Caryophyllene

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

Pharmacology & Research

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 flavouring. 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.

0. Evidence by application

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.

Application	Support	Rests on
Anti-inflammatory	█████░░░░░ 48%	CB2-knockout-validated in-vivo mouse edema model + receptor pharmacology 1Reference 1Gertsch J et al. · 2008In vitroBeta-caryophyllene is a dietary cannabinoid — in vitro receptor pharmacology + in-vivo mouse modelView study →
Analgesic (pain)	████░░░░░░ 44%	Mouse inflammatory & neuropathic pain models, CB2-dependent 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 & antidepressant-like	████░░░░░░ 40%	Mouse behavioural models, blocked by a CB2 antagonist 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 →

1. Anti-inflammatory

The defining study showed that orally administered β-caryophyllene reduced inflammatory paw edema in normal mice but not in CB2-knockout mice, proving the effect is CB2-mediated — and established it as a selective CB2 agonist (Ki ≈ 155 nM) ^{1Reference 1Gertsch J et al. · 2008In vitroBeta-caryophyllene is a dietary cannabinoid — in vitro receptor pharmacology + in-vivo mouse modelView study →}. CB2 sits on immune cells, so this is a clean, mechanism-anchored anti-inflammatory action.

Gap: demonstrated in mice with isolated compound; no human anti-inflammatory trials, and dietary intake is far below the doses used ^{1Reference 1Gertsch J et al. · 2008In vitroBeta-caryophyllene is a dietary cannabinoid — in vitro receptor pharmacology + in-vivo mouse modelView study →}.

2. Analgesic (pain)

In mouse models, oral β-caryophyllene reduced both late-phase (inflammatory) formalin pain and neuropathic pain responses, with the effect absent in CB2-knockouts or blocked by a CB2 antagonist — again pinning the action to CB2 ^{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 →}. It did not affect acute nociceptive pain.

Gap: animal models only; no human analgesia data, and the doses are pharmacological rather than dietary ^{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 →}.

3. Anxiolytic & antidepressant-like

In mice, acute β-caryophyllene produced anxiolytic effects (elevated plus maze, open field, marble burying) and antidepressant-like effects (forced swim, tail suspension), all abolished by the CB2 antagonist AM630 — consistent with a CB2-mediated mood action ^{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 →}.

Gap: rodent behavioural tests of debated human predictive value; no clinical mood data ^{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 →}.

Mechanisms

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

Clinical trials

Caryophyllene has no completed human therapeutic trials; it is well established as a food flavouring 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 flavouring (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 characterised for safety in humans.

Pregnancy & lactation

Dietary amounts are fine; concentrated supplements not established. Caryophyllene is consumed routinely in food (spices, herbs) with no concern at those levels. Concentrated supplements or essential oils have not been studied in pregnancy or breastfeeding, so those should be avoided in the absence of data.

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

1. 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/
2. 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/
3. 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/