast,
• 17:00
  but
• 17:00
  faster.
• 17:01
  So
• 17:01
  that's
• 17:01
  pretty
• 17:02
  unique
• 17:02
  too.
• 17:03
  Okay.
• 17:05
  So
• 17:05
  I
• 17:05
  hope
• 17:06
  you
• 17:06
  enjoyed
• 17:07
  these
• 17:07
  sections
• 17:08
  so
• 17:08
  far.
• 17:08
  I
• 17:09
  think
• 17:09
  they're
• 17:09
  pretty
• 17:09
  fun.
• 17:11
  You
• 17:11
  also
• 17:11
  have,
• 17:12
  you
• 17:12
  know,
• 17:12
  meds
• 17:12
  like
• 17:13
  clonidine
• 17:14
  out
• 17:14
  there
• 17:14
  and
• 17:14
  guanfacine.
• 17:15
  They
• 17:15
  kind
• 17:16
  of
• 17:16
  do
• 17:16
  the
• 17:16
  opposite
• 17:16
  of
• 17:17
  Remeron.
• 17:18
  Okay.
• 17:18
  So
• 17:18
  instead
• 17:18
  of
• 17:19
  blocking
• 17:20
  the
• 17:21
  autoreceptors,
• 17:22
  where
• 17:22
  you're
• 17:23
  yanking
• 17:23
  out
• 17:23
  inhibition,
• 17:24
  they
• 17:24
  stimulate
• 17:25
  them
• 17:25
  a
• 17:26
  little
• 17:26
  bit.
• 17:26
  Okay.
• 17:27
  And
• 17:27
  the
• 17:27
  autoreceptors,
• 17:28
  like,
• 17:28
  whoa,
• 17:28
  whoa,
• 17:29
  whoa.
• 17:29
  Like,
• 17:30
  so
• 17:30
  in
• 17:30
  other
• 17:31
  words,
• 17:31
  you're.
• 17:31
  You're
• 17:32
  kind
• 17:32
  of
• 17:32
  tricking
• 17:32
  that
• 17:32
  autoreceptor
• 17:33
  to
• 17:33
  go,
• 17:33
  oh,
• 17:33
  my
• 17:33
  God,
• 17:34
  we
• 17:34
  have
• 17:34
  tons
• 17:34
  of
• 17:34
  norepinephrine
• 17:35
  now.
• 17:36
  So
• 17:36
  it
• 17:36
  reduces
• 17:37
  norepinephrine
• 17:37
  firing
• 17:38
  and
• 17:38
  norepinephrine
• 17:39
  release,
• 17:39
  which
• 17:39
  can
• 17:39
  be
• 17:39
  very
• 17:39
  calming
• 17:40
  in
• 17:40
  the
• 17:40
  case
• 17:40
  of
• 17:41
  guanfacine
• 17:42
  or
• 17:42
  clonidine.
• 17:42
  Right.
• 17:43
  So
• 17:43
  when
• 17:43
  you
• 17:43
  hit
• 17:43
  that
• 17:44
  autoreceptor,
• 17:45
  right,
• 17:45
  you're
• 17:45
  kind
• 17:45
  of
• 17:46
  doing
• 17:46
  the
• 17:46
  opposite.
• 17:46
  You're,
• 17:46
  like,
• 17:47
  freaking
• 17:47
  him
• 17:47
  out,
• 17:47
  and
• 17:47
  you're.
• 17:48
  You're
• 17:48
  making
• 17:48
  him
• 17:48
  act.
• 17:50
  You
• 17:50
  know,
• 17:50
  you're
• 17:50
  kind
• 17:50
  of
• 17:50
  goading
• 17:51
  the
• 17:51
  bouncer
• 17:51
  into
• 17:51
  going
• 17:52
  in
• 17:52
  there
• 17:52
  and
• 17:52
  shutting
• 17:53
  everything
• 17:53
  down.
• 17:54
  Right?
• 17:54
  You're
• 17:54
  kind
• 17:54
  of
• 17:55
  like.
• 17:55
  You're
• 17:55
  kind
• 17:55
  of
• 17:55
  dancing
• 17:56
  in
• 17:56
  his
• 17:56
  face.
• 17:56
  You're
• 17:57
  kind
• 17:57
  of.
