Cannabis Science


What is Humulene and what does this cannabis terpene do?

Humulene, also known as α-caryophyllene, is a bicyclic sesquiterpene with an open-ring-shape structure (Figure 1). Together with isocaryophyllene (or (Z)-β-caryophyllene) it can be considered a close relative – chemically defined with the term “isomer”- of β-caryophyllene (meaning that these compounds both share the same molecular formula of β-caryophyllene, but have different structures.

The flavor and aroma profile of Humulene

Humulene has a typical woody-herbal scent with earthy notes and spicy-clove undertones, reminding a damp forest floor or a pile of autumn leaves; it is also responsible for the typical hoppy aroma and bitter taste of beer.

Humulene is the most abundant terpene in hops (Humulus lupulus) hence the name. This compound can also be found in other medicinal plants, such as cannabis, sage, and ginseng.

In cannabis, humulene is responsible for its aromatic profile one of the “big-eight” terpenes (together with myrcene, terpinolene, ocimene, limonene, α-pinene, linalool, and β-caryophyllene (BCP)), and one of the most abundant sesquiterpenes (together β-caryophyllene, bergamotene, and farnesene) of cannabis pistillate flowers, independent of the stage of inflorescence.

The medicinal properties of Humulene

From the pharmacological point of view, humulene exhibits numerous activities: It shows powerful anti-inflammatory properties, both topical and systemic equal to dexamethasone in an animal model, and analgesic if administered both locally and orally, or by aerosol.

Small amounts of essential oil containing humulene also revealed to have potent anti-bacterial properties, particularly against Staphylococcus aureus strains.

In recent studies, humulene has revealed antitumor properties, often potentiated by the entourage effect of other terpenes, particularly β-caryophyllene and isocaryophyllene:

  • According to a 2007 study, humulene has shown anti-tumor activity and a toxic effect on cancer cells, if administered in association with its isomer isocaryophyllene. Furthermore, if combined with β-caryophyllene (at non-toxic concentration), humulene and isocaryophyllene significantly increase their anticancer activity on human breast cancer adenocarcinoma (MCF-7) cells (cell growth inhibited by about 75% and 90% respectively for humulene and isocaryophyllene when combined with β-caryophyllene, compared to 50% and 70% when administered alone).
  • Such an effect of the interaction between these terpenes against cancer cell proliferation was further confirmed in a 2016 study, showing that the antiproliferative activity of humulene was enhanced by the concomitant administration of its isomers isocaryophyllene and β-caryophyllene.
  • Humulene can produce reactive oxygen species (ROS) – a group of highly reactive chemicals, which may act as cancer suppressors. The synergistic action of β-caryophyllene potentiates the antineoplastic effect of humulene in inducing programmed cell death (a phenomenon called “apoptosis”).

Among other interesting properties of humulene, there is a protective role against hydrogen peroxide (H2O2)-induced cell death in rat’s brain cells and spinal cord called “astrocytes”.

Finally, humulene can inhibit fruit fly mating, thus defending plants and their products from the attack of such insects.

Medical properties summary:

  • Anti-inflammatory
  • Antibacterial
  • Analgesic
  • Anti-cancer
  • Defensive action against predators


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