Can We Beat the Opioid Crisis?

Pharmaceutical scientists play a key role.

By Christopher R. McCurdy, Ph.D., FAAPS, President

We have all heard about the opioid crisis in the U.S. It is so critical that life expectancy numbers have dropped for the second year in a row.¹ In 2016, 42,000 people died from opioid abuse. The U.S. has about 4 percent of the world’s population but about 27 percent of the world’s drug overdose deaths.

What is happening, and what can we do about it?

My research at the University of Florida’s College of Pharmacy focuses on the design, synthesis, and development of drugs to treat pain and drug abuse. For more than 20 years, I have dedicated my research to opioid, Neuropeptide FF (NPFF), and sigma receptor ligand/probe design, synthesis, pharmacological evaluation, and development. So I have a deep professional interest in this issue.

What are we doing on a national level?

The Food and Drug Administration (FDA) recently released a draft guidance Opioid Dependence: Developing Depot Buprenorphine Products for Treatment. As its name implies, the guidance offers tips on the study of sustained-release “depot” buprenorphine products that are injected or implanted to treat opioid addiction. FDA Commissioner Scott Gottlieb has said, “One of the critical ways the FDA can play a role is by encouraging more widespread innovation and development of medication for use in medication-assisted treatments.”²

The U.S. Senate health committee recently proposed S. 2680, The Opioid Crisis Response Act of 2018. This proposed bill aims to improve the ability of a number of agencies, governors, experts, and families to address the crisis.³ The House of Representatives recently passed the Advancing Cutting Edge (ACE) Research Act, which would grant the National Institutes of Health’s request to move outside the constraints of a typical contract, grant, or cooperative agreement. The act would allow NIH to partner with innovative companies on cutting-edge research to get nonaddictive pain medications to those in need.⁴

NIH recently released its $500 million opioid research plan, the HEALing Communities Study, which will work within existing health care and criminal justice settings to develop models of care designed to expand access to medications and help patients stay with their treatment. The study is part of NIH’s Helping to End Addiction Long-term (HEAL) initiative.⁵

President Donald Trump also has an Initiative to Stop Opioid Abuse and Reduce Drug Supply and Demand.⁶

These initiatives show that the country is working on this crisis at the highest levels.

In my research, I have worked in several areas to address addiction and pain. I have discovered unique and selective tools for sigma receptors, NPFF receptors, and opioid receptors. I have dedicated a significant portion of my career to developing novel sigma receptor ligands, in collaboration with a variety of interdisciplinary groups, to generate and optimize selective ligands which could serve as critical experimental tools, and more recently, as potential medication development leads to attenuate the effects of cocaine, methamphetamine, and pain. Most notably, our collaborative research team has developed a PET/MR imaging diagnostic agent for visualizing the origins of chronic, neuropathic pain by interacting with sigma receptors at the site of nerve damage. First-in-human studies are currently under way in a phase 1 trial at Stanford University.

I have also worked extensively on Kratom (Mitragyna speciosa), investigating it for opioid withdrawal syndrome.  This natural product, indigenous to Southeast Asia, has been a significant source of controversy, and the Drug Enforcement Agency and FDA have issued concerns and warnings about this product, and rightfully so. There are very few regulations in place to ensure that what a consumer is purchasing is actually what they believe they are purchasing. Consequently, it has been contaminated with various pharmaceuticals as well as human pathogens, like Salmonella.⁷ Thus, it is a true “buyer beware” marketplace.

