"Of the 70,237 drug overdose deaths in the United States in 2017, approximately two thirds (47,600) involved an opioid (1). In recent years, increases in opioid-involved overdose deaths have been driven primarily by deaths involving synthetic opioids other than methadone (hereafter referred to as synthetic opioids) (1). CDC analyzed changes in age-adjusted death rates from 2017 to 2018 involving all opioids and opioid subcategories* by demographic characteristics, county urbanization levels, U.S. Census region, and state. During 2018, a total of 67,367 drug overdose deaths occurred in the United States, a 4.1% decline from 2017; 46,802 (69.5%) involved an opioid (2). From 2017 to 2018, deaths involving all opioids, prescription opioids, and heroin decreased 2%, 13.5%, and 4.1%, respectively. However, deaths involving synthetic opioids increased 10%, likely driven by illicitly manufactured fentanyl (IMF), including fentanyl analogs (1,3)."

"For the top 15 drugs:

"• Among drug overdose deaths that mentioned at least one specific drug, oxycodone ranked first in 2011,heroin from 2012 through 2015, and fentanyl in 2016.

"• In 2011 and 2012, fentanyl was mentioned in approximately 1,600 drug overdose deaths each year, but mentions increased in 2013 (1,919 deaths),2014 (4,223 deaths), 2015 (8,251 deaths), and 2016(18,335 deaths). In 2016, 29% of all drug overdose deaths mentioned involvement of fentanyl.

"• The number of drug overdose deaths involving heroin increased threefold, from 4,571 deaths or 11% of all drug overdose deaths in 2011 to 15,961 deaths or 25% of all drug overdose deaths in 2016.

"• Throughout the study period, cocaine ranked second or third among the top 15 drugs. From 2014 through 2016, the number of drug overdose deaths involving cocaine nearly doubled from 5,892 to 11,316.

"• The number of drug overdose deaths involving methamphetamine increased 3.6-fold, from 1,887 deaths in 2011 to 6,762 deaths in 2016.

"• The number of drug overdose deaths involving methadone decreased from 4,545 deaths in 2011 to 3,493 deaths in 2016."

According to the Centers for Disease Control, using data available for analysis on September 5, 2018, there were a reported 70,652 deaths attributed to drug overdose in the US for the year ending December 2017. Some deaths were still under investigation. The CDC projects that the total for 2017 will be 72,222.

Of these:
Opioids were detected in 47,863 reported deaths, and are predicted to be involved in 49,031 deaths.
Synthetic opioids, excluding methadone, were detected in 28,644 reported deaths, and are predicted to be involved in 28,644 deaths.
Heroin was detected in 15,585 reported deaths, and is predicted to be involved in 15,941 deaths.
Natural and semi-synthetic opioids were detected in 14,553 reported deaths, and are predicted to be involved in 14,940 deaths.
Cocaine was detected in 14,065 reported deaths, and is predicted to be involved in 14,612 deaths.
Psychostimulants with abuse potential were detected in 10,420 reported deaths, and are predicted to be involved in 10,703 deaths.
Methadone was detected in 3,209 reported deaths, and is predicted to be involved in 3,286 deaths.

Note: Categories are not mutually exclusive because deaths may involve more than one drug.

"Multiple studies that have examined why some persons who abuse prescription opioids initiate heroin use indicate that the cost and availability of heroin were primary factors in this process. These reasons were generally consistent across time periods from the late 1990s through 2013.^34-41 Some interviewees made reference to doctors generally being less willing to prescribe opioids as well as to increased attention to the issue by law enforcement, which may have affected the available supply of opioids locally.^38,40"

"First, factors related to death investigation might affect rate estimates involving specific drugs. At autopsy, the substances tested for, and circumstances under which tests are performed to determine which drugs are present, might vary by jurisdiction and over time. Second, the percentage of deaths with specific drugs identified on the death certificate varies by jurisdiction and over time. Nationally, 19% (in 2014) and 17% (in 2015) of drug overdose death certificates did not include the specific types of drugs involved. Additionally, the percentage of drug overdose deaths with specific drugs identified on the death certificate varies widely by state, ranging from 47.4% to 99%. Variations in reporting across states prevent comparison of rates between states. Third, improvements in testing and reporting of specific drugs might have contributed to some observed increases in opioid-involved death rates. Fourth, because heroin and morphine are metabolized similarly (9), some heroin deaths might have been misclassified as morphine deaths, resulting in underreporting of heroin deaths. Finally the state-specific analyses of opioid deaths are restricted to 28 states, limiting generalizability."

"Pain is a significant public health problem. Chronic pain alone affects approximately 100 million U.S. adults. Pain reduces quality of life, affects specific population groups disparately, costs society at least $560-635 billion annually (an amount equal to about $2,000 for everyone living in the United States), and can be appropriately addressed through population health-level interventions."

"There has been a significant increase in cancer patients and survivors being unable to access their opioid prescriptions since 2016, when the Centers for Disease Control and Prevention (CDC) finalized opioid prescribing guidelines."

Percent of cancer patients and survivors who report being unable to get opioid prescription pain medication because the pharmacy did not have the particular drug in stock:
December 2016: 16%
May 2018: 41%

Percent of cancer patients and survivors who report being questioned by a pharmacist about why they needed their opioid pain medication:
December 2016: 16%
May 2018: 35%

Percent of cancer patients and survivors who report being unable to get their prescription pain medication because the pharmacist would not fill it for whatever reason even though the pharmacist had it in stock?
December 2016: 12%
May 2018: 27%

Percent of cancer patients and survivors who report being unable to get their opioid prescription pain medication because their insurance would not cover it:
December 2016: 11%
May 2018: 30%

Percent of cancer patients and survivors who report that their insurance company has limited them to just one pharmacy to go to for filling their opioid prescription pain medication.
December 2016: 14%
May 2018: 32%

Percent of cancer patients and survivors who report that their insurance company has reduced the number of times their opioid prescription can be refilled:
December 2016: 21%
May 2018: 36%

Percent of cancer patients and survivors who report that their insurance company has reduced the number of pills in their opioid prescription pain medication:
December 2016: 19%
May 2018: 25%

"According to the Medical Expenditure Panel Survey, the annual share of US adults who were prescribed opioids decreased from 12.9 percent in 2014 to 10.3 percent in 2016, and the decrease was concentrated among adults with shorter-term rather than longer-term prescriptions. The decrease was also larger for adults who reported moderate or more severe pain (from 32.8 percent to 25.5 percent) than for those who reported lessthan-moderate pain (from 8.0 percent to 6.6 percent). In the same period opioids were prescribed to 3.75 million fewer adults reporting moderate or more severe pain and 2.20 million fewer adults reporting less-thanmoderate pain. Because the decline in prescribing primarily involved adults who reported moderate or more severe pain, these trends raise questions about whether efforts to decrease opioid prescribing have successfully focused on adults who report less severe pain."

"A growing number of restrictions on opioid prescribing are already impacting these patient populations."

