Functional interactions between cannabinoids, omega-3 fatty acids, and peroxisome proliferator-activated receptors: Implications for mental health pharmacotherapies
Written by Tony Jung | Roger Hudson | Walter Rushlow | Steven R. Laviolette
Cannabis contains a plethora of phytochemical constituents with diverse neurobio- logical effects. Cannabidiol (CBD) is the main non-psychotropic component found in cannabis that is capable of modulating mesocorticolimbic DA transmission and may possess therapeutic potential for several neuropsychiatric disorders. Emerging evi- dence also suggests that, similar to CBD, omega-3 polyunsaturated fatty acids may regulate DA transmission and possess therapeutic potential for similar neuropsychi- atric disorders. Although progress has been made to elucidate the mechanisms un- derlying the therapeutic properties of CBD and omega-3s, it remains unclear through which receptor mechanisms they may produce their purported effects. Peroxisome proliferator-activated receptors are a group of nuclear transcription factors with mul- tiple isoforms. PPARγ is an isoform activated by both CBD and omega-3, whereas the PPARα isoform is activated by omega-3. Interestingly, the activation of PPARγ and PPARα with selective agonists has been shown to decrease mesocorticolimbic DA activity and block neuropsychiatric symptoms similar to CBD and omega-3s, raising the possibility that CBD and omega-3s produce their effects through PPAR signaling. This review will examine the relationship between CBD, omega-3s, and PPARs and how they may be implicated in the modulation of mesocorticolimbic DAergic abnormalities and associated neuropsychiatric symptoms.