Olivier Civelli did not expect his research to lead him to integrative medicine. Yet, this is where the molecular biologist finds his latest journey of discovery is taking him.
Civelli is recognized as the pioneer of reverse pharmacology. Using this process, he was the first to decipher the structure of the D2 dopamine receptor, which is central to movement, reward and addiction; find other dopamine receptors; and devise a new approach to discover novel neurotransmitters.
“It’s somewhat a surprise,” he said, “the fact that I went from finding receptors to finding new neurotransmitters in animals, and then saying, ‘Now I’m going into plants.’”
We said, that’s interesting, we have found something fun, something which could, you know, prevent the morphine tolerance and therefore, opioid tolerance. And that could
Olivier Civelli, PhD
be of interest for fighting the opioid epidemic.
As he points out, however, his research has long been related to opioids. And, the pain killer morphine was derived from the opium plant. So, there is a through-line to his story.
Civelli holds joint appointments as a professor of pharmaceutical sciences in the School of Pharmacy & Pharmaceutical Sciences and professor of developmental and cell biology in the School of Biological
Sciences.
He is also the Eric and Lila Nelson Chair of Neuropharmacology. In 2021, the renowned researcher was named a Samueli Scholar in recognition of the potential for his work to impact integrative health, joining seven UCI colleagues in the inaugural class of awardees.
Through a research collaboration between UCI and the Chinese Academy of Sciences (CAS), Civelli applied reverse pharmacology to screen traditional Chinese analgesics, testing nearly 10 therapeutic plants for their pain-relief abilities. Only the alkaloid dehydrocorybulbine (DHCB) found in Corydalis yanhusuo induced a reproducible effect.
They found that the extract had a stabilizing, analgesic effect when combined with morphine.
“We said, that’s interesting, we have found something fun, something which could, you know, prevent the morphine tolerance and therefore, opioid tolerance,” Civelli said. “And that could be of interest for fighting the opioid epidemic.”
Corydalis yanhusuo is a flower in the poppy family – often called poppies. It has been used as an analgesic in traditional Chinese medicine for centuries. It is considered safe for use for a limited time, except in pregnant or breastfeeding individuals. DHCB is found in the extract.
Although DHCB has been shown to be effective, it needs to be evaluated for any toxicity before it can be used or developed as a drug. It’s also possible that chemical modification of the compound could lead to a more potent pharmaceutical.
“Professor Civelli’s research is an excellent example of how researchers in our school are investigating the scientific evidence for botanicals as potential sources for new treatment or preventative modalities,” said Jan Hirsch, founding dean of the School of Pharmacy & Pharmaceutical Sciences.
Just as opium research led to morphine, Civelli believes it is possible that a Corydalis yanhusuo alkaloid, perhaps even DHCB, could one day be used to reduce drug dependence. The Samueli Scholar plans to investigate the flower’s active component(s) and test the use of the extract in acute, inflammatory, and chronic pain to fully understand its role in limiting adverse effects of morphine.
“You never know where it goes. I mean, for me, what keeps me alive, is going to my lab and discussing with my students, ‘Okay, we found something new. What is the next step to bring it to patients?’” said Civelli.
