From the New England Journal of Medicine
May 31, 2017
By Nora D. Volkow, M.D, and Francis S. Collins, M.D., Ph.D.
Opioid misuse and addiction is an ongoing and rapidly evolving public health crisis, requiring innovative scientific solutions. In response, and because no existing medication is ideal for every patient, the National Institutes of Health (NIH) is joining with private partners to launch an initiative in three scientific areas:
- developing better overdose-reversal and prevention interventions to reduce mortality, saving lives for future treatment and recovery;
- finding new, innovative medications and technologies to treat opioid addiction; and
- finding safe, effective non-addictive interventions to manage chronic pain.
Every day more than 90 Americans die from opioid overdoses. Death results from the opioid’s antagonistic effect on brainstem neurons that control breathing. In other words, the victim succumbs to respiratory failure. Naloxone can be used effectively to reduce the effect of opioid intoxication, thereby reversing the overdose, if it is administered in time. Although naloxone has saved tens of thousands of lives, overdoses frequently occur when no one else is around, and often no one arrives quickly enough to administer it.
Overdose fatalities have also been fueled by the increased availability of very powerful synthetic opioids such as fentanyl and carfentanil (50-100 times and 5,000-10,000 times more potent than heroin respectively). Misuse or accidental exposure to these drugs (e.g., when laced in heroin) is associated with very high overdose risk, and naloxone doses that can often reverse prescription-opioid or heroin overdoses may be ineffective. New and improved approaches are needed to prevent, detect and reverse overdoses.
Treatments for Opioid Addiction
The partnership will also focus on opioid addiction (the most serious form of opioid use disorder), which is a chronic, relapsing illness. Abundant research has shown that sustained treatment over years or even a lifetime is often necessary to achieve and maintain long-term recovery. Currently, there are only three medications approved for treatment: methadone, buprenorphine, and extended-release naltrexone. These medications, coupled with psychosocial support [such as rehab and 12-step programs] are the current standard of care for reducing illicit opioid use, relapse risk, and overdoses, while improving social function. There is a clear need to develop new treatment strategies for opioid use disorders. New pharmacologic approaches aim to modulate activity of the reward circuitry of the brain.
Non-Addictive Treatment for Chronic Pain
The third area of focus is chronic pain treatment: over-prescription of opioid medications reflects in part the limited number of alternative medications for chronic pain. Thus, we cannot hope to prevent opioid misuse and overdose without addressing the treatment needs of people with moderate-to-severe chronic pain. Though more cautious opioid prescribing is an important first step, there is a clear need for safer, more effective treatments.
Foremost is the plan to develop formulations of opioid pain medication with built-in abuse deterrent properties that are more difficult to manipulate for snorting or injecting, the routes of administration most frequently associated with misuse because of their more immediate rewarding effects. Such formulations, however, can still be misused orally and still lead to addiction. Thus, a more promising long-term avenue to addressing pain treatment will involve developing a powerful non-addictive analgesic. There are some fascinating x-ray crystallography studies going on that look promising.
Non-pharmacologic approaches being explored today, including brain-stimulation technologies such as high-frequency repetitive transcranial magnetic stimulation (rTMS, already FDA-approved for depression), have shown efficacy in multiple chronic pain conditions. At a more preliminary stage are viral-based gene therapies and transplantation of progenitor cells to treat pain. NIH researchers are investigating the use of gene therapy to deliver a potent anti-inflammatory protein directly to painful sites. Pre-clinical studies show powerful and long-lasting effects in reducing pain without side effects such as numbness, sedation, addiction, or tolerance.
In April 2017, the NIH began discussions with pharmaceutical companies to accelerate progress on identifying and developing new treatments that can end the opioid crisis. Some advances may occur rapidly, such as improved formulations of existing medications, opioids with abuse-deterrent properties, longer-acting overdose-reversal drugs, and repurposing of treatments approved for other conditions. Others may take longer, such as opioid vaccines, and novel overdose-reversal medications. For all three areas, the goal is to cut in half the time typically required to develop new safe and effective therapeutics.
As noted throughout the history of medicine, science is one of the strongest allies in resolving public health crises. Ending the opioid epidemic will not be any different. In the past few decades, we have made remarkable strides in our understanding of the biologic mechanisms that underlie pain and addiction. But intensified and better-coordinated research is needed to accelerate the development of medications and technologies to prevent and treat these disorders. The scope of the tragedy of addiction and overdose deaths plaguing our country is daunting. The partnership between NIH and others will take an all hands on deck approach to developing and delivering the scientific tools that will help end the opiate epidemic in America and prevent it from reemerging in the future.
Volkow, N. and Collins, F. (May 31, 2017). “The Role of Science in Addressing the Opioid Crisis.” The New England Journal of Medicine. DOI: 10.1056/NEJMsr1706626
Volkow, L. (May 31, 2017). “All Scientific Hands On Deck to End the Opioid Crisis.” [Web blog comment]. Retrieved from : https://www.drugabuse.gov/about-nida/noras-blog/2017/05/all-scientific-hands-deck-to-end-opioid-crisis