Dr. Anjali Rajadhyaksha, professor of neuroscience in pediatrics and Associate Dean of Program Development and Dr. Francis Lee, interim Dean at Weill Cornell Medicine have been awarded an R01 from the National Institute on Drug Abuse their study entitled, “Circuit and Synaptic Mechanisms of Endocannabinoid-Opioid Crosstalk.”
The current opioid crisis has contributed to drug overdoses becoming the leading cause of death for Americans under the age of 50 years, with a constant increase in overdose deaths among adolescents. Opioids (morphine, oxycodone, fentanyl) remain the main line of medications for pain management, underscoring the urgent need for new non-opioid treatment options or adjuvant therapies that eliminate the addictive properties, but not the analgesic aspects of these medications.
Adolescence is an important developmental period between childhood and adulthood during which the brain is highly plastic and influenced by a variety of environmental factors. Exposure to substances of abuse during adolescence can impact the developing brain and lead to abnormalities in brain function including neurocognitive performance.
In this study, Dr. Rajadhyaksha will target the brain’s endocannabinoid signaling pathway to reduce the addictive properties of opioids while sparing the analgesic effects. Preliminary data finds that enhancing levels of the endocannabinoid 2-AG in the brain can alleviate the rewarding properties of opioids morphine and oxycodone but not its analgesic effects. Her team will use in vivo fluorescence brain imaging, optogenetic, and chemogenetic tools to investigate how the endocannabinoid 2-AG regulates opioid-mediated reward behaviors.
Overall, the new study aims to reduce the addictive properties of opioids, as well as identify new mechanisms that could be targeted for treating opioid dependence and alternatives to opioids for pain management.