Beta-caryophyllene: the pepper terpene that targets CB2

Plants owe their smell to terpenes, a family of volatile molecules. Beta-caryophyllene gives the peppery, woody notes of black pepper, clove, hops, rosemary and basil. It is a sesquiterpene with 15 carbon atoms, which makes it heavier and less volatile than myrcene or limonene and their 10.

Hemp produces it as well. According to the 2008 study described below, it can account for up to 35% of the essential oil of Cannabis sativa. The same authors put typical dietary intake at 10 to 200 mg a day, mostly from spices.

Several flowers in the Phytogrammes catalogue are described as having a woody, resinous profile marked by β-caryophyllene, NYC Diesel and Skunk among them. Our article on the role and chemistry of terpenes situates BCP among the other aromatic compounds of hemp.

Jürg Gertsch and colleagues at ETH Zurich published their paper in the Proceedings of the National Academy of Sciences in July 2008, under a blunt title: "Beta-caryophyllene is a dietary cannabinoid". Three measurements sum up their results.

• (E)-beta-caryophyllene binds selectively to the CB2 receptor and activates it, with an affinity constant (Ki) of 155 nanomolar; a lower Ki means stronger binding.
• Its binding to the CB1 receptor, which produces the psychoactive effects of THC, is not significant.
• In mice, an oral dose of 5 mg per kilogram strongly reduced an inflammation induced in the paw; in mice lacking the CB2 receptor, it had no such effect.

CB2 receptors are found mainly on immune cells and in the body's periphery. When the authors write "dietary cannabinoid", they describe how the molecule behaves pharmacologically; chemically it belongs to another family. The role of these two receptors is explained in our article on the endocannabinoid system.

In pharmacology, a result gains weight once another team reproduces it. In 2020, researchers at the University of Otago in New Zealand tested five cannabis terpenes, BCP among them, on the CB1 and CB2 receptors. Their paper in Frontiers in Pharmacology concludes that none of these terpenes acts directly on these receptors, except perhaps for a weak interaction between BCP and CB2. They found no functional effect, whether the terpenes were tested alone or with THC or CBD.

The 2008 study is not refuted by this disagreement. What it shows is that test conditions affect the result, and that an affinity measured in a test tube tells you nothing about what happens after inhalation or a meal. It also undermines the idea, discussed in our article on the entourage effect, that terpenes strengthen CBD by acting on cannabinoid receptors.

The human studies that exist are small. In 2022 a German team was the first to measure what becomes of BCP when swallowed: 24 healthy volunteers received a single 100 mg dose, either as an oil or in an emulsified formulation. With the oil, blood levels peaked after about 3 hours. The authors' starting point was the poor oral absorption seen in animals, and the emulsified formulation doubled the amount that reached the blood.

That same year, an Iranian trial published in Appetite gave 52 women either 100 mg of BCP a day or a placebo for 8 weeks. Scores on a food addiction questionnaire dropped further with BCP than with placebo, at the limit of statistical significance. Weight, appetite, mood and the hormones measured showed no change relative to placebo. A trial this size cannot attribute any effect to BCP, still less to the quantities present in a flower.

Under Regulation (EC) No 1334/2008, beta-caryophyllene appears on the EU list of authorised flavourings as FL 01.007. JECFA, the Joint FAO/WHO Expert Committee on Food Additives, assessed it in 2004 under number 1324. It found no safety concern at the intake levels linked to its use as a flavouring. EFSA went over the file again in 2015 in its group evaluation FGE.78Rev2, following new genotoxicity data and a 90-day study in rats.

This has two practical consequences. Finding it in a food or a flower is ordinary, and its presence does not make the product a cannabinoid preparation. Nor can any health claim be attached to it, because Regulation (EC) No 1924/2006 allows only claims on the EU list and BCP is not on it. A seller who writes that a BCP product acts on inflammation breaks the rules, whatever the animal studies say.

Many vaporisation charts list a boiling point of around 130 °C for beta-caryophyllene. The source of that figure appears in the PubChem entry: 264 to 266 °F, about 130 °C, measured at 14 mm of mercury, a partial vacuum below 2% of atmospheric pressure. At normal pressure, 760 mm, the same entry gives 256 to 259 °C.

Terpenes begin to evaporate well below their boiling point, so some of the BCP is released at lower temperatures. That does not make 130 °C a vaporiser setting. Our guide to vaporisation temperatures lists the useful steps with their sources.

In practice, very little. Time, heat and light make terpenes evaporate. A flower that still smells clearly of pepper has above all been well dried and stored, which tells you about freshness and promises no effect. Our article on drying and curing explains why.

The batch certificate of analysis remains the document to read, with the cannabinoid levels and Δ⁹-THC below 0.30%. If the laboratory has also quantified terpenes, BCP is listed as a percentage of mass. Measurement methods are described on the laboratory page, and the woody references are in the CBD flowers category.