Journal:The cannabis terpenes - Revision history

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	[[Category:~~CannaQAwiki~~ journal articles on cannabis terpenes]]		[[Category:LIMSwiki journal articles on cannabis terpenes]]

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	{\| border="0" cellpadding="5" cellspacing="0" width="850px"		{\| border="0" cellpadding="5" cellspacing="0" width="850px"
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	\| style="background-color:white; padding-left:10px; padding-right:10px;" \|<blockquote>'''Fig. 1''' The evolution of the Chinese characters of the word “''Cannabis sativa''” or “Ma” ('''a'''), and the place of origin of the ~~cannabis~~ plant in the southern Caspian sea near Iran ('''b''')</blockquote>		\| style="background-color:white; padding-left:10px; padding-right:10px;" \|<blockquote>'''Fig. 1''' The evolution of the Chinese characters of the word “''Cannabis sativa''” or “Ma” ('''a'''), and the place of origin of the ''Cannabis'' plant in the southern Caspian sea near Iran ('''b''')</blockquote>
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	==Taxonomy and localization of cannabis terpenes==		==Taxonomy and localization of cannabis terpenes==
	Cannabis belongs to the small family of flowering plants known as [[Cannabaceae]], which includes hop and Celtis berry. It is a dicotylate angiosperm that gives incomplete (lacking of petals) and also imperfect flower types with the separated sexual organs. The flower bears only pistils, known as pistillate flowers (or female flowers), and those with only the stamens are called staminate (or male flowers). In nature, ''Cannabis'' produces either male or female flowers (dioecious); however, under short-day conditions, it may give both male and female flowers or monoecious. Plants are able to grow as high as three meters, or smaller depending on the varieties and the conditions of growth. The flowers often initiate as groups of flowers or as an axillary bud (Figure 2a and 2b). The stem consists of the outermost layer of the epidermis, which is thin and coarse, and the primary and secondary layers that provide the better fiber quality. The innermost, which is the lignified secondary blast fiber, give the best fiber quality.<ref>{{Citation \|last=Horne \|first=Matthew R.L. \|date=2020 \|title=Bast fibres \|url=https://linkinghub.elsevier.com/retrieve/pii/B9780128183984000074 \|work=Handbook of Natural Fibres \|language=en \|publisher=Elsevier \|pages=163–196 \|doi=10.1016/b978-0-12-818398-4.00007-4 \|isbn=978-0-12-818398-4 \|access-date=}}</ref><ref>{{Cite journal \|last=Réquilé \|first=Samuel \|last2=Le Duigou \|first2=Antoine \|last3=Bourmaud \|first3=Alain \|last4=Baley \|first4=Christophe \|date=2018-11 \|title=Peeling experiments for hemp retting characterization targeting biocomposites \|url=https://linkinghub.elsevier.com/retrieve/pii/S0926669018306125 \|journal=Industrial Crops and Products \|language=en \|volume=123 \|pages=573–580 \|doi=10.1016/j.indcrop.2018.07.012}}</ref>		''Cannabis'' belongs to the small family of flowering plants known as [[Cannabaceae]], which includes hop and Celtis berry. It is a dicotylate angiosperm that gives incomplete (lacking of petals) and also imperfect flower types with the separated sexual organs. The flower bears only pistils, known as pistillate flowers (or female flowers), and those with only the stamens are called staminate (or male flowers). In nature, ''Cannabis'' produces either male or female flowers (dioecious); however, under short-day conditions, it may give both male and female flowers or monoecious. Plants are able to grow as high as three meters, or smaller depending on the varieties and the conditions of growth. The flowers often initiate as groups of flowers or as an axillary bud (Figure 2a and 2b). The stem consists of the outermost layer of the epidermis, which is thin and coarse, and the primary and secondary layers that provide the better fiber quality. The innermost, which is the lignified secondary blast fiber, give the best fiber quality.<ref>{{Citation \|last=Horne \|first=Matthew R.L. \|date=2020 \|title=Bast fibres \|url=https://linkinghub.elsevier.com/retrieve/pii/B9780128183984000074 \|work=Handbook of Natural Fibres \|language=en \|publisher=Elsevier \|pages=163–196 \|doi=10.1016/b978-0-12-818398-4.00007-4 \|isbn=978-0-12-818398-4 \|access-date=}}</ref><ref>{{Cite journal \|last=Réquilé \|first=Samuel \|last2=Le Duigou \|first2=Antoine \|last3=Bourmaud \|first3=Alain \|last4=Baley \|first4=Christophe \|date=2018-11 \|title=Peeling experiments for hemp retting characterization targeting biocomposites \|url=https://linkinghub.elsevier.com/retrieve/pii/S0926669018306125 \|journal=Industrial Crops and Products \|language=en \|volume=123 \|pages=573–580 \|doi=10.1016/j.indcrop.2018.07.012}}</ref>


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	===Cannabis sesquiterpenes===		===Cannabis sesquiterpenes===
	β-Caryophyllene, with a spicy (pepper) aroma, is the most available sesquiterpenoid in ~~cannabis~~ plants and extracts, especially after decarboxylation. It is an agonist with the CB2 receptor, without psychoactivity.<ref name=":11" /> It is also responsible for the anti-inflammatory effects of cannabis.<ref name=":12" /> This sesquiterpene is also proven to give gastroprotective, analgesic, anticancerogenic, antifungal, antibacterial, antidepressant, anti-inflammatory, antiproliferative, antioxidant, anxiolytic, analgesic, and neuroprotective effects.<ref name=":4" /> Caryophyllene oxide, which gives off a lemon balm-like scent, is proven to have anti-fungal and insecticidal properties.<ref name=":3" />		β-Caryophyllene, with a spicy (pepper) aroma, is the most available sesquiterpenoid in ''Cannabis'' plants and extracts, especially after decarboxylation. It is an agonist with the CB2 receptor, without psychoactivity.<ref name=":11" /> It is also responsible for the anti-inflammatory effects of cannabis.<ref name=":12" /> This sesquiterpene is also proven to give gastroprotective, analgesic, anticancerogenic, antifungal, antibacterial, antidepressant, anti-inflammatory, antiproliferative, antioxidant, anxiolytic, analgesic, and neuroprotective effects.<ref name=":4" /> Caryophyllene oxide, which gives off a lemon balm-like scent, is proven to have anti-fungal and insecticidal properties.<ref name=":3" />

	==The cannabis chemovars==		==The cannabis chemovars==

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	==Terpene biosynthesis in cannabis==		==Terpene biosynthesis in cannabis==
	The energy required for plant growth and development derives from photosynthesis, respiration, and transpiration with O<sub>2</sub>, CO<sub>2</sub>, nutrients, and water. The energy is restored in the form of primary chemical ingredients that plants later exploit. These primary metabolites include carbohydrates, lipids, proteins, and nucleic acids. However, during cycles of growth and reproduction, plants might be challenged by stresses including hard environmental conditions, pests, and herbivores. Plants then produce different groups of compounds called secondary metabolites that are used as defenses to those challenges. For example, it can produce compounds that draw in pollinators, including birds to help them in the fertilization process or seed dispersion.<ref>{{Cite journal \|last=Schwachtje \|first=Jens \|last2=Baldwin \|first2=Ian T. \|date=2008-03 \|title=Why does herbivore attack reconfigure primary metabolism? \|url=https://pubmed.ncbi.nlm.nih.gov/18316639 \|journal=Plant Physiology \|volume=146 \|issue=3 \|pages=845–851 \|doi=10.1104/pp.107.112490 \|issn=0032-0889 \|pmc=2259057 \|pmid=18316639}}</ref> These compounds are produced in different forms and are exploited for their biological functionalities<ref>{{Citation \|last=Sommano \|first=Sarana \|date=2013-11-30 \|editor-last=P. M \|editor-first=Visakh \|editor2-last=Iturriaga \|editor2-first=Laura B. \|editor3-last=Ribotta \|editor3-first=Pablo Daniel \|title=Effect of Food Processing on Bioactive Compounds \|url=https://onlinelibrary.wiley.com/doi/10.1002/9781118865606.ch11 \|work=Advances in Food Science and Nutrition \|language=en \|publisher=John Wiley & Sons, Inc. \|place=Hoboken, NJ, USA \|pages=361–390 \|doi=10.1002/9781118865606.ch11 \|isbn=978-1-118-86560-6 \|access-date=2021-10-26}}</ref>; for example, alkaloids such as morphine and codeine in opium give psychoactive and pain relief activity to mammals. Phenolics and flavonoids found in the skins of fruits and berries possess antioxidant activity.<ref>{{Cite journal \|last=Sommano \|first=Sarana \|last2=Caffin \|first2=Nola \|last3=Kerven \|first3=Graham \|date=2013-08-18 \|title=Screening for Antioxidant Activity, Phenolic Content, and Flavonoids from Australian Native Food Plants \|url=http://www.tandfonline.com/doi/abs/10.1080/10942912.2011.580485 \|journal=International Journal of Food Properties \|language=en \|volume=16 \|issue=6 \|pages=1394–1406 \|doi=10.1080/10942912.2011.580485 \|issn=1094-2912}}</ref> Sulfur containing compounds such as allicin in garlic can be used to reduce lipoglycerides in the blood and also have the ability to stimulate appetite.<ref>{{Cite journal \|last=Sunanta \|first=Piyachat \|last2=Chung \|first2=Hsiao‐Hang \|last3=Kunasakdakul \|first3=Kaewalin \|last4=Ruksiriwanich \|first4=Warintorn \|last5=Jantrawut \|first5=Pensak \|last6=Hongsibsong \|first6=Surat \|last7=Sommano \|first7=Sarana Rose \|date=2020-08 \|title=Genomic relationship and physiochemical properties among raw materials used for Thai black garlic processing \|url=https://onlinelibrary.wiley.com/doi/10.1002/fsn3.1762 \|journal=Food Science & Nutrition \|language=en \|volume=8 \|issue=8 \|pages=4534–4545 \|doi=10.1002/fsn3.1762 \|issn=2048-7177 \|pmc=PMC7455981 \|pmid=32884733}}</ref> Saponin glycoside in soap nuts can be used as a surfactant<ref>{{Cite journal \|last=Wisetkomolmat \|first=Jiratchaya \|last2=Suppakittpaisarn \|first2=Pongsakorn \|last3=Sommano \|first3=Sarana Rose \|date=2019-01-03 \|title=Detergent Plants of Northern Thailand: Potential Sources of Natural Saponins \|url=https://www.mdpi.com/2079-9276/8/1/10 \|journal=Resources \|language=en \|volume=8 \|issue=1 \|pages=10 \|doi=10.3390/resources8010010 \|issn=2079-9276}}</ref>, and finally, the terpenoids, which are main ingredients found in plants containing essential oils<ref>{{Cite journal \|last=Tangpao \|first=Tibet \|last2=Chung \|first2=Hsiao-Hang \|last3=Sommano \|first3=Sarana \|date=2018-10-24 \|title=Aromatic Profiles of Essential Oils from Five Commonly Used Thai Basils \|url=http://www.mdpi.com/2304-8158/7/11/175 \|journal=Foods \|language=en \|volume=7 \|issue=11 \|pages=175 \|doi=10.3390/foods7110175 \|issn=2304-8158 \|pmc=PMC6262289 \|pmid=30352978}}</ref>, are used as food additives, and some depict psychoactive ability and aroma characteristics such as those found in cannabis.		The energy required for plant growth and development derives from photosynthesis, respiration, and transpiration with O<sub>2</sub>, CO<sub>2</sub>, nutrients, and water. The energy is restored in the form of primary chemical ingredients that plants later exploit. These primary metabolites include carbohydrates, lipids, proteins, and nucleic acids. However, during cycles of growth and reproduction, plants might be challenged by stresses including hard environmental conditions, pests, and herbivores. Plants then produce different groups of compounds called secondary metabolites that are used as defenses to those challenges. For example, it can produce compounds that draw in pollinators, including birds to help them in the fertilization process or seed dispersion.<ref>{{Cite journal \|last=Schwachtje \|first=Jens \|last2=Baldwin \|first2=Ian T. \|date=2008-03 \|title=Why does herbivore attack reconfigure primary metabolism? \|url=https://pubmed.ncbi.nlm.nih.gov/18316639 \|journal=Plant Physiology \|volume=146 \|issue=3 \|pages=845–851 \|doi=10.1104/pp.107.112490 \|issn=0032-0889 \|pmc=2259057 \|pmid=18316639}}</ref> These compounds are produced in different forms and are exploited for their biological functionalities<ref>{{Citation \|last=Sommano \|first=Sarana \|date=2013-11-30 \|editor-last=P. M \|editor-first=Visakh \|editor2-last=Iturriaga \|editor2-first=Laura B. \|editor3-last=Ribotta \|editor3-first=Pablo Daniel \|title=Effect of Food Processing on Bioactive Compounds \|url=https://onlinelibrary.wiley.com/doi/10.1002/9781118865606.ch11 \|work=Advances in Food Science and Nutrition \|language=en \|publisher=John Wiley & Sons, Inc. \|place=Hoboken, NJ, USA \|pages=361–390 \|doi=10.1002/9781118865606.ch11 \|isbn=978-1-118-86560-6 \|access-date=2021-10-26}}</ref>; for example, alkaloids such as morphine and codeine in opium give psychoactive and pain relief activity to mammals. Phenolics and flavonoids found in the skins of fruits and berries possess antioxidant activity.<ref>{{Cite journal \|last=Sommano \|first=Sarana \|last2=Caffin \|first2=Nola \|last3=Kerven \|first3=Graham \|date=2013-08-18 \|title=Screening for Antioxidant Activity, Phenolic Content, and Flavonoids from Australian Native Food Plants \|url=http://www.tandfonline.com/doi/abs/10.1080/10942912.2011.580485 \|journal=International Journal of Food Properties \|language=en \|volume=16 \|issue=6 \|pages=1394–1406 \|doi=10.1080/10942912.2011.580485 \|issn=1094-2912}}</ref> Sulfur containing compounds such as allicin in garlic can be used to reduce lipoglycerides in the blood and also have the ability to stimulate appetite.<ref>{{Cite journal \|last=Sunanta \|first=Piyachat \|last2=Chung \|first2=Hsiao‐Hang \|last3=Kunasakdakul \|first3=Kaewalin \|last4=Ruksiriwanich \|first4=Warintorn \|last5=Jantrawut \|first5=Pensak \|last6=Hongsibsong \|first6=Surat \|last7=Sommano \|first7=Sarana Rose \|date=2020-08 \|title=Genomic relationship and physiochemical properties among raw materials used for Thai black garlic processing \|url=https://onlinelibrary.wiley.com/doi/10.1002/fsn3.1762 \|journal=Food Science & Nutrition \|language=en \|volume=8 \|issue=8 \|pages=4534–4545 \|doi=10.1002/fsn3.1762 \|issn=2048-7177 \|pmc=PMC7455981 \|pmid=32884733}}</ref> Saponin glycoside in soap nuts can be used as a surfactant<ref>{{Cite journal \|last=Wisetkomolmat \|first=Jiratchaya \|last2=Suppakittpaisarn \|first2=Pongsakorn \|last3=Sommano \|first3=Sarana Rose \|date=2019-01-03 \|title=Detergent Plants of Northern Thailand: Potential Sources of Natural Saponins \|url=https://www.mdpi.com/2079-9276/8/1/10 \|journal=Resources \|language=en \|volume=8 \|issue=1 \|pages=10 \|doi=10.3390/resources8010010 \|issn=2079-9276}}</ref>, and finally, the terpenoids, which are main ingredients found in plants containing essential oils<ref name=":10">{{Cite journal \|last=Tangpao \|first=Tibet \|last2=Chung \|first2=Hsiao-Hang \|last3=Sommano \|first3=Sarana \|date=2018-10-24 \|title=Aromatic Profiles of Essential Oils from Five Commonly Used Thai Basils \|url=http://www.mdpi.com/2304-8158/7/11/175 \|journal=Foods \|language=en \|volume=7 \|issue=11 \|pages=175 \|doi=10.3390/foods7110175 \|issn=2304-8158 \|pmc=PMC6262289 \|pmid=30352978}}</ref>, are used as food additives, and some depict psychoactive ability and aroma characteristics such as those found in cannabis.

