Clinical effects of a single dose of cannabinoids to patients with chronic lymphocytic leukemia

Abstract

This phase II clinical trial investigates a one-time oromucosal dose of tetrahydrocannabinol/cannabidiol (THC/CBD) in 23 patients with indolent leukemic B cell lymphomas. Primary endpoint was a significant reduction in leukemic B cells. Grade 1 − 2 adverse events were seen in 91% of the patients; most common were dry mouth (78%), vertigo (70%), and somnolence (43%). After THC/CBD a significant reduction in leukemic B cells (median, 11%) occurred within two hours (p = .014), and remained for 6 h without induction of apoptosis or proliferation. Normal B cells and T cells were also reduced. CXCR4 expression increased on leukemic cells and T cells. All effects were gone by 24 h. Our results show that a single dose of THC/CBD affects a wide variety of leukocytes and only transiently reduce malignant cells in blood. Based on this study, THC/CBD shows no therapeutic potential for indolent B cell lymphomas (EudraCT trial no. 2014-005553-39).

Keywords:

• Chronic lymphocytic leukemia
• lymphoma
• cannabinoids
• diurnal rhythm
• CXCR4
• THC
• CBD

Acknowledgments

The authors thank the Department of Clinical Pathology personnel for their assistance with flow cytometry analyses and Professor Eva Kimby for comments on the manuscript.

Author contributions

C.M.M., B.E.W., K.S., and H.R.J. recruited patients; C.M.M. collected clinical data; M.M. and A.M.W. performed and analyzed ex vivo experiments; B.E.W. did the statistical analysis; M.M. and B.E.W. prepared figures; O.B. and G.P. performed the pharmacology assays; C.M.M., B.S., and B.E.W. designed the study; M.M., C.M.M., A.M.W., B.C., B.S., and B.E.W. wrote the article; all authors have read and agreed to the published version of the manuscript.

Disclosure statement

The authors have no conflict of interest.

Additional information

Funding

This research was funded by Karolinska Institutet (B.S.), The Cancer Society in Stockholm (B.S.), The Swedish Research Council (B.S.), CIMED (B.S), The Swedish Cancer Society (B.S. and B.E.W.), Svenska Sällskapet för Medicinsk Forskning (SSMF), Svenska läkaresällskapet (B.E.W.), and Stockholm County Council (B.S. and B.E.W.).