this March the FDA approved the first
new chemical mechanism for fighting
depression in decades it's a nasal spray
of ketamine most commonly known for its
use as a tranquilizer how do drugs like
these affect the brain and what's new
about this one let's start from the
bottom we think the activity of neurons
in your brain produce your experiences
and behaviors while these cells are
famously electrical the connections
between them are chemical where neurons
connect with others they let out little
bursts of chemicals which can encourage
or prevent the next neuron from becoming
active any chemical that's used in this
way is called a neurotransmitter the
most common neurotransmitters in the
brain are glutamate and GABA which are
both present in around half of all
neural connections glutamate is
excitatory it tends to cause neurons to
fire more and in gaba is inhibitory it
tends to shut them off you may also have
heard of dopamine serotonin and
norepinephrine the stuff in EpiPens
these are some of the most common
neurotransmitters known to affect
behavior in the brain we've actually
discovered over 200 neurotransmitters
which are used by a whole zoo of
different neuron types drugs that affect
the brain are often found to imitate
bolster or suppress natural
neurotransmitters a lot of what we know
about the behavioral roles of
neurotransmitters comes from seeing the
effects of psychoactive drugs that
interact with them this is the case for
depression as well we still don't know
for sure what depression is at the
neural level because it presents in so
many different ways for different people
right now like most psychological
disorders we're still working backwards
from what we can observe behaviorally
for example we know depression is marked
by symptoms such as low mood fatigue
mental fog and suicidal thoughts and the
1960s scientists noticed that some drugs
which changed serotonin levels in the
brain had mood related side-effects
those that lowered serotonin tended to
cause depressive symptoms while those
that raised it tended to alleviate them
this led to the serotonin hypothesis the
idea that depression was related to a
decrease in serotonin SSRIs or selective
serotonin reuptake inhibitors were
developed to treat depression by
increasing serotonin activity
unfortunately low serotonin isn't the
whole story for depression many other
neurotransmitters are also altered in
patients with depression and just
raising serotonin levels alone isn't
always enough around 1/3 of patients
with depression don't seem to respond to
SSRIs enter ketamine ketamine interferes
with glutamate signaling remember that
glutamate is the major neurotransmitter
that makes neurons more active and it's
in around half of all the connections in
your brain as you can imagine
interfering with it has some pretty
wide-ranging effects at high doses
ketamine effectively disconnects higher
and lower brain areas cutting people off
from the outside world making it
impossible to see here field pain or
even produce memories this is great for
patients undergoing surgeries or other
medical interventions especially because
it preserves heart and lung function
unlike most sedatives ketamine was
approved for medical use in the US and
1970 and saw heavy application and
surgeries following the Vietnam War low
doses of ketamine were first found to
affect depression in the late 90s
antidepressant effects were seen within
hours of taking the drug and could last
for weeks this was very different from
SSRIs which for some reason can take
months to reach full effect and wear off
quickly when you stop taking them
research is still just beginning but
ketamine seems to do more than
temporarily affect glutamate signaling
it somehow causes the brain to produce
more chemicals that are basically neural
fertilizers helping neurons to grow new
connections when combined with other
treatments like cognitive behavioral
therapy this could allow some patients
to rapidly develop new pathways that
help them to better regulate their
emotions studies have shown that more
than half of patients respond to
ketamine even when SSRIs don't work
due to its immediate and lasting action
ketamine is poised to become an
invaluable tool for treating depression
of course it's important to be cautious
this is a very new treatment we have
only observed patients for up to a year
after receiving it
ketamine can also cause hallucinations
and has the potential for addiction and
abuse as a result the FDA has only
approved it for patients with moderate
to severe depression who have not
responded to at least two other
medications despite these limitations
ketamine holds a lot of promise it
represents an entirely new way of
treating depression by interacting with
glutamate as research continues that may
lead us to a whole new family of drugs
and a deeper understanding of the neuro
chemistry of depression thanks for
watching and stay curious
[Music]