	Terpenes are hydrocarbons with small isoprene units linked to one another to form chains, while terpenoids are oxygen-containing terpenes. Four types of terpenes/terpenoids are usually found in the ''Cannabis'' plant<ref name=":4" />:		Terpenes are hydrocarbons with small isoprene units linked to one another to form chains, while terpenoids are oxygen-containing terpenes. Four types of terpenes/terpenoids are usually found in the ''Cannabis'' plant<ref name=":4" />:
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	*triterpenes (30C) of six isoprene units		*triterpenes (30C) of six isoprene units

	To date, more than 200 volatiles have been reported from the different cannabis genotypes, of which 58 monoterpenes and 38 sesquiterpenes have been characterized.<ref>{{Cite journal \|last=Ross \|first=Samir A. \|last2=ElSohly \|first2=Mahmoud A. \|date=1996-01-01 \|title=The Volatile Oil Composition of Fresh and Air-Dried Buds of Cannabis sativa \|url=https://pubs.acs.org/doi/10.1021/np960004a \|journal=Journal of Natural Products \|language=en \|volume=59 \|issue=1 \|pages=49–51 \|doi=10.1021/np960004a \|issn=0163-3864}}</ref><ref>{{Cite journal \|last=Turner \|first=C. E. \|last2=Elsohly \|first2=M. A. \|last3=Boeren \|first3=E. G. \|date=1980-03 \|title=Constituents of Cannabis sativa L. XVII. A review of the natural constituents \|url=https://pubmed.ncbi.nlm.nih.gov/6991645 \|journal=Journal of Natural Products \|volume=43 \|issue=2 \|pages=169–234 \|doi=10.1021/np50008a001 \|issn=0163-3864 \|pmid=6991645}}</ref><ref>{{Cite journal \|last=Wanas \|first=Amira S. \|last2=Radwan \|first2=Mohamed M. \|last3=Chandra \|first3=Suman \|last4=Lata \|first4=Hemant \|last5=Mehmedic \|first5=Zlatko \|last6=Ali \|first6=Abbas \|last7=Baser \|first7=Khc \|last8=Demirci \|first8=Betul \|last9=ElSohly \|first9=Mahmoud A. \|date=2020-05 \|title=Chemical Composition of Volatile Oils of Fresh and Air-Dried Buds of Cannabis c hemovars, Their Insecticidal and Repellent Activities \|url=http://journals.sagepub.com/doi/10.1177/1934578X20926729 \|journal=Natural Product Communications \|language=en \|volume=15 \|issue=5 \|pages=1934578X2092672 \|doi=10.1177/1934578X20926729 \|issn=1934-578X}}</ref><ref>{{Cite journal \|last=Rice \|first=Somchai \|last2=Koziel \|first2=Jacek A. \|date=2015-12-10 \|editor-last=Glendinning \|editor-first=John I. \|title=Characterizing the Smell of Marijuana by Odor Impact of Volatile Compounds: An Application of Simultaneous Chemical and Sensory Analysis \|url=https://dx.plos.org/10.1371/journal.pone.0144160 \|journal=PLOS ONE \|language=en \|volume=10 \|issue=12 \|pages=e0144160 \|doi=10.1371/journal.pone.0144160 \|issn=1932-6203 \|pmc=PMC4684335 \|pmid=26657499}}</ref> Figure 5a illustrates a [[Chromatography\|chromatogram]] of the terpene extract from the floral tissue of cannabis. Among others, the major monoterpene components are [[limonene]], [[Myrcene\|β-myrcene]], [[Pinene\|α-pinene]], and [[linalool]], with traces of α-terpinolene and [[Ocimene\|tran-ocimene]]<ref>{{Cite journal \|last=Ternelli \|first=Marco \|last2=Brighenti \|first2=Virginia \|last3=Anceschi \|first3=Lisa \|last4=Poto \|first4=Massimiliano \|last5=Bertelli \|first5=Davide \|last6=Licata \|first6=Manuela \|last7=Pellati \|first7=Federica \|date=2020-07-15 \|title=Innovative methods for the preparation of medical Cannabis oils with a high content of both cannabinoids and terpenes \|url=https://pubmed.ncbi.nlm.nih.gov/32334134 \|journal=Journal of Pharmaceutical and Biomedical Analysis \|volume=186 \|pages=113296 \|doi=10.1016/j.jpba.2020.113296 \|issn=1873-264X \|pmid=32334134}}</ref><ref>{{Cite journal \|last=Wang \|first=Chi-Tsan \|last2=Ashworth \|first2=Kirsti \|last3=Wiedinmyer \|first3=Christine \|last4=Ortega \|first4=John \|last5=Harley \|first5=Peter C. \|last6=Rasool \|first6=Quazi Z. \|last7=Vizuete \|first7=William \|date=2020-07 \|title=Ambient measurements of monoterpenes near Cannabis cultivation facilities in Denver, Colorado \|url=https://linkinghub.elsevier.com/retrieve/pii/S1352231020302478 \|journal=Atmospheric Environment \|language=en \|volume=232 \|pages=117510 \|doi=10.1016/j.atmosenv.2020.117510}}</ref> (Figure 5b), while predominate sesquiterpenes are [[Caryophyllene\|E-caryophyllene]], caryophyllene oxide, E-β-farnesene, and β-caryophyllene.<ref>{{Cite journal \|last=Abdollahi \|first=Mahnaz \|last2=Sefidkon \|first2=Fatemeh \|last3=Calagari \|first3=Mohsen \|last4=Mousavi \|first4=Amir \|last5=Mahomoodally \|first5=M. Fawzi \|date=2020-11 \|title=Impact of four hemp (Cannabis sativa L.) varieties and stage of plant growth on yield and composition of essential oils \|url=https://linkinghub.elsevier.com/retrieve/pii/S092666902030710X \|journal=Industrial Crops and Products \|language=en \|volume=155 \|pages=112793 \|doi=10.1016/j.indcrop.2020.112793}}</ref> The cannabinoids are biologically synthesized from diterpene structures to form phenol terpenoids, which account for almost a quarter of all metabolites.<ref name=":4" /> Thus, the combination of the terpenes provides the unique aromas to different strains.		To date, more than 200 volatiles have been reported from the different cannabis genotypes, of which 58 monoterpenes and 38 sesquiterpenes have been characterized.<ref>{{Cite journal \|last=Ross \|first=Samir A. \|last2=ElSohly \|first2=Mahmoud A. \|date=1996-01-01 \|title=The Volatile Oil Composition of Fresh and Air-Dried Buds of Cannabis sativa \|url=https://pubs.acs.org/doi/10.1021/np960004a \|journal=Journal of Natural Products \|language=en \|volume=59 \|issue=1 \|pages=49–51 \|doi=10.1021/np960004a \|issn=0163-3864}}</ref><ref>{{Cite journal \|last=Turner \|first=C. E. \|last2=Elsohly \|first2=M. A. \|last3=Boeren \|first3=E. G. \|date=1980-03 \|title=Constituents of Cannabis sativa L. XVII. A review of the natural constituents \|url=https://pubmed.ncbi.nlm.nih.gov/6991645 \|journal=Journal of Natural Products \|volume=43 \|issue=2 \|pages=169–234 \|doi=10.1021/np50008a001 \|issn=0163-3864 \|pmid=6991645}}</ref><ref name=":11">{{Cite journal \|last=Wanas \|first=Amira S. \|last2=Radwan \|first2=Mohamed M. \|last3=Chandra \|first3=Suman \|last4=Lata \|first4=Hemant \|last5=Mehmedic \|first5=Zlatko \|last6=Ali \|first6=Abbas \|last7=Baser \|first7=Khc \|last8=Demirci \|first8=Betul \|last9=ElSohly \|first9=Mahmoud A. \|date=2020-05 \|title=Chemical Composition of Volatile Oils of Fresh and Air-Dried Buds of Cannabis c hemovars, Their Insecticidal and Repellent Activities \|url=http://journals.sagepub.com/doi/10.1177/1934578X20926729 \|journal=Natural Product Communications \|language=en \|volume=15 \|issue=5 \|pages=1934578X2092672 \|doi=10.1177/1934578X20926729 \|issn=1934-578X}}</ref><ref>{{Cite journal \|last=Rice \|first=Somchai \|last2=Koziel \|first2=Jacek A. \|date=2015-12-10 \|editor-last=Glendinning \|editor-first=John I. \|title=Characterizing the Smell of Marijuana by Odor Impact of Volatile Compounds: An Application of Simultaneous Chemical and Sensory Analysis \|url=https://dx.plos.org/10.1371/journal.pone.0144160 \|journal=PLOS ONE \|language=en \|volume=10 \|issue=12 \|pages=e0144160 \|doi=10.1371/journal.pone.0144160 \|issn=1932-6203 \|pmc=PMC4684335 \|pmid=26657499}}</ref> Figure 5a illustrates a [[Chromatography\|chromatogram]] of the terpene extract from the floral tissue of cannabis. Among others, the major monoterpene components are [[limonene]], [[Myrcene\|β-myrcene]], [[Pinene\|α-pinene]], and [[linalool]], with traces of α-terpinolene and [[Ocimene\|tran-ocimene]]<ref>{{Cite journal \|last=Ternelli \|first=Marco \|last2=Brighenti \|first2=Virginia \|last3=Anceschi \|first3=Lisa \|last4=Poto \|first4=Massimiliano \|last5=Bertelli \|first5=Davide \|last6=Licata \|first6=Manuela \|last7=Pellati \|first7=Federica \|date=2020-07-15 \|title=Innovative methods for the preparation of medical Cannabis oils with a high content of both cannabinoids and terpenes \|url=https://pubmed.ncbi.nlm.nih.gov/32334134 \|journal=Journal of Pharmaceutical and Biomedical Analysis \|volume=186 \|pages=113296 \|doi=10.1016/j.jpba.2020.113296 \|issn=1873-264X \|pmid=32334134}}</ref><ref>{{Cite journal \|last=Wang \|first=Chi-Tsan \|last2=Ashworth \|first2=Kirsti \|last3=Wiedinmyer \|first3=Christine \|last4=Ortega \|first4=John \|last5=Harley \|first5=Peter C. \|last6=Rasool \|first6=Quazi Z. \|last7=Vizuete \|first7=William \|date=2020-07 \|title=Ambient measurements of monoterpenes near Cannabis cultivation facilities in Denver, Colorado \|url=https://linkinghub.elsevier.com/retrieve/pii/S1352231020302478 \|journal=Atmospheric Environment \|language=en \|volume=232 \|pages=117510 \|doi=10.1016/j.atmosenv.2020.117510}}</ref> (Figure 5b), while predominate sesquiterpenes are [[Caryophyllene\|E-caryophyllene]], caryophyllene oxide, E-β-farnesene, and β-caryophyllene.<ref>{{Cite journal \|last=Abdollahi \|first=Mahnaz \|last2=Sefidkon \|first2=Fatemeh \|last3=Calagari \|first3=Mohsen \|last4=Mousavi \|first4=Amir \|last5=Mahomoodally \|first5=M. Fawzi \|date=2020-11 \|title=Impact of four hemp (Cannabis sativa L.) varieties and stage of plant growth on yield and composition of essential oils \|url=https://linkinghub.elsevier.com/retrieve/pii/S092666902030710X \|journal=Industrial Crops and Products \|language=en \|volume=155 \|pages=112793 \|doi=10.1016/j.indcrop.2020.112793}}</ref> The cannabinoids are biologically synthesized from diterpene structures to form phenol terpenoids, which account for almost a quarter of all metabolites.<ref name=":4" /> Thus, the combination of the terpenes provides the unique aromas to different strains.


