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

Cannabinoid Receptors in Human Brain

Van Loere et al., 2007.

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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

Emergency Department Visits Involving

Selected Drugs: 2008

Source: SAMHSA, 2008 DAWN.

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

For More Info Visit

NIDA’s Website @

www.drugabuse.gov

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