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A Nasal Spray That Shoots Nanosized Opioids to the Brain May Help People Avoid Addiction

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As doctors and scientists struggle to turn the tide of the opioid crisis, which killed more than 63,000 Americans in 2016, there are others looking further ahead, trying to create a world where addiction can’t take hold in the first place. One such approach, created by a team of scientists in the U.K., is a nasal spray that shoots a naturally produced opioid straight to the brain—seemingly without causing the euphoric high and tolerance that can lead to dependence.

As per The Guardian:

Scientists at University College London found they could alleviate pain in animals with a nasal spray that delivered millions of soluble nanoparticles filled with a natural opioid directly into the brain. In lab tests, the animals showed no signs of becoming tolerant to the compound’s pain-relieving effects, meaning the risk of overdose should be far lower.


When we take opioids like morphine as drugs, they’re absorbed throughout the body, affecting everything from our brain to the gut. This explains why they can cause everything from euphoria to pain relief to constipation. They also lose their effectiveness the longer we take them, causing users to need more of the drug to get the same results, thanks in part to the specific type of opioid receptors they activate.

Scientists have found that another class of opioids found in the body—the enkephalins—seem to avoid causing this pattern of dependence while still having a pain-killing effect, likely due to the different receptors they activate. But it’s been impossible to develop enkephalin-based painkillers, because they break down too quickly in the body and can’t cross the brain-blood barrier through pills or injections, meaning they can’t actually affect our perception of pain.


According to Ijeoma Uchegbu, professor of pharmaceutical nanoscience at the University College London, the technology his team developed gets around this hurdle in two ways.

First, they envelope the enkephalin in a proprietary polymer, creating nanosized particles that can sneak through the blood-brain barrier via the nasal spray. Second, the particles dissolve at a steady rate, allowing the enkephalin to work its magic over time.


“You need a delivery system for these natural opioids or they do not get into the brain through the nose and do not work,” Uchegbu said via email. “We have solved that problem.”

Better still, because the enkephalin only reaches the brain and doesn’t seep into the body elsewhere, it also seems to avoid causing many of the other side-effects other opioids do. And in their latest animal research, published this November in the Journal of Controlled Release, the drug, known as NM0127, even seemed to work in mice who were already tolerant to morphine. That finding, if it holds true in people, could be especially substantial.


“[W]hat this means is that when patients are tolerant to morphine they could be offered NM0127,” Uchegbu said. “There is not much you can currently offer a patient that is tolerant to morphine.”

The dosed mice also didn’t show any signs of craving, such as reward-seeking behavior. But further tests will have to confirm whether that’s really the case, the authors wrote.


Early research has suggested NM0127 might be as potent at painkilling as morphine injected under the skin, Uchegbu said, and the team is developing it as a drug to treat bursts of chronic cancer pain that can’t be relieved through other painkillers.

Ultimately, though, no matter how promising an experimental drug sounds, it still has to pass through a rigorous set of clinical trials before that hype can be validated. To that end, Uchegbu and his team are hoping to meet with the FDA this year in order to begin human testing.


The startup Uchegbu and others have founded around this technology, Nanometrics, is also developing other products they say are an upgrade to existing drugs. These include a lower-dose formulation of a common immunosuppressant used to treat dry eye syndrome, and an anti-fungal drug that would be less toxic to the kidneys.

[Journal of Controlled Release via The Guardian]