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	The following subsections discuss the important cannabis terpene groups and their synergistic and functional properties.		The following subsections discuss the important cannabis terpene groups and their synergistic and functional properties.

			===Cannabis monoterpene===
			The monoterpenes α-pinene and β-pinene inhibit the activity of acetylcholinesterase in the brain. Therefore, it is claimed to aid memory and minimize cognitive dysfunction induced by THC intoxication.<ref>{{Cite journal \|last=Miyazawa \|first=Mitsuo \|last2=Yamafuji \|first2=Chikako \|date=2005-03-09 \|title=Inhibition of acetylcholinesterase activity by bicyclic monoterpenoids \|url=https://pubmed.ncbi.nlm.nih.gov/15740071 \|journal=Journal of Agricultural and Food Chemistry \|volume=53 \|issue=5 \|pages=1765–1768 \|doi=10.1021/jf040019b \|issn=0021-8561 \|pmid=15740071}}</ref> The characteristic of pine scent possesses antiseptic activity.<ref name=":10" /><ref name=":12">{{Cite journal \|last=Gaggiotti \|first=Sara \|last2=Palmieri \|first2=Sara \|last3=Della Pelle \|first3=Flavio \|last4=Sergi \|first4=Manuel \|last5=Cichelli \|first5=Angelo \|last6=Mascini \|first6=Marcello \|last7=Compagnone \|first7=Dario \|date=2020-04 \|title=Piezoelectric peptide-hpDNA based electronic nose for the detection of terpenes; Evaluation of the aroma profile in different Cannabis sativa L. (hemp) samples \|url=https://linkinghub.elsevier.com/retrieve/pii/S0925400520300447 \|journal=Sensors and Actuators B: Chemical \|language=en \|volume=308 \|pages=127697 \|doi=10.1016/j.snb.2020.127697}}</ref><ref>{{Cite journal \|last=Sriwichai \|first=Trid \|last2=Sookwong \|first2=Phumon \|last3=Siddiqui \|first3=Mohammed Wasim \|last4=Sommano \|first4=Sarana Rose \|date=2019-07 \|title=Aromatic profiling of Zanthoxylum myriacanthum (makwhaen) essential oils from dried fruits using different initial drying techniques \|url=https://linkinghub.elsevier.com/retrieve/pii/S0926669019301888 \|journal=Industrial Crops and Products \|language=en \|volume=133 \|pages=284–291 \|doi=10.1016/j.indcrop.2019.03.031}}</ref> β-myrcene is known to have the analgesic effect of THC and CBD by stimulating the release of endogenous opioids through the α2-adrenergic receptor dependent mechanism.<ref name=":13">{{Cite journal \|last=Maayah \|first=Zaid H. \|last2=Takahara \|first2=Shingo \|last3=Ferdaoussi \|first3=Mourad \|last4=Dyck \|first4=Jason R.B. \|date=2020-07 \|title=The molecular mechanisms that underpin the biological benefits of full-spectrum cannabis extract in the treatment of neuropathic pain and inflammation \|url=https://linkinghub.elsevier.com/retrieve/pii/S0925443920301162 \|journal=Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease \|language=en \|volume=1866 \|issue=7 \|pages=165771 \|doi=10.1016/j.bbadis.2020.165771}}</ref><ref>{{Cite journal \|last=Rao \|first=V S N \|last2=Menezes \|first2=A M S \|last3=Viana \|first3=G S B \|date=2011-04-12 \|title=Effect of myrcene on nociception in mice \|url=https://academic.oup.com/jpp/article/42/12/877/6164538 \|journal=Journal of Pharmacy and Pharmacology \|language=en \|volume=42 \|issue=12 \|pages=877–878 \|doi=10.1111/j.2042-7158.1990.tb07046.x \|issn=2042-7158}}</ref> Thus, if the level of myrcene is >0.5%, it may result in a “couch lock” effect, while low levels of myrcene (>0.5% myrcene) can produce a higher level of energy.<ref name=":4" /> This compound offers a musky or hop-like fragrance with the functions of antioxidant and anticarcinogens.<ref name=":3" /><ref name=":12" /> Even though it has been postulated that limonene, with its citrus aroma, has a low affinity for cannabinoid receptors, this monoterpene boosts up the level of serotonin and dopamine, thereby inducing the anxiolytic, anti-stress, and sedative effects of CBD.<ref name=":13" /><ref>{{Cite journal \|last=Meschler \|first=J \|date=1999-03 \|title=Thujone Exhibits Low Affinity for Cannabinoid Receptors But Fails to Evoke Cannabimimetic Responses \|url=https://linkinghub.elsevier.com/retrieve/pii/S0091305798001956 \|journal=Pharmacology Biochemistry and Behavior \|volume=62 \|issue=3 \|pages=473–480 \|doi=10.1016/S0091-3057(98)00195-6}}</ref> The floral fragrance of linalool could assist with anxiety through aromatherapy.<ref name=":12" />

			===Cannabis sesquiterpenes===
			β-Caryophyllene, with a spicy (pepper) aroma, is the most available sesquiterpenoid in cannabis plants and extracts, especially after decarboxylation. It is an agonist with the CB2 receptor, without psychoactivity.<ref name=":11" /> It is also responsible for the anti-inflammatory effects of cannabis.<ref name=":12" /> This sesquiterpene is also proven to give gastroprotective, analgesic, anticancerogenic, antifungal, antibacterial, antidepressant, anti-inflammatory, antiproliferative, antioxidant, anxiolytic, analgesic, and neuroprotective effects.<ref name=":4" /> Caryophyllene oxide, which gives off a lemon balm-like scent, is proven to have anti-fungal and insecticidal properties.<ref name=":3" />

