Effects of Marijuana On Brain, Body & Behavior. Nora D. Volkow, MD Director

Transcription

1 Effects of Marijuana On Brain, Body & Behavior Nora D. Volkow, MD Director

2 Marijuana is the Most Commonly Used Illicit Drug In the U.S. Over 111 million Americans have tried it at least once An estimated 2.4 million Americans used it for the first time in National Survey on Drug Use and Health, SAMHSA, Tetrahydrocannabinol (THC) Active Ingredient in Marijuana

3 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.

4 Percentage of U.S. 12 th Grade Students Reporting Past Month Use of Cigarettes, Marijuana and Alcohol Alcohol Marijuana Cigarettes SOURCE: University of Michigan, 2013 Monitoring the Future Study.

5 % 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.

6 Constituents of MJ and the Cannabinoid System delta-9-tetrahydrocannabinol delta-9-tetrahydrocannabivarin delta-8-tetrahydrocannabinol cannabigerol cannabinol cannabichromene cannabidiol

7 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

8 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

9 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.

10 Does marijuana use negatively affect the brain?

11 ACC/CBL Cannabinoid CB1 Receptors in Human Brain are Downregulated in Marijuana Abusers Marijuana Abusers Controls Van Loere et al., Hirvonen et al., Mol Psychiatry 2013

12 Brain abnormalities associated with long-term heavy cannabis use Hippocampus Amygdala L (yellow) and R (blue) amygdala L(red) and R(green) hippocampus morphology and function of hippocampus has been linked to reduced memory performance in heavy cannabis users Hippocampal and amygdalar volumes were smaller in cannabis users than in controls. Yucel et al., Arch Gen Psychiatry Jun;65(6):

13 BRAIN DEVELOPMENT & THC

14 Change in Full-Scale IQ (in standard deviation units) Persistent Cannabis Users Show Neuropsychological Decline from Childhood to Midlife Dunedin prospective study of 1037 Ss born 1972/73, Adolescent Vulnerability 1 Diagnosis 2 Diagnoses 3 Diagnoses Tested for IQ at age 13 and 38y. Tested THC use ages 18, 21, 26, 32 and 38y p=.44 p=.09 p=.02 Cannabis Dependent Before Age 18 (n=17) Not Cannabis Dependent Before Age 18 (n=57) Cannabis Dependent Before Age 18 (n=12) Not Cannabis Dependent Before Age 18 (n=21) Cannabis Dependent Before Age 18 (n=23) Not Cannabis Dependent Before Age 18 (n=14) Source: Meier MH et al., PNAS Early Edition 2012.

15 Early (<18y) Long-Term Cannabis Use Decreases Axonal Fiber Connectivity Precuneus to splenium Fimbria of hippocampus, hippocampal commissure and Splenium Axonal paths with reduced connectivity (measured with diffusion-weighted MRI) in cannabis users (n=59) than in controls (N=33). Zalesky et al Brain 2012.

16 AMOTIVATION & THC

17 Cannabis Use and Later Life Outcomes Are Dose Dependent % welfare dependent (ages 21-25) % Unemployed (ages 21-25) mean personal income in thousands of NZ $ at age 25 % gained university degree by age to to to to 99 Never # of occasions using Cannabis ages Number of occasions using Cannabis between ages Source: Fergusson and Boden. Addiction, 103, pp , 2008.

18 Correlations between Urine Concentration of THC and D2R availability (RAC BP ND ) in Cannabis Users (n = 10) Marijuana abusers with heavier consumption had lower Striatal D2R Albrecht DS et al., Drug and Alcohol Depend 2013;128:52-57.

19 DA Synthesis Capacity in Cannabis Abusers Reduced striatal DA synthesis capacity in cannabis users relative to controls Striatal DA synthesis and apathy (AES-S score) 18 F DOPA Bloomfield et al., Psychopharm 2014.

20 Odds ratio Cannabis-associated psychosis CANNABIS AND SCHIZOPHRENIA Study of Swedish Conscripts (n=45 570) CANNABIS AND SCHIZOPHRENIA-Like Longitudinal prospective Dunedin study (n=1037) Cases of Sz per 1, Risk of schizophrenia-like psychosis at age 26 years <50 >50 No of times cannabis taken 1 0 Cannabis users by age 15 years Cannabis users by age 18 years Andréasson et al Lancet, 1987 Arseneault et al BMJ 2002

21 THC OF TODAY

22 Percentage Number of Samples Average Delta-9 THC Concentration Per Year n D-9 THC%

23 Mean Concentrations of THC, Ethanol & Amphetamines In Whole Blood Samples From Drivers Apprehended By The Police Suspected Of Driving Under The Influence THC Amphetamine & Methamphetamine Ethanol Vindenes V et al.,forensic Sci Internati 2013; 226(1 3):

24 % of admissions Increased Marijuana Treatment Admissions 1993 and 2007 Emergency Department Visits Involving Selected Drugs: Alcohol Cocaine Heroin Marijuana Source: SAMHSA, TEDS 1993 & Source: SAMHSA, 2008 DAWN.

25 Changes in Marijuana Policy in the USA

26 Odds Ratio Map Of States That Legalized Marijuana By 2004 passed laws legalizing MJ Outcomes of Interest Past Year MJ Abuse/Dependence Past Year MJ Use Past Year MJ Abuse/Dependence Among Current Users NESARC: National Epidemiologic Survey on Alcohol and Related Conditions Cerda M et al. Drug and Alcohol Dependence 2012; 120:

27 Proportion Of Drivers In A Fatal Motor Vehicle Crash Who Were Marijuana-Positive In Colorado and 34 States Without Medical Marijuana Laws From Proportion of Marijuana Positive Drivers (%) Proportion of drivers in fatal motor vehicle crash who were marijuana-positive in Colorado increased post-marijuana commercialization (2009) Year Salomonsen-Sautel S et al., Drug and Alcohol Dependence 2014,

28 12 th Graders Past Year Marijuana Use vs. Perceived Risk of Occasional Marijuana Use Past Year Use Perceived Risk SOURCE: University of Michigan, 2013 Monitoring the Future Study