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The entourage effect: how good is the evidence?

The entourage effect is the idea that whole-plant extracts work better than pure CBD. It is plausible, but controlled human trials have not confirmed it.

Facts checked 13 November 20266 min readHow we research

The entourage effect is the idea that the many compounds in cannabis work better together than any one of them does alone, so a whole-plant extract should beat pure CBD. It is a plausible hypothesis. It has not been confirmed in controlled human trials, and a 2023 review of the research warned against promoting it as proven.1

Where did the idea come from?

The term was introduced in 1998 by the scientists Shimon Ben-Shabat and Raphael Mechoulam. They were not talking about plant extracts. They had found that some inactive molecules in the body seemed to increase the activity of the body’s own cannabinoids, and they called this an “entourage effect”.2

A year later the same authors suggested the idea might explain why herbal medicines sometimes seem to work better than their isolated ingredients. Other writers then extended it to cannabis, proposing that minor cannabinoids and terpenes add to the effects of THC and CBD.2

So the concept moved a long way from its starting point: from an observation about molecules in the body to a general claim about cannabis products.

What exactly is being claimed?

“The entourage effect” covers several different claims, and they do not all stand or fall together.

Claim State of the evidence
Terpenes boost cannabinoids at cannabinoid receptors Tested in the laboratory. Mostly negative34
Full-spectrum CBD works better than pure CBD Not shown in any head-to-head randomised trial, apart from one small pilot5
CBD reduces the unwanted effects of THC Mixed. Some studies support it, a controlled study did not6
THC and CBD together work better than THC alone Some trial evidence for particular products that contain THC2

The last row is about THC-containing medicines. It is not evidence that CBD oil needs other plant compounds to work.

What is the evidence for it?

An analysis of epilepsy studies. The study most often quoted is a 2018 analysis that pooled 11 studies with 670 patients with treatment-resistant epilepsy. About 71% of patients on CBD-rich extracts were reported to have improved, against about 36% on purified CBD, and the extract group used much lower average doses.2

This sounds persuasive until you look at how it was done. The studies were observational, not randomised. They involved different patients, different products and different definitions of “improved”. When the stricter measure was used (at least a 50% drop in seizures), the two groups did not differ significantly, and about 10% of patients in each group became seizure-free.2

A pain trial with THC. In one randomised trial, an extract containing THC and CBD (nabiximols) did better than placebo while a THC-dominant extract did not.2 This suggests CBD may add something to THC in that setting. It is a finding about a THC medicine.

One small pilot. In a pilot study of 44 people with alcohol use disorder, a full-spectrum product supplying 150 mg of CBD a day reduced craving more than a broad-spectrum product or placebo.5 The sample was small and the result needs repeating.

One mouse and cell study. A laboratory study reported that some terpenes had cannabinoid-like effects and added to cannabinoid activity.7

What is the evidence against it?

Terpenes do not act at cannabinoid receptors. In a 2019 study, six common cannabis terpenes did not activate CB1 or CB2 receptors and did not change THC’s signalling there.3 A 2020 study reached the same result for THC, CBD and one of the body’s own cannabinoids, and its authors concluded there was enough data “to rule out direct interactions with either cannabinoid receptor” as the explanation.4 A third study found no terpene effect on cannabinoid actions at two other targets, TRPA1 and TRPV1.8

The 2020 authors added an honest caveat: their work “cannot rule out the existence of an entourage effect” through some other route.4

Combining cannabinoids can cancel a benefit. In a trial of 62 people with type 2 diabetes, the cannabinoid THCV lowered fasting blood glucose when given alone. The benefit disappeared when it was combined with CBD.9 Mixtures do not always add up.

CBD did not change the effects of cannabis. In a controlled study of 31 cannabis smokers, taking up to 800 mg of CBD beforehand made no difference to the effects of smoked cannabis.6

The best evidence for CBD is for pure CBD. The trials that led to CBD being registered as an epilepsy medicine used a purified product.10

What do reviewers conclude?

A 2023 scoping review found that the published research “provides limited evidence” for the entourage effect as a stable and predictable phenomenon, and cautioned against presenting it as established.1

A 2020 critical review was blunter. Its title asks whether the entourage effect is better described as “hodge-podge hashish”, and it questions the “rebranding, marketing, and expectations” attached to cannabis mixtures.11

Who is making the argument?

It is worth checking who stands to gain. The author of a widely cited paper arguing for the entourage effect declared that he directs a research institute serving clients “engaged in cannabis commerce”.2 Funding is worth checking on the other side too. One of the main laboratory studies that failed to find an effect states that all its research costs were paid by a private company.4

The entourage effect is also heavily used in marketing, as the critical review cited above points out.11 That does not make the idea false. It is a reason to ask for trials.

What difference between products is proven?

