Cannabidiol for the Prevention of Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation: Results of a Phase II Study

Abstract

Graft-versus-host-disease (GVHD) is a major obstacle to successful allogeneic hematopoietic cell transplantation (alloHCT). Cannabidiol (CBD), a nonpsychotropic ingredient of Cannabis sativa, possesses potent anti-inflammatory and immunosuppressive properties. We hypothesized that CBD may decrease GVHD incidence and severity after alloHCT. We conducted a phase II study. GVHD prophylaxis consisted of cyclosporine and a short course of methotrexate. Patients transplanted from an unrelated donor were given low-dose anti-T cell globulin. CBD 300 mg/day was given orally starting 7 days before transplantation until day 30. Forty-eight consecutive adult patients undergoing alloHCT were enrolled. Thirty-eight patients (79%) had acute leukemia or myelodysplastic syndrome and 35 patients (73%) were given myeloablative conditioning. The donor was either an HLA-identical sibling (n = 28), a 10/10 matched unrelated donor (n = 16), or a 1-antigen-mismatched unrelated donor (n = 4). The median follow-up was 16 months (range, 7 to 23). No grades 3 to 4 toxicities were attributed to CBD. None of the patients developed acute GVHD while consuming CBD. In an intention-to-treat analysis, we found that the cumulative incidence rates of grades II to IV and grades III to IV acute GVHD by day 100 were 12.1% and 5%, respectively. Compared with 101 historical control subjects given standard GVHD prophylaxis, the hazard ratio of developing grades II to IV acute GVHD among subjects treated with CBD plus standard GVHD prophylaxis was .3 (P = .0002). Rates of nonrelapse mortality 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 at 12 and 18 months were 20% and 33%, respectively. The combination of CBD with standard GVHD prophylaxis is a safe and promising strategy to reduce the incidence of acute GVHD. A randomized double-blind controlled study is warranted. (clinicaltrials.gov: NCT01385124).

A systematic review of cannabidiol dosing in clinical populations

“…Lastly, it was found that doses of 5 mg/kg/d prevented occurrence of graft‐ vs ‐host disease in a phase II clinical trial ( n = 48) and 5–10 mg/kg/d doses have been shown in a case report to remove withdrawal symptoms from a patient with cannabis dependency …”

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

“…Indeed, CBD has been suggested as a promising treatment also for autoimmune myocarditis and possibly other autoimmune disorders, and it might be useful for organ transplantation (466). Very recently, the positive results of a phase II study that assessed the safety and efficacy of CBD in the prevention of acute graft-versus-host-disease were reported (931).…”

Focus on cannabinoids and synthetic cannabinoids

“…However, Δ9‐THC administration was associated with side effects including drowsiness, dizziness, ataxia, and blurred vision. In a multicenter, double‐blind, placebo‐controlled study, THC:CBD extract and Δ9‐THC extract alone were also effective for management of pain resistant to strong opioids . Cannabinoid use for pain management has also been evaluated in a few clinical studies, especially for the treatment of both neuropathic and chronic rheumatic pain.…”