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	The most usable part for hemp is the stem in particular, while parts usually with trichomes are the most usable for cannabis. The level of THC is graded as >2% of dry weight, and flowers give a much higher terpene content, which becomes sticky to the touch.<ref name=":5">{{Cite journal \|last=Cai \|first=Changyong \|last2=Yu \|first2=Wang \|last3=Wang \|first3=Chaoyun \|last4=Liu \|first4=Lianglei \|last5=Li \|first5=Fenfang \|last6=Tan \|first6=Zhijian \|date=2019-08 \|title=Green extraction of cannabidiol from industrial hemp (Cannabis sativa L.) using deep eutectic solvents coupled with further enrichment and recovery by macroporous resin \|url=https://linkinghub.elsevier.com/retrieve/pii/S0167732218365899 \|journal=Journal of Molecular Liquids \|language=en \|volume=287 \|pages=110957 \|doi=10.1016/j.molliq.2019.110957}}</ref> Some researchers do not agree with the separation of the two by the chemical compositions. Morphologically, the leaf of cannabis is broader and the color is darker compared to that of hemp. Many recent studies have attempted to separate the combinations of terpene composition in several species of Cannabaceae where it is apparent that hemp and the Indica cannabis are closely related. For example, hemp can also yield terpene profiles similar to those of marijuana.<ref>{{Cite journal \|last=Wiebelhaus \|first=Nancy \|last2=Hamblin \|first2=D’Nisha \|last3=Kreitals \|first3=Natasha M. \|last4=Almirall \|first4=Jose R. \|date=2016-11 \|title=Differentiation of marijuana headspace volatiles from other plants and hemp products using capillary microextraction of volatiles (CMV) coupled to gas-chromatography–mass spectrometry (GC–MS) \|url=https://linkinghub.elsevier.com/retrieve/pii/S2468170916300285 \|journal=Forensic Chemistry \|language=en \|volume=2 \|pages=1–8 \|doi=10.1016/j.forc.2016.08.004}}</ref>		The most usable part for hemp is the stem in particular, while parts usually with trichomes are the most usable for cannabis. The level of THC is graded as >2% of dry weight, and flowers give a much higher terpene content, which becomes sticky to the touch.<ref name=":5">{{Cite journal \|last=Cai \|first=Changyong \|last2=Yu \|first2=Wang \|last3=Wang \|first3=Chaoyun \|last4=Liu \|first4=Lianglei \|last5=Li \|first5=Fenfang \|last6=Tan \|first6=Zhijian \|date=2019-08 \|title=Green extraction of cannabidiol from industrial hemp (Cannabis sativa L.) using deep eutectic solvents coupled with further enrichment and recovery by macroporous resin \|url=https://linkinghub.elsevier.com/retrieve/pii/S0167732218365899 \|journal=Journal of Molecular Liquids \|language=en \|volume=287 \|pages=110957 \|doi=10.1016/j.molliq.2019.110957}}</ref> Some researchers do not agree with the separation of the two by the chemical compositions. Morphologically, the leaf of cannabis is broader and the color is darker compared to that of hemp. Many recent studies have attempted to separate the combinations of terpene composition in several species of Cannabaceae where it is apparent that hemp and the Indica cannabis are closely related. For example, hemp can also yield terpene profiles similar to those of marijuana.<ref>{{Cite journal \|last=Wiebelhaus \|first=Nancy \|last2=Hamblin \|first2=D’Nisha \|last3=Kreitals \|first3=Natasha M. \|last4=Almirall \|first4=Jose R. \|date=2016-11 \|title=Differentiation of marijuana headspace volatiles from other plants and hemp products using capillary microextraction of volatiles (CMV) coupled to gas-chromatography–mass spectrometry (GC–MS) \|url=https://linkinghub.elsevier.com/retrieve/pii/S2468170916300285 \|journal=Forensic Chemistry \|language=en \|volume=2 \|pages=1–8 \|doi=10.1016/j.forc.2016.08.004}}</ref>

	Three types of glandular trichomes are characterized based upon their surface morphology, namely bulbous, sessile, and stalked (Figure 4a).<ref>{{Cite journal \|last=Hammond \|first=Charles T. \|last2=Mahlberg \|first2=Paul G. \|date=1977-09 \|title=MORPHOGENESIS OF CAPITATE GLANDULAR HAIRS OF CANNABIS SATIVA (CANNABACEAE) \|url=https://onlinelibrary.wiley.com/doi/10.1002/j.1537-2197.1977.tb11948.x \|journal=American Journal of Botany \|language=en \|volume=64 \|issue=8 \|pages=1023–1031 \|doi=10.1002/j.1537-2197.1977.tb11948.x}}</ref> Bulbous trichomes are the smallest, while sessile trichomes appear on the epidermis with a short stalk and a globose head comprised of a multicellular disc of secretory cells and a subcuticular metabolite storage cavity. Similarly, the stalked trichomes are slightly larger with a globose head elevated above the epidermal surface by a multicellular stalk.<ref>{{Cite web \|last=Potter, D. \|date=March 2009 \|title=The Propagation, Characterisation and Optimisation of Cannabis sativa L. as a Phytopharmaceutical \|url=https://extractionmagazine.com/wp-content/uploads/2018/06/THE-PROPAGATION-CHARACTERISATION-AND-OPTIMISATION-OF-CANNABIS-SATIVA-L-AS-A-PHYTOPHARMACEUTICAL.pdf \|format=PDF \|publisher=King’s College London}}</ref> In cannabis, the sessile and stalked trichomes differ not only in morphology, but they also have distinct fluorescent properties, number of cells in their secretory disc, and terpene profiles.<ref>{{Cite journal \|last=Livingston \|first=Samuel J. \|last2=Quilichini \|first2=Teagen D. \|last3=Booth \|first3=Judith K. \|last4=Wong \|first4=Darren C. J. \|last5=Rensing \|first5=Kim H. \|last6=Laflamme-Yonkman \|first6=Jessica \|last7=Castellarin \|first7=Simone D. \|last8=Bohlmann \|first8=Joerg \|last9=Page \|first9=Jonathan E. \|last10=Samuels \|first10=A. Lacey \|date=2020-01 \|title=Cannabis glandular trichomes alter morphology and metabolite content during flower maturation \|url=https://pubmed.ncbi.nlm.nih.gov/31469934 \|journal=The Plant Journal: For Cell and Molecular Biology \|volume=101 \|issue=1 \|pages=37–56 \|doi=10.1111/tpj.14516 \|issn=1365-313X \|pmid=31469934}}</ref> The stalked glandular trichomes of mature flowers have a globular head consisting of an enlarged disc greater than eight secretory cells known to be rich in cannabinoids and monoterpenes (Figure 4b). The sessile trichomes are mainly found on sugar leaves (Figure 4c). They have eight secretory cells that produce fewer cannabinoids and higher proportions of sesquiterpenes.		Three types of glandular trichomes are characterized based upon their surface morphology, namely bulbous, sessile, and stalked (Figure 4a).<ref>{{Cite journal \|last=Hammond \|first=Charles T. \|last2=Mahlberg \|first2=Paul G. \|date=1977-09 \|title=MORPHOGENESIS OF CAPITATE GLANDULAR HAIRS OF CANNABIS SATIVA (CANNABACEAE) \|url=https://onlinelibrary.wiley.com/doi/10.1002/j.1537-2197.1977.tb11948.x \|journal=American Journal of Botany \|language=en \|volume=64 \|issue=8 \|pages=1023–1031 \|doi=10.1002/j.1537-2197.1977.tb11948.x}}</ref> Bulbous trichomes are the smallest, while sessile trichomes appear on the epidermis with a short stalk and a globose head comprised of a multicellular disc of secretory cells and a subcuticular metabolite storage cavity. Similarly, the stalked trichomes are slightly larger with a globose head elevated above the epidermal surface by a multicellular stalk.<ref>{{Cite web \|last=Potter, D. \|date=March 2009 \|title=The Propagation, Characterisation and Optimisation of Cannabis sativa L. as a Phytopharmaceutical \|url=https://extractionmagazine.com/wp-content/uploads/2018/06/THE-PROPAGATION-CHARACTERISATION-AND-OPTIMISATION-OF-CANNABIS-SATIVA-L-AS-A-PHYTOPHARMACEUTICAL.pdf \|format=PDF \|publisher=King’s College London}}</ref> In cannabis, the sessile and stalked trichomes differ not only in morphology, but they also have distinct fluorescent properties, number of cells in their secretory disc, and terpene profiles.<ref name=":9">{{Cite journal \|last=Livingston \|first=Samuel J. \|last2=Quilichini \|first2=Teagen D. \|last3=Booth \|first3=Judith K. \|last4=Wong \|first4=Darren C. J. \|last5=Rensing \|first5=Kim H. \|last6=Laflamme-Yonkman \|first6=Jessica \|last7=Castellarin \|first7=Simone D. \|last8=Bohlmann \|first8=Joerg \|last9=Page \|first9=Jonathan E. \|last10=Samuels \|first10=A. Lacey \|date=2020-01 \|title=Cannabis glandular trichomes alter morphology and metabolite content during flower maturation \|url=https://pubmed.ncbi.nlm.nih.gov/31469934 \|journal=The Plant Journal: For Cell and Molecular Biology \|volume=101 \|issue=1 \|pages=37–56 \|doi=10.1111/tpj.14516 \|issn=1365-313X \|pmid=31469934}}</ref> The stalked glandular trichomes of mature flowers have a globular head consisting of an enlarged disc greater than eight secretory cells known to be rich in cannabinoids and monoterpenes (Figure 4b). The sessile trichomes are mainly found on sugar leaves (Figure 4c). They have eight secretory cells that produce fewer cannabinoids and higher proportions of sesquiterpenes.


