CBGA Was the Most Potent Cannabinoid at Blocking a Channel Linked to Cancer and Kidney Disease | Research

The takeaway

Among common cannabinoids tested, cannabigerolic acid (CBGA) most potently inhibited the TRPM7 ion channel, a target implicated in cancer, stroke, and kidney disease, by interacting with its kinase domain.

Cannabinoid pharmacology researchers and those studying TRPM7 in disease

CBGA was the strongest TRPM7 inhibitor among all cannabinoids tested

What the researchers found

CBGA had the strongest inhibitory effect on TRPM7 channels among all major and minor cannabinoids tested. The inhibition required a functional kinase domain, was enhanced by intracellular Mg-ATP and free Mg2+, and was reduced by intracellular calcium. CBGA also inhibited native TRPM7 channels in B lymphocytes.

Why it matters

TRPM7 is involved in cancer progression, stroke damage, and kidney disease. Finding that a naturally occurring cannabinoid (CBGA) potently and specifically blocks this channel opens a new therapeutic research direction for these serious conditions.

The numbers in context

CBGA was the strongest TRPM7 inhibitor among all tested cannabinoids. About half of tested cannabinoids suppressed TRPM7 to some degree. CBGA interacted with the channel's selectivity filter via hydrogen bonds and van der Waals contacts.

How the study worked

In vitro electrophysiology study using HEK293 cells expressing TRPM7-GFP. Calcium imaging and patch-clamp recordings measured TRPM7-mediated responses. Molecular docking and dynamics simulations investigated binding mechanisms. Multiple cannabinoids were tested and compared.

What this study cannot tell us

In vitro study only. The relevance of TRPM7 blockade to actual disease outcomes in living organisms is not established. CBGA pharmacokinetics and bioavailability in vivo are not addressed. The study does not demonstrate therapeutic efficacy, only mechanism of action.

How to read the evidence

Mechanistic in vitro study with electrophysiology and molecular modeling; establishes mechanism but not therapeutic application.

When this study was published

2024 study

The bigger picture

CBGA is the precursor to CBD, THC, and other cannabinoids, and is found at high levels in some hemp varieties. If its TRPM7-blocking property translates to therapeutic benefit, it could expand the medical applications of cannabinoids well beyond their current uses.

Questions still open

Would CBGA reach therapeutic concentrations at the TRPM7 channel in vivo? Could CBGA be developed as a TRPM7 inhibitor for cancer or kidney disease? How does CBGA compare to existing TRPM7 inhibitors in clinical development?

Common questions

What is CBGA and why does it matter?

CBGA (cannabigerolic acid) is the precursor to CBD and THC, found in high levels in some hemp varieties. This study found it is the most potent cannabinoid at blocking TRPM7, a channel implicated in cancer, stroke, and kidney disease.

Could CBGA treat cancer or kidney disease?

It is too early to say. This study showed CBGA blocks a channel involved in these diseases, but this is lab-based evidence. Whether CBGA could be developed as a therapeutic requires much more research.

Read the original research

Cannabigerolic Acid (CBGA) Inhibits the TRPM7 Ion Channel Through its Kinase Domain.

Function (Oxford, England), 5(1), zqad069

View on PubMed ↗Publisher’s paper ↗

Citation

Suzuki, Sayuri; Wakano, Clay; Monteilh-Zoller, Mahealani K; Cullen, Aaron J; Fleig, Andrea; Penner, Reinhold. (2024). Cannabigerolic Acid (CBGA) Inhibits the TRPM7 Ion Channel Through its Kinase Domain.. Function (Oxford, England), 5(1), zqad069. https://doi.org/10.1093/function/zqad069