1) Marijuana legalization is increasing as more states legalize medical and recreational use, while potency of the drug has also increased. 2) Regular marijuana use, especially beginning in adolescence, is associated with risks of addiction and other health issues like drops in IQ. However, perceived risks of marijuana are declining. 3) More research is needed to fully understand the complex relationships between marijuana use and mental health issues like schizophrenia, as well as the long-term effects of marijuana on the brain. 4) Large longitudinal studies are underway to help determine how marijuana may affect adolescent brain development and function.

1. The Shifting Marijuana Legal Environment:
Linking Epidemiology and Neuroscience
Wilson M. Compton, MD, MPE
Deputy Director

2. 1 to 2 Days
23%
3 to 5 Days
17%
6 to 19 Days
19%
20 or More
Days
41%
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

3. Increasing Potency of Marijuana (% Δ-9 THC)
SOURCE: University of Mississippi Marijuana Project
%
0
2
4
6
8
10
12
14
16
∆-9 THC

4. 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
11
8
5
23
0
5
10
15
20
25
30
35
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)

5. 0
20
40
60
80
100
75 77 79 81 83 85 87 89 91 93 95 97 99 01 03 05 07 09 11 13
Past Year Use Perceived Risk
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.
%

6. Source of Marijuana* among 12th Graders in 2012
and 2013, by State Policy
0
20
40
60
80
100
Medical Marijuana States Non-Medical Marijuana States
**
**
*Categories not mutually exclusive
** Statistically significant difference SOURCE:University of Michigan, 2013 Monitoring the Future Study
%

7. Methods of Using Marijuana Among
12th Grade Past Year Users, 2014
0.0
20.0
40.0
60.0
80.0
100.0
Smoking In Food In Drink Other
Non-MMJ States MMJ States
SOURCE: University of Michigan, 2014 Monitoring the Future Study

8. Non-users
used
1 Dx
used
2 Dx
used
3 Dx
-8
-6
-4
-2
0
2
AveragePointDifferenceinIQscore
(IQatage38–IQatage13)
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

9. Silins, et al., Lancet Psychiatry 2014;1:286-293
HS Complete
Never
< Monthly
Monthly +
Weekly +
Daily
0
0.2
0.4
0.6
0.8
1
1.2
HS Complete
O.R.
0
5
10
15
20
Cannabis
Depend
O.R.
0
2
4
6
8
10
Other Illicit
Drug
O.R.
0
1
2
3
4
5
6
7
8
Suicide Attempt
O.R.
MoreTeenage Use of Cannabis Associated with
Worse Outcomes in 20’s (3 Australia/New Zealand Studies)

10. 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

11. 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)

12. Subcortical structures evaluated for group differences
between daily marijuana users and nonusers.
Weiland B J et al. J. Neurosci. 2015;35:1505-1512

13. 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

14. Adolescent Brain Cognitive Development
National 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

15. 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, HIV
NIH research (across NIDA, NCI, NINDS, NIAID, etc.)
focuses on THC, CBD, and compounds that alter the
function of the endocannabinoid system.