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NORA VOLKOW RX DRUG ABUSE | HEROIN SUMMIT 2016

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ATALANTA 28-31 MARZO 2016 | 1. Rx Drug Abuse and Heroin Where is Science Leading Us? Nora D. Volkow, M.D. Director @NIDAnews National Institute on Drug Abuse
2. Numbers in Millions Prescription Drug Misuse/Abuse is a Major Problem in the US Source: SAMHSA, 2014 National Survey on Drug Use and Health ...

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NORA VOLKOW RX DRUG ABUSE | HEROIN SUMMIT 2016

  1. 1. Rx Drug Abuse and Heroin Where is Science Leading Us? Nora D. Volkow, M.D. Director @NIDAnews National Institute on Drug Abuse
  2. 2. Numbers in Millions Prescription Drug Misuse/Abuse is a Major Problem in the US Source: SAMHSA, 2014 National Survey on Drug Use and Health, 2015. 4.7 4.9 5.1 5 4.8 4.9 4.8 4.3 4.8 4.2 3.9 2.1 2.2 2.1 2.1 2 2.2 2.2 2 2.3 2 2 1.2 1.1 1.4 1.2 1.1 1.2 1.1 1 1.3 1.3 1.4 0.3 0.3 0.4 0.3 0.2 0.3 0.4 0.2 0.2 0.2 0.3 0 1 2 3 4 5 6 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 Current Drug Use Rates in Persons Ages 12+ Past Year Nonmedical Use of Psychotherapeutic Drugs Persons Ages 12+ Opioid Abuse 0.4 0.5 1.1 1.5 6.5 22.2 27 0 10 20 30 Heroin Inhalants Hallucinogens Cocaine Psychotherapeutics Marijuana Any Illicit Drug
  3. 3. Past Month & Past Year Heroin Use Persons Aged 12 or Older SAMHSA, 2014 National Survey on Drug Use and Health, 2015. 404 314 398 379 560 373 455 582 621 620 669 681 914 166 119 166 136 339 161 213 193 239 281 335 289 435 0 100 200 300 400 500 600 700 800 900 1000 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 NumbersinThousands Abuse of Opioid Medications has led to a Rise in Heroin Abuse Past Year Past Month YEAR Thousands
  4. 4. 4,030 4,400 5,528 7,456 8,517 9,857 10,928 13,723 14,408 14,800 15,597 16,651 16,917 16,007 16,235 18,893 Opioid Analgesic Overdose Deaths in the USA 1,9601,8421,779 2,0892,0801,8782,0092,088 2,399 3,041 3,278 3,036 4,397 5,925 8,257 10574 0 2,000 4,000 6,000 8,000 10,000 12,000 Heroin Overdose Deaths in the USA Centers for Disease Control and Prevention. Wide-ranging Online Data for Epidemiologic Research (WONDER), Multiple-Cause-of-Death file, 2000–2014. 2015 (http://www .cdc .gov/ nchs/ data/health_policy/ AADR_ drug_ poisoning_involving_OA_Heroin_US_2000-2014 .pdf)
  5. 5. Analgesic Mechanisms of Mu Opiate Drugs (Heroin, Vicodin, Morphine) Pain Ascending input Descending modulation Dorsal horn Dorsal root ganglion Peripheral nerve Spinothalmic Tract Peripheral nociceptors Trauma Opioids Alpha2 agonists Local anesthetics Anti-inflammatory drugs Local anesthetics Opioids Alpha2 agonists Local anesthetics Thalamus (pain) ACC (pain) PAG (pain) Accumbens (reward)
  6. 6. How Can Research Help? • PAIN: Develop Less Abusable Analgesics & Alternative Therapeutics • OVERDOSES: User Friendly Naloxone •ADDICTION: New Medications & Immunotherapies • Pharmacogenomics (Precision Medicine) • Implementation Science
  7. 7. Opioid deterrent formulations Development of Safer Analgesics Pro-drugs Tamper resistant formulation Drug combinations with adverse effects if injected Non-Opioid based analgesics Cannabinoids; Inflammatory mediators; Ion channel blockers Non-pharmacological mechanisms and treatments Surgical interventions for pain; Neural stimulation technologies for chronic pain; Spinal cord stimulation
  8. 8. Abuse-Resistant Opioid Prodrug (i.e., Signature Therapeutics) PAIN: Less Abusable Analgesics
  9. 9. BIOMARKERS OF PAIN PBR28 Binding is Increased in Thalamus of Patients with Low Back Pain Marco L. Loggia et al. Brain 2015;138:604-615. Thalamic PBR28 binding was inversely correlated with perception of pain
  10. 10. How Can Research Help? Non-Medication Strategies For the Treatment of PAIN and ADDICTION Transcranial Magnetic Stimulation (TMS) Magnets induce current in the brain Examples: Neuronavigation Guided (Stereotaxic) rTMS used in treating Mild Traumatic Brain Injury-Related Headaches (MTBI-HA) Spinal Cord Stimulation (SCS) Minimally invasive procedure placing SCS leads into the epidural space Lamer TJ et al., Mayo Clinic Proceedings 2016; 91: 246-258. Leung et al., Pain Physician 2016;19: E347-353.
