What Are Cannabis Flavonoids? Health Benefits and Uses

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What Are Cannabis Flavonoids? Medical Benefits and Uses

Cannabis flavonoids are a group of natural compounds that give cannabis plants their distinctive colors, aromas, and flavors. They are also responsible for some of the beneficial effects of cannabis, such as anti-inflammatory, antioxidant, and neuroprotective effects.

What Do Flavonoids Do?

Flavonoids have multiple roles in cannabis plants. They protect the plants from UV radiation, pests, pathogens, and environmental stress. They also modulate the production and activity of cannabinoids and terpenes, the main active compounds in cannabis.

Flavonoids may also have beneficial effects on human health. They may interact with the endocannabinoid-system, a network of receptors and molecules that regulate various physiological processes such as pain, mood, appetite, memory, and inflammation. They may also modulate the activity of enzymes and transporters that affect the metabolism and bioavailability of cannabinoids and other drugs.

How Do Flavonoids Work In The Body?

Flavonoids work in different ways depending on their structure, concentration, and target.

Some flavonoids may bind to cannabinoid receptors (CB1 and CB2) or other receptors (such as PPARs, TRPVs, and GPR55) and either activate or inhibit them.
Some flavonoids may inhibit or induce enzymes (such as CYPs, FAAH, and COX) that break down or synthesize cannabinoids and other compounds.
Some flavonoids may affect the expression or function of transporters (such as ABCs, SLCs, and GLUTs) that move cannabinoids and other molecules across cell membranes.

The effects of flavonoids may also depend on their interactions with other compounds in cannabis or in the body. For example, some flavonoids may enhance or reduce the effects of cannabinoids by modulating their absorption, distribution, metabolism, or excretion.

Some flavonoids may also act synergistically or antagonistically with other flavonoids or terpenes to produce entourage effects.

What Are The Benefits and Uses of Flavonoids?

Flavonoids have a range of benefits for different health conditions and wellness goals. Some of the potential health benefits are:

Antioxidant: Flavonoids can scavenge free radicals and protect cells from oxidative damage, which is associated with aging and many diseases. They can also modulate the expression and activity of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx).
Anti-inflammatory: Flavonoids can inhibit the production and release of pro-inflammatory mediators, such as cytokines, prostaglandins, and leukotrienes. They can also suppress the activation of inflammatory pathways, such as nuclear factor-kappa B (NF-κB), mitogen-activated protein kinases (MAPKs), and cyclooxygenases (COXs).
Anti-cancer: Flavonoids can induce apoptosis (programmed cell death) and autophagy (self-digestion) of cancer cells, as well as inhibit their proliferation, migration, invasion, and angiogenesis (blood vessel formation). They can also modulate the expression and activity of various oncogenes (cancer-promoting genes) and tumor suppressor genes (cancer-inhibiting genes).
Neuroprotective: Flavonoids can protect neurons from various insults, such as ischemia (lack of blood supply), excitotoxicity (overstimulation by glutamate), neuroinflammation, and neurodegeneration. They can also enhance neurogenesis (new neuron formation), synaptic plasticity (neural adaptation), and cognitive function.
Other effects: Flavonoids may also have anti-diabetic, anti-obesity, anti-allergic, anti-microbial, anti-viral, anti-fungal, anti-parasitic, anti-ulcer, hepatoprotective (liver-protecting), cardioprotective (heart-protecting), and bone-protective effects.

Flavonoids may be used as natural supplements or adjuvants for various health conditions, such as chronic pain, inflammation, cancer, neurodegenerative diseases, metabolic disorders, allergic reactions, infections, ulcers, liver diseases, cardiovascular diseases, and osteoporosis.

However, more clinical trials are needed to confirm the safety and efficacy of cannabis flavonoids in humans.

How Do Flavonoids Interact With Cannabinoids and Terpenes?

Flavonoids may enhance the effects of cannabinoids and terpenes through a phenomenon called the entourage effect. This means that the combination of different compounds in cannabis may produce synergistic effects that are greater than the sum of their individual effects.

For example, some flavonoids may increase the bioavailability of cannabinoids by inhibiting their metabolism or facilitating their absorption. Some flavonoids may also modulate the activity of cannabinoid receptors or other receptors that cannabinoids interact with. Some terpenes may also enhance the absorption or penetration of flavonoids into cells or tissues.

