title: Amphipathic interactions of cannabinoids with membranes. A comparison between delta 8-THC and its O-methyl analog using differential scanning calorimetry, X-ray diffraction and solid state 2H-NMR.
abstract: The effects of (-)-delta 8-tetrahydrocannabinol (delta 8-THC) and its biologically inactive O-methyl ether analog on model phospholipid membranes were studied using a combination of differential scanning calorimetry (DSC), small angle X-ray diffraction and solid state 2H-NMR. The focus of this work is on the amphipathic interactions of cannabinoids with membranes and the role of the free phenolic hydroxyl group which is the only structural difference between these two cannabinoids. Identically prepared aqueous multilamellar dispersions of phosphatidylcholines in the absence and presence of cannabinoids were used. The DSC thermograms and X-ray diffraction patterns of these preparations allowed us to detect the strikingly different manners in which these two cannabinoids affect the thermotropic properties and the thickness of the bilayer. In order study the effects of the cannabinoids on different regions of the bilayer, we used solid state 2H-NMR with four sets of model membranes from dipalmitoylphosphatidylcholine deuterated in different sites, viz., the choline trimethylammonium head group, or one of the following three groups in the acyl chains; the 2'-methylene, 7'-methylene, 16'-methyl groups. Analysis of quadrupolar splittings indicated that delta 8-THC resides near the bilayer interface and the inactive analog sinks deeper towards the hydrophobic region. The temperature dependence of the solid state 2H-NMR spectra showed that, during the bilayer phase transition, the disordering of the choline head groups is a separate event from the melting of the acyl chains, and that amphipathic interactions between delta 8-THC and the membrane separate these two events further apart in temperature. The inactive analog lacks the ability to induce such a perturbation.
authors.affiliation: School of Pharmacy, University of Connecticut, Storrs 06269.
authors.forename: D P
authors.initials: DP
authors.lastname: Yang
authors.forename: T
authors.initials: T
authors.lastname: Mavromoustakos
authors.forename: K
authors.initials: K
authors.lastname: Beshah
authors.forename: A
authors.initials: A
authors.lastname: Makriyannis
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism*; D002152:Calorimetry, Differential Scanning; D002186:Cannabinoids / Q000378:metabolism*; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000378:metabolism; D008051:Lipid Bilayers; D009682:Magnetic Resonance Spectroscopy; D013696:Temperature; D014961:X-Ray Diffraction
chemical_list: D002186:Cannabinoids; D008051:Lipid Bilayers; D015060:1,2-Dipalmitoylphosphatidylcholine; C035731:delta-8-tetrahydrocannabinol; D013759:Dronabinol