Opioid overdoses may one day be cured by marijuana compounds

In the U.S., more than half a million people died from overdoses involving opioids between 1999 and 2020.
Sade Agard
An interesting twist: Marijuana and pills concept image
An interesting twist: Marijuana and pills concept image


In an interesting twist, researchers are now looking to cannabidiol (CBD), a component of marijuana, as a possible alternative to the popular opioid antidote, naloxone, according to new research presented at the American Chemical Society (ACS) Spring 2023 on March 28.

Better yet, rather than replacing naloxone, CBD could work alongside it. That is, CBD was found to reduce the binding of fentanyl- a powerful synthetic opioid- thereby boosting the effects of naloxone. 

How can CBD reverse opioid overdoses?

Opioids are drugs prescribed to relieve pain but are frequently sold illegally. The medications can be fatal if used in excess since they might impair breathing.

Fentanyl and its synthetic relatives bind to opioid receptors in the brain more strongly than other drugs in this class, such as heroin or morphine.

"Fentanyl-class compounds account for more than 80 percent of opioid overdose deaths, and these compounds aren't going anywhere — it's just too much of an economic temptation for dealers," said Alex Straiker, Ph.D., the project's co-principal investigator in a press release.

"Given that naloxone is the only drug available to reverse overdoses, I think it makes sense to look at alternatives."

By competing with drug molecules for the same receptor binding sites, naloxone reverses an overdose. However, fentanyl binds more quickly than naloxone does. Thus multiple doses of the antidote may be necessary to reverse these types of overdoses, according to mounting research.

"Our work opens the door to making new blockers that work through a different mechanism," explained Jessica Gudorf - a graduate student in VanNieuwenhze's group who presented the work at ACS.

The current endeavor was motivated by earlier research that suggested CBD might interfere with opioid binding. Here, a team from Germany discovered that CBD accelerated the effects of naloxone, forcing the receptors to release opioids.

Now, Gudorf and colleagues changed the structure of CBD to produce derivatives. They evaluated these new compounds using the only opioid employed in lab experiments- DAMGO.

Opioid overdoses may one day be cured by marijuana compounds
CBD (yellow stick structure) interferes with binding of an opioid (green and red) by stabilizing an opioid receptor (gray) in its inactive form.

She kept an eye on a molecular signal that weakens when this medicine binds to measure the compounds' effectiveness. From these feedback tests, Gudorf refined the structures she developed.

Ultimately, the team came down to 15 compounds, which they tested against fentanyl at various quantities, both with and without naloxone.

Many compounds outperformed naloxone in opioid blocking and could decrease fentanyl binding even at 'incredibly low' concentrations.

When coupled with the naloxone antidote, two of the derivatives also boosted its effectiveness. 

Since then, the team has started testing the most effective compounds in mice. In these tests, they will investigate whether these substances change the behaviors connected to fentanyl use.

"We hope our approach leads to the birth of new therapeutics, which, in the hands of emergency personnel, could save even more lives," concluded Taryn Bosquez-Berger, a graduate student in Straiker's group.

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