no slide title - american psychological association · no slide title author: dr. joanna fowler...
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Nora D. Volkow, M.D. Director
National Institute on Drug Abuse National Institutes of Health
MARIJUANA’S Effects on Brain, Body
& Behavior
• An estimated 2.4 million Americans used it for the first time in 2009
National Survey on Drug Use and Health, SAMHSA, 2010.
Marijuana is the Most Commonly Used Illicit Drug In the U.S.
Tetrahydrocannabinol (THC)
Active Ingredient in Marijuana
• Over 104 million Americans have tried it at least once
Use of Specific Illicit Drugs in Lifetime
Among Persons 12 or Older, 2009
Source: 2009 NSDUH, SAMHSA, 2010.
`
Thousands
104,446
35,046
36,599
21,755
37,256
21,930
3,683
22,448
8,605
Natural and Drug Reinforcers Increase Dopamine in NAc
VTA/SN
nucleus accumbens
frontal cortex
Drugs of abuse increase DA in the Nucleus
Accumbens, which is believed to trigger the
neuroadaptions that result in addiction
150
125
100 0 20 40 60 80
MARIJUANA
% o
f B
as
al R
ele
as
e
0
100
200
300
400
500
600
700
800
900
1000
1100
0 1 2 3 4 5 hr
AMPHETAMINE
% o
f B
as
al R
ele
as
e
0
50
100
150
200
0 60 120 180
Time (min)
% o
f B
as
al R
ele
as
e
Empty
Box Feeding
Di Chiara et al.
FOOD
Tanda, et al, Science 1997.
Long Term Effects of Marijuana Addiction: About 9% of users may become dependent, 1 in 6 who start use in
adolescence, 25-50% of daily users
32
15
9
17
118
5
23
0
5
10
15
20
25
30
35
Per
cen
t
* Nonmedical Use
Source: Anthony JC et al., 1994
Estimated Prevalence of Dependence Among Users
* *
Cannabinoids in Brain
AC
g Gia b
Plasma membrane
Anandamide
O
N H
OH
2-Arachidonoylglycerol (2-AG)
O
O OH
OH
Cannabinoid Receptors
CB1
CB2
Endogenous Cannabinoid Ligands
Anandamide
2-Arachidonoylglycerol
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Cannabinoid Receptors Are Located
Throughout the Brain and Regulate:
• Brain Development
• Memory and Cognition
• Motivational Systems
• & Reward
• Appetite
• Immunological Function
• Reproduction
• Movement Coordination
• Pain Regulation
• & Analgesia
ADDICTION IS A DEVELOPMENTAL DISEASE it starts in adolescence and childhood
NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003.
Age
Age at tobacco, at alcohol and at cannabis use dependence as per DSM IV
0.0%
0.2%
0.4%
0.6%
0.8%
1.0%
1.2%
1.4%
1.6%
1.8%
5 10 15 21 25 30 35 40 45 50 55 60 65 Per
cen
tage
in e
ach
age
gro
up
wh
o
dev
elop
fir
st-t
ime
dep
end
ence
THC ALCOHOL
TOBACCO
Source: Gruber, AJ et al., Psychological Medicine, 33, pp. 1415-1422, 2003.
Graduated College
Household Income < $30,000
Satisfaction with Self & Life
General Happiness Level
Per
cent
Subjective Ratings
Source: Lynskey, MT et al., JAMA, 289, pp. 427-433, 2003.
Drug Use Outcomes in Twin Pairs (n =234)
Discordant for Cannabis Use Before Age 17
Od
ds
Rati
o
Tracings of left (yellow) and
right (blue) amygdalae and left
(red) and right (green)
hippocampI.
Hippocampal (A) and amygdalar (B)
volumes were smaller in cannabis users
than in non using control subjects.
Hippocampus Amygdala Brain abnormalities
associated with long-term
heavy cannabis use
Jucel et al., Arch Gen Psychiatry. 2008 Jun;65(6):694-701.
High Rates of Comorbid Mood & Anxiety Disorders Among
Respondents with Marijuana Dependence (NESARC)
61
49 47
20 24
10 9 14
21
27
21 20 16 17
4 3 2 1 4 5
9 4
0
10
20
30
40
50
60
70
Per
cen
t
Marijuana Dependence General Population
Adolescent Cannabis Use Increases the Risk for Adult
Psychosis in Genetically Vulnerable Individuals
0
2
4
6
8
10
12
14
16
18
20
Met/Met Val/Met Val/Val
% w
ith
sch
izo
ph
ren
iform
dis
ord
er a
t a
ge
26
COMT Genotype
no adolescent cannabis use
adolescent cannabis use
Source: Caspi, A. et al. Biol. Psychiatry, 57: 1117-1127; 2005. Source: Caspi, A. et al., Biol. Psychiatry, 57: 1117-1127; 2005.
