CBD derivatives may aid naloxone in reversing opioid overdoses
Addiction plagues Americans, and many are seeking alternatives to pharmaceuticals like cannabis medicine. In addition, researchers continue researching how cannabinoids could impact addiction recovery, leading to preliminary findings that CBD reverses overdoses.
Opioids include fast-acting fentanyl, oxycodone, hydrocodone, codeine, morphine, and new street iterations. The CDC reported that 81.9% of fatal overdose deaths in 2021 were due to opioids. Additionally, a 2021 report in StatPearls states that over 2.1 million people in the United States are affected by opioid use disorder, and worldwide, there are over 120,000 deaths attributed to the substance.
Naloxone is a prescription nasal spray that can reverse an opioid overdose. The opioid antagonist attaches to opioid receptors and reverses the effects of the opioids. However, it is not as effective for a fentanyl overdose. Synthetic opioids bind more tightly to receptors than heroin and morphine, making it more difficult for naloxone to reverse the effects of the substances.
Research presented by graduate student Jessica Gudorf at the American Chemical Society Spring 2023 event shows that naloxone can have a heightened effect when paired with CBD, according to a press release obtained by GreenState. The Indiana University Bloomington research team is led by co-principal investigators Alex Straiker, Ph.D. and Michael VanNieuwenhze, Ph.D.
“Given that naloxone is the only drug available to reverse overdoses, I think it makes sense to look at alternatives,” said co-principal investigator Dr. Alex Straiker.
A 2006 study from Germany that found CBD lessened the grip of opioids on receptors by slightly altering the shape of opioid receptors inspired the IUB research team. The study also showed that CBD forced the opioids to release from receptors when combined with naloxone.
Researchers measured these results by assessing the rate of attraction, detraction, and equilibrium between opioid receptors and CBD molecules using kinetic binding studies.
Gudorf altered the shape of the CBD molecule to create derivatives of the cannabinoids that lab mate Taryn Bosquez-Berger tested in cells with an opioid only used in lab studies. When opioids bind to the receptors, the molecular signal diminishes, so researchers studied this signal to isolate derivatives that created the desired outcome.
That research left the team with 15 structures to test against fentanyl and fentanyl in combination with naloxone. Bosquez-Berger reported that even “incredibly low” amounts of multiple derivatives could reduce fentanyl binding, performing better than naloxone. Two of the 15 structures had a synergistic effect with naloxone.
The team is now testing the various structures on mice as they work to verify these preliminary results. Now they are also studying whether the compounds change fentanyl-associated behaviors.
“Ideally, we would like to discover a more potent replacement for naloxone,” VanNieuwenhze said in the press release distributed by the American Chemical Society, “However, finding something that works synergistically with it, reducing the amount needed to treat an overdose, would also be a success.”
“We hope our approach leads to the birth of new therapeutics, which, in the hands of emergency personnel, could save even more lives,” Bosquez-Berger concluded.