In a recent press release Joseph A. Califano, Jr., Chairman and President of the National Center on Addiction and Substance Abuse at Columbia University called for a major shift in American attitudes about substance abuse and addiction and a top to bottom overhaul in the nation���s healthcare, criminal justice, social service, and eduction systems to curtail the rise in illegal drug use and other substance abuse. Califano, in 2005, also noted that while America has been congratulating itself on curbing increases in alcohol and illicit drug use and in the decline in teen smoking, abuse and addi- tion of controlled prescription drugs-opioids, central nervous system depressants and stimu- lants-have been stealthily, but sharply rising. All the statistics continue to show that prescrip- tion drug abuse is escalating with increasing emergency department visits and unintentional deaths due to prescription controlled substances. While the problem of drug prescriptions for controlled substances continues to soar, so are the arguments of undertreatment of pain. The present state of affairs show that there were 6.4 million or 2.6% Americans using prescription-type psychotherapeutic drugs nonmedi- cally in the past month. Of these, 4.7 million used pain relievers. Current nonmedical use of prescription-type drugs among young adults aged 18-25 increased from 5.4% in 2002 to 6.3% in 2005. The past year, nonmedical use of psychotherapeutic drugs has increased to 6.2% in the population of 12 years or older with 15.172 million persons, second only to marijuana use and three times the use of cocaine. Parallel to opioid supply and nonmedical prescription drug use, the epidemic of medical drug use is also escalating with Americans using 80% of world���s supply of all opioids and 99% of hydrocodone. Opioids are used extensively despite a lack of evidence of their effectiveness in improving pain or functional status with potential side effects of hyperalgesia, negative hormonal and immune effects, addiction and abuse. The multiple reasons for continued escalation of pre- scription drug abuse and overuse are lack of education among all segments including phy- sicians, pharmacists, and the public ineffective and incoherent prescription monitoring pro- grams with lack of funding for a national prescription monitoring program NASPER and a reactive approach on behalf of numerous agencies. This review focuses on the problem of prescription drug abuse with a discussion of facts and fallacies, along with proposed solutions. Key words: Prescription drug abuse, opioid abuse, opioid misuse, National Drug Control Policy, NASPER, prescription drug monitoring programs. Pain Physician 2007 10:399-424 Health Policy Review National Drug Control Policy and Prescription Drug Abuse: Facts and Fallacies From: Pain Management Center of Paducah, KY. Dr. Manchikanti is CEO of the American Society of Interventional Pain Physicians, Medical Director of the Pain Management Center of Paducah, KY, and Associate Clinical Professor of Anesthesiology and Perioperative Medicine, University of Louisville, Louisville, KY. Address Correspondence: Laxmaiah Manchikanti, MD 2831 Lone Oak Road Paducah, Kentucky 42003 E-mail: drm@apex.net Funding: None. Conflict of Interest: None. . Free Full manuscript: www.painphysicianjournal.com Laxmaiah Manchikanti, MD www.painphysicianjournal.com Pain Physician 2007 10:399-424��� ISSN 1533-3159

Pain Physician: May 2007 10:399-424 400 www.painphysicianjournal.com erate the growing problem of illicit drug use and pre- scription controlled substance abuse. Yet, the number of prescriptions for controlled substances continue to soar along with arguments for undertreatment of pain and education for increased prescription and availability of controlled substances with continued funding for numerous programs whose effectiveness have not been proven yet. Figure 1 illustrates the increase of controlled sub- stances abuse from 1992 to 2003, in comparison to US population and prescriptions written for controlled substances, but, newer statistics are even more impres- sive. From 1992 to 2005, the US population increased 15%, whereas, during this period adults abusing con- trolled substances increased 98%. The 2005 NSDUH Survey showed 6.4 million persons