β-Caryophyllene

Aroma and sensory profile

Beta-caryophyllene is the spice note that is not hot. Fragrance references type it spicy and describe the neat material as sweet, woody, spice, clove, and dry; its flavor is spicy, clove, woody, nut skin, powdery, and peppery [1]. It carries the woody depth of black pepper and clove without eugenol's medicinal bite or piperine's pungency, which is why it reads as warm and dusty rather than sharp. In blends it is a fixative-like base for pepper, clove, and cinnamon accords.

The molecule is a sesquiterpene, larger and heavier than the monoterpenes on this site, with a nine-membered ring fused to a four-membered one and two stereocenters. The natural form is (-)-(E)-beta-caryophyllene, the (1R,9S) isomer, and the CAS number used in commerce refers to that isomer specifically [1]. The (Z) isomer, isocaryophyllene, and the (+) enantiomer exist, but no source reviewed here describes how the (+) form smells, so this profile does not compare them.

Effects and research

Beta-caryophyllene stands apart because its mechanism is known. In 2008, (E)-beta-caryophyllene was shown to bind the cannabinoid CB2 receptor selectively, with a Ki of 155 nanomolar, and to act as a functional CB2 agonist; at 500 nanomolar it inhibited lipopolysaccharide-induced proinflammatory cytokine expression in human peripheral blood, and oral doses of 5 milligrams per kilogram strongly reduced carrageenan-induced inflammation in wild-type mice but not in mice lacking CB2 receptors [2]. CB2 is the peripheral, immune-associated cannabinoid receptor; CB1 is the one behind THC's psychoactivity, and beta-caryophyllene does not act there.

Human trials exist but are small. In a randomized, double-blind, placebo-controlled trial, 66 subjects with dyspepsia took 126 milligrams per day for eight weeks; dyspepsia symptoms improved and serum interleukin-1-beta fell [3]. In another, women with obesity and food addiction took 100 milligrams daily in a softgel with a meal for eight weeks and showed significantly reduced Yale Food Addiction Scale scores versus placebo [4]. A pharmacokinetic study in 24 healthy adults found a single 100 milligram oral dose is absorbed, with a self-emulsifying formulation roughly doubling exposure [5].

Not every model responds. In human cartilage cells stimulated with interleukin-1-beta, E-caryophyllene was inactive where myrcene and limonene reduced nitric oxide production [6], a reminder that CB2 agonism does not translate to every inflammatory setting. No trial has tested inhaled beta-caryophyllene in people.

Natural sources

Beta-caryophyllene is the signature sesquiterpene of the spice cupboard. In black pepper it is the largest single component of the seed oil at 37.42 percent, and it reaches 50.50 percent in the leaf oil [7]. Clove bud oil is at least half eugenol, with the remaining 10 to 40 percent made up of eugenyl acetate, beta-caryophyllene, and alpha-humulene [8]. Its richest source is copaiba oil-resin from South American Copaifera trees, where authentic samples ran 38.58 to 45.77 percent, with reports up to 87 percent in Copaifera officinalis and as low as 33 percent in Copaifera langsdorffii [9]. It is also, as the 2008 paper noted, a major component of cannabis, and the most abundant sesquiterpene in most cannabis chemotypes, though at a fraction of the concentration in copaiba or pepper oil [2].

Boiling point and vaporization

PubChem compiles the boiling point of (-)-caryophyllene as 256 °C from JECFA and 256 to 259 °C at atmospheric pressure from the Human Metabolome Database [12]. This profile uses 256 °C (493 °F). The 130 °C figure that circulates in terpene charts is not an atmospheric boiling point: the same record lists 264 to 266 °F at 14 mmHg from CAMEO Chemicals, a vacuum-distillation value copied without its pressure [12]. At 256 °C beta-caryophyllene is the highest-boiling terpene on this site, about 60 °C above linalool, which is why pepper and clove aromas survive a long braise and why it is the last terpene to leave a heated product. No thermal degradation study of beta-caryophyllene was found; the dabbing study that produced benzene and methacrolein tested only monoterpenes.

Safety and regulation

Beta-caryophyllene is listed by the US Food and Drug Administration as a permitted synthetic flavoring substance at 21 CFR 172.515, alongside caryophyllene alcohol and beta-caryophyllene oxide [10]. The eight-week human trials at 100 to 126 milligrams per day reported no safety signal [3][4].

Its skin story differs from the monoterpenes. Beta-caryophyllene begins to oxidize immediately on air exposure and loses almost half its mass in five weeks, but the major product is caryophyllene oxide rather than a hydroperoxide; caryophyllene oxide is an allergen of moderate strength, and beta-caryophyllene air-exposed for ten weeks showed only weak sensitizing capacity in the local lymph node assay [11]. The same authors note that oxidized beta-caryophyllene is a rare sensitizer compared with oxidized limonene and linalool [11]. Aged clove or copaiba products are the exposure to consider, but the risk is lower than for citrus or lavender materials. No cancer classification applies.

Industries and uses

Fragrance: beta-caryophyllene supplies dry woody-spice depth in pepper, clove, and oriental accords and holds well because it is far less volatile than the monoterpenes [1]. Culinary: it carries FDA flavoring status and is a natural constituent of black pepper, clove, and cinnamon leaf, contributing clove and pepper notes without heat [1][7][8][10]. Aromatherapy: copaiba and clove oils, its two richest sources, are staple materials, and copaiba's traditional use for inflammation is the one aromatherapy claim with a receptor mechanism behind it, though only oral doses have been tested in people [2][9].