Changes in Brain Glucose Metabolism During Marijuana Intoxication
Volkow, N.D. et al., Psychiatry Research: Neuroimaging, 67, pp. 29-38, 1996.
Cerebellar activity is impaired during intoxication
Potency: Increased THC Content in Seized Marijuana,
1983-2009
Sources: The University of Mississippi Potency Monitoring Project
0
1
2
3
4
5
6
7
8
9
10
Pe
rce
nt T
HC
Increased Marijuana Treatment Admissions
1993 and 2007
0
10
20
30
40
50
60
Alcohol Cocaine Heroin Marijuana
Per
cen
t o
f A
dm
issi
on
s
1993 2007
Source: SAMHSA, TEDS 1993 & 2007
Percentage of U.S. 12th Grade Students Reporting Past
Month Use of Cigarettes &Marijuana, 1975 to 2009
0
10
20
30
40
Pe
rce
nt Cigarettes
Marijuana
Source: The Monitoring the Future study, the University of Michigan
Changes in Attitude Lead to Changes in Use Marijuana Use and Perceived Risk among 12th Graders, 1975 to 2009
0
10
20
30
40
50
60
75 78 81 84 87 90 93 96 99 02 05 08
Pe
rce
nt
Past Year Use Perceived Risk
Source: The Monitoring the Future study, the University of Michigan
Source: Solowij N et al. Psychopharmacology (Berl.) 2011 Feb 17 [Epub ahead of print].
Relationships Between Total Words Recalled and Quantity, Frequency, Duration and Age of Onset
of Regular Cannabis Use T
ota
l W
ords R
ecall
ed (T
ria
ls I
-V)
Tota
l W
ords R
ecall
ed (T
ria
ls I
-V)
Tota
l W
ords R
ecall
ed (T
ria
ls I
-V)
Tota
l W
ords R
ecall
ed (T
ria
ls I
-V)
Quantity of Cannabis Use (cones/month) Frequency of Cannabis Use (days/month)
Duration of Regular Cannabis Use (years) Age of Onset of Regular Cannabis Use
Brain Glucose Metabolism in Controls and Marijuana Abusers
Volkow, N.D. et al., Psychiatry Research: Neuroimaging, 67, pp. 29-38, 1996.
Control
Marihuana Abuser
0.8
0.85
0.9
0.95
1
1.05
1.1
1.15
1.2
Control Abuser
Cer
ebel
lum
/Wh
ole
Bra
in
p < 0.01
Cerebellar metabolism is decreased in Marijuana Abusers
Depression Symptoms at Age 10 by Trimester of Prenatal
Marijuana Exposure
Gray et al., 2005.
44
45
46
47
48
49
50
First Second Third
Me
an N
um
be
r o
f S
ym
pto
ms
Abstainer Light Moderate Heavy
p<.01 p <.05 p=ns
Prosper Multisite Community Study:
Less MJ & Inhalants 1.5 Yrs Past Baseline
Past Year Use
0
1
2
3
4
5
6
Marijuana Use Inhalant Use
2.8
3.6
4.8
5.8
Per
cen
t
Intervention Control
Spoth, Redmond, Shin, Greenberg, Clair, Feinberg (2007). Am J Prev Med, 32(5), 395-402.
Effects of THC and Lofexidine in a Human Laboratory Model of Marijuana Withdrawal and Relapse
Source: Haney, M et al., Psychopharmacology, 197, pp. 157-168, 2008.
Marijuana Craving
Capsule Strength
100
75
50
25
0
Ra
tin
gs
(mm
)
**
Sleep Latency (objective)
Fell Asleep Easily (subjective)
100
75
50
25
0
Min
**
*
Placebo THC Lofexidine THC/Lofex
Marijuana Relapse:
Money Spent on Self-Administration
25
20
15
10
5
0
Do
lla
rs (U
SD
)
**
Areas where Adolescents with Heavy Marijuana Use
(n=15) Showed Decreased Connectivity Compared to
Non Drug Users (n=15)
Decreased axial diffusivity is
depicted the right superior
temporal gyrus (first
column), the left posterior
internal capsule/thalamic
radiations (second column).
Ashtari et al., J Psychiatr Res. 43(3):189-204 2009.
Differences between: 16 year olds (adolescents) and 23-30 year olds (young adults)
Frontal Lobe
Subcortical Region
Source: Sowell, E.R. et al., Nature Neuroscience, 2(10), pp. 859-861, 1999
Subcortical
Frontal
Parietal
Occipital
Temporal
Differences in Gray Matter Density Between Adolescence and Young Adulthood