| Autor: |
Udoh M; Macquarie Medical School, Macquarie University, North Ryde, Australia., Santiago M; Macquarie Medical School, Macquarie University, North Ryde, Australia., Haneef S; Macquarie Medical School, Macquarie University, North Ryde, Australia., Rodger A; School of Natural Sciences, Macquarie University, North Ryde, Australia.; Present address: Research School of Chemistry, Australian National University, ACT 2601, Australia., Marlowe CK; A Division of InMed Pharmaceuticals, BayMedica, LLC, South San Francisco, California, USA., Barr PJ; A Division of InMed Pharmaceuticals, BayMedica, LLC, South San Francisco, California, USA., Connor M; Macquarie Medical School, Macquarie University, North Ryde, Australia. |
| Abstrakt: |
Introduction: Cannabichromene (CBC) is a minor constituent of cannabis that is a selective cannabinoid CB2 receptor agonist and activator of TRPA1. To date, it has not been shown whether (-)-CBC, (+)-CBC, or both can mediate these effects. In this study, we investigate the activity of the CBC enantiomers at CB1, CB2, and Transient receptor potential ankyrin 1 (TRPA1) receptors in vitro . Materials and Methods: CBC enantiomers were purified from synthetic CBC by chiral chromatography, and their optical activity was confirmed by spectroscopy. Human CB1 and CB2 receptor activity was measured using a fluorescent assay of membrane potential in stably transfected AtT20 cells. TRPA1 activation was measured using a fluorescent assay of intracellular calcium in stably transfected HEK293 cells. Results: The (-)-CBC activated CB2 with an EC 50 of 1.5 µM, to a maximum of 60% of (-)CP55940. (+)-CBC did not activate CB2 at concentrations up to 30 µM. Only 30 µM (-)-CBC produced detectable activation of CB1, (+)-CBC was inactive. Both (-)-CBC and (+)-CBC activated TRPA1; at 30 µM (-)-CBC produced an activation 50% of that of the reference agonist cinnamaldehyde (300 µM), 30 µM (+)-CBC activated TRPA1 to 38% of the cinnamaldehyde maximum. Discussion: It is unclear whether (-)-CBC is the sole or even the predominant enantiomer of CBC enzymatically synthesized in cannabis. This study shows that (-)-CBC is the active isomer at CB2 receptors, while both isomers activate TRPA1. The results suggest that medicinal preparations of CBC that target cannabinoid receptors would be most effective when (-)-CBC is the dominant isomer. |