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	The biosynthesis of these secondary-metabolite terpenes starts with the common isoprenoid diphosphate precursors (5C) through two paths, the plastidial methylerythritol phosphate (MEP) pathway and the cytosolic mevalonate (MEV) pathway.<ref name=":6" /><ref name=":7">{{Cite journal \|last=Booth \|first=Judith K. \|last2=Page \|first2=Jonathan E. \|last3=Bohlmann \|first3=Jörg \|date=2017-03-29 \|editor-last=Hamberger \|editor-first=Björn \|title=Terpene synthases from Cannabis sativa \|url=https://dx.plos.org/10.1371/journal.pone.0173911 \|journal=PLOS ONE \|language=en \|volume=12 \|issue=3 \|pages=e0173911 \|doi=10.1371/journal.pone.0173911 \|issn=1932-6203 \|pmc=PMC5371325 \|pmid=28355238}}</ref> These pathways regulate the different substrates available for terpene synthesis (TPS). The MEP converts pyruvate and glyceraldehyde-3-phosphate (G3P) into five-carbon building blocks, isopentenyl diphosphate (IPP), and dimethylallyl diphosphate (DMAPP) in the plastids.<ref>{{Cite journal \|last=Nagegowda \|first=Dinesh A. \|last2=Gupta \|first2=Priyanka \|date=2020-05 \|title=Advances in biosynthesis, regulation, and metabolic engineering of plant specialized terpenoids \|url=https://linkinghub.elsevier.com/retrieve/pii/S0168945220300595 \|journal=Plant Science \|language=en \|volume=294 \|pages=110457 \|doi=10.1016/j.plantsci.2020.110457}}</ref> The MEV pathway, on the other hand, alters three units of acetyl-CoA to IPP, which is then isomerized to DMAPP by IPP isomerase in cytosol. IPP and DMAPP are condensed into longer-chain isoprenoid diphosphates that include geranyl diphosphate (GPP) and farnesyl diphosphate (FPP).<ref name=":7" /> These linear isoprenoid diphosphates are substrates for monoterpene synthases (mono-TPS) and sesquiterpene synthases (sesqui-TPS), respectively, which diversify these precursors through enzymatic modifications such as hydroxylation, dehydrogenation, acylation, and glycosylation into the diverse ranges of mono- and sesquiterpenes.<ref>{{Cite journal \|last=Nagegowda \|first=Dinesh A. \|last2=Gupta \|first2=Priyanka \|date=2020-05 \|title=Advances in biosynthesis, regulation, and metabolic engineering of plant specialized terpenoids \|url=https://linkinghub.elsevier.com/retrieve/pii/S0168945220300595 \|journal=Plant Science \|language=en \|volume=294 \|pages=110457 \|doi=10.1016/j.plantsci.2020.110457}}</ref><ref name=":8">{{Cite journal \|last=Fellermeier \|first=M. \|last2=Eisenreich \|first2=W. \|last3=Bacher \|first3=A. \|last4=Zenk \|first4=M. H. \|date=2001-03 \|title=Biosynthesis of cannabinoids. Incorporation experiments with (13)C-labeled glucoses \|url=https://pubmed.ncbi.nlm.nih.gov/11248677 \|journal=European Journal of Biochemistry \|volume=268 \|issue=6 \|pages=1596–1604 \|doi=10.1046/j.1432-1033.2001.02030.x \|issn=0014-2956 \|pmid=11248677}}</ref> GPP is also a building block of cannabinoid biosynthesis (Figure 6).<ref name=":8" />		The biosynthesis of these secondary-metabolite terpenes starts with the common isoprenoid diphosphate precursors (5C) through two paths, the plastidial methylerythritol phosphate (MEP) pathway and the cytosolic mevalonate (MEV) pathway.<ref name=":6" /><ref name=":7">{{Cite journal \|last=Booth \|first=Judith K. \|last2=Page \|first2=Jonathan E. \|last3=Bohlmann \|first3=Jörg \|date=2017-03-29 \|editor-last=Hamberger \|editor-first=Björn \|title=Terpene synthases from Cannabis sativa \|url=https://dx.plos.org/10.1371/journal.pone.0173911 \|journal=PLOS ONE \|language=en \|volume=12 \|issue=3 \|pages=e0173911 \|doi=10.1371/journal.pone.0173911 \|issn=1932-6203 \|pmc=PMC5371325 \|pmid=28355238}}</ref> These pathways regulate the different substrates available for terpene synthesis (TPS). The MEP converts pyruvate and glyceraldehyde-3-phosphate (G3P) into five-carbon building blocks, isopentenyl diphosphate (IPP), and dimethylallyl diphosphate (DMAPP) in the plastids.<ref>{{Cite journal \|last=Nagegowda \|first=Dinesh A. \|last2=Gupta \|first2=Priyanka \|date=2020-05 \|title=Advances in biosynthesis, regulation, and metabolic engineering of plant specialized terpenoids \|url=https://linkinghub.elsevier.com/retrieve/pii/S0168945220300595 \|journal=Plant Science \|language=en \|volume=294 \|pages=110457 \|doi=10.1016/j.plantsci.2020.110457}}</ref> The MEV pathway, on the other hand, alters three units of acetyl-CoA to IPP, which is then isomerized to DMAPP by IPP isomerase in cytosol. IPP and DMAPP are condensed into longer-chain isoprenoid diphosphates that include geranyl diphosphate (GPP) and farnesyl diphosphate (FPP).<ref name=":7" /> These linear isoprenoid diphosphates are substrates for monoterpene synthases (mono-TPS) and sesquiterpene synthases (sesqui-TPS), respectively, which diversify these precursors through enzymatic modifications such as hydroxylation, dehydrogenation, acylation, and glycosylation into the diverse ranges of mono- and sesquiterpenes.<ref>{{Cite journal \|last=Nagegowda \|first=Dinesh A. \|last2=Gupta \|first2=Priyanka \|date=2020-05 \|title=Advances in biosynthesis, regulation, and metabolic engineering of plant specialized terpenoids \|url=https://linkinghub.elsevier.com/retrieve/pii/S0168945220300595 \|journal=Plant Science \|language=en \|volume=294 \|pages=110457 \|doi=10.1016/j.plantsci.2020.110457}}</ref><ref name=":8">{{Cite journal \|last=Fellermeier \|first=M. \|last2=Eisenreich \|first2=W. \|last3=Bacher \|first3=A. \|last4=Zenk \|first4=M. H. \|date=2001-03 \|title=Biosynthesis of cannabinoids. Incorporation experiments with (13)C-labeled glucoses \|url=https://pubmed.ncbi.nlm.nih.gov/11248677 \|journal=European Journal of Biochemistry \|volume=268 \|issue=6 \|pages=1596–1604 \|doi=10.1046/j.1432-1033.2001.02030.x \|issn=0014-2956 \|pmid=11248677}}</ref> GPP is also a building block of cannabinoid biosynthesis (Figure 6).<ref name=":8" />


			[[File:Fig6 Sommano Molecules21 25-24.png\|650px]]
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			{\|
			\| style="vertical-align:top;" \|
			{\| border="0" cellpadding="5" cellspacing="0" width="650px"
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			\| style="background-color:white; padding-left:10px; padding-right:10px;" \|<blockquote>'''Fig. 6''' The terpene biosynthesis pathway in cannabis. Abbreviations: DMAPP, dimethylallyl diphosphate; FPP, farnesyl diphosphate; IPP, isopentenyl diphosphate; GPP, geranyl diphosphate; mono-TPS, monoterpene synthase; sesqui-TPS, sesqiterpene synthase.</blockquote>
			\|-
			\|}
			\|}

			The biosynthetic pathway of cannabinoids involves the chemical joining process of the phenol with the terpenes to form the non-activate acidic forms (that largely determine their potency and pharmaceutical properties), including [[cannabichromene]] (CBC), [[cannabidiolic acid]] (CBDA), [[cannabigerol]] (CBG), [[cannabinol]] (CBN), [[cannabidivarin]] (CBDV), cannabidivarinic acid (CBDVA), [[cannabigerolic acid]] (CBGA), [[cannabicyclol]] (CBL), Δ<sup>8</sup>–tetrahydrocannabinol, [[tetrahydrocannabinolic acid]] (THCA), and [[tetrahydrocannabivarin]] (THCV).<ref>{{Cite journal \|last=Aliferis \|first=Konstantinos A. \|last2=Bernard-Perron \|first2=David \|date=2020 \|title=Cannabinomics: Application of Metabolomics in Cannabis (Cannabis sativa L.) Research and Development \|url=https://pubmed.ncbi.nlm.nih.gov/32457786 \|journal=Frontiers in Plant Science \|volume=11 \|pages=554 \|doi=10.3389/fpls.2020.00554 \|issn=1664-462X \|pmc=7225349 \|pmid=32457786}}</ref> These compounds, along with terpenes, are produced in the trichome structures available on the female cannabis flower.<ref name=":9" /> The highest concentration of the natural cannabinoids in cannabis are cannabidiolic acid (CBDA) and Δ<sup>9</sup>-tetrahydrocannabinoic acid (Δ9-THCA). The psychoactive metabolites such as Δ<sup>9</sup>–tetrahydrocannabinol and the non-psychoactive CBD are then activated through [[decarboxylation]] by heat treatments. It is also favored by several factors such as storage time and the use of alkaline conditions.<ref>{{Cite journal \|last=Masoud \|first=Asaad N. \|last2=Doorenbos \|first2=Norman J. \|date=1973-02 \|title=Mississippi-Grown Cannabis sativa L. III: Cannabinoid and Cannabinoid Acid Content \|url=https://linkinghub.elsevier.com/retrieve/pii/S0022354915388912 \|journal=Journal of Pharmaceutical Sciences \|language=en \|volume=62 \|issue=2 \|pages=313–315 \|doi=10.1002/jps.2600620229}}</ref><ref>{{Cite journal \|last=Grijó \|first=Daniel Ribeiro \|last2=Vieitez Osorio \|first2=Ignacio Alberto \|last3=Cardozo-Filho \|first3=Lúcio \|date=2018-12 \|title=Supercritical extraction strategies using CO2 and ethanol to obtain cannabinoid compounds from Cannabis hybrid flowers \|url=https://linkinghub.elsevier.com/retrieve/pii/S2212982018304220 \|journal=Journal of CO2 Utilization \|language=en \|volume=28 \|pages=174–180 \|doi=10.1016/j.jcou.2018.09.022}}</ref>

			The following subsections discuss the important cannabis terpene groups and their synergistic and functional properties.


	==References==		==References==

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← Older revision		Revision as of 20:33, 26 October 2021
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	*triterpenes (30C) of six isoprene units		*triterpenes (30C) of six isoprene units

