Secondary Metabolites of Cannabis

Secondary metabolites are chemical compounds that plants produce to fight against threats, adapt to environmental pressures and facilitate ecological relationships.

In cannabis, these compounds go beyond basic growth and survival functions. They’re responsible for the plant’s recreational and medicinal benefits, as well as the distinct flavors and aromas that differentiate strains. The secondary metabolites of cannabis are unique in that they can be tailored to address specific medicinal or recreational needs, influencing the plant’s market value.

In this blog post, we’ll explain the role of secondary metabolites, identify those found in cannabis and suggest how growers can enhance their production to increase crop quality.

What are secondary metabolites?

Plants produce two types of metabolites—primary and secondary:

  • Primary metabolites are involved in essential processes like photosynthesis, nutrient transport and respiration. Compounds such as carbohydrates and amino acids that are necessary for a plant’s survival fall under this category.
  • Secondary metabolites, by contrast, are inessential. They do, however, provide a competitive advantage, primarily by protecting plants from biotic and abiotic stress. Phenylpropanoids, for example, are a secondary metabolite that often accumulate in plants exposed to herbicides, UV radiation and other environmental stressors.[1] Many secondary metabolites have antibiotic, antifungal, antiviral and other health effects, which is why they are often used in pharmaceuticals. Some attract pollinators and contribute to unique plant characteristics like color, fragrance, flavor.[2]

These compounds are broadly classified based on their biosynthetic pathways (Figure 1).

Types of secondary metabolites in cannabis

Cannabis contains more than 545 identified compounds,[3] which includes multiple classes of secondary metabolites.

Cannabinoids

Cannabinoids are a set of phytochemicals unique to cannabis. At least 104 cannabinoids have been identified, with Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabigerol (CBG) the most studied due to their effects on humans. Mainly present as Δ9-tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA) and cannabigerolic acid (CBGA), these acidic forms are thermally unstable and readily convert to their active counterparts—THC and CBD—through decarboxylation when exposed to light or heat.[4] THC is known mainly for its psychoactive effects, while CBD is widely recognized for its medicinal benefits.

Cannabis plants are classified into three phenotypes based on THC content:[5]

  • Drug-type (phenotype I, also known as “marijuana”): >0.5% THC and <0.5% CBD.
  • Intermediate (phenotype II): mainly CBD, with THC levels varying.
  • Hemp or fiber (phenotype III): Low THC, often <0.3%.
Terpinoids

Terpenes, derived from terpenoids, are responsible for the unique aromas and flavors of cannabis strains. Cannabis contains more than 120 terpenoids, including 61 monoterpenoids, 52 sesquiterpenoids and five triterpenoids, mainly in the leaves, roots, flowers and essential oils.[6]

Phenolic compounds

Phenolic compounds include:

  • Flavonoids serve various biochemical, physiological and ecological functions. More than 20 flavonoids have been identified in cannabis, many of them contributing to the plant’s color. Flavonoids also include cannflavins, which have health benefits for humans, including anti-inflammatory and neuroprotective effects.[7]
  • Stilbenoids aid in plant defense, growth inhibition and pest resistance and exhibit antioxidant, antibacterial and antifungal properties.[8]
  • Lignan amides and phenolic amides protect plants from oxidative stress and damage by free radicals. They also deter pathogens and pests through antimicrobial and insect-repelling properties.[9]
Alkaloids

Alkaloids are bitter-tasting compounds that deter animals and insects from feeding on plants. They also offer analgesic, anti-inflammatory and antimicrobial benefits.[10]

Why secondary metabolites matter

Understanding secondary metabolites is crucial for cannabis growers seeking to maximize the economic value of their recreational or medicinal crops. Cannabinoids, for example, interact with the human endocannabinoid system, influencing processes like pain relief, anxiety reduction and anti-inflammatory responses.

Terpenes also enhance marketability by imparting the unique aromas and flavors of cannabis strains, ranging from earthy and fruity to piney and floral. Different terpenes produce different effects for cannabis users, further differentiating strains.

Focusing on heightening secondary metabolite production can amplify the “entourage effect”—a hypothesis that secondary metabolites work synergistically with THC to enhance its effects. Increasing secondary metabolites may therefore improve the user experience.

