Download The Brain and Marijuana - Boston Children`s Hospital

Marijuana:
Emerging Answers to
Frequently Asked Questions
Sion Kim Harris, PhD
Center for Adolescent Substance
Abuse Research
Children’s Hospital Boston
Harvard Medical School
Is marijuana addictive?
Number of People Aged 12+ Receiving
Drug Abuse Treatment in Past Year (2009)
1243
Marijuana
787
Cocaine
Pain meds
739
Stimulants
517
Heroin
507
443
Hallucinogens
Tranquilizers
421
0
250
500
750
1000
1250
1500
Numbers in Thousands
Source: Substance Abuse and Mental Health Services Administration. (2010). Results from the 2009 National Survey on Drug Use and Health: Volume I.
Summary of National Findings (Office of Applied Studies, NSDUH Series H-38A, HHS Publication No. SMA 10-4586Findings). Rockville, MD.
Marijuana is especially addictive
for teens …
• More 15 to 17-year-olds are in
treatment for a primary diagnosis of
marijuana dependence than for all
other illegal drugs combined.
Source: Data from the Treatment Episodes Data Set (TEDS), SAMHSA, 2008
Risk of Marijuana Abuse or
Dependence by Age of First Use
% with MJ Disorder
20
15
17
16
10
11
8
5
4
0
13
15
17
19
Age at First Use
21+
Source: Substance Abuse and Mental Health Services Administration. (2010). Results from the 2009 National Survey on Drug Use and Health: Volume I.
Summary of National Findings (Office of Applied Studies, NSDUH Series H-38A, HHS Publication No. SMA 10-4586Findings). Rockville, MD.
Risk of Alcoholism by
Age of First Drink
% with Alcohol Disorder
60
50
40
47
45
38
30
32
28
20
15
10
17
11
9
20
>=21
0
<=13
14
15
16
17
18
19
Age at First Drink
Source: Hingson RW, Heeren T, Winter MR. Age at drinking onset and alcohol dependence. Arch Pediatr Adolesc Med. 2006;160:739-746.
Why is the teen brain more
susceptible to addiction?
The Reward Circuit
Expectation of reward
Source: NIDA
Ventral-Tegmental
Area
marijuana
Source: NIDA
Marijuana is no exception…
Source: French ED, Dillon K, Wu X. Cannabinoids excite dopamine neurons in the ventral tegmentum and substantia
nigra. NeuroReport 8, 649–652 (1997)
Brain areas with greatest differences
between adolescent and adult brains
Front
Back
Source: Sowell ER, Thompson PM, Holmes CJ, Jernigan TL, Toga AW. In vivo evidence for post-adolescent brain
maturation in frontal and striatal regions. Nature Neuroscience. 1999;2:859 – 861. Used with permission.
The nucleus accumbens (NAcc)
in teen brains behaves
differently from adult brains…
Functional brain imaging (fMRI) study of
NAcc activation in children, teens, adults
Children ages 7-11
Small Reward
Teens ages 13-17
Adults ages 23-29
Large Reward
Source: Galvan A, Hare AT, Parra, CE, Penn J, Voss H, Glover G, Casey BJ, Earlier Development of the Accumbens Relative to
Orbitofrontal Cortex Might Underlie Risk-Taking Behavior in Adolescents. Journal of Neuroscience, 2006,26(25):6885–6892
The prefrontal cortex (the “brakes”)
develops more slowly…
Adolescence
Adult
(about age 25)
Source: Casey BJ, et al., Development Reviews. 2008; 28(1): 62-77
Source: Casey BJ, Getz S, Galvan A. The adolescent brain. Dev Rev. 2008;28(1):62-77. Used with permission.
And…
NAcc-PFC
connectivity is
not fully mature
in the teen brain
Key Point #1
Teen brains have higher risk for
addiction than adults when exposed to
HIGHLY REWARDING stimuli due to…
 greater reward sensitivity
 incomplete networking of the
brain
 faster learning (neuroplasticity)
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Risk for addiction is much higher when…





Family history of any addiction
Chronic stress
Emotional trauma
Chronic sleep deprivation
Etc.
