Cannabis has been used as a medicine for centuries. However, because of political interference and prohibition in current times, research has been limited about the benefits and applications of this plant to a variety of health problems and diseases. Dr. Ethan Russo, Director of Research and Development for the International Cannabis and Cannabinoids Institute (ICCI), has dedicated much of his career to changing that by conducting medical research with cannabis and bringing attention to the benefits of cannabis and the need for more studies through his own research, published work, and conference presentations. Dr. Russo recently spoke with us about some of his recent research efforts, cannabis dosing, and his continued push to change the stigma against cannabis as a medicine.
How did you first become interested in cannabis research? What challenges have you faced in doing such research?
Ethan Russo: I have always been interested in psychopharmacology, which is critical to the disciplines of neurology and psychiatry that I have practiced and researched. After a sabbatical in the Amazon rainforest in Peru studying the medicinal plants of the Machiguenga, I became embroiled in the cannabis controversy in 1996, the same year that medicinal cannabis became legal in California. I spent the next four years attempting to gain U.S. government approval to study cannabis treatment in migraines, to no avail despite the U.S. Food and Drug Administration’s (FDA) approval of my Investigational New Drug application in 1999. To this day, the study that I had planned on migraines has never been done.
The greatest challenge in cannabis research remains political and institutional opposition to its performance. Only reforms in the laws will change that status.
What has been the most surprising discovery for you so far regarding cannabis research?
Russo: My answer may be a surprise, that being the discovery that cannabis research and therapeutics remain so controversial in the U.S. despite the incredible body of evidence surrounding the discovery of the endocannabinoid system and the many successful clinical trials of cannabis-based medicines demonstrating their safety, efficacy, and consistency. This is the simple explanation of why I have worked for foreign companies for most of the last 23 years, currently as Director of Research and Development for the International Cannabis and Cannabinoids Institute (ICCI), a European Centre of Excellence in Prague.
In a recent article (1), you discussed the potential use of cannabis-based medicine to treat a variety of neurological disorders such as intractable epilepsy, brain tumors, Parkinson disease, Alzheimer disease, and traumatic brain injury (TBI) or chronic traumatic encephalopathy (CTE). Can you tell us about the research in those areas?
Russo: I will address each area briefly; full details are available in the first reference, which is available to everyone on open source.
Epilepsy has been treated with cannabis for more than 1000 years in the historical literature, but has only had scientific investigation in the last 40 years, culminating in the 2018 approval by the FDA of Epidiolex (GW Pharmaceuticals), a 97% pure cannabidiol preparation. However, cannabis contains numerous other anticonvulsant substances including tetrahydrocannabinol (THC), cannabidivarin (CBDV), tetrahydrocannabivarin (THCV), tetrahydrocannabinolic acid (THCA), and the terpenoid linalool. There is a great opportunity for the development of additional cannabis-based anticonvulsants.
Brain tumors remain very difficult to treat effectively, but cannabinoids show great promise as agents that complement conventional chemotherapy and radiation, prolonging survival, and, in some instances, produce long-term remissions. A recent clinical trial showed striking results in glioblastoma multiforme, the most deadly brain cancer, with extended life spans in people taking Sativex (GW Pharmaceuticals) oromucosal cannabis spray in conventional doses along with temozolomide. On a theoretical basis, it may be possible to treat “benign” brain tumors that are normally unresponsive to chemotherapy with other cannabis components such as THCA.
Parkinson disease remains a difficult degenerative brain condition to treat. It is caused, in part, by a deficiency of the neurotransmitter, dopamine. However, it is much more complicated than that, and available drugs fail to halt its progression of various symptoms such as tremor, rigidity, and progressive dementia. Therapeutic trials to date have had mixed results in treating its signs and symptoms, but long-term treatment with THCA and cannabidiol (CBD) may show promise. Formal randomized controlled trials are necessary.
- E. Russo, "Cannabis therapeutics and the future of neurology." Front. Integr. Neurosci. 12, 51, 10.3389/fnint.2018.00051 (2018). https://www.frontiersin.org/articles/10.3389/fnint.2018.00051/full.
- C.A. MacCallum and E.B. Russo, "Practical considerations in medical cannabis administration and dosing." Eur. J. Intern. Med. 49, 12–18 https://doi.org/10.1016/j.ejim.2018.01.004 (2018).
- M. Backes, Cannabis Pharmacy: The Practical Guide to Medical Marijuana (Black Dog and Leventhal Publishers, New York, New York, 2017).
- B. Goldstein, Cannabis Revealed: How the World's Most Misunderstood Plant Is Healing Everything from Chronic Pain to Epilepsy (Bonni S. Goldstein MD Incorporated, Los Angeles, California, 2016).
- N. Whiteley, Chronic Relief: A Guide to Cannabis for the Terminally and Chronically Ill (Alivio, LLC, Austin, Texas, 2016).