Cannabinoid receptor complexes are elevated in the brains of people with multiple sclerosis

What the researchers found

Using proximity ligation assays and immunohistochemistry on postmortem brain samples, researchers identified CB1R-GPR55 and CB2R-GPR55 heteromers in the human prefrontal cortex for the first time. Both receptor complexes were more abundant in grey matter than white matter and were significantly upregulated in MS patients versus controls.

Why it matters

Receptor heteromers behave differently than individual receptors. The discovery that cannabinoid receptor complexes are upregulated in MS brains opens a new avenue for targeted therapies that could be more precise than current cannabinoid treatments.

The numbers in context

CB1R-GPR55 and CB2R-GPR55 heteromers identified for the first time in human prefrontal cortex. Both more abundant in grey matter. Both significantly increased in MS brain samples versus controls.

How the study worked

In situ proximity ligation assays and immunohistochemical techniques on postmortem prefrontal cortex samples from MS patients and control subjects to identify and quantify cannabinoid receptor heteromers.

What this study cannot tell us

Postmortem tissue study cannot determine whether receptor upregulation is a cause or consequence of MS pathology. Small sample sizes typical of postmortem brain studies. Prefrontal cortex findings may not generalize to other brain regions affected by MS.

How to read the evidence

Novel molecular discovery using validated techniques on human tissue, but postmortem design and likely small sample size limit clinical translation.

When this study was published

2024 publication.

The bigger picture

Cannabinoids already show benefits in MS for spasticity and pain, but through poorly understood mechanisms. The discovery of upregulated receptor complexes specific to MS brains could explain why cannabinoids help and suggest how to make better-targeted treatments.

Questions still open

• Do these receptor complexes represent a compensatory response to neuroinflammation or a driver of MS pathology?
• Could drugs targeting GPR55-cannabinoid receptor heteromers specifically offer advantages over current MS treatments?

Common questions

Read the original research

Heteromers Formed by GPR55 and Either Cannabinoid CB1 or CB2 Receptors Are Upregulated in the Prefrontal Cortex of Multiple Sclerosis Patients.

International journal of molecular sciences, 25(8)

Citation

Menéndez-Pérez, Carlota; Rivas-Santisteban, Rafael; Del Valle, Eva; Tolivia, Jorge; Navarro, Ana; Franco, Rafael; Martínez-Pinilla, Eva. (2024). Heteromers Formed by GPR55 and Either Cannabinoid CB1 or CB2 Receptors Are Upregulated in the Prefrontal Cortex of Multiple Sclerosis Patients.. International journal of molecular sciences, 25(8). https://doi.org/10.3390/ijms25084176

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