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Abstract and Figures

Terpenes are the primary constituents of essential oils and are responsible for the aroma characteristics of cannabis. Together with the cannabinoids, terpenes illustrate synergic and/or entourage effect and their interactions have only been speculated in for the last few decades. Hundreds of terpenes are identified that allude to cannabis sensory attributes, contributing largely to the consumer’s experiences and market price. They also enhance many therapeutic benefits, especially as aromatherapy. To shed light on the importance of terpenes in the cannabis industry, the purpose of this review is to morphologically describe sources of cannabis terpenes and to explain the biosynthesis and diversity of terpene profiles in different cannabis chemovars.
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molecules
Review
The Cannabis Terpenes
Sarana Rose Sommano 1,2,3,* , Chuda Chittasupho 3,4, Warintorn Ruksiriwanich 3,4 and
Pensak Jantrawut 3,4
1Plant Bioactive Compound Laboratory, Faculty of Agriculture, Chiang Mai University,
Chiang Mai 50100, Thailand
2Cluster of Agro Bio-Circular-Green Industry (Agro BCG), Chiang Mai University,
Chiang Mai 50100, Thailand
3Cluster of Research and Development of Pharmaceutical and Natural Products Innovation for
Human or Animal, Chiang Mai University, Chiang Mai 50200, Thailand; chuda.c@cmu.ac.th (C.C.);
warintorn.ruksiri@cmu.ac.th (W.R.); pensak.j@cmu.ac.th (P.J.)
4Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University,
Chiang Mai 50200, Thailand
*Correspondence: sarana.s@cmu.ac.th
Academic Editor: Luca Valgimigli
Received: 6 November 2020; Accepted: 8 December 2020; Published: 8 December 2020


Abstract:
Terpenes are the primary constituents of essential oils and are responsible for the aroma
characteristics of cannabis. Together with the cannabinoids, terpenes illustrate synergic and/or
entourage eect and their interactions have only been speculated in for the last few decades.
Hundreds of terpenes are identified that allude to cannabis sensory attributes, contributing largely to
the consumer’s experiences and market price. They also enhance many therapeutic benefits, especially
as aromatherapy. To shed light on the importance of terpenes in the cannabis industry, the purpose of
this review is to morphologically describe sources of cannabis terpenes and to explain the biosynthesis
and diversity of terpene profiles in dierent cannabis chemovars.
Keywords: essential oil; hemp; marijuana; trichomes; volatile profile
1. Introduction
Cannabis sativa L. or cannabis is a herbaceous annual that has a long history of use around the
world as fiber, food, oil as well as medicine. Depending on the purposes of utilization, they can be
called by dierent names; for example, “hemp” as a fiber and textile crop and “recreational cannabis”,
or known in the USA as marijuana. Aside from its quality as an industrial textile, the psychoactive
properties have labeled a grey stigma to cannabis plants as being an illicit drug with many informal
names including pot, dope, grass, weed, Mary Jane, bud, hash, bhang, kef, ganja, locoweed, reefer,
doob, spli, toke, and roach. It has been forbidden to grow in many countries due to the psychoactive
ingredients contained [
1
]. In a medical sense, many recent studies have advised that the increase in
cannabis use was in association with psychiatric symptoms including depression and anxiety [
2
,
3
].
However, many users still exclusively endorse its recreational purpose [
4
,
5
]. As a result, there has been
a strong movement toward correcting negative attitudes of the cannabis and attempts have been made
in trying to remove this plant from narcotic lists. In Thailand, for instance, as from 2020, cannabis strains
such as
Molecules 2020, 25, 5792; doi:10.3390/molecules25245792 www.mdpi.com/journal/molecules
Review
The Cannabis Terpenes
Sarana Rose Sommano
1,2,3,
*, Chuda Chittasupho
3,4
, Warintorn Ruksiriwanich
3,4
and
Pensak Jantrawut
3,4
1
Plant Bioactive Compound Laboratory, Faculty of Agriculture, Chiang Mai University, Chiang Mai 50100,
Thailand
2
Cluster of Agro Bio-Circular-Green Industry (Agro BCG), Chiang Mai University, Chiang Mai 50100,
Thailand
3
Cluster of Research and Development of Pharmaceutical and Natural Products Innovation for Human or
Animal, Chiang Mai University, Chiang Mai 50200, Thailand; chuda.c@cmu.ac.th (C.C.);
warintorn.ruksiri@cmu.ac.th (W.R.); pensak.j@cmu.ac.th (P.J.)
