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Terpenes  &  
"entourage effect"

Russo, EB 2011, ‘Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid[CH1]  entourage effects’, British Journal of Pharmacology, vol. 163, pp. 1344–1364

Review article: examines the therapeutic effects of cannabis terpenoids (limonene, myrcene, a-pinene, linalool, b-caryophyllene, caryophylleneoxide, nerolidol and phytol), and their role in the entourage effect with CBD and THC. 


  • Terpenoids share a precursor with phytocannabinoids


  • They display unique therapeutic effects that may contribute meaningfully to the entourage effects of cannabis-based medicinal extracts.


  • Scientific evidence is presented for non-cannabinoid plant components as putative antidotes to intoxicating effects of THC that could increase its therapeutic index.

Surendran S, Qassadi F, Surendran G, Lilley D & Heinrich M 2021, “Myrcene—What Are the Potential Health Benefits of This Flavouring and Aroma Agent?”, Frontiers in Nutrition, vol. 8: doc 699666.

doi: 10.3389/fnut.2021.699666


Review article about Myrcene:

  • Myrcene (b-myrcene) is an abundant monoterpene which occurs as a major constituent in many plant species, including cannabis.

  • The main reported biological properties of b-myrcene are

    • anxiolytic and sedative effects

    • antioxidant activity - which can be attributed by the presence of conjugated double bonds that create chain breaking antioxidant activity.

    • anti-ageing – as an antioxidant compound, it may play a protective role against UVB-induced skin photo-ageing.

    • anti-inflammatory activity – Its ability to lessen inflammation occurs via  prostaglandin E-2 (PGE-2)

    • analgesia  - b-Myrcene has shown central and peripheral analgesic effects


  • Discussion of safety of b-myrcene in terms of

    • Adverse skin reactions

    • Acute toxicity (low), subacute and sub chronic toxicity

    • Teratogen

    • Mutagenicity, genotoxicity

    • Carcinogenicity


  • b-myrcene has shown promising health benefits in many animal studies. Human studies are lacking. 

Review article:
the "entourage effect" of full spectrum CBD

Russo EB 2019, "The Case for the Entourage Effect and Conventional Breeding of Clinical Cannabis: No Strain, No Gain", Frontiers of Plant Science, vol. 9, pp. 1969.


Review article summary:

  • some evidence points to the potential for whole plant-derived CBD to be more effective than isolate or highly purified CBD,

  • suggesting that other cannabinoids or terpenes may have additive or synergistic effects with CBD.

  • In 1998, Professors Raphael Mechoulam and Shimon Ben-Shabat posited that the endocannabinoid system demonstrated an “entourage effect” in which a variety of “inactive” metabolites and closely related molecules markedly increased the activity of the primary endogenous cannabinoids, anandamide and 2-arachidonoylglycerol. They also postulated that this helped to explain how botanical drugs were often more efficacious than their isolated components

  • Although the single molecule synthesis remains the dominant model for pharmaceutical development, the concept of botanical synergy has been amply demonstrated contemporaneously, invoking the pharmacological contributions of “minor cannabinoids” and cannabis terpenoids to the plant’s overall pharmacological effect.

Lists examples of cases that support entourage effect:

  • In animal studies of analgesia, pure CBD produces a biphasic dose-response curve such that smaller doses reduce pain responses until a peak is reached, after which further increases in dose are ineffective. 

  • CONVERSELY - the application of a full spectrum CBD eliminates the biphasic response in favour of a linear dose-response curve such that the botanical extract is analgesic at any dose with no observed ceiling effect.

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