Alas, research on pill popping does just that, kicking the painkiller addiction immunity myth to the curb with a comic book zeal that has many providers of patient and palliative care antsy for the (+)-naloxone avenger to stage a more prominent comeback.
International collaborators from the University of Adelaide and the University of Colorado Boulder have pitched an intriguing storyline detailing the possible end to painkiller addiction via the championing of the drug (+)-naloxone, a mirror-image molecule of an overdose antidote found to block the brain’s immune-addiction response in rats. The study, published in the Journal of Neuroscience, re-routes assumptions harking the central nervous system’s pain-pleasure region as the prime driver of addictive tendencies, putting instead more emphasis on properties in the immune system. Specifically, the new report suggests that the highest level of negative opioid effects, which dictate elements such as tolerance and withdrawal, are spurred by immune cells in the brain rather than pleasure-pain neurons.
“Our studies have shown conclusively that we can block addiction via the immune system of the brain, without targeting the brain’s wiring,” said lead author Mark Hutchinson, MD, ARC Research Fellow in the University of Adelaide’s School of Medical Sciences, in a UC Boulder press release. “Both the central nervous system and the immune system play important roles in creating addiction, but our studies have shown we only need to block the immune response in the brain to prevent cravings for opioid drugs.”
When rodents were administered (+)-naloxone alongside opioid drugs like morphine, common signifiers of addiction were sparse; attempts made by the rats to self-administer the drugs were practically non-existent and preferences for the place they received opioids were not developed when naloxone’s plus side was involved.
“This is a paradigm shift in how one views drug reward,” lead author Linda Watkins, PhD, of the University of Colorado, Boulder told Times health. “All prior concepts of why drugs like opioids are rewarding, why drugs become abused, have focused exclusively on neurons.”
An opioid inverse agonist, naloxone has been used for years to treat heroin and morphine overdoses by counteracting brain and respiratory system depression. Naloxone’s antagonist (+)-naloxone — born from the union of naloxone and opioid buprenorphine to make suboxone — essentially blocks the immune-addiction response, amplifying a painkiller's affect relief-wise while preventing unhealthy dependence.
“The drug (+)-naloxone automatically shuts down the addiction,” Hutchinson said. “It shuts down the need to take opioids, it cuts out behaviors associated with addiction, and the neurochemistry in the brain changes – dopamine, which is the chemical important for providing that sense of ‘reward’ from the drug, is no longer produced.”
“The drug that we’ve used to block addiction, (+)-naloxone, is a non-opioid mirror-image drug that was created by Dr. Kenner Rice in the 1970s,” Watkins added. “We believe this will prove extremely useful as a co-formulated drug with morphine, so that patients who require relief for severe pain will not become addicted but still receive pain relief. This has the potential to lead to major advances in patient and palliative care.”
Whereas the rats rate (+)-naloxone as a plus, human clinical trials have yet to get the greenlight. And as Chris Holmwood, MD, a clinician with Drug and Alcohol Services in South Australia, posited in an AM radio broadcast, faith in (+)-naloxone can only go so far without clinical trials to back it.
"The key is how these animal studies are then translated into some clinical studies in humans and then what the outcomes of the human studies are,” Holmwood said. “You know, so that translation process is going to be the critical part of it. But I mean it's very interesting. I think it opens up some possibilities to be able to help people who are on pain medication but running into trouble, people who might be at risk of running into trouble who aren't yet on pain medication but actually require it and thirdly, you know, how do you actually help people who are already opiate-dependent, who are addicted if you like. And so you know it'll open up some opportunities for them as well. So I think it's very exciting.”
With the need for chronic pain relief sans addiction more prevalent than ever, Watkins confirmed that she and her colleagues are doing what they can to arrange for human trials.
“We are trying to [raise the funds to] start a company to take this to clinical trials,” she said. “There is a huge unmet need for effective therapies for chronic pain.”
The hope is that these trials will begin in the next 18 months.
Another study conducted by scientists from The Scripps Research Institute hails a related drug, naltrexone, as one component that lessens cocaine addiction in rats as well.Find more information on the (+)-naloxone study here.