Chronological Review and Rational and Future Prospects of Cannabis-Based Drug Development

Abstract

Despite the surge in cannabis chemistry research and its biological and medical activity, only a few cannabis-based pharmaceutical-grade drugs have been developed and marketed to date. Not many of these drugs are Food and Drug Administration (FDA)-approved, and some are still going through regulation processes. Active compounds including cannabinergic compounds (i.e., molecules targeted to modulate the endocannabinoid system) or phytocannabinoid analogues (cannabinoids produced by the plant) may be developed into single-molecule drugs. However, since in many cases treatment with whole-plant extract (whether as a solvent extraction, galenic preparation, or crude oil) is preferred over treatment with a single purified molecule, some more recently developed cannabis-derived drugs contain several molecules. Different combinations of active plant ingredients (API) from cannabis with proven synergies may be identified and developed as drugs to treat different medical conditions. However, possible negative effects between cannabis compounds should also be considered, as well as the effect of the cannabis treatment on the endocannabinoid system. FDA registration of single, few, or multiple molecules as drugs is a challenging process, and certain considerations that should be reviewed in this process, including issues of drug–drug interactions, are also discussed here.

Specific Compositions of Cannabis sativa Compounds Have Cytotoxic Activity and Inhibit Motility and Colony Formation of Human Glioblastoma Cells In Vitro

“…Combinations of cannabis compounds identified in extract fractions of a high-THC cannabis strain have significant cytotoxic activity against GBM cell lines A172 and U87. The activity of F4 and F5 was higher than that of the crude extract, suggesting that fractionation in this case, as in other cases [28,29,35], may increase extract activity. This adds to a growing list of studies that show that fractionation and determination of active fractions (in this case, F4 and F5) allow the identification of molecules and/or their combinations from cannabis that are active for particular action [35].…”

“…The activity of F4 and F5 was higher than that of the crude extract, suggesting that fractionation in this case, as in other cases [28,29,35], may increase extract activity. This adds to a growing list of studies that show that fractionation and determination of active fractions (in this case, F4 and F5) allow the identification of molecules and/or their combinations from cannabis that are active for particular action [35]. In this study, the two fractions were composed of different combinations of phytomolecules, with CBG and THC as the most abundant in F4 and F5, respectively.…”

Influence of Technological Maturity on the Secondary Metabolites of Hemp Concentrate (Cannabis sativa L.)

“…In general, the main interest of hemp research is the content of cannabidiol (CBD), the non-psychoactive phytocannabinoid. Pre-clinical and clinical studies show potential therapeutic uses of CBD for several diseases [ 11 ]. The demand for this compound is rising, resulting in the expansion of different types of uses.…”

In Silico and In Vitro Analysis of Major Cannabis-Derived Compounds as Fatty Acid Amide Hydrolase Inhibitors

“…Of them, Δ 9 -tetrahydrocannabinol (THC) is the main psychoactive ingredient [ 2 ]. Additional cannabinoids with biological activity are cannabidiol (CBD), cannabinol (CBN), cannabichromene (CBC), Δ 9 -tetrahydrocannabivarin (THCV) and cannabigerol (CBG) [ 4 , 5 ], all shown in Figure 1 a.…”

“…To date, several studies have interrogated the effects of cannabis-derived compounds on the major eCB-binding receptors [ 4 , 5 ], whereas little is known on their potential interaction with rFAAH [ 46 ] or hFAAH [ 47 ]. Here, we sought to fill this gap by investigating the potential interaction of some relevant cannabis-derived compounds with both enzymes, through the combination of in silico computational analysis and in vitro activity assays.…”