Pain management has become complicated for healthcare professionals. Striking the right balance between alleviating patient pain, especially when it disrupts treatment, and acting responsibly amidst a historic opioid epidemic becomes increasingly important to reduce addiction, hospitalizations and deaths.

To do so, many providers have turned to alternative forms of pain treatment before prescribing opiates, ranging from stretching routines to hydrotherapies. Unfortunately, opioids remain a top choice for chronic pain management even though they carry serious risks along with them. But could cannabis legalization hold the key to changing that?

Prescription Painkillers and the Opioid Epidemic

It's no secret there is an opioid problem in the U.S., and many healthcare providers have put forth their best efforts to reduce opioid prescriptions in recent years. After a peak of 255,207,954 prescriptions in 2012, doctors made a concerted effort to reduce those numbers. By 2020, they only wrote 142,816,781 prescriptions, a 44% decrease. That dropped the per capita opioid prescription rate from 81.3 per 100 patients to 43.3, according to the CDC.

Still, despite efforts to reduce the rate of prescription, opioid-based medications remain highly effective for treating chronic pain and the traditional lack of a safer, effective alternative has put doctors between a rock and a hard place. In persistent or severe cases of pain, opioids are still a common option for many providers.

Even as the toll of the opioid epidemic grows, so too does the industry. According to the Journal of the American Medical Association (JAMA), the opioid industry is worth an estimated $70 billion globally, with 100 patients prescribed opioid-based medications in the U.S. alone.

The lack of safe, effective alternatives to opioid-based painkillers has limited the progress providers can make at reducing prescription rates and continually worsened the opioid epidemic.

In 2020, overdose deaths involving any opioid totaled 68,630, the vast majority of which were caused by fentanyl, according to the National Institute on Drug Abuse. That means opioids were responsible for nearly three out of every four drug overdose deaths in the U.S. that year. These numbers make clear that finding a viable alternative for pain management that gives providers a non-opioid medication option is critical.

Cannabinoids and Pain Management

Cannabis legalization and renewed research into the therapeutic potential of the plant may hold the key to a breakthrough in pain management. By studying cannabinoids, unique compounds found in the plant that interact with the human endogenous cannabinoid system (ECS), researchers are determining how to make more effective pain medications.

The ECS regulates a wide range of functions throughout the human body, including central nervous system processes like pain perception. It does so through the production of endocannabinoids like 2-Arachidonoylglycerol (2-AG) and anandamide, which influence cannabinoid receptors throughout the body, known as the CB1 receptors and CB2 receptors.

Interestingly, botanical cannabinoids found in the cannabis plant — such as Tetrahydrocannabinol (THC) or Cannabidiol (CBD) — interact with the ECS in much the same ways as the endocannabinoids our bodies naturally produce. In some cases, this makes them effective at relieving pain. THC and CBD, for example, are thought to derive their nociceptive properties, thanks to the way they interact with the CB2 receptor, which is thought to play a role in inflammatory and immunocompetent cells.

By taking the lessons researchers learn from studying these botanical cannabinoids and how they influence the ECS, pharmaceutical manufacturers are producing pure, synthetic cannabinoids to address symptoms like pain without the adverse side effects associated with opioid medications. That effort has yielded synthetic cannabinoids like dronabinol and nabilone, which are effective at alleviating pain and nausea in cancer patients. However, there remain strides to be made when it comes to synthetic cannabinoids for pain management.

Synthetic cannabinoids in general remain very much a fledgling industry, and pain management is a frontier in the space. Today, there are only four FDA-approved cannabinoid pharmaceuticals on the market — the CBD-based anticonvulsant known as Epidiolex™ and synthetic forms of THC Marinol (dronabinol), Syndros (dronabinol) and Cesamet (nabilone).

Unfortunately, while none of these cannabinoids have shown the negative side effects or risk of abuse that opioids carry, none have proven effective enough at pain management to replace opioid-based pain medications. As a result, some manufacturers are now exploring what are known as neat cannabinoids — 100% pure synthetics of compounds like THC and CBD that offer consistently effective, reliable results.

The remaining challenge is how to best deliver these neat synthetic cannabinoids, which is something the pharmaceutical cannabinoid space is now working out. Nanoparticle delivery systems offer promise when it comes to minimizing doses, shortening the onset of effects to provide instant relief, and maximizing the duration of those effects to reduce the frequency of administration.

But this isn't the same thing as the "nano" products that adult-use cannabis companies and CBD businesses have been touting in their marketing materials. It's a clinical-grade medication that takes cannabinoid medicine to the next level.

With nanoparticle delivery systems, neat synthetic cannabinoids can be administered by swabbing the inside of a patient's cheek, allowing the cannabinoids to absorb directly into circulation through the buccal membrane in the mouth. This route of administration circumvents first-pass metabolism, meaning cannabinoids delivered this way are highly bioavailable compared to other routes of administration. This allows lower dosages to be absorbed more quickly, providing fast-acting, long-lasting relief, even to patients with chronic pain.

Cannabinoid Medicines Are a Viable Alternative to Opioids

With the development of neat synthetic cannabinoids and nanoparticle delivery systems, the cannabinoid pharmaceutical space is closer than ever to disrupting opioids and providing a safer, effective alternative. And given that the opioid epidemic continues to claim more lives each year, time is of the essence. Giving providers and patients a meaningful alternative to treating pain would directly translate to lives saved.

The growth potential for cannabinoid medicines is huge if pharmaceutical manufacturers can figure it out. Market analysis from Grandview Research projects that the cannabinoid pharmaceutical space will grow from $943.5 million in 2021 to $68 billion in 2028, a massive compound annual growth rate of 104.3%. Pain management is central to recognizing this growth potential and limiting the harm of the opioid epidemic.

Of course, in order to realize the clinical-grade benefits of cannabinoid medications for pain management, manufacturers will need to satisfy regulatory agencies like the Food and Drug Administration (FDA) with clinical trials demonstrating the safety and efficacy of their products. hat effort is ongoing, as biotech companies gather real-world evidence (RWE) and engage in pre-clinical trials to demonstrate the potential power of synthetic cannabinoid medications. Could we finally be on the cusp of discovering a viable alternative to opioids?

(Sean Hall is the CEO of MedLab Clinical Ltd.)

CBD has numerous health benefits.