Figure 1: Between the years 1999 and 2017, the number of deaths caused by opioid overdose skyrocketed, nearing 50,000 in 2017. Picture source: Wikimedia Commons
Anahita Kodali —
Opioid abuse in the US has been a well scrutinized topic over the last few years. Studies have shown that between 21 to 29% of patients misuse opioids that are prescribed for chronic pain. Opioid abuse, taking into account healthcare, loss of productivity, addiction therapy, and law enforcement, costs the US nearly 80 billion dollars annually [1]. Because of the ever-rising use of opioids, it has become increasingly important to study the impact of opioid dependence on the body. A team of researchers at the University of California San Diego School of Medicine, led by Drs. Giordano de Guglielmo and Marsida Kallupi in the Department of Psychiatry, attempted to further our knowledge by studying the impact of opioid dependence on rats. In their study, they reported that this dependence altered the rats’ brains significantly [2].
The team used several different technical approaches to complete their project, including behavior models, molecular biology, and electrophysiology. They found that oxycodone dependence caused changes in the nociceptin system in the central nucleus of the amygdala, which is the part of the brain that controls the transmission of pain [3]. Addiction caused downregulation of nociceptin. When this happened, rats that were highly addicted to opioids experienced higher rates of activation of GABA receptors, which are receptors that regulate communication in the brain. Restoration of normal regulation rates of nociceptin led to normalization of GABA receptor activation, which allowed the researchers to conclude that downregulation of nociceptin could be at least partially responsible for addiction behavior [4].
These findings have significant implications for the future of opioid addiction treatment. Currently, the most popular opioid dependence treatment option is opioid maintenance therapy, which involves patients using alternative medicines instead of opioids to manage their pain. Unfortunately, there are currently only 3 FDA approved alternative medications – methadone, buprenorphine and naltrexone, and they all have shortcomings when compared to opioids. This project at UC San Diego leads the effort to create drugs that target the nociceptin system, which may be more effective at treating opioid addiction than alternative therapies[3]. As the death toll from opioid overdose and other drug abuse continues to rise, researchers must continue to study the impacts of illicit drug use on the body to continue making strides towards better treatment.
References:
[1] Opioid Overdose Crisis. (22 January, 2019). National Institute on Drug Abuse. Retrieved from https://www.drugabuse.gov/drugs-abuse/opioids/opioid-overdose-crisis
[2] Opioid dependence found to permanently change brains of rats. (24 January, 2020). Medical Xpress. Retrieved from https://medicalxpress.com/news/2020-01-opioid-permanently-brains-rats.html
[3] Meunier, J.-C. (2006). Nociceptin. ScienceDirect. Retrieved from https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/nociceptin
[4] Marsida Kallupi et al, Nociceptin attenuates the escalation of oxycodone self-administration by normalizing CeA–GABA transmission in highly addicted rats, Proceedings of the National Academy of Sciences (2020). DOI: 10.1073/pnas.1915143117