• 17:57
  You're,
• 17:57
  like,
• 17:57
  twerking
• 17:58
  at
• 17:58
  him,
• 17:59
  and
• 17:59
  it's
• 17:59
  gonna
• 17:59
  make
• 18:00
  him
• 18:00
  very
• 18:00
  agitated,
• 18:01
  okay?
• 18:02
  And
• 18:02
  so
• 18:02
  you're.
• 18:03
  You're
• 18:03
  provoking
• 18:03
  him
• 18:04
  to
• 18:04
  shut
• 18:04
  the
• 18:04
  party
• 18:04
  down
• 18:05
  very
• 18:05
  quickly
• 18:06
  as
• 18:06
  opposed
• 18:06
  to
• 18:06
  yanking
• 18:07
  him
• 18:07
  out
• 18:07
  of
• 18:07
  the
• 18:07
  club.
• 18:08
  And
• 18:08
  when
• 18:08
  you
• 18:09
  yank
• 18:09
  him
• 18:09
  out
• 18:09
  of
• 18:09
  the
• 18:09
  club,
• 18:11
  of
• 18:11
  course,
• 18:11
  you
• 18:11
  have
• 18:11
  less
• 18:12
  inhibition
• 18:12
  completely.
• 18:13
  So
• 18:13
  just
• 18:13
  know
• 18:13
  that
• 18:14
  there's.
• 18:14
  You
• 18:14
  can
• 18:14
  agonize
• 18:15
  these
• 18:15
  autoreceptors
• 18:16
  on
• 18:16
  purpose
• 18:17
  for
• 18:17
  clinical
• 18:17
  effects
• 18:18
  like
• 18:18
  clonidine
• 18:18
  and
• 18:18
  guanfacine,
• 18:20
  so
• 18:20
  you
• 18:20
  can
• 18:20
  cool
• 18:20
  down
• 18:21
  the
• 18:21
  norepinephrine
• 18:22
  firing
• 18:22
  and
• 18:22
  norepinephrine
• 18:23
  release,
• 18:23
  which
• 18:23
  can
• 18:23
  be
• 18:23
  very
• 18:24
  therapeutic
• 18:24
  in
• 18:24
  certain
• 18:24
  people
• 18:25
  and
• 18:25
  in
• 18:25
  certain
• 18:25
  parts
• 18:26
  of
• 18:26
  the
• 18:26
  brain.
• 18:27
  Not
• 18:27
  all
• 18:27
  parts
• 18:27
  of
• 18:27
  the
• 18:27
  brain,
• 18:28
  okay.
• 18:28
  Because
• 18:29
  remember,
• 18:29
  we
• 18:29
  also
• 18:30
  stimulate
• 18:31
  receptors
• 18:32
  in
• 18:32
  postsynaptics.
• 18:33
  Receptors.
• 18:34
  We
• 18:34
  could
• 18:34
  talk
• 18:34
  about
• 18:35
  that
• 18:35
  in
• 18:35
  a
• 18:35
  different
• 18:35
  episode.
• 18:35
  But
• 18:36
  remember,
• 18:36
  when
• 18:36
  you
• 18:37
  stimulate
• 18:38
  postsynaptic
• 18:39
  alpha
• 18:40
  2
• 18:40
  receptors
• 18:40
  in
• 18:40
  the
• 18:40
  prefrontal
• 18:41
  cortex,
• 18:42
  which
• 18:42
  guanfacine
• 18:43
  also
• 18:43
  does,
• 18:44
  that
• 18:44
  actually
• 18:44
  helps
• 18:45
  working
• 18:45
  memory
• 18:45
  and
• 18:46
  impulse
• 18:46
  control.
• 18:47
  Okay.
• 18:48
  Kind
• 18:48
  of
• 18:49
  a
• 18:49
  different
• 18:49
  mechanism.
• 18:49
  I
• 18:50
  don't
• 18:50
  want
• 18:50
  to
• 18:50
  confuse
• 18:50
  you
• 18:50
  with
• 18:51
  that,
• 18:51
  but
• 18:51
  at
• 18:51
  the
• 18:51
  end
• 18:52
  of
• 18:52
  the
• 18:52
  day,
• 18:52
  the
• 18:52
  goal.
