Terpene Synergy: Exploring the Latest Entourage Effect Research

• Terpene Synergy Study 
• Findings and Implications
• Past Entourage Effect Research
• Why Terpene Testing Is Essential

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Cannabinoids like THC and CBD get well-deserved credit for delivering cannabis’ primary effects. However, this multifaceted plant contains hundreds of compounds, like minor cannabinoids, flavonoids, and terpenes that all contribute to the medicinal and physiological properties. A theory called the Entourage Effect posits terpenes, flavonoids, and cannabinoids actually work better together than individually. 

Research proving the Entourage Effect theory is relatively scant. However, a new terpene synergy study adds credence to the claim that these compounds significantly impact cannabis experiences and effects.

Terpene Synergy Study 

The latest cannabis synergy study comes from Israel, investigating how individual terpenes activate CB1 receptors in the brain and nervous system CB1 receptors are binding sites that attach directly to cannabis compounds to unleash their effects. THC has a particularly strong affinity, or binding power, with CB1.

The study also looked at how terpenes might affect the way THC interacts with CB1, which could have potential applications in medicine.

CB1 receptors and other signaling molecules comprise the body’s endocannabinoid system (ECS), which serves critical functions independently of cannabis. The ECS regulates an essential range of health functions by binding with the body’s own natural cannabinoids, like anandamide to affect:

• Memory
• Sleep
• Mood
• Appetite
• Immune responses
• Pain control

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Study Methods

The study used a controlled drug-testing method called an in-vitro heterologous expression system (a test that occurs outside a living organism) to verify to what extent terpenes contribute to CB1 receptor activation. 

Researchers extracted THC from a THC-rich chemovar (strain) and verified its potency using High-Performance Liquid Chromatography (HPLC) equipment and analysis. 

They also obtained 16 purified terpenes, including pinene, limonene, myrcene, linalool, and humulene. 

To determine potential synergy, the team measured the CB1 receptor responses in three main experiment settings:

• 16 terpenes individually
• THC alone
• Various THC-terpene mixtures

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Findings and Implications

The study’s CB1 receptor measurements revealed remarkable entourage effect evidence:

• All terpenes individually activated CB1 receptors at about 10% to 50% of THC's activity.
• Terpenes combined with THC significantly increased CB1 receptor activity compared to THC alone. 
• Synergetic receptor activation was several times higher than THC alone in several cases.

These results verify that terpenes do bind with cannabinoid receptors like THC and can boost THC’s CB1 activation. The study also found that the degree of activation of the different terpenes was significant, especially when considering their low ratios to THC.

• Terpene concentrations are scant compared to THC. Yet they activated receptors at 10 and 50% of THC’s strength. So, a bit of terpene goes a long way.
• Some terpenes exhibited a noteworthy synergy with THC in CB1 receptor activation, where the combined effect of THC and terpenes was greater than the sum of their individual effects.

• Specific terpenes were β-pinene, borneol, geraniol, limonene, linalool, ocimene, sabinene, and terpineol,

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The results also strongly supported the fact that terpenes have a proportional effect on the interaction between THC and CB1 receptors. Interestingly, the most effective terpenes were not necessarily the most abundant.

According to the research team, these findings imply:

• “Whole plant” or “full spectrum” formulas might not necessarily be the most advantageous method. Instead, enriching extracts with the most synergetic terpenes could be a better method for tweaking chemovars (strains) for desired effects. 
• Such synergism may reduce the required THC dose for therapeutic purposes and offer flexibility in tailoring treatments to specific needs and populations, potentially minimizing THC-related adverse effects.
• Scientists could adjust chemovar compositions to treat various medicinal and personal needs better.

Past Entourage Effect Research

The latest terpene synergy adds to the growing body of research since Raphael Mechoulam first defined the “entourage effect” in 1998. The famous chemist described the theory as “a phenomenon of cannabinoids and terpenes synergizing in the body to maximize the plant's therapeutic and cognitive profile.” 

Past research suggests that cannabinoids and terpenes do interact with the body's endocannabinoid system (ECS) to produce health benefits, particularly regarding anxiety and pain relief. 

• University of Arizona Health Sciences researchers tested the entourage effect related to the plant's pain-relieving properties. They found that cannabis terpenes, including alpha-humulene, geraniol, linalool, and beta-pinene, mimicked THC’s pain-relieving properties.

• A comprehensive preclinical study using various animal models of anxiety-like behavior showed that plant-derived chemicals like terpenes and flavonoids possess anxiety-relieving properties. It suggests that combining terpenes with cannabinoids could enhance the mood-stabilizing effects attributed to THC and CBD. 

• A study found that the terpenes humulene, geraniol, linalool, and β-pinene produced cannabinoid behaviors in mice, suggesting terpenes can boost cannabinoid activity.

• A study exploring how cannabinoids can treat anxiety and seizures showed that a “pharmacokinetic entourage” effect could explain why low-dose CBD products containing a full spectrum of cannabinoids seem to have therapeutic impacts at relatively low doses.

Why Terpene Testing Is Essential

The mounting cannabis synergy research emphasizes that terpene testing is essential. 

Despite terpenes' relatively low amounts in hemp and cannabis plants, these compounds significantly contribute to the strain’s therapeutic effects. Brands that understand terpene potency can better craft, curate, and market their products with distinct characteristics based on  consumers’ needs and desired effects. 

Researcher Ethan Russo argued that the entourage effect was the key to breeding strains with specific effects, such as making “sativa” and “indica” products fit for energetic activity vs. relaxation and sedation. 

Indica and sativa strains don’t necessarily have genetic relevance. But:

• Indicas are typically rich in myrcene, a terpene known to induce relaxation and decrease anxiety
• Sativa strains often contain limonene, a terpene related to alertness and arousing behavior. 

Terpene testing is the best way to understand what strains can best serve people who want to use cannabis to achieve specific goals, whether medically or recreationally. It is also key to unlocking a vault of cannabis knowledge. 

By testing for terpenes and publishing the certificates of analysis (COAs), brands can document every strain’s full terpene and cannabinoid profile so customers can choose the right product based on the desired effects.

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The Bottom Line

The latest entourage effect research shows that various terpenes significantly activate CB1 receptors. Additionally, combining some terpenes with THC increased CB1 receptor activity compared to THC alone, often several times over. Terpenes are the next frontier in chemovar curation and designing targeted products for medicinal and personal needs. 

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ACS Laboratory reliably quantifies 30 + cannabinoids and 38 terpenes, more than any laboratory in the eastern US, and constantly works to develop new methods. Brands interested in testing can contact us today.