I was a young cannabis research student on my first trip abroad for an international research conference. Of all the places in the world to discover your first science, the cognitively liberal nation of the Netherlands and the beautiful city of Leiden were pretty high there. I didn’t know what to expect and in addition to presenting my first scientific poster, I had a first glimpse of the academic world. Events like these give us a glimpse into the future of research and medicine in this field. There were a lot of amazing memories made on this trip. But a few presentations from the week of presentations stood out to me. So much so that I sued the speakers to find out more about their study. One presentation was particularly powerful in framing the value this new area of research could bring to modern medicine, and I will share that study with you today.
Graft versus host disease (GVHD)
The field of transplantation medicine will see developments over the next few decades that will look like something out of a science fiction documentary. Currently, transplant treatments are hampered by our understanding of the immune response of those receiving treatments. More than 25,000 hematopoietic stem cell (HSCT) transplants are performed each year for the treatment of lymphomas, leukemias, immunodeficiency diseases, congenital metabolic abnormalities, hemoglobinopathies and myelodysplastic and myeloproliferative syndromes (Weisdorf, 2007).
Many variables impact GVHD results. Multivariate analysis of overall survival and relapse-free mortality (NRM) data showed that the likelihood of GVHD may be affected by age, prior acute GVHD, time from transplantation to cGVHD, type of donor, disease status at time of transplantation, GVHD prophylaxis, gender mismatch, serum bilirubin, Karnofsky score, and platelet count (Arora et al.2011).
GVHD affects a significant proportion of transplant patients, between 30% and 70% of patients, depending on the degree of matching between the donor tissue and that of the patient. GVHD is currently managed with a host of immunosuppressive drugs that promote the body’s uptake of donated tissues (Shlomchik, 2007). Cannabidiol is something that has recently been explored to help manage this immune response. 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 that CBD could have a positive impact on GVHD. This brings us to one of the most powerful medical studies that demonstrate the therapeutic potential of cannabinoids.
The article, published in Biology of Blood and Marrow Transplantation, aimed to explore the potential of CBD in GVHD. The team recruited 48 patients with leukemia or myelodysplastic syndrome. Patients transplanted from an unrelated donor received CBD 300 mg/day orally beginning 7 days before transplantation until day 30.
None of the patients developed acute GVHD while consuming CBD (i.e. before day 30). The median time to onset of acute GVHD was significantly shorter in the control group compared to the CBD group (20 versus 60 days, P = 0.001). One patient developed acute grade I GVHD and 7 patients developed acute grades II-IV GVHD after discontinuation of CBD. No grade III to IV toxicity has been attributed to CBD. Relapse-free mortality rates (deaths not associated with transplantation) at 100 days and 1 year after transplantation were 8.6% and 13.4%, respectively. Among patients who survived more than 100 days, the cumulative incidences of moderate to severe chronic GVHD at 12 and 18 months were 20% and 33%, respectively.
Figure 2. The GVHD ranking (Holler, Greinix and Zeiser, 2019)
Seeing these results for the first time alongside qualitative data in the form of patient testimonials and images was an incredibly profound experience that is difficult to replicate in a written format. The Israeli group’s study showed for the first time the potential role of CBD in preventing GVHD. Combining 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 to explore whether longer exposure to CBD can further reduce acute late GVHD and/or GVHD chronic. Additionally, CBD has been shown to induce apoptosis of myeloid and lymphoid leukemic cells both in vitro and in vivo (McKallip et al., 2006). Although this research has yet to be translated into human studies, there remains incredible potential for anti-leukemia benefits to be discovered yet. The safety of CBD has been noted even when given in conjunction with standard GVHD treatment. CBD has also been well tolerated by patients with no serious adverse effects due to its reported consumption. The group intends to validate these results in a prospective, placebo-controlled, double-blind, randomized study (Yeshurun et al.2015).
transplantation This study focused on patients undergoing hematopoietic stem cell transplants in patients with leukemia and explored the effectiveness of CBD against myeloablative conditions that involve total body irradiation. Patients receiving stem cell transplants are particularly susceptible to the debilitating symptoms of GVHD.
Experiencing this study in person, I was almost shocked 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 on cannabinoids and cannabis extremely difficult. Studies like this demonstrate the incredible potential of cannabinoids and the life-changing possibilities that are unlocked through research and science. Thank you to all the scholars who have spent the last decades resisting these restrictions and building legitimacy in this field. Scientists are the unspoken heroes who have provided legitimacy and evidence to support the emergence of the multi-billion dollar cannabis industry that will change lives around the world.
Science has not always been communicated in the most interesting or accessible ways. 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 at https://edu.globalcannabinoidsolutions.com/.
Arrah, M. et al. (2011) ‘Chronic GVHD Risk Score: An Analysis from the Center for International Blood and Marrow Transplant Research’, Blood. American Society of Hematology, 117(24), pp. 6714–6720. doi: 10.1182/BLOOD-2010-12-323824.
Burstein, S. (2015) ‘Cannabidiol (CBD) and its analogues: a review of their effects on inflammation’, Bioorganic and medicinal chemistry. Pergamum, 23(7), pp. 1377–1385. doi: 10.1016/J.BMC.2015.01.059.
Holler, E., Greinix, H. & Zeiser, R. (2019) “Acute graft versus host disease”, The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cell Therapies. Springer, p. 323–330. doi: 10.1007/978-3-030-02278-5_43.
McKallip, RJ et al. (2006) “Cannabidiol-induced apoptosis in human leukemia cells: a novel role of cannabidiol in regulating p22phox and Nox4 expression”, Molecular pharmacology. Mol Pharmacol, 70(3), p. 897–908. doi: 10.1124/MOL.106.023937.
Petrosino, S. et al. (2018) “Anti-inflammatory properties of cannabidiol, a non-psychotropic cannabinoid, in experimental allergic contact dermatitis”, Journal of Pharmacology and Experimental Therapeutics, 365(3), p. 652–663. doi: 10.1124/jpet.117.244368.
Shlomchik, WD (2007) “Graft versus Host Disease”, Nature Reviews Immunology 2007 7:5. Nature Publishing Group, 7(5), p. 340–352. doi: 10.1038/nri2000.
Weisdorf, D. (2007) ‘GVHD—Nuts and Bolts’, Hematology. American Society of Hematology, 2007(1), p. 62–67. doi: 10.1182/ASHEDUCATION-2007.1.62.
Yeshurun, M. et al. (2015) “Cannabidiol for the prevention of graft versus host disease after allogeneic hematopoietic cell transplantation: results from a phase II study”, Biology of blood and marrow transplantation, 21(10), p. 1770–1775. doi:10.1016/j.bbmt.2015.05.018.
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