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What other effects does
marijuana have on the
teen brain?
What is in Marijuana?
• Contains MANY chemicals including
– Delta-9-tetrahydrocannabinol
– Delta-8-tetrahydrocannabinol
– Cannabidiol
– Cannabinol
– Cannabichromene
– Cannabigerol
– Etc.
21 In
Source: Mechoulam R, Hanus L, The cannabinoid system from the point of view of a chemist.
Marijuana and Madness. ed. Castle, Murray. Cambridge University Press, 2004
What is in Marijuana?
• The main psychoactive chemical is
delta-9-tetrahydrocannabinol or
“THC”
• Marijuana’s potency and effects
depend on how much THC it
contains
22 In
Source: Mechoulam R, Hanus L, The cannabinoid system from the point of view of a chemist.
Marijuana and Madness. ed. Castle, Murray. Cambridge University Press, 2004
Has there been a change in
THC content in marijuana
over time?
Avg. % THC Content among Confiscated
Cannabis Products in U.S. (1993-2008)*
*Source: Mehmedic Z, et al., Journal of Forensic Science, 2010;55(5):1209-1217
* 46,211 samples
What else has been found in
marijuana?
Marijuana Contaminants
• Several studies show
fungi, mold, and
bacterial contamination
in most samples tested
• Evidence of Aspergillus
fungi exposure in most
marijuana smokers
tested compared to
1/10 non-smokers
Source: McLaren et al., Cannabis
potency and contamination: a review.
Addiction. 2006;103:1100-1109.
Marijuana Contaminants
• Aspergillus can produce mycotoxins
(carcinogenic) and cause lung infections
– could be fatal in people with
immune system problems
• Unlike tobacco, pesticide use is
unregulated for marijuana, and little
research done to date on amount in
marijuana
Tobacco vs. Marijuana Smoke
Tobacco vs. Marijuana Smoke
• Of the 74 chemicals and metals tested in
tobacco and marijuana smoke under
rigorously matched conditions…
– Marijuana smoke contained most of the
same carcinogenic chemicals as tobacco
smoke
– Amount of tar generated was the same
The Brain and Marijuana
30
Cannabinoid receptors in our brains?
Why?
• Endogenous cannabinoid
chemical called
Anandamide
• Important for modulating
release of many different
neurotransmitters
• Inhibitory effect
Source: Wilson RI, Nicoll RA. Endocannabinoid signaling in the brain. Science. 2002;296:678-682.
31
The Brain’s
Endocannabinoid
System
A brief primer on how neurons work…
After …
34
36
Source: Kraft, U. Scientific American Mind, 2006, p. 62-65
Endocannabinoid System Functions
• Cannabinoid receptors located on
neurons throughout brain
• Regulates levels of the brain’s major
inhibitory and excitatory
neurotransmitters (GABA and glutamate)
• Helps protect neurons from overactivity
that could lead to cell damage or death
Endocannabinoid System Part 2
• Shapes brain development by…
– guiding correct growth and positioning
of inhibitory and excitatory neurons
– controlling synaptic activity, thereby
shaping synaptic refinement, brain
connectivity and efficiency
– And more…
Source: Galve-Roperh I, Palazuelos J, Aguado T, Guzman M. Eur Arch Psychiatry Clin Neurosci. 2009;259:371-382.
Fooling the brain…
Source: NIDA
39
THC Binding Sites
Source: NIDA
40
What’s affected by THC?
Source: NIDA
41
Hippocampus
42
THC and Memory
• Cannabinoids inhibit glutamate release in
hippocampus, below the level needed to
trigger memory formation
• Anandamide exerts subtle, specific
inhibition (may play role in extinction of
fearful memories)
• THC causes widespread, prolonged
inhibition
Source: Iversen L. How cannabis works in the brain. In Marijuana and Madness. Ed. Castle & Murray, 2004.
