Caryophyllene Oxide

Aroma and sensory profile

Caryophyllene oxide smells like the wood its parent came from, after the spice has faded. Fragrance references type it woody with medium strength and describe it neat as sweet, fresh, dry, woody, and spicy, with a flavor of dry woody, cedar, old wood, carrot, ambrette, and amber [1]. Against beta-caryophyllene it is drier, less peppery, and more amber; the clove-and-pepper bite of the parent hydrocarbon is replaced by something closer to a cedar chest with a faint carrot-seed sweetness. It is a white crystalline solid melting at 60 to 62 °C [1], so it does not diffuse the way the parent does.

The molecule is the epoxide of beta-caryophyllene: a nine-membered ring fused to a cyclobutane, with the ring double bond converted to an oxirane, giving four stereocenters. The natural material is (−)-caryophyllene oxide, derived from natural (−)-beta-caryophyllene, and it is a standard chiral-pool starting material for synthesis [10]. No panel description of the mirror-image enantiomer was found, so no claim about how the two enantiomers differ in odor is made here.

Effects and research

No human trial of caryophyllene oxide was found. A 2016 review of caryophyllene and its oxide noted significant anticancer activity in numerous cancer cell lines and acknowledged that their antineoplastic effects have hardly been investigated in vivo [4]. The Research Institute for Fragrance Materials assessed it in 2020 [3].

The analgesic data are from mice. Oral caryophyllene oxide from Annona squamosa bark at 12.5 and 25 milligrams per kilogram showed central and peripheral analgesic and anti-inflammatory activity comparable to standard drugs [5]. Combined with paracetamol it produced synergistic antinociception in the formalin test through a mechanism independent of nitric oxide, opioid, serotonin, and ATP-sensitive potassium pathways, and the combination protected against ethanol-induced gastric lesions [7]. In rats it reduced carrageenan paw edema dose-dependently, with recovery of antioxidant enzymes and lower C-reactive protein and lipid peroxidation than indomethacin [8].

The sedation result is by inhalation, which matters. Caryophyllene oxide isolated from Siam weed leaf oil, where it makes up 43.75 percent, was tested in mice at 0.0004 to 0.04 milligrams in a 61-liter chamber and reduced locomotor activity by 56 to 57 percent; the authors called it a potent central depressant acting independently of GABAergic mechanisms [6]. Topically, nanoemulgels of the isolated compound showed stronger antiedematogenic activity than the same amount delivered in an oleoresin [9].

Natural sources

Caryophyllene oxide is present wherever beta-caryophyllene is, and in greater amount the older the material. The 2016 review describes both as present in a large number of plants worldwide [4]. Fragrance databases log it at 9.8 percent in Baccharis coridifolia oil, 2.5 percent in galangal oil, 1.25 percent in sweet basil oil, 1.1 percent in ayou wood oil, 0.8 to 0.95 percent in bois de rose leaf oil, 0.66 percent in betel leaf, and traces in allspice, angelica root, Artemisia, bay laurel, and beer [1]. Its richest reported source is the leaf oil of Chromolaena odorata, Siam weed, at 43.75 percent [6], and it was isolated from the bark of Annona squamosa, the sugar apple, for the analgesic work [5]. In cannabis it is a regular minor sesquiterpene.

Boiling point and vaporization

No measured boiling point for caryophyllene oxide appears in PubChem or in a primary paper found for this profile, so none is listed. PubChem carries no experimental boiling point for it [2]; fragrance references quote 279.68 °C at 760 mmHg but mark it as an estimate [1], and the 280 °C the site previously listed was that estimate. What can be said is that caryophyllene oxide is a fifteen-carbon epoxide and a crystalline solid melting at 60 to 62 °C [1], less volatile than its parent hydrocarbon; it melts into the surrounding oil rather than vaporizing. The mouse chamber study shows it is nonetheless volatile enough at ambient temperature to reach the airways in behaviorally active amounts [6]. No thermal degradation study was found.

Safety and regulation

Caryophyllene oxide is listed by the US Food and Drug Administration as a permitted synthetic flavoring substance at 21 CFR 172.515, as "β-Caryophyllene oxide" [11]. The Research Institute for Fragrance Materials set a no-expected-sensitization-induction level of 42.75 micrograms per square centimeter, found no phototoxic potential, and reported negative genotoxicity [3]. No cancer classification applies.

Its skin record is that of a mild sensitizer and irritant. The RIFM sensitization level is low compared with alcohols like geraniol, reflecting the reactivity of the epoxide, and under Europe's classification inventory about 46 percent of notifications flag it as a skin and eye irritant and 69 percent as toxic to aquatic life [2]. Unlike its parent, it is not a hydrocarbon and carries no aspiration hazard code.

Industries and uses

Fragrance: caryophyllene oxide supplies a dry, amber-cedar woody base and fixative in spice, woody, and oriental accords and is stocked as crystals [1]. Culinary: it holds FDA flavoring status and contributes dry woody, carrot-seed nuances at trace levels [1][11]. Aromatherapy: clove, black pepper, and aged lavender oils are its carriers; the sensitization level and the inhalation sedation data are the relevant notes [3][6].