An Unexpected Activity of a Minor Cannabinoid: Cannabicyclol (CBL) Is a Potent Positive Allosteric Modulator of Serotonin 5-HT_1A Receptor.

ABSTRACT: Cannabicyclol ((±)-CBL), a minor phytocannabinoid, is largely unexplored, with its biological activity previously undocumented. We studied its conversion from cannabichromene (CBC) using various acidic catalysts. Montmorillonite (K30) in chloroform at room temperature had the highest yield (60%) with minimal byproducts. Key reaction conditions, such as solvent, temperature, and time, significantly impacted the yield. The structure of (±)-CBL was confirmed via X-ray crystallography. Stability studies showed that (±)-CBL and its MCT oil dilution remain stable at 25-40 °C for three months. Radioligand binding assays revealed high affinity of CBL for the 5-HT_1A receptor but weak interaction with CB₁ and CB₂ receptors. At 10 μM and 1 μM, (±)-CBL inhibited [

SUBMITTER: Haghdoost M 

PROVIDER: S-EPMC11774245 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature