Beta-Caryophyllene (Sesquiterpene CB2 Agonist · Dietary Cannabinoid · Anti-inflammatory)
| Compound | Beta-Caryophyllene (BCP; (E)-BCP) |
| Chemical class | Terpenoid — Sesquiterpene (Bicyclic sesquiterpene; cyclobutane-containing) |
| CAS | 87-44-5 |
| Primary source | Piper nigrum (black pepper), Syzygium aromaticum (clove), Cannabis sativa (hemp), Copaiba balsam |
| Key applications | CB2 receptor agonist; anti-inflammatory; neuroprotective; analgesic; FDA-approved food flavouring GRAS |
| Claim strength | Moderate |
| Typical form | Black pepper essential oil constituent; clove oil; hemp terpene fraction; copaiba oil |
| Buy from Herbuno |
Black Pepper Extract Powder with Piperine | Kali Mirch → Black Pepper Liquid Extract (Water Soluble) - Piper nigrum → |
Name origin: From Caryophyllus (an old genus name for clove, from Greek karuophullon = nut leaf). Beta-caryophyllene is a bicyclic sesquiterpene with a unique cyclobutane ring — rare in natural products — fused to a nine-membered ring. The (E)- designation refers to the trans configuration of the exocyclic double bond. It is present in over 50% of all Cannabis sativa terpene profiles (one of the most abundant cannabis terpenes) and is abundant in black pepper, clove, copaiba, and many spice oils. Significance — dietary CB2 agonist: BCP’s most pharmacologically important property is that it is a selective full agonist at the cannabinoid CB2 receptor — without binding CB1 (the psychoactive receptor). This makes BCP the first identified dietary cannabinoid — a GRAS-approved food flavouring that simultaneously activates the endocannabinoid system. This discovery (Gertsch et al., PNAS 2008) was a paradigm shift in cannabinoid pharmacology and food science. Because it does not bind CB1, BCP produces no psychoactive effects. Because it is a food additive (GRAS in the US since 1965 as a flavouring agent), it occupies a unique regulatory space — dietary CB2 activation from normal food and supplement sources. Research trajectory: Since 2008, BCP’s CB2-mediated anti-inflammatory, neuroprotective, analgesic, and metabolic effects have been extensively characterised in preclinical models. Human clinical data remain limited — largely because BCP’s GRAS status and widespread food occurrence have not driven the pharmaceutical-level clinical investigation that novel drug candidates receive. Commercial source: Available from black pepper and clove extracts at Herbuno.
Evidence for Beta-Caryophyllene Applications
CB2 agonism — anti-inflammatory mechanism: BCP binds CB2 receptors (Ki ~155 nM) on immune cells (macrophages, microglia, mast cells, T-cells), reducing pro-inflammatory cytokine production (TNF-α, IL-1β, IL-6) via Gi protein-mediated inhibition of adenylyl cyclase and NF-κB. CB2 activation on microglia is particularly relevant for neuroinflammation — BCP reduces microglial activation in multiple neurological disease models. Claim strength: Moderate (mechanism established; human data limited).
Neuroprotection and pain modulation: In rodent models of neuropathic pain, BCP reduces allodynia and hyperalgesia via CB2 agonism in spinal cord microglia. In Alzheimer’s models, BCP reduces amyloid-beta burden and neuroinflammation. In Parkinson’s models, protection of dopaminergic neurons is documented. Oral bioavailability of BCP is moderate (~30% in rats); CNS penetration is documented. Claim strength: Moderate (animal; human data emerging).
Metabolic and hepatoprotective: BCP activates CB2 receptors in hepatic stellate cells and adipose tissue, reducing hepatic fibrosis in NAFLD models and improving insulin sensitivity in diabetic animal models. PPAR-α activation (separate from CB2) may contribute to lipid metabolism effects. Claim strength: Moderate (animal models).
Black Pepper Extract Powder with Piperine | Kali Mirch →
Black Pepper Liquid Extract (Water Soluble) - Piper nigrum →
Browse Standardised Extract Powders →
Dosage & Formulator Specification
No established human clinical dose. Animal model effective range: 10–50 mg/kg oral, suggesting human equivalent doses of 100–600 mg/day for a 70 kg adult (body surface area scaling). BCP as a pure terpene is a liquid at room temperature (bp 119–120°C/12 mmHg); commercial supplement formats use microencapsulated powder or blend it in oil. BCP is also present in black pepper and clove extracts alongside other bioactive compounds — specifying total BCP content by GC-MS is important. Regulatory note: BCP’s GRAS status as a food flavour (US) does not automatically confer dietary supplement status in all markets — confirm regulatory classification in target market. In EU, BCP as a flavouring ingredient in food is permitted; as a primary supplement active, Novel Food status may need assessment.
Frequently Asked Questions — Beta-Caryophyllene
Is beta-caryophyllene a cannabinoid?
Pharmacologically yes — BCP is a selective CB2 receptor agonist, meeting the pharmacological definition of a cannabinoid. However, it is not a phytocannabinoid in the structural sense (it lacks the terpenophenol structure of THC, CBD, and related phytocannabinoids) and does not derive from the olivetolic acid/geranyl pyrophosphate biosynthetic pathway that produces classical cannabinoids. BCP activates the same CB2 receptor as THC (at CB2) but has no CB1 affinity and no psychoactivity. Regulatorily, BCP is not scheduled as a controlled substance anywhere due to its GRAS food status.
Why is copaiba oil marketed as a CB2 agonist supplement?
Copaiba balsam (from Copaifera species of South America) contains 50–60% BCP by GC analysis — the highest BCP content of any commercially accessible natural product. This makes copaiba oil a practical high-BCP delivery format. The copaiba supplement market is primarily driven by BCP’s CB2 agonism for anti-inflammatory and pain applications. Black pepper and clove extracts contain lower BCP fractions (5–30% of essential oil) but are more established commercial ingredients.
How does BCP interact with other cannabis terpenes (the entourage effect)?
The cannabis entourage hypothesis proposes that terpenes like BCP, linalool, and myrcene modify the pharmacological effects of THC and CBD. For BCP specifically: BCP’s CB2 agonism may complement CBD’s indirect endocannabinoid modulation, and BCP may reduce CB1-mediated THC side effects by CB2-mediated anti-inflammatory counter-regulation. However, the entourage effect hypothesis remains controversial in the scientific literature — controlled human studies specifically evaluating BCP-THC or BCP-CBD pharmacological interactions are limited.
Does beta-caryophyllene appear in drug testing?
No — BCP is not a controlled substance and is not tested for in any standard drug screen. Standard cannabis drug screens (immunoassay and GC-MS) detect THC metabolites (11-nor-9-carboxy-THC), not terpenes. BCP consumption from food, supplements, or hemp-derived products will not cause a positive drug test for cannabis or any other controlled substance.
Related compounds: Parthenolide, Myrcene, Linalool, Caryophyllene Oxide
Claim-strength scale – High = multiple human RCTs; Moderate = limited trials or strong preclinical convergence; Emerging = early-stage lab or animal data.
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