The thermotropic and dynamic properties of the biologically active Delta(8)
-tetrahydrocannabinol (Delta(8)-THC) and its inactive congener O-methyl-Del
ta(8)-tetrahydrocannabinol (Me-Delta(8)-THC) in DPPC/cholesterol (CHOL) bil
ayers have been studied using a combination of DSC and solid-state NMR spec
troscopy. The obtained results showed differential effects of the two canna
binoids under study. These are summarized as follows: (a) the presence of t
he active compound fluidizes more significantly the DPPC/CHOL bilayers than
the inactive analog as it is revealed by DSC and NMR spectroscopy results;
(b) cholesterol seems to play a significant role in the way cannabinoids a
ct. in membrane bilayers; (c) the observed additional peaks in C-13/MAS-NMR
spectra which were cannabinoid specific offer an evidence of their differe
nt dynamic properties in membranes. In particular, the aromatic part of the
inactive cannabinoid appears more mobile than that of the active one. This
finding is in agreement with previously obtained X-ray data which locate t
he inactive cannabinoid in the hydrophobic core of the bilayer while the ac
tive one in the polar region; and (d) the observed downfield shift of C-1 c
arbon in the preparation containing the active cannabinoid is a strong evid
ence that Delta(8)-THC resides nearby the polar region where also cholester
ol is well known to locate itself. Such downfield shift is absent when Me-D
elta(8)-THC is resided in the membrane bilayer. These differential effects
of the two cannabinoids propose that the phospbolipid/cholesterol core of t
he membrane may play an important role in the mode of cannabinoid action by
regulating their thermotropic and dynamic properties. (C) 1999 Elsevier Sc
ience B.V. All rights reserved.