Last reviewed by Daniel Gana and Abraham Benavides, MD on 11/25/2024

Introduction

As the hemp product landscape continues to transform at a fast pace, it’s become increasingly common for some companies to market products labeled as full spectrum while deriving them primarily from isolates. However, the presence of select cannabinoid isolates and a few terpenes does not nearly equate to a true full-spectrum experience. 

The cannabis plant is a complex and meticulously designed organism, characterized by a unique synergy among its 750 components, including about 120 cannabinoids, 200 terpenes, and several flavonoids. This complex interplay is crucial for optimizing therapeutic effects, as each compound enhances the others’ efficacy in ways that isolated substances cannot achieve. Nature orchestrates these relationships, resulting in a balanced profile that supports overall wellness and amplifies the benefits of the plant. 

While cannabis shares certain terpenes with other plants, the ratios in which these compounds are combined significantly influences their interactions with various receptors in the body. The cannabis plant has evolved to produce a unique blend of compounds, allowing terpenes, flavonoids and cannabinoids to develop together in ways that enhance their individual and collective effects. This natural design is crucial for maximizing the therapeutic potential of the plant.

Accumulating research indicates that the entourage effect, which refers to the collaborative interaction of various cannabinoids, terpenes, and other compounds, is fundamental to achieving desired health benefits. This idea isn’t new, in fact it was first introduced by Dr. Mechoulam and team around the time of their discovery of the endocannabinoid system. It’s bolstered since then in several preclinical and few clinical studies, including trials in epilepsy, migraines, and multiple sclerosis. 

For instance, a 2020 study published in Medical Cannabis and Cannabinoids highlights that the synergistic ratios of cannabinoids and terpenes in whole-plant extracts can enhance therapeutic efficacy, providing effects not replicated by isolated compounds​. Another  2022 review article echoes how the varying constituent ratios and interactive complexity of cannabis ultimately determines the therapeutic response beyond just THC and CBD.

In this article, we explore why creating full-spectrum cannabis products from isolates is suboptimal as a whole and unlikely to yield the same therapeutic outcomes as those wholly derived from the hemp plant itself. By understanding the significance of natural compound interactions, we can better appreciate why only nature knows best when formulating effective hemp products.

Why natural active-spectrum and full-spectrum hemp products stand out

1. Synergistic Ratios Between Terpenes and Cannabinoids

When terpenes from other plants are combined with cannabinoids, their bioavailability, proportions, stability, purity, composition, and metabolic rates may not align as they do in whole-plant cannabis, potentially leading to altered or diminished effects. 

The concept of “synergistic ratios” highlights the unique balance in which these compounds are naturally produced, with each cannabis strain exhibiting its own distinctive profile. 

Unlike isolated cannabinoids or terpenes sourced from non-cannabis plants, the natural ratios within cannabis enhance compound interactions, resulting in amplified therapeutic and psychoactive effects. The significance of these synergistic ratios can be observed in various ways:

• Interdependent Synthesis Pathways

Terpenes and cannabinoids in cannabis share biosynthetic origins. Both types of compounds are derived from geranyl pyrophosphate (GPP).GPP is a precursor for both terpenoids (like myrcene, pinene, and limonene) and cannabinoids (like THC and CBD). 

This shared pathway suggests that as the plant develops, terpenes and cannabinoids evolve together, resulting in finely tuned ratios that affect how they are perceived and metabolized in the body. 

Because of this interconnected biosynthesis, terpene-cannabinoid ratios in cannabis are naturally balanced for maximized synergy, something less likely to occur when combining isolated terpenes with cannabinoids from different sources.

• Enhanced Binding Affinity and Potency

Studies show that specific cannabis terpenes, such as myrcene, can enhance the permeability of cell membranes, allowing cannabinoids like THC and CBD to bind more effectively to their respective receptors (CB1 and CB2). This effect increases the overall bioavailability and potency of cannabinoids through various routes. 

Terpenes can also modulate their psychoactive and  therapeutic effects. When combined in their natural ratios, terpenes and cannabinoids create a more powerful and sustained interaction at these receptor sites, contributing to effects like pain relief, anxiety reduction, or sedation.

