CBD and THC Reduced Drug Resistance in Cancer Cells by Decreasing P-Glycoprotein Expression | Research

The takeaway

Prolonged exposure (72 hours) to THC and CBD decreased P-glycoprotein expression in drug-resistant leukemia cells, increasing their sensitivity to the anti-cancer drug vinblastine, while short exposure had no effect.

Read this if you are interested in whether cannabinoids could enhance the effectiveness of chemotherapy drugs.

72-hour THC and CBD exposure decreased drug resistance protein P-gp and enhanced vinblastine sensitivity

What the researchers found

Researchers tested whether cannabinoids affect P-glycoprotein (P-gp), a transporter that pumps anti-cancer drugs out of cancer cells and is a major cause of multidrug resistance.

Short-term (1-hour) exposure to cannabinol, CBD, THC, and a synthetic cannabinoid did not inhibit P-gp drug efflux in either human leukemia cells or mouse cells with the MDR1 gene. This was different from the known P-gp inhibitor PSC833, which did block efflux.

However, prolonged (72-hour) exposure to THC and CBD decreased P-gp protein expression in leukemia cells, similar to the flavonoid curcumin. This reduction in P-gp correlated with increased intracellular drug accumulation and enhanced sensitivity to vinblastine, an anti-cancer drug normally pumped out by P-gp.

Why it matters

Multidrug resistance is a major obstacle in cancer chemotherapy. If cannabinoids can reduce expression of the drug resistance transporter P-gp, they might enhance the effectiveness of conventional chemotherapy drugs when used in combination. This is a fundamentally different mechanism from any direct anti-cancer effect.

The numbers in context

Short exposure (1h): no P-gp inhibition by any cannabinoid. Prolonged exposure (72h): THC and CBD decreased P-gp expression comparable to curcumin. Result: increased intracellular drug accumulation and enhanced vinblastine sensitivity.

How the study worked

In vitro cell study using a drug-resistant human leukemia cell line (CEM/VLB100) and MDR1-transfected mouse fibroblasts. Short-term (1 hour) and prolonged (72 hour) cannabinoid exposures. P-gp function measured by Rhodamine 123 efflux. P-gp expression, drug accumulation, and vinblastine sensitivity assessed.

What this study cannot tell us

In vitro cell line study. The concentrations and exposure times may not be achievable in patients. Only one drug-resistant cell line was tested in detail. The interaction between cannabinoids and chemotherapy drugs in vivo could be more complex than this simplified model suggests.

How to read the evidence

In vitro cell study providing preliminary mechanistic evidence. Important finding but requires extensive further research before clinical application.

When this study was published

Published in 2006. Research on cannabinoid-chemotherapy interactions has continued, but clinical evidence for this combination approach remains limited.

The bigger picture

This finding opens the possibility that cannabinoids could serve as chemotherapy sensitizers rather than direct anti-cancer agents. The time-dependent effect (72 hours needed, not 1 hour) suggests the mechanism involves changes in gene expression rather than direct transport inhibition.

Questions still open

Do cannabinoids reduce P-gp expression in tumor cells in vivo? Could combining cannabinoids with standard chemotherapy improve cancer treatment outcomes? What cannabinoid concentrations are needed at the tumor site?

Common questions

Can cannabinoids make chemotherapy more effective?

This cell study found that prolonged exposure to THC and CBD reduced expression of a drug-resistance protein in leukemia cells, making them more sensitive to the chemotherapy drug vinblastine. However, this is a laboratory finding and has not been confirmed in patients.

Do cannabinoids interfere with cancer treatment?

In this study, cannabinoids did not worsen drug resistance and actually reduced it over 72 hours. However, the interaction between cannabinoids and cancer drugs in actual patients is complex and not yet well-characterized.

Read the original research

The effects of cannabinoids on P-glycoprotein transport and expression in multidrug resistant cells.

Biochemical pharmacology, 71(8), 1146-54

View on PubMed ↗

Citation

Holland, M L; Panetta, J A; Hoskins, J M; Bebawy, M; Roufogalis, B D; Allen, J D; Arnold, J C. (2006). The effects of cannabinoids on P-glycoprotein transport and expression in multidrug resistant cells.. Biochemical pharmacology, 71(8), 1146-54.