Limonene

Limonene is a lemon-scented molecule, the main constituent of citrus peel oil; hemp makes it too. It is a terpene, not a cannabinoid: in the laboratory it acts neither on the CB1 receptor nor on the CB2 receptor, the receptors of THC. It is authorised as a food flavouring, but on exposure to air it oxidises into compounds that can cause contact allergies.

• CB1No measured activity

  No effect of its own; no change in the response to CP55,940 (1 µM) or in that to Δ9-THC in the presence of limonene at 10 µM

  Santiago et al. 2019, Cannabis Cannabinoid Res: no entourage effect at CB1 and CB2 (new tab) · membrane potential (FLIPR), AtT20 cells expressing human CB1; (R)-(+)-limonene from 1 nM to 100 µM

• CB2No measured activity

  No effect of its own; no change in the response to CP55,940 (1 µM) or in that to Δ9-THC in the presence of limonene at 10 µM

  Santiago et al. 2019, Cannabis Cannabinoid Res: no entourage effect at CB1 and CB2 (new tab) · membrane potential (FLIPR), AtT20 cells expressing human CB2; (R)-(+)-limonene from 1 nM to 100 µM

• CB1No measured activity

  No change in binding or in cAMP, alone or combined with Δ9-THC, cannabidiol or 2-AG

  Finlay et al. 2020, Front Pharmacol: cannabis terpenes do not act at cannabinoid receptors (new tab) · [3H]CP55,940 displacement, HEK membranes expressing human CB1, and cAMP inhibition (CAMYEL BRET); limonene at 10 µM

• CB2No measured activity

  No change in binding or in cAMP, alone or combined with Δ9-THC, cannabidiol or 2-AG

  Finlay et al. 2020, Front Pharmacol: cannabis terpenes do not act at cannabinoid receptors (new tab) · [3H]CP55,940 displacement, HEK membranes expressing human CB2, and cAMP inhibition (CAMYEL BRET); limonene at 10 µM

• TRPV1No measured activity

  No activation; no change in the response to capsaicin or to anandamide

  Heblinski et al. 2020, Cannabis Cannabinoid Res: cannabis terpenoids, TRPA1 and TRPV1 (new tab) · intracellular calcium (Calcium 5), HEK Flp-In T-Rex cells expressing human TRPV1; (R)-(+)-limonene at 10 µM

• TRPA1No measured activity

  No activation; no significant change in the responses to the agonists tested

  Heblinski et al. 2020, Cannabis Cannabinoid Res: cannabis terpenoids, TRPA1 and TRPV1 (new tab) · intracellular calcium (Calcium 5), HEK Flp-In T-Rex cells expressing human TRPA1; (R)-(+)-limonene at 10 µM

• A2AAgonist

  Park et al. 2011, Biochem Biophys Res Commun: limonene, an agonist ligand of adenosine A2A receptors (new tab) · radioligand binding (selective affinity for A2A); CHO cells expressing the human A2A receptor: rise in cAMP, protein kinase A activation, CREB phosphorylation and rise in cytosolic calcium

Sources: Myrcene, PubChem (HSDB), Limonene, NIST Chemistry WebBook, β-Caryophyllene, PubChem (JECFA), Linalool, PubChem (CRC Handbook), α-Pinene, PubChem (HSDB).

Limonene is a monoterpene, not a cannabinoid: it is a hydrocarbon with no oxygen atom, and published assays find no activity at the cannabinoid receptors. Its molecule carries one stereocentre, giving two enantiomers: (R)-(+)-limonene, or d-limonene, of which citrus peel oil is described as consisting (Matura 2002), and (S)-(−)-limonene, or l-limonene, which the terpene synthase CsTPS1FN of 'Finola' hemp forms, and which made up on average 12 ± 10% of the monoterpenes of 22 plants (Booth 2017). At the human CB1 and CB2 receptors, (R)-(+)-limonene up to 100 µM had no effect of its own and did not change the action of Δ9-THC in AtT20 cells (Santiago 2019), and limonene at 10 µM neither displaced the radioligand nor changed cAMP in HEK cells (Finlay 2020); the study by LaVigne (2021), which supports an 'entourage effect' of other terpenes, did not include it. In vitro, it behaves as an agonist of the adenosine A2A receptor (Park 2011). In humans, it has been given orally to seven healthy volunteers at 100 mg/kg (Crowell 1994) and to cancer patients in a phase I trial, whose maximum tolerated dose was 8 g/m² per day (Vigushin 1998); it circulates mainly as perillic acid, dihydroperillic acid and limonene-1,2-diol. The kidney tumours that d-limonene induces in male rats go through α2u-globulin, a protein specific to the male rat, a mechanism IARC judges not relevant to humans (Group 3, 1999); oxidised by air, however, limonene forms contact allergens (Karlberg 1994), to which 2.6% of 2 411 dermatitis patients reacted (Matura 2006).

European Union

No schedule of the 1961 and 1971 United Nations conventions covers limonene (INCB Yellow List, 65th edition, July 2026; Green List, 36th edition, 2025). In the Union, it is on the list of authorised flavouring substances (Implementing Regulation (EU) No 872/2012: FL 01.001 limonene, FL 01.045 d-limonene, FL 01.046 l-limonene). In cosmetics, entry 88 of Annex III to Regulation (EC) No 1223/2009, as worded by Regulation (EU) 2023/1545, requires it to be named in the ingredient list above 0.001% in leave-on products and 0.01% in rinse-off products, with a peroxide value below 20 millimoles per litre. Its harmonised CLP classification includes skin sensitisation (category 1B for d-limonene, category 1 for racemic limonene and l-limonene) and, for d-limonene, the aspiration hazard (Asp. Tox. 1). In the United States, limonene (d-, l- and dl-) is listed among the synthetic flavouring substances generally recognised as safe (21 CFR 182.60).

France

Not classified as a narcotic in France: limonene does not appear on the consolidated list of substances classified as narcotics published by the ANSM (updated 26/06/2026), which compiles the order of 22 February 1990 and the decisions of the Agency's director general. Its uses as a food flavouring and as a fragrance ingredient in cosmetics fall under European Union law.

Sources: EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA. Our method.

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