View source for Chemistry:Caryophyllene

{{chembox
| Watchedfields = changed
| verifiedrevid = 460021442
| Name = Caryophyllene
| ImageFile = 
| ImageFile1 = Beta-Caryophyllen.svg
| ImageName = beta-caryophyllene
| PIN = (1''R'',4''E'',9''S'')-4,11,11-Trimethyl-8-methylidenebicyclo[7.2.0]undec-4-ene
| SystematicName = 
| OtherNames = β-Caryophyllene<br />''trans''-(1''R'',9''S'')-8-Methylene-4,11,11-trimethylbicyclo[7.2.0]undec-4-ene
| IUPACName = 
| Section1 = {{Chembox Identifiers
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4444848
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 445740
| PubChem = 5281515
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = BHW853AU9H
| InChI = 1/C15H24/c1-11-6-5-7-12(2)13-10-15(3,4)14(13)9-8-11/h6,13-14H,2,5,7-10H2,1,3-4H3/b11-6+/t13-,14-/m1/s1
| InChIKey = NPNUFJAVOOONJE-GFUGXAQUBC
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C15H24/c1-11-6-5-7-12(2)13-10-15(3,4)14(13)9-8-11/h6,13-14H,2,5,7-10H2,1,3-4H3/b11-6+/t13-,14-/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = NPNUFJAVOOONJE-GFUGXAQUSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 87-44-5
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 10357
| SMILES = C1(=C)\CC/C=C(/CC[C@@H]2[C@@H]1CC2(C)C)C
}}
| Section2 = {{Chembox Properties
| C=15
| H=24
| Density = 0.9052 g/cm<sup>3</sup> (17&nbsp;°C)<ref>SciFinder Record, CAS Registry Number 87-44-5</ref>
| MeltingPt =
| BoilingPtC = 262 - 264 
| BoilingPt_ref= <ref>{{cite journal | last = Baker | first = R. R. | journal = Journal of Analytical and Applied Pyrolysis | date = 2004 | volume = 71 | issue = 1 | pages = 223–311 | doi=10.1016/s0165-2370(03)00090-1 | title=The pyrolysis of tobacco ingredients}}</ref>
  }}
| Section3 = 
| Section4 = 
| Section5 = 
| Section6 = 
}}

'''Caryophyllene''' ({{IPAc-en|ˌ|k|ær|i|oʊ-|ˈ|f|ɪ|l|iː|n}}), more formally '''(−)-β-caryophyllene,''' '''(BCP)''', is a natural bicyclic [[Chemistry:Sesquiterpene|sesquiterpene]] that is a constituent of many [[Chemistry:Essential oil|essential oil]]s, especially clove oil, the oil from the stems and flowers of ''[[Biology:Syzygium aromaticum|Syzygium aromaticum]]'' (cloves),<ref name="pmid11482764">{{cite journal |last1=Ghelardini |first1=C. |last2=Galeotti |first2=N. |last3=Di Cesare Mannelli |first3=L. |last4=Mazzanti |first4=G. |last5=Bartolini |first5=A. |title=Local anaesthetic activity of beta-caryophyllene |journal=Farmaco |volume=56 |issue=5–7 |pages=387–389 |year=2001 |pmid=11482764 |doi= 10.1016/S0014-827X(01)01092-8|hdl=2158/397975 |hdl-access=free }}</ref> the essential oil of ''[[Biology:Cannabis sativa|Cannabis sativa]]'', [[Biology:Copaiba|copaiba]], [[Biology:Rosemary|rosemary]],<ref name="pmid18670820"/> and [[Biology:Hops|hops]].<ref>{{cite web|first=G.|last=Tinseth|title=Hop Aroma and Flavor|date=January–February 1993|work=Brewing Techniques|url=http://realbeer.com/hops/aroma.html|access-date= July 21, 2010}}</ref> It is usually found as a mixture with isocaryophyllene (the ''cis'' double bond isomer) and [[Chemistry:Humulene|α-humulene]] (obsolete name: α-caryophyllene), a ring-opened isomer.  Caryophyllene is notable for having a [[Chemistry:Cyclobutane|cyclobutane]] ring, as well as a ''trans''-double bond in a 9-membered ring, both rarities in nature. 