One difference is not in doubt. Full-spectrum products contain THC. In a study of 14 patients taking a full-spectrum, high-CBD extract for four weeks, the authors concluded that people using such products may test positive for THC on a urine drug screen.12

That has real consequences for work, sport and driving in Australia. See Will CBD show up on a drug test? and full spectrum vs broad spectrum vs isolate.

The bottom line

The entourage effect is a reasonable scientific question that has not been answered. It would take randomised trials comparing a full-spectrum product with the same dose of pure CBD, in the same kind of patients, to settle it. Almost none exist.

Until they do, “full spectrum works better” is a claim, not a finding. The choice between product types is one for a prescriber, who will weigh the known issue (THC content) more heavily than the unproven one. See how we grade evidence.

Footnotes

  1. Scoping review of the evidence for the cannabis entourage effect, 2023. https://pubmed.ncbi.nlm.nih.gov/37535820/ ↩ ↩2

  2. Russo EB. The case for the entourage effect and conventional breeding of clinical cannabis: no “strain,” no gain. Frontiers in Plant Science, 2019. https://www.frontiersin.org/articles/10.3389/fpls.2018.01969/full ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7

  3. Santiago M, et al. Absence of entourage: terpenoids commonly found in Cannabis sativa do not modulate the functional activity of THC at human CB1 and CB2 receptors. Cannabis and Cannabinoid Research, 2019. https://pubmed.ncbi.nlm.nih.gov/31559333/ ↩ ↩2

  4. Finlay DB, Sircombe KJ, Nimick M, Jones C, Glass M. Terpenoids from cannabis do not mediate an entourage effect by acting at cannabinoid receptors. Frontiers in Pharmacology, 2020. https://www.frontiersin.org/articles/10.3389/fphar.2020.00359/full ↩ ↩2 ↩3 ↩4

  5. Pilot trial of full-spectrum and broad-spectrum hemp CBD in alcohol use disorder. PubMed Central. https://pmc.ncbi.nlm.nih.gov/articles/PMC12066606 ↩ ↩2

  6. World Health Organization, Expert Committee on Drug Dependence. Cannabidiol (CBD) critical review report, 2018. https://cdn.who.int/media/docs/default-source/controlled-substances/whocbdreportmay2018-2.pdf ↩ ↩2

  7. Study reporting that cannabis terpenes are cannabimimetic and enhance cannabinoid activity in mice and cells. PubMed Central. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050080/ ↩

  8. Study of cannabis terpenes and cannabinoid actions at TRPA1 and TRPV1 channels. PubMed Central. https://pmc.ncbi.nlm.nih.gov/articles/PMC7759271/ ↩

  9. Jadoon KA, et al. Efficacy and safety of cannabidiol and tetrahydrocannabivarin on glycemic and lipid parameters in patients with type 2 diabetes. Diabetes Care, 2016. https://pubmed.ncbi.nlm.nih.gov/27573936/ ↩

  10. Epidiolex (cannabidiol) oral solution, United States prescribing information. DailyMed, National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8bf27097-4870-43fb-94f0-f3d0871d1eec ↩

  11. Cogan PS. The “entourage effect” or “hodge-podge hashish”: the questionable rebranding, marketing, and expectations of cannabis polypharmacy. Expert Review of Clinical Pharmacology, 2020. https://doi.org/10.1080/17512433.2020.1721281 ↩ ↩2

  12. Dahlgren MK, et al. Urinary tetrahydrocannabinol after 4 weeks of a full-spectrum, high-cannabidiol treatment. JAMA Psychiatry, 2021. https://pubmed.ncbi.nlm.nih.gov/33146684/ ↩

Common questions

Is the entourage effect real?

It is unproven. A 2023 scoping review found the literature provides limited evidence for it as a stable, predictable effect and warned against promoting it as established. It remains a hypothesis that has not been confirmed in controlled human trials.

Is full-spectrum CBD better than isolate?

There is no good evidence that it is. No head-to-head randomised trial has shown full-spectrum CBD beating pure CBD for any condition, apart from one small pilot in alcohol use disorder. The strongest evidence for CBD, in epilepsy, comes from a purified product.

Who came up with the entourage effect?

The term was introduced in 1998 by the scientists Shimon Ben-Shabat and Raphael Mechoulam. They were describing how inactive molecules in the body seemed to boost the activity of the body's own cannabinoids, not plant extracts.

Do I need THC for CBD to work?

No evidence shows that. The trials that established CBD as an epilepsy medicine used purified CBD without THC. Adding THC brings its own effects and risks, including intoxication, impaired driving and positive drug tests.

This page is general information, not medical or legal advice. Laws and evidence change; we show the date we last checked the facts at the top of every page. Talk to your doctor or pharmacist before starting, stopping or changing any medicine.

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