Biological Potential of Varinic-, Minor-, and Acidic Phytocannabinoids

While natural Δ⁹-tetrahidrocannabinol (Δ⁹THC), cannabidiol (CBD), and their therapeutic potential have been extensively researched, some cannabinoids have not been widely investigated. The present article compiles data from the literature that highlights research on and the therapeutic possibilities of lesser known phytocannabinoids, which we have divided into varinic, acidic, and “minor” (i.e., cannabinoids that are not present in high quantities in common varieties of Cannabis sativa L). A growing interest in these compounds, which are enriched in some cannabis varieties, has already resulted in enough preclinical information to show that they are promising therapeutic agents for a variety of diseases. Each phytocannabinoid has a “preferential” mechanism of action, and often target the cannabinoid receptors CB₁ and/or CB₂. The recent resolution of the structure of cannabinoid receptors demonstrates the atypical nature of cannabinoid binding, and that different binding modes depend on the agonist or partial agonist/inverse agonist, which allows for differential signaling, even acting on the same cannabinoid receptor. In addition, other players and multiple signaling pathways may be targeted/engaged by phytocannabinoids, thereby expanding the mechanistic possibilities for therapeutic use.