Humulene

Humulene is a terpene, a volatile molecule made by many plants, starting with the hops used in beer, which gave it its name, and hemp. It is not a cannabinoid: unlike its close cousin beta-caryophyllene, it does not attach to the CB2 receptor. Its action at the CB1 receptor remains disputed, with opposite results in mice and in rats, and no clinical trial in humans has been found.

• CB2No measured activity

  No displacement of the radioligand from human CB2 (Ki > 20 µM), unlike β-caryophyllene (Ki = 155 nM) in the same assay (Gertsch 2008)

  Gertsch et al. 2008, PNAS: β-caryophyllene, a dietary cannabinoid (new tab) · [3H]CP55,940 displacement, human CB2

• CB2Not established

  ERK phosphorylation in cells expressing CB2, but α-humulene also activates ERK, without sensitivity to rimonabant, in CHO cells lacking a cannabinoid receptor: attribution to CB2 is not established (LaVigne 2021)

  LaVigne et al. 2021, Sci Rep: cannabimimetic cannabis terpenes (new tab) · ERK phosphorylation, CHO cells expressing human CB2

• CB1Agonist

  Low-potency activation, visible only at high concentrations (500 µM for ERK, effect blocked by rimonabant); partial cAMP inhibition, no β-arrestin 2 recruitment, partial radioligand displacement with no fittable curve. The authors do not rule out an indirect effect, via the membrane or via 2-AG (LaVigne 2021)

  LaVigne et al. 2021, Sci Rep: cannabimimetic cannabis terpenes (new tab) · CHO cells expressing human CB1: ERK phosphorylation, cAMP inhibition, β-arrestin 2 recruitment, [3H]CP55,940 binding

• CB1No measured activity

  Neither a THC-like discriminative effect nor a tetrad effect (catalepsy, rotarod, tail-withdrawal latency, temperature); at 32 mg/kg, the THC ED50 shifted from 0.61 to 1.52 mg/kg. Authors' conclusion: no effect consistent with brain CB1 agonism (Carey 2024)

  Carey, Ghodrati & France 2024, Behav Pharmacol: discriminative effects of cannabis terpenes in rats (new tab) · in vivo: THC discrimination (3.2 mg/kg i.p.) and tetrad, α-humulene 32 to 320 mg/kg s.c., male Sprague-Dawley rats

• CYP3AInhibitor

  Significant, non-competitive inhibition of CYP3A activity; caryophyllene oxide is the most potent inhibitor of the three sesquiterpenes tested (Nguyen 2017)

  Nguyen et al. 2017, Chem Biol Interact: inhibition of hepatic CYP3A (new tab) · rat and human liver microsomes

Sources: Myrcene, PubChem (HSDB), Limonene, NIST Chemistry WebBook, β-Caryophyllene, PubChem (JECFA), Linalool, PubChem (CRC Handbook), α-Pinene, PubChem (HSDB).

α-Humulene, formerly called α-caryophyllene, is a terpene and not a cannabinoid: this fifteen-carbon sesquiterpene is the ring-opened isomer of β-caryophyllene (Gertsch 2008). The difference matters. Where β-caryophyllene binds the human CB2 receptor (Ki = 155 nM), α-humulene does not displace the radioligand from that receptor (Ki > 20 µM; Gertsch 2008). At CB1 the picture is contradictory: LaVigne et al. (2021) describe a low-potency activation of human CB1 in cell culture, at high concentrations, and tetrad-like effects in mice at 200 mg/kg given intraperitoneally, partly blocked by rimonabant; Carey et al. (2024) found in rats, up to 320 mg/kg given subcutaneously, neither a THC-like effect in drug discrimination nor tetrad effects. The studies often cited for the lack of terpene activity at cannabinoid receptors (Santiago 2019, Finlay 2020) did not test it. In rodents, α-humulene isolated from Cordia verbenacea reduced carrageenan-induced paw oedema and the production of TNF-α and IL-1β (Fernandes 2007), notably at 50 mg/kg orally in mice (Passos 2007), and in ovalbumin-sensitised mice it reduced the recruitment of eosinophils into the airways (Rogerio 2009). In mice, its oral bioavailability is 18% (Chaves 2008). No clinical trial in humans has been found (Dalavaye 2024). A major constituent of hop essential oil, which gave it its name, it accounts on average for 19% of the sesquiterpenes in the flowers of the hemp « Finola » (Booth 2017).

European Union

Absent from the schedules of the United Nations conventions of 1961 (INCB Yellow List, 65th edition, July 2026) and 1971 (Green List, 36th edition, 2025). In the European Union, it does not appear in the Union list of flavouring substances adopted by Implementing Regulation (EU) No 872/2012, where its isomer β-caryophyllene carries the number FL 01.007, and it has no harmonised classification under the CLP Regulation (ECHA, EC No 229-816-7).

France

Not classified as a narcotic in France: a terpene with no cannabinoid skeleton, α-humulene is named neither in the order of 22 February 1990 listing narcotic substances nor in the ANSM consolidated list (update of 26/06/2026, checked on 27/10/2026).

Sources: EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA. Our method.

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