4
Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200,
Thailand
* Correspondence: sarana.s@cmu.ac.th
Academic Editor: Luca Valgimigli
Received: 6 November 2020; Accepted: 8 December 2020; Published: 8 December 2020
Abstract: Terpenes are the primary constituents of essential oils and are responsible for the aroma
characteristics of cannabis. Together with the cannabinoids, terpenes illustrate synergic and/or
entourage effect and their interactions have only been speculated in for the last few decades.
Hundreds of terpenes are identified that allude to cannabis sensory attributes, contributing largely
to the consumer’s experiences and market price. They also enhance many therapeutic benefits,
especially as aromatherapy. To shed light on the importance of terpenes in the cannabis industry,
the purpose of this review is to morphologically describe sources of cannabis terpenes and to explain
the biosynthesis and diversity of terpene profiles in different cannabis chemovars.
Keywords: essential oil; hemp; marijuana; trichomes; volatile profile
1. Introduction
Cannabis sativa L. or cannabis is a herbaceous annual that has a long history of use around the
world as fiber, food, oil as well as medicine. Depending on the purposes of utilization, they can be
called by different names; for example, “hemp” as a fiber and textile crop and “recreational cannabis”,
or known in the USA as marijuana. Aside from its quality as an industrial textile, the psychoactive
properties have labeled a grey stigma to cannabis plants as being an illicit drug with many informal
names including pot, dope, grass, weed, Mary Jane, bud, hash, bhang, kef, ganja, locoweed, reefer,
doob, spliff, toke, and roach. It has been forbidden to grow in many countries due to the psychoactive
ingredients contained [1]. In a medical sense, many recent studies have advised that the increase in
cannabis use was in association with psychiatric symptoms including depression and anxiety [2,3].
However, many users still exclusively endorse its recreational purpose [4,5]. As a result, there has
been a strong movement toward correcting negative attitudes of the cannabis and attempts have been
made in trying to remove this plant from narcotic lists. In Thailand, for instance, as from 2020,
cannabis strains such as ญชง (hemp) and ญชา (marijuana) are legally grown for industrial fiber or
medicinal purposes under the controlled level of active metabolites including cannabinoids of Δ9–
tetrahydrocannabinol (THC) and cannabidiol (CBD) [6]. While focus has paid attention primarily to
the bioactive functions of the cannabinoids, the hydrocarbon terpenes could also offer interesting
entourage effects that could ideally synergize or downstream their effects [7]. Eminently, with the
(hemp) and
Molecules 2020, 25, 5792; doi:10.3390/molecules25245792 www.mdpi.com/journal/molecules
Review
The Cannabis Terpenes
Sarana Rose Sommano
1,2,3,
*, Chuda Chittasupho
3,4
, Warintorn Ruksiriwanich
3,4
and
Pensak Jantrawut
3,4
1
Plant Bioactive Compound Laboratory, Faculty of Agriculture, Chiang Mai University, Chiang Mai 50100,
Thailand
2
Cluster of Agro Bio-Circular-Green Industry (Agro BCG), Chiang Mai University, Chiang Mai 50100,
Thailand
3
Cluster of Research and Development of Pharmaceutical and Natural Products Innovation for Human or
Animal, Chiang Mai University, Chiang Mai 50200, Thailand; chuda.c@cmu.ac.th (C.C.);
warintorn.ruksiri@cmu.ac.th (W.R.); pensak.j@cmu.ac.th (P.J.)
