The Shifting Marijuana Legal Environment: Linking

Epidemiology and Neuroscience

Wilson M. Compton, MD, MPE

Deputy Director

1 to 2 Days23%

3 to 5 Days16%

6 to 19 Days19%

20 or More Days41%

Among Current Marijuana Users, Two In Five Are Daily or Almost Daily Users

Source: SAMHSA, 2013 National Survey on Drug Use and Health (September 2014).

19.8 Million Past Month Users of Marijuana in 2013

Number of Days Used Marijuana in the Past Month

Increasing Potency of Marijuana (% Δ-9 THC)

SOURCE: University of Mississippi Marijuana Project

%

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

2013

2014

0

2

4

6

8

10

12

14

16

∆-9 THC

Addiction: About 9% of users may become dependent

(~1 in 6 who start in adolescence, and 25-50% of daily users)32

15

9

17

118

5

23

05

101520253035

Percent

* Nonmedical Use Source: Anthony JC et al., 1994

Estimated Prevalence of Dependence Among Users

**

Similarly, 8.9% estimated lifetime DSM-IV Dependence among marijuana users (NESARC data collected 2001-2005, Lopez-Quintero et

al., 2011)

75

76

77

78

79

80

81

82

83

84

85

86

87

88

89

90

91

92

93

94

95

96

97

98

99

0 1 2 3 4 5 6 7 8 9 10

11

12

13

14

0

20

40

60

80

100

Past Year Use

Perceived Risk is Correlated with Use of Marijuana:

12th Graders’ Use vs. Perceived Risk of Occasional MJ Use

SOURCE: University of Michigan, 2014 Monitoring the Future Study

Denotes significant difference between 2013 and 2014.

%

Source of Marijuana* among 12th Graders in 2012 and 2013, by State

Policy

Given friend

B

ought friend

B

ought dealer/s

tranger

G

iven relativ

e

O

ther method

B

ought relativ

e

T

ook relativ

e

T

ook friend

O

wn MMJ Rx

Someone else's MMJ Rx0

20

40

60

80

100Medical Marijuana States Non-Medical Marijuana States

**

**

*Categories not mutually exclusive ** Statistically significant difference SOURCE: University of Michigan, 2013 Monitoring the Future Study

%

Methods of Using Marijuana Among

12th Grade Past Year Users, 2014

Smoking In Food In Drink Other0.0

20.0

40.0

60.0

80.0

100.0

Non-MMJ States MMJ States

SOURCE: University of Michigan, 2014 Monitoring the Future Study

Non-usersused 1 Dx

used 2 Dx

used 3 Dx

-8

-6

-4

-2

0

2

Avera

ge P

oin

t D

iffere

nce

in

IQ

sco

re

(IQ

at

ag

e 3

8 –

IQ

at

ag

e 1

3)

Persistent Marijuana Users Show A Significant IQ Drop between

Childhood and Midlife

Source: Meier MH et al., PNAS Early Edition 2012

Followed 1,037 individuals from birth to age 38. Tested marijuana use at 18, 21, 26, 32 and 38. Tested for IQ at ages 13 and 38

Silins, et al., Lancet Psychiatry 2014;1:286-293

HS Complete0

0.2

0.4

0.6

0.8

1

1.2

Never< MonthlyMonthly +Weekly +Daily

HS Complete0

0.2

0.4

0.6

0.8

1

1.2

O.R.

Cannabis Depend

0

5

10

15

20O.R.

Other Illicit Drug

0

2

4

6

8

O.R.

Suicide At-tempt

012345678

O.R.

More Teenage Use of Cannabis Associated with Worse Outcomes in

20’s (3 Australia/New Zealand Studies)

Cannabis May be Causally Associated with Schizophrenia

Giordano, Ohlsson, Sundquist, Sundquist, Kendler Psychological Medicine 2015

Baseline After 1 Yr After 5 Yrs After 7 Yrs

General Pop'n 10.44 9.19 5.95 4.24

Relative Pairs:

1st Cousin 9.40 8.37 5.85 4.05

Paternal 1/2 Sib 9.15 8.42 6.12 4.18

Maternal 1/2 Sib 6.00 5.85 3.42 2.58

Full Sibs 5.07 4.47 2.80 1.98

MZ Twins* 3.92 3.38 2.63 1.67

* Extrapolated

Risk (Odds Ratios) of hospital diagnosis of schizophrenia after prior registration for cannabis abuse in: (i) general population and (ii) co-relatives, allowing time

from exposure to disease to vary by 1-7 years

Schizophrenia Risk May Cause Cannabis Use

Power, Verweij, Zuhair, Montgomery, Henders, Heath, Madden, Medland, Wray, Martin. Molecular Psych 2014

Mean standardized schizophrenia polygenic risk scores for twin pairs of with neither (n=272), one (n=273) or both twins (n=445) reporting cannabis use.

P = 0.001 (Ordinal Regression)

Subcortical structures evaluated for group differences between daily marijuana users

and nonusers.

Weiland B J et al. J. Neurosci. 2015;35:1505-1512

Complexity in Long-Term MJ (n=48) v. Controls (n=62)

Filbey et al. PNAS Nov 10, 2014

MJ users had significantly less bilateral orbitofrontal gyri volume

Trend suggests FA of the forceps minor

tract initially increased then

decreased

Higher functional and structural OFC connectivity

Adolescent Brain Cognitive DevelopmentNational Longitudinal Study

NIDA, NIAAA, NCI, NICHD, NIMHD, ORWH, NIMH, NINDS, OBSSR

Ten year longitudinal study of 10,000 children from

age 10 to 20 years to assess effects of drugs on

individual brain development trajectories  

Marijuana as Medicine?

•Promise lies in purified ingredients or synthetic compounds with more selectivity, less adverse effects

•Applications: pain, nausea, wasting, obesity, muscle spasticity, addiction, inflammatory conditions, HIVNIH research (across NIDA, NCI, NINDS,

NIAID, etc.) focuses on THC, CBD, and compounds that alter the function of the

endocannabinoid system.