# Releasing the Full Potential of Cannabis through Biotechnology
## 5 Releasing the Full Potential of Cannabis  
Recently, renewed interest emerged in the medical effects of cannabinoids CBD [63]. Although best known for the psychoactive effects of THC, other phytocannabinoids such as CBD showed therapeutic potential for disease treatments from neurological diseases to cancer [63]. By 2021, medical Cannabis and cannabinoids were fully or partially decrimin-malized in most developed countries and major developed economies [64]. At present, the medical Cannabis market is growing fast worldwide, with $3.5 billion at retail prices last year, which is expected to be $20.2 billion after five years [65].  
Currently, the investigation of gene and trait associations in Cannabis is lagging due to its highly heterogeneous genomes [66]. Despite the large variability observed in important traits, genetic mechanisms controlling these traits remain mostly unknown in Cannabis, making it difficult to improve desirable traits through conventional breeding. Due to the multiple usages of this plant, studies are directed to decipher proper ways to fix its desirable characteristics, such as the CRISPR technology.  
As shown in Figure 1, CRISPR technology can help to release the full potential of Cannabis with traits improved. In response to the burgeoning market of medicine cannabinoids, research on Cannabis and cannabinoid biosynthesis have expanded significantly in recent ten years. The multiplex mutation system in CRISPR can be useful for cannabinoid metabolic engineering. For instance, the CRISPR/Cas9 technology can be applied to knock out the duplicates of THCAS gene, silence the THCAS gene via a single editing step, and even create transgenic Cannabis plants with zero THC. Increasing the accumulation of cannabinoids is another hot spot in the current study. It has been reported that upregulates of cannabinoid synthases (CBDAS and THCAS) would not promote cannabinoid biosynthesis, and the enzymatic steps for CBG production are critical for the biosynthesis of CBD and THC [67]. Gene editing allows breeders to modify the rate-limiting enzymes which participate in CBGA biosynthesis, such as GPP synthase, prenyltransferase, tetraketide synthase, or olivetolic acid cyclase. Besides, cannabinoids are synthesized and stored in the storage cavity of glandular trichomes, which can avoid the cytotoxicity of these metabolites [67]. Increasing trichome density is another feasible approach to enhance endogenous phytocannabinoid synthesis and storage capacity. By overexpressing the MYB1 gene from _Artemisia annuua_, transgenic Cannabis displayed a higher average number of trichomes than the empty vector control [68]. As the homologous genes of AaMYB1, several MYB genes in hemp have been predicted to enhance trichome formation as well as CBDA synthesis [68; 69]. Engineering these genes would result in overproduction or accumulation of cannabinoids above wild-type levels. Another widely used product of Cannabis is fiber, made from the plant stem. Suppression or knock out of genes responsible for lignin formation, such as the patatin-related phospholipase AIIIs, would affect Cannabis growth with less lignified stems and finally improve the fiber quality [70].  
In releasing the full potential of Cannabis, another issue that needs to be addressed is the breeding time. For this question, [PERSON] et al. (2022) proposed that Doubled haploid (DH) technology could be used as it has been successfully applied in a variety of other major traditional crops [71]. Moreover, [PERSON] et al. (2022) envisioned that once DH technology is successfully established in Cannabis, it could also be applied in gene editing [71]. The combination of the two technologies would allow for more rapid genetic improvement of this plant to better meet demand. Speeding up the breeding of Cannabis requires a more thorough understanding of its biology, which is poor now. [PERSON] et al. (2022) suggested that interdisciplinary approaches have great potential for Cannabis biological research [72].