NIH, private partners team up on opioid crisis initiative

The National Institutes of Health (NIH) has announced a partnership with private entities on a three-faceted scientific initiative to address the opioid crisis. The goals of the initiative are to:

• Develop better overdose reversal and prevention interventions to reduce overdose-related deaths
• Find new medications and technologies to treat opioid addiction
• Find safe, effective and non-addictive interventions to manage chronic pain

“This expands on our previous work by bringing forward a very specific initiative for public-private partnerships to help develop medications and therapeutics that can help address the problems linked with the opioid crisis and the problems generating the opioid crisis,” Nora Volkow, MD, director of NIH’s National Institute on Drug Abuse (NIDA), tells Addiction Professional.

Past partnerships between NIDA and pharmaceutical companies have resulted in the development of Narcan, the intranasal naloxone formulation, as well as the buprenorphine implant Probuphine.

In this latest initiative, efforts to reverse and prevent opioid-related overdoses will be concentrated on two areas. The first is developing stronger, longer-acting formulations of antagonists such as naloxone to counteract high-potency synthetic opioids, including fentanyl and carfentanil, which have driven up opioid-related overdose fatalities in recent years. The second area of focus centers on studying physiological signals that can predict an impending overdose. This knowledge could facilitate the creation of a wearable device that detects an overdose, put out an alert for help and/or automatically inject naloxone.

In regards to the treatment of opioid use disorders, NIH is studying new pharmacologic approaches that aim to modulate activity of the reward circuit through antagonists of applicable receptors. In a paper published in the New England Journal of Medicine, Volkow writes that vaccines against prescription opioids, heroin and fentanyl have shown promise in preclinical studies.

Lastly, on the development of safer, non-addictive treatments for chronic pain, Volkow says the NIH’s work will be divided into two categories: interventions for pain medications based on the opioid system and those independent of the opioid system.

“In the opioid system, what we’re looking for is are there opioid drugs that can have analgesic effects that will be less addictive and produce fewer side effects like depression,” Volkow says. “As we now know much better about how the opioids signal through these receptors and how we can manipulate molecules such that we can influence that intercellular signaling cascade, it’s become possible, at least theoretically, to generate the opioid drugs that have an analgesia but are not rewarding.”

Pharmaceutical companies have invested in opioid medications that reach the brain more slowly, which prevents them from being abused, as drugs that don’t get to the brain rapidly have fewer rewarding effects and are, as a result, less addictive.

“That has led the FDA to come up with a designation that’s called abuse deterrent formulation,” Volkow says. “It’s an opioid that can’t be crushed or inhaled, or an opioid that gets absorbed slowly. That’s the lowest hanging fruit. We want to push these other areas that are higher risk, but in the long range are likely to be much more promising.”

Regarding pain treatments that are independent of the opioid system, one area up for examination that Volkow points to is the sensitivity of nerve cells to pain stimulation that are dependent on channels that allow the entry of sodium or calcium. NIH is researching medications that can potential block such channels.

“Those interventions are fascinating because what you’re basically doing is preventing the production of pain,” Volkow says. “It’s not that you are decreasing the sensitivity of the nerve cell to the pain stimulant. You’re actually interfering with it, blocking the production of the pain signaling. It’s very interesting and very promising.”