Ethan Russo, MD, Founder/CEO of CReDO Science – Interview Series

With the partial rescheduling of federal cannabis in the U.S. and its many impending ripple effects, there are understandably numerous questions about how the plant will be studied from a medical standpoint. While some private institutions and companies are already researching their various scientific components, federal funding and backing could add a whole new layer of legitimacy—and potentially influence future reform.

For a deeper look into the scientific research side of cannabis and how its medical applications could become more recognized and utilized at the federal level, mycannabis.com spoke with Dr. Ethan Russo, MD, Founder and CEO of CReDO Science.

What fields of medicine did you mainly study while attending UMass Chan Medical School? Were plant/natural medicines even discussed at all throughout your studies?

My medical school curriculum was quite standard and I remember nothing focusing on plant medicines. Perhaps there was passing mention of original sources of a particular chemical from a natural source, but the emphasis was certainly on basic pharmacology and the development of new chemical entities. Herbal medicines and natural methods were areas in which I had teenage interest that I had to regenerate subsequently after becoming disenchanted with the results that “conventional medicine” was providing to my patients. Fortunately for me, this tangential fork in the road certainly rekindled my passion for medicine and likely vastly prolonged what might have been a much shorter career in the healing arts.

Because of my interest in neurology, my elective time in medical school was focused on pediatric and adult neurology and I did my community medicine project in a state hospital with an amazing population of institutionalized patients with rare conditions.

When it comes to medical specialties, why did you decide on neurology? What most interested you about that field compared to other fields of medicine?

This was an evolution. I started out interested in the brain, but from the standpoint of psychology, creativity and the like. I was reading Freud’s The Interpretation of Dreams in my spare time when I was 16. When I hit college, I could have gone in the direction of anthropology, Middle Eastern Studies or psychology. The first two fell out of contention quickly, and I planned a career in psychiatry and psychopharmacology, but in my second year, I took a course in physiological psychology, and was fascinated by the intricate neural networks that are fundamental to the workings of the brain. So, at age 19, the focus became neurology. Later, in medical school, it became clear to me that pediatric neurology was the more interesting sub-specialty, once again after exposure to an inspiring mentor.

In residency training, my total focus was on clinical work, and I had no real interest in doing research. That only came later when the limitations of medicine in neurology practice became dramatically apparent.

What first caught your professional attention about cannabis and its possibilities? Was it the many ways in which cannabis interacts with the brain or something else?

I knew about the medical benefits of cannabis in 1970, when my coed friends touted its benefits on dysmenorrhea (menstrual pain). My extracurricular reading was also key in terms of understanding how cannabis and psychedelics expanded consciousness and stimulated novel thinking and concepts. As a neurology resident at the Veteran’s Administration Hospital in Seattle in 1980, I saw a gentleman who added cannabis to his pipe tobacco, and in the process markedly reduced the frequency and severity of his hospitalizations for myasthenia gravis (an autoimmune disorder producing weakness and even paralysis). Decades later, that indication has still not been properly investigated.

Once I was in neurology practice in Montana, some of my multiple sclerosis patients gained benefit on their symptoms. After a sabbatical in the rainforest in Peru working with the Machiguenga tribe in 1995, I knew that I wanted to transition my practice toward one incorporating botanical medicine, and cannabis was paramount among them. In 1996, Proposition 215 was passed, serving as the catalyst for medicinal use and research on cannabis. I was fascinated with the science of the plant and the endocannabinoid system, and began writing and publishing on it, as well as discussing cannabis as an alternative treatment to my patients. Neurological conditions are particularly fertile ground for such interventions.

When working with GW Pharmaceuticals, what kinds of research and studies were they doing on cannabis plants? Since your time with them started in 2003, and this was before a lot of major cannabis reform, how was the GW team allowed to study cannabis plants without any legal issues?

GW Pharmaceuticals began growing the plant and developing cannabis-based pharmaceuticals in 1998, following licensing from the British Home Office to initiate the studies. Geoffrey Guy, the founder and chairman convinced the powers that be that British patients were using cannabis, and rather than have the law flouted, it made sense to investigate properly and develop it as a pharmaceutical that met standards of safety, efficacy and consistency. I came on as a consultant that year, and moved to a full-time position as Senior Medical Advisor in 2003.

A couple of happy accidents vastly accelerated GW’s progress. HortaPharm, a company founded in the Netherlands by American ex-pats was about to lose its license to grow cannabis and had pioneered selective breeding for various cannabis compounds. The sale of that company to GW provided a headstart that shaved years off the required research and development. The second bit of luck was that an extensive “glasshouse” operation came up for sale in a secret location in England (I’ll never tell!). Between the two, it was only two years between inception and the beginning of clinical studies of cannabis-based medicines in patients.

The development program eventually leading to approvals of Sativex (cannabis extract with about equal proportions of THC and CBD) for spasticity in multiple sclerosis in 30 countries extra-USA), and Epidiolex (highly purified CBD extract) for epilepsy associated with Dravet and Lennox-Gastaut syndromes and seizures in tuberous sclerosis (FDA-approved and in countries around the world).

During the early years, the company was also funding research in Europe and Israel on the basic science behind THC, CBD, but also the “minor cannabinoids,” tetrahydrocannabivarin (THCV), cannabigerol (CBG) and others. This became possible through the selective breeding (without genetic modification, CRISPR technology or the like) of cannabis chemovars that were rich in specific phytocannabinoids. This body of work became the foundation of much of what we know today about those compounds.