Caryophyllene is one of the chemical compounds that contributes to the [[Chemistry:Odor|aroma]] of [[Biology:Black pepper|black pepper]].<ref name="pmid12462618">{{cite journal |last1=Jirovetz |first1=L. |last2=Buchbauer |first2=G. |last3=Ngassoum |first3=M. B. |last4=Geissler |first4=M. |title=Aroma compound analysis of ''Piper nigrum'' and ''Piper guineense'' essential oils from Cameroon using solid-phase microextraction–gas chromatography, solid-phase microextraction–gas chromatography–mass spectrometry and olfactometry |journal=Journal of Chromatography A |volume=976 |issue=1–2 |pages=265–275 |date=November 2002 |pmid=12462618 |doi= 10.1016/S0021-9673(02)00376-X}}</ref>

== Pharmacology ==
β-Caryophyllene acts as a full agonist of the [[Biology:Cannabinoid receptor type 2|Cannabinoid receptor type 2]] (CB2 receptor) in rats.<ref name="Ceccarelli Fiorenzani Pessina et al 2020">{{cite journal |last1=Ceccarelli |first1=Ilaria |last2=Fiorenzani |first2=Paolo |last3=Pessina |first3=Federica |last4=Pinassi |first4=Jessica |last5=Aglianò |first5=Margherita |last6=Miragliotta |first6=Vincenzo |last7=Aloisi |first7=Anna Maria |title=The CB2 Agonist β-Caryophyllene in Male and Female Rats Exposed to a Model of Persistent Inflammatory Pain |journal=Frontiers in Neuroscience |date=18 August 2020 |volume=14 |pages=850 |doi=10.3389/fnins.2020.00850| pmc=7461959  |pmid=33013287 |doi-access=free }}</ref> β-Caryophyllene has a binding affinity of Ki = 155nM at the CB2 receptors in mice.<ref>{{cite journal |last1=Alberti |first1=Thaís Barbosa |last2=Barbosa |first2=Wagner Luiz Ramos |last3=Vieira |first3=José Luiz Fernandes |last4=Raposo |first4=Nádia Rezende Barbosa |last5=Dutra |first5=Rafael Cypriano |title=(−)-β-Caryophyllene, a CB2 Receptor-Selective Phytocannabinoid, Suppresses Motor Paralysis and Neuroinflammation in a Murine Model of Multiple Sclerosis |journal=International Journal of Molecular Sciences |date=1 April 2017 |volume=18 |issue=4 |pages=691 |doi=10.3390/ijms18040691 |pmid=28368293 |pmc=5412277 |doi-access=free }}</ref> β-Caryophyllene has been shown to have anti-inflammatory action linked to its CB2 receptor activity in a study comparing the pain killing effects in mice with and without CB2 receptors with the group of mice without CB2 receptors seeing little benefit compared to the mice with functional CB2 receptors.<ref name="Ceccarelli Fiorenzani Pessina et al 2020"/> β-Caryophyllene has the highest cannabinoid activity compared to the ring opened isomer α-caryophyllene [[Chemistry:Humulene|Humulene]] which may modulate CB2 activity.<ref>{{cite journal |last1=Hashiesh |first1=Hebaallah Mamdouh |last2=Sharma |first2=Charu |last3=Goyal |first3=Sameer N. |last4=Sadek |first4=Bassem |last5=Jha |first5=Niraj Kumar |last6=Kaabi |first6=Juma Al |last7=Ojha |first7=Shreesh |title=A focused review on CB2 receptor-selective pharmacological properties and therapeutic potential of β-caryophyllene, a dietary cannabinoid |journal=Biomedicine & Pharmacotherapy |date=1 August 2021 |volume=140 |pages=111639 |doi=10.1016/j.biopha.2021.111639 |pmid=34091179 |s2cid=235362290 |doi-access=free }}</ref> To compare binding, [[Chemistry:Cannabinol|Cannabinol]] (CBN) binds to the CB2 receptors as a partial agonist with an affinity of CB2 Ki = 126.4 nM<ref>{{cite book |last1=Russo |first1=Ethan B. |last2=Marcu |first2=Jahan |title=Cannabinoid Pharmacology |chapter=Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads |series=Advances in Pharmacology |date=2017 |volume=80 |pages=67–134 |doi=10.1016/bs.apha.2017.03.004 |pmid=28826544 |isbn=978-0-12-811232-8 }}</ref> while Delta-9-[[Biology:Tetrahydrocannabinol|Tetrahydrocannabinol]] binds to the CB2 receptors as a partial agonist with an affinity of Ki = 36nM.<ref>{{cite journal |last1=Bow |first1=Eric W. |last2=Rimoldi |first2=John M. |title=The Structure–Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation |journal=Perspectives in Medicinal Chemistry |date=28 June 2016 |volume=8 |pages=17–39 |doi=10.4137/PMC.S32171 |pmid=27398024 |pmc=4927043 }}</ref>

