Opioids and Marijuana. Bertha K Madras, PhD Professor of Psychobiology Department of Psychiatry Harvard Medical School

Transcription

1 Opioids and Marijuana Bertha K Madras, PhD Professor of Psychobiology Department of Psychiatry Harvard Medical School Bertha_madras@hms.harvard.edu

2 Trends Use Rates Addiction and death Overview Cannabinoid- Opioid Connection Biology Evidence Children at Risk Adolescents Developing Fetus Transgenerations

3 Trends Use Rates Addiction and death

4 Trends: Marijuana and Heroin Use % Using % Using Marijuana Marijuana 26+ Heroin Heroin Center for Behavioral Health Statistics and Quality. (2015). Behavioral health trends in the United States: Results from the 2014 National Survey on Drug Use and Health (HHS Publication No. SMA , NSDUH Series H-50). Retrieved from

5 Trends: Rising Treatment Admissions 20% ~ 23% of those who use heroin become dependent on it Percent of All Admissions 16% 12% 8% Heroin Other Opiates 4% 0% TEDS data: admissions to treatment ages 12+ for abuse of alcohol and/or drugs in facilities reporting to State administrative data systems. Data: admissions records received, processed through 10/17/13. TEDS admissions: not individuals; report up to three substances of abuse that led to the treatment episode.

6 Trends: Rising Opioid Poisoning Deaths Heroin or Prescription Opioids Opioid analgesics Opioid Rx: 16,235 Heroin Heroin: 8,257 Both: 1,342 Source: CDC/NCHS, National Vital Statistics System, Mortality

7 % Using During Pregnancy Marijuana Use During Pregnancy 72.9% of pregnant teens in rehab admissions used marijuana % Using During Pregnancy Age Age Age Calvigioni, Hurd, Harkany, Keimpema Neuronal substrates and functional consequences of prenatal cannabis exposure Eur Child Adolesc Psychiatry DOI /s y; Substance Abuse and Mental Health Services Administration, Results from the 2013 National Survey on Drug Use and Health: Summary of National Findings, NSDUH Series H-48, HHS Publication No. (SMA)

8 # Newborns Born in Withdrawal is Rising Fetus Mother Tolia VN, Patrick SW, Bennett MM, Murthy K, Sousa J, Smith PB, Clark RH, Spitzer AR. Increasing Incidence of the Neonatal Abstinence Syndrome in U.S. Neonatal ICUs. N Engl J Med Apr 26. [Epub ahead of print]

9 Complications of Opioid Use: Brain function Opiate effects on cognition Deficits Attention Concentration Recall Visual - spatial skills Speed of responding Long-term deficits executive function Inhibition of inappropriate responses Gruber SA, Silveri MM, Yurgelun-Todd DA. Neuropsychological consequences of opiate use. Neuropsychol Rev Sep;17(3):

10 Complications of I.V. Opioid Use Infections Bad Chemistry Normal human brains (top) INFECTIONS Viral Bacterial Hepatitis B Meningitis Hepatitis C Osteomylitis HIV/AIDS Abcess Parkinson s MPTP Snow et al, J Neurol Neurosurg Psychiatry 2000;68:

11 Complications of Opioid Use: Poorer Physical Health Increased risk of early death Increased blood pressure Overweight or underweight Abnormal liver function Increased blood sugar

12 Complications of I.V. Use: Overdose Shallow, slow breathing Pinpoint pupils Slow heart rate Low body temperature Stupor or coma Death, fixed, dilated pupils

13 Overview Cannabinoid-Opioid Connection Biology Evidence

14 Heroin or Morphine Enhance Reward of Other Drugs, including THC: psychoactive chemical in marijuana Psychostimulants: cocaine, methamphetamine Nicotine Alcohol

15 Cannabinoid and Opioid (Δ) Receptors Exist in Proximity on Same Cortical Cells Rozenfeld R, Bushlin I, Gomes I, Tzavaras N, Gupta A, et al. (2012) Receptor Heteromerization Expands the Repertoire of Cannabinoid Signaling in Rodent Neurons. PLoS ONE 7(1): e doi: /journal.pone

16 Cannabinoid-Opioid Connection Children at Risk Adolescent Developing Fetus THC Exposure Long Before Conception

17 Adolescent Marijuana Use and Opioid Addiction: twin study Twins A started marijuana before 17, Twins B after age 17: Twin A is 4X more likely to develop opioid addiction Use Mj pre-17 % Addicted to Opioids Use Mj post-17 Michael T. Lynskey; Andrew C. Heath; Kathleen K. Bucholz JAMA, January 22/29, 2003 Vol 289,

18 THC Exposure during Rodent Adolescence Primes Brain to Seek More Heroin After Maturation Ellgren M, Spano SM, Hurd YL. Adolescent cannabis exposure alters opiate intake and opioid limbic neuronal populations in adult rats. Neuropsychopharmacology Mar;32(3):

19 Adult Rats Exposed to THC in utero Show Enduring behavioral, brain impairment related to opioid reward/stress system Longer: Vulnerability to self-administer heroin Shorter: Time to first heroin-seeking session Increased: Response to lower doses of heroin Increased: Heroin seeking after a mild stress Increased: Heroin-seeking if access to heroin removed Spano MS, Ellgren M, Wang X, Hurd YL. Prenatal cannabis exposure increases heroin seeking with allostatic changes in limbic enkephalin systems in adulthood. Biol Psychiatry Feb 15;61(4):

20 THC Exposure Prior to Conception Affects Offspring! Step 1 Step 2 Step 3 Step 4 Step 5 Adolescent THC No THC Grow up No THC Mate No THC Babies born No THC Babies mature Seek Heroin more Stopping marijuana long before parenting children, may still increase a child s heroin-seeking? Szutorisz H, Dinieri JA, Sweet E, Egervari G, Michaelides M,Carter JM, Ren Y, Miller ML, Blitzer RD, Hurd YL. Parental THC Exposure Leads to Compulsive Heroin-Seeking and Altered Striatal Synaptic Plasticity in the Subsequent Generation. Neuropsychopharmacology May;39(6):

21 Marijuana and Heroin Human young adolescent marijuana users As adults: Use and abuse heroin, other drugs more Rodent adolescents exposed to THC Adults seek heroin more avidly Rodent pregnant females exposed to THC Rodent adolescent male, females exposed to THC long before mating; later produce offspring Adult offspring consume more heroin Show impaired brain and behavior (opioid reward/stress system) Adult offspring consume more heroin Show more heroin withdrawal Show other brain, behavioral changes

22 Opioid Use fell dramatically from 1907/08 to 2006 % USERS / Asia World Source: UN Office on Drugs and Crime, 2008 Report