title: Isolation and Pharmacological Evaluation of Minor Cannabinoids from High-Potency Cannabis sativa.
abstract: Seven new naturally occurring hydroxylated cannabinoids (1-7), along with the known cannabiripsol (8), have been isolated from the aerial parts of high-potency Cannabis sativa. The structures of the new compounds were determined by 1D and 2D NMR spectroscopic analysis, GC-MS, and HRESIMS as 8α-hydroxy-Δ(9)-tetrahydrocannabinol (1), 8β-hydroxy-Δ(9)-tetrahydrocannabinol (2), 10α-hydroxy-Δ(8)-tetrahydrocannabinol (3), 10β-hydroxy-Δ(8)-tetrahydrocannabinol (4), 10α-hydroxy-Δ(9,11)-hexahydrocannabinol (5), 9β,10β-epoxyhexahydrocannabinol (6), and 11-acetoxy-Δ(9)-tetrahydrocannabinolic acid A (7). The binding affinity of isolated compounds 1-8, Δ(9)-tetrahydrocannabinol, and Δ(8)-tetrahydrocannabinol toward CB1 and CB2 receptors as well as their behavioral effects in a mouse tetrad assay were studied. The results indicated that compound 3, with the highest affinity to the CB1 receptors, exerted the most potent cannabimimetic-like actions in the tetrad assay, while compound 4 showed partial cannabimimetic actions. Compound 2, on the other hand, displayed a dose-dependent hypolocomotive effect only.
authors.affiliation: †National Center for Natural Products Research, ‡Department of Pharmaceutics and Drug Delivery, and §Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, Mississippi 38677, United States.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Radwan
authors.affiliation: †National Center for Natural Products Research, ‡Department of Pharmaceutics and Drug Delivery, and §Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, Mississippi 38677, United States.
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: ElSohly
authors.affiliation: †National Center for Natural Products Research, ‡Department of Pharmaceutics and Drug Delivery, and §Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, Mississippi 38677, United States.
authors.forename: Abir T
authors.initials: AT
authors.lastname: El-Alfy
authors.affiliation: †National Center for Natural Products Research, ‡Department of Pharmaceutics and Drug Delivery, and §Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, Mississippi 38677, United States.
authors.forename: Safwat A
authors.initials: SA
authors.lastname: Ahmed
authors.affiliation: †National Center for Natural Products Research, ‡Department of Pharmaceutics and Drug Delivery, and §Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, Mississippi 38677, United States.
authors.forename: Desmond
authors.initials: D
authors.lastname: Slade
authors.affiliation: †National Center for Natural Products Research, ‡Department of Pharmaceutics and Drug Delivery, and §Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, Mississippi 38677, United States.
authors.forename: Afeef S
authors.initials: AS
authors.lastname: Husni
authors.affiliation: †National Center for Natural Products Research, ‡Department of Pharmaceutics and Drug Delivery, and §Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, Mississippi 38677, United States.
authors.forename: Susan P
authors.initials: SP
authors.lastname: Manly
authors.affiliation: †National Center for Natural Products Research, ‡Department of Pharmaceutics and Drug Delivery, and §Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, Mississippi 38677, United States.
authors.forename: Lisa
authors.initials: L
authors.lastname: Wilson
authors.affiliation: †National Center for Natural Products Research, ‡Department of Pharmaceutics and Drug Delivery, and §Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, Mississippi 38677, United States.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Seale
authors.affiliation: †National Center for Natural Products Research, ‡Department of Pharmaceutics and Drug Delivery, and §Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, Mississippi 38677, United States.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Cutler
authors.affiliation: †National Center for Natural Products Research, ‡Department of Pharmaceutics and Drug Delivery, and §Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, Mississippi 38677, United States.
authors.forename: Samir A
authors.initials: SA
authors.lastname: Ross
mesh_terms: D000700:Analgesics; D000818:Animals; D002186:Cannabinoids / Q000737:chemistry / Q000302:isolation & purification*; D002188:Cannabis / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000031:analogs & derivatives; D008401:Gas Chromatography-Mass Spectrometry; D051379:Mice; D008922:Mississippi; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D019906:Nuclear Magnetic Resonance, Biomolecular; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism
chemical_list: D000700:Analgesics; D002186:Cannabinoids; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C022214:cannabiripsol; D013759:Dronabinol; C025351:delta(9)-tetrahydrocannabinolic acid