According to a survey conducted for the American Cancer Society Cancer Action Network and the Patient Quality of Life Coalition:

Patients answering yes to "Has your doctor indicated his or her treatment options for your pain were limited by laws, guidelines, or your insurance coverage?"
Patients Being Treated For Cancer: 48%
Patients Being Treated For Chronic Pain: 40%
Patients Being Treated For Other Serious Illnesses: 56%

Patients answering yes to "Has your insurance company or pharmacy required you to only have opioid prescriptions from one doctor?"
Patients Being Treated For Cancer: 36%
Patients Being Treated For Chronic Pain: 25%
Patients Being Treated For Other Serious Illnesses: 26%

Patients answering yes to "Has your doctor refused to give you a prescription for an opioid plan medication?"
Patients Being Treated For Cancer: 35%
Patients Being Treated For Chronic Pain: 25%
Patients Being Treated For Other Serious Illnesses: 36%

Patients answering yes to "Has the pharmacist give you only part of your opioid prescription (for example: for 7 days instead of 30 days the prescription was written), and told you to call your doctor for a new prescription if you need more?"
Patients Being Treated For Cancer: 31%
Patients Being Treated For Chronic Pain: 18%
Patients Being Treated For Other Serious Illnesses: 21%

Patients answering yes to "Have you been unable to get your opioid prescription pain medication because the pharmacist or pharmacy sent you home without your prescription because they had to contact your doctor before filling the prescription?"
Patients Being Treated For Cancer: 26%
Patients Being Treated For Chronic Pain: 30%
Patients Being Treated For Other Serious Illnesses: 22%

Patients answering yes to "Has the pharmacist given you only part of your opioid prescription (for example: for 7 days instead of 30 days the prescription had been written), and told you to come back if you need more?"
Patients Being Treated For Cancer: 25%
Patients Being Treated For Chronic Pain: 26%
Patients Being Treated For Other Serious Illnesses: 26%

Patients answering yes to "Has your doctor or pharmacist told you that you have been flagged in their system as a potential opioid abuser?"
Patients Being Treated For Cancer: 21%
Patients Being Treated For Chronic Pain: 14%
Patients Being Treated For Other Serious Illnesses: 11%

"In 2016, an estimated 6.2 million Americans aged 12 or older misused psychotherapeutic drugs at least once in the past month, which represent 2.3 percent of the population aged 12 or older (Figures 18 and 19). Of the four categories of prescription drugs that are presented in this report, prescription pain relievers were the most commonly misused by people aged 12 or older. The 6.2 million people aged 12 or older who misused prescription psychotherapeutic drugs in the past month included 3.3 million who misused prescription pain relievers in that period. Approximately 2.0 million people aged 12 or older misused prescription tranquilizers in the past month. An estimated 1.7 million people aged 12 or older misused prescription stimulants, and 497,000 (0.5 million) misused prescription sedatives in the past month.

"An estimated 389,000 adolescents aged 12 to 17 misused psychotherapeutic drugs at least once in the past month, which rounds to the estimate of 0.4 million adolescents shown in Figure 19. Stated another way, about 1 in 60 adolescents (1.6 percent) were current misusers of psychotherapeutic drugs. An estimated 1.6 million young adults aged 18 to 25 were current misusers of psychotherapeutic drugs, which corresponds to 4.6 percent of young adults. There were 4.2 million adults aged 26 or older who were current misusers of psychotherapeutic drugs, or 2.0 percent of adults in this age group."

"It is well-documented that unrelieved pain continues to be a serious public health problem for the general population in the United States.^1-8 This issue is particularly salient for children,^9-14 the elderly,^15-19 people of racial and ethnic subgroups,^20-24 people with developmental disabilities,^25;26 people in the military or military veterans^27-30 as well as for those with diseases such as cancer,^31-36 HIV/AIDS,^37-40 or sickle-cell disease.^41-43 Clinical experience has demonstrated that adequate pain management leads to enhanced functioning and quality of life, while uncontrolled severe pain contributes to disability and despair.^4;44"

"Opioid analgesics are useful in managing acute and chronic pain. They are sometimes underused in patients with severe acute pain or with pain and a terminal disorder such as cancer, resulting in needless pain and suffering. Reasons for undertreatment include
"• Underestimation of the effective dose
"• Overestimation of the risk of adverse effects
"Generally, opioids should not be withheld when treating acute, severe pain; however, simultaneous treatment of the condition causing the pain usually limits the duration of severe pain and the need for opioids to a few days or less. Also, opioids should generally not be withheld when treating cancer pain; in such cases, adverse effects can be prevented or managed, and addiction is less of a concern.
"In patients with chronic noncancer pain, nonopioid therapy should be tried first (see Chronic Pain : Treatment). Opioids should be used when the benefit of pain reduction outweighs the risk of adverse effects and of drug misuse. If nonopioid therapy has been unsuccessful, opioid therapy should be considered. In such cases, obtaining informed consent may help clarify the goals, expectations, and risks of treatment and facilitate education and counseling about misuse. Patients receiving chronic (> 3 mo) opioid therapy should be regularly assessed for pain control, adverse effects, and signs of misuse. If patients have persistent severe pain despite increasing opioid doses, do not adhere to the terms of treatment, or have deteriorating physical or mental function, opioid therapy should be tapered and stopped.
"Physical dependence (development of withdrawal symptoms when a drug is stopped) should be assumed to exist in all patients treated with opioids for more than a few days. Thus, opioids should be used as briefly as possible, and in dependent patients, the dose should be tapered to control withdrawal symptoms when opioids are no longer necessary. Patients with pain due to an acute, transient disorder (eg, fracture, burn, surgical procedure) should be switched to a nonopioid drug as soon as possible. Dependence is distinct from addiction, which, although it does not have a universally accepted definition, typically involves compulsive use and overwhelming involvement with the drug including craving, loss of control over use, and use despite harm."

"Because opioid analgesics have both a medical indication and an abuse liability, their prescribing, dispensing, and administration, indeed their very availability in commerce, is governed by a combination of policies, including international treaties and U.S. federal and state laws and regulations. The main purpose of these policies is drug control: to prevent diversion and abuse of prescription medications. However, international and federal policies also express clearly a second purpose of drug control, that being availability: recognizing that many opioids (referred to in law as narcotic drugs or controlled substances) are necessary for pain relief and that governments must ensure their adequate availability for medical and scientific purposes. When both control and availability are appropriately recognized in public policy, and implemented in everyday practice, this is referred to as a balanced approach (American Medical Association?Department of Substance Abuse, 1990; Cooper, Czechowicz, Petersen, & Molinari, 1992; Drug Enforcement Administration et al., 2001; Fishman, 2012; Gilson, 2010a; Gilson, Joranson, Maurer, Ryan, & Garthwaite, 2005; Joranson & Dahl, 1989; Office of National Drug Control Policy, 2011; Woodcock, 2009; World Health Organization, 2011a)."

"Mild to moderate acute pain is often relieved by physical interventions—such as the application of ice, transcutaneous electrical nerve stimulation (TENS), massage or stretching, and/or bracing—along with a mild analgesic such as an NSAID or acetaminophen. More severe pain often requires opioid therapy, which will be discussed in depth below. When appropriately skilled clinicians are available in a system that is comfortable supporting such treatments, nerve blocks or spinal infusions can sometimes control more severe acute pain. Examples of common acute pain procedures are rib blocks for rib fractures or thoracic incisions; epidural infusions for thoracic, abdominal, or lower body surgery or trauma; and brachial plexus infusions for upper extremity postsurgical or trauma-related pain.
"Clinicians should generally not let concerns about addiction deter them from using opioids that are needed for severe acute pain. Carefully supervised short-term use of opioids in the context of time-limited treatment of such pain has not been documented to affect the long-term course of addictive disorders. Rather, inadequate pain control and treatment that frustrates, stresses, or confuses patients may lead to relapse (Wasan et al., 2006)."

"A number of barriers to effective pain care involve the attitudes and training of the providers of care. First, health professionals may hold negative attitudes toward people reporting pain and may regard pain as not worth their serious attention. As discussed in detail in Chapter 2, patients can be at a particular disadvantage if they are members of racial or ethnic minorities, female, children, or infirm elderly. They also may have less access to care if they are perceived as drug seeking or if they have, or are perceived to have, mental health problems. A literature review showed that people with pain, especially women, often have attitudes and goals that are different from, and sometimes opposed to, the attitudes and goals of their practitioners; patients seek to have their pain legitimized, while practitioners focus on diagnosis and therapy (Frantsve and Kerns, 2007). Consumers testified before the committee that patients often believe practitioners trivialize pain, which makes them feel even worse. Researchers working with patient focus groups have noted the 'perceived failures of providers to fully respect, trust, and accept the patient, to offer positive feedback and support, and to believe the participants’ reports of the severity and adverse effects of their pain' (Upshur et al., 2010, p. 1793)."

"The research findings noted above need to be set against the testimony of people with pain, many of whom derive substantial relief from opioid drugs. This tension perhaps reflects the complex nature of pain as a lived experience, as well as the need for biopsychosocial assessments and treatment strategies that can maximize patients’ comfort and minimize risks to them and society. Regardless, the majority of people with pain use their prescription drugs properly, are not a source of misuse, and should not be stigmatized or denied access because of the misdeeds or carelessness of others."