Finally, in addition to increasing market value, secondary metabolites benefit plant health. By providing antifungal, antibacterial and pest-repellent effects, they establish a multi-layered, synergistic defense system that helps plants thrive in challenging environments.

How to increase secondary metabolites

A cannabis plant’s secondary metabolite content and dry weight are primarily influenced by genetics (breeding and phenotype),[11] so strain selection is the first step toward achieving high secondary metabolite concentrations. That includes selecting a high-potency mother plant, which can be used for asexual propagation through tissue culture, creating batch-to-batch consistency in cannabinoid content and profile.

While genetics play a major role, cultivation practices also significantly impact secondary metabolite levels. Growers should consider the following factors:

Growing medium

Although research is limited, one study found that using a coconut fiber substrate with better drainage increased yields of THCA (a THC precursor) and CBGA, as well as overall growth rates. Substrates with lower container capacity also produced higher cannabis yields and THC content.[12]

Light

Light intensity and wavelength help guide secondary metabolite production. Different wavelengths influence the production of different cannabinoids, with blue-rich light able to stimulate CBGA accumulation (Figure 2).[13] Avoid overexposure, which can cause photoinhibition and reduce growth, while insufficient light can limit photosynthetic activity and reduce yield.

Figure 2. The impact of wavelengths on Cannabis
sativa L
. secondary-metabolite responses, with corresponding photoreceptors
(↑: increase; Δ: varying depended on light treatments; ↓: decrease; ?:
unknown). Image source: Eichhorn Bilodeau, Samuel, Bo-Sen Wu, Anne-Sophie
Rufyikiri, Sarah MacPherson, and Mark Lefsrud. 219. “An Update on Plant
Photobiology and Implications for Cannabis Production.” Frontiers in Plant
Science 10. https://doi.org/10.3389/fpls.2019.00296.

Temperature and humidity

Keeping the temperature and humidity within the right range ensures optimal growth and production. Research shows that THC can be up to 30 times higher when cannabis is grown at 24°C compared to lower temperatures, and humidity is kept to moderate levels (50% versus 80%).[14]

Nutrients

Balanced fertilization, with the right concentrations and precise ratios of macro- and micronutrients, is critical for cannabinoid production. While overfertilization may reduce THC, some stress induced by nutrient deficiencies may increase phytocannabinoid production.[15]

Stress induction

Controlled stressors can enhance metabolite production. Ultraviolet B radiation has been shown to increase THC concentrations,[16] while drought stress can stimulate secondary metabolite accumulation, making irrigation control a key aspect of crop steering.

Supplementing rhizobacteria

Inoculating cannabis with plant growth-promoting rhizobacteria can boost cannabinoid levels. One study found that inoculating cannabis with Mucilaginibacter sp. during the vegetative stage increased flower dry weight, CBD and THC content, while inoculation during the flowering stage enhanced terpene accumulation.[17]

Conclusion

Secondary metabolites are why cannabis is sought after for recreational and medicinal effects. By selecting a good strain and mother plant, and following best cultivation practices, growers can increase the concentration of these desirable compounds and improve their crop’s economic value in terms of price per weight.

Emerald Harvest Team

[1] Altaf Reshi, Zubair, Waquar Ahmad, Alexander S Lukatkin, and Saad Bin Javed. 2023. “From Nature to Lab: A Review of Secondary Metabolite Biosynthetic Pathways, Environmental Influences, and In Vitro Approaches.” Metabolites 8: 895. https://doi.org/10.3390/metabo13080895.

[2] Anjali, Sumit Kumar, Tulasi Korra, et. al. 2023. “Role of plant secondary metabolites in defense and transcriptional regulation in response to biotic stress.” Plant Stress 8: 100154. https://doi.org/10.1016/j.stress.2023.100154.

[3] Gonclaves, Joana, Tiago Rosado, Sofia Soares, et. al. 2019. “Cannabis and Its Secondary Metabolites: Their Use as Therapeutic Drugs, Toxicological Aspects, and Analytical Determination.” Medicines 6 (1): 31. https://doi.org/10.3390/medicines6010031.

[4] Wang, Mei, Yan-Hong Wang, Bharathi Avula, et. al. 2016. “Decarboxylation Study of Acidic Cannabinoids: A Novel Approach Using Ultra-High-Performance Supercritical Fluid Chromatography/Photodiode Array-Mass Spectrometry.” Cannabis and Cannabinoid Research 1 (1): 262-271. https://doi.org/10.1089/can.2016.0020.

