Functional interactions between cannabinoids, omega-3 fatty acids, and peroxisome proliferator-activated receptors: Implications for mental health pharmacotherapies

Cannabis contains a plethora of phytochemical constituents with diverse neurobiological 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 evidence also suggests that, similar to CBD, omega-3 polyunsaturated fatty acids may regulate DA transmission and possess therapeutic potential for similar neuropsychiatric disorders. Although progress has been made to elucidate the mechanisms underlying 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 multiple 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.