Non-Cannabinoid Metabolites of Cannabis sativa L. with Therapeutic Potential

Abstract

The cannabis plant (Cannabis sativa L.) produces an estimated 545 chemical compounds of different biogenetic classes. In addition to economic value, many of these phytochemicals have medicinal and physiological activity. The plant is most popularly known for its two most-prominent and most-studied secondary metabolites—Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Both Δ9-THC and CBD have a wide therapeutic window across many ailments and form part of a class of secondary metabolites called cannabinoids—of which approximately over 104 exist. This review will focus on non-cannabinoid metabolites of Cannabis sativa that also have therapeutic potential, some of which share medicinal properties similar to those of cannabinoids. The most notable of these non-cannabinoid phytochemicals are flavonoids and terpenes. We will also discuss future directions in cannabis research and development of cannabis-based pharmaceuticals. Caflanone, a flavonoid molecule with selective activity against the human viruses including the coronavirus OC43 (HCov-OC43) that is responsible for COVID-19, and certain cancers, is one of the most promising non-cannabinoid molecules that is being advanced into clinical trials. As validated by thousands of years of the use of cannabis for medicinal purposes, vast anecdotal evidence abounds on the medicinal benefits of the plant. These benefits are attributed to the many phytochemicals in this plant, including non-cannabinoids. The most promising non-cannabinoids with potential to alleviate global disease burdens are discussed.

The Effects of Cannabis sativa L. Extract on Oxidative Stress Markers In Vivo

“…However, this study was intended to investigate the effect of the whole extract of Cannabis sativa L. on oxidative stress markers. The antioxidant activity of CBDA was found to be low in vitro, and thus it could be concluded that other compounds (flavonoids or/and terpenoids) in the extract also have an effect on oxidative stress markers, which corroborates literature data claiming that flavonoids and terpenoids have a wide therapeutic window [15].…”

“…Cannabis sativa L. produces multiple chemical compounds of different biogenetic classes [ 15 ], and many studies have demonstrated the antioxidant activity of Cannabis in vitro [ 19 , 22 ]. The phenolic compounds are mainly responsible for the antioxidant activity, while hemp seeds due to their active compounds, have health benefits such as lowering the cholesterol level in the blood or alleviating constipation and are also useful in the treatment of cardiovascular diseases [ 11 , 23 ].…”

“…Cannabinoids such as tetrahydrocannabinol (THC), cannabinol, and cannabidiol (CBD) have been found to be potent lipophilic antioxidants [ 13 ], and antioxidant activity of CBD and THC has been reported [ 14 ]. However, hemp produces other metabolites that could demonstrate antioxidant activity, as well [ 15 ]. Pollastro et al reported that hemp synthesizes characteristic molecules, such as prenylated flavonoids, stilbenoid derivatives, and lignamides, which require further investigations [ 16 ].…”

Wonder or evil?: Multifaceted health hazards and health benefits of Cannabis sativa and its phytochemicals

“…Several analytical methods, such as optical rotatory dispersion (ORD) and electronic circular dichroism (CD) based studies, liquid chromatography coupled to high resolution tandem mass spectrometry (LC - MS / MS), headspace solid phase microextraction (HS-SPME), overpressured layer chromatography (OPLC), high-performance thin-layer chromatography (HPTLC), high-performance liquid chromatography with diode array detector (HPLC-DAD), liquid chromatography with high resolution mass spectrometry (LC-HRMS), gas chromatography with flame ionization detector (GC-FID) and gas chromatography – mass spectrometry (GC–MS)-based qualitative and quantitative determination, nuclear magnetic resonance (NMR) and mass spectrometry (MS) based structural determination have played a critical role in phytochemical profiling of different medicinal and nontherapeutic cultivars ( Calvi et al, 2018 ). The content of tetrahydrocannabinol and cannabidiol in any cultivar is essentially important for its main prescribed and ‘legally safe’ recommendation ( Raderman, 2016 , Lowe et al, 2021 ). Therefore, commercially marketed cultivars must be studied for all possible types of synergistic interactions and chemical components present to determine the safe use of Cannabis as a useful medicinal herb ( Jin et al, 2017 ).…”

Antimicrobial and Antiviral (SARS-CoV-2) Potential of Cannabinoids and Cannabis sativa: A Comprehensive Review

“…Caflanone, a secondary metabolite from non-cannabinoid extracts of C. sativa [ 183 ] inhibited a number of entry factors for human corona virus hCov-OC43, pro-inflammatory cytokines (IL-1β, IL-6, IL-8, Mip-1α, TNF-α), ABL-2, cathepsin L, PI4Kiiβ and AXL-2 [ 184 ]. TNF-α was reduced by THC in a mouse model of Staphylococcal enterotoxin-B (SEB)-mediated ARDS [ 185 ] and in human cell line in vitro models [ 173 ].…”