Caryophyllene

Which caryophyllene? Unqualified “caryophyllene” almost always means β-caryophyllene — the CB2-active bicyclic sesquiterpene described here. Two related names are different compounds with their own pages: α-caryophyllene is a synonym for humulene, and the oxidation product is caryophyllene oxide.

Caryophyllene at a Glance

beta-Caryophyllene is the peppery sesquiterpene of black pepper, cloves and cannabis — and one of the most commonly eaten terpenes in the human diet.

It is the one common plant terpene that is a selective cannabinoid CB2 receptor agonist. That gives it something most terpenes lack: a defined receptor mechanism for its anti-inflammatory activity, and a dietary cannabinoid that produces no intoxication, since CB2 sits on immune cells rather than in the brain.

It is approved as a food additive, which makes its exposure history unusually well established.

What It's Used For

Caryophyllene (β-caryophyllene) is the bicyclic sesquiterpene behind much of the peppery, woody bite of black pepper, cloves and cannabis, and it’s already in most people’s diet as a flavoring. What sets it apart from other plant terpenes is a genuine cannabinoid mechanism: it is a selective functional agonist at the CB2 receptor (the immune-tissue cannabinoid receptor) with negligible activity at CB1 — so it engages the endocannabinoid system’s anti-inflammatory arm without any psychoactivity ^{1Reference 1Gertsch J et al. · 2008In vitroBeta-caryophyllene is a dietary cannabinoid — in vitro receptor pharmacology + in-vivo mouse modelView study →}.

That landmark finding — “β-caryophyllene is a dietary cannabinoid” — anchors a body of preclinical work on inflammation, pain and mood. As with the minor cannabinoids, the caveat is that this evidence is animal- and cell-level, using isolated caryophyllene at doses well above dietary intake.

Defined mechanism:a selective CB2 agonist (Ki ≈ 155 nM) with negligible CB1 binding — the one common dietary terpene with a cannabinoid-receptor action ^{1Reference 1Gertsch J et al. · 2008In vitroBeta-caryophyllene is a dietary cannabinoid — in vitro receptor pharmacology + in-vivo mouse modelView study →}.

Preclinical signals:CB2-dependent anti-inflammatory effect in mice ^{1Reference 1Gertsch J et al. · 2008In vitroBeta-caryophyllene is a dietary cannabinoid — in vitro receptor pharmacology + in-vivo mouse modelView study →}; analgesia in inflammatory and neuropathic pain models ^{2Reference 2Klauke AL et al. · 2014AnimalThe cannabinoid CB2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain — mouse modelView study →}; anxiolytic and antidepressant-like effects in mice ^{3Reference 3Bahi A et al. · 2014AnimalBahi A, Al Mansouri S, Al Memari E, et al. (2014). β-Caryophyllene, a CB2 receptor agonist, produces multiple behavioral changes relevant to anxiety and depression in mice — mouse model. Physiology & Behavior. https://pubmed.ncbi.nlm.nih.gov/24930711/View study →}.

The honest headline:no human therapeutic trials — the benefits are preclinical, at isolated doses above what food provides.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. For caryophyllene every entry is animal/in-vitro, so scores stay modest by design. Each application links to its write-up.

Mechanisms

Target / pathway	Effect	Relevant to
CB2 receptor selective agonism (Ki ≈ 155 nM)	anti-inflammatory, analgesic, mood — without psychoactivity	inflammationpainmood
Negligible CB1 binding	non-intoxicating	—
PPAR / downstream anti-inflammatory signaling (reported)	cytokine modulation	inflammation

Clinical trials

Caryophyllene has no completed human therapeutic trials; it is well established as a food flavoring and fragrance, with therapeutic interest confined to preclinical work.

Completed	Planned	Terminated	Preclinical
—(therapeutic)	Early interest	—	Extensive

Last checked: July 2026.

Toxicity & Safety

As a common component of the human diet, caryophyllene is regarded as well tolerated and is an approved food flavoring (GRAS). Concentrated essential oils rich in it can irritate skin in some people. Because it activates CB2, theoretical interactions with cannabinoid-based medicines are sometimes raised, but caryophyllene is not psychoactive and does not act on CB1. The gap between safe dietary exposure and the higher isolated doses used in animal studies means supplement-level dosing is simply not characterized for safety in humans.

Dosage

There is no established human therapeutic dose for caryophyllene beyond its ordinary presence in food. The effects above come from animal studies using isolated compound at mg/kg doses that do not translate to human use, and concentrated supplements lack a research-backed dosing basis. This is not a recommendation.

References

Gertsch J, Leonti M, Raduner S, et al. (2008). Beta-caryophyllene is a dietary cannabinoid — in vitro receptor pharmacology + in-vivo mouse model. Proceedings of the National Academy of Sciences USA. https://pubmed.ncbi.nlm.nih.gov/18574142/
Klauke AL, Rácz I, Pradier B, et al. (2014). The cannabinoid CB2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain — mouse model. European Neuropsychopharmacology. https://pubmed.ncbi.nlm.nih.gov/24210682/
Bahi A, Al Mansouri S, Al Memari E, et al. (2014). β-Caryophyllene, a CB2 receptor agonist, produces multiple behavioral changes relevant to anxiety and depression in mice — mouse model. Physiology & Behavior. https://pubmed.ncbi.nlm.nih.gov/24930711/