"In our study, there was greater evidence for an association between substance use and chronic pain among inpatients than among MMTP [Methadone Maintenance Treatment Program] patients. Among inpatients, there were significant bivariate relationships between chronic pain and pain as a reason for first using drugs, multiple drug use, and drug craving. In the multivariate analysis, only drug craving remained significantly associated with chronic pain. Not surprisingly, inpatients with pain were significantly more likely than those without pain to attribute the use of alcohol and other illicit drugs, such as cocaine and marijuana, to a need for pain control. These results suggest that chronic pain contributes to illicit drug use behavior among persons who were recently using alcohol and/or cocaine. Inpatients with chronic pain visited physicians and received legitimate pain medications no more frequently than those without pain, raising the possibility that undertreatment or inability to access appropriate medical care may be a factor in the decision to use illicit drugs for pain."

"Opioid medications present some risk of abuse by patients as well. A structured review of 67 studies found that 3 percent of chronic noncancer pain patients regularly taking opioids developed opioid abuse or addiction, while 12 percent developed aberrant drug-related behavior (Fishbain et al., 2008). A recent analysis revealed that half of patients who received a prescription for opioids in 2009 had filled another opioid prescription within the previous 30 days, indicating that they were seeking and obtaining more opioids than prescribed by any single physician (NIH and NIDA, 2011)."

"Prescribers wrote 82.5 OPR [Opioid Pain Reliever] prescriptions and 37.6 benzodiazepine prescriptions per 100 persons in the United States in 2012 (Table). LA/ER [Long-Acting or Extended Release] OPR accounted for 12.5%, and high-dose OPR accounted for 5.1% of the estimated 258.9 million OPR prescriptions written nationwide. Prescribing rates varied widely by state for all drug types. For all OPR combined, the prescribing rate in Alabama was 2.7 times the rate in Hawaii."

"Undertreatment of pain among African Americans has been well documented. For example, children with sickle-cell anemia (a painful disease that occurs most often among African Americans) who presented to hospital emergency departments (EDs) with pain were far less likely to have their pain assessed than were children with long-bone fractures (Zempsky et al., 2011).
"In general, moreover, a number of studies have shown that physicians tend to prescribe less analgesic medication for African Americans than for whites (Bernabei et al., 1998; Edwards et al., 2001; Green and Hart-Johnson, 2010). A study that used a pain management index to evaluate pain control found that blacks were less likely than whites to obtain prescriptions for adequate pain relief, based on reported pain severity and the strength of analgesics provided. Because such an index is a way to quantify a person’s response to pain medication alone, it is likely that people in this study did not receive other types of treatment for pain either."

"Migraine headaches are a major public health problem affecting more than 28 million persons in this country.¹ Nearly 25 percent of women and 9 percent of men experience disabling migraines.^2,3 The impact of these headaches on patients and their families is tremendous, with many patients reporting frequent and significant disability.⁴ The economic burden of migraine headaches in the United States is also tremendous. Persons with migraines lose an average of four to six work days each year, with an annual total loss nationwide of 64 to 150 million work days. The estimated direct and indirect costs of migraine approach $17 billion.^5,6 Despite the prevalence of migraines and the availability of multiple treatment options, this condition is often undiagnosed and untreated.⁷ About one half of patients stop seeking medical care for their migraines, in part because of dissatisfaction with the therapy they have received.⁴"

"Costly team care, expensive medications, and procedural interventions—all common types of treatment for pain—are not readily obtained by the 19 percent of Americans under age 65 who lack health insurance coverage (Holahan, 2011) or by the additional 14 percent of under-65 adults who are underinsured (Schoen et al., 2008). Together, these groups make up one-third of the nation’s population. Lack of insurance coverage also may contribute to disparities in care. An inability to pay for pain care is especially prevalent among minorities and women (Green et al., 2011). As discussed above, even for people with insurance coverage, third-party reimbursement systems tend not to cover or to cover well psychosocial services and team approaches that represent the best care for people with the most difficult pain problems. Surmounting this barrier may require coordinated action by advocates for improvement."

"Adequate pain treatment and follow-up may be thwarted by a mix of uncertain diagnosis and the societal stigma that is applied, consciously or unconsciously, to people reporting pain, particularly if they do not respond readily to treatment. Questions and reservations may cloud perceptions of clinicians, family, employers, and others: Is he really in pain? Is she drug seeking? Is he just malingering? Is she just trying to get disability payments? Certainly, there is some number of patients who attempt to 'game the system' to obtain drugs or disability payments, but data and studies to back up these suspicions are few. The committee members are not naïve about this possibility, but believe it is far smaller than the likelihood that someone with pain will receive inadequate care. Religious or moral judgments may come into play: Mankind is destined to suffer; giving in to pain is a sign of weakness. Popular culture, too, is full of dismissive memes regarding pain: Suck it up; No pain, no gain."

"Mixed results were noted for prescription opioids, with increases in indicators for prescription opioids as a key finding reported by representatives in two areas—New York City and San Francisco—based on treatment admissions data (primary treatment admissions for opioids/opiates other than heroin increased in 2012 from 2011 in New York City), numbers of prescriptions (the Prescription Drug Monitoring Programs in both New York City and San Francisco showed increases in numbers of prescriptions in 2012), death data (unintentional opioid analgesic poisoning deaths increased in New York City by 65 percent from 2005 to 2011), and ED visit data (visits involving prescription opioids/other opiates increased in New York City from 2010 to 2011 and in San Francisco from 2004 to 2011). A decline in indicators for prescription opioids/opiates other than heroin was reported as a key finding in three other CEWG areas—Maine, Seattle, and South Florida/Miami-Dade and Broward Counties. Deaths related to prescription opioids/opiates other than heroin declined from 2011 to 2012 in Seattle and both Miami-Dade and Broward Counties in South Florida. Treatment admissions and drug reports among drug items seized and analyzed in NFLIS laboratories declined in 2012 from 2011 in the two South Florida counties. Arrests showed decreases in Maine from 2011 to 2012, and reported use of prescription-type opiates in the last month to 'get high' among high school students decreased significantly from 2010 to 2012 in the Seattle area."

"Objective: To examine the effect on the trade in opioids through online illicit markets (“cryptomarkets”) of the US Drug Enforcement Administration’s ruling in 2014 to reschedule hydrocodone combination products.

"Design: Interrupted time series analysis.

"Setting: 31 of the world’s largest cryptomarkets operating from October 2013 to July 2016.

"Main outcome measures: The proportion of total transactions, advertised and active listings for prescription opioids, prescription sedatives, prescription steroids, prescription stimulants, and illicit opioids, and the composition of the prescription opioid market between the US and elsewhere.

"Results: The sale of prescription opioids through US cryptomarkets increased after the schedule change, with no statistically significant changes in sales of prescription sedatives, prescription steroids, prescription stimulants, or illicit opioids. In July 2016 sales of opioids through US cryptomarkets represented 13.7% of all drug sales (95% confidence interval 11.5% to 16.0%) compared with a modelled estimate of 6.7% of all sales (3.7% to 9.6%) had the new schedule not been introduced. This corresponds to a 4 percentage point yearly increase in the amount of trade that prescription opioids represent in the US market, set against no corresponding changes for comparable products or for prescription opioids sold outside the US. This change was first observed for sales, and later observed for product availability. There was also a change in the composition of the prescription opioid market: fentanyl was the least purchased product during July to September 2014, then the second most frequently purchased by July 2016.

"Conclusions: The scheduling change in hydrocodone combination products coincided with a statistically significant, sustained increase in illicit trading of opioids through online US cryptomarkets. These changes were not observed for other drug groups or in other countries. A subsequent move was observed towards the purchase of more potent forms of prescription opioids, particularly oxycodone and fentanyl."

"• Naloxone access laws that ease restrictions on naloxone possession and distribution are associated with a 20% reduction overdose deaths among African-Americans.
"• Good Samaritan laws, providing immunity from prosecution for those calling emergency services, are associated with broad reductions in overdose deaths, reducing overdose deaths by 13% overall.
"• None of these harm reduction measures result in increase in opioid or heroin use.
"• These laws are effective at reducing overdose mortality without creating additional opioid use. Correspondingly, these measures should be considered an important part of the strategy used to address the opioid epidemic."

