Why Are PRESCRIPTION DRUGS Abused … And What Can We Do About It? Nora D. Volkow, M.D. Director Prescription Drug Misuse/Abuse is aMajor Problem in the US Current Drug Use Rates in Persons Ages 12+ 22.5 (8.7% ) Illicit Drugs Marijuana 18.1 (7.0%) Psychotherapeutics 6.1 Cocaine 1.4 Hallucinogens 1.0 Inhalants 0.6 Heroin 0.3 0 (2.4%) (0.5%) (0.4%) (0.2%) (0.1%) 5 10 15 20 Numbers in Millions Source: SAMHSA, 2011 National Survey on Drug Use and Health, 2012. 25 Why Do People Abuse Prescription Drugs? frontal cortex nucleus accumbens VTA/SN 700 600 500 400 300 200 100 0 % of Basal Release Dopamine Neurotransmission % of Basal Release These prescription drugs, like other drugs of abuse (cocaine, heroin, marijuana) 1100 1000 AMPHETAMINE raise brain dopamine levels 900 800 0 1 2 3 4 5 hr Time After Amphetamine FOOD 200 150 100 50 Empty Box Feeding 0 0 60 120 Time (min) 180 Di Chiara et al. Opioids: Examples: OxyContin, Vicodin How They Work… Attach to opioid receptors in the brain and spinal cord, blocking the transmission of pain messages and causing an increase in the activity of dopamine Opioids are Generally Prescribed for: • • • Postsurgical pain relief Management of acute or chronic pain Relief of coughs and diarrhea Thalamus (pain) NAc (reward) Amydala (reward) Similarities Between Illicit and Prescription Drugs Stimulants Example: Ritalin How They Work… Enhance brain activity by increasing the activity of brain excitatory chemical messengers, such as norepinephrine and dopamine, leading to mental stimulation Stimulants Are Generally Prescribed For: • ADHD • Narcolepsy • Depression that does not respond to other treatments • Asthma that does not respond to other treatment Similarities Between Illicit and Prescription Drugs Cocaine and Ritalin Act on the Same Sites in the Brain Distribution of Dopamine Transporter in the Human Brain 100% Adderall 11% Volkow, et al. (BNL) Methamphetamine What is the Difference Between Therapeutic Use and Abuse? • Dose and Frequency of Dosing Lower, fixed regimes vs higher, escalating use • Route of Administration Oral vs injection, smoking, snorting • Expectation of Drug Effects Expectation of clinical benefits vs euphoria “high” • Context of Administration School, clinic, home vs bar, discotheque Rewarding Effects of Drugs Depend on How Fast they Get into the Brain % Peak [11C]Cocaine in brain [11C]Ritalin in brain 100 100 80 80 60 60 40 40 20 20 0 Reward Reward 0 0 10 20 30 40 50 60 70 80 0 10 20 30 40 50 60 70 80 iv cocaine 0.06 0.05 0.05 0.04 0.04 0.03 0.03 Fast!! 0.02 0.01 0 0 iv Ritalin 0.06 Fast!! 0.02 0.01 20 40 60 80 100 120 Time (minutes) 0 0 20 40 60 80 100 120 Time (minutes) Uptake in Striatum (nCi/cc) Uptake in Striatum (%/cc) Time (min) oral Ritalin 0.0035 0.003 0.0025 0.002 Slow!! 0.0015 0.001 0.0005 00 20 40 60 80 100 120 Time (minutes) Cocaine (iv) and Ritalin (iv) are rewarding but Ritalin (oral) is not. The slow brain uptake of oral Ritalin allows treatment without reward Unexpected MP 70 % Change Glucose Metabolism Was Greatly Increased By the Expectation of the Drug 30 25 20 15 10 5 0 Expected MP Increases in Metabolism Were About 50% Larger When MP Was Expected Than Unexpected 0 µmol/100g/min Source: Volkow, ND et al., Journal of Neuroscience, 23, pp. 11461-11468, December 2003. What Has Raised Our Attention to the Problem of Prescription Drug Abuse? Drug OD in the US Have More Than Tripled since 1990 and INCREASES Greater for Women (Five-FOLD) More Than 5-Fold Increase In Treatment Admissions For Prescription Painkillers In the Past Decade 180,000 157,171 160,000 12 142,124 140,000 122,185 10 120,000 98,386 100,000 