	To date, more than 200 volatiles have been reported from the different cannabis genotypes, of which 58 monoterpenes and 38 sesquiterpenes have been characterized.<ref>{{Cite journal \|last=Ross \|first=Samir A. \|last2=ElSohly \|first2=Mahmoud A. \|date=1996-01-01 \|title=The Volatile Oil Composition of Fresh and Air-Dried Buds of Cannabis sativa \|url=https://pubs.acs.org/doi/10.1021/np960004a \|journal=Journal of Natural Products \|language=en \|volume=59 \|issue=1 \|pages=49–51 \|doi=10.1021/np960004a \|issn=0163-3864}}</ref><ref>{{Cite journal \|last=Turner \|first=C. E. \|last2=Elsohly \|first2=M. A. \|last3=Boeren \|first3=E. G. \|date=1980-03 \|title=Constituents of Cannabis sativa L. XVII. A review of the natural constituents \|url=https://pubmed.ncbi.nlm.nih.gov/6991645 \|journal=Journal of Natural Products \|volume=43 \|issue=2 \|pages=169–234 \|doi=10.1021/np50008a001 \|issn=0163-3864 \|pmid=6991645}}</ref><ref>{{Cite journal \|last=Wanas \|first=Amira S. \|last2=Radwan \|first2=Mohamed M. \|last3=Chandra \|first3=Suman \|last4=Lata \|first4=Hemant \|last5=Mehmedic \|first5=Zlatko \|last6=Ali \|first6=Abbas \|last7=Baser \|first7=Khc \|last8=Demirci \|first8=Betul \|last9=ElSohly \|first9=Mahmoud A. \|date=2020-05 \|title=Chemical Composition of Volatile Oils of Fresh and Air-Dried Buds of Cannabis c hemovars, Their Insecticidal and Repellent Activities \|url=http://journals.sagepub.com/doi/10.1177/1934578X20926729 \|journal=Natural Product Communications \|language=en \|volume=15 \|issue=5 \|pages=1934578X2092672 \|doi=10.1177/1934578X20926729 \|issn=1934-578X}}</ref><ref>{{Cite journal \|last=Rice \|first=Somchai \|last2=Koziel \|first2=Jacek A. \|date=2015-12-10 \|editor-last=Glendinning \|editor-first=John I. \|title=Characterizing the Smell of Marijuana by Odor Impact of Volatile Compounds: An Application of Simultaneous Chemical and Sensory Analysis \|url=https://dx.plos.org/10.1371/journal.pone.0144160 \|journal=PLOS ONE \|language=en \|volume=10 \|issue=12 \|pages=e0144160 \|doi=10.1371/journal.pone.0144160 \|issn=1932-6203 \|pmc=PMC4684335 \|pmid=26657499}}</ref> Figure 5a illustrates a [[Chromatography\|chromatogram]] of the terpene extract from the floral tissue of cannabis. Among others, the major monoterpene components are [[limonene]], [[Myrcene\|β-myrcene]], [[Pinene\|α-pinene]], and [[linalool]], with traces of α-terpinolene and [[Ocimene\|tran-ocimene]]<ref>{{Cite journal \|last=Ternelli \|first=Marco \|last2=Brighenti \|first2=Virginia \|last3=Anceschi \|first3=Lisa \|last4=Poto \|first4=Massimiliano \|last5=Bertelli \|first5=Davide \|last6=Licata \|first6=Manuela \|last7=Pellati \|first7=Federica \|date=2020-07-15 \|title=Innovative methods for the preparation of medical Cannabis oils with a high content of both cannabinoids and terpenes \|url=https://pubmed.ncbi.nlm.nih.gov/32334134 \|journal=Journal of Pharmaceutical and Biomedical Analysis \|volume=186 \|pages=113296 \|doi=10.1016/j.jpba.2020.113296 \|issn=1873-264X \|pmid=32334134}}</ref><ref>{{Cite journal \|last=Wang \|first=Chi-Tsan \|last2=Ashworth \|first2=Kirsti \|last3=Wiedinmyer \|first3=Christine \|last4=Ortega \|first4=John \|last5=Harley \|first5=Peter C. \|last6=Rasool \|first6=Quazi Z. \|last7=Vizuete \|first7=William \|date=2020-07 \|title=Ambient measurements of monoterpenes near Cannabis cultivation facilities in Denver, Colorado \|url=https://linkinghub.elsevier.com/retrieve/pii/S1352231020302478 \|journal=Atmospheric Environment \|language=en \|volume=232 \|pages=117510 \|doi=10.1016/j.atmosenv.2020.117510}}</ref> (Figure 5b), while predominate sesquiterpenes are [Caryophyllene\|E-caryophyllene]], caryophyllene oxide, E-β-farnesene, and β-caryophyllene.<ref>{{Cite journal \|last=Abdollahi \|first=Mahnaz \|last2=Sefidkon \|first2=Fatemeh \|last3=Calagari \|first3=Mohsen \|last4=Mousavi \|first4=Amir \|last5=Mahomoodally \|first5=M. Fawzi \|date=2020-11 \|title=Impact of four hemp (Cannabis sativa L.) varieties and stage of plant growth on yield and composition of essential oils \|url=https://linkinghub.elsevier.com/retrieve/pii/S092666902030710X \|journal=Industrial Crops and Products \|language=en \|volume=155 \|pages=112793 \|doi=10.1016/j.indcrop.2020.112793}}</ref> The cannabinoids are biologically synthesized from diterpene structures to form phenol terpenoids, which account for almost a quarter of all metabolites.<ref name=":4" /> Thus, the combination of the terpenes provides the unique aromas to different strains.		To date, more than 200 volatiles have been reported from the different cannabis genotypes, of which 58 monoterpenes and 38 sesquiterpenes have been characterized.<ref>{{Cite journal \|last=Ross \|first=Samir A. \|last2=ElSohly \|first2=Mahmoud A. \|date=1996-01-01 \|title=The Volatile Oil Composition of Fresh and Air-Dried Buds of Cannabis sativa \|url=https://pubs.acs.org/doi/10.1021/np960004a \|journal=Journal of Natural Products \|language=en \|volume=59 \|issue=1 \|pages=49–51 \|doi=10.1021/np960004a \|issn=0163-3864}}</ref><ref>{{Cite journal \|last=Turner \|first=C. E. \|last2=Elsohly \|first2=M. A. \|last3=Boeren \|first3=E. G. \|date=1980-03 \|title=Constituents of Cannabis sativa L. XVII. A review of the natural constituents \|url=https://pubmed.ncbi.nlm.nih.gov/6991645 \|journal=Journal of Natural Products \|volume=43 \|issue=2 \|pages=169–234 \|doi=10.1021/np50008a001 \|issn=0163-3864 \|pmid=6991645}}</ref><ref>{{Cite journal \|last=Wanas \|first=Amira S. \|last2=Radwan \|first2=Mohamed M. \|last3=Chandra \|first3=Suman \|last4=Lata \|first4=Hemant \|last5=Mehmedic \|first5=Zlatko \|last6=Ali \|first6=Abbas \|last7=Baser \|first7=Khc \|last8=Demirci \|first8=Betul \|last9=ElSohly \|first9=Mahmoud A. \|date=2020-05 \|title=Chemical Composition of Volatile Oils of Fresh and Air-Dried Buds of Cannabis c hemovars, Their Insecticidal and Repellent Activities \|url=http://journals.sagepub.com/doi/10.1177/1934578X20926729 \|journal=Natural Product Communications \|language=en \|volume=15 \|issue=5 \|pages=1934578X2092672 \|doi=10.1177/1934578X20926729 \|issn=1934-578X}}</ref><ref>{{Cite journal \|last=Rice \|first=Somchai \|last2=Koziel \|first2=Jacek A. \|date=2015-12-10 \|editor-last=Glendinning \|editor-first=John I. \|title=Characterizing the Smell of Marijuana by Odor Impact of Volatile Compounds: An Application of Simultaneous Chemical and Sensory Analysis \|url=https://dx.plos.org/10.1371/journal.pone.0144160 \|journal=PLOS ONE \|language=en \|volume=10 \|issue=12 \|pages=e0144160 \|doi=10.1371/journal.pone.0144160 \|issn=1932-6203 \|pmc=PMC4684335 \|pmid=26657499}}</ref> Figure 5a illustrates a [[Chromatography\|chromatogram]] of the terpene extract from the floral tissue of cannabis. Among others, the major monoterpene components are [[limonene]], [[Myrcene\|β-myrcene]], [[Pinene\|α-pinene]], and [[linalool]], with traces of α-terpinolene and [[Ocimene\|tran-ocimene]]<ref>{{Cite journal \|last=Ternelli \|first=Marco \|last2=Brighenti \|first2=Virginia \|last3=Anceschi \|first3=Lisa \|last4=Poto \|first4=Massimiliano \|last5=Bertelli \|first5=Davide \|last6=Licata \|first6=Manuela \|last7=Pellati \|first7=Federica \|date=2020-07-15 \|title=Innovative methods for the preparation of medical Cannabis oils with a high content of both cannabinoids and terpenes \|url=https://pubmed.ncbi.nlm.nih.gov/32334134 \|journal=Journal of Pharmaceutical and Biomedical Analysis \|volume=186 \|pages=113296 \|doi=10.1016/j.jpba.2020.113296 \|issn=1873-264X \|pmid=32334134}}</ref><ref>{{Cite journal \|last=Wang \|first=Chi-Tsan \|last2=Ashworth \|first2=Kirsti \|last3=Wiedinmyer \|first3=Christine \|last4=Ortega \|first4=John \|last5=Harley \|first5=Peter C. \|last6=Rasool \|first6=Quazi Z. \|last7=Vizuete \|first7=William \|date=2020-07 \|title=Ambient measurements of monoterpenes near Cannabis cultivation facilities in Denver, Colorado \|url=https://linkinghub.elsevier.com/retrieve/pii/S1352231020302478 \|journal=Atmospheric Environment \|language=en \|volume=232 \|pages=117510 \|doi=10.1016/j.atmosenv.2020.117510}}</ref> (Figure 5b), while predominate sesquiterpenes are [[Caryophyllene\|E-caryophyllene]], caryophyllene oxide, E-β-farnesene, and β-caryophyllene.<ref>{{Cite journal \|last=Abdollahi \|first=Mahnaz \|last2=Sefidkon \|first2=Fatemeh \|last3=Calagari \|first3=Mohsen \|last4=Mousavi \|first4=Amir \|last5=Mahomoodally \|first5=M. Fawzi \|date=2020-11 \|title=Impact of four hemp (Cannabis sativa L.) varieties and stage of plant growth on yield and composition of essential oils \|url=https://linkinghub.elsevier.com/retrieve/pii/S092666902030710X \|journal=Industrial Crops and Products \|language=en \|volume=155 \|pages=112793 \|doi=10.1016/j.indcrop.2020.112793}}</ref> The cannabinoids are biologically synthesized from diterpene structures to form phenol terpenoids, which account for almost a quarter of all metabolites.<ref name=":4" /> Thus, the combination of the terpenes provides the unique aromas to different strains.


	==References==		==References==

Shawndouglas: Saving and adding more.

2021-10-26T20:33:07Z

Saving and adding more.

