(Newswire.net — September 21, 2018) — The opioid epidemic continues to be a major health crisis in the United States, and it’s going to get worse before it gets better. The number of deaths via overdose per year is rising, with the nationwide cost of the epidemic estimated to be nearly $500 billion.
Healthcare providers, lawmakers, scientists, and social workers are all scrambling to find a way to halt this epidemic, or at least stop the bleeding. The problem is, no single law or regulation could possibly overcome the challenges of addiction or the practical necessity of opioid pain killers. Fortunately, teams of researchers have made significant progress on new substances, which could provide severe pain relief without the high risk of leading users to addiction.
Painkillers and Addiction
Opioids are dangerous, in part, because they bind to a cell membrane protein called the mu-opioid receptor, or MOR. When activated, MOR triggers a molecular cascade that leads to pain relief in the body, as well as the activation of beta-arrestin2, which leads to respiratory depression, and a spike in euphoria and dopamine, which can trigger addictionlike behaviors.
Of course, addiction is more complicated than a simple chemical reaction. Certain people may be genetically predisposed to addiction, and factors like mental health and environmental influences can steer people toward or away from harmful substances.
One of the biggest motivating factors for this wave of opioid addiction is the ready availability of opioid pain medications, as well as their excessive prescription. Opioid pain medications are cheap, easy to prescribe, easy to get, and heavily in circulation. That makes it easy for “normal” people to develop an addiction to these substances, and makes it easy for people addicted to opioid medications to find ways to continue their habit. People are disinclined to turn down pain medications because they’re so effective, insurance companies are disinclined to stop production because they’re so cheap, and doctors are disinclined to stop prescribing medications because they’re so convenient and effective.
The Latest Efforts
One of the latest efforts is on a drug called NKTR-181, a modification of traditional oxycodone, which is designed to maintain the drug’s painkilling effects while lessening its ability to influence addiction. Researchers have adjusted oxycodone by adding a molecular tail—polyethylene glycol—which has been used in other drugs as a way to extend the lifespan of medications in the blood.
The new version of the drug crosses the blood-brain barrier up to 70 times more slowly than traditional oxycodone (in animal studies). This allows the medication to provide pain relief, but without the sharp spike of euphoria and dopamine. Hypothetically, a more stable release of dopamine and a more gradual introduction of the pain relief effects could drastically lessen side effects of the drug, including its addictive potential.
This approach isn’t without its downsides, however. Other researchers have pointed out that a time-release coating could simply be dismantled, allowing existing addicts to bypass this engineered safety mechanism and still get the spike of dopamine to which they’ve grown accustomed.
Another recent foray into experimental pain relief medications is AT-121. This compound stimulates both MOR and the nociception opioid receptor (NOR), which may have the potential to counteract the effects of MOR while reinforcing its pain relief effects. Rhesus monkeys provided with AT-121 experienced pain relief about 100 times greater than they experienced with a similar dose of morphine, yet exhibited no addictive behaviors, no respiratory depression, and most amazingly, no tolerance to the substance when given further doses.
Still other avenues of research are attempting to find medications that spur pain relief without activating any opioid receptors. This can be done by making long-term changes to neural synapses, habituating subjects to pain.
Could This Solve the Problem?
A pain medication that could provide levels of relief similar to opioids without the addictive or destructive potential would be ideal in halting the over-prescription of opioid medications, but they alone can’t solve this crisis. They can’t reverse time and undo the damage already done by previously prescribed opioid medications, so we need to offer more support and treatment options for people currently struggling with addiction.
We also need to pay closer attention to synthetic opioids, which as of 2016, surpassed prescription opioids in terms of total overdose deaths. Still, every step toward resolving one facet of the opioid epidemic is a step worth taking, and these newly researched pain medication options therefore have the power to prevent at least some instances of addiction and overdose death. It may be years before we move from animal trials to human trials and widespread acceptance, but the early results for almost every new category of opioid replacement are promising.