New research points to CBD’s potential in tackling opioid misuse

Early studies suggest that CBD could hold potential in tackling opioid misuse, from curbing cravings to reducing the effects of overdose. 

A mounting evidence base suggests that increasing access to cannabis may be linked to a reduction in opioid use, as many patients find it to be an effective alternative to their conventional pain-relieving medications. 

Now, two early studies suggest that cannabidiol (CBD), a non-intoxicating compound found in cannabis, could be used as a tool to help mitigate the effects of opioid misuse.

The US Centers for Disease Control and Prevention estimates that more than half a million people died from drug overdoses involving opioids between 1999 and 2020, a figure that continues to rise. In 2022 the CDC published guidelines intended to reduce the prescribing of opioids.

Meanwhile a recent study from researchers from State University of New York at Albany and the New York State Department of Health found that medical cannabis products were associated with substantial long-term decreases in the daily use of prescription opioids among patients living with chronic pain.

CBD to curb opioid cravings

In what is thought to be the first comprehensive study of the behavioural and physiological effects of inhaled vapour from high-CBD whole-plant cannabis extract, researchers from Washington State University and Legacy Research Institute in Portland, found CBD was able to reduce opioid reward in female rats.

The whole-plant extract was ‘modestly efficacious’ in reducing neuropathic pain in rats with spared nerve injury (SNI) and ‘chronic exposure’ did not affect ‘lung cytoarchitecture or estrous cycle’, or induce cognitive impairment or social withdrawal. 

In addition, CBD was shown to reduce fentanyl self-administration in rats, with and without neuropathic pain, and ‘reduced the rewarding effects of morphine’.

“The ability of WPE to reduce opioid reward and drug seeking behaviour appears quite robust and of great clinical utility,” the authors say.

“Combined, these results suggest that although high-CBD vapour has modest analgesic effects, it has a robust safety profile, no abuse potential, and it significantly reduces opioid reward in females.

“Clinical studies examining high-CBD WPE as an adjunct treatment during opioid use disorder are highly warranted.”

CBD as an alternative to naloxone?

Elsewhere, researchers are looking to CBD as a possible alternative to the popular opioid antidote, naloxone.

Naloxone reverses an overdose by competing with the drug molecules for the same binding sites on the receptors. However, this medication is less effective against powerful synthetic opioids, such as fentanyl, which is responsible for around 80% of overdose deaths.

Scientists from the Indiana University Bloomington, are investigating compounds based on CBD that reduce fentanyl binding and boost the effects of naloxone.

Their work is based on research published in 2006, when a group based in Germany concluded that CBD hampered opioid binding indirectly by altering the shape of the receptor. When used with naloxone, they found CBD accelerated the medication’s effect, forcing the receptors to release opioids.

To augment these effects those behind the latest study altered CBD’s structure to generate derivatives. They then tested these new compounds in cells with a substance called DAMGO, an opioid used only in lab studies and measured their success at varying concentrations against fentanyl, with and without naloxone. 

Several derivatives could reduce fentanyl binding even at what they describe as ‘incredibly low’ concentrations, while also outperforming naloxone’s opioid-blocking performance. Two of these also showed a synergistic effect when combined with the antidote.

The team has since begun testing the most successful derivatives in mice. In these experiments, they are investigating whether these compounds alter behaviours associated with taking fentanyl.

Michael VanNieuwenhze, PhD co-principal investigator for the project, said: “Ideally, we would like to discover a more potent replacement for naloxone. However, finding something that works synergistically with it, reducing the amount needed to treat an overdose, would also be a success.”

Taryn Bosquez-Berger, a graduate student who also worked on the study, adds: “We hope our approach leads to the birth of new therapeutics, which, in the hands of emergency personnel, could save even more lives.”

The researchers are presenting their results at the spring meeting of the American Chemical Society (ACS), taking place from 26-30 March.

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