4
Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200,
Thailand
* Correspondence: sarana.s@cmu.ac.th
Academic Editor: Luca Valgimigli
Received: 6 November 2020; Accepted: 8 December 2020; Published: 8 December 2020
Abstract: Terpenes are the primary constituents of essential oils and are responsible for the aroma
characteristics of cannabis. Together with the cannabinoids, terpenes illustrate synergic and/or
entourage effect and their interactions have only been speculated in for the last few decades.
Hundreds of terpenes are identified that allude to cannabis sensory attributes, contributing largely
to the consumer’s experiences and market price. They also enhance many therapeutic benefits,
especially as aromatherapy. To shed light on the importance of terpenes in the cannabis industry,
the purpose of this review is to morphologically describe sources of cannabis terpenes and to explain
the biosynthesis and diversity of terpene profiles in different cannabis chemovars.
Keywords: essential oil; hemp; marijuana; trichomes; volatile profile
1. Introduction
Cannabis sativa L. or cannabis is a herbaceous annual that has a long history of use around the
world as fiber, food, oil as well as medicine. Depending on the purposes of utilization, they can be
called by different names; for example, “hemp” as a fiber and textile crop and “recreational cannabis”,
or known in the USA as marijuana. Aside from its quality as an industrial textile, the psychoactive
properties have labeled a grey stigma to cannabis plants as being an illicit drug with many informal
names including pot, dope, grass, weed, Mary Jane, bud, hash, bhang, kef, ganja, locoweed, reefer,
doob, spliff, toke, and roach. It has been forbidden to grow in many countries due to the psychoactive
ingredients contained [1]. In a medical sense, many recent studies have advised that the increase in
cannabis use was in association with psychiatric symptoms including depression and anxiety [2,3].
However, many users still exclusively endorse its recreational purpose [4,5]. As a result, there has
been a strong movement toward correcting negative attitudes of the cannabis and attempts have been
made in trying to remove this plant from narcotic lists. In Thailand, for instance, as from 2020,
cannabis strains such as ญชง (hemp) and ญชา (marijuana) are legally grown for industrial fiber or
medicinal purposes under the controlled level of active metabolites including cannabinoids of Δ9–
tetrahydrocannabinol (THC) and cannabidiol (CBD) [6]. While focus has paid attention primarily to
the bioactive functions of the cannabinoids, the hydrocarbon terpenes could also offer interesting
entourage effects that could ideally synergize or downstream their effects [7]. Eminently, with the
(marijuana) are legally grown for industrial fiber or medicinal purposes
under the controlled level of active metabolites including cannabinoids of
9–tetrahydrocannabinol
(THC) and cannabidiol (CBD) [
6
]. While focus has paid attention primarily to the bioactive functions
of the cannabinoids, the hydrocarbon terpenes could also oer interesting entourage eects that could
ideally synergize or downstream their eects [
7
]. Eminently, with the rise in the legal cannabis industry,
interest has been made around cannabis terpenes as they contribute many of the dierent aromatic
Molecules 2020,25, 5792; doi:10.3390/molecules25245792 www.mdpi.com/journal/molecules
Molecules 2020,25, 5792 2 of 16
characteristics that influence the diverse varieties of cannabis strains [
8
]. Within the scope of this
review, we provide the general background history of cannabis discovery and the importance of the
terpenes. The taxonomy and morphology of the cannabis, particularly the localization of the terpenes,
are discussed. More importantly, the chemistry, biosynthesis, and diversity of terpenes in dierent
cannabis genotypes are of major interest in this review.