• 18:53
  The
• 18:53
  concept
• 18:53
  of
• 18:54
  this
• 18:54
  lecture
• 18:55
  today
• 18:55
  or
• 18:55
  this
• 18:55
  discussion
• 18:56
  today
• 18:57
  is
• 18:57
  that
• 18:57
  our
• 18:57
  meds
• 18:58
  act
• 18:58
  very
• 18:59
  differently
• 19:00
  and.
• 19:00
  And
• 19:01
  very
• 19:01
  elegantly.
• 19:02
  And
• 19:02
  to
• 19:03
  have
• 19:03
  an
• 19:03
  understanding
• 19:03
  of
• 19:04
  what
• 19:04
  they
• 19:04
  do
• 19:04
  and
• 19:04
  why,
• 19:05
  it
• 19:05
  really
• 19:05
  empowers
• 19:06
  you
• 19:06
  as
• 19:06
  a
• 19:06
  clinician
• 19:06
  to
• 19:07
  understand
• 19:07
  why
• 19:07
  there's
• 19:07
  a
• 19:08
  delay.
• 19:09
  You
• 19:10
  know,
• 19:10
  what
• 19:11
  we
• 19:11
  can
• 19:11
  do
• 19:11
  to
• 19:11
  get
• 19:12
  out
• 19:12
  of
• 19:12
  that
• 19:12
  delay,
• 19:13
  maybe
• 19:13
  throw
• 19:13
  in
• 19:14
  a
• 19:14
  Rembron
• 19:14
  there,
• 19:15
  lazadone
• 19:15
  there.
• 19:16
  Maybe
• 19:16
  understanding
• 19:17
  why.
• 19:18
  If
• 19:18
  your
• 19:18
  patient
• 19:19
  is
• 19:19
  incredulous
• 19:19
  that
• 19:20
  they're
• 19:20
  still
• 19:20
  depressed
• 19:20
  and
• 19:21
  anxious
• 19:21
  and
• 19:21
  they
• 19:21
  don't
• 19:21
  know
• 19:22
  why
• 19:22
  and
• 19:22
  they
• 19:22
  feel
• 19:22
  helpless,
• 19:23
  well,
• 19:24
  knowing
• 19:24
  the
• 19:24
  how
• 19:24
  and
• 19:24
  why
• 19:25
  behind
• 19:25
  this
• 19:25
  gives
• 19:25
  them
• 19:26
  a
• 19:26
  window
• 19:27
  into
• 19:27
  understanding
• 19:28
  why
• 19:28
  something
• 19:28
  like
• 19:29
  ketamine
• 19:29
  might
• 19:29
  work.
• 19:30
  Why?
• 19:30
  Because
• 19:30
  if
• 19:31
  you
• 19:31
  don't
• 19:31
  explain
• 19:31
  it,
• 19:32
  they're
• 19:32
  just
• 19:33
  going
• 19:33
  to
• 19:33
  implicitly
• 19:33
  assume
• 19:34
  that
• 19:34
  whatever
• 19:34
  you
• 19:34
  recommend
• 19:35
  next
• 19:35
  is
• 19:35
  like
• 19:36
  another
• 19:36
  thing
• 19:36
  we're
• 19:36
  trying.
• 19:37
  And
• 19:37
  oh,
• 19:37
  it's
• 19:37
  all
• 19:37
  hopeless
• 19:38
  because
• 19:38
  I,
• 19:38
  everything
• 19:38
  I'm
• 19:38
  trying
• 19:39
  is
• 19:39
  hopeless.
• 19:39
  But
• 19:40
  no,
• 19:40
  you
• 19:40
  can
• 19:40
  explain
• 19:41
  that
• 19:41
  genetically.
• 19:42
  You
• 19:42
  might
• 19:42
  have
• 19:43
  very
• 19:43
  recept
• 19:43
  sensitive
• 19:44
  autoreceptors
• 19:45
  and
• 19:45
  say
• 19:45
  it
• 19:45
  in
• 19:45
  your
• 19:45
  own
• 19:46
  language,
• 19:46
  say
• 19:46
  it
• 19:46
  in
• 19:46
  your
• 19:46
  own
• 19:46
  way.
