Making Medical Cannabis History

In the recent annals of medical cannabis history, a defining moment came in 2013 when CNN Health Correspondent Sanjay Gupta reported on how the seemingly miraculous antiseizure effects of cannabidiol (CBD) transformed the life of a five-year-old Colorado resident, Charlotte Figi. Where 17 other anti-epilepsy medications had failed to control Charlotte’s grand mal seizures, a CBD-rich cannabis oil extract brought them down to almost zero.

Suddenly, arguing that cannabis had no therapeutic benefit became untenable and medical cannabis acquired a new legitimacy – even if the U.S. government is still playing catch-up seven years later.

As fate would have it, Charlotte and her devoted parents were lucky to get some prescient advice from an unsung hero. Without the willingness of a self-confessed “conservative” physician to recommend high CBD/low THC cannabis for Charlotte, we might still be living in a far more hostile medical cannabis environment.

That physician is Alan Shackelford, MD.

A Doctor’s Education

Shackelford’s journey to becoming Charlotte’s physician began as a young undergraduate, when he chose to study at Heidelberg University in Germany because it allowed him to satisfy his interest in both scientific research and practicing medicine.

“I was involved with quite a lot of research at the University of Heidelberg,” Dr Shackelford explained to Project CBD. “We studied the immune response of the urological system, both the kidney and the bladder and the urethra, and did animal studies, preclinical studies as well as clinical studies, and I published or co-authored about five papers while I was in medical school.”

On his return to the United States, the young Shackelford studied the immunological consequences of dietary lipid manipulation as a research fellow in nutritional science at Harvard Medical School, where he also researched the influence of behavior on the development of disease and its progression, cure or treatment.

When Project CBD enquired whether even then Shackelford had a more holistic view of medicine, he insists he was still faithful to his more traditional background.

“I was still quite conservative, but I knew that there were other ways to approach things aside from simply the standard schoolbook approach. So, I had an open mind, and I always looked for better ways to do things to treat illness. And there will always be better ways to do things, and new and innovative ways to treat illness that improve upon what we were already doing.”

After finishing his third fellowship in Boston, Dr Shackelford moved to Denver, Colorado, where he worked in occupational medicine. Medicinal use of cannabis was not yet legal in the Centennial State, and it was not something he was therapeutically familiar with.

“There were apocryphal sorts of reports of anecdotal information that it was potentially beneficial to stimulate appetite or for pain or suppression in nausea. But it wasn’t really on the radar,” he admits.

With the new millennium, Colorado became the seventh state to pass a medical marijuana bill, and after a slow start the first patients began to trickle through Shackelford’s door.

“People began to request it. They began to approach their doctors and say that they wanted to try it. Then one of my patients said, ‘Hey, I want to do it. I want to see if it helps.’ So I was intrigued, but also reluctant because, again, I looked into the literature and found next to nothing.”

When his first patient managed to wean himself off opiates, Shackelford’s interest was piqued. But he was struck by an overall lack of medical literature supporting the use of medical cannabis in patients. Ever the investigator, Shackelford made it his business to seek out any scientific research that existed at that time.

The Stars Align for Charlotte

“Just a short time before Paige Figi called, I had read a paper [“Chronic Administration of Cannabidiol to Healthy Volunteers and Epileptic Patients”] that Professor Mechoulam had published in 1980. So, when I learned that Charlotte was having three hundred grand mal seizures, I of course thought about that paper, which was very clear that CBD was beneficial in reducing seizures in seven of the eight subjects.”

This was back in 2012, when CBD strains were generally considered a stoner’s inconvenience , rather than a therapeutic goldmine.

“So, again, fortuitously,” recalls Shackelford, “I’d heard that there was a very high CBD, low or lowish THC plant available in Colorado. And that was another of those pieces of the puzzle. They just kind of came together at the right time at the right place. I had an obligation to this little girl and to her family to do what I could and use the knowledge that I had accumulated, including knowing about this high CBD plant and having read Raphi Mechoulam’s paper.”

“It was very imprecise,” admits Shackelford. “I said, we want three milligrams per kilo of body weight or about a milligram-and-a-half per pound, but we had no way of measuring the amount of CBD in the extract… Paige took [the CBD-rich cannabis] back to Colorado Springs. It was extracted into an oil, and she gave it to Charlotte with cessation of her seizures for an entire week… Charlotte continued to have seizures here and there, but she was having 300 a week and in that first week she had none. And that was absolutely remarkable. That said to me, this is incredibly important.”

