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

Transcription

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

2 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, Tetrahydrocannabinol (THC) Active Ingredient in Marijuana

3 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, ,446 Thousands Source: 2009 NSDUH, SAMHSA, 2010.

4 % of Basal Release % of Basal Release % of Basal Release Natural and Drug Reinforcers Increase Dopamine in NAc frontal cortex AMPHETAMINE hr MARIJUANA nucleus accumbens VTA/SN Tanda, et al, Science FOOD Drugs of abuse increase DA in the Nucleus Accumbens, which is believed to trigger the neuroadaptions that result in addiction Empty Box Feeding Time (min) Di Chiara et al.

5 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 * * * Nonmedical Use Source: Anthony JC et al., 1994

6 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)

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

8 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

9 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% 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.

10 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 , 2003.

11 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 , 2003.

12 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 Jun;65(6):

13 Percent High Rates of Comorbid Mood & Anxiety Disorders Among Respondents with Marijuana Dependence (NESARC) Marijuana Dependence General Population

14 Adolescent Cannabis Use Increases the Risk for Adult Psychosis in Genetically Vulnerable Individuals % with schizophreniform disorder at age no adolescent cannabis use adolescent cannabis use Met/Met Val/Met Val/Val COMT Genotype Source: Caspi, A. et al., Biol. Psychiatry, 57: ; Source: Caspi, A. et al. Biol. Psychiatry, 57: ; 2005.

15 Changes in Brain Glucose Metabolism During Marijuana Intoxication Cerebellar activity is impaired during intoxication Volkow, N.D. et al., Psychiatry Research: Neuroimaging, 67, pp , 1996.

16 Percent THC Potency: Increased THC Content in Seized Marijuana, Sources: The University of Mississippi Potency Monitoring Project

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

18 Percent of Admissions Increased Marijuana Treatment Admissions 1993 and Alcohol Cocaine Heroin Marijuana Source: SAMHSA, TEDS 1993 & 2007

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

20 Percent Changes in Attitude Lead to Changes in Use Marijuana Use and Perceived Risk among 12 th Graders, 1975 to Past Year Use Perceived Risk Source: The Monitoring the Future study, the University of Michigan

21 For More Info Visit NIDA s

22 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].

23 Cerebellum/Whole Brain Brain Glucose Metabolism in Controls and Marijuana Abusers Control Marihuana Abuser p < Control Abuser Cerebellar metabolism is decreased in Marijuana Abusers Volkow, N.D. et al., Psychiatry Research: Neuroimaging, 67, pp , 1996.

24 Mean Number of Symptoms Depression Symptoms at Age 10 by Trimester of Prenatal Marijuana Exposure p<.01 p=ns p < First Second Third Abstainer Light Moderate Heavy Gray et al., 2005.

25 Percent Prosper Multisite Community Study: Less MJ & Inhalants 1.5 Yrs Past Baseline Past Year Use Intervention Control Marijuana Use Inhalant Use Spoth, Redmond, Shin, Greenberg, Clair, Feinberg (2007). Am J Prev Med, 32(5),

26 Dollars (USD) Ratings (mm) Min Effects of THC and Lofexidine in a Human Laboratory Model of Marijuana Withdrawal and Relapse Marijuana Craving Capsule Strength 25 ** Marijuana Relapse: Money Spent on Self-Administration 0 Sleep Latency (objective) * Fell Asleep Easily (subjective) ** ** 5 0 Placebo THC Lofexidine THC/Lofex Source: Haney, M et al., Psychopharmacology, 197, pp , 2008.

27 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):

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