what is marijuana?
cannabis sativa plant
leaves, stems flowers
delta‐9‐tetrahydrocannabinol
= Δ9‐THC
main psychoactive ingredient
Δ9‐THC is the main psychoactive ingredient
CB1receptor
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
endocannabinoids – ligands for CB1
N‐arachidonylethanolamine
anandamide(AEA)
2‐arachidonoylglycerol
2‐AG
arachidonate‐derived
neuroactive lipids
what areas of the brain process marijuana?
hypothalamus
basal ganglia
ventral striatum
amygdala
cortex
hippocampus
cerebellum
brainstem
“Neuroscience, the scientific study of the biology of the brain, has made great strides over the past decade in revealing that remarkable changes occur in the brain during the second decade of life.
Contrary to long‐held ideas that the brain was mostly grown up – “fully cooked” – by the end of childhood, it is now clear that adolescence is a time of profound brain growth and change.”
Weinberger, Elvevag, & Giedd, 2005
Giedd, J. N. (2008) Journal of Adolescent Health 42, 335–343
white matter
increase during adolescence
increase into 50’s (frontal, temporal)
corpus callosum greatest increase
during adolescence
gray matter
increases volume until early teens
decreases until old age
Giedd, J. N. (2008) Journal of Adolescent Health 42, 335–343
teen brain … is different
puberty changes everything
mood swings, slammed doors, rash decisions
brain is to blame –and the hormones
do not have reasoning as adults
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
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
Amygdala increases in size, which causes the teen’s
emotional centers to be in hyper‐drive
pre‐synaptic
post‐synaptic Voltage‐dependent
Ca++ channels open & Ca++enters the terminal.
Xmtr is released from
synaptic vesicle
Xmtr binds to receptor and the channel opens.
Post‐synaptic depolarization opens voltage‐dependent Ca++channels
which activates endocannabionid
synthesis. Ca++
How do endocannabinoids affect synaptic transmission?
endocannabinoid signaling is critical during development
infancy childhoodadolescence12‐17 years
oldadulthood
Brain maturation continues through adolescence.
robust neurodevelopment
brain maturation continues hippocampusprefrontal cortex
synaptic pruningreceptor distributionvolumetric growth
myelination
CB1 receptors increase dramatically from infancy to young adulthood.
hypothalamus
basal ganglia
ventral striatum
amygdala
cortex
hippocampus
cerebellumbrainstem
CB1 receptor expression changes over time
dramatic increase during development
frontal cortex, striatum &
hippocampusMato et al., 2003
endocannabinoid ligand expression changes during adolescence.
hypothalamus
basal ganglia
ventral striatum
amygdala
cortex
hippocampus
cerebellumbrainstem
AEA and 2‐AG expression changes
AEA – onset of puberty for females in
hypothalamus
2‐AG expression changes in PFC & N. Accumbens
Mato et al., 2003
disruption of normative endocannabinoid signalling during adolescence may have long‐standing consequences on adult brain function
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
10% eventually commit suicide
most experience a lifetime of disability
high emotional family burden
real‐faker.deviantart.com
Lewis, DA, Hashimoto, T and Volk, DW (2005) Nature Reviews Neuroscience 6:312‐324.
Psychosis:
distortions in inferential thinking
perceptual disturbances
auditory hallucinations
delusions ‐fixed, false beliefs that are firmly held in the face of contradictory evidence
hallucinations
voices distinct from one’s own thoughts
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 riskenvironmental events during development
advanced paternal age at time of conception
frequent cannabis use during adolescence
environmental events during development
advanced paternal age at time of conception
frequent cannabis use
during adolescence
genetics + environment
Schizophrenia is more than psychosis.
impairments
social
occupationalattentionvolitioncapacity for
pleasureexpression of emotion
language (fluency & production)
inferential thinkingperception
disturbances in brain function
Rubino, T and Parolaro, D (2008) Molecular and Cellular Endocrinology 286S S108–S113
Does cannabis use increase the risk of schizophrenia?
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.
Internal info
The cortex encodes, stores & combinesinformation about the external and internal environment in terms of rhythmic activity.
rhythmic activity
Somogyi, P. & Klausberger, T. (2005) J. Physiol 562.
Somogyi, P. & Klausberger, T. (2005) J. Physiol 562.
basket cell resets
pyramicalcell firing
a single inhibitory pulse will synchronize
two pyramidal
cells
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
basal ganglia
ventral striatum
amygdala
cortex
hippocampus
cerebellum
brainstem