| Summary: | I have investigated the pharmacological properties of cannabichromene (CBC), cannabigerol (CBG) and Δ<sup>8</sup>-tetrahydrocannabivarin (Δ<sup>8</sup>-THCV). A concentrations in the micromolar range, CBG binds to the cannabinoid CB<sub>1</sub> and CB<sub>2</sub> receptors and acts as a CB<sub>1</sub> receptor antagonist. In the functional [<sup>35</sup>S]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 α<sub>2</sub>-adrenoceptor agonist, and behaves as a competitive 5-HT<sub>1A</sub> antagonist at concentrations ranging from 300 nM to 10 μM. Further experiments were conducted to explore interactions between established 5-HT<sub>1A</sub> ligands and the CB<sub>1</sub> receptor. In mouse brain membranes, although not in hCB<sub>1</sub> transfected cells, the 5-HT<sub>1A</sub> receptor agonist, 8-OH-DPAT, has the ability both to displace [<sup>3</sup>H]CP55940 from specific binding sites and to modulate the rate of [<sup>3</sup>H]CP55940 dissociation from these sites. These results may reflect the presence of CB<sub>1</sub>-5-HT<sub>1A</sub> dimers in the brain. Δ<sup>9</sup>-THCV has been reported to be a potent CB<sub>2</sub> receptor antagonist with a <i>K</i><sub>B</sub> value lower than its binding affinity for CB<sub>2</sub>. Experiments were performed in the cAMP assay to establish if Δ<sup>8</sup>-THCV did in fact target the CB<sub>2</sub> receptor. Antagonism of Δ<sup>8</sup>-THCV was attempted by using a selection of compounds but unfortunately these either behaved as inverse agonists in the assay or as partial agonists. Δ<sup>8</sup>-THCV induced agonism was <i>Pertussis </i>toxin sensitive. In untransfected CHO cells, Δ<sup>8</sup>-THCV did not stimulate or inhibit forskolin induced stimulation of cAMP, hence the effects of Δ<sup>8</sup>-THCV are most likely CB<sub>2</sub> dependent. As CBG was found to behave as a potent α<sub>2</sub>-adrenoceptor agonist and 5-HT<sub>1A</sub> receptor antagonist, it may be useful clinically, for example for the treatment of depression. Interactions between the 5-HT<sub>1A</sub> and CB<sub>1</sub> receptors need to be explored more fully, not least because it might be possible to exploit such interactions in the clinic.
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