Abstract Cannabidiol (CBD), a bicyclic non-psychoactive cannabinoid biosynthesized by Cannabis spp. of plants, has attracted significant interest in the past decade due to its therapeutic properties. In 2018, the US FDA approved Epidiolex®, a CBD-based drug for the treatment of two rare epileptic seizure disorders. CBD possesses two chiral centers at C3 and C4 on its terpenoid moiety and exhibits cis–trans stereoisomerism along the C3–C4 bond axis. (−)-trans-(3R,4R)-CBD, the natural CBD, is biosynthesized by the cannabis plant, while the unnatural (+)-trans-(3S,4S)-CBD is obtained via chemical synthesis. Both trans isomers exhibit broad in vitro and in vivo biological activities; typically, the unnatural stereoisomer (+)-trans-CBD and its derivatives exhibited more potent activities in comparison to the corresponding (−)-trans isomers. On the other hand, cis-CBD isomers...