Opioids and Marijuana Bertha K Madras, PhD Professor of Psychobiology Department of Psychiatry Harvard Medical School Bertha_madras@hms.harvard.edu
Trends Use Rates Addiction and death Overview Cannabinoid- Opioid Connection Biology Evidence Children at Risk Adolescents Developing Fetus Transgenerations
Trends Use Rates Addiction and death
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 Trends: Marijuana and Heroin Use 33 31 29 27 25 23 21 % Using % Using Marijuana 18-25 Marijuana 26+ Heroin 18-25 Heroin 26+ 1.2 1 0.8 0.6 0.4 19 0.2 17 15 2002 2004 2006 2008 2010 2012 2014 0 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 15-4927, NSDUH Series H-50). Retrieved from http://www.samhsa.gov/data/
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% 1993 1995 1997 1999 2001 2003 2005 2007 2009 2011 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 2012 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.
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
% Using During Pregnancy Marijuana Use During Pregnancy 72.9% of pregnant teens in rehab admissions used marijuana 16 14 12 10 8 6 4 2 0 % Using During Pregnancy Age 15-17 Age 18-25 Age 26-44 Calvigioni, Hurd, Harkany, Keimpema Neuronal substrates and functional consequences of prenatal cannabis exposure Eur Child Adolesc Psychiatry DOI 10.1007/s00787-014-0550-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) 14-4863. 2014.
# 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. 2015 Apr 26. [Epub ahead of print]
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. 2007 Sep;17(3):299-315
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;68:313 316
Complications of Opioid Use: Poorer Physical Health Increased risk of early death Increased blood pressure Overweight or underweight Abnormal liver function Increased blood sugar
Complications of I.V. Use: Overdose Shallow, slow breathing Pinpoint pupils Slow heart rate Low body temperature Stupor or coma Death, fixed, dilated pupils
Overview Cannabinoid-Opioid Connection Biology Evidence
Heroin or Morphine Enhance Reward of Other Drugs, including THC: psychoactive chemical in marijuana Psychostimulants: cocaine, methamphetamine Nicotine Alcohol
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): e29239. doi:10.1371/journal.pone.0029239 http://127.0.0.1:8081/plosone/article?id=info:doi/10.1371/journal.pone.0029239
Cannabinoid-Opioid Connection Children at Risk Adolescent Developing Fetus THC Exposure Long Before Conception
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 5 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 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, 427-433
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. 2007 Mar;32(3):607-15.
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. 2007 Feb 15;61(4):554-63.
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. 2014 May;39(6):1315-23.
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
Opioid Use fell dramatically from 1907/08 to 2006 % USERS 4 3.5 3 2.5 2 1.5 1 0.5 1907/08 2006 0 Asia World Source: UN Office on Drugs and Crime, 2008 Report