  11. 11. Precision Medicine CYP2B6 is the main determinant of methadone elimination; its gene CYP2B6 is highly polymorphic. Most significant variant is CYP2B6*6, which has reduced expression and activity and occurs commonly in Africans, Asians, and Hispanics. Kharasch et al., Anesthesiology. 2015;123(5):1142-1153. Individuals with CYP2B6*6 had higher blood concentrations of R- and S-methadone after one oral dose (11 mg); due to reduced elimination Genetic testing might help identify individuals at risk for methadone overdose and could be useful in guiding methadone dosing R-methadone S-methadone
  12. 12. AA, compared with G carriers, had greater MOR in anterior cingulate (ACC), accumbens (NAc), and thalamus (THA) Peciña M et al., Neuropsychopharmacology 2015. •A118G SNP at OPRM1, is functional: it affects receptor levels in brain • 118G as well as other variants have been associated with increased risk for addiction to opiates and with worse clinical severity for overdoses. The Target Of Opioids Is the µ Opioid Receptor and the Gene That Encodes (OPRM1) Is Polymorphic Hancock et al., Biol Psychiatry. 2015. Manini et al., J Med Toxicol. 2013. G carrier AA
  13. 13. OVERDOSES: User Friendly Naloxone Naloxone Nasal Spray Development Needle-free, unit-dose, ready-to-use opioid overdose antidote Adapt Pharma NARCAN nasal spray APPROVED BY FDA, November 18, 2015 Image courtesy of ADAPT Pharma, Inc. $37.50 per 4mg NARCAN Nasal Spray device How Can Research Help?
  14. 14. Opioid OD Death were Reduced In Communities that Implemented Nasal Naloxone Distribution Program Unadjusted Unintentional Opioid-Related Overdose Death Rates Unadjusted Opioid-Related Acute Care Hospital Utilization Rates Walley AY et al., BMJ 2013. Intranasal Naloxone Administration By Police First Responders In Ohio Intranasal naloxone administration by police first responders is associated with decreased OD deaths Rando et al., Am J Emerg Med 2015.
  15. 15. Medications for Opioid Addiction effect no effect agonist antagonist an agonist drug has an active site of similar shape to the endogenous ligand so binds to the receptor and produces the same effect an antagonist drug is close enough in shape to bind to the receptor but not close enough to produce an effect. It also takes up receptor space and so prevents the endogenous ligand from binding OpioidEffect Full Agonist (Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone) Log Dose Source: SAMHSA, 2012 National Survey on Drug Use and Health, 2013.