Caryophyllene helps to improve cold tolerance at low ambient temperatures. Wild giant pandas frequently roll in horse manure, which contains beta-caryophyllene/caryophyllene oxide, to inhibit [[Biology:TRPM8|transient receptor potential melastatin 8 (TRPM8)]], an archetypical cold-activated ion channel of mammals.<ref>{{cite journal |last1=Zhou |first1=Wenliang |last2=Yang |first2=Shilong |last3=Li |first3=Bowen |last4=Nie |first4=Yonggang |last5=Luo |first5=Anna |last6=Huang |first6=Guangping |last7=Liu |first7=Xuefeng |last8=Lai |first8=Ren |last9=Wei |first9=Fuwen |title=Why wild giant pandas frequently roll in horse manure |journal=Proceedings of the National Academy of Sciences |date=22 December 2020 |volume=117 |issue=51 |pages=32493–32498 |doi=10.1073/pnas.2004640117 |pmid=33288697 |pmc=7768701 |bibcode=2020PNAS..11732493Z |doi-access=free }}</ref>

ß-caryophyllene could be efficiently used in the fight against cancer. For example, in an ''in vitro'' human colorectal adenocarcinoma study β-caryophyllene used alone did not inhibited cancer cell growth, but a combination of β-caryophyllene 10 µg/mL<sup>−1</sup> and Paclitaxel 0.025 µg/mL<sup>−1</sup> resulted in 189% cancer cell growth inhibition (compared to Paclitaxel used alone).<ref>{{cite journal | pmc=5889900 | year=2018 | last1=Blowman | first1=K. | last2=Magalhães | first2=M. | last3=Lemos | first3=M. F. | last4=Cabral | first4=C. | last5=Pires | first5=I. M. | title=Anticancer Properties of Essential Oils and Other Natural Products | journal=Evidence-Based Complementary and Alternative Medicine | volume=2018 | pages=1–12 | doi=10.1155/2018/3149362 | pmid=29765461 | doi-access=free }}</ref>

== Safety == 
Caryophyllene has been given GRAS (generally regarded as safe) designation by the FDA and is approved by the FDA for use as a food additive, typically for flavoring.<ref>https://ntp.niehs.nih.gov/ntp/htdocs/chem_background/exsumpdf/betacaryophyllene_508.pdf {{Bare URL PDF|date=March 2022}}</ref><ref name="accessdata.fda.gov">{{Cite web|url=https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=172.515&SearchTerm=caryophyllene|title = CFR - Code of Federal Regulations Title 21}}</ref> Rats given up to 700mg/kg daily for 90 days did not produce any significant toxic effects <ref>{{cite journal | doi=10.1177/1091581816655303 | title=Toxicological Evaluation of β-Caryophyllene Oil | year=2016 | last1=Schmitt | first1=D. | last2=Levy | first2=R. | last3=Carroll | first3=B. | journal=International Journal of Toxicology | volume=35 | issue=5 | pages=558–567 | pmid=27358239 | s2cid=206689471 | doi-access=free }}</ref> Caryophyllene has an LD50 of 5,000mg/kg in mice<ref>https://www.sigmaaldrich.com/US/en/sds/ALDRICH/W225207</ref><ref>https://www.carlroth.com/medias/SDB-A432-AU-EN.pdf?context=bWFzdGVyfHNlY3VyaXR5RGF0YXNoZWV0c3wyNzQzMDV8YXBwbGljYXRpb24vcGRmfHNlY3VyaXR5RGF0YXNoZWV0cy9oOWMvaDAyLzkwMjM0NDcyNjk0MDYucGRmfGI0MTk3NmNjN2U0Yjg4NjU2NWNmYWY2YWRkMTQzNjM0OWQxNGYxMmU2N2NlYzMyMTY0ZjljZWQ5YzRhM2YzYmY</ref>

