Mimea|Phytopedia
Mimea
Phenolics

What are Cannflavins? The Unique Cannabis Flavonoids with Anti-Inflammatory Activity

In 1985, a PhD student in London isolated two compounds from cannabis that inhibited inflammatory markers 30 times more effectively than aspirin—in cell culture. Those compounds, cannflavins A and B, have been quietly sitting in the scientific literature ever since.

18 min read2,902 words

Cannabis has roughly 750 identified metabolites. Most of the conversation lives in two lanes: cannabinoids (THC, CBD, CBG, CBN, etc.) and terpenes (myrcene, limonene, pinene, and the rest of the aromatic family). But there's a third class of compounds that's been sitting in peer-reviewed literature since 1985, barely discussed outside of academic circles: flavonoids. And within that group, cannabis has its own unique subfamily: cannflavins.

Here's what they are, what they do (and crucially, what they don't do), and why they're relevant to the broader conversation about what's actually in the plant.


The Short Version

Cannflavins are prenylated flavonoids unique to Cannabis sativa. Four have been identified so far: cannflavin A, cannflavin B, cannflavin C, and isocannflavin B.

In 1985, researcher Marilyn Barrett isolated cannflavins A and B from cannabis and found they inhibited prostaglandin E2 (PGE2) production in human rheumatoid arthritis synovial cells—about 30 times more effectively than aspirin in that specific in vitro assay.[^1][^2]

That is the foundational finding. Everything else is context around it.

Important qualifier up front: All bioactivity data on cannflavins comes from cell culture and in vitro studies. There are no human clinical trials. No approved therapeutic uses. No dosing guidelines. This is a research story, not a medical one. We're going to hold that line throughout this article.


Discovery: London, 1985

The Researcher

Marilyn Barrett was a PhD student at the University of London's School of Pharmacy in the mid-1980s. Her research objective was to identify compounds in cannabis that could inhibit prostaglandin E2 (PGE2), an inflammatory mediator present in synovial cells cultured from the knee joints of patients undergoing surgery for rheumatoid arthritis.[^1]

The standard anti-inflammatory agents at the time—aspirin, indomethacin, and other NSAIDs—worked by inhibiting cyclooxygenase (COX) enzymes, which are upstream of PGE2 synthesis. Barrett was looking for compounds that might work via a different mechanism.

The Isolation

Barrett's team took a cannabinoid-free ethanolic extract of Cannabis sativa L. and isolated a compound they initially called "Cannflavin" (singular). In the 1985 Biochemical Pharmacology paper, they described it as "distinct from cannabinoids based on isolation procedures and biological properties."[^1]

In 1986, they published a follow-up in Experientia identifying two structurally related prenylated flavones: Cannflavin A and Cannflavin B.[^2]

The Result

In the cell culture assay, cannflavins A and B inhibited PGE2 production with potency roughly 30 times greater than aspirin. They were less potent than indomethacin, but the structural novelty was enough to warrant publication.

The papers were published. Cannabis prohibition was in full effect. Research funding dried up. The discovery sat in the literature for three decades.


What Is a Flavonoid? (Chemistry Primer)

Before we go further, let's establish the baseline.

Flavonoids in General

Flavonoids are a broad class of polyphenolic plant secondary metabolites with a characteristic C6-C3-C6 carbon skeleton: two aromatic rings (A and B) connected by a three-carbon bridge (C).

You encounter flavonoids constantly if you eat plants:

  • Quercetin (onions, apples, tea)
  • Kaempferol (broccoli, kale)
  • Apigenin (parsley, chamomile)
  • Luteolin (celery, thyme)

Flavonoids are studied heavily in food chemistry and plant biology for their antioxidant properties in vitro and their role in plant defense against UV radiation, pathogens, and herbivores.

Cannabis Flavonoids

Cannabis contains more than 20 flavonoids. Most are common across the plant kingdom:

  • Flavones: apigenin, luteolin, orientin, vitexin, isovitexin
  • Flavonols: quercetin, kaempferol

But cannabis also produces a small subfamily that's (mostly) unique to the genus: the cannflavins.

What Makes Cannflavins Different

Cannflavins are prenylated and geranylated flavonoids. That means they have a prenyl group (C5 isoprene unit) or geranyl group (C10 isoprene unit) attached to the flavonoid backbone.