"When observed within approximately 1 to 12 months after heroin onset, an estimated 23% to 38% of new heroin users have become dependent on heroin. Rank-order correlation and post hoc exploratory analyses prompt a hypothesis of recently increased odds of becoming dependent on heroin.

"Seeking estimates for comparison, we found 3 published studies on how often heroin dependence was found among people who have used heroin at least once in their lifetime. The National Comorbidity Survey (1990-1992) estimate was 23% dependence rate (with a standard error [SE] of 5%); National Epidemiologic Survey on Alcohol and Related Conditions (2001-2002) estimate (SE) was 28% (4%); and National Epidemiologic Survey on Alcohol and Related Conditions-III (2012-2013) estimate (SE) was 25% (2%).^4,6 These 3 values yield a random-effects meta-analysis summary of 26%, with a 95% CI of 22% to 29%, which clearly overlaps this study’s overall finding of 23% to 38% of all participants becoming heroin dependent soon after first heroin use."

"Of the 1,000,453 opioid recipients (81.7%) with at least 6 months of follow-up, 51.1% were female, and the median age was 17 years (interquartile range, 16-18 years). Among these adolescents, the estimated cumulative incidence of LTOT [Long Term Opioid Therapy] after first opioid receipt was 1.1 (95% CI, 1.1-1.2) per 1000 recipients within 1 year, 3.0 (95% CI, 2.8-3.1) per 1000 recipients within 3 years, 8.2 (95% CI, 7.8-8.6) per 1000 recipients within 6 years, and 16.1 (95% CI, 14.2-18.0) per 1000 recipients within 10 years. The prevalence of mental health conditions and treatments in this sample is shown in eTable 3 in the Supplement.

"All mental health conditions and treatments were associated with higher rates of transitioning from a first opioid prescription to long-term therapy. Table 2 provides the estimated incidence of LTOT among those with and without mental health conditions and treatments.Adjusted relative increases in the rate of LTOT ranged from a factor of 1.73 for ADHD [Attention-Deficit/Hyperactivity Disorder] (hazard ratio [HR], 1.73; 95% CI, 1.54-1.95) to approximately 4-fold for benzodiazepines (HR, 3.88; 95%CI, 3.39-4.45) and nonopioid SUDs [Substance Use Disorders] (HR, 4.02;95%CI, 3.48-4.65) to 6-fold for non benzodiazepine hypnotics (HR, 6.15; 95%CI, 5.01-7.55) and to nearly 9-fold for OUD [Opioid Use Disorder] (HR, 8.90; 95%CI, 5.85-13.54). In addition, relative to no condition, the number of condition types was also associated with higher LTOT rates (1 condition: HR, 2.21; 95% CI, 2.01-2.43; 2 or more conditions: HR, 4.01; 95% CI, 3.62-4.46).

"Given the strong associations for OUD, we explored other mental health factors and opioid receipt among those with preexisting OUD. These adolescents were more likely than
adolescents without OUD to have other mental health conditions and treatments (eTable 4 in the Supplement). For example, 76.1% of adolescents with OUD had other SUDs, 61.0% had depressive disorders, and 52.6% had received an SSRI [Selective Serotonin Reuptake Inhibitor]. During follow-up, those with preexisting OUD received opioid drugs similar to those received by adolescents without OUD, although the former were more likely to receive certain opioids (eg, oxycodone and tramadol; eTable 5 in the Supplement). Of those with preexisting OUD, 15.5% filled a prescription for OUD medication treatment during follow-up."

"The opioid epidemic is a public health crisis that is at least partially driven by harms associated with POM [Prescription Opioid Medication] use. States are passing laws allowing use of MC [Medical Cannabis] and patients are using MC, but currently there is little understanding of how this influences POM use or of MC-related harms. This literature review provides preliminary evidence that states with MC laws have experienced reported decreases in POM use, abuse, overdose, and costs. However, existing evidence is limited by significant methodological shortcomings; so, general conclusions are difficult to draw.

"The use of MC as an alternative to POMs for pain management warrants additional empirical attention as a potential harm reduction strategy. NASEM (2017) recommends more clinical trials to elucidate appropriate MC forms, routes of administration, and combination of products for treating pain, but access to MC products to fully evaluate these questions is challenging due to federal regulations. However, the recently funded National Institutes of Health longitudinal study to research the impacts of MC on opioid use is a critical step in the right direction (National Institute of Health, 2017, Williams, 2017). MCs potential as an alternative pain treatment modality to help mitigate the major public health opioid crisis, could be a missed opportunity if data on safety, efficacy, and outcomes are not collected and explored. Health care practitioners, particularly nurses who are charged with ensuring patient comfort, have a vested interest in providing viable alternatives to POMs when appropriate, as part of an integrative approach to pain management, and must advocate for more research to better understand the public health implications and risks and benefits of such alternatives."

"DEA has increased enforcement efforts to prevent abuse and diversion of OxyContin. From fiscal year 1996 through fiscal year 2002, DEA initiated 313 investigations involving OxyContin, resulting in 401 arrests. Most of the investigations and arrests occurred after the initiation of the action plan. Since the plan was enacted, DEA initiated 257 investigations and made 302 arrests in fiscal years 2001 and 2002. Among those arrested were several physicians and pharmacists. Fifteen health care professionals either voluntarily surrendered their controlled substance registrations or were immediately suspended from registration by DEA. In addition, DEA reported that $1,077,500 in fines was assessed and $742,678 in cash was seized by law enforcement agencies in OxyContin-related cases in 2001 and 2002."

"Neuropathic pain (NP) is defined as pain caused by a lesion or disease of the central or peripheral somatosensory nervous system.[1] NP affects between 5% and 10% of the US population [2] and examples include diabetic neuropathy, complex regional pain syndrome, radiculopathy, phantom limb pain, HIV sensory neuropathy, multiple sclerosis-related pain, and poststroke pain.[3]"

Researchers used data from the American Productivity Audit to measure lost productivity in the US due to common pain conditions. In an article published in the Journal of the American Medical Association in 2003, they reported that "Overall, the estimated $61.2 billion per year in pain-related lost productive time in our study accounts for 27% of the total estimated work-related cost of pain conditions in the US workforce."

"Our estimate of $61.2 billion per year in pain-related lost productive time does not include costs from⁴ other causes. First, we did not include lost productive time costs associated with dental pain, cancer pain, gastrointestinal pain, neuropathy, or pain associated with menstruation. Second, we do not account for pain-induced disability that leads to continuous absence of 1 week or more. Third, we did not consider secondary costs from other factors such as the hiring and training of replacement workers or the institutional effect among coworkers. Taking these other factors into consideration could increase, decrease, or have no net effect on health-related lost productive time cost estimates. Fourth, we may be prone to underestimating current lost productive time among those with persistent pain problems (eg, chronic daily headache). To the extent that these workers remain employed,they may adjust both their performance and perception of their performance over time. The latter, a form of perceptual accommodation, makes it difficult to accurately ascertain the impact of a chronic pain condition on work in the recent past through self-report."

"An important message from epidemiologic studies cited by Blyth and colleagues (2010) is 'the universal presence across populations of characteristic subgroups of people with an underlying propensity or increased risk for chronic pain, in the context of a wide range of different precipitating or underlying diseases and injuries' (p. 282). These vulnerable subgroups are most often those of concern to public health.⁵ Increased vulnerability to pain is associated with the following:
"• having English as a second language,
"• race and ethnicity,
"• income and education,
"• sex and gender,
"• age group,
"• geographic location,
"• military veterans,
"• cognitive impairments,
"• surgical patients,
"• cancer patients, and
"• the end of life.
"Many of these same groups also are at risk of inadequate treatment."

