Effects of Marijuana On Brain, Body & Behavior Marijuana is the Most Commonly Used Illicit Drug In the US Nora D Volkow, MD Director Over million Americans have tried it at least once An estimated million Americans used it for the first time in National Survey on Drug Use and Health, SAMHSA, 3 Tetrahydrocannabinol (THC) Active Ingredient in Marijuana ADDICTION IS A DEVELOPMENTAL DISEASE it starts in adolescence and childhood oup who dence age in each age gro p first-time depen Percenta develop % % % % % % % % % % TOBACCO THC ALCOHOL 3 3 Age Age at tobacco, at alcohol and at cannabis use dependence as per DSM IV NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 3 3 Percentage of US th Grade Students Reporting Past Month Use of Cigarettes, Marijuana and Alcohol Alcohol Marijuana 9 9 93 9 9 9 97 9 99 3 7 9 3 SOURCE: University of Michigan, 3 Monitoring the Future Study Cigarettes
Natural and Drug Reinforcers Increase Dopamine in NAc frontal cortex nucleus accumbens VTA/SN Drugs of abuse increase DA in the Nucleus Accumbens, which is believed to trigger the neuroadaptions that result in addiction 9 7 3 % of Basal Release % of Basal Release % of Basal Release AMPHETAMINE 3 hr MARIJUANA Tanda, et al, Science 997 Empty Box Feeding FOOD Time (min) Di Chiara et al Constituents of MJ and the Cannabinoid System delta-9-tetrahydrocannabinol l d l delta-9-tetrahydrocannabivarin delta--tetrahydrocannabinol cannabigerol cannabinol cannabichromene cannabidiol Cannabinoid Receptors Are Located Throughout the Brain and Regulate: Brain Development Memory & Cognition Motivational Systems & Reward Appetite Immunological Function Reproduction Movement Coordination Pain Regulation & Analgesia Long Term Effects of Marijuana Addiction: About 9% of users may become dependent, in who start use in adolescence, -% of daily users Percent Estimated Prevalence of Dependence Among Users 3 3 3 7 9 * * * Nonmedical Use Source: Anthony JC et al, 99 3
Drug Use Outcomes in Twin Pairs (n =3) Discordant for Cannabis Use Before Age 7 Does marijuana use negatively affect the developing brain and an individual s personal trajectory into adulthood? Odds Ratio Source: Lynskey, MT et al, JAMA, 9, pp 7-33, 3 Cannabis Use and Later Life Outcomes Are Dose Early Marijuana Use and Intensity of Use are Associated with Educational Attainment % welfare dependent (ages -) % Unemployed (ages -) mean personal income in thousands of NZ $ at age % gained university degree by age + 3 to 399 to 99 to 99 to 99 Never # of occasions using Cannabis ages - Number of occasions using Cannabis between ages - High School Completion Low Intensity Med/High Intensity < Age > Age -%** -%*** -% -%*** Young people who begin marijuana use at a young age and use it intensively have a higher probability of dropping out of high school University Entrance Score < Age > Age % -% -%** * -9% For those that do successfully complete high school and obtain a university entrance score, med-high intensity use is associated with scores on average percentiles lower than their peers Source: Fergusson and Boden Addiction, 3, pp 99-97, *** p<, ** p< Source: Cobb-Clark et al http://ftpizaorg/dp779pdf 3
Persistent Cannabis Users Show Neuropsychological Decline from Childhood to Midlife Dunedin prospective study of 37 Ss born 97/73, Tested for IQ at age 3 and 3y Tested THC use ages,,, 3 and 3y ange in Full-Scale IQ andard deviation units) Ch (in st - - - Adolescent Vulnerability Diagnosis Diagnoses 3 Diagnoses - p= p=9 p= Cannabis Before Age (n=7) Not Cannabis Before Age (n=7) Cannabis Before Age (n=) Not Cannabis Before Age (n=) Cannabis Before Age (n=3) Not Cannabis Before Age (n=) Source: Meier MH et al, PNAS Early Edition Early (<y) 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=9) than in controls (N=33) Zalesky et al Brain DA Synthesis Capacity in Cannabis Abusers AMOTIVATION & THC Reduced striatal DA synthesis capacity in cannabis users relative to controls Striatal DA synthesis and apathy (AES-S score) F DOPA Bloomfield et al, Psychopharm
Methylphenidate Induced Changes in [ C]Raclopride (Dopamine Marker) in Controls and Marijuana Abusers and Negative Emotionality Marijuana Abusers Effects of THC on Mental Illness Females (n=) Males (n=) Healthy Controls High 9 7 3 HIGH Time (min) 9 9 7 7 Pulse (BPM) DV (PL MP) @ P < HEART RATE Time (min) Brain reactivity to DA stimulation by MP along with its behavioral and cardiovascular effects are attenuated in Marijuana Abusers; and their reduced DA reactivity in VS is associated with negative emotionality (NEM) Volkow et al, PNAS Cannabinoid CB Receptors in Human Brain are Downregulated in Marijuana Abusers Brain abnormalities associated with long-term heavy cannabis use Hippocampus Amygdala Marijuana Abusers Controls BL ACC/CB L (yellow) and R (blue) amygdala L(red) and R(green) hippocampus Van Loere et al, 7 Hirvonen et al, Mol Psychiatry 3 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;():9-7