Prenylation is a relatively rare modification in flavonoid chemistry. It's what makes cannflavins structurally distinct—and harder to detect with standard analytical methods.

Chemical structures:

  • Cannflavin A: Prenylated chrysoeriol derivative (5-hydroxy-4'-methoxyflavone with prenyl side chain)
  • Cannflavin B: Prenylated chrysoeriol derivative (different prenylation position than A)
  • Cannflavin C: Geranylated derivative (C10 side chain instead of C5)
  • Isocannflavin B: Structural isomer of cannflavin B

If you're not a chemist, the takeaway is: cannflavins are flavonoids with an extra hydrocarbon tail that makes them behave differently from common flavonoids like quercetin or apigenin.


Biosynthesis: How Cannabis Makes Cannflavins

For 30+ years after Barrett's discovery, nobody knew how cannabis made cannflavins. The pathway was a black box.

That changed in 2019.

The Breakthrough (Rea et al., 2019)

A team led by researchers at the University of Guelph identified the two key enzymes in the cannflavin biosynthetic pathway:[^3]

  1. CsOMT21 (O-methyltransferase): Converts luteolinchrysoeriol (methylation step)
  2. CsPT3 (aromatic prenyltransferase): Converts chrysoeriolcannflavin A + cannflavin B (prenylation step)

Full pathway:

Luteolin (common flavone precursor)
  ↓ CsOMT21 (methylation)
Chrysoeriol
  ↓ CsPT3 (prenylation)
Cannflavin A + Cannflavin B

Why This Mattered

Identifying the biosynthetic genes means you can:

  • Engineer heterologous production systems (yeast, bacteria, tobacco plants) to produce cannflavins without growing cannabis
  • Screen cannabis cultivars for CsOMT21 and CsPT3 expression to identify high-cannflavin chemovars
  • Study enzyme kinetics to understand why some strains produce more cannflavins than others

The University of Guelph researchers partnered with Anahit International Corp. (Toronto) to license the technology for commercial biosynthetic production.[^3] As of 2024, no commercial cannflavin products are publicly available at scale, but the pathway is the foundation for future production.


Bioactivities: What Cannflavins Do (In the Lab)

Here's where we have to be precise about language. All cannflavin bioactivity research is from cell culture, enzyme assays, or in vitro systems. There are no published human clinical trials. No animal efficacy studies in peer-reviewed literature. No approved medical uses.

What follows is what the laboratory research shows.

Anti-inflammatory Activity (Cell Culture)

PGE2 inhibition:

  • Cannflavin A: IC₅₀ = 0.7 μM
  • Cannflavin B: IC₅₀ = 0.7 μM[^4]

mPGES-1 inhibition (microsomal prostaglandin E synthase-1):

  • Cannflavin A: IC₅₀ = 1.8 μM
  • Cannflavin B: IC₅₀ = 3.7 μM[^4]

5-lipoxygenase modulation: Both cannflavin A and B demonstrated inhibitory activity on the 5-lipoxygenase pathway (another branch of arachidonic acid metabolism involved in inflammatory signaling).[^4]

TLR4-induced cytokine/chemokine inhibition: A 2024 study found cannflavin A inhibited TLR4-induced chemokine and cytokine expression in human macrophages, suggesting effects on innate immune signaling pathways.[^5]

Mechanism Summary

Cannflavins appear to modulate multiple points in the inflammatory cascade:

  • Prostaglandin synthesis (COX pathway downstream)
  • Leukotriene synthesis (5-LOX pathway)
  • Cytokine/chemokine signaling (innate immunity)

These are all in vitro observations. The relevance to human physiology—at what dose, via what route of administration, with what safety profile—remains unknown.

Other Reported Activities (Pre-clinical Only)

  • TrkB signaling modulation (neuronal pathways): A 2022 bioRxiv preprint (not yet peer-reviewed in a journal) reported effects on TrkB receptor signaling in neuronal cells.[^6]
  • Antioxidant activity: Common to the flavonoid class broadly; not unique to cannflavins.

Distribution in the Cannabis Plant

If cannflavins have such potent in vitro activity, you might expect them to be abundant in cannabis flower. They are not.

