In glioblastoma cells from human tumors, THC reduced cell proliferation through the orphan receptor GPR55 rather than the classic CB1 or CB2 cannabinoid receptors, and this effect was abolished by CBD.
Neuro-oncology researchers and scientists studying cannabinoid receptor pharmacology.
THC anti-tumor effect worked through GPR55, not CB1/CB2, and CBD blocked it
What the researchers found
THC reduced Ki67-positive (proliferating) glioblastoma cells, but this effect was blocked by the GPR55 antagonist CID16020046, not by CB1 or CB2 antagonists. The GPR55 agonist LPI produced similar effects to THC. Unexpectedly, CBD abolished THC's anti-proliferative effect, while CBD alone had no effect. All cells expressed CB1, CB2, GPR18, and GPR55.
Why it matters
Most cannabis cancer research focuses on CB1 and CB2 receptors. This study identifies GPR55 as the key receptor for THC anti-tumor effects in glioblastoma, opening a new therapeutic target. The finding that CBD blocks THC's effect is clinically important for patients using THC/CBD combinations.
The numbers in context
Patient-derived glioblastoma cells. THC reduced Ki67+ cells. GPR55 antagonist CID abolished THC effect. CB1, CB2, GPR18 antagonists did not. LPI (GPR55 agonist) replicated THC effect. CBD blocked both THC and LPI effects.
How the study worked
In vitro study using glioblastoma cells isolated from human tumor samples. Ki67 immunocytochemistry measured proliferation after 24-hour cannabinoid exposure. Receptor involvement determined by selective pharmacological blockade of CB1 (AM281), CB2 (AM630), GPR18 (O-1918), and GPR55 (CID16020046).
What this study cannot tell us
In vitro study only. Patient-derived cells may not fully represent tumor behavior in vivo. Short exposure (24 hours). Proliferation marker (Ki67) is one aspect of tumor biology. Cannot predict clinical anti-tumor effects.
How to read the evidence
In vitro study with human tumor cells and rigorous pharmacological characterization. Preliminary for clinical translation.
When this study was published
2021 in vitro study using patient-derived glioblastoma cells.
The bigger picture
The CBD-blocking-THC finding is counterintuitive since many cancer patients use THC/CBD combinations. If GPR55 is the relevant target in glioblastoma, THC alone or GPR55-specific drugs might be more effective than THC/CBD combinations.
Questions still open
- Would GPR55-targeted drugs be more effective than THC for glioblastoma? Why does CBD block THC's effect through GPR55? Should glioblastoma patients avoid CBD when using THC for potential anti-tumor effects?
Common questions
Does THC kill brain cancer cells?
Why is the CBD finding concerning?
Read the original research
THC Reduces Ki67-Immunoreactive Cells Derived from Human Primary Glioblastoma in a GPR55-Dependent Manner.
Cancers, 13(5)
Citation
Kolbe, Marc Richard; Hohmann, Tim; Hohmann, Urszula; Ghadban, Chalid; Mackie, Ken; Zöller, Christin; Prell, Julian; Illert, Jörg; Strauss, Christian; Dehghani, Faramarz. (2021). THC Reduces Ki67-Immunoreactive Cells Derived from Human Primary Glioblastoma in a GPR55-Dependent Manner.. Cancers, 13(5). https://doi.org/10.3390/cancers13051064
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