or 2.6% of the population 12 years or older in the United States used prescription type psychotherapeutic drugs nonmedi- cally in the past month (6). Nonmedical use of psycho- therapeutic drugs in the past year increased to 15.172 million or 6.2% of the US population of 12 years or older (6). Similarly, lifetime nonmedical use of psycho- therapeutics increased to 48.709 million persons or 20% of the United States population of 12 years or older. Further, in the past year, initiation of substance use among persons aged 12 or older, nonmedical use of psychotherapeutics, was 2.526 million. The only sil- ver lining is that nonmedical use of therapeutic drugs among 12-17 year olds decreased in 2005 compared to 2002 and 2003, whereas it significantly increased for 18-25 year olds from 2002 to 2005. The National Institute on Drug Abuse (NIDA) on the eve of unveiling its first consumer publication to JAbuse oseph A. Califano, Jr., Chairman and President of the National Center on Addiction and Substance at Columbia University (CASA), on May 7, 2007 issued a press release on the state of the affairs of illicit drug use and the diversion and abuse of controlled prescription drugs in the United States (1). Califano, a former U.S. Secretary of Health, Education, and Welfare, called for a major shift in American attitudes about substance abuse and addiction and a top to bottom overhaul in the nation���s healthcare, criminal justice, social service, and education systems, in awakening the power of parenting, to curtail the rise in illegal drug use and other substance abuse. He called substance abuse and addiction a chronic disease of epidemic proportions with physical, psychological, emotional, and spiritual elements that require continuing and holistic care (1,2). Americans, constituting only 4% of the world���s population, consume 80% of the global supply of opi- oids, 99% of the global supply of hydrocodone, and two-thirds of the world���s illegal drugs (1-4). Conse- quently, the sum of all the measures on the current war on drugs has not been able to reduce the nation���s substance abuse and addiction. Califano, also in a July 2005 editorial on the diver- sion and abuse of controlled prescription drugs in the United States (5) noted the following: ���While America has been congratulating itself in recent years on curbing increases in alcohol and il- licit drug abuse and in the decline in teen smoking, abuse and addiction of controlled prescription drugs - opioids, central nervous system depressants and stimulants - have been stealthily, but sharply, rising. Between 1992 and 2003, while the US population in- creased 14%, the number of people abusing controlled prescription drugs jumped 81% - twice the increase in the number of people abusing marijuana, 5 times the number abusing cocaine and 60 times the increase in the number abusing heroin. Controlled prescription drugs like OxyContin, Ritalin, and Valium are now the fourth most abused substances in America behind only marijuana, alcohol, and tobacco.��� Consequently, as in prior years, multiple surveys of non-prescription drug abuse (6-10), emergency de- partment visits for prescription controlled drugs (11- 15) and unintentional deaths due to prescription con- trolled substances (16-20) have been steadily rising. Further, the activities of the White House Office of National Drug Control Policy (21-23), numerous hear- ings held by Congress, the Administration, and various agencies at the federal and state levels (4,24,25) reit- Fig. 1. Increase of controlled substance abuse from 1992 to 2003, in comparison to US population and prescriptions written for controlled substances. 1992 2003 212%���Number of 12- to 17-year-olds abusing Controlled Substances 542%���New Abuse of Prescription Opioids Among Teenagers 150%���Prescriptions written for Controlled Substances 81%���Adults abusing Controlled Substances 14%���US Population Percent Increase 0 100 200 300 400 500 600 700

