Opioid+Drug+Crisis

=**Introduction**= [|Drug overdose] is currently the number one cause of unintentional injury-related death in the United States. Nearly 100 Americans die from drug overdose every day, and prescription [|opioid drugs] such as OxyContin and Vicodin continue to account for a significant portion of those deaths (Creech, Christopher T., et al. 2016). Prescription or synthetic opioids are powerful drugs most notably characterized by their inability to induce and analgesic effect. Over the past few decades, physicians around the world have become increasingly willing to prescribe opioids for the treatment of chronic pain. The increasing use and recreational misuse of opioid drugs has since been accompanied by steep increases in opioid related mortality. In 2014 alone, 18,893 lethal overdoses in the United States were related to prescription opioids and 10,574 due to heroin (Chopra et al., 2017). Despite the growing number of treatment options for substance use disorders, relapse rates remain as high as 91% with millions of misusers still at risk.

**Opium Poppy: History**
Opioids are a class of drugs naturally found in the opium poppy plant. The earliest reference to opium growth and use is in 3,400 B.C. when the opium poppy was cultivated in lower Mesopotamia (Southwest Asia). By the 19th century, isolated compounds from opium such as morphine were commonly used as a pain killer by soldiers during the Civil War era. While therapeutic use of compounds derived from the opium poppy predates written history, the use and marketing of synthetic opioids did not come about until 1989 (Dhalla, 2011). With the invention of the hypodermic needle in 1853, isolated opium derivatives like morphine began to be used in minor surgical procedures to treat neuralgia, eventually giving rise to the medicalization of opioids.

**Clinical Use**
Despite the growing concerns for addiction, withdrawal, and questionable drug efficacy, there are few pharmaceuticals superior to opiates for the treatment of pain (Walwyn et al., 2010). Stress resulting from untreated pain can lead to immunosuppression, exacerbation of underlying medical conditions, and a range of psychological symptoms including severe emotional distress and sleep deprivation. Opioids work by acting on receptors in specific brain regions which register the sensation of pain. Activation of these opioid receptors can also be coupled with induced feelings of euphoria and relaxation.

**Regulation of Opioids & Rise of an Epidemic**
For the beginning of the 19th century, there was no regulation of cocaine or opioid drugs in the United States. It wasn't until the [|Harrison Narcotics Tax Act] of 1914 that the manufacturing, distributing, and importing of opium began to be regulated (Vadivelu et al., 2018). Furthermore, [|addiction] was not yet recognized and a disease and thus physicians who provided prescription maintenance of stock of these drugs to addicted patients were by law incarcerated or lost their licenses. The illegalization of addiction, in part, resulted in inadequate treatment of pain states. By the 20th century, however, the [|American Pain Society] designated "pain as the fifth vital sign" which further advocated for the widespread use of opioid drugs. A second driving force identified by Weiner et al. for the evolution of widespread opioid use is the heavy influence of the pharmaceutical industry on the prescription of opioids, particularly in marketing the utilization of opioid drugs for non-cancer pain. As such, the indication for opioid use soon expanded from that of cancer and palliative care to generalized pain management for patients in clinical settings. This grew to be a primary driving force for the lengthy and high-dose prescription treatment plans provided to patients today. Purdue Pharma, for example, the manufacturer for Oxycontin, expended nearly $200 million to promote the drug in 2001, which resulted in an increase in the prescription of Oxycontin by almost 10-fold to nearly 6.2 million annual prescriptions the following year (Van Zee A., 2009).

Populations Impacted
The range of patients who have become addicted to opioids following the onset of the opioid epidemic has expanded across numerous demographics and socioeconomic populations. In the 1960s, more than 80% of the patients enrolled in opioid abuse treatment programs were males living in urban, inner-city regions who abused heroin. In contrast to this, by 2010, the vast majority of patients who were enrolled in such programs were middle-class women from rural regions, of which 90% were Caucasian. Currently, the US makes up less than 5% of the world's population but is responsible for more than 80% of the world's consumption of opioid pain analgesics (Vadivelu et al., 2018).

Among those affected by the opioid epidemic include US veterans. Children who participate competitively in sports are also a current cohort of individuals who are at especially high risk for opioid misuse. In one longitudinal study done by Veliz et al. found that compared to adolescents who were not involved in sports, adolescents involved in organized sports were two times more likely to be prescribed an opioid, at greater risk for medical misuse of an opioid with the intention of getting high by 4-fold, and at greater risk for medical misuse of an opioid by 10-fold (Vadivelu et al., 2018).

Costs and Effects of Long-Term Opioid Use
The economic costs associated with the epidemic focus primarily on healthcare costs which show that opioid abusers utilize significant more healthcare resources than non-addicted peers (White et al., 2005). It 2013, the estimated cost for prescription opioid overdose, abuse, and dependence in the United States was $78.5 billion. Of this cost, 73% was attributed to nonfatal consequences, including healthcare spending, criminal justice costs, and lost productivity due to addiction and incarceration (United States Council of Economic Advisors, 2017). For 2015, White House estimates on the economic burden of the opioid crisis stood at approximately $504 billion, accounting for 2.8% of the US annual gross domestic product.



Beyond the economic burdens, other risks associated with long-term opioid use include psychiatric or behavioral disorders, substance use disorders, depression, anxiety, ideas for suicide or other self-injury, increased risk for motor vehicle crashes, and sleep disorders. It is estimated that nearly 1.7% of patients with opioid prescriptions become long-term opioid users (six months or longer) (NewsRx, 2017).

Potential Solutions
Given the complex state of the current crisis, efforts fo pharmacological development of opioid drug alternatives continues to be of high public interest. In response to this, many local and state public health organizations employ agents such as naloxone hydrochloride interventions to combat opioid overdose (Creech et al., 2016). Naloxone, an easy-to-use medication that can be administered intramuscularly or intranasaly, is capable of reversing the effects of opioid overdose in timely manner. Despite no potential for abuse, naloxone is only available as a prescription and limited in its distribution due to legislative restriction.

Other current proposed opioid alternatives include compounds such as Kratom and Ibogaine, both of which are derived from herbal material based on Asian remedies which contain medicinally relevant alkaloids and biochemical elements for pain management (Ward et al., 2011). With much lower risk for addiction or symptomatology compared to opioids, natural analgesic compounds such as these continue to be studied for their long-term efficacy.

With the increasing need for a pharmacological alternative, many pharmaceutical companies continue to research the potential for an opioid drug alternative. Xalud Therapeutics, for example, has recently advertised a product (named XT-150) which uses gene therapy to treat pain in a manner that is fundamentally different from other drugs, such as opioids currently on the market for the treatment of chronic pain (BioSpace, 2018).

Conclusion
While the search for a viable long-term pharmacological alternative continues, greater emphasis continues to be placed on increasing health care provider and patient education. Numerous factors, including the inappropriate prescription of opioids, opioid misuse, abuse, and dependence, have contributed to the current crisis. As such, while the development for an opioid alternative appears optimistic, the current state of the epidemic remains a significant issue and will not resolve easily.

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