== Chemistry ==
The first [[Chemistry:Total synthesis|total synthesis]] of caryophyllene in 1964 by E. J. Corey was considered one of the classic demonstrations of the possibilities of synthetic organic chemistry at the time.<ref>{{cite journal |last1=Corey |first1=E. J. |last2=Mitra |first2=R. B. |last3=Uda |first3=H. |title=Total Synthesis of ''d'',''l''-Caryophyllene and ''d'',''l''-Isocaryophyllene |journal=Journal of the American Chemical Society |year=1964 |volume=86 |issue=3 |pages=485–492 |doi=10.1021/ja01057a040}}</ref>

== Metabolism and derivatives==
14-Hydroxycaryophyllene oxide ([[Chemistry:Carbon|C]]<sub>15</sub>[[Chemistry:Hydrogen|H]]<sub>24</sub>[[Chemistry:Oxygen|O]]<sub>2</sub>) was isolated from the urine of [[Biology:Rabbit|rabbit]]s treated with (−)-caryophyllene (C<sub>15</sub>H<sub>24</sub>). The [[Physics:X-ray crystallography|X-ray]] [[Chemistry:Crystal structure|crystal structure]] of 14-hydroxycaryophyllene (as its [[Chemistry:Acetate|acetate]] derivative) has been reported.<ref name="Asakawa">
   {{Unbulleted list citebundle
      |{{*}} {{cite journal |last1=Asakawa |first1=Y. |last2=Taira |first2=Z. |last3=Takemoto |first3=T. |last4=Ishida |first4=T. |last5=Kido |first5=M. |last6=Ichikawa |first6=Y. |title=X-Ray Crystal Structure Analysis of 14-Hydroxycaryophyllene Oxide, a New Metabolite of (—)-Caryophyllene, in Rabbits |journal=Journal of Pharmaceutical Sciences |date=June 1981 |volume=70 |issue=6 |pages=710–711 |doi=10.1002/jps.2600700642 |url=10.1002/jps.2600700642 |language=en | pmid=7252830 | s2cid=38358882}}
      |{{*}} {{cite journal | last1=Adams | first1=T.B. | last2=Gavin | first2=C. Lucas | last3=McGowen | first3=M.M. | last4=Waddell | first4=W.J. | last5=Cohen | first5=S.M. | last6=Feron | first6=V.J. | last7=Marnett | first7=L.J. | last8=Munro | first8=I.C. | last9=Portoghese | first9=P.S. | last10=Rietjens | first10=I.M.C.M. | last11=Smith | first11=R.L. | title=The FEMA GRAS assessment of aliphatic and aromatic terpene hydrocarbons used as flavor ingredients | journal=Food and Chemical Toxicology | publisher=Elsevier BV | volume=49 | issue=10 | year=2011 | issn=0278-6915 | doi=10.1016/j.fct.2011.06.011 | pages=2471–2494 | s2cid=207734236 | pmid=21726592}}
      |{{*}} {{cite journal | year=2005 | volume=2 | issue=5 | last=Ishida | first=Takashi | publisher=John Wiley & Sons, Inc (Swiss Chemical Society) | pages=569–590 | s2cid=22213646 | pmid=17192005 | doi=10.1002/cbdv.200590038 | journal=Chemistry & Biodiversity | issn=1612-1872 | title=Biotransformation of Terpenoids by Mammals, Microorganisms, and Plant-Cultured Cells}}
   }}
</ref>

The [[Biology:Metabolism|metabolism]] of caryophyllene progresses through (−)-caryophyllene oxide (C<sub>15</sub>H<sub>24</sub>O) since the latter compound also afforded 14-hydroxycaryophyllene (C<sub>15</sub>H<sub>24</sub>O) as a [[Biology:Metabolite|metabolite]].<ref>{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/1742210#section=Top|title=Caryophyllene oxide – C<sub>15</sub>H<sub>24</sub>O |website=[[Biology:PubChem|PubChem]]|access-date=September 8, 2016}}</ref>

:Caryophyllene (C<sub>15</sub>H<sub>24</sub>) → caryophyllene oxide (C<sub>15</sub>H<sub>24</sub>O) → 14-hydroxycaryophyllene (C<sub>15</sub>H<sub>24</sub>O) → 14-hydroxycaryophyllene oxide ([[Chemistry:Carbon|C]]<sub>15</sub>[[Chemistry:Hydrogen|H]]<sub>24</sub>[[Chemistry:Oxygen|O]]<sub>2</sub>).

