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

MARIJUANA’S Effects on Brain, Body & Behavior Nora D. Volkow, M.D. Director National Institute on Drug Abuse National Institutes of Health

Marijuana is the Most Commonly Used Illicit Drug In the U.S. • Over 104 million Americans have tried it at least once • An estimated 2.4 million Americans used it for the first time in 2009 Tetrahydrocannabinol (THC) Active Ingredient in Marijuana National Survey on Drug Use and Health, SAMHSA, 2010.

Use of Specific Illicit Drugs in Lifetime Among Persons 12 or Older, 2009 ` 104,446 35,046 36,599 21,755 37,256 21,930 3,683 22,448 8,605 Thousands Source: 2009 NSDUH, SAMHSA, 2010.

1100 Natural and Drug Reinforcers 1000 AMPHETAMINE % of Basal Release 900 Increase Dopamine in NAc 800 700 600 500 400 300 200 100 frontal 0 cortex 0 1 2 3 4 5 hr 150 MARIJUANA % of Basal Release 125 nucleus accumbens VTA/SN 100 0 20 40 60 80 Tanda, et al, Science 1997. 200 % of Basal Release FOOD 150 100 Empty Drugs of abuse increase DA in the Nucleus 50 Box Feeding Accumbens, which is believed to trigger the 0 0 60 120 180 neuroadaptions that result in addiction Time (min) Di Chiara et al.

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 Estimated Prevalence of Dependence Among Users 35 32 30 23 25 Percent 20 17 15 15 11 9 8 10 5 5 0 * * * Nonmedical Use Source: Anthony JC et al., 1994

Cannabinoids in Brain Cannabinoid Receptors Plasma membrane AC CB1 G i a g CB2 b O N OH H Endogenous Cannabinoid Ligands Anandamide Anandamide 2-Arachidonoylglycerol O OH O OH 2-Arachidonoylglycerol (2-AG)

Cannabinoid Receptors in Human Brain Van Loere et al., 2007.

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 Percentage in each age group who develop first-time dependence 1.8% TOBACCO THC 1.6% ALCOHOL 1.4% 1.2% 1.0% 0.8% 0.6% 0.4% 0.2% 0.0% 5 10 15 21 25 30 35 40 45 50 55 60 65 Age Age at tobacco, at alcohol and at cannabis use dependence as per DSM IV NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003.

Subjective Ratings Percent Graduated Household Satisfaction General College Income with Self Happiness < $30,000 & Life Level Source: Gruber, AJ et al., Psychological Medicine, 33, pp. 1415-1422, 2003.

Drug Use Outcomes in Twin Pairs (n =234) Discordant for Cannabis Use Before Age 17 Odds Ratio Source: Lynskey, MT et al., JAMA, 289, pp. 427-433, 2003.

Brain abnormalities Hippocampus Amygdala associated with long-term heavy cannabis use Tracings of left (yellow) and right (blue) amygdalae and left Hippocampal (A) and amygdalar (B) (red) and right (green) volumes were smaller in cannabis users hippocampI. than in non using control subjects. 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) 70 61 Marijuana Dependence General Population 60 49 47 50 Percent 40 27 30 24 21 21 20 20 17 20 16 14 10 9 9 10 5 4 4 4 3 2 1 0

Adolescent Cannabis Use Increases the Risk for Adult Psychosis in Genetically Vulnerable Individuals 20 % with schizophreniform no adolescent cannabis use 18 adolescent cannabis use 16 disorder at age 26 14 12 10 8 6 4 2 0 Met/Met Val/Met Val/Val COMT Genotype 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 Cerebellar activity is impaired during intoxication Volkow, N.D. et al., Psychiatry Research: Neuroimaging, 67, pp. 29-38, 1996.

Potency: Increased THC Content in Seized Marijuana, 1983-2009 10 9 8 7 Percent THC 6 5 4 3 2 1 0 Sources: The University of Mississippi Potency Monitoring Project

Emergency Department Visits Involving Selected Drugs: 2008 Source: SAMHSA, 2008 DAWN.

Increased Marijuana Treatment Admissions 1993 and 2007 60 1993 2007 Percent of Admissions 50 40 30 20 10 0 Alcohol Cocaine Heroin Marijuana Source: SAMHSA, TEDS 1993 & 2007

Percentage of U.S. 12th Grade Students Reporting Past Month Use of Cigarettes &Marijuana, 1975 to 2009 40 30 Cigarettes Percent 20 Marijuana 10 0 Source: The Monitoring the Future study, the University of Michigan

Changes in Attitude Lead to Changes in Use Marijuana Use and Perceived Risk among 12 th Graders, 1975 to 2009 Past Year Use Perceived Risk 60 50 40 Percent 30 20 10 0 75 78 81 84 87 90 93 96 99 02 05 08 Source: The Monitoring the Future study, the University of Michigan

For More Info Visit NIDA’s Website @ www.drugabuse.gov

Relationships Between Total Words Recalled and Quantity, Frequency, Duration and Age of Onset of Regular Cannabis Use Total Words Recalled (Trials I-V) Total Words Recalled (Trials I-V) Frequency of Cannabis Use (days/month) Quantity of Cannabis Use (cones/month) Total Words Recalled (Trials I-V) Total Words Recalled (Trials I-V) Duration of Regular Cannabis Use (years) Age of Onset of Regular Cannabis Use Source: Solowij N et al. Psychopharmacology (Berl.) 2011 Feb 17 [Epub ahead of print].

Brain Glucose Metabolism in Controls and Marijuana Abusers Control 1.2 p < 0.01 Cerebellum/Whole Brain 1.15 1.1 1.05 Marihuana Abuser 1 0.95 0.9 0.85 0.8 Control Abuser Cerebellar metabolism is decreased in Marijuana Abusers Volkow, N.D. et al., Psychiatry Research: Neuroimaging, 67, pp. 29-38, 1996.

Depression Symptoms at Age 10 by Trimester of Prenatal Marijuana Exposure 50 p<.01 p=ns p <.05 49 48 Mean Number of Symptoms 47 46 45 44 First Second Third Abstainer Light Moderate Heavy Gray et al., 2005.

Prosper Multisite Community Study: Less MJ & Inhalants 1.5 Yrs Past Baseline Past Year Use Intervention Control 6 5.8 5 4.8 Percent 4 3.6 3 2.8 2 1 0 Marijuana Use Inhalant Use 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 Sleep Latency Marijuana Craving 100 (objective) 100 Ratings (mm) 75 * ** 75 Min 50 50 25 ** 25 0 0 Fell Asleep Easily Capsule Strength (subjective) Marijuana Relapse: Money Spent on Self-Administration 25 Dollars (USD) 20 15 ** 10 5 0 Placebo THC Lofexidine THC/Lofex Source: Haney, M et al., Psychopharmacology, 197, pp. 157-168, 2008.

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 in Gray Matter Density Between Adolescence and Young Adulthood Differences between: 16 year olds (adolescents) and 23-30 year olds (young adults) Frontal Lobe Subcortical Region Subcortical Frontal Parietal Occipital Temporal Source: Sowell, E.R. et al., Nature Neuroscience, 2(10), pp. 859-861, 1999