• Cannabis-Specific Terpene Modulation

Terpenes found in cannabis, such as β-caryophyllene, act directly on the endocannabinoid receptors (especially CB2) and are uniquely positioned to enhance or complement cannabinoids like CBD in ways that non-cannabis-derived terpenes may not. 

The ratios in which these compounds naturally occur in cannabis appear optimized for this modulatory effect, where even slight shifts can lead to significant changes in therapeutic outcomes. Research suggests that attempts to replicate this with terpenes sourced from other plants, or worse synthetic terpenes, often result in weaker or altered effects because the cannabinoids and terpenes lack the fine-tuned balance.

• Terpene-Cannabinoid Ratios Influence on Entourage Effect

A recent study published in MDPI explores how natural terpene-cannabinoid ratios impact the entourage effect, indicating that whole-plant cannabis extracts retain significantly higher efficacy compared to isolated components mixed in post-production. 

This efficacy is likely because terpenes such as limonene and linalool support cannabinoids by enhancing the sensory, therapeutic, and metabolic pathways through which cannabinoids exert their effects.

Presence of other therapeutic compounds and phytonutrients 

Full-spectrum hemp products contain more than just terpenes and cannabinoids; the hemp plant also has beneficial compounds like flavonoids, fatty acids, vitamins, and minerals. 

Together, these natural components enhance the overall effectiveness of cannabinoids. 

• Role of Flavonoids:

Flavonoids in cannabis also contribute to synergy with cannabinoids and terpenes, enhancing the therapeutic effects of the whole plant through the entourage effect. Flavonoids are secondary metabolites with antioxidant, anti-inflammatory, and neuroprotective properties. 

Cannabis contains unique flavonoids called cannflavins, notably cannflavin A and B. These are yet to be identified in other plants and have strong anti-inflammatory effects, which may enhance the action of cannabinoids like CBD. 

Cannflavins A and B are shown to inhibit pro-inflammatory enzymes like COX-2, similar to the way NSAIDs (nonsteroidal anti-inflammatory drugs) work, but without their side effects. Recent research shows they are 30 times more effective than aspirin in inhibiting PGE2 release when assayed in human rheumatoid cells. 

This strong anti-inflammatory effect complements the action of cannabinoids and terpenes, which also target inflammation through different pathways. When combined, these compounds could provide a more robust anti-inflammatory effect than cannabinoids alone.

Flavonoids are reported to increase the bio-accessibility of compounds in the gut, and this activity may extend to cannabinoids, even though more research is needed in this aspect. They may improve the bioavailability of cannabinoids by reducing their degradation in the body. By modulating enzymes involved in cannabinoid metabolism, flavonoids can allow cannabinoids to remain active in the system for longer, thereby enhancing their effectiveness. 

Removing flavonoids from full-spectrum cannabis products may lead to loss of synergistic effects, reduced therapeutic potency, and altered pharmacokinetics.

• Fatty Acids

Hemp is rich in essential fatty acids, particularly omega-3 (alpha-linolenic acid) and omega-6 (linoleic acid), which are vital for various bodily functions and support overall health. 

These fatty acids can enhance the absorption of cannabinoids and terpenes due to their lipophilic nature, allowing for better incorporation of these compounds into cell membranes.

• Vitamins and Minerals

Hemp contains essential vitamins (like vitamin E) and minerals that support general health. These compounds can indirectly influence the effectiveness of cannabinoids by promoting overall wellness, which can enhance the therapeutic experience. 

While not directly involved in the entourage effect, these nutrients support the body’s antioxidant systems, allowing cannabinoids and terpenes to work more effectively at the cellular level.

Conclusion

BioSource Botanicals preserves the full therapeutic power of hemp by retaining a rich profile of active compounds, including flavonoids, fatty acids, terpenoids, and essential vitamins and minerals. These natural elements work synergistically with cannabinoids and terpenes, enhancing their effects through the entourage effect.

Most hemp products lose these essential compounds during extraction, limiting their true full-spectrum quality. BioSource Botanicals solves this with a proprietary extraction process that keeps hemp’s natural composition and ratios intact. Our Certificates of Analysis confirm the presence of beneficial flavonoids, significantly boosting product potency, even at micro-doses.

