CBD Compounds Could Potentially Reverse Opioid Overdoses

CBD Compounds Could Potentially Reverse Opioid Overdoses

US researchers have conducted a study on the potential of CBD as a solution for opioid overdoses. In recent times, there has been a push in the US to make naloxone available over the counter. While naloxone has saved lives, it is less effective against potent synthetic opioids like fentanyl.

During the American Chemical Society (ACS) hybrid meeting on March 28, 2023, a team presented their findings that CBD-based compounds can reduce fentanyl binding and enhance the effects of naloxone. Dr. Alex Straiker, co-principal investigator of the project, stated, “Fentanyl compounds are responsible for more than 80 percent of opioid overdose deaths. Considering that naloxone is the only available drug to reverse overdoses, it makes sense to explore alternatives.”

CBD as an alternative

Dr. Michael VanNieuwenhze, the project’s other co-principal investigator, explained, “We are aiming to discover a more potent substitute for naloxone. However, it would also be wise to find something that works synergistically with it, reducing the required dosage to treat an overdose.” Compared to substances like heroin or morphine, fentanyl and other synthetic opioids bind more strongly to opioid receptors in the brain. Naloxone reverses an overdose by competing with these molecules for the same binding sites on the receptors. Fentanyl binds very easily.

The researchers were inspired by earlier studies suggesting that CBD might interfere with opioid binding. In a 2006 study conducted by a group based in Germany, it was concluded that CBD indirectly hindered opioid binding by altering the shape of the receptor. When combined with naloxone, CBD accelerated the drug’s effects, causing the receptors to release opioids. Jessica Gudorf, a graduate student in VanNieuwenhze’s group, modified the structure of CBD to create derivatives in order to enhance these effects.

CBD compounds

Taryn Bosquez-Berger, a graduate student in Straiker’s group, tested these new compounds on cells containing DAMGO, an opioid used only in laboratory studies. To evaluate their effectiveness, he monitored a molecular signal that decreases when this type of drug is bound. With the results from these experiments, Gudorf further refined the generated structures.

Eventually, the team narrowed down their selection to 15 structures, which were tested against fentanyl at various concentrations, both with and without naloxone. Several derivatives showed the ability to reduce fentanyl binding, even at extremely low concentrations. They also outperformed naloxone. Two of these derivatives also displayed a synergistic effect when combined with naloxone.

The team has now moved on to testing the more successful derivatives on mice. In these experiments, they will assess whether these compounds modify the behaviors associated with fentanyl use. Bosquez-Berger concluded, “We hope that our approach will lead to new therapies that can save even more lives.”

Source: drugtargetreview.com (EN)

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