Seeking alternative treatments to tackle the opioid crisis

By George Mathew, MD

Efforts to address the opioid crisis are manyfold. Prescription drug monitoring programs (PDMPs), grant programs, the use of waiver programs, and the implementation of initiatives similar to patient-centered medical homes are all being used by states with varying degrees of success.

These programs are, however, just the tip of the iceberg in terms of innovative methods to prevent or overcome opioid abuse. As public and private sectors work alone and in partnership, there is renewed focus on discovering (1) new, nonaddictive pain strategies, (2) ways to prevent relapse during addiction management, and (3) new ways to leverage data and technology to address the growing opioid epidemic.

New pain management strategies

There is growing research into non-opioid pain therapies as well as alternative ways to improve pain therapies to remove or reduce the likelihood of addiction and other side effects:

  • Pfizer and Lilly will this year seek U.S. Food and Drug Administration (FDA) approval for tanezumab, a new type of non-opioid pain medication for chronic pain in patients with osteoarthritis and chronic back pain.
  • University of North Carolina (UNC)-Chapel Hill researchers and collaborators have uncovered the structure of opioid receptors, an important first step in developing opioids that relieve pain without causing severe side effects. The idea is to target the kappa opioid receptor (KOR) because drugs that bind to KORs don’t cause addiction or death from overdose, said the senior author of the study, Dr. Bryan Roth. One company, Cara Therapeutics, is conducting phase 2 studies into a product that targets the body’s peripheral KOR receptors to treat acute pain, chronic pain and pruritus.
  • Clinical studies into a TrkA inhibitor for the treatment of chronic pain are underway, and studies are ongoing for a sigma-1 antagonist to manage nerve-related pain. A proprietary synthetic formulation from Centrexion, which is in phase 2b studies, met primary endpoints for osteoarthritis knee pain without the risks of dependence or abuse. And Hydra Biosciences has completed phase 1 studies into a transient receptor potential (TRP) channel blocker to treat painful diabetic neuropathy by blocking pain signals directly to the area in which pain is occurring, rather than acting in the brain, as opioids do.
  • In a paper published in Science, researchers in Germany discuss a method to alter Fentanyl to work only at lower pH, so it could potentially target the site of injury rather than the central nervous system. Nonclinical research has so far shown no addiction potential.
  • Medical marijuana is also being investigated as an alternative to opioid medication; however, the complexity of the endocannabinoid system makes it difficult to inhibit specific pain pathways without side effects, such as cognitive impairment and addiction. It does, nevertheless, show promise in treating some conditions, such as spasticity in multiple sclerosis.
  • A growing body of research examines the use of virtual reality as a new form of medication-free pain treatment. While cognitive behavior therapy and mindfulness have been found to be effective in treating pain, few patients practice these techniques. Virtual reality, on the other hand, lets patients put on a visor for 20 minutes to achieve the same effects as mindfulness.

In addition, the National Institutes of Health (NIH) is partnering with many biopharmaceutical companies and academic research centers to uncover nonaddictive painkillers and strategies to manage pain, innovative treatments and technologies to treat opioid use disorders (OUD), and improved preventions and interventions to save lives.

Preventing relapse

Another line of research has been to develop ways to prevent opioid relapse and overdose. An example is a project to evaluate the addition of an opioid antagonist in a subcutaneous implant to treat OUD. Opiant, which develops therapies for OUD, and drug delivery developer Titan are collaborating on a product to deliver constant therapeutic levels of an opioid agonist for up to 6 months. The goal is to replace the monthly naltrexone injections with longer-term treatment to improve recovery and reduce the chance of relapse.

Efforts continue to address opioid withdrawal. The FDA has granted marketing approval for a device, the NSS-2 Bridge, that provides patients with relief from opioid withdrawal symptoms. The device works by emitting electrical pulses to stimulate branches of certain cranial nerves.

The saying that prevention is better than cure is apt in opioid abuse. Toward that end, the Adolescent Brain Cognitive Development (ABCD) study, an NIH initiative, has recruited more than 7,500 adolescents and their families for a study into brain development and child health in the United States. A key objective is to understand the long-term effect of substance abuse and other environmental exposures on the developing brain. The study is enabled thanks to several technological breakthroughs, including noninvasive neuroimaging, informatics and big data that make it easy to share and analyze anonymized data.

Commitment to innovation

The U.S. government remains committed to addressing the opioid crisis through a variety of measures. In December 2017, the Department of Health and Human Services hosted a code-a-thon, inviting innovators to compete for three $10,000 prizes in the areas of prevention track coding, treatment track coding and usage track coders. Among the winners were the Origami Innovation team for its system that tracks overdoses in real time; the Opioid Prescriber Awareness Tool, which allows physicians to compare their opioid prescribing habits to those of their peers; and Visionist Inc.’s Take Back America, which “focuses on take-back programs at pharmacies where opioids can be returned”, according to mobihealth news.

Disruptive technologies hold promise in the battle to overcome OUD. Among the breakthrough developments are:

  • The use of smartphones and mobile technology to give healthcare providers information about opioids
  • Wearables to help patients tackle pain
  • Big data and analytics to help identify patients at risk or those abusing the system
  • Digital mapping to give officials the data they need to respond to a public health crisis
  • Telemedicine, which could be particularly helpful when treating patients in remote areas

Innovation in the areas of new medications, new therapies to address OUD, and digital technologies will all be important if the United States is to markedly reduce the costly and burdensome opioid crisis.

George Mathew, M.D. is the Chief Medical Officer for the North American Healthcare organization for DXC. In this role, he serves as the clinical expert and healthcare thought leader to our healthcare clients in transforming the healthcare marketplace. Dr. Mathew graduated from Boston University School of Medicine and completed his residency in Internal Medicine at Greenwich Hospital/Yale University in Connecticut.


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