brain weight by age - aacpdm - american academy for ... · receptor binding in brain tissue ... •...
TRANSCRIPT
Cannabinoid Biology and
Marijuana Policy Sharon Levy, MD, MPH
Assistant Professor of Pediatrics Boston Children’s Hospital
Harvard Medical School
Director, Adolescent Substance Abuse Program Division of Developmental Behavioral Pediatrics
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MMaarriijjuuaannaa PPoolliicy
Brain Weight by Age
Source: Dekaban, A.S. and Sadowsky, D. Annals of Neurology, 4:345-356, 1978
New
born
FemalesMales
Age
Adult size
Source: Gogtay et al. PNAS. 2004:101(21):8174-8179.
motivationemotion
CerebellumAmygdala
Nucleus Accumbens
Prefrontal cortex
Planning, Organizing, Impulse control Physical
coordination,Sensory processing
Slide adapted from Ken Winters, PhD.
Toddler milestones:
balance, walking,
coordinationPreschool milestones:
emotional regulationSchool age
milestones:
achievement
Adolescent
milestones: impulse
control
Casey BJ, et al., Development Reviews. 2008; 28: 62-77.
Nucleus Accumbens
Prefrontal
Cortex
Adult Adolescent
Fu
nct
ion
al
De
velo
pm
en
t
Age
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
Children ages 7-11 Teens ages 13-17 Adults ages 23-29
“Taken together, we found no significant
substitution effect between alcohol and
marijuana. Rather, an uptick in availability
seems to increase the prevalence of
concurrent use of alcohol and marijuana.”
-Guohua Li, MD, PhD
Mailman School professor of Epidemiology
Article accessed at: http://www.mailman.columbia.edu/news/half-young-victims-fatal-crashes-nine-us-states-used-either-alcohol-or-marijuana
In reference to: Keyes KM, Brady JE, Li G. Effects of minimum legal drinking age on alcohol and marijuana use: evidence from toxicological
testing data for fatally injured drivers aged 16 to 25 years. Inj Epidemiol. 2015;2(1):1.
Delta-9-
tetrahydrocannabinol Anandamide
Cannabinoid Binding Sites
Source: NIDA
FrontBack
In 1988 researchers Allyn Howlett and William Devane
discovered cannabinoid receptors in the brain and called them
cannabinoid 1 receptors (CB1) (Devane et al., 1988). In 1992
researchers discovered an endogenous cannabinoid and called
it anandamide (Devane et al., 1992).
17
Source: Kraft, U. Scientific American Mind, 2006, p. 62-65
The neuron’s “volume control”: dials
down neuron activity when too strong
Source: Kraft, U. Scientific
Receptor binding in brain tissue
Compound Potency relative to THC
(-)-Delta9-THC 1
Anandamide .47*
*The affinity of anandamide for cannabinoid receptors ranges from about one-fourth to
one-half that of THC . The differences depend on the cells or tissue that are tested and on
the experimental conditions, such as the binding assay used.
Joy J, Watson SJ, Benson JJ, eds. Cannabinoids and animal physiology. In: Marijuana and Medicine: Assessing the Science Base. Washington DC:
Division of Neuroscience and Behavioral Health - Institute of Medicine. National Academies Press; 1999:288
Source: Iversen L. How cannabis works in the brain. In Marijuana and Madness. Ed. Castle & Murray, 2004.
Oxford University Press.
