Dr. Ethan Russo, legendary cannabis researcher and Founder & CEO of CreDO Science joined the GCI Content Hub in conversation.
As someone who has been at the helm of cannabis research since before the endocannabinoid system entered common parlance, how does it feel to now live in a world that is reawakening to the therapeutic potentials of cannabis, as legalization continues to spread across the globe?
While I am heartened by the slow political progress on liberalization of cannabis laws globally, there is absolutely no room for complacency, which is always the clear enemy of progress. Relentless effort for change is the required tact. This is particularly true in the USA, where the public is clearly in favor of legalization, but federal legislation has stalled despite state-by-state progress. The voice of the people has been silenced. I am old enough to recall that during the 1970s, cannabis decriminalization was at the threshold, only to retrogress totally into the dark ages of drug policy during the Reagan administration. Past may yet again become prelude. The roadblocks to research remain very much active, and biomedical research funding remains woefully inadequate.
Politics aside, the science of cannabis and cannabinoids progresses steadily. Advances are evident, and yet, much work remains. Much of the world remains stuck on cannabis isolates, with all the attention on tetrahydrocannabinol (THC) and cannabidiol (CBD) to the exclusion of 148 or more other cannabinoids that the plant produces. What we know about them so far is that each has unique therapeutic properties that portend a revolution in medicine to address the key clinical targets of pain, cancer, inflammation, and psychiatric disorders. Huge gaps remain in research efforts—a clear one is the area of gynecology, which was a favored area of cannabis therapeutics in the 19th century, but which is mired in a therapeutic straight-jacket contemporaneously, as misguided policies render it an investigational gulag. No researcher need apply.
The relationship between cannabis and mental health is complex and there is a lot of research emerging in this area. With this in mind, what cannabinoids, or combinations of cannabinoids, do you believe hold the most promise to replace (or work synergistically alongside) traditional psychiatric medicines?
Psychiatry is certainly among the final frontiers of cannabis therapeutics. While it was a clear focus of Moreau de Tours in France in 1845 when Indian hemp came to Europe, it barely receives any research attention today, and remains a forbidden territory.
The role of cannabis as an agent producing opiate-sparing and treatment for addiction to other substances has been known for almost 200 years, and yet today, in the midst of an epidemic of despair, some 100,000 overdose deaths were registered in the USA in 2021. THC, when properly utilized, has a definite role to play in this context, but one that can be optimized by judicious combination with cannabidiol, and caryophyllene, both of which have solid basic science evidence for benefit on neurological pathways of addiction.
CBD as an isolate in high doses has already proven safe and effective in two Phase II clinical trials in schizophrenia. Results may even be better with properly constituted cannabis extracts. Recent research has demonstrated the essential role of the endocannabinoid system in depression, neuroplasticity and neurogenesis, and therefore cannabis-based medicines may yet provide the progress that has failed to appear from conventional psychopharmacology.
Cannabigerol (CBG) has emerged on the scene as a uniquely effective anti-anxiety agent without sedation or evidence of dependency, marking it as an extremely promising alternative to currently available options. [article link: Survey of Patients Employing Cannabigerol-Predominant Cannabis Preparations (ethanrusso.org)].
Judicious blending of phytocannabinoids and terpenoids may offer clear advantages in symptomatic treatment of dementia and even offer the prospect of slowing or even arresting disease progression in Alzheimer disease and other degenerative disorders.
Your work around Cannabinoid Hyperemesis Syndrome (CHS) is fascinating. Until recently, CHS has been an enigmatic disorder with characteristics that are not well understood. What did your research uncover about this perplexing condition?
Cannabinoid hyperemesis syndrome (CHS) was first reported in 2004 as a constellation of severe nausea, vomiting and abdominal pain coupled with an unusual behavioral quirk of compulsive hot water bathing to allay symptoms, all occurring in the context of heavy chronic cannabis usage. The pattern has remained essentially the same since, whereas the incidence of the affliction is more apparent due to a combination of better recognition and heightened risk due to the increasing availability of high concentrations of THC. CHS sufferers are unfortunately highly reticent to accept the idea that cannabis is making them sick, and the requirement for abstention to break the cycle of symptoms is commonly ignored with inevitable recurrence of the syndrome’s hallmarks.