U.S. Research Roadblocks

When Dr. Sanjay Gupta interviewed Shackelford for the CNN documentary, he was already exploring the possibility of researching the antiseizure effects of cannabis in Israel, having met with Professor Mechoulam and the head of the Israeli Medical Cannabis Program. But when CNN broadcast “Weed” in 2013, the physician knew without question the direction his research must go.

“I was inundated with phone calls from people from all over the world who had children who were suffering just as Charlotte had,” remembers Shackelford. “Of course, it’s traumatic for the child, but it’s the impact on the family that is also significant and tragic in many cases. Lots of these people were very desperate to get help for their children. And that propelled me with even more urgency down the road of wanting to investigate it, perfect it, and make it available to children everywhere.”

But Shackelford, like many other cannabinoid researchers, found their proposals stymied by the institutional bias against funding research into the medical use of the plant. With therapeutic-oriented research into cannabis generally thwarted in the United States, Shackelford decided his best option was Israel if he wanted to investigate the medical potential of cannabis.

“Israel was very open and had been very open since the late 1960s, early 1970s to researching cannabis,” says Shackelford. “You still have to jump through hoops to research in Israel, but those hoops don’t even exist here in the US, or now they do somewhat but at that time, it was impossible to try to do it. Israel clearly was the place that I needed to go to be able to do the studies I thought were necessary to understand cannabis better and create much more effective medicines that truly were more medical than recreational. And that’s still true.”

Eyeing the Medical Market

Eight years after Paige Figi extracted her daughter Charlotte’s CBD oil from the CBD-rich flowers Dr. Shackelford had found, the world is now awash with CBD products, including Charlotte’s Web, named after little Charlotte.

And yet for doctors, making medical cannabis recommendations still does not guarantee their patients will be able to source quality, standardised cannabis products – something that remains a great frustration for Dr. Shackelford.

This has led him to launch Shackelford Pharma, a company incorporated in Canada, but with most research taking place in Israel . “I was a bit reluctant to lend my name, because I didn’t want it to be about me,” he admits. “I want this undertaking to be about the patients that are going to benefit from the work we do. But I was overruled. Shackelford Pharma is now up and running, and it’s going to achieve all the kinds of goals that we’ve been talking about for all these years.

“I want to investigate neurological pain in things like trigeminal neuralgia and neuropathic pain. Pain, in general, is extraordinarily interesting, and we don’t have great treatments for pain that are safe and reliable. We can see that from the opiate crisis, as well as problems related to nonsteroidal anti-inflammatories where more than 100,000 mostly older Americans are hospitalised every year for the treatment of side effects. So medicines that we think of as being pretty benign actually aren’t, and if we can improve upon that – just the treatment of pain with cannabis as an effective and very safe treatment – we will have made dramatic improvements. Well, we are looking at all of it.”

One might assume from the word ‘pharma’ that Shackelford will be researching clinical applications of single molecule or synthetic cannabinoids, but whole plant cannabis will not be ignored. His goal is to create much more effective treatments for epilepsy, pain, and other conditions by carefully assessing the role of specific cannabinoids, as well as whole plant varietals.

“We’ll be able to look at the whole plant and isolated individual cannabinoids because they do have benefit in and of themselves,” said Shackelford, adding: “We aren’t abandoning the whole plant by any means. It’s extremely interesting and I think a very exciting moment.”

With Cannabis Comes Hope

Nor has Dr Shackelford abandoned his patients from his practice in Denver, whom he continues to counsel.

“The discovery of cannabis as a treatment option,” says Shackelford, “not an alternative but as a treatment option, now has given me a great deal more hope and confidence that the real thorny problems, the therapeutic problems that plague all of us, may actually have a different solution, something that we can actually turn to. So, I’ve become much more hopeful about the future of medicine, but also more hopeful as a person.

“On a personal level it is just incredibly satisfying to see someone blossom, to see someone go back to work and provide for their families… All of those things are so incredibly and profoundly moving to me that I feel like I have made a difference. And I think that one of the biggest things any of us as humans, but certainly as physicians, can hope for is to make a difference in people’s lives. I’m extremely humbled and grateful to think that perhaps my openness, or at least lack of reluctance to explore this as an option, has maybe made the world a better place. That’s pretty cool.”

In memory of Charlotte Figi, who succumbed to COVID-19.

---

The full interview with Dr. Alan Shackelford is available on the podcast Cannabis Voices. Mary Biles, a UK-based journalist, educator, and Project CBD contributing writer, is the author of The CBD Book (Harper Collins, UK). © Copyright, Project CBD. May not be reprinted without permission.

---

Project CBD is made possible by the support of our partners.