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

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.

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.

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.

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.

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.