• 19:47
  You
• 19:47
  can
• 19:47
  use
• 19:47
  the
• 19:47
  word
• 19:47
  thermostat
• 19:48
  to
• 19:49
  help
• 19:49
  them
• 19:49
  understand
• 19:49
  it.
• 19:50
  Um,
• 19:50
  but
• 19:50
  if
• 19:50
  you
• 19:51
  take
• 19:51
  the
• 19:51
  time
• 19:51
  and
• 19:52
  educate
• 19:52
  them,
• 19:52
  they
• 19:53
  won't
• 19:53
  be
• 19:53
  as
• 19:53
  hopeless
• 19:54
  because
• 19:54
  it's
• 19:54
  like,
• 19:54
  well,
• 19:54
  yeah,
• 19:55
  I
• 19:55
  actually
• 19:55
  have
• 19:55
  a
• 19:55
  lot
• 19:56
  of
• 19:56
  hope
• 19:56
  for
• 19:56
  ketamine
• 19:56
  because
• 19:57
  this
• 19:57
  is
• 19:57
  a
• 19:57
  completely
• 19:58
  different
• 19:59
  way.
• 19:59
  We're
• 19:59
  trying
• 20:00
  to
• 20:00
  curb
• 20:01
  my
• 20:01
  depressive
• 20:01
  symptoms.
• 20:02
  And
• 20:03
  you
• 20:03
  know,
• 20:04
  you
• 20:04
  have
• 20:04
  the
• 20:04
  neuroplasticity
• 20:05
  and
• 20:05
  AMPA
• 20:06
  and
• 20:06
  all
• 20:06
  these
• 20:06
  different
• 20:07
  mechanisms
• 20:07
  there,
• 20:09
  whether
• 20:10
  you
• 20:10
  move
• 20:10
  to
• 20:10
  Luvox
• 20:11
  and
• 20:11
  you
• 20:11
  do
• 20:12
  the
• 20:12
  sigma
• 20:13
  agonism,
• 20:14
  right?
• 20:14
  So
• 20:14
  we
• 20:14
  talked
• 20:15
  all
• 20:15
  about
• 20:15
  the
• 20:15
  sigma
• 20:16
  receptor
• 20:16
  and
• 20:16
  how
• 20:16
  interesting
• 20:17
  that
• 20:17
  is
• 20:17
  and
• 20:17
  the
• 20:17
  neuroprotection
• 20:18
  there,
• 20:18
  the
• 20:18
  anti
• 20:18
  inflammatory
• 20:19
  piece,
• 20:19
  right?
• 20:20
  So
• 20:20
  knowing
• 20:20
  the
• 20:20
  how
• 20:21
  and
• 20:21
  why
• 20:21
  of
• 20:21
  your
• 20:21
  meds
• 20:22
  allows
• 20:23
  you
• 20:23
  to
• 20:23
  explain
• 20:23
  to
• 20:23
  your
• 20:24
  patients
• 20:24
  why
• 20:24
  we're
• 20:24
  doing
• 20:24
  things.
• 20:25
  And
• 20:25
  that
• 20:25
  does
• 20:25
  thereby
• 20:26
  breed
• 20:27
  hope,
• 20:27
  which
• 20:28
  is
• 20:28
  a
• 20:28
  really
• 20:28
  cool
• 20:29
  concept.
• 20:29
  All
• 20:30
  right,
• 20:30
  my
• 20:30
  friends,
• 20:32
  I
• 20:32
  always
• 20:32
  say
• 20:33
  this,
• 20:34
  but
• 20:34
  there
• 20:34
  is
• 20:35
  a
• 20:36
  really
• 20:36
  big
• 20:36
  difference
• 20:36
  between
• 20:37
  good
• 20:37
  and
• 20:37
  great
• 20:38
  clinicians.
• 20:38
  And
• 20:38
  it's
• 20:38
  usually
• 20:39
  because
• 20:39
  the
• 20:39
  great
• 20:39
  ones
• 20:40
  understand
• 20:40
  the
• 20:40
  how
• 20:41
  and
• 20:41
  the
• 20:41
  why
• 20:41
  of
• 20:41
  what
• 20:42
  they're
• 20:42
  doing.
• 20:42
  Patients
• 20:42
  smell
• 20:43
  that
• 20:43
  a
• 20:44
  mile
• 20:44
  away.
