When talking about cannabis, we often think of individual compounds such as THC or CBD. However, for years, scientists and professionals in the sector have begun to look beyond isolated ingredients. What happens when the different components of the plant interact with each other? The answer to that question has given rise to an increasingly explored hypothesis: the entourage effect.
This concept proposes that the effects of cannabis might not depend solely on a specific cannabinoid, but on the joint action of various compounds such as terpenes, flavonoids, and other secondary cannabinoids. It is an idea that has captured interest both in wellness contexts and in research spaces. In this article, we walk you through to find out what’s been observed, what has been suggested in studies, and why this approach could be key to better understanding the potential of cannabis.
The Entourage Effect of Cannabis: An Evolving Hypothesis
The entourage effect refers to a possible synergy between the different compounds present in cannabis. Rather than acting separately, these components could influence each other and produce broader effects, different from those that each one would have on its own. This could help explain why two cannabis strains, even with similar levels of THC or CBD, can generate different responses. The difference could be in their complete chemical profile, i.e. in the combination of many compounds working together.
For those who approach cannabis from curiosity or personal experience, this concept opens up new questions: Does the aroma have an influence? Does the presence of compounds that are almost not mentioned matter? Does it make sense to prefer products that preserve all the elements of the plant? It is in this type of question that the complexity and possibilities opened up by the entourage effect are observed.
Origin of the term in scientific research
The concept was introduced by Ben-Shabbat et al. (1998), who were researching the endocannabinoid system of the human body. They observed that some compounds that did not generate clear effects on their own could, on the other hand, enhance the effects of other substances that did interact directly with the body’s receptors. This idea that some elements “accompany” and reinforce others gave rise to the name of the entourage effect.
Years later, researcher Ethan Russo (2011) took up the concept and applied it to plant cannabis. His proposal was that cannabinoids and terpenes could have combined effects that modify both the observed benefits and the possible side effects. Some examples he proposed include CBD’s ability to reduce anxiety caused by THC, or the possibility that certain terpenes soften the cognitive impact of THC itself.
Which Cannabis Compounds Might Be Involved in the Entourage Effect
This section allows us to take a closer look at the various chemical actors that might be involved in the entourage effect. Beyond the most well-known ones such as CBD or THC, there would be a whole network of components that interact in complex ways. Understanding their role could help you make more judicious choices between different cannabis products.
Secondary cannabinoids: CBG, CBN, and CBC interacting with THC and CBD
Cannabinoids are the most well-known active compounds in cannabis, but there is more variety in this category than is usually mentioned. In addition to THC and CBD, there are others such as CBG (cannabigerol), CBN (cannabinol), and CBC (cannabichromene). These so-called “secondary” cannabinoids are not minor in importance: it has been proposed that they could influence how CBD works or alter the way the overall effect of the product is perceived.
Sainz Cort (2024) explains that each plant variety has a different chemotype. This means that the percentages of cannabinoids and other compounds vary naturally, generating unique combinations. It is precisely in this diversity that the key to understanding why the same percentage of CBD produces different effects depending on the variety could be found.
Cannabis terpenes and their possible modulating effect
Terpenes are the compounds responsible for the characteristic aroma of cannabis, but their function could go beyond smell. Some research has suggested that they may also influence the nervous system, interacting with cannabinoid receptors or modifying the bioavailability of other compounds.
For example, myrcene has been associated with feelings of relaxation, limonene with more active moods, and pinene with possible greater mental clarity. Voicu et al. (2019) found that some of these terpenes have an affinity for receptors such as CB2, which are involved in the regulation of the immune system. While these effects are still being studied, the possibility of aroma and effects going hand in hand is one of the reasons terpenes generate so much interest.
Flavonoids and Less-Studied Compounds: An Expanding Field
To a lesser extent, flavonoids are also present in cannabis. They are natural compounds found in many plants that may have antioxidant or anti-inflammatory properties. Marinotti and Sarill (2020) mention that these elements, although not always considered protagonists, could act as complementary pieces that enrich the overall profile of the product.
There is still much to discover about its specific role, but its presence is another part of the natural complexity of cannabis.
Possible benefits of the entourage effect in cannabis according to scientific studies
Understanding how the entourage effect might work opens new doors to different potential applications of hemp and other cannabis strains. Here are the contexts in which studies have begun to explore their usefulness.
Inflammation and the immune system: interaction between terpenes and cannabinoids
One of the main focuses of research has been inflammation. The immune system regulates many functions of the body and responds to damage, infection, or imbalances. Some studies have observed that the joint action of cannabinoids such as CBD with specific terpenes could have an impact on inflammatory processes.
For example, Voicu et al. (2019) highlighted the role of myrcene and limonene when combined with CBD or THC. In these cases, a modulation of the inflammatory response was observed in experimental models. These early tests are valuable clues for future lines of research.
Pain, anxiety, and emotional well-being: effects observed in full extracts
On another level, chronic pain and emotional imbalances have also been studied. Ethan Russo (2019) collected evidence in which full-spectrum extracts, i.e., those that retain several natural compounds from the plant, offered similar or even better responses than CBD isolate. The interesting thing is that this happened with smaller amounts and with better overall tolerance on the part of users.
These observations point to a possible greater efficiency of whole extracts, which could translate into products that offer a better balance between efficacy and safety.
