Material guide: beta-caryophyllene — it has a named receptor target, and that receptor has nothing to do with smell

About 5 minutes.

Short version

• Name: beta-caryophyllene, CAS 87-44-5, C15H24, MW 204.36 — a bicyclic sesquiterpene
• FEMA 2252, JECFA 1324, FLAVIS 01.007, CoE 2118, structure class I, FCC listed Yes
• Odour type: spicy; odour: sweet, woody, spicy, clove, dry
• Strength: medium; substantivity 44 hours; vapour pressure 0.013 mmHg
• Assay: 80.00 to 100.00 (twenty points, among the wider ranges here)
• Optical rotation: −5.00 to −10.00
• Suppliers: 61
• GHS: H302, harmful if swallowed (acute toxicity Category 4)

It is everywhere

The notes field is direct:

Constit. of clove, cinnamon, mint, eucalyptus, thyme, lemon balm and many other oils. The main source is the clove tree Eugenia caryophyllata.

And the occurrence field is among the longest I have seen, running on with percentages — allamanda flower oil (Brazil) at 15.70%, allspice, amyris wood oil at trace, angelica seed CO2 extract at 0.50%, and so on for lines.

This is the kind of molecule you are already using without knowing it. Put clove, cinnamon or allspice in a formula and beta-caryophyllene is in there.

The receptor it binds is not in your nose

The title of Gertsch and colleagues' 2008 PNAS paper is the conclusion: "Beta-caryophyllene is a dietary cannabinoid".

Their finding:

the widespread plant volatile (E)-beta-caryophyllene selectively binds to the CB2 receptor (Ki = 155 ± 4 nM) and … is a functional CB2 agonist.

The abstract adds layers:

• Molecular docking identified a putative binding site in CB2, showing π-π stacking with residues F117 and W258.
• On binding it inhibits adenylate cyclase, produces intracellular calcium transients, and weakly activates the mitogen-activated kinases Erk1/2 and p38 in primary human monocytes.
• At 500 nM it inhibits lipopolysaccharide-induced proinflammatory responses.

The paper is explicit on one point: the CB1 receptor is responsible for psychomodulatory effects, and this molecule is selective for CB2 — whose activation is regarded as a candidate strategy for inflammation, pain, atherosclerosis and osteoporosis.

For perfume formulation the implication is nil. You will not reach those concentrations on skin, and the paper is not about odour.

But it is worth recording, because it is the second kind of "molecule doing something other than smell" in this database. The first is WS-3, whose flavour field says "trigeminal effect" outright — cooling travels through temperature receptors, not olfactory ones. Beta-caryophyllene takes a third route: an immune-system receptor.

One molecule can be a fragrance material, a flavour material and a receptor ligand, and those are three separate facts.

The GHS field contradicts the toxicity field

This record carries an internal contradiction you can check yourself.

GHS classification field:

Acute toxicity, Oral (Category 4), H302 — Harmful if swallowed

Toxicity field:

oral-rat LD50 [sex: M,F] > 5000 mg/kg, one dose tested (Hart & Wong, 1971)

GHS acute oral categories are cut by LD50: Category 1 ≤ 5, Category 2 ≤ 50, Category 3 ≤ 300, Category 4 ≤ 2000, Category 5 ≤ 5000 mg/kg.

A substance with an LD50 above 5000 falls outside Category 5, not into Category 4.

The two fields are more than two categories apart.

I do not know which is right. It could be a different study, species or sample purity (this material's assay range runs 80 to 100), or a conservative classification, or simply an entry error. But with those two cells on one record, at least one of them needs rechecking.

(GHS classifications are supplier-declared and need not agree between suppliers, which I also noted for angelica root oil. Toxicity-field data quality was worse on rhodinol, where marketing copy ran straight on from the LD50.)

Assay and optical rotation are both ranges

• Assay 80 to 100 — twenty points. Supplier entries include "beta-Caryophyllene 90%" as well as "BETA CARYOPHYLLENE NATURAL" and "NAT".
• Optical rotation −5.00 to −10.00 — a range, as with rhodinol.

This is common for naturally sourced sesquiterpenes: they are fractionated out of essential oils, and what you get depends on the feedstock. "Natural" and synthetic will not match on this field.

(The three causes of a wide assay range are in How wide is the assay window. Beta-caryophyllene belongs to "isolated from a natural, ratio varies with feedstock" — which is actually a fourth cause beyond the three I set out there.)

How to use it

• It bridges spicy and woody. Clove and dry wood in the odour field connect it to the eugenol and cinnamaldehyde line, and it is far gentler than either (medium strength, 44 hours).
• Forty-four hours is a middle note, not a base. Vapour pressure 0.013 mmHg.
• Ask about purity and origin when buying. An 80-to-100 range plus a natural/synthetic distinction can put two bottles far apart.
• It may already be in your formula. Clove, cinnamon, allspice and eucalyptus all bring it along.
• Do not change how you use it because of the CB2 paper. That has nothing to do with perfume exposure.

What this doesn't establish

• I have not smelled it. The whole article is fields, database-wide counts and one paper.
• Gertsch's work is in vitro receptor binding and cell experiments. Ki = 155 nM is a binding affinity, not a dose for any human effect, and dermal exposure from a perfume is unrelated to that system. I cite it to show the molecule has a known non-olfactory target, not to imply any health effect.
• I point out the GHS-versus-toxicity contradiction without resolving it. I did not consult the original GHS dossier or the Hart & Wong 1971 report.
• The LD50 thresholds for GHS categories are the general rule; actual classification also weighs other data and expert judgement, so "should be outside Category 5" is a simplified inference.
• I have no data on how the assay range and the rotation range relate. Both may reflect feedstock, or they may be independent.
• The percentages in the occurrence field carry no method or sample provenance.