September is Pain Awareness Month.

In 2001, dozens of healthcare and consumer organizations established September as Pain Awareness Month, focusing on pharmaceutical and over-the-counter pain solutions. Seventeen years later, California has legal adult-use cannabis, which has been used to manage pain since, well … throughout human history.

It’s sadly true that scientific study lags far behind centuries of people using marjuana as medicine. Add the growing popularity of CBD, the non-psychoactive cannabinoid that’s also shown promise for pain relief without the THC high, and it’s clear that the potential far outpaces our current understanding of how and why cannabis helps with pain and discomfort.

[CANNABIS FOR PAIN | Science backs the plant’s painkilling reputation]

To kick off Pain Awareness Month, Eaze spoke with Dr. Sue Sisley, the Arizona scientist on the brink of unveiling the first clinical, triple-blind, placebo-controlled study to determine whether cannabis can be effective in treating military veterans suffering from PTSD.

Sisley says her work with the cannabis-focused Scottsdale Research Institute is just four out of 76 trial patients away from completion, the end of a decade-long struggle against obstacles including the U.S. government and the University of Arizona.

Here, Sisley answers our questions about cannabis and pain management, and gives an update on the status of her historic work, whose outcome will remain unknown by anyone until its release in the coming months.

Eaze: As of this moment, what’s the state of research on cannabis for pain management?

Sisley: Sadly, I think we’re still in the infancy of this work. But there was enough data on cannabis for pain that the National Academy of Sciences, which ranked over 10,000 articles based on scientific credibility, concluded that there was strong scientific evidence to support that cannabis is good for pain management. We don’t have comprehensive random controlled trials that look at how to treat cannabis for pain. How do you harness the plant for a new patient, where do they start? Those are some of the practice guidelines that are still missing.

Eaze: Why has that not started already?

Sisley: The U.S. government has systematically impeded cannabis efficacy research. Most of our taxpayer dollars are spent attempting to uncover all the negative side effects and addiction potenial.

Eaze: Even if that weren’t the case, do you think it’s possible to map the effects of different strain and terpene profiles?

Sisley: It’s hard to imagine that we’d have a clear path with any of this. It all really depends on where the money gets invested. We can’t do clinical trials without millions of dollars. It cost $2.3 million for us to study 76 subjects in PTSD; imagine what it would cost to research phenotypes across a big sample of patients!

We’ve got a lot of good people with high aspirations for that, nonprofits, even just the genetic mapping is already a big step toward getting closer to what we call “precision medicine.” To understand what’s the genetic map of the strain, and how do humans respond to that clinically – but you have that issue where each patient is unique, and one person might respond differently from another.

Eaze: What do you believe to be the best cannabis remedy for pain relief?

It’s so complex. In our PTSD study, we’re not measuring pain, but we’re seeing some of the veterans during the course of the 10-week study take themselves off their opiods without guidance from us, because they feel like the study drug is adequately addressing their pain. It’s really remarkable. So that was a big surprise secondary effect. Fortunately, one corollary from this opioiod epidemic is that we’re finally seeing government funding for research into cannabis as a substitute for opioids.

Eaze: Forgetting the science for a moment – deep in your soul, what do you just know cannabis does for pain?

Sisley: I can confidently say that it does reduce pain intensity. It doesn’t exactly wipe out pain or cure pain. It takes the edge off the pain so patients can be more functional. Especially for neuropathic pain. That one is solid. It definitely seems to work for spasticity in a variety of neurological conditions, and not just MS – in general. And there’s no question that it has quite a big role in suppressing nausea and vomiting.

[SEE ALSO: Cannabis for nausea: Queasy relief is a cannabis core competency]

A lot of patients claim to be using cannabis for anxiety and depression, but in the lab, I’m also seeing people developing anxiety within 10 minutes of smoking one of the batches from the federal government. And that can be confusing for the new user. They assume cannabis is relaxing but it depends on which chemovar you are using.

“When you embark on cannabis as a medicine, you have to go on your own personal odyssey to find out what’s your best fit.”

The issue is that the plant is so complex. When we talk to the lay public about the cannabis plant, and the hundreds of phenotypes that have different effects, this is the problem: Everybody has to go on their own personal journey. When you embark on cannabis as a medicine, you have to go on your own personal odyssey to find out what’s your best fit.

It’s just like any pharmaceutical I’d prescribe, the majority of them don’t work. Especially for neuropathic pain. We have to just experiment to get that perfect fit, and they’ll have to try several different prescriptions, different formulations until they hit that sweet spot.

Eaze: Where do you fall on CBD for pain relief?

Sisley: I’ve had so many patients report that CBD is working for them tremendously! I’m not a big advocate of isolated cannabinoids on their own. But I can’t ignore the vast amount of reports from all these patients claming they’re rubbing CBD lotion on joints, and getting relief. People who’ve had intractable pain for years. How do you explain that? That’s my frustration with the CBD market; they haven’t done the investment in the research side.

Eaze: How would you explain how cannabinoids help with pain? What are the biomechanics of it?

Sisley: Well, with opioids, we are dealing with opioid receptors on the brain; the molecule reacts with the area and causes a sensation of less pain. But cannabis is far more complex. The receptors we talk about the most are intimately intertwined with the nerves in the central nervous system. There’s evidence that there’s coupling between pain receptors and [endocannabinoid] receptors. There are lots of theories that cannabinoids block the communication between neurons. So a pain impulse that would normally fly up your spinal cord gets dampened in the interplay between the nervous system and ECS.

Eaze: Inflammation – which the body produces as an immunity response – comes up a lot when we talk about marijuana’s medicinal value.

Sisley: We’ve had some evidence that cannabis affects the inflammation response pathway. Pain is almost always accompanied by inflammation. Arthritis, colitis … ‘Itis’ means inflammation. So if you have a way of supressing the inflammatory pathway, then you get some subjective relief. We’ve never really quantified the degree of anti-inflammation. We’re doing that (in the PTSD study), drawing blood for markers of inflammation. We measure it pre-treatment and post-treatement to be able to see if the cannabis they’re taking is having an impact on the inflammatory process. Everbody claims it is anti-inflmamatory, but no one’s really measured that.

Eaze: Your PTSD study is 10 years in the making. How’s it coming along?

Sisley: We’re at the home stretch! It took us seven years to get under way; three years ago we finally commenced the trial, and it was always designed to be a three-year study. We just enrolled patient No. 72, so we have four more military vets that have to complete the protocol by the end of the year for us to finish on time.

Eaze: But there’s no way to see results until it’s over, right?

Sisley: Our final numbers in the pipeline are looking really promising. Then we’ll release the database, and then unblind everything. It’s completely walled off to me and all others since it’s triple-blind, and there’s a placebo control. That’s how we eliminate any chance of human bias.

Eaze: OK, we have to know: Knowing that smoking flower is part of the trial, how do you give a marijuana ‘placebo’?

Sisley: The governnment issues the placebo. They give us the same cannabis they’ve used for other batches, with the cannabinoids and terpenes taken out so it’s just inert plant material. It looks nearly the same and smokes the same, it just has no chemical effect. I’m just as curious as you, because we’ve had experienced users who were fooled by placebo in previous clinical trials.