"• Among persons aged 12 or older in 2011-2012 who used pain relievers nonmedically in the past year, 54.0 percent got the pain relievers they most recently used from a friend or relative for free (Figure 2.16). Nearly 1 in 5 (19.7 percent) received them through a prescription from one doctor (which was higher than the 17.3 percent in 2009-2010). Another 10.9 percent bought them from a friend or relative. In addition, 4.0 percent of these nonmedical users in 2011-2012 took pain relievers from a friend or relative without asking. An annual average of 4.3 percent got pain relievers from a drug dealer or other stranger; 1.8 percent got pain relievers from more than one doctor; 0.8 percent stole pain relievers from a doctor's office, clinic, hospital, or pharmacy (which was higher than the 0.2 percent in 2009-2010); and 0.2 percent bought the pain relievers on the Internet.
"• Among persons aged 12 or older in 2011-2012 who used pain relievers nonmedically in the past year and indicated that they most recently obtained the drugs from a friend or relative for free, 82.2 percent of the friends or relatives obtained the drugs from just one doctor (Figure 2.16). About 1 in 20 of these past year nonmedical users of pain relievers (5.4 percent) reported that the friend or relative got the pain relievers from another friend or relative for free, 4.1 percent reported that the friend or relative bought the pain relievers from a friend or relative, 1.4 percent reported that the friend or relative bought the pain relievers from a drug dealer or other stranger (which was lower than the 2.3 percent in 2009-2010), 1.3 percent reported that the friend or relative took the pain relievers from another friend or relative without asking, and 0.2 percent reported that the friend or relative bought the pain relievers on the Internet."

"Disparities in pain assessment and treatment on the basis of race and ethnicity are well documented.²⁹ Diminished ability to obtain access to opioid analgesics in local pharmacies is a significant barrier to quality pain care. The present investigation provides evidence that Michigan pharmacies in predominantly minority areas were significantly less likely to have sufficient prescription opioid analgesic supplies when compared with predominantly white areas. Regardless of median income and median age, significant differences were found in opioid analgesic availability on the basis of ethnic composition. These results support the findings of Morrison et al³⁸ that pharmacies in predominantly minority neighborhoods stock insufficient opioid analgesic supplies more so than those in predominantly white neighborhoods. However, these results also extend their findings by demonstrating the role of both social class and income on opioid analgesic availability. More specifically, the odds for not having sufficient opioid analgesic supplies are significantly higher among pharmacies in low income areas when compared with higher income areas, regardless of race. More importantly, we identified that the odds of having insufficient supplies in minority neighborhoods changed significantly on the basis of income (ie, high or low) (OR, 13.36 vs 54.42). Thus, social class and poverty seem to play a role for whites more so than minorities. Noncorporate pharmacies were also more likely to have sufficient opioid analgesic supplies than corporate pharmacies. These results suggest that if an opioid analgesic is prescribed for pain management, persons living in minority zip codes (even in higher income areas) or those living in low income zip codes (regardless of minority status) face additional barriers to quality pain care. Thus, vulnerable populations (eg, minorities and low income individuals) are at increased risk for inefficient and lesser quality pain care."

"We applied our composite probability distribution to each patient to calculate the probability that the patient was a member of the 'extreme' group. That is, we multiplied the size of each stratum of patients by its posterior probability of population 3 membership to estimate the total number of probable shoppers in the United States. Summing these probabilities, we estimated that of the 19 million patients in the US who purchased opioids in the first 60 days of 2008, 135,000 (0.7%) were members of this extreme population (Table 2).
"Although only a small fraction of active patients, members of this extreme population obtained an estimated 1.9% (4.3 million) of all 223 million opioid prescriptions dispensed during 2008, and 2.8% of all oxycodone prescriptions (Table 3). They purchased an average of 32 opioid prescriptions that year. When we accounted for the quantity of drugs prescribed, their share of the market was even larger: an estimated 4.0% of the total amounts of these drugs dispensed that year, or about 11.1 million grams. This was equivalent to approximately 5.4 million grams of morphine. This would have provided an average of 109 morphine equivalent milligrams per patient in this extreme group for every day in 2008."

"We determined per capita need of strong opioids for pain related to three important pain causes for 188 countries. These needs were extrapolated to the needs for all the various types of pain by using an adequacy level derived from the top 20 countries in the Human Development Index. By comparing with the actual consumption levels for relevant strong opioid analgesics, we were able to estimate the level of adequacy of opioid consumption for each country. Good access to pain management is rather the exception than the rule: 5.5 billion people (83% of the world’s population) live in countries with low to nonexistent access, 250 million (4%) have moderate access, and only 460 million people (7%) have adequate access. Insufficient data are available for 430 million (7%). The consumption of opioid analgesics is inadequate to provide sufficient pain relief around the world. Only the populations of some industrialized countries have good access."

"Opioid medications are essential not only for drug dependence treatment but also for pain management. WHO estimates that 5 billion people live in countries with little or no access to controlled medicines that are used to treat moderate to severe pain.⁹⁰ Up to 80% of the estimated 1 million patients in the end stages of AIDS are in great pain, but very few have access to pain relieving drugs⁹¹ because of insufficient knowledge among physicians, inadequate health systems, fears of addiction, antiquated laws, and unduly strict regulations.⁹²"

"The societal impact of CPD [controlled prescription drugs] diversion and abuse is considerable. Violent and property crime associated with CPD diversion and abuse has increased in all regions of the United States over the past 5 years, according to the National Drug Intelligence Center (NDIC) National Drug Threat Survey (NDTS). However, the association between crime and CPD diversion is reported much less frequently than the association between crime and illicit drugs. Increases in crime rates often result in higher budgetary expenditures for additional law enforcement resources. Moreover, the estimated cost of CPD diversion and abuse to public and private medical insurers is $72.5 billion a year,³ much of which is passed to consumers through higher health insurance premiums. Additionally, the abuse of prescription opioids is burdening the budgets of substance abuse treatment providers, particularly as prescription opioid abuse might be fueling heroin abuse rates in some areas of the United States."

According to a survey conducted by Roper Starch Worldwide for the American Pain Society in 1999, "Chronic pain as defined by this study is a severe and ever present problem. It can be as much of a problem to middle age adults as seniors and is one women are more likely to face than men. The majority of chronic pain sufferers have been living with their pain for over 5 years. Although the more common type is pain that flares up frequently versus being constant, it is still present on average almost 6 days in a typical week.
"About one third of all chronic sufferers describe their pain as being almost the worst pain one can possibly imagine. Their pain is more likely to be constant than flaring up frequently and two-thirds of them have been living with it for over 5 years."

According to a public opinion poll released in 1999, "It is estimated that 9% of the U.S. adult population suffer from moderate to severe non-cancer related chronic pain."

Nonmedical Use of Prescription Drugs

"In 2014, the estimate of 6.5 million Americans aged 12 or older who were current nonmedical users of psychotherapeutic drugs represents 2.5 percent of the population aged 12 or older (Figures 1 and 4). The 2014 estimate for current nonmedical use of psychotherapeutic drugs among people aged 12 or older was slightly lower than the estimates in 2006, 2007, 2009, and 2010 (ranging from 2.7 to 2.9 percent), and it was similar to the estimates in the other years between 2002 and 2013.¹⁹"

"• Nonmedical use of psychotherapeutics includes nonmedical use of any prescription-type pain relievers, tranquilizers, stimulants, or sedatives. Over-the-counter substances are not included. In 2013, there were approximately 2.0 million persons aged 12 or older who used psychotherapeutics nonmedically for the first time within the past year, which averages to about 5,500 initiates per day. The number of new nonmedical users of psychotherapeutics in 2013 was lower than the estimates for prior years from 2002 through 2012 (ranging from 2.3 million to 2.8 million).
"• In 2013, the numbers of initiates were 1.5 million for pain relievers, 1.2 million for tranquilizers, 603,000 for stimulants, and 128,000 for sedatives (Figure 5.6).
"• The number of new nonmedical users of pain relievers in 2013 (1.5 million) was lower than the numbers in 2002 through 2012 (ranging from 1.9 million to 2.5 million) (Figure 5.6). The number of past year initiates for nonmedical use of tranquilizers has been fairly stable from 2002 to 2013 (ranging from 1.1 million to 1.4 million). The number of initiates for nonmedical use of stimulants in 2013 was similar to the numbers in 2003, 2005, and in 2007 to 2012 (ranging from 602,000 to 715,000), but was lower than the numbers in 2002, 2004, and 2006 (ranging from 783,000 to 846,000). The number of initiates for nonmedical use of sedatives in 2013 was similar to the numbers in 2002, 2003, 2007 to 2009, 2011, and 2012 (ranging from 159,000 to 209,000), but was lower than the numbers in 2004 to 2006 and in 2010 (ranging from 240,000 to 267,000).
"• In 2013, the average age at first nonmedical use of any psychotherapeutics among recent initiates aged 12 to 49 was 22.4 years. Average ages at first nonmedical use were 21.6 years for stimulants, 21.7 years for pain relievers, 25.0 years for sedatives, and 25.4 years for tranquilizers. All of these 2013 estimates were similar to the corresponding estimates in 2012.
"• In 2013, the number of new nonmedical users of OxyContin® aged 12 or older was 436,000, which was similar to the estimates for prior years from 2004 through 2012. The average age at first use of OxyContin® among past year initiates aged 12 to 49 was similar in 2012 and 2013 (22.0 and 23.6 years, respectively)."

