Researchers have reported that compounds based on cannabidiol (CBD) reduce fentanyl binding and enhance the effects of naloxone, brand name Narcan, which is currently used to treat opioid overdoses, but is less effective against powerful synthetic opioids like fentanyl. The potential use of CBD as an alternative to naloxone for treating opioid overdoses has gained attention as fentanyl-class compounds account for over 80% of opioid overdose deaths.
Naloxone is an opioid antidote that has saved many lives, but it is less effective against powerful synthetic opioids like fentanyl. However, researchers from Indiana University have reported that CBD can reduce fentanyl binding and enhance the effects of naloxone. These findings were presented at the ACS Spring 2023 hybrid meeting in March.
It is important to note that the press release only provides us with initial information, and we are still awaiting a more official and detailed breakdown of the study and future studies on the topic. Nonetheless, the researchers' approach holds promise in finding alternatives to naloxone and developing new therapeutics that could save more lives in the future.
Synthetic opioids are a class of compounds prescribed to treat pain, but when taken in excess, they can interfere with breathing and potentially lead to lethal consequences. According to the U.S. Centers for Disease Control and Prevention, over half a million people died from overdoses involving opioids between 1999 and 2020. Fentanyl-class compounds account for over 80% of opioid overdose deaths, and naloxone (Narcan) is the only available drug to reverse overdoses. However, naloxone's effectiveness against synthetic opioids such as fentanyl is limited, and reversing such overdoses may require multiple doses of the antidote.
The researchers synthesized CBD to generate derivatives and tested them in cells with a substance called DAMGO, an opioid used only in lab studies. They then narrowed the field to 15 compounds and tested them at varying concentrations against fentanyl, with and without naloxone. Several of the compounds were able to reduce fentanyl binding at incredibly low concentrations and outperformed naloxone’s opioid-blocking performance, with two of them showing a synergistic effect when combined with the antidote. The most successful compounds are now currently being tested in mice to see if they alter behaviors associated with taking fentanyl.
Fentanyl is an opioid that binds to a specific part of the brain called the mu opioid receptor (µOR). In the case of an overdose, naloxone can reverse its effects by competing with the drug molecules for the same binding sites on the receptors. Naloxone is an opioid antagonist, which means that it can bind to opioid receptors and block the effects of other opioids like heroin, morphine, and oxycodone. However, fentanyl binds more strongly to these receptors, making naloxone less effective against it.
Unlike naloxone, which works by competing with the drug molecules for the same binding sites on the receptors, CBD-based compounds interfere with opioid binding by stabilizing an opioid receptor. Moreover, the researchers have reported that these compounds not only reduce fentanyl binding but also enhance the effects of naloxone, making them potentially more effective than traditional opioid antagonists. The development of new therapeutics based on CBD could, therefore, offer a new approach to treating opioid overdoses and save more lives in the hands of emergency personnel.
In conclusion, the recent findings reported by the researchers highlight the potential of CBD-based compounds as an alternative to naloxone in treating opioid overdoses caused by synthetic opioids like fentanyl. While naloxone is an effective opioid antidote, it requires a prescription and has reduced efficacy against synthetic opioids like fentanyl. The study's findings suggest that CBD may be a beneficial alternative, as it doesn't require a prescription and reduces fentanyl binding, boosting the effects of naloxone. The researchers believe that their approach could pave the way for the development of new therapeutics that have the potential to save more lives in the hands of emergency personnel.
Press Release Title: Marijuana-derived compounds could reverse opioid overdoses
Press Release Link: https://www.acs.org/pressroom/newsreleases/2023/march/marijuana-derived-compounds-could-reverse-opioid-overdoses.html
CBD (yellow stick structure) interferes with binding of an opioid (green and red) by stabilizing an opioid receptor (gray) in its inactive form.