www.painphysicianjournal.com 401 National Drug Control Policy and Prescription Drug Abuse explain the signs of addiction on March 5, 2007, re- ported that abuse and addiction to alcohol, nicotine, and illegal substances costs Americans upwards of half a trillion dollars a year (26). The National Center on Addiction and Substance Abuse at Columbia University in an update published in 2006, its third report (27), concluded that prescrip- tion controlled drugs continue to be as easy to buy over the Internet as candy, and anyone, including children, can readily obtain, without a prescription, highly addictive controlled substances from Internet drug pushers as long as a person has a credit card. Cal- ifano once again reiterated that not surprisingly, con- trolled prescription drug abuse is on the rise, today, with more adults and teens having reported abusing these drugs than having abused all other illicit drugs combined except marijuana. Even then pain is considered as undertreated by some, while opioid prescriptions are soaring (3). In re- cent medical news and perspectives of JAMA, it was shown that by far the most commonly used prescrip- tion analgesic in the United States is hydrocodone with acetaminophen which has been the most pre- scribed medication of any category for at least the past 5 years, with more than 100 million prescriptions in 2005, far exceeding the number of prescriptions for the second and third most prescribed medications- cholesterol-lowering atorvastatin with about 63 mil- lion prescriptions, and the antibiotic amoxicillin, with about 52 million prescriptions. In addition, in 2004, the United States used 99% of the global supply of the opioid hydrocodone, according to the 2005 report from the International Narcotics Control Board (3). Between 2000 and 2004, medical use of hydrocodone increased 60% domestically. In a recent letter to Members of Congress ti- tled ���Prescriptions Drugs: An Emerging Threat,��� John P. Walters, Director of White House Of- fice of National Drug Control Policy, expressed his deep concern that America���s leadership be aware of this burgeoning problem so that they can inform their communities about the dan- gers of prescription drug abuse (28). The National Drug Threat Assessment 2007 by the National Drug Intelligence Center US Department of Justice (29) reported that rates of pharmaceutical drug abuse exceeded that of all other drugs except marijuana re- sulting in a high number of pharmaceutical overdose deaths annually. Despite the alleged undertreatment of pain, based on the present statistics, it appears that opioids are overprescribed. Widely quoted literature about the undertreatment of pain, pertains to terminal illness, malignancy, post-operative pain and AIDS. Opioid prescriptions have increased substantially from 1997 to 2005, with increases in methadone prescriptions of 933%, oxycodone prescriptions of 588%, and hydro- codone prescriptions of 198% (Table 1). The increase in the legitimate use of opioids has been paralleled by a rise in abuse of these drugs with a 62.5% increase in opioid deaths during the 5-year period from 1999 to 2004 (16,17). Further, in pain management settings, as many as 90% of patients have been reported to receive opioids for chronic pain management (30,31). Multiple investigators (32-49) have shown prevalence of drug abuse around 20% and as high as 58% in the patients receiving opioids for chronic pain. Unfortu- nately, a significant proportion of chronic pain pa- tients also tend to use illicit drugs, with proportions increasing based on concurrent abuse of prescription controlled substances (32-49). The explosion of opioid use and abuse along with illicit drug use in chronic pain patients is sadly coupled with a lack of evidence of their long-term effectiveness in these patients. Our national drug control strategy, with billions of dollars spent each year, is not working. As Califano stated, ���All the huffing and puffing of the current war on drugs has not been able to blow down the nation���s house of substance abuse and addiction.��� Note the following glaring and startling facts (1,2): ��� The number of illegal drug users, which had dropped from a high of 25.4 million in 1979 to a quarter century low of 12 million in 1992, has risen to 20 million in 2005. 1997 2005 % of Change Methadone 518,737 5,362,815 933% Oxycodone 4,449,562 30,628,973 588% Fentanyl Base 74,086 387,928 423% Hydromorphone 241,078 781,287 244% Hydrocodone 8,669,311 25,803,544 198% Morphine 5,922,872 15,054,846 154% Meperidine 5,765,954 4,272,520 -26% Codeine 25,071,410 18,960,038 -24% Table 1. Retail sales of opioid medications (grams of medication 1997 ���2005 Source: http:www.deadiversion.usdoj.gov/arcos/retail_drug_summary/index.htmo