The entourage effect may explain why whole-plant cannabis extracts or products may have more benefits than isolated cannabinoids or synthetic versions. However, more research is needed to understand the exact mechanisms and outcomes of the interactions between flavonoids, cannabinoids, and terpenes.

How Many Flavonoids Are in Cannabis?

There are over 10,000 known flavonoids in nature, but those found in cannabis fall into six main subcategories:

1. Chalcones:

These flavonoids are brown shade pigments that are found in many plants, such as apples, strawberries, and tomatoes. Chalcones have antioxidant, anti-inflammatory, anti-fungal, and anti-cancer effects.

2. Flavones:

These flavonoids are yellow or white pigments that are found in many plants, such as parsley, celery, and chamomile. Flavones have anti-inflammatory, antioxidant, anti-allergic, and anti-cancer effects. Cannaflavin A, B, and C belong to this subcategory.

3. Isoflavonoids:

These flavonoids are mainly found in legumes, such as soybeans, peanuts, and lentils. Isoflavonoids have estrogen-like effects and can modulate hormone levels and metabolism. They also have antioxidant, anti-inflammatory, and anti-cancer properties.

4. Flavanones:

These flavonoids are yellow or orange pigments that are found in citrus fruits, such as oranges, lemons, and grapefruits. Flavanones have antioxidant, anti-inflammatory, anti-microbial, and anti-cancer effects. They can also affect cholesterol levels and blood pressure.

5. Anthoxanthins:

These flavonoids are white or pale yellow pigments that are found in many plants, such as onions, garlic, cauliflower, and cabbage. Anthoxanthins have antioxidant, anti-inflammatory, anti-microbial, and anti-cancer effects. They can also modulate blood sugar levels and prevent oxidative damage.

6. Anthocyanins:

These flavonoids are responsible for the red, purple, or blue color of many fruits and flowers. They are found in berries, grapes, eggplants, and red cabbage. They have antioxidant, anti-inflammatory, anti-cancer, and neuroprotective effects. Cannabis produces several anthocyanins, such as cyanidin, delphinidin, malvidin, pelargonidin, peonidin, and petunidin.

These Six Subgroups Contain More Than 20 Different Flavonoids That Have Been Identified in Marijuana Plants

Here are the nine most important ones and their therapeutic effects:

1. Cannflavins A, B, C:

Cannflavin A: This is a prenylated flavone that is unique to cannabis. Cannflavin A has potent anti-inflammatory effects that are 30 times more effective than aspirin. Cannflavin A may also inhibit the growth of certain cancer cells and protect the brain from oxidative stress.
Cannflavin B: Another prenylated flavone that is unique to cannabis. Cannflavin B has similar anti-inflammatory effects as cannflavin A but with a different chemical structure. Cannflavin B may also have anti-fungal and anti-microbial properties.
Cannflavin C: A geranylated flavone that is unique to cannabis. Cannflavin C has less anti-inflammatory effects than cannflavin A and B but has more antioxidant effects. Cannflavin C may also have neuroprotective effects by reducing the accumulation of amyloid-beta plaques in Alzheimer’s disease.

2. Apigenin:

This is a flavone that is also found in chamomile, parsley, celery, and other plants. Apigenin has anti-inflammatory, anti-anxiety, anti-cancer, and estrogenic effects. Apigenin may also modulate the activity of certain enzymes that metabolize cannabinoids, thus affecting their bioavailability and potency.

3. Luteolin:

This is another flavone that is also present in many fruits and vegetables. Luteolin has anti-inflammatory, anti-oxidant, anti-diabetic, and anti-cancer effects. Luteolin may also inhibit the growth of bacteria and fungi that can cause infections or spoilage of cannabis products.

4. Kaempferol:

This is a flavonol that is also abundant in tea, kale, beans, broccoli, spinach, and other plants. Kaempferol has anti-inflammatory, anti-oxidant, anti-diabetic, anti-cancer, and neuroprotective effects. Kaempferol may also enhance the activity of endocannabinoids, the natural cannabinoids produced by our bodies.

5. Quercetin:

This is another flavonol that is also found in many fruits, vegetables, seeds, and grains; for example, red onions, capers, and cabbage. Quercetin has anti-inflammatory, antioxidant, anti-allergic, antiviral, and anticancer effects. Quercetin can also interact with cannabinoid receptors and modulate their signaling.

6. Orientin:

This is a flavone glycoside that is also found in yellow pheasant’s eye, bamboo leaves, and basil. Orientin has antioxidant, anti-inflammatory, anti-diabetic, and neuroprotective effects. Orientin may also protect against oxidative stress and inflammation induced by THC.

