Miracle Drug? New Opioid replacement shows much promise.

A new pain relief drug appears set to revolutionise the way we treat pain, and importantly – it does not appear to be addictive. Roseanna Shanahan takes a look.

The poppy flower may look innocent and beautiful but it contains substances that have created havoc throughout the world. Many countries the world over are experiencing an opioid crisis. America's opioid crisis is certainly the worst, claiming hundreds of lives every week. This problem has reached our shores as well, with Ireland seeing a threefold increase in the prescription of oxycodone between 2006 and 2016, and a twofold increase in the prescription of fentanyl, a pain relief drug which is stronger than heroin.

There are many social and biological factors that lead to opioid addiction. For instance, the Irish health care system is flawed. Patients experience long waiting lists for surgery and for counselling, lengthening the time which they spend using opioids. The social stigma around addiction also prevents addicts from getting the help they need. Combine this with the fact that opioids are highly effective in dampening pain and evoking the feeling of euphoria in the brain, and patients stand little chance against overcoming the addictiveness of these drugs.

To eradicate this epidemic, alternative analgesics have become highly sought after. A newly developed drug called AT121 has shown promise in American preclinical trials carried out on rhesus monkeys. The results from this study were published in the journal of Science Translational Medicine in late August 2018. AT121 was found to kill pain and researchers reported that it is not addictive. It works by blocking the pathways that lead to opioid addiction in prescribed painkillers. In this study the monkeys in question were sat down and their tails placed in water baths of 50°C, which inflicted acute pain on them. Without a painkiller the animal would flinch and rapidly remove their tail from the warm water. But when the drug AT121 was administered, these monkeys showed an increase in their pain threshold - AT121 treated monkeys could withstand a greater level of pain from the water baths.

Ireland [has seen] a threefold increase in the prescription of oxycodone between 2006 and 2016

Similarly, capsaicin, which is the hot component in chilis, was placed on their tails. When AT121 was applied, the monkeys did not display any pain related behaviour. AT121 also showed to be better at treating pain than morphine. The monkeys were put through a different test to see whether AT121 had any addictive properties. Monkeys were provided with a vast amount of the drug that they could choose to self-administer. AT121-treated monkeys showed no interest in taking any more of the drug than that needed to kill their pain.

In contrast to this, monkeys treated with heroin continued to seek the drug as much as they could. Monkeys that were administered AT121 before they were administered the commonly prescribed opioid oxycodone showed less addictive behaviour, proving that it can help addicts to recover from opioid addiction as well. This drug is much safer than opioids in high doses too. Opioid related fatalities often occur due to either respiratory depression or cardiac difficulties. AT121 did not affect the lungs or heart in one monkey that was tested. The drug kills pain, without having any major side effects, and it is devoid of abuse potential.

When the drug AT121 was administered, these monkeys showed an increase in their pain threshold

However, it is important to note that these preclinical trials have many limitations. Mainly, that the nervous system of the animals tested is not a perfect replica of our own. Additionally, these experiments only measured short term pain, not the chronic pain that is experienced by many patients who use pain relief. Drug testing is a rigorous and lengthy journey, so those hoping for some relief will likely have to wait some time before this drug is approved by the various licensing agencies. For now, they may take solace in the promise that it has thus far shown.

AT121 did not affect the lungs or heart in one monkey that was tested

Other analgesics that can help combat the opioid crisis are THC and cannabinol, which are the main psychoactive properties of cannabis. Cannabis has been used medicinally for thousands of years - some of its first records of use date to 300 BC in China. An Irish doctor called Sir William O'Shaughnessy, who was born in 1808, was one of the first to introduce cannabis to western medicine. He discovered the analgesic properties of medicinal cannabis as he travelled throughout Asia. Today many people throughout the world use cannabis to kill chronic pain. In the United States, certain recovery programmes for heroin addicts use cannabis as means of weaning addicts off of opioids. These programmes have saved many lives from opioid overdose. Cannabis is a natural analgesic that has proved for thousands of years that it is efficient in killing pain. However Ireland, much like other countries, has strict laws governing medicinal cannabis use.

People suffer greatly everyday from chronic pain and hundreds die from opioid overdose. Perhaps in the future medicinal cannabis laws will become more widely-accepted, but if this doesn't happen the world has AT121 as a beacon of hope to tackle this opioid crisis.