Pain Physician: May 2007 10:399-424 402 www.painphysicianjournal.com ��� The number of teen illegal drug users, which had dropped from its 1979 high of 3.3 million to a low of 1.1 million in 1992, has more than doubled to 2.6 million in 2005. ��� From 1995 to 2005 the number of Americans abus- ing controlled prescription drugs jumped from 6.2 to 15.2 million. ��� One in 4 Americans will have an alcohol or drug problem at some point in their lives. ��� Among the patients suffering with chronic pain and receiving opioids, 1 in 5 abuse prescription controlled substances and approximately the same number of patients also use illicit drugs. Thus, the consequences of this epidemic are se- vere (1,2): ��� Almost a quarter of a trillion dollars of the nation���s yearly health care bill is attributable to substance abuse and addiction. ��� The national drug control strategy from White House spent over $10 billion dollars a year since its enactment in 1988 with no demonstrable re- sults in curbing drug abuse and addition, specifi- cally prescription controlled substance abuse. ��� The National All Schedules Prescription Reporting Act of 2005 signed into law by President Bush on August 11, 2005, has not been funded. Instead, an incoherent program by the DEA has been ap- propriated over the years. ��� While education about the undertreatment of pain, prevalence of pain and increasing levels of comfort among physicians prescribing opioids has fueled increased prescriptions of opioids with par- allel growth in the unintentional consequences of misuse, abuse and deaths, the education of phy- sicians and the public with reference to deleteri- ous effects of opioids, non-opioid management of chronic pain, abuse and addiction, hasnot been implemented. ��� Majority of prescription controlled substances for nonmedical use are obtained for free from a friend or relative (60%), purchased from a friend or relative (8%), taken from a friend or relative without asking (4%) and from prescriptions from one doctor (17%). Consequently, a mounting revolution is essential to control this problem. Changes are needed not only in the healthcare system, but also justice, social service, and education. This review will focus on the problem of prescription drug abuse and relevance of the Na- tional Drug Control Policy and will discuss multiple facts and fallacies, along with proposed solutions. State of IllIcIt Drug uSe The 2005 National Survey on Drug Use and Health (NSDUH), an annual survey sponsored by the Sub- stance Abuse and Mental Health Services Administra- tion provided the following statistics about the state illicit drug use in the United States (6). The survey con- sidered current use of an illicit drug during the month prior to the survey interview. ��� In 2005, an estimated 19.7 million Americans aged 12 or older or 8.1% of the population were cur- rent illicit drug users. ��� Illicit drugs include marijuana/hashish, cocaine includ- ing crack, heroin, hallucinogens, inhalants, or prescrip- tion-type psychotherapeutics used nonmedically. ��� The rate of current illicit drug use in 2005 was slightly higher than the rate in 2004 (8.1% vs 7.9%), but similar to 2003 and 2002 (8.2% and 8.3%). ��� The rates of current illicit drug use among youths aged 12 to 17 in 2005 was 9.9% similar to the rate in 2004, but significantly lower than 2002 (11.6% in 2002, 11.2% in 2003, 10.6% in 2004). ��� There were no significant changes in past month use of any illicit drugs among adults aged 18 to 25 between 2004 and 2005, except for cocaine use which increased from 2.1% to 2.6%. ��� Marijuana was the most commonly used illicit drug with 14.6 million past month users with a 6% population. ��� The rates remained same as in 2004 (6.1%), 2003 (6.2%) and 2002 (6.2%). ��� The rate of current marijuana use among youths aged 12 to 17 declined from 7.6% in 2004 to 6.8% in 2005. ��� The current cocaine use was reported in 2.4 mil- lion Americans aged 12 and older or 1% of the population. ��� Current use of cocaine in 2005 was slightly higher than 2004 (1% vs 0.8%), however, was not statisti- cally significant. ��� The current use of hallucinogens was by 1.1 mil- lion or 0.4%. ��� This included 0.2% who had used ecstasy and the estimates were similar to the corresponding esti- mates for 2004. ��� The current use of methamphetamine (0.2%) and past year use of 0.5%, did not change between 2004 and 2005, but the lifetime rate changed in 2005. ��� Even though, the lifetime rate declined from 4.9% in 2002 to 4.3% in 2005, the number of metham- phetamine users who are dependent on or abused some illicit drug did rise significantly during this

