By Emily Ledger
The medicinal use of cannabis has maintained or thousands of years, with scientific research slowly revealing the many secrets of the plant. While cannabinoids such as THC and CBD remain by far the most researched of the known cannabis compounds – but these are not the only cannabis derivatives that have been found to have impressive medicinal and therapeutic potential.
Cannflavins are a kind of flavonoid that are produced by the cannabis plant. More than 20 flavonoids have been identified in the cannabis plant, including cannflavins.
Several pre-clinical studies have demonstrated that these compounds may have potent therapeutic potential, most notable as anti-inflammatories. Some evidence also suggests that cannflavins may work in synergy with other cannabis compounds, including cannabinoids and terpenes, in a model known as the ‘entourage effect’.
A 2020 review of the existing evidene, titled: ‘Cannflavins – From plant to patient: A scoping review aimed to understand the existing evidence of the medial potential of cannflavins. The authors of the review identified relevant articles which referred to cannflavins regarding its “production, isolation and translation into medicinal use.”
Existing Research on the Potential of Cannflavins
A total of 26 relevant articles referring to cannflavins, including studies and articles regarding cultivation, extraction, pre-clinical and clinical research were included in the review. The majority of these studies detailed original research of Cannflavin A (CFL-A) (85%). Fewer assessed Cannflavin B (CFL-B) (46%), Cannflavin C (CFL-C) (4%) and Isocannflavin B (IsoB) (12%).
The existing literature demonstrates that CFL-A and CFL-B have promising anti-inflammatory potential. Some studies showed that this could be down to the potent inhibition of compounds (PGE2) that have been implicated in driving inflammation and inflammatory disease processes.
Evidence shows that mice with knockout mPGES-1 display “significantly reduced inflammation, particularly within rheumatoid arthritis models.
CFL-A and CFL-B have also been found to inhibit the production of 5-LO – the initial catalytic enzyme in the pathway for leukotriene synthesis from arachidonic acid. As Leukotrienes have been implicated in a wide range of inflammatory diseases, this inhibition may offer another pathway for utilising cannflavins as anti-inflammatories.
In addition, researchers from the University of Guelph in 1985 found that cannflavins were up to 30 times more effective than aspirin at reducing inflammation in cell models.
In 2019, researchers also identified the production pathway of these compounds which, naturally, are only produced in very small quantities by the Cannabis Sativa L. plant. This discovery could enable increased research into the medicinal potential of cannflavins in the future.
Antineoplastic (Tumour Prevention) Potential
Antineoplastic drugs are drugs that are used to treat cancer, due to their ability to prevent or inhibit the development of neoplasm (tumours).
One study included in the review assessed the neoplastic potential of a structural isomer of cannflavin B (IsoB) in in vitro and in vivo models of pancreatic cancer. This study found that when co-administered with 6 Gray (Gy) radiation in a smart radiotherapy biomaterial (SRB), IsoB demonstrated a statistically significant reduction in pancreatic tumour size.
When administered alongside radiotherapy, one study recorded that IsoB led to an improvement in overall survival when compared to controls. However, IsoB delivered on its own was not able to produce a significant effect on survival when compared to controls.
Further Evidence of Therapeutic Potential
Other studies included in the scoping review assessed the neuroprotective, anti-parasitic, and anti-viral properties of cannflavins.
One study found that CFL-A demonstrated neuroprotective effects against amyloid β fibrillation leading to an increased cell viability by up to 40% from baseline at concentrations below 10μM. However, at concentrations above 10μM, CFL-A demonstrated neurotoxicity.
Various studies have also found that cannflavins demonstrate anti-leishmanial activity against Leishmania donovani – a species of intracellular parasite. These findings indicate that cannflavins may have useful anti-parasitic potential.
There is growing evidence to demosnstrate that cannflavins may have significant therapeutic potentials in a number of research areas. The anti-inflammatory and antineoplastic properties of these compounds are the most investigated.
However, the findings of these studies are yet to be translated into a clinical setting, which is crucial for the developing our knowledge of the mechanisms by which these compounds work. The recent discovery of the biosynthetic pathway of CFL-A and CFL-B may offer a promising opportunity to expand the clinical research.
The authors who reviewed the existing literature in their scoping review concluded that, although the studies included in this review demonstrated promising results for the therapeutic potential of cannflavins, clinical validation of these findings is lacking. This review highlights that these areas of research require focused clinical evaluation in institutions with a track record of clinical transition across these research subjects.