The cannabis study that blew my mind

In my early days as a cannabis research student on my first trip overseas to an international research conference. Of all the places in the world to experience your first science conference, the cognitively liberal nation of the Netherlands and the beautiful town of Leiden was high on the list. Events like these afford us a glimpse into the future of research and medicine in this field as well as some much needed social interaction for the academics. I was gaining my first taste of the social side of the academic world and did not know what to expect. As well as this, I was frantically preparing for presenting my first scientific poster. Thankfully, all went well. I even survived a grilling from the two legends, Dr Ethan Russo and Professor Roger Pertwee, so would call the event a success!

A lot of incredible memories and connections were built on that trip. But a few studies from the week of presentations stood out to me. One of them, so much so, that we pursued the speakers to understand more about their study. One presentation was particularly powerful in framing the value that this new realm of research could bring to modern medicine and I shall share that study with you today.

 

Graft versus-host-disease (GVHD)

The field of transplantation in medicine will see developmentsover the next decades that resemble something from a sci-fi documentary. Atcurrent, transplant treatments are hindered by our understanding of the immune response of those receiving treatments. More than 25,000 hematopoietic stem cell transplantations (HSCTs) are performed each year for  the treatment of lymphoma, leukemia, immune-deficiency illnesses, congenital metabolic defects, hemoglobinopathies, and myelodysplastic and myeloproliferative syndromes (Weisdorf, 2007).

Many variables impact the outcomes of GVHD. Multivariate analysis of overall survival and nonrelapse mortality(NRM) data has shown GVHD likelihood can be impacted by age, prior acute GVHD,time from transplantation to cGVHD, donor type, disease status at transplantation, GVHD prophylaxis, gender mismatch, serum bilirubin, Karnofsky Fscore, and platelet count (Arora et al., 2011). Patients receiving transplanted stem cells are particularly susceptible to the debilitating symptoms of GVHD.

https://hcp.jakafi.com/graft-versus-host-disease/agvhd

GVHD affects a significant portion of transplant patient, anywhere between 30 & 70% of patients depending on how closely the donors tissue matches with the patient. GVHD is a currently managed with a host of immune suppressing drugs that support the body’s uptake of the donated tissue (Shlomchik, 2007). Cannabidiol, is something that has recently been explored to aid in this immune response management. The anti-inflammatory properties of the non-psychoactive compound are well documented (Burstein, 2015; Petrosino et al., 2018). Based on this alignment of principles, an Israeli group hypothesized CBD may positively impact the GVHD.  This brings us onto the study that was one of the most powerful medical studies that solidified the therapeutic potential of cannabinoids in medicine. The paper in question focused on patients undergoing hematopoietic stem cell transplantations in patient suffering from leukaemia and explored the efficacy of CBD in comparison with myeloablative conditions which involves total body irradiation.

 

The paper, published in Biology of Blood and Marrow Transplantation set out to explore the potential of CBD in GVHD. The team recruited 48 Patients with leukemia or myelodysplastic syndrome. Patients transplanted from an unrelated donor were given CBD 300 mg/day orally starting 7 days before transplantation until day 30.

None of the patients developed acute GVHD while consuming CBD (ie, before day 30). The median time to onset of acute GVHD was significantly shorter in the control group compared with the CBD group (20 versus 60 days, P = .001). One patient developed grade I acute GVHD, and 7 patients developed grades II to IV acute GVHD after CBD discontinuation. No grades III to IV toxicities were attributed to CBD. Rates of nonrelapse mortality (deaths not associated withthe transplant) at 100 days and at 1 year after transplantation were 8.6% and 13.4%, respectively. Among patients surviving more than 100 days, the cumulative incidences of moderate-to-severe chronic GVHD after 12 and 18 months were 20% and 33%, respectively.

(Holler, Greinix and Zeiser,2019)

Seeing these results for the first time alongside qualitative data in the form of patient testimonies and images was an incredibly profound experience thatis hard to replicate in a written format. The Israeli group's study showed for the first time the potential role of CBD in the prevention of GVHD. The combination of CBD with standard GVHD prophylaxis is a safe and promising strategy to reduce the incidence of acute GVHD.  Given that CBD was safe and well-tolerated and in light of the encouraging results the Israeli institution is planning a phase II trial aiming to explore if longer exposure to CBD may further reduce late-onset acute GVHD and/or chronic GVHD. Additionally, CBD has been shown to induce apoptosis of myeloid and lymphoid leukemic cells both in vitro andin vivo (McKallip et al.,2006). Despite this research not yet having been translated into human studies, there remains incredible potential for antileukemic benefits to befurther uncovered. The safety of CBD was noted even when administered in combination with the standard GVHD treatment. CBD was also well tolerated by patients with no severe adverse events due to its consumption being reported. The group intends to validate these results in a prospective, placebo-controlled, double-blind,randomized study (Yeshurun et al.,2015).

Experiencing this study in person, I was left in near shock at the impact of CBD on the lives of these patients and the improvement in their quality of life. Our strict drug policies have made research cannabinoids and cannabis extremely challenging. Studies like this demonstrate the incredible potential of cannabinoids and the life-changing possibilities that are being unlocked through research and science. Thank you to all of the researchers who have spent the last decades resisting these restrictions and building the legitimacy of this field. Scientists are the unspoken heroes who have brought legitimacy and evidence to support the emergence of the multibillion-dollar cannabis industry which will change lives across the globe.

Science hasn’t always been communicated through the most interesting or accessible mediums. To contribute to our beloved field, we have created a free education platform for the public. Our goal for this is to help the accessibility of cannabis science and knowledge to help others see the potential of cannabis.

Join us in bringing this important science to the masses Here : https://edu.globalcannabinoidsolutions.com/.

References

Arora, M. et al.(2011) ‘Chronic GVHD risk score: a Center for International Blood and MarrowTransplant Research analysis’, Blood. American Society of Hematology,117(24), pp. 6714–6720. doi: 10.1182/BLOOD-2010-12-323824.

Burstein, S. (2015) ‘Cannabidiol (CBD) and its analogs: a review of theireffects on inflammation’, Bioorganic & Medicinal Chemistry.Pergamon, 23(7), pp. 1377–1385. doi: 10.1016/J.BMC.2015.01.059.

Holler, E., Greinix, H. and Zeiser, R. (2019) ‘Acute Graft-Versus-HostDisease’, The EBMT Handbook: Hematopoietic Stem Cell Transplantation andCellular Therapies. Springer, pp. 323–330. doi:10.1007/978-3-030-02278-5_43.

Petrosino, S. et al. (2018) ‘Anti-inflammatory Properties ofCannabidiol, a Nonpsychotropic Cannabinoid, in Experimental Allergic ContactDermatitis’, Journal of Pharmacology and Experimental Therapeutics,365(3), pp. 652–663. doi: 10.1124/jpet.117.244368.

Shlomchik, W. D. (2007) ‘Graft-versus-host disease’, Nature ReviewsImmunology 2007 7:5. Nature Publishing Group, 7(5), pp. 340–352. doi:10.1038/nri2000.

Weisdorf, D. (2007) ‘GVHD—The Nuts and Bolts’, Hematology. AmericanSociety of Hematology, 2007(1), pp. 62–67. doi: 10.1182/ASHEDUCATION-2007.1.62.

Yeshurun, M. et al. (2015) ‘Cannabidiol for the Prevention ofGraft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation:Results of a Phase II Study’, Biology of Blood and MarrowTransplantation, 21(10), pp. 1770–1775. doi: 10.1016/j.bbmt.2015.05.018.