Caryophyllene oxide,<ref>{{cite journal |last1=Yang |first1=Depo |last2=Michel |first2=Laura |last3=Chaumont |first3=Jean-Pierre |last4=Millet-Clerc |first4=Joëlle |title=Use of caryophyllene oxide as an antifungal agent in an in vitro experimental model of onychomycosis |journal=Mycopathologia |date=1999 |volume=148 |issue=2 |pages=79–82 |doi=10.1023/a:1007178924408 |pmid=11189747 |s2cid=24242933 }}</ref> in which the [[Chemistry:Alkene|alkene]] group of caryophyllene has become an [[Chemistry:Epoxide|epoxide]], is the component responsible for cannabis identification by drug-sniffing dogs<ref>{{cite journal |last1=Russo |first1=Ethan B |title=Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects: Phytocannabinoid-terpenoid entourage effects |journal=British Journal of Pharmacology |date=August 2011 |volume=163 |issue=7 |pages=1344–1364 |doi=10.1111/j.1476-5381.2011.01238.x |pmid=21749363 |pmc=3165946 }}</ref><ref>{{cite journal | last1 = Stahl | first1 = E. | last2 = Kunde | first2 = R. | year = 1973 | title = Die Leitsubstanzen der Haschisch-Suchhunde | trans-title = The tracing substances of hashish search dogs | language = de | journal = Kriminalistik | volume = 27 | pages = 385–389 }}</ref> and is also an approved food additive, often as flavoring.<ref name="accessdata.fda.gov"/> Unlike beta-caryophyllene itself, caryophyllene oxide does not have cannabinoid activity.

