Study: Researchers Present Benefits of Entourage Effect

Researchers from Romania published the results of a study in the International Journal of Molecular Sciences exploring and analyzing the effects of various phytocannabinoids and terpenes working together.

Phytocannabinoids include any naturally occurring cannabinoid found in the plant, from the more commonly known THC, and CBD to less known CBC, CBG, CBN, and more. Researchers wrote that over 100 cannabinoids have been identified in the plant. “The complex interaction between phytocannabinoids and biological systems offers hope for novel treatment approaches and lays the groundwork for further developments in the field of cannabinoid-based medicine,” the study abstract explained. “This review summarizes the state of the field, points out information gaps, and emphasizes the need for more studies to fully realize the therapeutic potential of phytocannabinoids.”

Researchers explored the entourage effect, which is the combination of both cannabinoids and terpenes working together to create effects that “exceed the sum of their separate contributions.” While consuming a product with a single cannabinoid has its benefits, consuming more than one cannabinoid or terpene together can produce even stronger, more beneficial effects. “This synergy emphasizes how important it is to consider the entire plant when utilizing cannabis medicinally as opposed to just concentrating on individual cannabinoids,” researchers explained.

Researchers also briefly wrote about terpenes, which make up the aroma and flavor of various cannabis strains. “Standardizing the terpene profile helps maintain consistency in sensory attributes and may also impact the ‘entourage’ effect—the synergistic interaction between cannabinoids and terpenes.”

The study primarily reviewed the known effects and properties of various cannabinoids, many of which offer varying levels of benefit for anti-inflammatory effects, antioxidant effects, pain management, neurological disorders, psychiatric conditions, cancer treatment support, and more. “The exploration of novel phytocannabinoids is rapidly evolving, offering exciting prospects for future therapeutic applications,” researchers wrote. “Beyond well-established compounds like THC and CBD, the quest for novel cannabinoids widens the scope of potential treatments. Each cannabinoid, with its unique chemical structure, interacts differently with the ECS, suggesting tailored therapeutic effects for specific conditions. This exploration seeks to harness similar benefits while circumventing associated drawbacks.”

The study cited examples of THC having analgesic effects and has been found to help patients treat chronic pain, while CBD has been studied for its anti-inflammatory properties and is an anxiolytic, which has potential to reduce anxiety and stress.

CBG interacts with the body’s endocannabinoid system (specifically the CB1 and CB2 receptors) in a way that suggests it can “modulate the effects of other cannabinoids by influencing CB1 receptor activity.” It has also been studied for its anticancer properties. Similar breakdowns were provided for CBC, CBN, and THCV as well.

This research is the combined presentation from 99 sources to exhibit the benefits of cannabinoids, but spotlights the complex challenges regarding the legal status of cannabis in the U.S. and the EU. However, researchers noted that these laws and regulations are subject to change as more evidence is presented.

Researchers also added that at least in the U.S., more evidence will lead to an expansion in FDA approved products. Currently, only two products—Sativex^® (which contains both CBD and THC) and Epidiolex^® (which contains only CBD)—have been approved so far. Sativex^® was approved in 2010, while Epidiolex^® was approved in 2018. “CBD and THC should be accessible to patients with special prescriptions due to their potential benefits, especially for individuals with epilepsy refractory to other medications.”

Not all countries in Europe have access to Sativex^® and/or Epidiolex^®, which has led to an increase in a reliance on obtaining cannabis products online, and also increases the risk of illegal products that are not being tested for impurities and other harmful contaminants. Due to this, researchers recommended that cannabis products should be made available as a prescription to “lower addiction risk.” “Prescription retention in pharmacies after each refill or release can aid in monitoring usage,” researchers wrote. “Additionally, THC products should adhere to state-specific rules, potentially requiring a special prescription to curb misuse.”

In their conclusion, researchers summarized the many beneficial properties of phytocannabinoids and the need for more research. “By leveraging the synergistic effects of combination therapies and targeting multiple disease pathways, phytocannabinoids hold immense potential to revolutionize the future of pharmacotherapy and improve human health outcomes,” researchers said. “However, further research, regulatory clarity, and standardized protocols are needed to fully unlock their therapeutic benefits and ensure safe and effective use in clinical practice.”

Other researchers have presented similar evidence as well, such as one study published in October 2023. A study conducted by Zentrela and PAX showed evidence of the entourage effect (in this case, the application of multiple cannabinoids and terpenes) led to two times the psychoactive effects in comparison to participants who consumed just products with high levels of delta-9 THC.

Similar evidence has been found on mushrooms as well. A study published in February in the journal Molecular Psychiatry explained how full-spectrum psilocybin extract offers superior benefits compared to synthetic psilocybin. “This research not only underscores the superiority of extracts with diverse compounds but also highlights the feasibility of incorporating them into Western medicine due to the controlled nature of mushroom cultivation,” researchers wrote in a press release.