Roxana Damiescu – Natural product-based approaches to fight the opioid crisis

The life expectancy of American citizen for the year 2017 has been decreasing by one month, to 78.6 years, for the first time ever since World War I (1). However, the cause this time has been an increase of opioid drug overdoses associated with addiction to heroin or misuse of opioid drugs (fentanyl or oxycodone). But how did this happen? In 1996 Purdue Pharma, introduced OxyContin, controlled-release oxycodone on the market and started an aggressive marketing strategy to promote it. According to a statement of the Food and Drug Administration (FDA) OxyContin, not only provides pain relief for 12 hours, but due to its slow absorption it has low abuse potential (2). Consequently, this led to over-prescription of opioid drugs, especially oxycodone, and to widespread misuse, until it became obvious that these compounds are highly addictive (3). According to the Center for Disease Control and Prevention (CDC) between 1999 and 2017 over 700.000 people died of drug overdose, of these 68% involved an opioid, either prescribed or illegal, such as heroin (4).

In Europe over 8000 drug-induced deaths have been reported in 2017 and opioids, especially heroin, are involved in 8 out of 10 cases. According to the latest report of the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) statistically, United Kingdom (34%) and Germany (13%) account for almost half of the overdose deaths in Europe. While heroin continues to be the most common cause of drug-induced death in many developed countries, many European countries have reported increasing number of deaths associated with overdose of synthetic opioids like fentanyl (5).

Chronic pain has become a worldwide problem, affecting the life quality of patients. Current therapy strategies often include the use of opioids, which are highly effective for treating severe pain, but also cause strong side effects and often lead to overuse. Pain plays a very complex role in the human body, while acute pain is usually the result of an injury, chronic pain is considered a health condition. Additionally, little is known about the adaptive changes in the brain caused by chronic pain and opioids use, as well as the interactions between pain and opioids.

For thousands of years, medicinal plants have been an important source of new compounds, with therapeutic effects (6). In China, the opioid crisis has been a public health problem ever since 1980s and the Traditional Chinese Medicine (TCM) has been used against opioid addiction for over 200 years. Ginseng extracts are effective in inhibiting morphine dependence and tolerance as well as improving withdrawal symptoms (7). Another effective compound is scopolamine, which can be found in Daturae albae, flos. It restrains the cerebral cortex, causing an anesthetic effect and activates the respiration center (8). Levo-tetrahydropalmatine (L-THP) a compound isolated from Corydalis yanhusuo, is used in China (Rotundine) for its analgesic, hypnotic and sedating effect. A study conducted by Yang Z. et al showed that treatment of heroin addicts with L-THP reduces withdrawal symptoms and increases abstinence rate (9).

Although, there are various approaches to fight opioid addiction, none of them is sustainably satisfactory. The biggest challenge drug addicts face during treatment is the craving, which often leads to relapse. However, the underlying mechanisms influencing the brain during craving have not yet been elucidated, as such there is still no efficient anti-craving therapy. The goal of my project is to elucidate the mechanisms, which influence the brain regions during pain and craving and develop new strategies to fight the oppiod addiction, based on natural products derived from medicinal plants. Additionally by using ethics, sociology and American culture studies, I will show the impact the opioid crisis has on our culture and society. Through the interdisciplinary dialogue between life and natural sciences I aim to develop new ways to fight the opioid crisis, that will benefit our society.

Author: Roxana Damiescu

 

References:

  1. Xu J, Murphy SL, Kochanek KD, Bastian B, Arias E. Deaths: Final Data for 2016. Natl Vital Stat Rep. 2018;67(5):1-76.
  2. Timeline of Selected FDA Activities and Significant Events Addressing Opioid Misuse and Abuse
  3. Van Zee A. The Promotion and Marketing of OxyContin: Commercial Triumph, Public Health Tragedy. Am J Public Health. 2009;99(2):221-227
  4. https://www.cdc.gov/drugoverdose/epidemic/index.html
  5. http://www.emcdda.europa.eu/system/files/publications/11485/20193286_TD0319444ENN_PDF.pdf
  6. Kinghorn AD, Pan L, Fletcher JN, Chai H. The relevance of higher plants in lead compound discovery programs. J Nat Prod. 2011;74(6):1539-55
  7. Kin HS, Kang JG, Oh KW. Inhibition by ginseng total saponin of the development of morphine reverse tolerance and dopamine receptor supersensitivity in mice. Gen Pharmacol 1995; 26:1071–6
  8. Shi J, Liu Y, Fang Y, Xu G, Zai H, Lu L. Traditional Chinese medicine in treatment of opiate addiction. Acta Pharmacologica Sinica 2006; 27 (10): 1303–1308
  9. Yang Z, Shao YC, Li SJ, Fan M, Zhang MJ, Hao W, Jin GZ. Medication of l-tetrahydropalmatine Significantly Ameliorates Opiate Craving and Increases the Abstinence Rate in Heroin Users: A Pilot Study Acta Pharmacol Sin. 2008; 29(7): 781–788.