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 National Survey on Drug Use and Health, SAMHSA, 2010. Tetrahydrocannabinol (THC) Active Ingredient in Marijuana
Use of Specific Illicit Drugs in Lifetime Among Persons 12 or Older, 2009 ` 35,046 36,599 21,755 37,256 21,930 3,683 22,448 8,605 104,446 Thousands Source: 2009 NSDUH, SAMHSA, 2010.
% of Basal Release % of Basal Release % of Basal Release Natural and Drug Reinforcers Increase Dopamine in NAc frontal cortex 1100 1000 900 800 700 600 500 400 300 200 100 0 150 AMPHETAMINE 0 1 2 3 4 5 hr MARIJUANA nucleus accumbens VTA/SN 125 100 0 20 40 60 80 200 150 Tanda, et al, Science 1997. FOOD Drugs of abuse increase DA in the Nucleus Accumbens, which is believed to trigger the neuroadaptions that result in addiction 100 50 0 Empty Box Feeding 0 60 120 180 Time (min) Di Chiara et al.
Percent 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 30 25 20 15 10 5 0 32 15 9 17 11 8 5 23 * * * Nonmedical Use Source: Anthony JC et al., 1994
Cannabinoids in Brain Plasma membrane G ia b g AC Cannabinoid Receptors CB1 CB2 O Anandamide O N H O OH OH OH Endogenous Cannabinoid Ligands Anandamide 2-Arachidonoylglycerol 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% 1.6% 1.4% 1.2% 1.0% 0.8% 0.6% 0.4% 0.2% TOBACCO THC ALCOHOL 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.
Percent Subjective Ratings Graduated College Household Income < $30,000 Satisfaction General with Self Happiness & Life Level Source: Gruber, AJ et al., Psychological Medicine, 33, pp. 1415-1422, 2003.
Odds Ratio Drug Use Outcomes in Twin Pairs (n =234) Discordant for Cannabis Use Before Age 17 Source: Lynskey, MT et al., JAMA, 289, pp. 427-433, 2003.
Brain abnormalities associated with long-term heavy cannabis use Hippocampus Amygdala 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. Jucel et al., Arch Gen Psychiatry. 2008 Jun;65(6):694-701.
Percent High Rates of Comorbid Mood & Anxiety Disorders Among Respondents with Marijuana Dependence (NESARC) 70 60 50 40 30 20 10 0 61 20 Marijuana Dependence General Population 49 47 24 20 16 17 14 10 9 4 3 2 1 27 21 4 5 9 21 4
Adolescent Cannabis Use Increases the Risk for Adult Psychosis in Genetically Vulnerable Individuals % with schizophreniform disorder at age 26 20 18 16 14 12 10 8 6 4 2 0 no adolescent cannabis use adolescent cannabis use 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.
Percent THC Potency: Increased THC Content in Seized Marijuana, 1983-2009 10 9 8 7 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.
Percent of Admissions Increased Marijuana Treatment Admissions 1993 and 2007 60 50 1993 2007 40 30 20 10 0 Alcohol Cocaine Heroin Marijuana Source: SAMHSA, TEDS 1993 & 2007
Percent Percentage of U.S. 12th Grade Students Reporting Past Month Use of Cigarettes &Marijuana, 1975 to 2009 40 30 20 10 Cigarettes Marijuana 0 Source: The Monitoring the Future study, the University of Michigan
Percent Changes in Attitude Lead to Changes in Use Marijuana Use and Perceived Risk among 12 th Graders, 1975 to 2009 60 50 Past Year Use Perceived Risk 40 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
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Total Words Recalled (Trials I-V) Total Words Recalled (Trials I-V) 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) 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 Source: Solowij N et al. Psychopharmacology (Berl.) 2011 Feb 17 [Epub ahead of print].
Cerebellum/Whole Brain Brain Glucose Metabolism in Controls and Marijuana Abusers Control Marihuana Abuser 1.2 1.15 1.1 1.05 1 0.95 0.9 0.85 p < 0.01 0.8 Control Abuser Cerebellar metabolism is decreased in Marijuana Abusers Volkow, N.D. et al., Psychiatry Research: Neuroimaging, 67, pp. 29-38, 1996.
Mean Number of Symptoms Depression Symptoms at Age 10 by Trimester of Prenatal Marijuana Exposure 50 49 p<.01 p=ns p <.05 48 47 46 45 44 First Second Third Abstainer Light Moderate Heavy Gray et al., 2005.
Percent Prosper Multisite Community Study: Less MJ & Inhalants 1.5 Yrs Past Baseline Past Year Use Intervention Control 6 5 4 3 2 2.8 4.8 3.6 5.8 1 0 Marijuana Use Inhalant Use Spoth, Redmond, Shin, Greenberg, Clair, Feinberg (2007). Am J Prev Med, 32(5), 395-402.
Dollars (USD) Ratings (mm) Min Effects of THC and Lofexidine in a Human Laboratory Model of Marijuana Withdrawal and Relapse 100 75 50 25 0 Marijuana Craving Capsule Strength 25 ** 100 75 50 25 Marijuana Relapse: Money Spent on Self-Administration 0 Sleep Latency (objective) * Fell Asleep Easily (subjective) ** 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 Source: Sowell, E.R. et al., Nature Neuroscience, 2(10), pp. 859-861, 1999 Subcortical Region Subcortical Frontal Parietal Occipital Temporal