Source: Meier et al. Proceedings of the National Academy of Sciences. 2012. Available at:
www.pnas.org/cgi/doi/10.1073/pnas.1206820109
The Dunedin Study
N=1,037
1 2 3 4 5
Assessment ages
13 yrs(Pre-initiation)
18 yrs 21 yrs 32 yrs 38 yrs
Source: Meier et al. PNAS, 2012
The Dunedin Study
N=1,037
1 2 3 4 5
Assessment ages
13 yrs(Pre-initiation)
18 yrs 21 yrs 32 yrs 38 yrs
Source: Meier et al. PNAS, 2012
Never used
Mj dependent 2 yrs
Mj dependent 1 yr
Used, never diagnosed
Mj dependent 3+ yrs
Average IQ change:
•“Never used”
• 99.8 to 100.6
•“Mj dependent 3+ yrs”
• 99.7 to 93.9
Source: Meier et al. PNAS, 2012
Source: Arnone D, Barrick TR, Chengappa S et al. Corpus callosum damage in heavy marijuana use: Preliminary evidence
from diffusion tensor tractography and tract-based spatial statistics. NeuroImage, 2008; 41:1067-1074
Healthy non user Daily MJ user Schizophrenic patient
A meta-analysis of 6 studies found an increased risk of psychotic
outcome among those who used cannabis most frequently, compared
with non-users. (Adjusted odds ratio: 2.09, 95% CI: 1.54-2.84) Moore THM, Zammit S, Lingford-Hughes A, et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic
review. Lancet. 2007;370(9584):319–28. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17662880.
Marijuana Use and Psychotic Disorders
* Adjustments for: prior personality disorders at conscription, IQ, disturbed behavior in childhood, social adjustment, risky use of alcohol, smoking, early adulthood socioeconomic position, use of other drugs, brought up in a city. The category “Ever used cannabis” includes all individuals who reported cannabis use, including those who reported “>50 times”.
Griffith-Lendering, Addiction, 108(4), 733-740.
Manrique-GarciaBMC Psychiatry, 12, 112.
# Exposure # Cases HR Crude HR adjusted*
Never used
cannabis 39, 978 47 1 1
Ever used
cannabis 5,109 12 2.1 (1.1-3.8) 0.8 (.2-2.9)
>50 times 855 7 7.5 (3.4- 16.7) 7.4 (1.0 – 54.3)
Association between cannabis use and
schizoaffective disorder
Kuepper R, van Os J, Lieb R, Wittchen H-U, Höfler M, Henquet C. Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-
up cohort study. BMJ. 2011;342(mar01_1):d738. Available at: http://www.bmj.com/content/342/bmj.d738. Accessed May 8, 2015.
Conclusion: Cannabis use is a risk factor for the
development of incident psychotic symptoms. Continued
cannabis use might increase the risk for psychotic disorder
by impacting on the persistence of symptoms.
The evidence is consistent with the view that cannabis
increases risk of psychotic outcomes independently of
confounding and transient intoxication effects ....
Marijuana Policy
“Medical Marijuana” v. Cannabinoids
IOM poses
“compassionate” use
to relieve suffering in
terminally ill patients.
CA passes “medical
marijuana ballot
initiative
1990
1996
History of “Medical Marijuana”
CNN documentary
supporting “medical
marijuana”
2013
20 states and DC have
“medical marijuana
laws”
2014
Limited evidence of therapeutic efficacy of
medical marijuana
Condition Level of Evidence
Chemotherapy induced Nausea and
Vomiting in Adults Modest evidence1
Chronic Pain Insufficient evidence2
HIV/Aids and Anorexia associated with Aids Insufficient evidence3
Neurological Problems Insufficient evidence4
1. Borgelt LM, Franson KL, Nussbaum AM, Wang GS. The pharmacologic and clinical effects of medical cannabis. Pharmacotherapy. 2013;33(2):195–209..
2. Martín-Sánchez E, Furukawa TA, Taylor J, Martin JLR. Systematic review and meta-analysis of cannabis treatment for chronic pain.
3. Lutge EE, Gray A, Siegfried N. The medical use of cannabis for reducing morbidity and mortality in patients with HIV/AIDS. Cochrane database Syst. Rev..
4. Koppel BS, Brust JCM, Fife T, et al. Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders: report of the Guideline Development
Subcommittee of the American Academy of Neurology. Neurology. 2014;82(17):1556–63.