← Older revision		Revision as of 20:33, 26 October 2021
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	The first cannabinoid isolates used for medicinal purposes were produced in Czechoslovakia, and CBD was fully characterized for the first time in 1963, followed by the psychoactive THC in the following year.<ref>{{Cite journal \|last=Gaoni \|first=Y. \|last2=Mechoulam \|first2=R. \|date=1964-04 \|title=Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish \|url=https://pubs.acs.org/doi/abs/10.1021/ja01062a046 \|journal=Journal of the American Chemical Society \|language=en \|volume=86 \|issue=8 \|pages=1646–1647 \|doi=10.1021/ja01062a046 \|issn=0002-7863}}</ref><ref>{{Cite journal \|last=Šantavý, F. \|year=1964 \|title=Notes on the structure of cannabidiol compounds \|journal=Acta Universitatis Palackianae Olomucensis Facultatis Medicae \|volume=35 \|pages=5–9}}</ref><ref>{{Cite journal \|last=Adams \|first=Roger \|last2=Pease \|first2=D. C. \|last3=Cain \|first3=C. K. \|last4=Baker \|first4=B. R. \|last5=Clark \|first5=J. H. \|last6=Wolff \|first6=Hans \|last7=Wearn \|first7=R. B. \|date=1940-08 \|title=CONVERSION OF CANNABIDIOL TO A PRODUCT WITH MARIHUANA ACTIVITY. A TYPE REACTION FOR SYNTHESIS OF ANALOGOUS SUBSTANCES. CONVERSION OF CANNABIDIOL TO CANNABINOL \|url=https://pubs.acs.org/doi/abs/10.1021/ja01865a508 \|journal=Journal of the American Chemical Society \|language=en \|volume=62 \|issue=8 \|pages=2245–2246 \|doi=10.1021/ja01865a508 \|issn=0002-7863}}</ref> The discovery of cannabinoid receptors, CB1 and CB2, together with the full comprehension of the endocannabinoid system, helped us recognize the medicinal benefits of this plant.<ref>{{Cite journal \|last=Devane \|first=W. A. \|last2=Dysarz \|first2=F. A. \|last3=Johnson \|first3=M. R. \|last4=Melvin \|first4=L. S. \|last5=Howlett \|first5=A. C. \|date=1988-11 \|title=Determination and characterization of a cannabinoid receptor in rat brain \|url=https://pubmed.ncbi.nlm.nih.gov/2848184 \|journal=Molecular Pharmacology \|volume=34 \|issue=5 \|pages=605–613 \|issn=0026-895X \|pmid=2848184}}</ref><ref>{{Cite journal \|last=Devane \|first=William A. \|last2=Hanuš \|first2=Lumir \|last3=Breuer \|first3=Aviva \|last4=Pertwee \|first4=Roger G. \|last5=Stevenson \|first5=Lesley A. \|last6=Griffin \|first6=Graeme \|last7=Gibson \|first7=Dan \|last8=Mandelbaum \|first8=Asher \|last9=Etinger \|first9=Alexander \|last10=Mechoulam \|first10=Raphael \|date=1992-12-18 \|title=Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor \|url=https://www.science.org/doi/10.1126/science.1470919 \|journal=Science \|language=en \|volume=258 \|issue=5090 \|pages=1946–1949 \|doi=10.1126/science.1470919 \|issn=0036-8075}}</ref> In 1942, Simonsen and Todd<ref>{{Cite journal \|last=Simonsen \|first=J. L. \|last2=Todd \|first2=A. R. \|date=1942 \|title=32. Cannabis indica. Part X. The essential oil from Egyptian hashish \|url=http://xlink.rsc.org/?DOI=jr9420000188 \|journal=Journal of the Chemical Society (Resumed) \|language=en \|pages=188 \|doi=10.1039/jr9420000188 \|issn=0368-1769}}</ref> were the first researchers to separate terpene fractions from cannabinoids in the literature, and [[p-Cymene\|''p''-Cymene]] was reported as a main constituent from Egyptian hashish. Only in the past years have the terms "synergic" and "entourage effect" appeared in speculations by chemists all over the world in relation to cannabis compounds, included the terpenes.<ref>{{Cite journal \|last=Hanuš \|first=Lumír Ondřej \|last2=Hod \|first2=Yotam \|date=2020-08-10 \|title=Terpenes/Terpenoids in Cannabis: Are They Important? \|url=https://www.karger.com/Article/FullText/509733 \|journal=Medical Cannabis and Cannabinoids \|language=en \|volume=3 \|issue=1 \|pages=25–60 \|doi=10.1159/000509733 \|issn=2504-3889 \|pmc=PMC8489319 \|pmid=34676339}}</ref> The proposed synergies were first described as routes for the molecular regulation of endogenous cannabinoid activity.<ref>{{Cite journal \|last=Ben-Shabat \|first=Shimon \|last2=Fride \|first2=Ester \|last3=Sheskin \|first3=Tzviel \|last4=Tamiri \|first4=Tsippy \|last5=Rhee \|first5=Man-Hee \|last6=Vogel \|first6=Zvi \|last7=Bisogno \|first7=Tiziana \|last8=De Petrocellis \|first8=Luciano \|last9=Di Marzo \|first9=Vincenzo \|last10=Mechoulam \|first10=Raphael \|date=1998-07 \|title=An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity \|url=https://linkinghub.elsevier.com/retrieve/pii/S0014299998003926 \|journal=European Journal of Pharmacology \|language=en \|volume=353 \|issue=1 \|pages=23–31 \|doi=10.1016/S0014-2999(98)00392-6}}</ref> Russo<ref name=":3">{{Cite journal \|last=Russo \|first=Ethan B \|date=2011-08 \|title=Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects: Phytocannabinoid-terpenoid entourage effects \|url=https://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2011.01238.x \|journal=British Journal of Pharmacology \|language=en \|volume=163 \|issue=7 \|pages=1344–1364 \|doi=10.1111/j.1476-5381.2011.01238.x \|pmc=PMC3165946 \|pmid=21749363}}</ref> later proposed the unique therapeutic effect of cannabis terpenes that possibly play a role on the entourage effects of the medicinal properties of the cannabinoids. This phytocannabinoid-terpenoid synergy could potentially enhance the treatments of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal, and bacterial infections.<ref name=":2" /><ref name=":3" /><ref>{{Cite journal \|last=Gallily \|first=Ruth \|last2=Yekhtin \|first2=Zhannah \|last3=Hanuš \|first3=Lumír Ondřej \|date=2018 \|title=The Anti-Inflammatory Properties of Terpenoids from Cannabis \|url=https://pubmed.ncbi.nlm.nih.gov/30596146 \|journal=Cannabis and Cannabinoid Research \|volume=3 \|issue=1 \|pages=282–290 \|doi=10.1089/can.2018.0014 \|issn=2578-5125 \|pmc=6308289 \|pmid=30596146}}</ref><ref>{{Cite journal \|last=Baron \|first=Eric P. \|date=2018-07 \|title=Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain: An Update on Current Evidence and Cannabis Science \|url=https://pubmed.ncbi.nlm.nih.gov/30152161 \|journal=Headache \|volume=58 \|issue=7 \|pages=1139–1186 \|doi=10.1111/head.13345 \|issn=1526-4610 \|pmid=30152161}}</ref><ref>{{Cite journal \|last=Lewis \|first=Mark A. \|last2=Russo \|first2=Ethan B. \|last3=Smith \|first3=Kevin M. \|date=2018-03 \|title=Pharmacological Foundations of Cannabis Chemovars \|url=https://pubmed.ncbi.nlm.nih.gov/29161743 \|journal=Planta Medica \|volume=84 \|issue=4 \|pages=225–233 \|doi=10.1055/s-0043-122240 \|issn=1439-0221 \|pmid=29161743}}</ref>		The first cannabinoid isolates used for medicinal purposes were produced in Czechoslovakia, and CBD was fully characterized for the first time in 1963, followed by the psychoactive THC in the following year.<ref>{{Cite journal \|last=Gaoni \|first=Y. \|last2=Mechoulam \|first2=R. \|date=1964-04 \|title=Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish \|url=https://pubs.acs.org/doi/abs/10.1021/ja01062a046 \|journal=Journal of the American Chemical Society \|language=en \|volume=86 \|issue=8 \|pages=1646–1647 \|doi=10.1021/ja01062a046 \|issn=0002-7863}}</ref><ref>{{Cite journal \|last=Šantavý, F. \|year=1964 \|title=Notes on the structure of cannabidiol compounds \|journal=Acta Universitatis Palackianae Olomucensis Facultatis Medicae \|volume=35 \|pages=5–9}}</ref><ref>{{Cite journal \|last=Adams \|first=Roger \|last2=Pease \|first2=D. C. \|last3=Cain \|first3=C. K. \|last4=Baker \|first4=B. R. \|last5=Clark \|first5=J. H. \|last6=Wolff \|first6=Hans \|last7=Wearn \|first7=R. B. \|date=1940-08 \|title=CONVERSION OF CANNABIDIOL TO A PRODUCT WITH MARIHUANA ACTIVITY. A TYPE REACTION FOR SYNTHESIS OF ANALOGOUS SUBSTANCES. CONVERSION OF CANNABIDIOL TO CANNABINOL \|url=https://pubs.acs.org/doi/abs/10.1021/ja01865a508 \|journal=Journal of the American Chemical Society \|language=en \|volume=62 \|issue=8 \|pages=2245–2246 \|doi=10.1021/ja01865a508 \|issn=0002-7863}}</ref> The discovery of cannabinoid receptors, CB1 and CB2, together with the full comprehension of the endocannabinoid system, helped us recognize the medicinal benefits of this plant.<ref>{{Cite journal \|last=Devane \|first=W. A. \|last2=Dysarz \|first2=F. A. \|last3=Johnson \|first3=M. R. \|last4=Melvin \|first4=L. S. \|last5=Howlett \|first5=A. C. \|date=1988-11 \|title=Determination and characterization of a cannabinoid receptor in rat brain \|url=https://pubmed.ncbi.nlm.nih.gov/2848184 \|journal=Molecular Pharmacology \|volume=34 \|issue=5 \|pages=605–613 \|issn=0026-895X \|pmid=2848184}}</ref><ref>{{Cite journal \|last=Devane \|first=William A. \|last2=Hanuš \|first2=Lumir \|last3=Breuer \|first3=Aviva \|last4=Pertwee \|first4=Roger G. \|last5=Stevenson \|first5=Lesley A. \|last6=Griffin \|first6=Graeme \|last7=Gibson \|first7=Dan \|last8=Mandelbaum \|first8=Asher \|last9=Etinger \|first9=Alexander \|last10=Mechoulam \|first10=Raphael \|date=1992-12-18 \|title=Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor \|url=https://www.science.org/doi/10.1126/science.1470919 \|journal=Science \|language=en \|volume=258 \|issue=5090 \|pages=1946–1949 \|doi=10.1126/science.1470919 \|issn=0036-8075}}</ref> In 1942, Simonsen and Todd<ref>{{Cite journal \|last=Simonsen \|first=J. L. \|last2=Todd \|first2=A. R. \|date=1942 \|title=32. Cannabis indica. Part X. The essential oil from Egyptian hashish \|url=http://xlink.rsc.org/?DOI=jr9420000188 \|journal=Journal of the Chemical Society (Resumed) \|language=en \|pages=188 \|doi=10.1039/jr9420000188 \|issn=0368-1769}}</ref> were the first researchers to separate terpene fractions from cannabinoids in the literature, and [[p-Cymene\|''p''-Cymene]] was reported as a main constituent from Egyptian hashish. Only in the past years have the terms "synergic" and "entourage effect" appeared in speculations by chemists all over the world in relation to cannabis compounds, included the terpenes.<ref name=":4">{{Cite journal \|last=Hanuš \|first=Lumír Ondřej \|last2=Hod \|first2=Yotam \|date=2020-08-10 \|title=Terpenes/Terpenoids in Cannabis: Are They Important? \|url=https://www.karger.com/Article/FullText/509733 \|journal=Medical Cannabis and Cannabinoids \|language=en \|volume=3 \|issue=1 \|pages=25–60 \|doi=10.1159/000509733 \|issn=2504-3889 \|pmc=PMC8489319 \|pmid=34676339}}</ref> The proposed synergies were first described as routes for the molecular regulation of endogenous cannabinoid activity.<ref>{{Cite journal \|last=Ben-Shabat \|first=Shimon \|last2=Fride \|first2=Ester \|last3=Sheskin \|first3=Tzviel \|last4=Tamiri \|first4=Tsippy \|last5=Rhee \|first5=Man-Hee \|last6=Vogel \|first6=Zvi \|last7=Bisogno \|first7=Tiziana \|last8=De Petrocellis \|first8=Luciano \|last9=Di Marzo \|first9=Vincenzo \|last10=Mechoulam \|first10=Raphael \|date=1998-07 \|title=An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity \|url=https://linkinghub.elsevier.com/retrieve/pii/S0014299998003926 \|journal=European Journal of Pharmacology \|language=en \|volume=353 \|issue=1 \|pages=23–31 \|doi=10.1016/S0014-2999(98)00392-6}}</ref> Russo<ref name=":3">{{Cite journal \|last=Russo \|first=Ethan B \|date=2011-08 \|title=Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects: Phytocannabinoid-terpenoid entourage effects \|url=https://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2011.01238.x \|journal=British Journal of Pharmacology \|language=en \|volume=163 \|issue=7 \|pages=1344–1364 \|doi=10.1111/j.1476-5381.2011.01238.x \|pmc=PMC3165946 \|pmid=21749363}}</ref> later proposed the unique therapeutic effect of cannabis terpenes that possibly play a role on the entourage effects of the medicinal properties of the cannabinoids. This phytocannabinoid-terpenoid synergy could potentially enhance the treatments of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal, and bacterial infections.<ref name=":2" /><ref name=":3" /><ref>{{Cite journal \|last=Gallily \|first=Ruth \|last2=Yekhtin \|first2=Zhannah \|last3=Hanuš \|first3=Lumír Ondřej \|date=2018 \|title=The Anti-Inflammatory Properties of Terpenoids from Cannabis \|url=https://pubmed.ncbi.nlm.nih.gov/30596146 \|journal=Cannabis and Cannabinoid Research \|volume=3 \|issue=1 \|pages=282–290 \|doi=10.1089/can.2018.0014 \|issn=2578-5125 \|pmc=6308289 \|pmid=30596146}}</ref><ref>{{Cite journal \|last=Baron \|first=Eric P. \|date=2018-07 \|title=Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain: An Update on Current Evidence and Cannabis Science \|url=https://pubmed.ncbi.nlm.nih.gov/30152161 \|journal=Headache \|volume=58 \|issue=7 \|pages=1139–1186 \|doi=10.1111/head.13345 \|issn=1526-4610 \|pmid=30152161}}</ref><ref>{{Cite journal \|last=Lewis \|first=Mark A. \|last2=Russo \|first2=Ethan B. \|last3=Smith \|first3=Kevin M. \|date=2018-03 \|title=Pharmacological Foundations of Cannabis Chemovars \|url=https://pubmed.ncbi.nlm.nih.gov/29161743 \|journal=Planta Medica \|volume=84 \|issue=4 \|pages=225–233 \|doi=10.1055/s-0043-122240 \|issn=1439-0221 \|pmid=29161743}}</ref>