With the introduction of Active-Spectrum Hemp Extracts™, BioSource Botanicals sets a new standard in the full-spectrum market, offering extracts that maintain stable levels of minor cannabinoids like CBGA and CBDA for years. This groundbreaking approach can reshape the future of hemp-based wellness. Reach out for more information; we’re here to help.

References

1. 1. Al-Khazaleh, A. K., Zhou, X., Bhuyan, D. J., Münch, G. W., Al-Dalabeeh, E. A., Jaye, K., & Chang, D. (2024). The Neurotherapeutic Arsenal in Cannabis sativa: Insights into Anti-Neuroinflammatory and Neuroprotective Activity and Potential Entourage Effects. Molecules, 29(2), Article 2. https://doi.org/10.3390/molecules29020410
   2. Bautista, J. L., Yu, S., & Tian, L. (2021). Flavonoids in Cannabis sativa: Biosynthesis, Bioactivities, and Biotechnology. ACS Omega, 6(8), 5119. https://doi.org/10.1021/acsomega.1c00318
   3. Ben-Shabat, S., Fride, E., Sheskin, T., Tamiri, T., Rhee, M.-H., Vogel, Z., Bisogno, T., De Petrocellis, L., Di Marzo, V., & Mechoulam, R. (1998). An entourage effect: Inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. European Journal of Pharmacology, 353(1), 23–31. https://doi.org/10.1016/S0014-2999(98)00392-6
   4. Chacon, F. T., Raup-Konsavage, W. M., Vrana, K. E., & Kellogg, J. J. (2022). Secondary Terpenes in Cannabis sativa L.: Synthesis and Synergy. Biomedicines, 10(12), 3142. https://doi.org/10.3390/biomedicines10123142
   5. Chayasirisobhon, S. (2020). Mechanisms of Action and Pharmacokinetics of Cannabis. The Permanente Journal, 25, 19.200. https://doi.org/10.7812/TPP/19.200
   6. Moon, Y. J., Wang, X., & Morris, M. E. (2006). Dietary flavonoids: Effects on xenobiotic and carcinogen metabolism. Toxicology in Vitro, 20(2), 187–210. https://doi.org/10.1016/j.tiv.2005.06.048
   7. Naim-Feil, E., Elkins, A. C., Malmberg, M. M., Ram, D., Tran, J., Spangenberg, G. C., Rochfort, S. J., & Cogan, N. O. I. (2023a). The Cannabis Plant as a Complex System: Interrelationships between Cannabinoid Compositions, Morphological, Physiological and Phenological Traits. Plants, 12(3), Article 3. https://doi.org/10.3390/plants12030493
   8. Naim-Feil, E., Elkins, A. C., Malmberg, M. M., Ram, D., Tran, J., Spangenberg, G. C., Rochfort, S. J., & Cogan, N. O. I. (2023b). The Cannabis Plant as a Complex System: Interrelationships between Cannabinoid Compositions, Morphological, Physiological and Phenological Traits. Plants, 12(3), Article 3. https://doi.org/10.3390/plants12030493
   9. Procaccia, S., Lewitus, G. M., Feder, C. L., Shapira, A., Berman, P., & Meiri, D. (2022). Cannabis for Medical Use: Versatile Plant Rather Than a Single Drug. Frontiers in Pharmacology, 13, 894960. https://doi.org/10.3389/fphar.2022.894960
   10. Siracusa, L., Ruberto, G., & Cristino, L. (2023). Recent Research on Cannabis sativa L.: Phytochemistry, New Matrices, Cultivation Techniques, and Recent Updates on Its Brain-Related Effects (2018–2023). Molecules, 28(8), 3387. https://doi.org/10.3390/molecules28083387
   11. Sommano, S. R., Chittasupho, C., Ruksiriwanich, W., & Jantrawut, P. (2020). The Cannabis Terpenes. Molecules, 25(24), 5792. https://doi.org/10.3390/molecules25245792
   12. Zhang, J., Wang, H., Ai, C., Lu, R., Chen, L., Xiao, J., & Teng, H. (2024). Food matrix-flavonoid interactions and their effect on bioavailability. Critical Reviews in Food Science and Nutrition, 64(30), 11124–11145. https://doi.org/10.1080/10408398.2023.2232880