XX-COGS11-adolescent brains and marijuana...

Mary

Part-2

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


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


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


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?

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


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

XX-COGS11-adolescent brains and marijuana...

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