It almost sounds too good to be true: painkillers that could be more effective in relieving pain and less likely to result in dependence and addiction. But that's what researchers from the University of Adelaide and the University of Colorado are on their way to developing following a study on the potential of a drug called (+)-naloxone.
"It's a total game changer," said Linda Watkins, the lead author of the study, which was published last month in the Journal of Neuroscience. (+)-naloxone is a mirror image of the drug naloxone, used to treat opiate overdoses. Watkins and her team found that (+)-naloxone can alleviate pain more strongly when paired with opioids than the drugs would otherwise alone, while blocking some of the elements that lead to addiction.
Painkillers help millions of people who are battling cancer, recovering from surgery and suffering from chronic ailments, but they also represent a class of drugs that the CDC says are being abused at alarming rates. There were 14,800 painkiller-related overdose deaths in 2008 -- more than the number of heroine and cocaine overdose deaths combined. There's been a 300 percent increase in painkiller sales since 1999, and 12 million people admitted to using painkillers for non-medical reasons in 2010.
In an Associated Press report published in April, one expert pointed out that an increase in prescription drug use is tied to multiple factors, including a greater willingness on the part of doctors to prescribe the drugs, and physically dependent users "doctor shopping" so that they can keep getting their fix. And as addiction specialist Dr. Drew Pinsky pointed out to The Huffington Post last fall, adults and teens alike misperceive prescription drugs as substances that can be used without consequences because they're often coming from doctors rather than street corners.
This latest research from Watkins' team could prove to be significant in the effort to curb prescription drug abuse, in part because it approaches drug physiology in a new way. Watkins noted that in the past, researchers have primarily studied drug abuse and drug rewards in terms of how they relate to neurons. The new research shows that there may be another key player, known as glia, that influences how the body responds to drugs. Glia are immune-like cells that behave very differently than neurons, and they could prove crucial in understanding how pain and reward messages are transmitted.
"You can think of them as volume controls," Watkins said. "They can turn up pain and they can turn up drug reward, because when they become activated by things like pain, by things like opiates, they start releasing substances that are excitatory, that drive neurons wild."
What Watkins and her team found in their research is that when they paired morphine with (+)-naloxone, the drugs effectively blocked a receptor attached to the glial cells, making the pain-relieving aspects of the drug stronger while apparently negating drug rewards.
In one study performed, rats were put into two rooms, one of which had saline and one of which had morphine. Conditioned behavioral response dictates that the rats would want to return to the room that had the morphine in it. But once the rats were given (+)-naloxone with the morphine, they no longer showed a preference for that room and were just as attracted to the saline one.
"Now you have separation of effects," Watkins said. "You can enhance the ability of opiates to be good in the clinical control of pain while at the same time decreasing the abuse potential."
There are two ways the abuse potential is decreased, she noted: it's directly reduced by eliminating the reward, and it's indirectly reduced if opiates work better with the addition of (+)-naloxone, allowing users to require less opiates in the first place.
"If you have less opiates, you have less side effects, less abuse potential," Watkins said.
The research is in its early stages, and there remain many more questions that need to be answered. As Maia Szalavitz pointed out in Time, "it is not clear whether preventing the high would hinder certain aspects of pain relief in humans. Subjective experiences of opioid use suggest that the 'high' — the relief of anxiety and sense of distance from the pain — is not totally separate from the actual physical pain relief, and multiple previous efforts to dissociate the two have failed."
Szalavitz went on to argue that heroin was initially meant to be a less addictive form of morphine and that OxyContin was intended to be a less addictive painkiller. Those attempts at non-addictive opioids didn't pan out as hoped for.
Scientific American raised the issue over whether an addiction-proof painkiller might be of any help to someone already addicted to painkillers, noting that, "there’s a big difference between blocking the effects in a rat that’s only had a few days experience, and blocking them in a years-long addict. Reward related systems change very drastically after long-term exposure to drugs like morphine or heroin, and remember, this has not been tested in humans."
But Watkins believes an "addiction-proof painkiller" is something that could indeed become a reality.
"It's early on, but the data are suggestive of that," she said. "It certainly is worthy of a lot more study to see whether this may actually turn out to be the case."
Watkins also noted research from other scientists that shows the potential for a longer-acting version of (+)- naloxone to also curb drug cravings.
"You can take a person through detox to get them off of drugs, but the real question is whether they will stay off the drugs," Watkins said.
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