www.painphysicianjournal.com 403 National Drug Control Policy and Prescription Drug Abuse period from 164,000 in 2002 to 257,000 in 2005. ��� There were 6.4 million (2.6%) persons who used prescription-type psychotherapeutic drugs non- medically in the past month. ��� The estimates were similar to the corresponding estimate for 2004. epIDemIc of NoN-meDIcal preScrIptIoN Drug abuSe The National Survey on Drug Use and Health (NS- DUH) of 2005 (6) provided rather startling statistics as shown in Table 2. The type of illicit drugs used in past year among persons aged 12 or older from 1995 to 2005 increased for nonmedical use of psychothera- peutic drugs and overall use of any illicit drug, but de- creased slightly for marijuana and cocaine (6). In 2005, there were 6.4 million or 2.6% of persons aged 12 or older who used prescription-type psycho- therapeutic drugs nonmedically in the past month. Of these 4.7 million used pain relievers, 1.8 million used tranquilizers, 1.1 million used stimulants including 512,000 using methamphetamine, and 272,000 used sedatives (Fig. 2). The current nonmedical use of pre- scription-type drugs among young adults aged 18 to 25 increased from 5.4% in 2002 to 6.3% in 2005 (6). The majority of the increase was seen in pain reliever use which was 4.1% in 2002 and 4.7% in 2003, 2004, and 2005. In a report of patterns and trends in nonmedi- cal prescription pain reliever use from 2002 to 2005 (50), NSDUH reported that nonmedical use of prescrip- tion pain relievers among persons aged 12 or older remained relatively stable between 2002 and 2005 (nonsignificant increases were seen), 4.8% of the population or 11.4 million persons used a prescription pain reliever nonmedically in the 12 months prior to the survey and 57.7% of persons who first used pain relievers nonmedically in the past year used hydroco- done products and 21.7% used oxycodone products. As shown in Figure 3, the highest use of pain re- lievers nonmedically was in the 18 to 25 age group with males more likely than females to have used a prescription type pain reliever nonmedically in the past year (5.2% vs 4.4%). However among youths aged 12 to 17, females were more likely than males to have used pain relievers nonmedically in the past year (7.9% vs 6.8%) whereas males aged 18 to 25 and males aged 26 to 34 at higher rates than their female counterparts. Among adults aged 35 to 49 and those aged 50 or older, males and females had similar rates Table 2. Types of illicit drug use in past year among persons aged 12 or older from 1995 to 2005 (numbers in thousands). Source: www.samhsa.gov 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 Non-medical use of Psychotherapeutic drugs 6,166 (2.9%) 6,652 (3.1%) 6,111 (2.8%) 5,759 (2.6%) 9,220 (4.2%) 8,761 (3.9%) 11,102 (4.9%) 14,680 (6.2%) 14,986 (6.3%) 14,643 (6.1%) 15,172 (6.2%) Marijuana 17,755 (8.4%) 18,398 (8.6%) 19,446 (9.0%) 18,710 (8.6%) 19,102 (8.6%) 18,589 (8.3%) 21,086 (9.3%) 25,755 (11.0%) 25,231 (10.6%) 25,451 (10.6%) 25,375 (10.4%) Cocaine 3,664 (1.7%) 4,033 (1.9%) 4,169 (1.9%) 3,811 (1.7%) 3,742 (1.7%) 3,328 (1.5%) 4,186 (1.9%) 5,902 (2.5%) 5,908 (2.5%) 5,658 (2.4) 5,523 (2.3%) Total or Any Illicit Drug usage 22,662 (10.7%) 23,182 (10.8%) 24,189 (11.2%) 23,115 (10.6%) 25,402 (11.5%) 24,535 (11.0%) 28,409 (12.6%) 35,132 (14.9%) 34,993 (14.7%) 34,807 (14.5%) 35,041 (14.4%) 0 1,000 2,000 3,000 4,000 5,000 6,000 7,000 All Prescription Drugs Past Month Users. Ages 12 and Older (Thousands) Pain Relievers Tranquilizers Stimulants Sedatives 6,405 4,658 1,817 1,062 272 Fig. 2. Pain relievers account for the largest portion of non- medical use of prescription drugs. Source: SAMHSA, 2005 National Survey on Drug Use and Health (Sept. 2006).