What is the entourage effect in cannabis?

The entourage effect is the idea that the many compounds in cannabis, such as cannabinoids and terpenes, act differently together than each does alone. The term comes from a 1998 laboratory study of the body's own cannabinoids. For cannabis products it is still a hypothesis: a few small human studies support parts of it, others don't, and laboratory tests found that common terpenes do not act on cannabinoid receptors.

What is the entourage effect?

The entourage effect describes compounds that change each other's activity when they are present together. The phrase was first used in 1998 by a team that included the Israeli chemist Raphael Mechoulam. They studied 2-AG, one of the body's own cannabinoids, and found that two related fatty-acid compounds, which did nothing on their own, increased 2-AG's activity in laboratory tests and in mice (Ben-Shabat 1998). Our guide 2-AG and anandamide explains these endocannabinoids.

The idea was later applied to the cannabis plant. In a 2011 review, the cannabis researcher Ethan Russo proposed that terpenes and minor cannabinoids could add to or modify the effects of THC and CBD (Russo 2011). In 2019 he argued that the case for synergy was strong enough that a single molecule was unlikely to match whole-plant extracts (Russo 2019). These are reviews that set out a hypothesis; they are not trials that prove it.

How is the entourage effect supposed to work?

Two groups of compounds are usually named: cannabinoids such as THC, CBD and CBG, and terpenes, the aroma compounds of the plant, such as myrcene, limonene and linalool. The proposed mechanisms include compounds acting on different receptors at the same time, one compound changing how another is absorbed or broken down, and one compound softening another's unwanted effects.

Whether terpenes act at cannabinoid receptors is disputed. Beta-caryophyllene bound to and activated the CB2 receptor in a 2008 study (Gertsch 2008). But when researchers tested six common cannabis terpenes (alpha-pinene, beta-pinene, beta-caryophyllene, linalool, limonene and myrcene) in cells carrying human CB1 or CB2 receptors, none of them activated the receptors or changed how THC acted on them. The authors concluded that if an entourage effect between cannabinoids and terpenes exists, it does not happen at the CB1 or CB2 receptor (Santiago 2019).

A 2023 scoping review suggested that, where interactions occur, they can be described with ordinary pharmacology terms such as synergy and bioenhancement, as for other plant-based medicines (Christensen 2023).

Is the entourage effect real?

It is not proven, and it is not disproven. The 2023 review found that the pre-clinical and clinical studies used mostly simple methods and showed contradictory findings, and that the clinical data relied mostly on anecdotal and real-world evidence. It also noted that advocates see the effect as the reason many patients prefer full-spectrum products, while critics call the term unfounded and mainly a marketing term (Christensen 2023). The best-known human studies point in different directions:

• CBD before THC, 2013: healthy volunteers who took 600 mg of CBD before an injection of THC had less paranoia and less memory impairment than those given placebo (Englund 2013).
• CBD with THC, 2023: in 46 infrequent cannabis users, vaporised cannabis with up to three times as much CBD as THC did not change THC's effects on memory, psychotic symptoms or any other measure (Englund 2023).
• Limonene with THC, 2024: in 20 adults, inhaling limonene together with 30 mg of THC reduced ratings of feeling anxious and paranoid compared with THC alone. Other THC effects did not change, and limonene alone did nothing measurable (Spindle 2024).
• Extracts versus purified CBD, 2018: an analysis of 11 observational studies in treatment-resistant epilepsy found more reported improvement with CBD-rich extracts than with purified CBD, at lower average doses. When the usual threshold of at least 50% fewer seizures was applied, there was no difference between the two. The data were not from controlled trials (Pamplona 2018).

Studies like these test one or two compounds at a time, at doses chosen by the researchers. They do not show what a particular full-spectrum product does.

What does the entourage effect feel like?

There is no specific sensation that can be called the entourage effect. The idea is that the overall effect of a whole-plant extract differs from that of a single compound. In studies, this is measured as a change in the effects of THC, such as anxiety or paranoia ratings, not as a feeling of its own. Descriptions of what it "feels like" come from personal reports, not from controlled research.

Does the entourage effect apply to CBD oil?

Only to extracts that keep more than one compound. Whether a CBD oil can show an entourage effect depends on its type:

Combinations such as CBD with CBG or CBD with CBN are often marketed with the entourage effect. We are not aware of controlled human studies that test whether these specific combinations act differently from the single cannabinoids. For more on the types, read full spectrum vs broad spectrum vs isolate. Our full-spectrum oils have a THC specification below 0.2%, our broad-spectrum oils are THC-free, and both are cosmetic products for use on the skin; see our CBD oils.

Why is the entourage effect debated?

• Few controlled human trials: most work has been done in cells and animals, or relies on observational data.
• Too many combinations: cannabis contains more than 560 identified constituents (ElSohly 2017), so testing every pairing at realistic doses is not practical.
• Plants vary: the mix of cannabinoids and terpenes differs between varieties, harvests and extraction methods, which makes products hard to standardise and results hard to repeat.
• Commercial interest: the term is widely used in marketing, which critics say has run ahead of the science (Christensen 2023).