THC reduced glioblastoma cell proliferation through the GPR55 receptor, not the usual CB1/CB2

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.

Kolbe, Marc Richard et al.·Cancers·2021·Preliminary EvidenceAnimal StudyAnimal Study
RTHC-03251Animal StudyPreliminary Evidence2021RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Animal Study
Evidence
Preliminary Evidence
Sample
Not reported

What This Study 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.

Key Numbers

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 They Did This

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).

Why This Research 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 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.

What This Study Doesn't 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.

Questions This Raises

  • ?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?

Trust & Context

Key Stat:
THC anti-tumor effect worked through GPR55, not CB1/CB2, and CBD blocked it
Evidence Grade:
In vitro study with human tumor cells and rigorous pharmacological characterization. Preliminary for clinical translation.
Study Age:
2021 in vitro study using patient-derived glioblastoma cells.
Original Title:
THC Reduces Ki67-Immunoreactive Cells Derived from Human Primary Glioblastoma in a GPR55-Dependent Manner.
Published In:
Cancers, 13(5) (2021)
Database ID:
RTHC-03251

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / Observational
Case Report / Animal StudyOne case or non-human subjects
This study

Tests effects in animals (usually mice or rats), not humans.

What do these levels mean? →

Frequently Asked Questions

Does THC kill brain cancer cells?

In this lab study, THC reduced proliferation of glioblastoma cells from human tumors, but through the GPR55 receptor rather than the CB1/CB2 receptors previously assumed. This is a lab finding that has not been tested in patients.

Why is the CBD finding concerning?

CBD abolished THC's anti-proliferative effect on glioblastoma cells. Since many cancer patients use THC/CBD combinations, this raises the question of whether CBD might counteract THC's potential anti-tumor activity through GPR55.

Read More on RethinkTHC

Cite This Study

RTHC-03251·https://rethinkthc.com/research/RTHC-03251

APA

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

MLA

Kolbe, Marc Richard, et al. "THC Reduces Ki67-Immunoreactive Cells Derived from Human Primary Glioblastoma in a GPR55-Dependent Manner.." Cancers, 2021. https://doi.org/10.3390/cancers13051064

RethinkTHC

RethinkTHC Research Database. "THC Reduces Ki67-Immunoreactive Cells Derived from Human Pri..." RTHC-03251. Retrieved from https://rethinkthc.com/research/kolbe-2021-thc-reduces-ki67immunoreactive-cells

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.