==Natural sources==
The approximate quantity of caryophyllene in the [[Chemistry:Essential oil|essential oil]] of each source is given in square brackets (''[ ]''):
*[[Biology:Cannabis|Cannabis]] (''[[Biology:Cannabis sativa|Cannabis sativa]]'') [3.8–37.5% of [[Chemistry:Cannabis flower essential oil|cannabis flower essential oil]]]<ref>{{cite web |first1=V. |last1=Mediavilla |first2=S. |last2=Steinemann |url=http://www.internationalhempassociation.org/jiha/jiha4208.html |title=Essential oil of ''Cannabis sativa'' L. strains |publisher=International Hemp Association |access-date=11 July 2008}}</ref>
*Black caraway (''Carum nigrum'') [7.8%]<ref name="pmid16390196">{{cite journal |last1=Singh |first1=G. |last2=Marimuthu |first2=P. |last3=De Heluani |first3=C. S. |last4=Catalan |first4=C. A. |title=Antioxidant and biocidal activities of ''Carum nigrum'' (seed) essential oil, oleoresin, and their selected components |journal=Journal of Agricultural and Food Chemistry |volume=54 |issue=1 |pages=174–181 |date=January 2006 |pmid=16390196 |doi=10.1021/jf0518610 |hdl=11336/99544 |hdl-access=free }}</ref>
*[[Biology:Clove|Clove]]s (''Syzygium aromaticum'')<ref name="pmid11482764"/> [1.7–19.5% of clove bud essential oil]<ref>{{cite journal |last1=Alma |first1=M. Hakki |last2=Ertaş |first2=Murat |last3=Nitz |first3=Siegfrie |last4=Kollmannsberger |first4=Hubert |title=Chemical composition and content of essential oil from the bud of cultivated Turkish clove (Syzygium aromaticum L.) |journal=BioResources |date=23 May 2007 |volume=2 |issue=2 |pages=265–269 |doi=10.15376/biores.2.2.265-269 |doi-access=free }}</ref>
*[[Biology:Hops|Hops]] (''[[Biology:Humulus lupulus|Humulus lupulus]]'')<ref>{{cite journal |last1=Wang |first1=Guodong |last2=Tian |first2=Li |last3=Aziz |first3=Naveed |last4=Broun |first4=Pierre |last5=Dai |first5=Xinbin |last6=He |first6=Ji |last7=King |first7=Andrew |last8=Zhao |first8=Patrick X. |last9=Dixon |first9=Richard A. |title=Terpene Biosynthesis in Glandular Trichomes of Hop |journal=Plant Physiology |date=6 November 2008 |volume=148 |issue=3 |pages=1254–1266 |doi=10.1104/pp.108.125187 |pmid=18775972 |pmc=2577278 }}</ref> [5.1–14.5%]<ref name="issn02357216">{{cite journal|last1=Bernotienë|first1=G.|last2=Nivinskienë|first2=O.|last3=Butkienë|first3=R.|last4=Mockutë|first4=D.|year=2004|title=Chemical composition of essential oils of hops (''Humulus lupulus'' L.) growing wild in Auktaitija|journal=Chemija|volume=4|series=2|pages=31–36|url=http://www.elibrary.lt/resursai/LMA/Chemija/C-31.pdf|access-date=September 6, 2010|archive-date=March 7, 2023|archive-url=https://web.archive.org/web/20230307193722/http://www.elibrary.lt/resursai/LMA/Chemija/C-31.pdf|url-status=dead}}</ref>
*[[Biology:Basil|Basil]] (''[[Biology:Ocimum|Ocimum]]'' spp.)<ref name="pmid18095647">{{cite journal |last1=Zheljazkov |first1=V. D. |last2=Cantrell |first2=C. L. |last3=Tekwani |first3=B. |last4=Khan |first4=S. I. |title=Content, composition, and bioactivity of the essential oils of three basil genotypes as a function of harvesting |journal=Journal of Agricultural and Food Chemistry |volume=56 |issue=2 |pages=380–5 |date=January 2008 |pmid=18095647 |doi=10.1021/jf0725629 }}</ref> [5.3–10.5% ''[[Biology:Ocimum gratissimum|O. gratissimum]]''; 4.0–19.8% ''O. micranthum'']<ref name="issn14246376">{{cite journal |last1=Vasconcelos Silva |first1=M. G. |last2=Abreu Matos |first2=F. J. |last3=Oliveira Lopes |first3=P. R. |last4=Oliveira Silva |first4=F. |last5=Tavares Holanda |first5=M. |editor1-first=G. M. |editor1-last=Cragg |editor2-first=V. S. |editor2-last=Bolzani|editor3-first=G. S. R. S. |editor3-last=Rao |date=August 2, 2004 |title=Composition of essential oils from three ''Ocimum'' species obtained by steam and microwave distillation and supercritical CO<sub>2</sub> extraction |journal=Arkivoc |volume=2004 |issue=6 |pages=66–71 |doi=10.3998/ark.5550190.0005.609 |doi-access=free |hdl=2027/spo.5550190.0005.609 |hdl-access=free }}</ref>
*[[Biology:Oregano|Oregano]] (''Origanum vulgare'')<ref name="pmid17268981">{{cite journal |vauthors=Harvala C, Menounos P, Argyriadou N |title=Essential oil from ''Origanum dictamnus'' |journal=Planta Medica |volume=53 |issue=1 |pages=107–109 |date=February 1987 |pmid=17268981 |doi=10.1055/s-2006-962640 |s2cid=260278580 }}</ref> [4.9–15.7%]<ref name="issn15403580">{{cite journal |last1=Calvo Irabién |first1=L. M. |last2=Yam-Puc |first2=J. A. |last3=Dzib |first3=G. |last4=Escalante Erosa |first4=F. |last5=Peña Rodríguez |first5=L. M. |date=July 2009 |title=Effect of postharvest drying on the composition of Mexican oregano (''Lippia graveolens'') essential oil |journal=Journal of Herbs, Spices & Medicinal Plants |volume=15 |issue=3 |pages=281–287 |doi=10.1080/10496470903379001 |s2cid=86208062 }}</ref><ref>{{cite journal | pmid = 11336262 | volume=57 | issue=1 | title=The essential oil of ''Origanum vulgare'' L. ssp. ''vulgare'' growing wild in Vilnius district (Lithuania) | date=May 2001 | journal=Phytochemistry | pages=65–69 | doi=10.1016/s0031-9422(00)00474-x| last1=Mockutė | first1=D. | last2=Bernotienė | first2=G. | last3=Judžentienė | first3=A. | bibcode=2001PChem..57...65M }}</ref>
*[[Biology:Black pepper|Black pepper]] (''Piper nigrum'') [7.29%]<ref name="pmid12462618"/>
*[[Biology:Lavandula angustifolia|Lavender]] (''Lavandula angustifolia'') [4.62–7.55% of [[Chemistry:Lavender oil|lavender oil]]]<ref>{{cite journal | last1 = Prashar | first1 = A. | last2 = Locke | first2 = I. C. | last3 = Evans | first3 = C. S. | year = 2004 | title = Cytotoxicity of lavender oil and its major components to human skin cells | journal = Cell Proliferation | volume = 37 | issue = 3| pages = 221–229 | doi=10.1111/j.1365-2184.2004.00307.x | pmid=15144499| pmc = 6496511 }}</ref><ref>{{cite journal|last1=Umezu|first1=T.|last2=Nagano|first2=K.|last3=Ito|first3=H.|last4=Kosakai|first4=K.|last5=Sakaniwa|first5=M.|last6=Morita|first6=M.|title=Anticonflict effects of lavender oil and identification of its active constituents|journal=Pharmacology Biochemistry and Behavior|date=December 2006|volume=85|issue=4|pages=713–721|doi=10.1016/j.pbb.2006.10.026|pmid=17173962|s2cid=21779233}}</ref>
*[[Biology:Rosemary|Rosemary]] (''Rosmarinus officinalis'')<ref name="pmid18670820">{{cite journal |last1=Ormeño |first1=E. |last2=Baldy |first2=V. |last3=Ballini |first3=C. |last4=Fernández |first4=C. |title=Production and diversity of volatile terpenes from plants on calcareous and siliceous soils: effect of soil nutrients |journal=Journal of Chemical Ecology |volume=34 |issue=9 |pages=1219–1229 |date=September 2008 |pmid=18670820 |doi=10.1007/s10886-008-9515-2 |bibcode=2008JCEco..34.1219O |s2cid=28717342 }}</ref> [0.1–8.3%]{{citation needed|date=May 2019}}
*True cinnamon (''Cinnamomum verum'') [6.9–11.1%]<ref>{{cite journal |last1=Kaul |first1=Pran N |last2=Bhattacharya |first2=Arun K |last3=Rajeswara Rao |first3=Bhaskaruni R |last4=Syamasundar |first4=Kodakandla V |last5=Ramesh |first5=Srinivasaiyer |title=Volatile constituents of essential oils isolated from different parts of cinnamon (''Cinnamomum zeylanicum'' Blume) |journal=Journal of the Science of Food and Agriculture |date=1 January 2003 |volume=83 |issue=1 |pages=53–55 |doi=10.1002/jsfa.1277 |bibcode=2003JSFA...83...53K }}</ref>
*Malabathrum (''[[Biology:Cinnamomum tamala|Cinnamomum tamala]]'') [25.3%]<ref>{{cite journal |last1=Ahmed |first1=Aftab |last2=Choudhary |first2=M. Iqbal |last3=Farooq |first3=Afgan |last4=Demirci |first4=Betül |last5=Demirci |first5=Fatih |last6=Başer |first6=K. Hüsnü Can |title=Essential oil constituents of the spice ''Cinnamomum tamala'' (Ham.) Nees & Eberm |journal=Flavour and Fragrance Journal |date=2000 |volume=15 |issue=6 |pages=388–390 |doi=10.1002/1099-1026(200011/12)15:6<388::AID-FFJ928>3.0.CO;2-F |doi-access=free }}</ref>
*[[Biology:Cananga odorata|Ylang-ylang]] (''Cananga odorata'')  [3.1–10.7%]
*[[Biology:Copaiba|Copaiba]] oil (''[[Biology:Copaifera|Copaifera]]'')<ref>{{cite journal |last1=Leandro |first1=Lidiam Maia |last2=de Sousa Vargas |first2=Fabiano |last3=Barbosa |first3=Paula Cristina Souza |last4=Neves |first4=Jamilly Kelly Oliveira |last5=da Silva |first5=José Alexsandro |last6=da Veiga-Junior |first6=Valdir Florêncio |title=Chemistry and Biological Activities of Terpenoids from Copaiba (Copaifera spp.) Oleoresins |journal=Molecules |date=30 March 2012 |volume=17 |issue=4 |pages=3866–3889 |doi=10.3390/molecules17043866 |pmid=22466849 |pmc=6269112 |doi-access=free }}</ref><ref>{{cite journal |last1=Sousa |first1=João Paulo B. |last2=Brancalion |first2=Ana P.S. |last3=Souza |first3=Ariana B. |last4=Turatti |first4=Izabel C.C. |last5=Ambrósio |first5=Sérgio R. |last6=Furtado |first6=Niege A.J.C. |last7=Lopes |first7=Norberto P. |last8=Bastos |first8=Jairo K. |title=Validation of a gas chromatographic method to quantify sesquiterpenes in copaiba oils |journal=Journal of Pharmaceutical and Biomedical Analysis |date=March 2011 |volume=54 |issue=4 |pages=653–659 |doi=10.1016/j.jpba.2010.10.006 |pmid=21095089 |doi-access=free }}</ref>