Oxford University Press.
Teen Working Memory Performance
Source: Jacobsen et al. Impact of cannabis use on brain function in adolescents. Annals NY Acad
Sci. 2004.
44
THC effects after chronic use
• Suppresses cannabinoid receptor
function; reduces number of receptors
and decreases sensitivity to
anandamide, so it can’t do it’s job
• Causes too much excitation of
neurons, leading to “Excitotoxicity”
and cell damage/death
Source: Bossong MG, Niesink RJM. Adolescent brain maturation, the endogenous cannabinoid system and the neurobiology
of cannabis-induced schizophrenia. Progress in Neurobiology. 2010;92:370-385.
The brain seeks balance…
THC
Inhibition
Excitation
Source: Valenzuela CF, Alcohol and neurotransmitter actions. Alcohol Health & Research World, 1997; 21(2), 144-148.
More THC effects
• Hippocampal synaptic connections are
gradually lost due to continual
inhibition/suppression
• Dopamine receptors are damaged or lost
leading to “Reward deficiency”
Source: Bossong MG, Niesink RJM. Adolescent brain maturation, the endogenous cannabinoid system and the neurobiology
of cannabis-induced schizophrenia. Progress in Neurobiology. 2010;92:370-385.
NIDA
Key Point #2
The endocannabinoid system is
important in brain development…
 THC interferes with its proper
functioning
 Teen brain development is shaped by
experience
 Repeated THC exposure will change
brain development
49
Marijuana and Mental Illness
MANY longitudinal studies have found that
regular marijuana users, especially those
starting as teens, have higher rates of
paranoia, anxiety, depression, psychotic
symptoms, and schizophrenia as adults
Source: Malone DT et al. Adolescent cannabis use and psychosis: epidemiology and neurodevelopmental models. Brit J
Pharmacol. 2010;160:511-522
51
Similar altered white matter structure
found in the brains of schizophrenics
and teen marijuana users
Bava S, Frank LR, McQueeny T, Schweinsburg BC, Schweinsburg AD, Tapert SF. Altered white matter microstructure in adolescent substance users. Psychiatry Research
52
Neuroimaging. 2009;173:228-237.
Avg. % THC Content among Confiscated
Cannabis Products in U.S. (1993-2008)*
*Source: Mehmedic Z, et al., Journal of Forensic Science, 2010;55(5):1209-1217
* 46,211 samples
Avg. % THC Content among Confiscated
Cannabis Products in U.S. (1993-2008)*
% Cannabidiol
*Source: Mehmedic Z, et al., Journal of Forensic Science, 2010;55(5):1209-1217
* 46,211 samples
What else is affected by THC?
55
Fertility and Hormones
• Marijuana affects network
of glands, organs and
hormones involved in
growth, development and
energy levels
• Lowers fertility of males
and females through
lowered sperm count and
egg damage
Source: Wenger T, Croix D, Tramu G. The effect of chronic prepubertal
administration of marijuana (delta-9-tetrahydrocannabinol) on the
onset of puberty and the post-pubertal reproductive functions in
female rats. Biology of Reproduction. 1988;39:540-545.
And finally….
Does marijuana affect driving?
Marijuana and Driving
Studies of
performance show
that THC changes
attention, working
memory,
coordination,
reaction time, and
visual perception
58
Source: Becker et al., 2010; Medina et al., 2007; Jacobsen et al., 2004.
Marijuana and Traffic Fatalities
Percent of Fatally-Injured Drivers
Tested who were Drug-Positive
In 2009, among
drug-positive
traffic deaths,
marijuana was
most common
drug found,
accounting for
over 1 in 4 (28%)
Adapted by CESAR from National Highway Traffic Safety Administration (NHTSA), “Drug Involvement of Fatally Injured
Drivers,” Traffic Safety Facts, November 2010. Available online at http://www-nrd.nhtsa.dot.gov/Pubs/811415.pdf.
Any other questions?
Any Questions?
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