Last reviewed by Daniel Gana, MSc, Dr. Abraham Benavides, MD, and Brent Ristow PhD, JD 1/21/2025

Imagine crafting a masterpiece symphony but ignoring an entire section of the orchestra. That’s what happens when we focus solely on cannabinoids and terpenes, leaving flavonoids out of the conversation. These lesser-known compounds hold the key to unlocking cannabis’ full therapeutic potential, synergizing with their better-known counterparts to create effects that are greater than isolates.

It’s time to rewrite the narrative and give flavonoids their rightful place in the spotlight. Join us as we uncover how these hidden gems are reshaping the future of cannabis medicine and redefining what it truly means to experience the plant.

What are flavonoids?

Flavonoids are a diverse group of phytonutrients widely found in various plants, including hemp. They are responsible for the vivid color pigmentation in flowers, fruits, and vegetables, and account for approximately 10% of the compounds in cannabis. 

So far, scientists have identified more than 34 flavonoids in the hemp plant. These compounds include apigenin, luteolin, kaempferol, quercetin and a unique subclass known as the cannflavins. Cannflavins are prenylated (C5) and geranylated (C10) flavones that are relatively rare and mostly specific to the hemp plant.

Flavonoids are most abundant in cannabis leaves, with an estimated total concentration of approximately 1%. They are also present in flowers. Flavonoid concentration is influenced by the specific chemovar, with research indicating higher flavonoid levels in Chemovar III (high CBD, low THC) and Chemovar I (high THC). 

Among the identified flavonoids, vitexin stands out as the most abundant, with concentrations ranging from 0.12% to 0.17% in leaves and 0.02% to 0.06% in inflorescences. Unlike cannabinoids, flavonoid levels decline as the plant matures, emphasizing the importance of optimal harvesting and processing practices to preserve their bioactive potential.

Role of Flavonoids in Entourage Effect

As highlighted in our previous article, flavonoids play a crucial role in the entourage effect by enhancing the bioavailability of cannabinoids and terpenes, while also preventing their degradation. This synergistic relationship is essential in optimizing the overall cannabis experience. It may even explain why our Active Spectrum Extracts™, obtained from a proprietary extraction process, interact with the body at the mitochondrial level, promoting balance and overall wellness.

Unique Flavonoids found in Hemp

While over 34 flavonoids are identified in the hemp plant, we’ll focus on the cannabis-unique flavonoids known as cannflavin. There are 4 distinct flavonoids mostly found in hemp. They include: 

• Cannflavin A

Cannflavin A is one of the unique flavonoids found primarily in hemp, and is known for its potent anti-inflammatory properties. Although it is often associated with cannabis, it has also been identified in Mimulus bigelovii, a plant in the Phrymaceae family. 

Cannflavin A exhibits a promising ability to inhibit the production of pro-inflammatory mediators, contributing to its potential therapeutic effects. Its anti-inflammatory actions make it valuable in addressing conditions associated with chronic inflammation. 

• Cannflavin B

Cannflavin B is another unique flavonoid found in hemp, and has remarkable anti-inflammatory and antioxidant properties. 

This compound is part of the flavonoid subclass and, like cannflavin A, contributes to the entourage effect, amplifying the therapeutic benefits of cannabinoids. Research has shown that cannflavin A and B plays a key role in the plant’s natural defense mechanisms, offering protection against oxidative stress in the plant. 

• Cannflavin C

Cannflavin C is a unique flavonoid isolated from certain high-THC chemovars of Cannabis sativa. It shares similar bioactive properties to other cannflavins, including anti-inflammatory and antioxidant effects. Studies indicate that cannflavin C, like cannflavins A and B, plays a significant role in reducing inflammation by inhibiting the production of pro-inflammatory prostaglandins. 

• Isocannflavin B

Isocannflavin B is another flavonoid identified in Cannabis sativa. Though less is known about isocannflavin B, recent research shows it shares similar antioxidant and bioactive effects as Cannflavins A, B, and C, by binding to and inhibiting key enzymes in the inflammatory cascade. 

Therapeutic Roles of Cannabis Flavonoids

Cannabis flavonoids, especially cannflavins A, B, and C, offer significant therapeutic potential. Their actions work synergistically with cannabinoids and terpenes to improve their bioavailability and reduce their degradation, thereby contributing to a wide range of medicinal benefits. 

Below, we explore the various therapeutic roles of these powerful compounds.

• Anti-Inflammatory Effects

Cannflavins A and B are known for their potent anti-inflammatory properties. Research indicates that they inhibit the activity of microsomal PGE2 synthase-1 and 5-lipoxygenase, reducing the production of inflammatory mediators like PGE2 and leukotrienes. This makes them highly effective in managing inflammatory conditions, such as rheumatoid arthritis. 

In fact, cannflavins A and B have been shown to be 30 times more effective than aspirin in inhibiting PGE2 release in human rheumatoid cells, all while avoiding the gastrointestinal and renal side effects often associated with NSAIDs.

• Neuroprotective Role

Cannflavin A shows promise as a neuroprotective agent. In studies using neuronal PC12 cells, cannflavin A enhanced cell viability against amyloid β-induced cytotoxicity. By reducing amyloid β aggregation and fibril formation, cannflavin A may play a significant role in protecting neurons, potentially aiding in the treatment of neurodegenerative diseases like Alzheimer’s and more.

• Cancer-Fighting Potential

Cannflavins, particularly isocannflavin B (a synthetic derivative of cannflavin B), have demonstrated anticancer activity. Isocannflavin B is shown to suppress the spread of estrogen-dependent human breast cancer cells by inducing G0/G1 cell cycle arrest. It also increases apoptosis in pancreatic cancer cell lines, delaying both local and metastatic tumor progression in animal models. 

Cannflavin A induces autophagy-mediated cell death in bladder cancer cells, leading to its anticancer effects. This is evidenced by the reversal of its cytotoxicity when autophagy inhibitors, such as bafilomycin A and E-64d with pepstatin A, are used. 

• Antiparasitic Activity

Cannflavins have also shown antiparasitic properties. Cannflavin A and B exhibited moderate activity against Leishmania donovani, the parasite responsible for leishmaniasis, with effective inhibitory concentrations of 4.5 μg/mL and 5 μg/mL, respectively. Furthermore, cannflavin A demonstrates inhibitory activity against Trypanosoma brucei, a parasitic protozoan responsible for African sleeping sickness. 

• Antiviral Properties

Cannflavin A demonstrates strong antiviral properties, particularly against HIV-1, Dengue, and Zika viruses. Molecular docking studies reveal that cannflavin A can bind effectively to HIV-1 protease, an enzyme crucial for the virus’ infectivity. Additionally, it is shown to interact with several proteins of both Dengue and Zika viruses. 

Conclusion

Most hemp products on the market contain negligible or non-detectable concentrations of flavonoids. This is often due to the harsh extraction methods used or the absence of whole-plant cannabis extract in the starting material. 

At BioSource Botanicals, our proprietary extraction process allow us to provide the full chemical profile of the plant, including flavonoids and their canflavins, as demonstrated by our Certificates of Analysis (COAs). . This critical distinction may play a significant role in the exceptional results consistently observed in our use cases, showcasing the superiority of our carefully crafted products.

References:

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