Folic acid enhances the effects of cannabinoids at behavioral, cellular, and transcriptional levels Contribute

Joey B. Wong | earned $0

Recent interest in cannabinoid receptors as therapeutic targets has spurred the investigation into the physiochemical responses to their activation. The cannabinoid pathways in mammalian systems of adult male CD1 mice were investigated using a combinatorial approach based on folic acid mediated response.  Various tests of cannabimimetic activity of folic acid showed that the combination of folic acid with either AEA (N-arachidonoylethanolamine, ananamide) or THC (∆9tetrahydrocannabinol) amplified the effects of the cannabinoid.  Levels of cyclic AMP (cAMP) in brain tissue also show a marked reduction after the addition of folic acid to either AEA or THC at both 1 and 2.5 µM dose levels in comparison to the cannabinoid alone.  Genetic studies using CB1 -/- knockout mice suggest the existence of a CB3 receptor localized in the brain tissue of mice that has yet to be cloned or characterized.  In the CB1 knockout mice, addition of folic acid and THC resulted in a 129% increase of [3H]THC binding in the cortex and significant increases in all other areas of the brain when compared to THC alone. This indicates that folic acid is indeed affecting the neurotransmitter pathways of the cannabinoids by potentially acting with a third cannabinoid receptor. Using serial analysis of gene expression, it was found that transcription levels of genes shown to be up-regulated by cannabinoids were further increased upon addition of folic acid

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