Nevertheless, the research shows promise for Kratom to treat opioid use disorder, when the plant form is used in the traditional sense. Traditionally, Southeast Asians have used teas made from fresh leaves to replace opium to minimize withdrawal when opium or opioids are unavailable. In addition, it has been used successfully to wean addicts from traditional opioids.⁸ Although none of these traditional uses have been backed with controlled human trials, the anecdotal evidence shows great potential. In addition to this plant aiding in opioid use disorder, recent studies have shown there to be less respiratory depression associated with the alkaloids in the plant than the traditional opioids.⁹ This could indicate a better safety profile and an alternate source of new opioid analgesics. However, much research is still required to fully understand the potential for this traditional medicine. Our own research findings¹⁰ indicate that the major alkaloid, mitragynine, does not have abuse potential and may prove to be an alternative to current opioid use disorder treatments. Only further research and time will give us the answers we seek. Several individuals in the U.S. have reported successful conversion to Kratom from prescription or illicit opioid use, with a return to being productive members of society. Overall, it is important to realize that no controlled human clinical trials have been conducted to prove Kratom’s safety and efficacy. Until this can be accomplished and standards put in place, the controversy about this product and its use will continue.

The highest levels of government, the pharmaceutical industry, and academic laboratories are working to find solutions to the nation’s opioid crisis. There is great hope that we will find solutions, either from novel medications, natural solutions, or a greater understanding of addiction. Pharmaceutical scientists play a vital role and are at the forefront of developing a solution. We cannot do it alone; it will take efforts from all stakeholders (including the public). Addiction is a chronic disease and should be viewed as such. Still, there is a stigma attached to this disease as many still consider it a matter of choice. However, it has been well documented that our nation has overprescribed opioids and in some ways has created this crisis.

Where do we go from here?  Well, more research is needed, and alternative pain medications to opioids need to be approved. This involves targeting mechanisms that are outside the area of the opioid system, and we are focusing a lot of effort on these novel approaches. Pharmaceutical scientists will certainly help to advance these treatments to clinical trials and ultimately approval. Sadly, this takes time, and there is no easy, readily available solution. I encourage you to discuss this issue in the AAPS Communities  and submit hot topic and rapid fire programming ideas on this crisis for PharmSci 360. Bringing research to the forefront, especially in our nation’s capital, will invigorate the discussion and move us toward a solution.

REFERENCES

1. Erickson A. Opioid abuse in the U.S. is so bad it’s lowering life expectancy. Why hasn’t the epidemic hit other countries? The Washington Post. Published December 28, 2017. Accessed May 15, 2018.
2. FDA Offers Advice on Opioid Addiction Treatments. Pharmaceutical Science Update. AAPS Newsmagazine. Published April 25, 2018.
3. 2680, The Opioid Crisis Response Act of 2018. Accessed May 15, 2018.
4. House Passes Bill to Expedite NIH Opioid Research, Pharmaceutical Science Update. AAPS Newsmagazine. Published June 20, 2018.
5. NIH Details $500 Million Opioid Research Plan, Pharmaceutical Science Update. AAPS Newsmagazine. Published June 20, 2018.
6. Fact Sheet: President Donald J. Trump’s Initiative to Stop Opioid Abuse and Reduce Drug Supply and Demand webpage. White House website. Issued March 19, 2018. Accessed May 15, 2018.
7. Recalls, Market Withdrawals, & Safety Alerts web page. Food and Drug Administration website. Published May 1, 2018. Accessed June 20, 2018.
8. Ward J, Rosenbaum C, Hernon C, McCurdy CR, Boyer EW. Herbal medicines for the management of opioid addiction: safe and effective alternatives to conventional pharmacotherapy? CNS Drugs. 2011;25(12):999–1007. doi:10.2165/11596830-000000000-00000
9. Kruegel AC, Grundmann O. The medicinal chemistry and neuropharmacology of kratom: A preliminary discussion of a promising medicinal plant and analysis of its potential for abuse. Neuropharmacology. 2018;134(Pt A):108–120. doi:10.1016/j.neuropharm.2017.08.026. Epub 2017 Aug 19.
10. Hemby SE, McIntosh S, Leon JF, Cutler SJ, McCurdy CR. Abuse liability and therapeutic potential of the Mitragyna speciosa (kratom) alkaloids mitragynine and 7-hydroxymitragynine. Addiction Biology. In press.