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Title: Novel properties of the phytocannabinoids and their receptors
Author: Gauson, Lisa
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2009
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I have investigated the pharmacological properties of cannabichromene (CBC), cannabigerol (CBG) and Δ8-tetrahydrocannabivarin (Δ8-THCV).  A concentrations in the micromolar range, CBG binds to the cannabinoid CB1 and CB2 receptors and acts as a CB1 receptor antagonist.  In the functional [35S]GTPγS binding assay performed with mouse brain membranes, CBG also behaves as a potent partial agonist at concentrations less than 100 nM. CBG is an α2-adrenoceptor agonist, and behaves as a competitive 5-HT1A antagonist at concentrations ranging from 300 nM to 10 μM. Further experiments were conducted to explore interactions between established 5-HT1A ligands and the CB1 receptor.  In mouse brain membranes, although not in hCB1 transfected cells, the 5-HT1A receptor agonist, 8-OH-DPAT, has the ability both to displace [3H]CP55940 from specific binding sites and to modulate the rate of [3H]CP55940 dissociation from these sites.  These results may reflect the presence of CB1-5-HT1A dimers in the brain. Δ9-THCV has been reported to be a potent CB2 receptor antagonist with a KB value lower than its binding affinity for CB2.  Experiments were performed in the cAMP assay to establish if Δ8-THCV did in fact target the CB2 receptor.  Antagonism of Δ8-THCV was attempted by using a selection of compounds but unfortunately these either behaved as inverse agonists in the assay or as partial agonists.  Δ8-THCV induced agonism was Pertussis toxin sensitive.  In untransfected CHO cells, Δ8-THCV did not stimulate or inhibit forskolin induced stimulation of cAMP, hence the effects of Δ8-THCV are most likely CB2 dependent. As CBG was found to behave as a potent α2-adrenoceptor agonist and 5-HT1A receptor antagonist, it may be useful clinically, for example for the treatment of depression.  Interactions between the 5-HT1A and CB1 receptors need to be explored more fully, not least because it might be possible to exploit such interactions in the clinic.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Cannabinoids