• 20:45
  Now
• 20:45
  I
• 20:45
  built
• 20:45
  a
• 20:45
  whole
• 20:46
  Patreon
• 20:47
  library
• 20:48
  full
• 20:48
  of
• 20:49
  beautiful
• 20:49
  visuals,
• 20:50
  intuitive
• 20:50
  visuals
• 20:51
  that
• 20:51
  help
• 20:51
  you
• 20:51
  understand
• 20:52
  psychiatry
• 20:52
  quickly
• 20:53
  in
• 20:53
  a
• 20:53
  sticky
• 20:54
  way.
• 20:54
  And
• 20:55
  it
• 20:55
  will
• 20:55
  help
• 20:55
  you
• 20:56
  separate
• 20:56
  yourself
• 20:56
  from
• 20:57
  the
• 20:57
  goods
• 20:57
  to
• 20:57
  the
• 20:58
  greats.
• 20:58
  And
• 20:58
  patients
• 20:59
  will
• 20:59
  smell
• 20:59
  that
• 21:00
  a
• 21:00
  mile
• 21:00
  away.
• 21:00
  I
• 21:00
  am
• 21:01
  genuinely
• 21:01
  terrified
• 21:02
  to
• 21:02
  know
• 21:02
  who
• 21:02
  I
• 21:02
  would
• 21:02
  be
• 21:02
  as
• 21:03
  a
• 21:03
  clinician
• 21:03
  if
• 21:04
  I
• 21:04
  didn't
• 21:04
  have
• 21:04
  this
• 21:04
  library
• 21:05
  to
• 21:05
  fall
• 21:05
  back
• 21:05
  on.
• 21:06
  It
• 21:06
  has
• 21:06
  got
• 21:07
  so
• 21:07
  many
• 21:07
  beautiful
• 21:08
  visuals
• 21:08
  and
• 21:08
  lectures
• 21:09
  and
• 21:09
  pearl
• 21:09
  drops
• 21:10
  and
• 21:10
  rap
• 21:10
  songs
• 21:11
  and
• 21:11
  you
• 21:11
  name
• 21:11
  it.
• 21:11
  It's
• 21:11
  so
• 21:12
  much
• 21:12
  fun.
• 21:12
  It's
• 21:12
  such
• 21:12
  a
• 21:13
  great
• 21:13
  community
• 21:13
  of
• 21:13
  people
• 21:14
  and
• 21:14
  it's
• 21:14
  exciting
• 21:15
  because
• 21:15
  it
• 21:15
  makes
• 21:16
  psychiatry
• 21:16
  stick.
• 21:17
  I
• 21:17
  highly
• 21:17
  recommend,
• 21:17
  if
• 21:18
  there's
• 21:18
  one
• 21:18
  thing
• 21:18
  you
• 21:18
  don't
• 21:18
  forget
• 21:19
  today,
• 21:19
  my
• 21:19
  friends,
• 21:20
  before
• 21:20
  you
• 21:20
  go
• 21:20
  to
• 21:21
  bed,
• 21:22
  go
• 21:22
  to
• 21:22
  the
• 21:22
  show
• 21:22
  notes
• 21:23
  and
• 21:23
  become
• 21:23
  a
• 21:23
  Patreon
• 21:24
  member.
• 21:24
  You
• 21:24
  will
• 21:24
  not
• 21:24
  regret
• 21:25
  it.
• 21:25
  It
• 21:25
  is
• 21:25
  awesome.
• 21:25
  We
• 21:26
  would
• 21:26
  love
• 21:26
  to
• 21:26
  have
• 21:26
  you.
• 21:27
  We
• 21:27
  appreciate
• 21:27
  every
• 21:28
  one
• 21:28
  of
• 21:28
  you,
• 21:28
  by
• 21:28
  the
• 21:28
  way,
• 21:28
  for
• 21:29
  listening.
• 21:29
  Thank
• 21:30
  you
• 21:30
  all
• 21:30
  and
• 21:30
  see
• 21:30
  you
• 21:31
  next
• 21:31
  time
• 21:31
  here
• 21:31
  on
• 21:31
  Pearls
• 21:32
  and
• 21:32
  Prep.
• 21:32
  Bye.
• 21:33
  Bye.