adolescent brains and
marijuana use
Mary ET Boyle, Ph.D.
Department of Cognitive Science, UCSD
Adolescence is a time of
enormous opportunity
and of
enormous risk
Dr. Jay Giedd
Tough Subject
politics
shoulds
fear
crime
in this talk
what is marijuana?
the brain on marijuana
is the teen brain special?
current research
teenage brains
are really
different than…
…8 year old
brains…
MRI structural &
physiological imaging
… and adult
brains.
Longitudinal studies
from 3 – 30 years old
Giedd, J. N. (2008) Journal of Adolescent Health 42, 335–343
what is marijuana?
cannabis sativa
plant
leaves, stems
flowers
delta-9tetrahydrocannabi
nol
= Δ9-THC
main psychoactive
ingredient
Δ9-THC is the main psychoactive ingredient
Δ9-THC activates cannabinoid1
(CB1) receptor in the brain.
CB1 is expressed at high levels in
many brain areas
Two endogenous brain lipids have been
identified as CB1 ligands
CB1
receptor
endocannabinoids – ligands for CB1
N-arachidonylethanolamine
anandamide
(AEA)
2-arachidonoylglycerol
arachidonate-derived
neuroactive lipids
2-AG
what areas of the brain process marijuana?
hypothalamus
cortex
basal ganglia
hippocampus
ventral striatum
amygdala
cerebellum
brainstem
hormones
appetite
hypothalamus
cortex
basal ganglia
hippocampus
circadian
rhythms
sexual behavior
ventral striatum
amygdala
brainstem
cerebellum
motor controlled
planning
initiation of
actions
hypothalamus
cortex
basal ganglia
hippocampus
ventral striatum
termination of
actions
habit pathway
amygdala
brainstem
cerebellum
prediction
hypothalamus
cortex
basal ganglia
reward
hippocampus
ventral striatum
amygdala
brainstem
addiction?
cerebellum
anxiety
hypothalamus
cortex
basal ganglia
emotion
hippocampus
ventral striatum
amygdala
brainstem
fear
cerebellum
vomiting reflex
hypothalamus
cortex
basal ganglia
pain sensation
hippocampus
ventral striatum
amygdala
brainstem
sympathetic
nervous system
reactions
cerebellum
higher
cognitive
functions
hypothalamus
cortex
basal ganglia
hippocampus
ventral striatum
amygdala
brainstem
sensation
perception
cerebellum
judgment and
pleasure
memory
formation
hypothalamus
cortex
basal ganglia
ventral striatum
hippocampus
amygdala
brainstem
learning:
facts
cerebellum
sequences
places
motor control
hypothalamus
cortex
basal ganglia
coordination
hippocampus
ventral striatum
amygdala
brainstem
cerebellum
motor learning
doubles risk
of car accident
- DUI
what is marijuana?
the brain on marijuana
is the teen brain special?
current research
“Neuroscience research has shown that while
teenagers' feet may be done growing
by the end of high school,
their brains
are not.”
Rachel Tompa – www.berkeley.edu
white
matter
gray matter
increase during
adolescence
increases volume
until early teens
increase into 50’s
(frontal,
temporal)
decreases until
old age
corpus callosum
greatest increase
during
adolescence
Giedd, J. N. (2008) Journal of Adolescent Health 42, 335–343
is it the addition problem?
caffeine
adderall
video games
facebook
gambling
food
damage to ability to learn argument?
lack of
sleep
caffeine
drinks
poor diet
stress &
anxiety
Hill, C., et al. Arch. Dis. Child. 2007;92;637-643; Blankston, K. L. et al, Pediatrics in Review 2013;34;55
is it really a gateway drug?
Most cocaine
users started
with marijuana
Brain is changed
 more likely to
use other drugs
Young age +
regular use
Genetic
predisposition
Hall, W. D. and Lynskey, M. Drug and Alcohol Review, (January 2005), 24, 39 – 48
teen brain … is different
puberty changes
everything
do not have
reasoning as
adults
mood swings,
slammed doors,
rash decisions
brain is to blame –
and the hormones
prefrontal cortex
–involved in
complex decision
making
Prefrontal cortex is
one of the last
parts of the brain
to mature
Testosterone
increases
aggression and
irritability.