Tissue-Specific Distribution

Total flavonoid content by tissue:[^7]

  • Leaves: 0.34–0.44% of dry weight (highest)
  • Inflorescences (flower): 0.07–0.14% of dry weight
  • Stem bark: Minimal (trace amounts)
  • Roots: Not detected

Specific flavonoid concentrations:[^7]

  • Vitexin (most abundant): 0.12–0.17% in leaves, 0.02–0.06% in flower
  • Apigenin: 0.03–0.07% in leaves, 0.004–0.01% in flower
  • Cannflavins (estimated): <0.02% in flower

Cannflavins are present at such low levels that extracting meaningful quantities from plant material is not economically viable with current technology.

Why Leaves Have More

Flavonoids in general are concentrated in photosynthetically active tissues (leaves) where they serve roles in:

  • UV protection
  • Antioxidant defense
  • Pathogen resistance
  • Pollinator attraction (in flowers, but cannabis is wind-pollinated)

Cannabis leaves are typically discarded as waste in commercial cultivation. The data suggests that, from a pure flavonoid standpoint, leaves are a richer source than flower—but that doesn't mean leaves are a finished consumer product. Local regulations govern what plant material can be sold, and most jurisdictions restrict sales to flower and derivative extracts.


The Extraction Problem

Why You Don't Have Cannflavins in Your CBD Oil

Problem 1: Low abundance Cannflavins are present at <0.02% in flower. If you extract 1 kg of flower, you'd get at most 200 mg of cannflavins—if you could isolate them perfectly, which you can't.

Problem 2: Co-extraction with other flavonoids Standard ethanol or CO₂ extraction pulls flavonoids along with cannabinoids and terpenes, but cannflavins aren't separated from apigenin, quercetin, kaempferol, and the rest of the flavonoid mix. Without targeted purification, you have no idea how much cannflavin is in the extract.

Problem 3: Analytical challenge Until recently, there was no validated analytical method for quantifying cannflavins. A 2023 study published a validated LC-MS assay with a lower limit of quantification (LOQ) of 0.5 μg/mL,[^8] but this is a research-grade method, not something most cannabis labs run routinely.

Problem 4: No market demand (yet) Certificate of Analysis (COA) reports for cannabis products typically show:

  • Cannabinoid profile (THC, CBD, CBG, CBN, etc.)
  • Terpene profile (myrcene, limonene, etc.)
  • Heavy metals, pesticides, microbials

Flavonoids are not tested for. Consumers don't ask for them. Labs don't offer the assay. The feedback loop that drives product optimization doesn't exist for cannflavins.

Bottom line: If a product label says "contains cannflavins," ask for the COA with LC-MS quantification. If they don't have one, the claim is unsubstantiated.


Commercial Production: Biosynthesis as the Solution

Since extraction isn't viable, the industry is turning to biosynthetic production.

Heterologous Expression Systems

Researchers are developing biological systems to produce cannflavins outside cannabis:[^9]

  • Yeast fermentation (engineered Saccharomyces cerevisiae)
  • Bacterial systems (engineered E. coli with introduced CsOMT21 and CsPT3 genes)
  • Plant cell cultures (tobacco hairy root cultures, suspension cultures)

The idea: Insert the cannflavin biosynthesis genes into a fast-growing organism, feed it the precursor (luteolin or chrysoeriol), harvest cannflavins at industrial scale.

Licensing and Commercialization

Anahit International Corp. (Toronto) licensed a patent from the University of Guelph researchers to biosynthesize cannflavins A and B.[^3] As of 2024, no commercial products are publicly available, but this is the pathway the industry is pursuing.

Timeline guess (not a guarantee): If biosynthesis scale-up succeeds, cannflavin-containing products (dietary supplements, topicals, research reagents) could appear in 2-5 years. But only if:

  1. Biosynthesis yields are economically viable
  2. Regulatory pathways are clear (FDA, Health Canada, etc.)
  3. Consumer demand materializes

The Four Cannflavins: A, B, C, and Isocannflavin B

Cannflavin A

  • Discovery: Barrett et al., 1986[^2]
  • Structure: Prenylated chrysoeriol derivative (C5 prenyl side chain)
  • Bioactivity: PGE2 inhibition IC₅₀ = 0.7 μM (in vitro)
  • Abundance: Low (<0.01% in flower, estimated)