7. Isovitexin:

This is a flavone glycoside that is also found in passion flowers, cannabis, açaí palm, and oat. Isovitexin has antioxidant, anti-inflammatory, anti-diabetic, and anti-cancer effects. Isovitexin may also enhance the anti-inflammatory activity of CBD.

8. Vitexin:

This is a flavone glycoside that is also found in hawthorn, passionflower, pearl millet, and bamboo. Vitexin has antioxidant, anti-inflammatory, anti-diabetic, and cardioprotective effects. Vitexin may also reduce the anxiety and depression induced by THC.

9. β-sitosterol:

This is a phytosterol that is also found in many plant oils, nuts, seeds, grains, and avocados. Beta-sitosterol has anti-inflammatory, cholesterol-lowering, and prostate health benefits. It may also modulate the ECS and enhance the analgesic effect of cannabinoids.

How to Increase Flavonoids in Cannabis?

Flavonoids are found in most parts of the marijuana plant, except for the roots and seeds. However, the amount and type of flavonoids may differ depending on the strain, growing conditions, harvesting time, and processing methods.

If you want to increase the flavonoid content of your cannabis, you may want to consider the following factors:

1. Strain:

Some strains have higher flavonoid levels than others. For example, purple or blue strains tend to have more anthocyanins, which are flavonoids that give cannabis its color. Similarly, strains with a strong citrus or berry smell may have more flavanones or flavones, which are flavonoids that contribute to the aroma and flavor of cannabis. You can look for strains that have a high terpene profile or distinctive color, aroma, or flavor to get more flavonoids.

2. Growing conditions:

Flavonoids are influenced by the environmental factors that affect the cannabis plant. For instance, temperature, light intensity, pH level, nutrient availability, and stress can all affect flavonoid production and expression.

Generally, lower temperatures and higher light intensity can induce more anthocyanin synthesis, resulting in more colorful buds. However, too much stress or nutrient deficiency can also reduce the flavonoid content and quality.

3. Harvesting Time:

Flavonoids are more abundant in fresh cannabis than in dried or cured cannabis. This is because flavonoids are sensitive to heat, light, and air exposure, which can degrade them over time. Therefore, harvesting your cannabis at the right time can preserve more flavonoids.

Ideally, you should harvest your cannabis when the trichomes are mostly milky or cloudy, indicating peak cannabinoid and terpene production. You can also check the color of the pistils or hairs on the buds. When they turn from white to brown or red, it means that the buds are ripe and ready to harvest.

4. Processing Methods:

After harvesting your cannabis, you should dry and cure it properly to maintain its potency and quality. However, you should also avoid exposing it to high temperatures or direct sunlight, as this can destroy some of the flavonoids.

You should also store your cannabis in a cool, dark, and dry place in an airtight container to prevent oxidation and mold growth.

Additionally, you should avoid grinding your cannabis too finely or using harsh solvents or extraction methods that can strip away some of the flavonoids.

Cannabis Flavonoids vs Terpenes, What Are The Differences?

Both flavonoids and cannabis terpenes interact with the endocannabinoid system, which regulates various physiological and psychological processes in humans and animals; however, there are some differences:

Flavonoids are more stable and less affected by heat, light, and air than terpenes, which tend to evaporate or degrade over time.
Flavonoids are more water-soluble than terpenes, which are more oil-soluble. This affects how they are extracted and consumed.
Flavonoids have more diverse structures and functions than terpenes, which share a common building block called isoprene. Flavonoids can act as anti-inflammatory, anti-cancer, neuroprotective, anti-diabetic, anti-allergic, and anti-microbial agents, among others. Terpenes can modulate the effects of cannabinoids such as THC and CBD by enhancing or inhibiting their activity.
Flavonoids are more common and widespread in nature than terpenes, which are mostly found in plants of the order Lamiales, such as mint, lavender, rosemary, and cannabis. Flavonoids are present in fruits, vegetables, grains, tea, wine, chocolate, and many other foods and beverages.

Bottom Line

Flavonoids are an important component of the cannabis plant that has many benefits for your health and synergistic effects with cannabinoids. They can help with inflammation, pain, oxidative stress, immunity, mood, and cognition. By choosing strains that are high in these compounds, you can enjoy a more diverse and enjoyable medical cannabis experience.

FAQs about Cannabis Flavonoids

How are cannabis flavonoids produced?

