Interest in nonpsychotropic cannabinoids like cannabinol (CBN) is increasing for pain therapy. This study delivers critical insights into CBN’s metabolism and pharmacological effects, uncovering its therapeutic potential for pain reduction. Using metabolomics, we identify CBN-11-OH as the dominant metabolite, with lower levels of CBN-1′-OH and CBN-quinone. Computational simulations reveal CBN’s stability at the CYP2C9 active site, driving hydroxy metabolite formation. We report the intricate biotransformation of CBN by multiple cytochrome P450 enzymes. CBN and its metabolites exhibit mild anti-inflammatory effects in microglial cells, though less potent than cannabigerol and cannabichromene. Receptor activation assays further reveal that CBN-1′-OH acts as a partial CB1 agonist, while CBN and its metabolites antagonize CB1 and CB2 receptors. Notably, CBN and CBN-11-OH elevate intracellular Ca2+ levels in dorsal root ganglia sensory neurons─an effect linked to potential pain relief. These findings lay the groundwork for harnessing CBN and its metabolites in novel pain therapeutics.

Glaucoma is a group of neurodegenerative diseases that together are the leading cause of irreversible blindness worldwide. Myocilin-associated glaucoma is an inherited form of this disease, caused by....

Scientific Reports - Identification and biophysical characterization of Plasmodium peptide binding by common African HLAs

With a view toward the prominence of brominated intermediates in chemical synthesis, we describe here a biocatalytic scheme for the enzymatic bromination of 2-aminothiazoles using a marine macroalgal brominase in reaction conditions that are directly compatible with Suzuki–Miyaura cross-coupling reactions. Enzymatically delivered brominated thiazoles, without intermediary purification, are arylated in high yields. We demonstrate the applicability of the methodology described herein in derivatizing clinically administered cephalosporin antibiotics and prodrugs in an aqueous solvent and mild reaction conditions.

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