Leukemia is a group of blood cancers affecting the bone marrow and lymphatic system, characterized by an overproduction of abnormal white blood cells. (69F)

 

Best known cannabinoids for leukemia: CBD + THC (70F)

 

Best known terpenes for leukemia: thymol and d-limonene (71F, 72F)

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Main Subtypes of Leukemia

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Acute Myeloid Leukemia (AML)

 

     In AML, there is a rapid proliferation of myeloid precursor cells. It is more common in adults, and linked to genetic abnormalities like FLT3 mutations. (69F)

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Acute Lymphoblastic Leukemia (ALL)

 

In ALL, there is an overproduction of lymphoid precursors (B-cells or T-cells), and is the most common childhood leukemia. (69F)

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Chronic Myeloid Leukemia (CML)

 

     CML is a slow growing myeloproliferative disorder, typically associated with the Philadelphia chromosome (BCR–ABL fusion). There are elevated granulocytes and their precursors in CML. (69F)

 

 

Chronic Lymphocytic Leukemia (CLL)

 

     CLL has a slow accumulation of abnormal B-cells, and often occurs in older adults. CLL can vary in aggressiveness in different people. (69F)

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CB1 and CB2 expression required for AML apoptosis

 

 

     This study was to show the antiproliferative and proapoptotic effects that occurred in a subset of leukemias, mainly those from lymphoid lineage or Acute Myeloid Leukemia (AML) cells with lymphoid markers. CB1 and CB2 expression are required for THC-induced apoptosis of leukemia cells. Cells without CB1 and CB2 didn’t respond to THC. Large doses of THC were needed to kill the leukemia cells. That study supports further clinical testing of THC as a low-toxicity therapy option for a specific subset of acute leukemia patients who express CB receptors. (73F)

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CBD and THC synergy against leukemia

 

IC (50) for CBD and THC against HL60 leukemia cells

 

CBD = 8 µM (70F)

THC = 13 µM (70F)

CBD + THC = 4 µM (70F)

 

     The IC(50) of these cannabinoids show that a lower concentration of each CBD and THC is more effective at inducing apoptosis than using THC or CBD alone. If they are used alone, then a higher dose will be needed to treat leukemia. (70F)

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Combining Cannabinoids with Chemotherapy

 

     The most effective cannabinoid pairs further synergized when used alongside standard leukemia drugs (cytarabine, vincristine). They also sensitized leukemia cells to these cytotoxic agents, potentially lowering the required dose while maintaining efficacy. (70F)

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Scheduling Cannabinoids with Chemotherapy

 

     The order of administration is critical. Adding cannabinoids after chemotherapy yielded greater apoptosis, whereas reversing the order was less effective. Triple combinations (cannabinoid pairs + chemo) can be highly beneficial if timing is optimized. (70F)

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THC as an Anti-Leukemia Adjunct with Chemotherapy

 

     Using a low dose of THC at 1 µM, which is not enough to be cytotoxic on its own, sensitized leukemia cells to standard cytotoxic drugs. This reduced the IC(50) of chemotherapeutic drugs by 50%. THC’s effect on these cancer cells were from disrupting the MAPK/ERK pathway. (74F)

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THC’s induced apoptosis in Jurkat T leukemia cells

 

     THC induced apoptosis in Jurkat T leukemia cells by downregulating the Raf-1/MEK/ERK/RSK pathway. This suppression translocated BAD to the mitochondria, causing leukemic cell death. (75F)

 

     THC kills Jurkat cells mainly through the intrinsic (mitochondrial) pathway, and some contribution through extrinsic signals (FADD/caspase-8). This dual mechanism shows THC can be a potential therapy for immune-system malignancies, but the mitochondrial route is the bigger driver of apoptosis. THC induced apoptosis and temporarily stops if there is an overexpression of Bcl-2, but apoptosis will continue if exposed to THC for a longer period of time. Apoptosis occurs from cytochrome C release from mitochondria, and cleavage of BID and caspases 2, 8, and 9. (76F)

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Cannabinoids reverse multi drug resistance in T-lymphoblastoid leukemia

 

 

     Large amounts of P-glycoprotein reduce the effectiveness of chemotherapeutic drugs by pumping drugs out of cancer cells. A test shows what happens with a short (1 hour) exposure to CBD and THC, and a prolonged 72 hour exposure. (77F) The study used a dye, Rhodamine 123, to measure the efflux activity of P-glycoprotein. (78F)

 

     The 1-hour short exposure didn’t reduce P-glycoprotein expression or Rhodamine 123 efflux, showing that it was not effective in reversing drug resistance. A prolonged 72-hour exposure with THC or CBD was needed to downregulate P-gp and resensitize the leukemia cells to chemotherapy. (77F) This shows that frequent administration of CBD and THC was needed to inhibit P-glycoprotein, making the drug-resistant leukemia cells no longer drug resistant. Dronabinol (THC analog) for Acute Myeloid Leukemia (AML).

 

     In acute myeloid leukemia (AML), some white blood cells get stuck in the immature state, and cannot mature into functional blood cells. Dronabinol (THC analog) at low doses helped those immature cells differentiate into normal mature cells. Large doses of Dronabinol induced apoptosis in those cancer cells. The differentiation from the low dose changed the levels of O-linked β-N-acetyl glucosamine (O-GlcNAc) transferase (OGT), which is a new target for anti-leukemia research. (79F)

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Terpenes against Leukemia

 

 

Many terpenes have anti-cancer effects, but limonene and thymol have some known benefits against leukemia.

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D-limonene

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      D-limonene inhibits leukemia cell growth and induces apoptosis in HL-60 and K562 cells. This is from lowering bcl-2 and mutant p53 expression while raising BAX. (71F)

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Thymol

 

     Thymol induces cell death in HL-60 leukemia cells by increasing BAX, and lowering Bcl-2. Thymol activated caspases 3, 9, and 8, and cleaved PARP. It also stopped cell growth in the Sub G0/G1 phase, and caused cancerous DNA fragmentation. Thymol increased reactive oxygen species, including mitochondrial H2O2, and depolarized the mitochondrial membrane potential. (72F)

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     Adding these terpenes to the regimen of CBD and THC could help increase the effectiveness of all in treating leukemia. Lemon strains are available in THC and CBD. Thymol is not known as a cannabis terpene, but comes from the herb thyme which is easy to get. Doses would need to be researched and figured out to find the most ideal amount of each. More information about cannabis dosing is in the Breast Cancer section.