The Role of Science in Addressing the Opioid Crisis

The Role of Science in Addressing the Opioid Crisis — NEJM – Nora D. Volkow, M.D., and Francis S. Collins, M.D., Ph.D. – May 31, 2017

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:

  1. developing better overdose-reversal and prevention interventions to reduce mortality, saving lives for future treatment and recovery;
  2. finding new, innovative medications and technologies to treat opioid addiction; and
  3. finding safe, effective, nonaddictive interventions to manage chronic pain.

Each of these areas requires a range of short-, intermediate-, and long-term research strategies.

Overdose-Reversal Interventions

Overdoses result from an opioid’s agonist effects at the mu-opioid receptor (MOR), located on brainstem neurons that control breathing. The MOR antagonist naloxone can reverse an overdose, if it is administered shortly after the overdose occurs.

Overdose fatalities have also been fueled by the increased availability of very potent synthetic opioids such as fentanyl and carfentanil (50 and 5000 times as potent as heroin, respectively).

alternative interventions against opioid-induced respiratory depression, such as 5-hydroxytryptamine type 1A (5-HT1A) agonists, ampakines, and phrenic-nerve-stimulation devices, could protect persons at particularly high risk for overdose

Treatments for Opioid Addiction

This partnership will also focus on opioid addiction (the most severe form of opioid use disorder [OUD]), 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 treating OUD:

  1. methadone,
  2. buprenorphine, and
  3. extended-release naltrexone.

These medications coupled with psychosocial support are the current standard of care for reducing illicit opioid use, relapse risk, and overdoses, while improving social function.

However, limited access to providers and programs can create barriers to treatment.

Who is limiting the access?

There is a clear need to develop new treatment strategies for opioid-use disorders.

New pharmacologic approaches aim to modulate activity of the reward circuit through antagonists of the neurokinin-1 receptor and counteract the aversive state of withdrawal through antagonists of kappa-opioid receptors.

Vaccines against prescription opioids, heroin, and fentanyl, which induce antibodies to opioids in the bloodstream to keep them from entering the brain, have shown great promise in preclinical studies.

What happens if you’re vaccinated against opioids and then suffer a terribly painful accident, like being crushed in a car crash?

How can the pain of an emergency injury be treated in vaccinated individuals?

Similarly, long-lasting monoclonal antibodies against very potent synthetic opioids (e.g., fentanyl and its analogues) have the potential to prevent overdoses and relapses.

Nonaddictive Treatments for Chronic Pain

The third area of focus is chronic pain treatment: overprescription 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.

Opioids are the only direct and most effective medications for pain because they simulate our own body’s pain-dampening molecules.

But patients with prescribed opioids aren’t even the right problem to address – they’re not the ones overdosing.

One short-term goal is the development of formulations of opioid analgesics with 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 rewarding effects

Such formulations, however, can still be misused orally and still lead to addiction. Thus, a more promising longer-term avenue to advancing pain treatment is developing a new generation of powerful, nonaddicting opioid analgesics.

Compounds that target nonopioid pain pathways, such as the endocannabinoid system, are also being evaluated for chronic pain management.

There is strong evidence of the efficacy of cannabinoids, including tetrahydrocannabinol (THC), in treating pain. Medications that target the endocannabinoid system without producing the cognitive impairment and rewarding effects of marijuana could provide a powerful new tool

Yet, the DEA still insists that marijuana has “no medical properties”. A government becomes dysfunctional when different agencies pursue opposing goals. This is another aspect of how the DEA’s war on drugs is corrupting our society.

Therapeutics that antagonize inflammatory signals involved in pain have led to FDA-approved treatments for specific pain conditions, such as tumor necrosis factor inhibitors for rheumatoid arthritis and monoclonal antibodies to nerve growth factor for osteoarthritis

Nonpharmacologic approaches 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

Development of new pain treatments builds on a foundation of basic research on the complex pathophysiology of chronic pain and the mechanisms underlying the transition from acute to chronic pain.

Public–Private Partnerships

Recent NIH–industry partnerships, such as the Accelerating Medicines Partnership, demonstrate the power of public–private collaboration in speeding the development of new medications.

So our tax dollars are supporting research that will allow corporations to fleece us and make huge profits that we’ll never see a dime of.

As we have seen repeatedly in the history of medicine, science is one of the strongest allies in resolving public health crises.

Unfortunately, science, along with any other endeavor with potential profit, has been corrupted by money.

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