Early clinical studies of Sativex focused on symptoms of multiple sclerosis including spasticity, pain, bladder dysfunction and sleep disturbances. Epilepsy was another strong focus.

Unfortunately, because of funding and bandwidth constraints, many extremely promising leads remained undeveloped. For example, through the early studies, it was clear that cannabigerol (CBG) had myriad therapeutic benefits, but its investigation languished for 15 years. We are attempting to catch up now.

What are your duties as a member of the Cannabis Expert Panel for the United States Pharmacopeia (USP)? How do you advocate for more research and studies into cannabis?

As the only clinician on the USP panel, my efforts are to ensure that a focus remains on medical aspects of cannabis extraction and standardization. This is an extremely complex set of issues—basic definitions such as whole plant, broad spectrum, “strains” vs. chemovars, how cannabis is grown, what are allowable practices with respect to fertilization, pest control, extraction techniques, residual solvents, packaging, labeling, etc, etc. On the panel, I attempt to ensure that a therapeutic focus on herbal cannabis is maintained, and that concepts of botanical synergy and the “entourage effect” are not lost in the tendency of the industry to rush toward cannabinoid isolates, semi-synthetics and new chemical entities. The cannabis plant and patients who follow her frequently develop a beautiful mutualism or even symbiosis. That fact can be easily overlooked during scientific analysis and bureaucratic rulemaking.

How is CReDO Science LLC helping advance medical cannabis science research and opportunities?

Our work at CReDO Science is devoted to “Making Cannabis Safer and Better.” That represents a lot of territory, and has required constant pivoting to manage the changing landscape of laws. Our focus is directed toward several siloes of activity: 1) Development of our intellectual property portfolio, which includes cannabis-based formulations for consumers and industry, diagnostic testing related to the endocannabinoid system, and others, 2) Education on cannabis and the endocannabinoid system through conferences and online webinars, plus our educational platforms in partnership with MM411: Cannabis Education | Online Cannabis Certification Programs | MM411, 3) clinical consulting services for companies developing their own products. Currently, we are engaged with three companies, all outside the USA, on cannabis-based medicine pharma track programs.

How does your medical background and neurology specialty provide you with a better understanding of your role as Chief Medical Officer for Andira Pharmaceuticals?

It is crucial. Fortunately, Dana Lambert, PhD, the Founder and CEO of the company also comes from a clinical background as a hospital pharmacist who was able to experience the patient experience first-hand with all its challenges and demands. The striving for more effective therapies from cannabis and a better patient experience are prime motivations at the company. The pipeline of cannabis-based pharmaceuticals for revolutionary anti-microbial treatment, wound healing, and primary treatment of cancer with their obvious value as “disruptive technologies” portend to be headline news in the coming years.

My role there may be less neurologically focused, but having been through the regulatory process at GW Pharmaceuticals, and working as study physician and pharmacovigilance officer in some 20+ Phase I-III clinical trials certainly provided experiences that are transferable to the current development program. Over the years, I’ve had to refocus on many different disciplines under the broad topic of medical care. However, that is what keeps it intellectually challenging and interesting.

Where do you see major cannabis research going in the future? How did the recent rescheduling here in America and its subsequent ripple effects within multiple government departments change how cannabis is researched?

While the planned rescheduling may reduce the bureaucratic and logistical challenges inherent with Schedule I with its onerous security and intrusive demands, it remains to be seen how the system will perform. There have been murmurings from DC to the extent that the FDA will now consider “real world experience” in the drug development process, which would be a necessary development given the many shortcomings and pitfalls of the randomized controlled trial paradigm. While I hope for improvement, it will remain the case that most of my research and consultation work will occur extra-USA, much as it has been for the last 30 years.

Beyond that, we will be seeing a great deal more evidence for the therapeutic value of the “minor cannabinoids,” and other cannabis compounds such as the terpenoids and flavonoids. The range of therapeutic possibilities for cannabis is nothing short of astonishing. Cannabigerol (CBG) has vast potential applications as an antibiotic component, non-intoxicating, non-sedating anti-anxiety agent, and chemotherapeutic agent. On that score, the future is bright, but only if the research receives the funding that it merits.

What are some major reforms for cannabis science and research on the international level? Outside of the US, what are some other countries that are already and will continue to pave the way for medical cannabis research?

While there is a great deal of freedom with respect to cannabis commerce in the USA, this is extremely jurisdictional and inconsistent. In many ways, we are behind the curve on research, whereas more developments have from Israel and Europe, especially Spain and Italy. Canada and Australia, with populations 1/10th that of the United States, certainly pull far above their weight on the research side. Many other countries contribute, but all face stigma, disbelief and onerous restrictions of one sort or another. Cannabis is a very talented plant whose many secret attributes continue to remain for us to discover. Yes, there are potential side effects to cannabis, mainly attributable to THC excesses, and there are some people who should not use it. However, in all honesty, all these problems are easily avoidable with proper use and dose titration, and pale in comparison to the risks of most “conventional” drugs. Here and abroad, we need to have the shackles removed for research activities. Oversight and monitoring: yes! Prohibition and repression: no!

Thank you for joining us, Dr. Russo! For more information on CReDO Science, please visit its website.