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Bertha K Madras, PhD© Professor of Psychobiology Department of Psychiatry Harvard Medical School [email protected] © Opioids and Marijuana
Bertha K Madras, PhD© Professor of Psychobiology Department of Psychiatry Harvard Medical School [email protected]
©Opioids and Marijuana
Overview
Trends
Use Rates
Addiction and death
Cannabinoid-Opioid
Connection
Biology
Evidence
Children at Risk
Adolescents
Developing Fetus
Trans-generations
Trends
Use Rates
Addiction and death
Trends: Marijuana and Heroin Use
15
17
19
21
23
25
27
29
31
33
2002 2004 2006 2008 2010 2012 2014
Marijuana 18-25 Marijuana 26+
0
0.2
0.4
0.6
0.8
1
1.2
20
02
20
03
20
04
20
05
20
06
20
07
20
08
20
09
20
10
20
11
20
12
20
13
20
14
Heroin 18-25 Heroin 26+
% Using % Using
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
Percent
of All
Admissions
19921993
19941995
19961997
19981999
20002001
20022003
20042005
20062007
20082009
20102011
2012
0%
4%
8%
12%
16%
20%
Heroin
Other Opiates
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.
~ 23% of those who use heroin become dependent on it
Trends: Rising Opioid Poisoning Deaths
Heroin or Prescription Opioids
Source: CDC/NCHS, National Vital Statistics System, Mortality
Opioid Rx: 16,235 Opioid analgesics
Heroin
Heroin: 8,257 Both: 1,342
72.9% of pregnant teens in rehab admissions used marijuana
Marijuana Use During Pregnancy
% U
sin
g D
uri
ng
Pre
gnan
cy
0
2
4
6
8
10
12
14
16
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.
% Using During Pregnancy
# 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]
Opiate effects on cognition
Deficits • Attention
• Concentration
• Recall
• Visual - spatial skills
• Speed of responding
Long-term deficits • executive function
• Inhibition of inappropriate responses
Complications of Opioid Use: Brain function
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
Viral Bacterial
Hepatitis B Meningitis
Hepatitis C Osteomylitis
HIV/AIDS Abcess
Infections Bad Chemistry
Snow et al, J Neurol Neurosurg Psychiatry 2000;68:313–316
Normal human brains (top)
Parkinson’s MPTP
Complications of Opioid Use: Poorer Physical Health
Abnormal liver function
Increased blood sugar
Overweight or underweight
Increased risk of early death
Increased blood pressure
•Shallow, slow breathing
•Pinpoint pupils
•Slow heart rate
•Low body temperature
•Stupor or coma
•Death, fixed, dilated pupils
Complications of I.V. Use: Overdose
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
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 and Opioid (Δ) Receptors Exist in Proximity on Same Cortical Cells
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
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
Use Mj pre-17 Use Mj post-17
Michael T. Lynskey; Andrew C. Heath; Kathleen K. Bucholz JAMA, January 22/29, 2003—Vol 289, 427-433
% Addicted to Opioids
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
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.
• 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
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.
Adolescent THC
THC Exposure Prior to Conception Affects Offspring!
No THC
Grow up No THC
Mate No THC
Babies born No THC
Babies mature Seek Heroin more
Step 1 Step 2 Step 3 Step 4 Step 5
Marijuana and Heroin
As adults: Use and abuse heroin, other drugs more
Human young adolescent marijuana
users
Adults seek heroin more avidly Rodent adolescents
exposed to THC
Adult offspring consume more heroin
Show impaired brain and behavior
(opioid reward/stress system)
Rodent pregnant females exposed to THC
Adult offspring consume more heroin
Show more heroin withdrawal
Show other brain, behavioral changes
Rodent adolescent male, females exposed to THC
long before mating;
later produce offspring
Source: UN Office on Drugs and Crime, 2008 Report
0
0.5
1
1.5
2
2.5
3
3.5
4
Asia World
1907/08
2006
% U
SER
S Opioid Use fell dramatically from 1907/08 to 2006