Estrogen enlarges
the hippocampus
more in girls
Giedd, J. N. (2008) Journal of Adolescent Health 42, 335–343
teen underdeveloped decision
processing affects everything
Amygdala increases in size,
which causes the teen’s
emotional centers to be in
hyper-drive
all decisions
risk taking
decisions – teens
have higher levels
of dopamine too
lack of impulse
control –
prefrontal and
serotonin
teens prefrontal
cortex is similar to
a damaged adult’s
prefrontal cortex
moral decision
knowledge and
doing disconnect
emotion control
Giedd, J. N. (2008) Journal of Adolescent Health 42, 335–343
what is marijuana?
the brain on marijuana
is the teen brain special?
current research
How do endocannibinoids affect synaptic transmission?
Voltagedependent Ca++
channels open
& Ca++ enters
the terminal.
post-synaptic
Xmtr is released
from synaptic
vesicle
pre-synaptic
Xmtr binds to
receptor and the
channel opens.
Post-synaptic
depolarization
opens voltagedependent Ca++
channels 
which activates
endocannabionid
synthesis.
Ca++
endocannabinoid signaling is critical during development
Brain maturation continues through adolescence.
infancy
childhood
adolescence
12-17 years old
adulthood
robust neurodevelopment
brain maturation continues
hippocampus
prefrontal cortex
synaptic pruning
receptor distribution
volumetric growth
myelination
CB1 receptors increase dramatically from infancy to young adulthood.
CB1 receptor
expression
changes over
time
hypothalamus
cortex
basal ganglia
hippocampus
dramatic
increase during
development
ventral striatum
amygdala
cerebellum
brainstem
frontal cortex,
striatum &
hippocampus
Mato et al., 2003
endocannabinoid ligand expression changes during adolescence.
AEA and 2-AG expression
changes
hypothalamus
cortex
basal ganglia
hippocampus
AEA – onset of puberty
for females in
hypothalamus
ventral striatum
amygdala
cerebellum
brainstem
2-AG expression changes in
PFC &
N. Accumbens
disruption of normative endocannabinoid signalling
during adolescence may have long-standing
consequences on adult brain function
Mato et al., 2003
Rubino, T and Parolaro, D (2008) Molecular and Cellular Endocrinology 286S S108–S113
Schizophrenia is a devastating illness.
1% of world
population
emerges: late
adolescence or
early adulthood
most experience
a lifetime of
disability
high emotional
family burden
real-faker.deviantart.com
10% eventually
commit suicide
Lewis, DA, Hashimoto, T and Volk, DW (2005) Nature Reviews Neuroscience 6:312-324.
voices distinct from
one’s own thoughts
Psychosis:
distortions in
inferential
thinking
perceptual
disturbances
auditory
hallucinations
hallucinations
delusions -fixed, false beliefs that
are firmly held in the face of
contradictory evidence
Lewis, DA, Hashimoto, T and Volk, DW (2005) Nature Reviews Neuroscience 6:312-324.
Risk of developing schizophrenia
risk is directly proportional to being genetically related to someone
affected by schizophrenia
degree of risk conferred for each susceptibility gene is small
twin studies:
only 50% is accounted for by genes – the rest is environmental risk
environmental events increase risk
environmental
events during
development
advanced paternal
age at time of
conception
frequent cannabis
use during
adolescence
environmental
events during
development
frequent cannabis
use during
adolescence
genetics + environment
advanced
paternal age
at time of
conception
Schizophrenia is more than psychosis.
impairments
disturbances in brain function
social
perception
inferential
thinking
language
(fluency &
production)
expression
of emotion
capacity for
pleasure
volition
attention
occupational
Does cannabis use
increase the risk of
schizophrenia?
Rubino, T and Parolaro, D (2008) Molecular and Cellular Endocrinology 286S S108–S113
Lewis, DA, Hashimoto, T and Volk, DW (2005) Nature Reviews Neuroscience 6:312-324.
Tanaka, S. (2008) BMC Neuroscience 9:41
Tanaka, S. (2008) BMC Neuroscience 9:41
Somogyi, P. & Klausberger, T. (2005) J. Physiol 562.
The cortex encodes, stores & combines
information about the external and internal
environment in terms of rhythmic activity.
Internal
info
rhythmic activity
Somogyi, P. & Klausberger, T. (2005) J. Physiol 562.
a single
inhibitory
pulse will
synchronize
two
pyramidal
cells
basket cell
resets
pyramical cell
firing
Somogyi, P. & Klausberger, T. (2005) J. Physiol 562.
IPSPs in theta frequency
caused tighter synchrony
so – does cannabis use
during adolescence increase
the risk of Sx?
Malone, D. T., et al (2010) British Journal of Pharmacology, 160, 511–522
Malone, D. T., et al (2010) British Journal of Pharmacology, 160, 511–522
what now?
hypothalamus
cortex
basal ganglia
hippocampus
ventral striatum
amygdala
cerebellum
brainstem