leukemia cells express functional CB1 and CB2 receptors (Moaddel et al., 2011).

THC is the most studied cannabinoid in leukemia treatment.

Studies with THC shown cytotoxic properties induced by apoptosis in leukemia cells (Herrera et al., 2005; Jia et al., 2006; Liu et al., 2008).

This apoptosis looks to be mediated by intrinsic pathways involving ceramide-dependent mitochondrial stimulation (Herrera et al., 2006; Lombard et al., 2005).

Also, other CB1/2 agonists showed leukemia cell growth and proliferation inhibition (Gallotta et al., 2010; Yrjölä et al., 2015).

CBD showed cell activation modulation too, but the mechanism failed to show G protein-coupled receptor pathways, suggesting unknown internal mechanisms (Giudice et al., 2007).

Literature:

Gallotta, D., Nigro, P., Cotugno, R., Gazzerro, P., Bifulco, M., and Belisario, M.A. (2010). Rimonabant-induced apoptosis in leukemia cell lines: activation of caspase-dependent and -independent pathways. Biochem. Pharmacol. 80, 370–380.

Giudice, E.D., Rinaldi, L., Passarotto, M., Facchinetti, F., D’Arrigo, A., Guiotto, A., Carbonare, M.D., Battistin, L., and Leon, A. (2007). Cannabidiol, unlike synthetic cannabinoids, triggers activation of RBL-2H3 mast cells. J. Leukoc. Biol. 81, 1512–1522.

Herrera, B., Carracedo, A., Diez-Zaera, M., Guzmán, M., and Velasco, G. (2005). p38 MAPK is involved in CB2 receptor-induced apoptosis of human leukaemia cells. FEBS Lett. 579, 5084–5088.

Herrera, B., Carracedo, A., Diez-Zaera, M., Gómez del Pulgar, T., Guzmán, M., and Velasco, G. (2006). The CB2 cannabinoid receptor signals apoptosis via ceramide-dependent activation of the mitochondrial intrinsic pathway. Exp. Cell Res. 312, 2121–2131.

Jia, W., Hegde, V.L., Singh, N.P., Sisco, D., Grant, S., Nagarkatti, M., and Nagarkatti, P.S. (2006). Delta9-tetrahydrocannabinol-induced apoptosis in Jurkat leukemia T cells is regulated by translocation of Bad to mitochondria. Mol. cancer Res. MCR 4, 549–562.

Liu, W.M., Scott, K.A., Shamash, J., Joel, S., and Powles, T.B. (2008). Enhancing the in vitro cytotoxic activity of Delta9-tetrahydrocannabinol in leukemic cells through a combinatorial approach. Leuk. Lymphoma 49, 1800–1809.

Lombard, C., Nagarkatti, M., and Nagarkatti, P.S. (2005). Targeting cannabinoid receptors to treat leukemia: role of cross-talk between extrinsic and intrinsic pathways in Delta9-tetrahydrocannabinol (THC)-induced apoptosis of Jurkat cells. Leuk. Res. 29, 915–922.

Moaddel, R., Rosenberg, A., Spelman, K., Frazier, J., Frazier, C., Nocerino, S., Brizzi, A., Mugnaini, C., and Wainer, I.W. (2011). Development and characterization of immobilized cannabinoid receptor (CB1/CB2) open tubular column for on-line screening. Anal. Biochem. 412, 85–91.

Yrjölä, S., Sarparanta, M., Airaksinen, A.J., Hytti, M., Kauppinen, A., Pasonen-Seppänen, S., Adinolfi, B., Nieri, P., Manera, C., Keinänen, O., et al. (2015). Synthesis, in vitro and in vivo evaluation of 1,3,5-triazines as cannabinoid CB2 receptor agonists. Eur. J. Pharm. Sci. Off. J. Eur. Fed. Pharm. Sci. 67, 85–96.