  16. 16. Opioid Agonist Treatments Decreased Heroin OD Deaths Baltimore, Maryland, 1995-2009 Heroin overdoses Buprenorphine patients Methadone patients Challenge: Compliance with daily intake Solution: Develop long acting medications Schwartz RP et al., Am J Public Health 2013. How Can Research Help? 565 143 2900 25000 49000 55000 60000 0 10000 20000 30000 40000 50000 60000 70000 0 100 200 300 400 500 600 1995 1996 1997 1998 1999 #onBuprenorphineTreatment #ofOpioidODDeaths # of Opioid Deaths Ling et al. J Subst Abuse Tx 2002;23:87-92. Auriacombe et al. JAMA 2001;285:45. Buprenorphine Reduced OD Opioid OD declined 75% after buprenorphine introduced in France ADDICTION: New Medications & Immunotherapies
  17. 17. 0 0 0 0 0 0 Percent Source: O’Brien CP et al., Poster presentation at the Annual Meeting of the College on Problems of Drug Dependence, June 2015. All Recorded Overdose Events, Both Fatal and Non-fatal, Occurred In the Control Group No overdoses occurred in the naltrexone group, even after discontinuation of XR-NTX
  18. 18. NEW THERAPEUTICS for Opioid Use Disorder Extended release medications (improve compliance) IMPLANTABLE Buprenorphine Probuphine™ (6 months) EVA polymer Probuphine® 26 mm long,2.5mm diameter Buprenorphine FDA’s Final Decision Initially Expected Feb 27, 2016 Delayed 3 months Rosenthal RN et al., Addiction 2013;105: 2141-2149. % of Urines Negative (out of 72) for Opioids Across Weeks 1 to 24 Placebo Sublingual Buprenorphine ……………………......... Probuphine is designed to release sustained therapeutic drug levels in patients with opioid addiction for up to six months %ofPatientsFailingtoExceed EachPossibleCriterionofSuccess Buprenorphine Implants
  19. 19. Lack of uptake of medication-assisted treatment Addiction Specialty Programs Offering Services As % of all programs surveyed (N=345) Within adopting programs, % of eligible patients receiving Rx Opioid Tx Meds: Methadone 7.8 41.3 Buprenorphine 20.9 37.3 Tablet naltrexone 22.0 10.9 Knudsen et al, 2011, J Addict Med; 5:21-27. TOO FEW ARE TREATED Implementation Science: Expanding MAT
  20. 20. 78% 37% 45% 0 20 40 60 80 100 Buprenorphine Referral Brief Intervention %engagedinTX 30thdaypost randomization D’Onofrio JAMA. 2015. ED-initiated Buprenorphine Increased Engagement In Addiction Tx, Reduced Self-reported Illicit Opioid Use & Decreased Use Of Inpatient Addiction Tx Services 5.4 5.4 5.6 0.9 2.3 2.4 0 1 2 3 4 5 6 Buprenorphine Referral Brief Intervention Baseline DaysofSelf-Reported IllicitOpioidUseinthe Past7Days Implementation Science: Expanding MAT How Can Research Help?
  21. 21. HHS Strategy To Address Opioid-Drug Related Overdose, Death and Dependence • Providing training and educational resources, including updated prescriber guidelines, to assist health professionals in making informed prescribing decisions • Increasing use of naloxone • Expanding the use of Medication-Assisted Treatment (MAT)
  22. 22. Opioid Prescribing After a Nonfatal OD: Association With Repeated Overdose Ann Intern Med. 2016. Repeated OD Despite the fact that opioid discontinuation after overdose is associated with lower risk for repeated overdose, almost all patients continue to receive prescription opioids after an overdose.
  23. 23. PAIN: Develop Less Abusable Analgesics and Alternative Therapeutics National Pain Strategy ”HHS Secretary should develop a comprehensive, population health-level strategy for pain prevention, treatment, management, education, reimbursement and research ..." ORWH OBSSR NIDA NIDCR NINDS NIA NINR NICHD NIAMS NCCIH NIH Pain Consortium Centers of Excellence in Pain Education Goal: Improve pain treatment through education How Can Research Help?
  24. 24. • NIDA CoEs established in 2007 to help fill gaps in medical education curricula related to both illicit drugs and Rx drug abuse • Medical schools at CoEs have developed a diverse portfolio of innovative curriculum resources about how to identify and treat patients struggling with SUD Resources for Medical Students, Resident Physicians & Faculty NIDA
  25. 25. THE APPALACHIAN REGION The Appalachian Region includes all of West Virginia and parts of Alabama, Georgia, Kentucky, Maryland, Mississippi, New York, North Carolina, Ohio, Pennsylvania, South Carolina, Tennessee, & Virginia. The Region is home to more than 25 million people and covers 420 counties & almost 205,000 square miles. February 25, 2016 ARC Partners with NIDA to Improve Opioid Intervention Services in Appalachia • With ARC support, NIDA will provide one-year research grants to address the dramatic increase in adverse outcomes of opioid injection drug use in Appalachia. • Findings will help build a foundation for improved intervention programs and larger-scale research efforts to provide services addressing this growing public health threat. • Applications are due April 28.
  26. 26. Antibodies reduce amount of drug in the brain Capillary Blood Flow Brain Targets drugs, not receptors Capillary Blood Flow Brain Antibodies Vaccine Binding sites ADDICTION: New Medications & Immunotherapies How Can Research Help?

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