Cannflavin B

  • Discovery: Barrett et al., 1986[^2]
  • Structure: Prenylated chrysoeriol derivative (prenyl at different position than A)
  • Bioactivity: PGE2 inhibition IC₅₀ = 0.7 μM (in vitro)
  • Abundance: Low, similar to A

Cannflavin C

  • Discovery: Reported 2008 (cited in secondary literature; primary source not widely accessible)
  • Structure: Geranylated derivative (C10 geranyl side chain instead of C5 prenyl)
  • Bioactivity: Limited data published
  • Abundance: Likely even lower than A and B

Isocannflavin B

  • Discovery: Mentioned in recent reviews[^5]
  • Structure: Isomer of cannflavin B
  • Bioactivity: Limited data
  • Abundance: Trace

Key point: Most research focuses on cannflavins A and B. C and isocannflavin B are less well-characterized.


What This Does Not Mean

We've gone through the chemistry, the biosynthesis, the bioactivity data. Now let's be explicit about what this research does not support:

"Cannflavins treat inflammation." All bioactivity data is from cell culture. No clinical trials.

"Cannabis is anti-inflammatory because of cannflavins." Cannflavins are present at <0.02% in flower. You'd need to isolate and concentrate them to test this hypothesis, which hasn't been done in humans.

"Cannflavins are 30× more potent than aspirin." True in one specific cell culture assay (PGE2 inhibition in rheumatoid synovial cells). Not tested in whole organisms.

"You're getting cannflavins in your CBD oil." Probably not in meaningful amounts. No validated testing, no quantified products on the market.

"Cannabis leaves are medicinal because they have more flavonoids." Leaves have higher total flavonoid content than flower, but (1) no clinical data supports therapeutic use, and (2) local laws govern what plant material can be sold.

What the research does support:

  • Cannflavins are a structurally unique class of prenylated flavonoids found in cannabis
  • They demonstrated potent anti-inflammatory activity in cell culture studies
  • They are present at very low concentrations in the plant
  • Biosynthetic production methods are under development
  • This is a compound class of biomedical research interest

That is the boundary.


FAQs

Are cannflavins in my CBD oil?

Probably not in quantifiable amounts. Standard extraction pulls flavonoids along with cannabinoids, but cannflavins are present at <0.02% in flower. Without targeted purification and LC-MS quantification, there's no way to know. If a product claims "contains cannflavins," ask for the COA with validated testing.

Can I buy cannflavin supplements?

As of 2024, no commercial cannflavin products are widely available. Anahit International licensed biosynthesis technology, but products haven't reached the market yet.

Are cannflavins unique to cannabis?

Mostly. Cannflavin A has been found in Mimulus bigelovii (a plant in the Phrymaceae family),[^4] but cannflavins B and C appear to be cannabis-specific. The prenylated flavonoid structural class exists in other plants (hops, licorice), but the specific cannflavin compounds are rare.

How do cannflavins compare to cannflavin C?

Cannflavins A and B are prenylated (C5 side chain). Cannflavin C is geranylated (C10 side chain). There's much less published research on cannflavin C, so direct potency comparisons aren't available in peer-reviewed literature.

Why did research stall for 30 years after Barrett's discovery?

Cannabis prohibition made large-scale research and funding nearly impossible. Barrett's discovery was published in the mid-1980s, but cannabis remained a Schedule I controlled substance in most jurisdictions. Research funding, clinical trials, and commercial development weren't viable until legal frameworks shifted in the 2010s-2020s.

What's the difference between cannflavins and cannabinoids?

Cannabinoids (THC, CBD, CBG, etc.) are terpenophenolic compounds that interact with the endocannabinoid system (CB1, CB2 receptors). Cannflavins are prenylated flavonoids (polyphenolic compounds) that do not interact with cannabinoid receptors. They're chemically distinct classes with different mechanisms of action.

Are there cannflavin-rich cannabis strains?

Possibly, but there's no public database of strain-specific cannflavin profiles. The 2019 biosynthesis study identified the genes (CsOMT21, CsPT3), so in theory, you could screen cultivars for expression levels. But without commercial testing labs offering cannflavin quantification, this data doesn't exist yet.

Can I make cannflavin extract at home?