Flavonoids are synthesized from phenylalanine, an amino acid that is derived from shikimic acid, a common precursor of many plant secondary metabolites.

Phenylalanine is converted into cinnamic acid by phenylalanine ammonia-lyase (PAL), then into p-coumaric acid by cinnamate 4-hydroxylase (C4H). P-coumaric acid is activated into p-coumaroyl-CoA by 4-coumarate: CoA ligase (4CL), then condensed with three molecules of malonyl-CoA by chalcone synthase (CHS) to form naringenin chalcone.

Naringenin chalcone is then cyclized into naringenin by chalcone isomerase (CHI), which is the common precursor of all flavonoids.

Naringenin can be further modified by various enzymes to produce different subclasses of flavonoids, such as flavones, flavonols, flavanones, flavanols, anthocyanins, and proanthocyanidins. The biosynthesis of cannaflavins involves two additional steps: prenylation and geranylation.

Prenylation is the addition of a five-carbon unit (prenyl group) to naringenin by prenyltransferase (PT), while geranylation is the addition of a ten-carbon unit (geranyl group) to naringenin by geranyltransferase (GT). The exact genes and enzymes responsible for these reactions in cannabis are still unknown.

Where are flavonoids found in cannabis?

Flavonoids are distributed throughout most tissues of the marijuana plant, except for the roots and seeds. They are mainly concentrated in the flowers (buds), leaves, stems, and trichomes (glandular hairs).

The profile and content of flavonoids vary depending on the plant’s developmental stage, environmental conditions, genetic factors, and cultivation methods.

Flavonoids are usually extracted along with cannabinoids and terpenes in full-spectrum or broad-spectrum CBD products. These products may offer enhanced benefits due to the entourage effect, which is the synergistic interaction of different phytochemicals in cannabis.

Are flavonoids psychoactive?

No, flavonoids do not have psychoactive effects by themselves. However, they may modulate the psychoactive effects of cannabinoids by interacting with cannabinoid receptors or influencing their metabolism.

What are the side effects of flavonoids?

Flavonoids may have some side effects depending on the dose, individual sensitivity, and interaction with other substances. Some of these side effects may include nausea, diarrhea, drowsiness, dry mouth, or low blood pressure.

To avoid these side effects, it is advisable to start with low doses or consume flavonoids with food or water. It is also important to consult with a doctor before using them if you are taking any medications or supplements that may interact with them.

Some examples of drugs that may interact with flavonoids are blood thinners (e.g., warfarin), anticoagulants (e.g., heparin), antiplatelets (e.g., aspirin), antidepressants (e.g., fluoxetine), anticonvulsants (e.g., phenytoin), antibiotics (e.g., ciprofloxacin), antifungals (e.g., ketoconazole), antihistamines (e.g., diphenhydramine), antihypertensives (e.g., lisinopril), anti-inflammatories (e.g., ibuprofen), antipsychotics (e.g., haloperidol), immunosuppressants (e.g., cyclosporine), opioids (e.g., morphine), sedatives (e.g., diazepam), or steroids (e.g., prednisone).

Are flavonoids legal?

Flavonoids are legal in most countries, as they are naturally present in many foods and beverages. However, some flavonoids may interact with certain medications or have side effects at high doses. Therefore, it is advisable to consult a doctor before taking flavonoid supplements or consuming large amounts of flavonoid-rich foods.

Do flavonoids affect the color of the cannabis?

One type of flavonoid that causes purple hues in some cannabis strains is anthocyanin. This flavonoid may also produce red or blue colors in other plants, depending on the pH levels. Purple flavonoid strains are cannabis varieties that have high levels of anthocyanin in their flowers, giving them a distinct purple appearance.

How can I consume flavonoids?

Flavonoids are present in all parts of the cannabis plant, but they are more concentrated in the flowers, leaves, and stems. You can consume flavonoids by:

Smoking or vaping cannabis: This is the most common way of consuming flavonoids, but it also exposes you to harmful combustion products and reduces the bioavailability of some flavonoids.
Eating or drinking cannabis: This is a safer way of consuming flavonoids, but it also requires decarboxylation (heating) to activate some of them. You can make your own edibles or beverages with cannabis butter or oil, or buy ready-made products from dispensaries or online stores.
Applying cannabis topically: This is a localized way of consuming flavonoids that can help with skin conditions, muscle soreness, and joint pain. You can use cannabis creams, balms, lotions, or oils that contain cannabis extracts or infusions.