*Not one single study has ever included children
Effects of State Medical Marijuana
Laws on Health Outcomes Relevant
for Youth
From Dr. Rosalie Pacula. “Effect of Medical Marijuana on the Health of the Young” at
Pediatric Academic Societies on April 28th, 2015
Any MML Law Source
Prevalence of youth MJ use NS Pacula,
2015
Effects of State Laws on Health
Outcomes Relevant for Youth
From Dr. Rosalie Pacula. “Effect of Medical Marijuana on the Health of the Young” at
Pediatric Academic Societies on April 28th, 2015
Any MML
Law
Legal
Dispensaries Source
Prevalence of youth
MJ use NS NS
Pacula,
2015
Youth Treatment
Admissions for MJ
disorders
Decreased Increased Pacula,
2015
Effects of State Laws on Health
Outcomes Relevant for Youth
From Dr. Rosalie Pacula. “Effect of Medical Marijuana on the Health of the Young” at
Pediatric Academic Societies on April 28th, 2015
Any MML
Law
Legal
Dispensaries Source
Alcohol Treatment
Admissions Decreased Increased
Pacula, 2013
Heaton, 2015
Youth Alcohol
Involved Fatality Decreased Increased
Pacula, 2013
Sevigny, 2015
Youth Opioid
Treatment
Admissions
NS NS Powell, 2015
The problem with R&D
• mid 19th century: <1% of tobacco
consumed as smoked cigarettes
Kluger, Richard. (1996). Ashes to Ashes. New York: Knopf; Ford, Barry. (1994). Smokescreen. Perth, Australia: Halcyon
• 1880: Flue curing made tobacco inhalable
• Bonsack Machine could produce 70,000 cigs/day
• American Tobacco Co. created monopoly
• 1900: 1 out of 3 tobacco users smoked cigs
• 1947: 45% American adults smoked
• 1950: asbestos filter and ammonia free-base
introduced
• 1957: First Surgeon General Report
Source: Malone DT et al. Adolescent cannabis use and psychosis: epidemiology and neurodevelopmental models. Brit J
Pharmacol. 2010;160:511-522
0%
2%
4%
6%
8%
10%
199419951996199719981999200020012002200320042005200620072008
1
9
9
4
2
0
0
8
Year
<4%
9%
Content of THC in marijuana has
increased over time
Effects of State Laws on Health
Outcomes Relevant for Youth
From Dr. Rosalie Pacula. “Effect of Medical Marijuana on the Health of the Young” at
Pediatric Academic Societies on April 28th, 2015
Any MML
Law
Legal
Dispensaries Source
Potency of marijuana
(%THC) NS Increased
Sevigny,
2014
Serving size: 1/4 cookie
• Pure cannabis oils (100%) THC are now available.
• “Because they're so potent, you don't need a large
amount to get high.”
– The Wire, May 15, 2013
• “Reduces exposure to other
toxins.”
Research on high potency THC
• Increases risk of psychosis Br J Psychiatry. 2009 Dec;195(6):488-91
• Decreases age of onset psychosis Schizophr Bull. 2014 Nov;40(6):1509-17.
• Impairs “creative thinking” Psychopharmacology (Berl). 2014 Oct 7.
Exclusive: “Skinnygirl Marijuana”, a Strain of Pot
That Won’t Cause the Munchies!
Skinnygirl cocktails creator:
“She read about how profitable the cannabis
industry is and wants to get in on that.”
-US Magazine online
Sk
“
in
3. The AAP opposes legalization marijuana … and
supports studying the effects of recent laws to
better understand the impact and define best
policies to, reduce adolescent marijuana use.
0500
1,0001,5002,0002,5003,0003,5004,0004,5005,000
Suspensions
Expulsions
http://www.cde.state.co.us/cdereval/suspend-expelcurrent
Drug-related School Suspensions and
Expulsions in Colorado, 2004-2014
Summary
• Marijuana use during adolescence is associated with increased mental health disorders and cognitive decline.
• There is enough evidence to suggest some of these relationships are causal.
• New products are driving up THC exposure for users.
• Surveillance infrastructure may be insufficient as harms are not typically medical.