Complex cases: epilepsy, cancer and neurodegenerative diseases
In more delicate contexts such as epilepsy, the entourage effect has also been considered. Some research has suggested that the combination of multiple cannabinoids could enhance the effectiveness of certain treatments. In the case of cancer, for example, it has been observed in cell models that compounds such as THC, THCA, and CBG could influence certain tumor cells (Russo, 2019).
Its possible antioxidant and anti-inflammatory effects in neurodegenerative diseases are also being explored. It is important to note that these fields are at an early stage and that these types of more advanced uses are always carried out with very rigorous medical monitoring and observation. However, it is important to mention them because they further open up the field of possibilities for the entourage effect and the potential uses of cannabinoids.
Differences Between Complete Extracts and Isolated Cannabis Compounds
The way a cannabis product is presented can also influence how its effect is experienced. That’s why it’s important to understand the difference between whole, broad extracts, and isolated compounds.
What studies have observed on whole extracts
Full spectrum extracts preserve the plant’s natural variety of compounds. This includes major cannabinoids such as CBD, but also other cannabinoids, terpenes, and flavonoids. Marinotti and Sarill (2020) observed that this type of formulation offered similar or better results than the use of isolated compounds, with a lower frequency of side effects.
Based on these studies, it could be that secondary compounds are modulating or complementing CBD’s main action. This natural interaction could allow for a more balanced response by the body. For those who want to experiment with the entourage effect but prefer to avoid THC altogether, there are also broad spectrum extracts that preserve all the richness of the plant with the exception of this cannabinoid that some might want to avoid due to its well-known psychoactive effects. However, it is important to mention that, in the case of legal oils and extracts in Spain, such as those that Maionais has for you, full-spectrum extracts have very minimal amounts of THC, below 0.2%. This means that even these more complete products avoid psychoactive effects, but they do possess traces of THC that could contribute to the entourage effect.
When CBD isolate may be preferred over a full extract
Despite the potential advantages of whole extracts, in certain cases the use of CBD isolate may be more suitable. For example, when you need very precise control over the components, or when it is a priority to completely avoid the presence of THC or other cannabinoids.
Marinotti and Sarill (2020) also documented that CBD isolate showed greater inhibitory potency on lymphocyte activation compared to more complete extracts. This suggests that, in some specific contexts, pure compounds could offer more direct or controlled responses. Choosing between one format or the other will always depend on the particular needs and the type of product you are looking for.
Current Debate on the Entourage Effect in Cannabis
As interest in the entourage effect grows, so does the debate around its definition and applicability. This is normal in any emerging field, and is part of the process of knowledge construction.
Criticisms of the term from pharmacology
Some authors have suggested that the concept of the entourage effect has been used in an imprecise way. Authors such as Christensen et al. (2023) agree that a more rigorous language from pharmacology would be needed to describe these interactions. They propose that, rather than being effects exclusive to cannabinoids, they are synergies and interactions between chemicals and molecules, and that seeing them in this way could help to better understand what exactly is happening between them.
These criticisms do not deny that there are interactions, but point to the need to better understand how they work. Questioning the term is part of taking the discussion to a more precise level, where specific studies can be designed to test hypotheses more clearly.
Studies Supporting the Interaction Between Cannabis Compounds
Despite the debate, many studies continue to explore the possibility of cannabis compounds acting synergistically. Sainz Cort (2024) points out that preserving natural chemical diversity could make a difference in how the effects are perceived and how well certain products are tolerated.
Even those who call for greater rigor recognize that there are patterns that deserve to be investigated. The important thing is that interest in these combinations is maintained within a responsible and evidence-based framework.
Maionais and his attention to the natural synergy of cannabis
From our experience as a shop specialising in CBD flowers, CBD oils and CBD hash, we at Maionais are interested in the developments around the entourage effect. While this phenomenon is still under investigation, more and more people are valuing products that preserve the full profile of the plant.
That’s why Maionais CBD invites you to continue learning about the compounds that make this plant so special, and to try it for yourself thanks to our CBD oils with different compositions and combinations that allow you to find the perfect option for you.
References
- 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
- Christensen, C., Rose, M., Cornett, C., & Allesø, M. (2023). Decoding the Postulated Entourage Effect of Medicinal Cannabis: What It Is and What It Isn’t. Biomedicines, 11(8), 2323. https://doi.org/10.3390/biomedicines11082323
- Marinotti, O. & Sarill, M. (2020) Differentiating Full-Spectrum Hemp Extracts from CBD Isolates: Implications for Policy, Safety and Science, Journal of Dietary. Supplements, DOI: 10.1080/19390211.2020.1776806
- Russo E. B. (2011). Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. British Journal of Pharmacology, 163(7), 1344–1364. https://doi.org/10.1111/j.1476-5381.2011.01238.x
- Sainz-Cort, A. (2024) What is the entourage effect?. Gorilla Grillz blog. Available in https://www.gorillagrillz.com/efecto-sequito/
- Voicu, V., Brehar, F.-M., Toader, C., Covache-Busuioc, R.-A., Corlatescu, A. D., Bordeianu, A., Costin, H. P., Bratu, B.-G., Glavan, L.-A., & Ciurea, A. V. (2023). Cannabinoids in Medicine: A Multifaceted Exploration of Types, Therapeutic Applications, and Emerging Opportunities in Neurodegenerative Diseases and Cancer Therapy. Biomolecules, 13(9), 1388. https://doi.org/10.3390/biom13091388
