MARIJUANAS Effects on Brain, Body & Behavior Nora D. Volkow, - - PowerPoint PPT Presentation

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

% of Basal Release

100 200 300 400 500 600 700 800 900 1000 1100 1 2 3 4 5 hr

AMPHETAMINE

% of Basal Release 50 100 150 200 60 120 180

Time (min)

% of Basal Release 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 11 8 5 23 5 10 15 20 25 30 35 Percent

* 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

Percentage in each age group who develop first-time dependence 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

Percent

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

Odds Ratio

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

10 20 30 40 50 60 70

Percent

Marijuana Dependence General Population

Adolescent Cannabis Use Increases the Risk for Adult Psychosis in Genetically Vulnerable Individuals

2 4 6 8 10 12 14 16 18 20 Met/Met Val/Met Val/Val % with schizophreniform disorder at age 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

1 2 3 4 5 6 7 8 9 10 Percent THC

Emergency Department Visits Involving Selected Drugs: 2008

Source: SAMHSA, 2008 DAWN.

Increased Marijuana Treatment Admissions 1993 and 2007

10 20 30 40 50 60 Alcohol Cocaine Heroin Marijuana Percent of Admissions 1993 2007

Source: SAMHSA, TEDS 1993 & 2007

Percentage of U.S. 12th Grade Students Reporting Past Month Use of Cigarettes &Marijuana,

1975 to 2009

10 20 30 40

Percent 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

10 20 30 40 50 60 75 78 81 84 87 90 93 96 99 02 05 08 Percent 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

• f Regular Cannabis Use

Total Words Recalled (Trials I-V) Total Words Recalled (Trials I-V) Total Words Recalled (Trials I-V) Total Words Recalled (Trials 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 Cerebellum/Whole Brain

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 Mean Number of Symptoms 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

1 2 3 4 5 6 Marijuana Use Inhalant Use 2.8 3.6 4.8 5.8 Percent 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 Ratings (mm) **

Sleep Latency (objective) Fell Asleep Easily (subjective)

100 75 50 25 Min ** * Placebo THC Lofexidine THC/Lofex Marijuana Relapse: Money Spent on Self-Administration

25 20 15 10 5

Dollars (USD) **

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