The Entourage Effect with CBD: Are There Full spectrum Benefits for Topicals?
Since cannabis has gone mainstream, there has been a growing discussion around a theory called the entourage effect. This theory, popularized by cannabis researcher Ethan B. Russo, suggests that the active ingredients produced by cannabis work better together rather than in isolation.
While it remains only a hypothesis, this hasn't stopped brands from hopping on the bandwagon to hype their products based on these assumed synergistic benefits. The entourage theory has become so widely believed that it’s been written about by major media outlets, from WIRED to CNN to the Scientific American.
But what do we really know about the entourage effect? Specifically, is there any credence to the benefits of the entourage effect with topicals? Here we look at the theory, where the research stands, and what we know of its applications for cannabis topicals.
What Is the Entourage Effect?
In 1998, Professors Raphael Mechoulam and Shimon Ben-Shabat proposed that the endocannabinoid system experiences an "entourage effect," where various "inactive" metabolites and related molecules significantly boost the activity of the main endogenous cannabinoids (anandamide and 2-arachidonoylglycerol).
This theory also suggested that botanical compounds are often more effective than their isolated components. Although single-molecule synthesis remains the dominant model in pharmaceutical development, current research is examining evidence of botanical synergy. When it comes to cannabis, this means exploring the contributions of minor cannabinoids and perhaps even terpenes.
But of course, as this theory has shifted from scientific theory into public consciousness, it has also lost some nuance. Although this theory is applied widely as a marketing tactic, especially for full-spectrum CBD products, the entourage effect remains just a hypothesis based on preliminary research.
Preliminary Evidence for the Entourage Effect
One animal study published in 2015 looked at CBD for pain relief. The authors examined how pure CBD showed a biphasic dose-response curve, where smaller doses reduced pain up to a certain point, after which higher doses became ineffective. However, when a full-spectrum cannabis extract with equivalent CBD doses was delivered, the biphasic response was replaced by a linear dose-response curve. The study reported, "It is likely that other components in the extract synergize with CBD to achieve the desired anti-inflammatory action that may contribute to overcoming the bell-shaped dose-response of purified CBD."
In a phase 2 clinical trial, researchers supplied patients with a full-spectrum high-CBD sublingual solution for four weeks. The small patient cohort reported reduced anxiety symptoms and experienced few side effects. Patients also experienced improvements in mood, sleep, and quality of life. This was achieved with a smaller dose than another study using higher doses of isolated CBD for anxiety, published in 2019.
A notable study published in Frontiers in Plant Science discussed how different cannabinoids and terpenes work together to enhance their effects on the endocannabinoid system, which regulates various physiological processes.
A study in the British Journal of Pharmacology emphasized the importance of terpenes in the entourage effect. It showed how these compounds can influence the pharmacokinetics and pharmacodynamics of cannabinoids, potentially leading to improved therapeutic outcomes.
While none of these examples reach any final conclusions about the entourage effect, they are nevertheless illuminating.
As a recent Narrative Scoping Review determined, "The [entourage effect] has significant implications for the medical use of cannabinoid-containing products and their prescription," but "further research and evidence are needed to establish the clinical efficacy, safety, and regulatory framework for these products."
Does the Entourage Effect Apply to Topicals?
Studies of the entourage effect have focused on ingested cannabinoids rather than topical applications. Cannabinoid-infused topicals are widely popular, with many manufacturers working with full-spectrum extracts due to their beliefs about the synergistic benefits
When applied topically, cannabinoids such as THC and CBD bind to cannabinoid receptors in the skin, influencing local cell signaling and potentially offering therapeutic benefits. There is also some suggestion that terpenes could provide synergistic value similar to the benefits of ingested cannabis.
Why don't we know more about the synergies of cannabinoids as applied to skin? Studying the entourage effect in topicals presents unique challenges. The skin's complex barrier properties and the localized nature of topical applications make it difficult to measure and compare effects accurately. More research is needed to fully understand how the entourage effect might operate in topical cannabis products.
The New Frontier of the Entourage Effect: Topicals
As discussed, the entourage effect is still a largely theoretical idea. While there is some suggestion that ingested cannabinoids and terpenes work together synergistically for greater benefit, there hasn't been any real study of this idea in skincare.
Considering the global CBD skincare market hit USD 964.1 million in 2022, there is an extraordinary need to better understand the entourage effect and its implications for skin care. Is it more than just a marketing ploy? More controlled study is required before brands can make any genuine claims.