8 82,359 80,000 71,048 60,824 60,000 40,000 6 52,664 45,882 37,649 4 28,326 100 people die from drug overdoses every day in the US 2 20,000 0 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 0 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 *Deaths are those for which poisoning by drugs (illicit, prescription, and over-the-counter) was the underlying cause. Source: SAMHSA Treatment Episode Data Set (TEDS), 2000-2010 National Vital Statistics System. Drug Overdose Death Rates by State 2008. CDC Vital Signs, July 2013. Number of Opioid Prescriptions Dispensed by U.S. Retail Pharmacies, Years 1991-2011 250 Opioids Hydrocodone Oxycodone Prescriptions (millions) 219 200 192 180 169 150 131 139 144 151 158 120 100 76 78 80 86 91 96 100 109 50 0 IMS’s Source Prescription Audit (SPA) & Vector One®: National (VONA) 201 202 210 Overdose Deaths Prescriptions The Dynamic Relationship between Rates of Opioid Prescriptions and Rates of Opioid-Related Overdose Deaths in the US 2002 2006 Source: IMS Vector One National , CDC Wonder, & the US Census 2009 Opioids Overdose Death by Age Group, US, 2008 Opioid Prescriptions by Age 20 to 29 No. of Prescriptions (millions) 35 30 to 39 40+ 159 180 160 30 30 140 25 120 20 100 19 15 80 60 10 40 6 5 2 - 2002 2006 2009 20 Rate per 100,000 10 to 19 No. of Prescriptions, Age 40+ (millions) 0 to 9 - 2012 IMS Health, Vector One® National Paulozzi LJ, J Safety Res 2012; 43(4): 283-289. Specific Drug Involvement in Pharmaceutical Overdose Deaths USA, 2010 120 100 100 PERCENT 80 Drug Involvement in Pharmaceutical Overdose Deaths Opioid Analgesic Involvement in Deaths for Specific Drugs 77.2 75.2 65.5 58 57.6 60 54.2 50 40 29.4 17.6 20 7.8 6.1 1.3 0.1 0 Opioid Analgesics Antiepileptic & Benzodiazepines Antiparkinsonism Drugs Barbiturates Antidepressants Antipsychotic & Neuroleptic Drugs Jones, CM et al. JAMA, February 20, 2013; 309(7): 657-659. Other Psychotropic Drugs Source of Prescription Drugs (how they obtained the drugs they most recently used nonmedically) Rates averaged across 2009 and 2010 60.0% 55.0% Percent 50.0% 40.0% 30.0% 20.0% 17.3% 11.4% 10.0% 4.8% 4.4% 0.4% 0.0% Given by a Bought from a Took from Through a From drug friend/relative friend/relative friend/relative prescription dealer or for free without from one other stranger asking doctor Source: 2010 National Survey on Drug Use and Health, SAMHSA 2011. Bought on internet Prescription Drug Abuse: What can be done? • Medications -- Less abusable analgesics -- Easy to administer Naloxone • Clinician Information and Education • Primary Prevention Uptake in Striatum (nCi/cc) Need for New Medications • Develop medications with 0.0035 0.003 0.0025 0.002 0.0015 0.001 0.0005 00 lower abuse potential Slow!! 20 40 60 80 100 120 Time (minutes) • Develop slow release formulations (low dose and long duration) • Develop novel formulations to reduce abuse liability Overdose Intervention • Naloxone Distribution for opioid overdose victims. The potential for direct intervention to save lives. • Naloxone Nasal Spray Development Needle-free, unit-dose, ready-to-use opioid overdose antidote NIDA STTR Grantee – AntiOp, Inc., Daniel Wermeling, CEO Contact: E-mail: [email protected], Tel: 859-221-4138 Education for Healthcare Providers CME Courses developed by NIDA & Medscape Education, funded by ONDCP Safe Prescribing for Pain Skills and tools clinicians can use to screen for and prevent abuse in patients with pain Managing Pain Patients Who Abuse Rx Drugs Learn symptoms of opioid addiction and dependence in patients with chronic pain, and how to screen for, prevent, and treat such conditions