Technically possible but not practical. You'd need:

  1. Large amounts of cannabis leaf material (where flavonoids are most concentrated)
  2. Chromatography equipment to separate cannflavins from other flavonoids
  3. LC-MS to quantify and verify purity

This is beyond home extraction capabilities. And in most jurisdictions, processing cannabis leaves into concentrates may not be legal.


What We're Watching For

Research Gaps to Fill

  • Human clinical trials: Even a Phase I safety study would be valuable
  • Strain-specific profiling: Which cultivars produce the most cannflavins?
  • Cannflavin C characterization: Structure confirmation, bioactivity data
  • Entourage effect studies: Do cannflavins interact with cannabinoids or terpenes?

Commercial Developments

  • Biosynthesis scale-up: Will Anahit International or other companies bring products to market?
  • Analytical methods: Will standard cannabis testing labs start offering cannflavin quantification?
  • Regulatory pathways: How will FDA/Health Canada classify biosynthetically produced cannflavins?

We'll update this article as peer-reviewed research and commercial developments appear.


Bottom Line

Cannflavins are prenylated flavonoids unique to cannabis, first isolated in 1985 by Marilyn Barrett. In cell culture studies, they demonstrated anti-inflammatory activity roughly 30 times more potent than aspirin. Research stalled for decades due to cannabis prohibition. The biosynthetic pathway was identified in 2019, enabling potential commercial production via engineered microorganisms.

They're present at very low levels in the plant (<0.02% in flower), so you're not getting meaningful amounts in standard cannabis products. No human clinical trials exist. No approved therapeutic uses. This is a research story, not a medical one.

But it's a compelling research story—and one more piece of evidence that the chemistry of cannabis is far more complex than the THC/CBD conversation captures.

— Nug


References

[^1]: Barrett ML, Scutt AM, Evans FJ. Isolation from Cannabis sativa L. of cannflavin—a novel inhibitor of prostaglandin production. Biochemical Pharmacology. 1985;34(11):2019-2024. PubMed: 3859295

[^2]: Barrett ML, Gordon D, Evans FJ. Cannflavin A and B, prenylated flavones from Cannabis sativa L. Experientia. 1986;42(4):452-453. PubMed: 3754224

[^3]: Rea KA, Casaretto JA, Al-Abdul-Wahid MS, et al. Biosynthesis of cannflavins A and B from Cannabis sativa L. Phytochemistry. 2019;164:162-171. PubMed: 31151063

[^4]: Werz O, Seegers J, Schaible AM, et al. Cannflavins from hemp sprouts, a novel cannabinoid-free hemp food product, target microsomal prostaglandin E2 synthase-1 and 5-lipoxygenase. PhytoMedicine. 2020;74:152935. PubMed: 32858172

[^5]: Flores-Sanchez IJ, Pec J, Fei J, et al. Chemistry and Biological Activities of Cannflavins of the Cannabis Plant. Cannabis and Cannabinoid Research. 2024;9(1):18-29. PMC10714118

[^6]: Interference of Neuronal TrkB Signaling by the Cannabis-Derived Flavonoids Cannflavins A and B. bioRxiv preprint, 2022. bioRxiv (Not yet peer-reviewed in journal)

[^7]: Andre CM, Hausman JF, Guerriero G. Cannabis sativa: The Plant of the Thousand and One Molecules. Frontiers in Plant Science. 2016;7:19. Referenced in: Secondary Metabolites Profiled in Cannabis Inflorescences, Leaves, Stem Barks, and Roots. Scientific Reports. 2020;10:3309. PMC7039888

[^8]: Watkins R, Wu L, Zhang C, et al. A validated method for detection of cannflavins in hemp extracts. Journal of Chromatography B. 2023;1228:123819. ScienceDirect

[^9]: Yang X, Barajas-Azpeleta R, Huchelmann A, et al. Flavonoids in Cannabis sativa: Biosynthesis, Bioactivities, and Biotechnology. ACS Omega. 2021;6(7):4910-4919. PMC7931196


Disclosures: This article summarizes peer-reviewed research on cannflavins. It is not medical advice. It does not diagnose, treat, cure, or prevent any condition. Phytopedia is a knowledge platform, not a healthcare provider. All bioactivity data discussed is from in vitro (cell culture) studies. No human clinical trials have been published. Consult a healthcare professional for medical questions.


Have questions about this topic?

Join the Mimea community to discuss with fellow cannabis enthusiasts.

More from Phenolics