"In 2004, 6.0 million persons were current users of psychotherapeutic drugs taken nonmedically (2.5 percent). These include 4.4 million who used pain relievers, 1.6 million who used tranquilizers, 1.2 million who used stimulants, and 0.3 million who used sedatives. These estimates are all similar to the corresponding estimates for 2003.
"There were significant increases in the lifetime prevalence of use from 2003 to 2004 in several categories of pain relievers among those aged 18 to 25. Specific pain relievers with statistically significant increases in lifetime use were Vicodin®, Lortab®, or Lorcet® (from 15.0 to 16.5 percent); Percocet®, Percodan®, or Tylox® (from 7.8 to 8.7 percent); hydrocodone products (from 16.3 to 17.4 percent); OxyContin® (from 3.6 to 4.3 percent); and oxycodone products (from 8.9 to 10.1 percent)."

"There are several factors that may have contributed to the abuse and diversion of OxyContin. OxyContin's formulation as a controlled- release opioid that is twice as potent as morphine may have made it an attractive target for abuse and diversion. In addition, the original label’s safety warning advising patients not to crush the tablets because of the possible rapid release of a potentially toxic amount of oxycodone may have inadvertently alerted abusers to possible methods for misuse. Further, the rapid growth in OxyContin sales increased the drug's availability in the marketplace and may have contributed to opportunities to obtain the drug illicitly. The history of abuse and diversion of prescription drugs in some geographic areas, such as those within the Appalachian region, may have predisposed some states to problems with OxyContin. However, we could not assess the relationship between the growth in OxyContin prescriptions or increased availability with the drug's abuse and diversion because the data on abuse and diversion are not reliable, comprehensive, or timely."

"Among persons aged 12 or older in 2010-2011 who used pain relievers nonmedically in the past year, 54.2 percent got the pain relievers they most recently used from a friend or relative for free (Figure 2.14). Another 12.2 percent bought them from a friend of relative (which was higher than the 9.9 percent in 2008-2009). In addition, 4.4 percent of these nonmedical users in 2010-2011 took pain relievers from a friend or relative without asking. More than one in six (18.1 percent) indicated that they got the drugs they most recently used through a prescription from one doctor. Less than 1 in 20 users (3.9 percent) got pain relievers from a drug dealer or other stranger, 1.9 percent got pain relievers from more than one doctor, and 0.3 percent bought them on the Internet. These other percentages were similar to those reported in 2008-2009."

"Conventional wisdom suggests that the abuse potential of opioid analgesics is such that increases in medical use of these drugs will lead inevitably to increases in their abuse. The data from this study with respect to the opioids in the class of morphine provide no support for this hypothesis. The present trend of increasing medical use of opioid analgesics to treat pain does not appear to be contributing to increases in the health consequences of opioid analgesic abuse."

"There is some evidence that higher prescribed doses increase the risk of drug overdose among individuals treated with opioids for chronic non-cancer pain.⁴ Specifically, the risk of drug-related adverse events is higher among individuals prescribed opioids at doses equal to 50 mg/d or more of morphine. The association of opioid prescribing patterns with risk of over-dose may vary across groups of patients; opioid treatment recommendations for pain are typically specific to particular subgroups such as those with chronic noncancer pain,⁵ cancer-related pain, and substance use disorders.⁶ However, potential subgroup differences in opioid prescribing have not been examined."

"Insurance fraud is the main financier and enabler of drug diversion. Even so, few health insurers understand the pivotal role insurance fraud plays in a diversion epidemic that costs insurers up to $72.5 billion a year.
"More specifically:
"• Swindlers and drug abusers obtain the bulk of their illicit prescription narcotics through fraudulent insurance claims for bogus prescriptions, treating phantom injuries and other illegal deceptions;
"• Drug diversion drains health insurers of up to $72.5 billion a year, including up to $24.9 billion annually for private insurers. The losses include insurance schemes, plus the larger hidden costs of treating patients who develop serious medical problems from abusing the addictive narcotics they obtained through the swindles;
"• Insurers are potentially vulnerable to enormous liability lawsuits for failing to reasonably prevent fraud schemes that kill and injure people addicted by diversion schemes. Drug manufacturers and pharmacists already face such lawsuits."

"According to IMS Health data, the annual number of OxyContin prescriptions for noncancer pain increased nearly tenfold, from about 670,000 in 1997 to about 6.2 million in 2002. In contrast, during the same 6 years, the annual number of OxyContin prescriptions for cancer pain increased about fourfold, from about 250,000 in 1997 to just over 1 million in 2002. The noncancer prescriptions therefore increased from about 73 percent of total OxyContin prescriptions to about 85 percent during that period, while the cancer prescriptions decreased from about 27 percent of the total to about 15 percent. IMS Health data indicated that prescriptions for other schedule II opioid drugs, such as Duragesic and morphine products, for noncancer pain also increased during this period. Duragesic prescriptions for noncancer pain were about 46 percent of its total prescriptions in 1997, and increased to about 72 percent of its total in 2002. Morphine products, including, for example, Purdue's MSContin, also experienced an increase in their noncancer prescriptions during the same period. Their noncancer prescriptions were about 42 percent of total prescriptions in 1997, and increased to about 65 percent in 2002."

"By 2002, opioid analgesics were involved in more deaths than either of the illicit drugs responsible for most urban drug abuse in the 1990s: heroin and cocaine. These trends are generally consistent with trends in drug-related emergency department visits reported by DAWN from 1997 to 2002: a 101.4% increase in opioid analgesics, a 23.7% increase in cocaine, and a 32.2% increase in heroin.

"The increased involvement of these analgesics is related to exponential growth in their domestic sales over the past decade as physicians began to treat chronic pain with stronger analgesics.¹⁰ Oxycodone sales in grams increased 402.9% from 1997 to 2002; methadone (excluding that used in narcotics treatment programs) increased 410.8%; and fentanyl increased 226.7%.11 OxyContin, introduced in 1996, accounted for 68% of oxycodone sales by 2002."

"According to a 2001 HIDTA [High Intensity Drug Trafficking Area] report, the Appalachian region, which encompasses parts of Kentucky, Tennessee, Virginia, and West Virginia, has been severely affected by prescription drug abuse, particularly pain relievers, including oxycodone, for many years. Three of the four states -- Kentucky, Virginia, and West Virginia -- were among the initial states to report OxyContin abuse and diversion. Historically, oxycodone, manufactured under brand names such as Percocet, Percodan, and Tylox, was among the most diverted prescription drugs in Appalachia. According to the report, OxyContin has become the drug of choice of abusers in several areas within the region. The report indicates that many areas of the Appalachian region are rural and poverty-stricken, and the profit potential resulting from the illicit sale of OxyContin may have contributed to its diversion and abuse. In some parts of Kentucky, a 20-milligram OxyContin tablet, which can be purchased by legitimate patients for about $2, can be sold illicitly for as much as $25. The potential to supplement their incomes can lure legitimate patients into selling some of their OxyContin to street dealers, according to the HIDTA report."