Cannabis-Associated Psychosis Odds ratio Study of Swedish Conscripts (n=7) r, Cases per 3 Andréasson et al Lancet, 97 < > No of times cannabis taken Prospective Dunedin study (n=37) 9 Risk of schizophrenia-like psychosis py at age years 7 3 Cannabis users by age years Cannabis users by age years Arseneault et al BMJ Regular Cannabis Use Increases Schizophrenia Risk in those with AKT AKT(T/T) rs973 AKT(C/T) genotype AKT(C/C) Odds Ratio Never used cannabis Used cannabis at week ends or less Used cannabis everyday AKT(T/T) AKT(C/T) AKT(C/C) GXE model: p*= Di Forti et al, Biological Psychiatry, 3 Effect of High Potency Cannabis on Risk of Psychosis Never used cannabis Hash<than weekly Hash at week ends Hash daily Skunk<than weekly Skunk at week ends 9 9 Adjusted OR RM Murray, and M Di Forti Institute of Psychiatry, London UK 9) 7* * THC OF TODAY Increases over Time in the Potency of Tetrahydrocannabinol (THC) in Marijuana and the Number of Emergency Department Visits Involving Marijuana, Cocaine, or Heroin 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 Volkow ND et al, NEJM 37(3), June, Vindenes V et al,forensic Sci Internati 3; ( 3): 97-
Proportion Of Drivers In A Fatal Motor Vehicle Crash Who Were Marijuana-Positive In Colorado and 3 States Without Medical Marijuana Laws From 99- th Graders Past Year Marijuana Use vs Perceived Risk of REGULAR Marijuana Use s (%) n of Marijuana Positive Driver Proportion Proportion of drivers in fatal motor vehicle crash who were marijuana-positive in Colorado increased post-marijuana commercialization c o (9) ly Use (Percent) Dail Perceived Risk Daily Use 9 7 3 Perceiv ved Risk (Percent) Year Salomonsen-Sautel S et al, Drug and Alcohol Dependence, http://dxdoiorg//jdrugalcdep Source: The Monitoring the Future study, SOURCE: University of Michigan, 3 Monitoring the Future Study Can the USA Afford the Risk of Further Increases in Cannabis Use? Prevalence of Cannabis Use among High School Students Past Month Use, Percentages, 7 and USA 7 International Rankings of Educational Achievement, Adolescent Brain Cognition and Development National Longitudinal Study NIDA, NIAAA, NCI, NICHD Ten year longitudinal study of children from age to years to assess effects of drugs on individual brain development trajectories 7 USA ranks th compared with 3 European countries Program for International Assessment (PISA) USA students ranked 3 th in mathematics, th in reading, and 7 th in science 7
nature science Level of Confidence in the Evidence for Adverse Effects of Marijuana on Health and Well-Being Effect Overall Level of Confidence* Addiction to marijuana and other substances --------------- High Abnormal brain development ----------------------------------- Progression to use of other drugs ------------------------------- Schizophrenia ------------------------------------------------------- Depression or anxiety --------------------------------------------- Medium Medium Medium Medium Diminished lifetime achievement ------------------------------- High Motor vehicle accidents ------------------------------------------- High Symptoms of chronic bronchitis -------------------------------- High Lung cancer --------------------------------------------------------- Low Volkow ND et al N Engl J Med ;37:9-7 Maximum Frequency Of Cannabis Use Before Age 7 Years, And Each Young Adult Outcome clear and consistent associations and dose-response relations were found between the frequency of adolescent cannabis use and all adverse young adult outcomes Changes in Marijuana Policy in the USA sted Odds Ratios Adjus Cannabis Dependence Less than Monthly Monthly or More Weekly or More Daily High School Degee Depression Other Illicit Suicide Completion Attainment Drug Use Attempt Silins E et al, The Lancet September Welfare Dependence
Odds Ratio States that Legalized Marijuana Use For Medical Purposes Have Significantly Higher Rates Of Marijuana Use and of Marijuana Abuse and Dependence Past Year MJ Abuse/Dependence 9 Past Year MJ Use 3 Past Year MJ Abuse/Dependence Among Current Users Map of States that Legalized Medical Marijuana by passed laws legalizing medical MJ Percent Marijuana Consumption by American Indians on or Near Reservations % Regular Use AIAN 7 MTF 3 th th th Regular Marijuana Use Age of Initiation 9 3 9 Age in Years 3 NESARC: National Epidemiologic Survey on Alcohol and Related Conditions Cerda M et al Drug and Alcohol Dependence ; : 7 33 Beauvais et al, - and 9-3 ICPSR3-v Ann Arbor, MI: Inter-university Consortium for Political and Social Research [distributor], --;Johnston et al, New NIDA Resources 9