(The FASEB Journal. 2008;22:lb622)
© 2008 FASEB
Pharmacological Characterization of Minor Cannabinoid Constituents
Abir El-Alfy1,
Samir Ross2,
Suzanne Childress1,
Lisa Wilson1,
Yan Tong Xu3,
Eddy Viard4,
Eddy Viard4,
Mohamed Radwan2,
Safwat Ahmed5,
Desmond Slade2,
Mahmoud ElSohly2 and
Rae Matsumoto1
1 Pharmacology,
2 National Center for Natural Products Research, University of Mississippi, University, MS,
3 Pharmacology, University of Mississippi, Unievrsity, MS,
4 Pharmacology,
5 National Center for Natural Products Research, University of Mississippi, University, MO
ABSTRACT
The goal of this study was to evaluate the pharmacological actions of several poorly characterized cannabinoid constituents isolated from Cannabis. Sixteen hydroxylated cannabinoids were isolated from Cannabis extract and identified using standard NMR techniques. The identified compounds were then evaluated in CB1 receptor binding assays using rat brain homogenates and [3H]CP55,940 as the radioligand. The CB1 receptor binding assay showed that a few of the isolated compounds exhibited moderate affinities to the CB1 receptors with Ki values ranging from 200 to 800 nM. These compounds were evaluated using male Swiss Webster mice in the established tetrad assay. In this assay, the cannabinoid receptor agonists 
9-THC and CP55,940 caused a dose dependent reduction in locomotor activity, catalepsy, hypothermia, as well as antinociception. Four compounds showed significant cannabinoid-like activity comparable to that of 9-THC. The 9-THC analog SAA-52-38 demonstrated significant analgesic, cataleptic, as well as hypothermic actions at 10 and 20 mg/kg doses (p<0.001). Similarly, the 8-THC analogs MRRoss-01-45-28-46 and SAA-53-20 showed significant cannabinoid-like activity (p<0.001 and p<0.01 respectively). Current studies are underway to further characterize the therapeutic potential of these as well as other cannabinoids. Grant Number P20RR021929 from the National Center for Research Resources.