=== Biosynthesis ===
Caryophyllene is a common [[Chemistry:Sesquiterpene|sesquiterpene]] among plant species. It is biosynthesized from the common [[Biology:Terpene|terpene]] precursors [[Chemistry:Dimethylallyl pyrophosphate|dimethylallyl pyrophosphate]] (DMAPP) and [[Chemistry:Isopentenyl pyrophosphate|isopentenyl pyrophosphate]] (IPP). First, single units of DMAPP and IPP are reacted via an [[Chemistry:SN1 reaction|S<sub>N</sub>1]]-type reaction with the loss of [[Chemistry:Pyrophosphate|pyrophosphate]], catalyzed by the enzyme GPPS2, to form [[Chemistry:Geranyl pyrophosphate|geranyl pyrophosphate]] (GPP). This further reacts with a second unit of IPP, also via an [[Chemistry:SN1 reaction|S<sub>N</sub>1-type reaction]] catalyzed by the enzyme IspA, to form [[Chemistry:Farnesyl pyrophosphate|farnesyl pyrophosphate]] (FPP). Finally, FPP undergoes QHS1 enzyme-catalyzed intramolecular cyclization to form caryophyllene.<ref>{{cite journal |last1=Yang |first1=Jianming |last2=Li |first2=Zhengfeng |last3=Guo |first3=Lizhong |last4=Du |first4=Juan |last5=Bae |first5=Hyeun-Jong |title=Biosynthesis of β-caryophyllene, a novel terpene-based high-density biofuel precursor, using engineered ''Escherichia coli'' |journal=Renewable Energy |date=December 2016 |volume=99 |pages=216–223 |doi=10.1016/j.renene.2016.06.061 }}</ref>