"Until 2011, the DEA had increased the quota for oxycodone every year since 2002¹⁰¹ with the exception of 2008, when the quota remained unchanged from 2007.¹⁰² In 2010, the quota for oxycodone available for sale was 105,500,000 grams.¹⁰³ In 2002, the quota for oxycodone available for sale was 34,482,000 grams, which means that over that eight-year period, the DEA permitted a 206% increase in the oxycodone quota.¹⁰⁴ The DEA decreased the quota to 98,000,000 grams in 2011.¹⁰⁵ OxyContin is available in seven dosage strengths, ranging from ten milligram to eighty milligram tablets.¹⁰⁶ Although oxycodone is used in other medications, if one assumes, for illustrative purposes, that OxyContin was the only medication manufactured from oxycodone, the 2010 quota would permit the production of between 15,050,000,000 (for ten milligram tablets) and 1,881,250,000 (for eighty milligram tablets) tablets of OxyContin. Although the DEA has the power to limit OxyContin production through its quota authority, the DEA has dramatically increased the availability of oxycodone over the last eight years. While this may be warranted for legitimate users, the increase remains in stark contrast to the limited availability of addiction-assistance medications.¹⁰⁷ Additionally, while the rate of marijuana dependence or abuse has remained steady over the last eight years, the number of people suffering from pain reliever dependence or abuse has increased from 1.5 million to 1.9 million over the same period of time.¹⁰⁸"

"According to law enforcement reporting, some individuals and criminal groups divert CPDs [controlled prescription drugs] through doctor-shopping and use insurance fraud to fund their schemes. In fact, Aetna, Inc. reports that nearly half of its 1,065 member fraud cases in 2006 (the latest year for which data are available) involved prescription benefits, and most were related to doctor-shopping, according to the Coalition Against Insurance Fraud (CAIF). CAIF further reports that diversion of CPDs collectively costs insurance companies up to $72.5 billion annually, nearly two-thirds of which is paid by public insurers. Individual insurance plans lose an estimated $9 million to $850 million annually, depending on each plan’s size; much of that cost is passed on to consumers through higher annual premiums."

According to the United Nations Office on Drugs and Crime:

In the United States in 2015 (the most recent year for which data are available), the wholesale price of black tar heroin ranged from $12,000 to $100,000 per kilogram; the wholesale price of South American heroin ranged from $10,000 to $100,000 per kilogram and the price of southwest Asian heroin ranged from $50,000 to $85,000 per kilogram.

In Mexico in 2015 (the most recent year for which data are available), the wholesale price of heroin was $35,000 per kilogram.

In Colombia in 2015 (the most recent year for which data are available), the wholesale price of raw opium was $694.50 per kilogram; the wholesale price of illicit morphine was $3,746.10 per kilogram; and the wholesale price of heroin was $5,523.90 per kilogram.

In Hong Kong in 2015 (the most recent year for which data are available), the wholesale price of heroin ranged from $47,603.70 to $51,152.10 per kilogram.

In Thailand in 2015 (the most recent year for which data are available), the wholesale price of opium ranged from $519.70 to $779.50 per kilogram; the wholesale price of heroin ranged from $9,146.30 to $12,472.30 for 700 grams.

In Afghanistan in 2015 (the most recent year for which data are available), the wholesale price of raw opium was $150 per kilogram; the wholesale price of heroin was $2,229.50 per kilogram; and the wholesale price of high purity heroin was $3,294.50 per kilogram.

In Pakistan in 2015 (the most recent year for which data are available), the wholesale price of raw opium ranged from $322 to $439 per kilogram; the wholesale price of illicit morphine ranged from $600.90 to $1089 per kilogram; and the wholesale price of heroin ranged from $2,469.50 to $3,468.10 per kilogram.

In 2010, a kilogram of heroin typically sold for an average wholesale price of $2,527.60 in Pakistan. The 2010 wholesale price for a kilogram of heroin in Afghanistan ranged around $2,266. In Colombia, a kilogram of heroin typically sold for $10,772.3 wholesale in 2010. In the United States in 2010, a kilogram of heroin ranged in price between $33,000-$100,000.

"Alabama and Idaho now join Georgia, Iowa, Kansas, Maine, Massachusetts, Michigan, Montana, Oregon, Rhode Island, Vermont, Virginia, Washington, and Wisconsin as having the most balanced policies in the country related to pain management, including with the appropriate use of pain medications for legitimate medical purposes. Over time, these 15 states took advantage of available policy templates and resources, and repealed all excessively restrictive and ambiguous policy. This achievement does not mean that their work is finished, because policy needs to be properly implemented (see next section). Importantly, there is no ceiling on policy quality, so states with high grades should continue to explore how additional policy can help to improve access to pain management while avoiding the adoption of restrictive requirements or limitations. In fact, 25 states that achieved an A for positive language in the past have continued to adopt policy language promoting appropriate pain management during this evaluation timeframe.^h"

"Current voluntary strategies to reduce opioid abuse include
"• the clinician’s assessment in a history and physical exam that includes psychosocial factors, family history, and risk of abuse;
"• the clinician’s regular monitoring of the progress of patients on opioids and assessment for aberrant behavior that may indicate abuse;
"• random urine drug screening and pill counts for patients at risk;
"• state prescription drug monitoring programs (the U.S. Justice Department and other agencies have cooperated in forming an interstate information exchange for such programs);
"• new drug formulations intended to prevent abuse by (1) hindering the extraction of active ingredients through physical barrier mechanisms, (2) releasing agents that neutralize the opioid effects when products are tampered with, and (3) introducing substances that cause unpleasant side effects when drugs are consumed to excess (Fishbain et al., 2010); and
"• removing unused drugs from home medicine cabinets and disposing of them at 'drug take-back' events (see Box 2-4 in Chapter 2) (Office of National Drug Control Policy, 2010)."

"The AMA [American Medical Association] supports the position that:
"1. physicians who appropriately prescribe and/or administer controlled substances to relieve intractable pain should not be subject to the burdens of excessive regulatory scrutiny, inappropriate disciplinary action, or criminal prosecution. It is the policy of the AMA that state medical societies and boards of medicine develop or adopt mutually acceptable guidelines protecting physicians who appropriately prescribe and/or administer controlled substances to relieve intractable pain before seeking the implementation of legislation to provide that protection;
"2. education of medical students and physicians to recognize addictive disorders in patients, minimize diversion of opioid preparations, and appropriately treat or refer patients with such disorders; and
"3. the prevention and treatment of pain disorders through aggressive and appropriate means, including the continued education of physicians in the use of opioid preparations."

"Almost half¹⁴ of global opium is legally produced for processing into various opiate based medicines. Any country can formally apply to the UN’s Commission on Narcotic Drugs to cultivate, produce and trade in licit opium, under the auspices of the UN Single Convention on Narcotics Drugs 1961 and under the supervision and guidance of the International Narcotic Control Board (INCB). As of 2001 there were eighteen countries that do, including Australia, Turkey, India, China and the UK."

"There have been significant advances in implementing PDMPs, 49 states and Washington, D.C. now have operational PDMPs. PDMPs help providers understand their patients’ medication histories, as well as problematic behaviors that signal a need for more in-depth conversations about pain and substance use. The Bureau of Justice Assistance (BJA) supported PDMP expansion grants in 11 states in 2015. ONC, SAMHSA, and CDC all have funded research and standards development for PDMP improvements. The IHS, DoD, and VA have piloted the integration of PDMP systems within their electronic health records systems. In July 2016, both VA and IHS announced new policies that require prescribers to check the PDMP prior to making a decision to prescribe controlled medications.
"Historically, the ability of states to share data has been limited, but agencies are currently involved in efforts to enhance the interoperability of state PDMPs. At the time of this writing, two electronic data sharing hubs are operational, enabling 43 states to work through one or both to share PDMP data with at least one other state. Funding from BJA and DoD has been used to enhance this interstate data sharing.
"PDMPs are only one approach to monitoring. The DoD, VA, and CMS all have initiated drug utilization review programs for some of their patient populations to better coordinate care for individuals who are prescribed opioid medications. Many hospitals administer patient surveys to determine whether their pain was managed adequately. CMS has proposed new questions for these surveys that avoid the perception that performance is linked to prescribing opioid medications for pain control.¹⁴"

"Even well-intentioned policies have exacerbated the link between opioid use and infectious disease. For instance, prescription drug monitoring programs and other measures to limit access to prescription opioids triggered a transition to heroin and, eventually, injection use among people who had become dependent on prescription pain relievers. At the same time, primary care clinics have not adequately screened, treated, and retained patients in treatment for substance use disorders. The resulting increase in the number of people who inject drugs has also increased the overall risk of infectious disease outbreaks. Other policies have similarly exacerbated the link between opioid use disorder and infectious diseases. For instance, policies that limit access to sterile syringes tend to increase infectious disease risk among people who inject drugs, as do the broad array of “war on drugs” policies that incarcerate individuals rather than connect them to treatment and harm-reduction programs. A number of studies have demonstrated that such programs—especially syringe services—lead to a net reduction in substance use through active referral, engagement, and retention in substance use disorder treatment."