	==Taxonomy and localization of cannabis terpenes==		==Taxonomy and localization of cannabis terpenes==
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	==Terpene biosynthesis in cannabis==		==Terpene biosynthesis in cannabis==
			The energy required for plant growth and development derives from photosynthesis, respiration, and transpiration with O<sub>2</sub>, CO<sub>2</sub>, nutrients, and water. The energy is restored in the form of primary chemical ingredients that plants later exploit. These primary metabolites include carbohydrates, lipids, proteins, and nucleic acids. However, during cycles of growth and reproduction, plants might be challenged by stresses including hard environmental conditions, pests, and herbivores. Plants then produce different groups of compounds called secondary metabolites that are used as defenses to those challenges. For example, it can produce compounds that draw in pollinators, including birds to help them in the fertilization process or seed dispersion.<ref>{{Cite journal \|last=Schwachtje \|first=Jens \|last2=Baldwin \|first2=Ian T. \|date=2008-03 \|title=Why does herbivore attack reconfigure primary metabolism? \|url=https://pubmed.ncbi.nlm.nih.gov/18316639 \|journal=Plant Physiology \|volume=146 \|issue=3 \|pages=845–851 \|doi=10.1104/pp.107.112490 \|issn=0032-0889 \|pmc=2259057 \|pmid=18316639}}</ref> These compounds are produced in different forms and are exploited for their biological functionalities<ref>{{Citation \|last=Sommano \|first=Sarana \|date=2013-11-30 \|editor-last=P. M \|editor-first=Visakh \|editor2-last=Iturriaga \|editor2-first=Laura B. \|editor3-last=Ribotta \|editor3-first=Pablo Daniel \|title=Effect of Food Processing on Bioactive Compounds \|url=https://onlinelibrary.wiley.com/doi/10.1002/9781118865606.ch11 \|work=Advances in Food Science and Nutrition \|language=en \|publisher=John Wiley & Sons, Inc. \|place=Hoboken, NJ, USA \|pages=361–390 \|doi=10.1002/9781118865606.ch11 \|isbn=978-1-118-86560-6 \|access-date=2021-10-26}}</ref>; for example, alkaloids such as morphine and codeine in opium give psychoactive and pain relief activity to mammals. Phenolics and flavonoids found in the skins of fruits and berries possess antioxidant activity.<ref>{{Cite journal \|last=Sommano \|first=Sarana \|last2=Caffin \|first2=Nola \|last3=Kerven \|first3=Graham \|date=2013-08-18 \|title=Screening for Antioxidant Activity, Phenolic Content, and Flavonoids from Australian Native Food Plants \|url=http://www.tandfonline.com/doi/abs/10.1080/10942912.2011.580485 \|journal=International Journal of Food Properties \|language=en \|volume=16 \|issue=6 \|pages=1394–1406 \|doi=10.1080/10942912.2011.580485 \|issn=1094-2912}}</ref> Sulfur containing compounds such as allicin in garlic can be used to reduce lipoglycerides in the blood and also have the ability to stimulate appetite.<ref>{{Cite journal \|last=Sunanta \|first=Piyachat \|last2=Chung \|first2=Hsiao‐Hang \|last3=Kunasakdakul \|first3=Kaewalin \|last4=Ruksiriwanich \|first4=Warintorn \|last5=Jantrawut \|first5=Pensak \|last6=Hongsibsong \|first6=Surat \|last7=Sommano \|first7=Sarana Rose \|date=2020-08 \|title=Genomic relationship and physiochemical properties among raw materials used for Thai black garlic processing \|url=https://onlinelibrary.wiley.com/doi/10.1002/fsn3.1762 \|journal=Food Science & Nutrition \|language=en \|volume=8 \|issue=8 \|pages=4534–4545 \|doi=10.1002/fsn3.1762 \|issn=2048-7177 \|pmc=PMC7455981 \|pmid=32884733}}</ref> Saponin glycoside in soap nuts can be used as a surfactant<ref>{{Cite journal \|last=Wisetkomolmat \|first=Jiratchaya \|last2=Suppakittpaisarn \|first2=Pongsakorn \|last3=Sommano \|first3=Sarana Rose \|date=2019-01-03 \|title=Detergent Plants of Northern Thailand: Potential Sources of Natural Saponins \|url=https://www.mdpi.com/2079-9276/8/1/10 \|journal=Resources \|language=en \|volume=8 \|issue=1 \|pages=10 \|doi=10.3390/resources8010010 \|issn=2079-9276}}</ref>, and finally, the terpenoids, which are main ingredients found in plants containing essential oils<ref>{{Cite journal \|last=Tangpao \|first=Tibet \|last2=Chung \|first2=Hsiao-Hang \|last3=Sommano \|first3=Sarana \|date=2018-10-24 \|title=Aromatic Profiles of Essential Oils from Five Commonly Used Thai Basils \|url=http://www.mdpi.com/2304-8158/7/11/175 \|journal=Foods \|language=en \|volume=7 \|issue=11 \|pages=175 \|doi=10.3390/foods7110175 \|issn=2304-8158 \|pmc=PMC6262289 \|pmid=30352978}}</ref>, are used as food additives, and some depict psychoactive ability and aroma characteristics such as those found in cannabis.

			Terpenes are hydrocarbons with small isoprene units linked to one another to form chains, while terpenoids are oxygen-containing terpenes. Four types of terpenes/terpenoids are usually found in the ''Cannabis'' plant<ref name=":4" />:

			*monoterpenes (10C) of two isoprene units
			*sesquiterpenes (15C) of three isoprene units
			*diterpenes (20C) of four isoprene units
			*triterpenes (30C) of six isoprene units

			To date, more than 200 volatiles have been reported from the different cannabis genotypes, of which 58 monoterpenes and 38 sesquiterpenes have been characterized.<ref>{{Cite journal \|last=Ross \|first=Samir A. \|last2=ElSohly \|first2=Mahmoud A. \|date=1996-01-01 \|title=The Volatile Oil Composition of Fresh and Air-Dried Buds of Cannabis sativa \|url=https://pubs.acs.org/doi/10.1021/np960004a \|journal=Journal of Natural Products \|language=en \|volume=59 \|issue=1 \|pages=49–51 \|doi=10.1021/np960004a \|issn=0163-3864}}</ref><ref>{{Cite journal \|last=Turner \|first=C. E. \|last2=Elsohly \|first2=M. A. \|last3=Boeren \|first3=E. G. \|date=1980-03 \|title=Constituents of Cannabis sativa L. XVII. A review of the natural constituents \|url=https://pubmed.ncbi.nlm.nih.gov/6991645 \|journal=Journal of Natural Products \|volume=43 \|issue=2 \|pages=169–234 \|doi=10.1021/np50008a001 \|issn=0163-3864 \|pmid=6991645}}</ref><ref>{{Cite journal \|last=Wanas \|first=Amira S. \|last2=Radwan \|first2=Mohamed M. \|last3=Chandra \|first3=Suman \|last4=Lata \|first4=Hemant \|last5=Mehmedic \|first5=Zlatko \|last6=Ali \|first6=Abbas \|last7=Baser \|first7=Khc \|last8=Demirci \|first8=Betul \|last9=ElSohly \|first9=Mahmoud A. \|date=2020-05 \|title=Chemical Composition of Volatile Oils of Fresh and Air-Dried Buds of Cannabis c hemovars, Their Insecticidal and Repellent Activities \|url=http://journals.sagepub.com/doi/10.1177/1934578X20926729 \|journal=Natural Product Communications \|language=en \|volume=15 \|issue=5 \|pages=1934578X2092672 \|doi=10.1177/1934578X20926729 \|issn=1934-578X}}</ref><ref>{{Cite journal \|last=Rice \|first=Somchai \|last2=Koziel \|first2=Jacek A. \|date=2015-12-10 \|editor-last=Glendinning \|editor-first=John I. \|title=Characterizing the Smell of Marijuana by Odor Impact of Volatile Compounds: An Application of Simultaneous Chemical and Sensory Analysis \|url=https://dx.plos.org/10.1371/journal.pone.0144160 \|journal=PLOS ONE \|language=en \|volume=10 \|issue=12 \|pages=e0144160 \|doi=10.1371/journal.pone.0144160 \|issn=1932-6203 \|pmc=PMC4684335 \|pmid=26657499}}</ref> Figure 5a illustrates a [[Chromatography\|chromatogram]] of the terpene extract from the floral tissue of cannabis. Among others, the major monoterpene components are [[limonene]], [[Myrcene\|β-myrcene]], [[Pinene\|α-pinene]], and [[linalool]], with traces of α-terpinolene and [[Ocimene\|tran-ocimene]]<ref>{{Cite journal \|last=Ternelli \|first=Marco \|last2=Brighenti \|first2=Virginia \|last3=Anceschi \|first3=Lisa \|last4=Poto \|first4=Massimiliano \|last5=Bertelli \|first5=Davide \|last6=Licata \|first6=Manuela \|last7=Pellati \|first7=Federica \|date=2020-07-15 \|title=Innovative methods for the preparation of medical Cannabis oils with a high content of both cannabinoids and terpenes \|url=https://pubmed.ncbi.nlm.nih.gov/32334134 \|journal=Journal of Pharmaceutical and Biomedical Analysis \|volume=186 \|pages=113296 \|doi=10.1016/j.jpba.2020.113296 \|issn=1873-264X \|pmid=32334134}}</ref><ref>{{Cite journal \|last=Wang \|first=Chi-Tsan \|last2=Ashworth \|first2=Kirsti \|last3=Wiedinmyer \|first3=Christine \|last4=Ortega \|first4=John \|last5=Harley \|first5=Peter C. \|last6=Rasool \|first6=Quazi Z. \|last7=Vizuete \|first7=William \|date=2020-07 \|title=Ambient measurements of monoterpenes near Cannabis cultivation facilities in Denver, Colorado \|url=https://linkinghub.elsevier.com/retrieve/pii/S1352231020302478 \|journal=Atmospheric Environment \|language=en \|volume=232 \|pages=117510 \|doi=10.1016/j.atmosenv.2020.117510}}</ref> (Figure 5b), while predominate sesquiterpenes are [Caryophyllene\|E-caryophyllene]], caryophyllene oxide, E-β-farnesene, and β-caryophyllene.<ref>{{Cite journal \|last=Abdollahi \|first=Mahnaz \|last2=Sefidkon \|first2=Fatemeh \|last3=Calagari \|first3=Mohsen \|last4=Mousavi \|first4=Amir \|last5=Mahomoodally \|first5=M. Fawzi \|date=2020-11 \|title=Impact of four hemp (Cannabis sativa L.) varieties and stage of plant growth on yield and composition of essential oils \|url=https://linkinghub.elsevier.com/retrieve/pii/S092666902030710X \|journal=Industrial Crops and Products \|language=en \|volume=155 \|pages=112793 \|doi=10.1016/j.indcrop.2020.112793}}</ref> The cannabinoids are biologically synthesized from diterpene structures to form phenol terpenoids, which account for almost a quarter of all metabolites.<ref name=":4" /> Thus, the combination of the terpenes provides the unique aromas to different strains.