You may have heard about an opioid crisis over in the US; it was declared a public health emergency in 2017 amid 130 deaths every day from opioid-related drug overdoses and 2.1 million people with an opioid use disorder.

In Australia, the problem doesn’t exist on the same scale, but still poses headaches: the rate of fatal overdoses from opioid use more than doubled in the 10 years to 2016.

Solutions are needed, with the cost to America alone worth more than half a trillion dollars according to some estimates, and Australian small cap health and biotech companies are recognising the opportunity, says Paul Rennie, chief of one of those companies, Paradigm (ASX:PAR).

Paradigm is well-known for its early clinical trial success in treating osteoarthritis by repurposing the drug pentosan polysulfate sodium.

One of the primary endpoints of the trials that have led to success has been a “clinically and statistically meaningful” reduction in knee pain, raising hopes that PPS may be used as an alternative to opioids.

“One of the reasons doctors have almost been forced into using medication like opioids is because patients suffering from chronic pain are looking for something that will reduce it,” Rennie tells Stockhead.

“They know over-the-counter analgesics and stuff like Panadol and Nurofen don’t address such pain, nor its symptoms.”

And this is where PPS may come in. The company told the market yesterday that it had discovered why PPS reduced pain – it inhibits the production of the nerve growth factor (NGF), a biomolecule involved in regulating growth, maintenance, proliferation, and survival of certain neurons. NGF is released in high concentrations in the process of inflammation, which leads to increased pain perception.

Paradigm’s phase II clinical trial has shown that PPS reduces pain, has anti-inflammatory effects and can also help preserve the integrity of the knee joint.

“We are hoping what we can do is replicate the results in phase III study, and eventually treat patients with chronic pain issues with PPS,” Rennie says. “This would give doctors an alternative to opioids.”

PPS is not addictive, Rennie says. The company is progressing towards phase III trials and a high proportion of the patients will be from the US, to satisfy FDA requirements.

“We’ve shown it works in more than 500 patients who’ve been treated with the drug in trials or under the TGA’s special access scheme,” he adds. “Phase III trials will see us try to replicate the results in up to 1000 patients.”

Zelda Therapeutics (ASX:ZLD) is another company looking to provide a solution, with its gambit being medicinal cannabis.

It is expected to read out results from a phase I trial by the end of this calendar year. The company is providing treatment for nine patients currently being prescribed opioid treatments for chronic pain.

The test patients will be provided with whole plant marijuana extract in both single and repeat doses. Zelda’s first goal is to confirm safety and tolerance levels, before assessing any changes in pain, mood and sleep patterns.

Zelda managing director Dr Richard Hopkins said the company would apply a full plant extract “containing THC and CBD” in phase I of the trial, ahead of hopeful phase II trials.

“If successful, the outcome of these trials will likely have immediate impact in major global markets where opioid overuse and addiction is a major problem,” Hopkins said.

Other ASX stocks involved include Medical Developments (ASX:MVP), which is trying to commercialise its Penthrox “green whistle” emergency pain relief device and methoxyflurane drug and Mayne Pharma (ASX:MYX) currently has its drug Kapanol listed on the pharmaceutical benefits scheme for use in chronic severe disabling pain in patients unresponsive to non-opioid analgesics.