"States with PDMPs [prescription drug monitoring programs] have experienced considerable reductions in the time and effort required by law enforcement and regulatory investigators to explore leads and the merits of possible drug diversion cases. The presence of a PDMP helps a state reduce its illegal drug diversion, but diversion activities may increase in contiguous states without PDMPs."

"States with PDMPs have realized benefits in their efforts to reduce drug diversion. These include improving the timeliness of law enforcement and regulatory investigations. For example, Kentucky's state drug control investigators took an average of 156 days to complete the investigation of an alleged doctor shopper prior to the implementation of the state's PDMP. The average investigation time dropped to 16 days after the program was established. In addition, law enforcement officials in Kentucky and other states view the programs as a deterrent to doctor shopping, because potential diverters are aware that any physician from whom they seek a prescription may first examine their prescription drug utilization history based on PDMP data."

"The presence of a PDMP [prescription drug monitoring program] may also have an impact on the use of drugs more likely to be diverted. For example, DEA rank-ordered all states for 2000 by the number of OxyContin prescriptions per 100,000 people. Eight of the 10 states with the highest number of prescriptions-West Virginia, Alaska, Delaware, New Hampshire, Florida, Pennsylvania, Maine, and Connecticut-had no PDMPs, and only 2 did-Kentucky and Rhode Island. Six of the 10 states with the lowest number of prescriptions-Michigan, New Mexico,14 Texas, New York, Illinois, and California-had PDMPs, and 4-Kansas, Minnesota, Iowa, and South Dakota-did not."

"Officials from DEA, the Alliance [National Alliance for Model State Drug Laws], and state PDMPs told us that states considering establishing a PDMP, or expanding an existing one, face several challenges. These include educating the public and policymakers about the extent of prescription drug diversion and abuse in their state and the benefits of a PDMP, responding to the concerns of physicians, patients, and pharmacists regarding the confidentiality of prescription information, and funding the cost of program development and operations. Given a state's particular funding availability and budget priorities, program costs can be a major hurdle. The start-up costs for the three most recent PDMPs were $415,000 for Kentucky, $134,000 for Nevada, and $50,000 for Utah. Estimated annual operating costs for these PDMPs varied from a high of about $500,000 in Kentucky, to $150,000 in Utah and $112,000 in Nevada. Costs in these three states vary because of differences in the PDMP systems implemented, the number of pharmacies reporting drug dispensing data, and the number of practitioners and law enforcement agencies seeking information from the systems."

"The existence of a PDMP [prescription drug monitoring program] within a state, however, appears to increase drug diversion activities in contiguous non-PDMP states. When states begin to monitor drugs, drug diversion activities tend to spill across boundaries to non-PDMP states. One example is provided by Kentucky, which shares a boundary with seven states, only two of which have PDMPs—Indiana and Illinois. As drug diverters became aware of the Kentucky PDMP’s ability to trace their drug histories, they tended to move their diversion activities to nearby nonmonitored states. OxyContin diversion problems have worsened in Tennessee, West Virginia, and Virginia—all contiguous non-PDMP states—because of the presence of Kentucky’s PDMP, according to a joint federal, state, and local drug diversion report."

"CAM holds special appeal for many people with pain for several reasons:
"• deficits in the way that many physicians treat pain, using only single modalities without attempting to track their effectiveness for a particular person over time or to coordinate diverse approaches;
"• the higher preponderance of pain in women (see Chapter 2), given that 'women are more likely than men to seek CAM treatments; (IOM, 2005, p. 10); and
"• a welcoming, less reserved attitude toward people with pain on the part of CAM practitioners and an apparent willingness to listen to the story of a patient’s pain journey.
"Whatever the reasons, pain is a common complaint presented to CAM practitioners (NIH and NCCAM, 2010). In 2007, 44 percent of people with pain or neurologic conditions sought help from CAM practitioners (Wells et al., 2010).
"In 2002, three-fifths of people who turned to CAM for relief of back pain found a 'great deal' of benefit as a result (Kanodia et al., 2010). The National Center for Complementary and Alternative Medicine’s strategic plan, released in February 2011, supports the development of better strategies for managing back pain, in particular."

"Medical therapies are not providing sufficient relief, since the majority of chronic pain sufferers, especially those with severe pain, have also turned to non-medicinal therapies. The primary one is a hot/cold pack. Surprisingly, almost all of the major non-medicinal therapies currently used are perceived as providing more relief by their users than OTCs, the most widely used medicines; the one exception are herbs/dietary supplements/vitamins which are perceived as offering the least amount of relief than any medicines or other major non-medicinal therapies.
"The overall favorable perceptions of non-medicinal therapies are driven by those with moderate pain. Although those with very severe pain are more likely to use them, they have a significantly lower opinion of their efficacy versus medicinal therapies."

"Opioids are associated with adverse events such as sedation and dizziness that could potentially impact driving or work safety⁸³. However, some studies suggest that opioids do not necessarily impair or may improve psychomotor and cognitive functioning in patients on opioids for chronic noncancer pain.^224-227"

"In an analysis of death certificate data from 1999 to 2010, we found that states with medical cannabis laws had lower mean opioid analgesic overdose mortality rates compared with states without such laws. This finding persisted when excluding intentional overdose deaths (ie, suicide), suggesting that medical cannabis laws are associated with lower opioid analgesic overdose mortality among individuals using opioid analgesics for medical indications. Similarly, the association between medical cannabis laws and lower opioid analgesic overdose mortality rates persisted when including all deaths related to heroin, even if no opioid analgesic was present, indicating that lower rates of opioid analgesic overdose mortality were not offset by higher rates of heroin overdose mortality. Although the exact mechanism is unclear, our results suggest a link between medical cannabis laws and lower opioid analgesic overdose mortality."

"A small, but significant, percent of chronic pain sufferers have at one time or another turned to alcohol for relief; this occurred more often among middle age adults and men."

"Pain was very prevalent in representative samples of 2 distinct populations with chemical dependency, and chronic severe pain was experienced by a substantial minority of both groups. Methadone patients differed from patients recently admitted to a residential treatment center in numerous ways and had a significantly higher prevalence of chronic pain (37% vs. 24%). Although comparisons with other studies of pain epidemiology are difficult to make because of methodological differences, the prevalence of chronic pain in these samples is in the upper range reported in surveys of the general population. The prevalence of chronic pain in these chemically dependent patients also compares with that in surveys of cancer patients undergoing active therapy, approximately a third of whom have pain severe enough to warrant opioid therapy."

"Chronic pain sufferers are having difficulty in finding doctors who can effectively treat their pain, since almost one half have changed doctors since their pain began; almost a fourth have made at least 3 changes. The primary reasons for a change are the doctor not taking their pain seriously enough, the doctor's unwillingness to treat it aggressively, the doctor's lack of knowledge about pain and the fact they still had too much pain. This level of frustration is significantly higher among those with very severe pain where the majority have changed doctors at least once and almost of every 3 have done it 3 or more times. Their primary reason for changing was still having too much pain after treatment."

"Chronic pain sufferers currently taking narcotic pain relievers differ from other chronic pain sufferers as to the severity of their pain, being less likely to have it under control, changing doctors more often, requiring more intensive treatment at hospitals, taking more pills per day, more likely following their doctors prescribed regimen and lastly, to being referred to a specialized program/clinic for their pain."