Bertha K Madras, PhD Professor of Psychobiology Department of Psychiatry Harvard Medical School McLean Hospital bmadras@partners.org
Users The Brain Adolescent Marijuana Safety Marijuana and Opioids Protecting Youth
Endocannabinoids Present In Many Organs and Blood CB1 receptors BRAIN Heart Pancreas Muscle Testis, ovaries Uterus Prostate Vascular tissue Immune cells CB2 receptors CB2 receptors BLOOD CELLS IMMUNE CELLS Brain Heart Adrenal Intestinal tract Pancreas Bone Smooth muscle Reproductive organs
Marijuana initiation begins early: 12-17 years 2,500,000 2,000,000 1,500,000 1,000,000 500,000 0 Marijuana Rx Pain meds Heroin Alcohol Cigarettes 12-17 y 18-25 y 26+
30 25 20 15 10 5 0 Smoke Binge Alcohol Heavy Alcohol Illicit Drugs NO YES DuPont RL, Han B, Shea CL, Madras BK. Drug use among youth: National survey data support a common liability of all drug use. Prev Med. 2018 May 16;113:68-73.
350,000 300,000 250,000 200,000 150,000 100,000 50,000 0 Tobacco Products 2015 2016 Alcohol
120,000 2015 2016 30,000 2015 2016 2,500 2015 2016 100,000 25,000 2,000 80,000 20,000 1,500 60,000 15,000 1,000 40,000 10,000 20,000 5,000 500 0 Marijuana 0 Opioids 0 Cocaine
Marijuana affects many brain regions with important functions ecb/cb1r: anxiolysis, reward, motor suppression, sleep induction, lipogenesis Is cannabinoid system related to thrift, to help humans survive during starvation?
% perceiving Risk 100 90 80 70 60 50 40 30 20 10 0 Marijuana perception of risk low, decreasing 34.3 36.3 27.7 High risk 93.3 94.2 94.1 High risk 86.3 87.4 87.3 40.3 44.2 Marijuana Heroin Cocaine Alcohol 5+ drinks 2014 2015 2016 44.4 High risk 71.2 72.8 72.8 Tobacco 1+ packs/day
Brain structure Brain function Social function Cognitive function Peer influence
Brain Behavior Addiction Cognition Motivation Psychiatric diseases Driving Use of other drugs
MRI DTI RS fmri Task fmri MRS Conclusions: Marijuana-related brain changes Robust in adolescent brain Some associated with impaired function Silveri, M.M., et al., Neurobiological signatures associated with alcohol and drug use in the human adolescent brain. Neurosci. Biobehav. Rev. (2016), http://dx.doi.org/10.1016/j.neubiorev.2016.06.042
High: can lead to increasing use and addiction Perception: distorted Judgment: impaired (driving, unplanned sex) Balance, coordination: impaired Attention, concentration, problem solving: impaired Learning and memory impaired Crean RD, Crane NA, Mason BJ. An evidence based review of acute and long-term effects of cannabis use on executive cognitive functions. Journal of Addiction Medicine 2011;5:1-8;Pope HG Jr, et al. Early-onset cannabis use and cognitive deficits: what is the nature of the association? Drug Alcohol Depend. 2003 Apr 1;69(3):303-10.; (Pope and Yurgelun-Todd (1996) Solowij et al. 2002, Fletcher et al., 1996,McHale and Hunt,2008; Porter, & Frampton, 2007 et al., 2002; Harvey et al, 2007; Solowij & Pesa, 2010 ; Novaes et al. 2008; Battisti et al., 2010 ; Schweinsburg A. D., Brown S. A., Tapert S. F. The influence of marijuana use on neurocognitive functioning in adolescents. Curr Drug Abuse Rev 2008; 1: 99; Lisdahl K. M., Wright N. E., Medina-Kirchner C., Maple K. E., Shollenbarger S. Considering cannabis: the effects of regular cannabis use on neurocognition in adolescents and young adults. Curr Addict Rep 2014; 1: 144 56.
Addiction risk Ratio % All 1 in 9 11.4% + Mid-teen start 30.6%* 1 in 6 17% Daily use 1 in 2-3 25-50% *Hasin DS et al.,. Prevalence of Marijuana Use Disorders in the United States Between 2001-2002 and 2012-2013. JAMA Psychiatry. 2015 Dec 1;72(12):1235-42. +Compton WM, Han B, Jones CM, Blanco C, Hughes A. Marijuana use and use disorders in adults in the USA, 2002-14: analysis of annual cross-sectional surveys. Lancet Psychiatry. 2016 Oct;3(10):954-964.
I.Q. Change Tested marijuana use marijuana use disorder at ages 18,21,26,32,38 Tested I.Q. at 13, 38 By age 38, those tested for CUD at all test times lost I.Q. points Meier M, PNAS, 2012 2 1 0-1 -2-3 -4-5 -6-7 Never used CUD 1 CUD 2 CUD 3 Series 1 1-1.6-2.4-5.9
3 Increased risk for adverse outcome 2.5 2 1.5 1 0.5 0 Any mental illness Serious mental illness Unemployed Probation or parole Gov. assistance Marijuana ever use Marijuana past year Marijuana 200 days past year CM Jones Analysis of 2015-2016 NSDUH Public Use File Data
20 Increased risk with marijuana use 18 16 14 12 10 8 6 4 2 0 Cannabis dependence Other Illicit drug use Suicide Attempt Les than monthly Monthly + Weekly + Daily
Marijuana or THC [high] Marijuana implicated Marijuana not necessary nor sufficient Use precedes psychosis Poorer outcomes if Ever use marijuana Frequent use and/or high THC can cause acute, transient, dose-dependent psychosis direct cause of psychosis, schizophrenia (genetics, environment contribute) to develop schizophrenia independent of alcohol or other drugs use persists after first episode psychosis increases risk of schizophrenia ~2-fold increases risk of schizophrenia 6-fold
Brain changes Addiction Deficits Amotivation Psychosis Safety
Odds ratio 9 8 7 6 5 4 3 2 1 Rx opiod misuse Cannabis use Opiod Use Disorder Pain, use Cannabis Olfson M, Wall MM, Liu SM, Blanco C. Cannabis Use and Risk of Prescription Opioid Use Disorder in the United States. Am J Psychiatry. 2017 Sep 26:appiajp201717040413.
Opioid overdose deaths
Millions of victims globally have succumbed to addiction - a contemporary version of slavery Addiction destroys autonomy and free will Addiction especially threatens young people An essential priority is to protect the brains of children and youth
The prevention of addiction among youth is a high priority, and achievable by rejecting the use of marijuana and other substances. The underlying reasons for this priority need to be conveyed to youth and their parents.. Educate the public with up-to-date scientific information on how drugs affect the brain, body and behavior Clarify why legalization of marijuana and other drugs is poor public policy, poor public health policy and poor legal policy.