[5] Hesami, Mohsen, Marco Pepe, Milad Alizadeh, Aida Raket, Austin Baiton, and Andrew Maxwell Phineas Jones. 2020. “Recent advances in cannabis biotechnology.” Industrial Crops and Products 158: 113026. https://doi.org/10.1016/j.indcrop.2020.113026.

[6] Lowe, Henry, Blair Steele, Joseph Bryant, Ngeh Toyang, Wilfred Ngwa. 2021. “Non-Cannabinoid Metabolites of Cannabis sativa L. with Therapeautic Potential.” Plants 10 (2): 400. https://doi.org/10.3390/plants10020400.

[7]Abdel-Kader, Maged S., Mohamed M Radwan, Ahmed M. Metwaly, Ibrahim H. Eissa, Arno Hazekamp, and Mahmoud A. ElSohly. 2023. “Chemistry and Biological Activities of Cannflavins of the Cannabis Plant.” Cannabis and Cannabinoid Research 8 (6): 974-985. https://doi.org/10.1089/can.2023.0128.

[8] Alireza Salami, Seyed, Federico Martinelli, Antonio Giovino, Ava Bachari, Neda Arad, and Nitin Mantri. 2020. “It Is Our Turn to Get Cannabis High: Put Cannabinoids in Food and Health Baskets.” Molecules 25 (18): 4036. https://doi.org/10.3390/molecules25184036.

[9] Izzo, Luana, Luigi Castaldo, Alfonso Narvaez, et. al. 2020. “Analyss of Phenolic Compounds in Commercial Cannabis sativa L. Inflorescences Using UHPLC-Q-Orbitrap HRMS.” Molecules 25 (3): 631. https://doi.org/10.3390/molecules/25030631.

[10] ScienceDirect. “Alkaloid.” Accessed December 2, 2024. https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/alkaloid.

[11] Caplan, Deron, Mike Dixon, and Youbin Zheng. 2019. “Increasing Inflorescence Dry Weight and Cannabinoid Content in Medicinal Cannabis Using Controlled Drought Stress.” HortScience 54 (5): 964-969. https://doi.org/10.21273/HORTSCI13510-18.

[12] Trancoso, Ingrid, Guilherme A.R. de Souza, Paulo Ricardo dos Santos, et. al. 2022. “Cannabis sativa L.: Crop Management and Abiotic Factors That Affect Phytocannabinoid Production.” Agronomy 12 (7): 1492. https://doi.org/10.3390/agronomy12071492.

[13] Danziger, Nadav, and Nirit Bernstein. 2021. “Light matters: Effect of light spectra on cannabinoid profile and plant development of medical cannabis (Cannabis sativa L.).” Industrial Crops and Products 164. https://doi.org/10.1016/j.indcrop.2021.113351.

[14] Paris, M., F. Boucher, and L. Cosson. 1975. “The Constituents of Cannabis sativa Pollen.” Economic Botany 29 (3): 245-253. https://doi.org/10.1007/BF02873173.

[15] Trancoso, Ingrid, Guilherme A.R. de Souza, Paulo Ricardo dos Santos, et. al. 2022. “Cannabis sativa L.: Crop Management and Abiotic Factors That Affect Phytocannabinoid Production.” Agronomy 12 (7): 1492. https://doi.org/10.3390/agronomy12071492.

[16] Caplan, Deron, Mike Dixon, and Youbin Zheng. 2019. “Increasing Inflorescence Dry Weight and Cannabinoid Content in Medicinal Cannabis Using Controlled Drought Stress.” HortScience 54 (5): 964-969. https://doi.org/10.21273/HORTSCI13510-18.

[17] Lyu, Dongmei, Rachel Backer, Fabrice Berrue, Camilo Martinez-Farina, Joseph P M Hui, and Donald Lawrence Smith. 2023. “Plant Growth-Promoting Rhizobacteria (PGPR) with Microbial Growth Broth Improve Biomass and Secondary Metabolite Accumulation of Cannabis sativa L.” Journal of Agricultural and Food Chemistry 71 (19): 7268-7277. https://doi.org/10.1021/acs.jafc.2c06961.

Share

Leave a comment

Your email address will not be published. Required fields are marked *

top