The etiology of CHS remained a mystery until recently. Clearly, overstimulation of the CB1 receptor seems to be the trigger but fails to explain why the disorder affects some and not others. Various fringe theories include pesticide or neem exposure, but the toxicology of those substances does not match the symptom complex of CHS.
Our team went in search of the evidence of genetic susceptibility. CHS patients with a standing diagnosis and the full constellation of active symptoms were recruited and underwent genomic testing in comparison to control participants with comparable heavy cannabis usage (averaging 4 grams of herbal cannabis per day), but who lacked CHS symptoms. The results were striking and uncovered single nucleotide polymorphisms (snp) that were statistically significant five genes in comparison to controls. These included mutations on CYP2C9 (the main metabolic enzyme breaking down THC), COMT (the metabolic enzyme for dopamine), DRD2 (the gene encoding the dopamine D2 receptor), TRPV1 (the gene for a receptor affecting pain and temperature) and ABCA1 (the ATP-binding cassette transporter gene affecting cholesterol metabolism). [article link: Cannabinoid Hyperemesis Syndrome Survey and Genomic Investigation (ethanrusso.org), and page for additional information: CHS Facts! – Cannabinoid Hyperemesis Syndrome (what-is-chs.com)].
These findings mesh nicely in explaining the peculiar phenomenology of CHS, but also highlight additional risk factors for affected patients, including addiction to other substances, a plethora of psychiatric risk factors and susceptibility to diabetes and dementia later in life. The public health implications of these findings are important given the increasing availability of high potency THC preparations and the current capability for screening cannabis consumers at risk.
Traditional medical treatment is typically reactive, seeking to fix or ameliorate certain illnesses/conditions once they come to the fore, rather than taking a more proactive approach that is focussed on prevention. In what way do you believe the advent of plant-based medicines moves us closer towards being more proactive than reactive when it comes to healthcare and wellness?
The bulk of medical expenditures are related to chronic diseases, inflammation, and end-of-life care. All of these point to the dire need for preventative maintenance as opposed to the predominant medical paradigm of intervention after the fact, usually with limited gains. The world of plants offers us better insights into proper diet and longevity, evidenced by such data as the myriad health benefits of the Mediterranean diet with its emphasis on fruits and vegetables, and olive oil with their anti-inflammatory components.
A neglected area has been the health attributes of flavonoids, the pigmented components of many fruits and berries. My suspicion is that these are going to turn out to be as or more important than vitamins in future health maintenance.
Various other plants hold out promise as adaptogens, including ginseng, ashwagandha, Rhodiola et al. Arguably, cannabis with its numerous anti-inflammatory properties and anti-carcinogenic components also fits in this category. The prebiotic fibers from Acacia senegal, burdock root and others that are so lacking in modern Western diets also portend to balance the microbiome and help prevent Type II diabetes mellitus and the ravages of the metabolic syndrome.
Looking at the way illnesses/conditions are typically diagnosed, developments in diagnostic tools and the movement towards more personalised medicine – how do you believe plant medicine can be leveraged, as we move into a more sophisticated form of healthcare in years to come?
Modern medicine has devolved into remote consultation, often quite brief, with no hands-on examination and over-reliance on diagnostic tests. Prescription medicine after prescription medicine is heaped on without regard to innate toxicities and drug-drug interactions. My opinion is that the wiser course is preventative and should properly consider botanical treatment first given its efficacy and notable safety margins, with pharmaceutical intervention to follow only when necessary. Much as we might prefer to rest on the laurels of modern medicine and its successes, this fails to account for two irrefutable facts: 1) Humankind survived, sometimes extremely well, throughout the vast majority of its sojourn using plants as medicine long before the era of synthetic pharmaceuticals (mostly the last century), and 2) A tremendous morbidity and mortality accompanies the practice of “modern pharmacotherapeutics.”
I am no Luddite; there is a proper place for technology. Certainly, a great boon to personalized medicine has come to us in the form of genomic testing. This provides not only screening for genetically transmitted disorders, but also can tell us much about how a person will metabolize certain medicines and what susceptibilities they might harbor now, or in the future. Genomic testing can also be applied to assess the state of a person’s endocannabinoid system and suggest biochemical profiles of cannabis-based medicines that might provide advantages, as well as determining which ones are best avoided.
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