Drug overdoses from opioids are currently the leading cause of accidental death in the US, killing at least 130 people a day. They cause more deaths than gun homicides and car crashes combined, according to a Yale University study.

What makes these drug-related overdoses unique is that a large proportion of the opioids used are obtained legally, with medical professionals prescribing them to treat moderate and severe pain. The prescription medications linked to opioid overdoses are known to be highly addictive, and if misused can lead to dependency.

This situation has only been exacerbated by dodgy dealings where pharma companies bribed doctors to prescribe their opioids to patients who do not require the degree of pain relief that the opioid brings.

Opioid overdoses have been a serious problem since the late 1990s, however, as the death rate climbed and the costs of tackling overdoses escalated to $174.9bn in 2018 (according to a report by the Society of Actuaries) US President Donald Trump declared the situation a health crisis and emergency in 2017.

Initial solutions to the US opioid crisis

Department of Health and Human Services (HHS) secretary in 2017 Thomas E Price stated: “At HHS, we’re ready to fight alongside the millions of Americans who are trying to find recovery or help their loved ones do so. The Trump Administration is committed to bringing everything the federal government has to bear on this health emergency.”

This spurred regulators and public health authorities into action to try and tackle the situation. In addition to commitments to better supporting people in recovery and finding new ways to aid pain management, US authorities at a state and federal level initiated law suits against opioid producers for their part in the crisis. Two huge opioid manufacturers – Insys and Purdue Pharma – have declared bankruptcy as a result of these legal challenges.

Although it is crucial and a welcome step that people are being held accountable for the opioid crisis that came to a head in the US in 2019, looking forward to the 2020s, we need solutions to prevent a repeat of this addiction and overdose crisis.

Crucially, there need to be innovations that do not just improve the response to overdoses, but that address the underlying issues and prevent dependency and overdoses happening at all.

Developing non-opioid painkillers

Opioids are extremely effective and life-changing for people experiencing serious chronic pain. However, the escalating opioid crisis suggests that there is an urgent need for alternative, non-opiate-based, non-addictive pain drugs. Academia and the pharma industry are successfully stepping up to make this a reality.

One example is Astraea Therapeutics’ AT-121. Discovered using computer modelling, AT-121 binds to the same receptor as opioids morphine and oxycodone – the mu opioid receptor. However, Astraea’s drug also binds to another opioid receptor – the nociception/orphaninFq peptide (NOP) receptor, which is believed to block unwanted side effects of some opioids. This double binding property also seems to enhance AT-121’s pain relieving efficacy.

Pre-clinical and clinical studies of AT-121 have also confirmed that repeated treatment with the drug, which is necessary for chronic pain patients, does not produce physical dependency, tolerance or excessive pain. Tolerance is a huge problem associated with certain opioids, which means that it is common for patients to be addicted to pain killers that are not actually effectively relieving their pain.

Another similar example is Centrexion’s CNTX-0290, which is a small molecule somatostatin receptor type 4 (SSTR4) agonist. Somatostatin has a central role in regulating pain, particularly through the SSTR4 pathway. Interestingly, pharma giant acquired this Phase I drug from Centrexion in May 2019, showing that large pharma is also committed to, and sees the opportunity of, pharmaceutical solutions to the opioid crisis.

Improving packaging of opioid drugs

In the shorter term, while innovative new products are being discovered, researched and developed, the US Food and Drug Administration (FDA) are looking at how to prevent overdose risks by improving the packaging of opioids.

Proposals may include requiring pharma companies to package opioids so each dose is sealed individually in a blister pack, rather than in traditional bottles where a 30 day prescription of pills are loose. This approach would also allow doctors to prescribe smaller quantities of opioids to patients. One company that is working to create these types of packaging is Keystone Folding Box.

There are also projects underway to create even more sophisticated solutions, such as smart pill bottles, that limit access to drugs outside of allocated time periods, and may even be able to alert medical professionals of an attempted overdose.

Moving towards non-pharmacological methods

It is important to note that the trend of primarily relying on drugs and perceiving pain as curable isn’t the only way to manage the symptoms. Instead, there are non-pharmacological methods, such as physical and other forms of therapy, which can help patients with pain management, particularly in the long term where opioids struggle to retain efficacy.

For instance, cognitive behavioural therapy (CBT) helps people to change negative thoughts and behaviours, and therefore, with regards to pain management, to alter their awareness of pain and develop better coping skills so the pain affects their quality of life less.

The benefit of non-pharmacological approaches in pain management is increasingly becoming recognised by US authorities, such as HHS, which is researching how insurance policies could also reimburse non-drug approaches to treating chronic pain, which would help to open up this option to more patients.

This brings the US more in line with countries like Japan and China where prescribing opioids has largely been avoided and been replaced with techniques like massage and lifestyle changes.

Embracing technology to support patients

Facilitating this move away from using drugs to solve problems is technology. Approved by the FDA, Pear Therapeutics ’ reSET is a digital therapeutic app allowing doctors to prescribe CBT courses to patients with opioid dependency. Therefore, allowing addicts to transition away from harmful opioids and towards a known-to-be-effective alternative option for both addiction and pain management over a 12 week period.

reSET has had remarkable success so far with 82.4% of those using the opioid-specific app remaining in therapy, compared to 68.4% not using the app. Researchers believe its efficacy is because it reprograms the brain’s reward system, which has been distorted by opioids, so that good behaviour or abstinence is rewarded.

Another example is Hey, Charlie, created by a Massachusetts Institute of Technology graduate with personal experience of watching a friend deal with opioid addiction.

Hey, Charlie encourages recovering users to identify contacts that may encourage them to relapse and locations where they might be tempted to use. The app then encourages them to avoid those people or locations and reach out to supportive friends. Health professionals are informed of these social interactions, providing them with a 360 degree, 24/7 view of their patient beyond short appointments, and ultimately improving care and treatment.