:[[File:Wiki Project - Caryophyllene 1.svg|thumb|left|800px|Biosynthesis of caryophyllene]]{{clear-left}}

==Compendial status==
* [[Chemistry:Food Chemicals Codex|Food Chemicals Codex]]<ref name=rffs>{{cite web
 |last=The United States Pharmacopeial Convention 
 |title=Revisions to FCC, First Supplement 
 |url=http://www.usp.org/fcc/FCC61SBallotResultsWebPostingReport01.html 
 |access-date=29 June 2009 
 |url-status=dead 
 |archive-url=https://web.archive.org/web/20100705122159/http://www.usp.org/fcc/FCC61SBallotResultsWebPostingReport01.html 
 |archive-date=5 July 2010 
}}</ref><ref name=cs>{{cite web
 | author = Therapeutic Goods Administration
 | title = Chemical substances
 | url = http://www.tga.gov.au/docs/pdf/aan/aanchem.pdf
 | access-date = 29 June 2009
 | archive-url = https://web.archive.org/web/20110422122647/http://www.tga.gov.au/docs/pdf/aan/aanchem.pdf
 | archive-date = 22 April 2011
 | url-status = dead
 }}</ref>

==Notes and references==
{{Reflist|2}}

{{Cannabinoids}}
{{Cannabinoidergics}}


[[Category:Flavors]]
[[Category:Cannabinoids]]
[[Category:Sesquiterpenes]]
[[Category:Alkene derivatives]]
[[Category:Hydrocarbons]]
[[Category:CB2 receptor agonists]]
[[Category:Cyclobutanes]]

{{Sourceattribution|Caryophyllene}}