2. The Cannabis Discovery and Its Importance as a Source of Terpene
Cannabis has a long history dating back approximately to just after the Ice Age as cord and textile
scraps made of cannabis fiber have been found in historic caves in the Czech Republic [
9
,
10
]. In the
19th century, the plant was recorded as originating near the southern area of the Caspian Sea near Iran
(Figure 1b) [
11
,
12
]. It was later confirmed by the chemotaxonomy of the essential oil from cannabis
of diverse origins and most of the cannabis phenotypes collected around the globe had chemical
ingredients similar to those of Central Asian origin [
13
]. In previous days, it was known as the original
fiber plant in Asian culture. Seed and seed oil extracts were also used as food [
11
,
14
]. The first record of
cannabis in the literature in China can be dated to approximately 5000 years ago as written by emperor
Chen Nong who was then known as the father of Chinese agriculture. The Chinese alphabet “Ma”
was created using the mimic of the cannabis drying process (Figure 1a). The letter was adjusted to
describe the male plant, “his” separated from the female plant, “chu” for the quality of the fiber [
15
,
16
].
In 500 BC, the use of cannabis spread worldwide from Asia to Europe and to Africa through the silk
road. In the 19th century, hemp was popular in the western world as a fiber crop that had superior
qualities [
17
,
18
]. It is not too surprising therefore that cannabis is today known as an ideal plant in terms
of sustainability. In a period of rapid industrial growth, hemp became the industrial crop as countries
raced against one another toward modernity. In addition to the world textile industry, the plant began
to be known for medical issues. It was believed that during the 19th century, there were thousands of
cannabis medicines available, produced by more than 280 manufacturers [
19
]. The growth and the
interest in this fiber crop crashed after the attempt to add it to the narcotic list with opium during the
Geneva convention in 1925 [19].
Figure 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).
The first cannabinoid isolates used for medicinal purposes was in Czechoslovakia, and CBD
was fully characterized for the first time in 1963, followed by the psychoactive THC in the following
year [
20
22
]. 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 [
23
,
24
]. In 1942,
Simonsen and Todd [
25
] were the first researchers who put terpene fractions as a separate category from
the cannabinoids and p-cymene was reported as a main constituent from Egyptian hashish. Only in the
Molecules 2020,25, 5792 3 of 16
past years have the terms synergic and/or entourage eect of the other cannabis compounds including
those of the terpenes been speculated by chemists all over the world [
26
]. It was first described as
routes for the molecular regulation of endogenous cannabinoid activity [27]. Russo [28] documented
the unique therapeutic eect of cannabis terpenes that possibly played a role on the entourage eects
of the medicinal properties of the cannabinoids. This phytocannabinoid-terpenoid synergy could
enhance the treatments of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal,
and bacterial infections [7,2831].
3. Taxonomy and Localization of the Cannabis Terpenes
Cannabis belongs to the small family of 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 3 m 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,b). 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 [32,33].
Figure 2.
The cannabis plant var. Kees’ Old School Haze
®
(available at https://dutch-passion.com)
(a) and their flower buds var. Gorilla Glue (available at http://www.seedstockers.com) (b).
Leaves are palmate with 5–7 leaflets. The male flower (Figure 3a) has no petals, usually with five
yellowish tepals, and five anthers yielded pollen. The female flower (Figure 3b) had a single-ovulate
and was enriched with the trichome structures, which are the localization of the cannabinoids and the
terpenes as shown in Figure 3c. These terpenes are responsible for the defense and interaction with
herbivores and pests.
Taxonomists classified cannabis plants into three species in the early days: (i) C. sativa Linnaeus,
(ii) C. indica Lamarck, and (iii) C. ruderalis [
34
,
35
]. Today, many researchers are convinced that the
cannabis that grows commercially is C. sativa L, but the subvariety “sativa” should be known as hemp
and the subvariety “Indica” should be called recreational cannabis or marijuana. The dierences
in these subvarieties are shown in Table 1. The usable part for hemp is the stem in particular,
while parts usually with trichomes are the usable parts for the 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 [
36
]. 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.
Molecules 2020,25, 5792 4 of 16
Many recent studies have attempted to separate the combination of the 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 [37].
Figure 3.
The cannabis staminate flowers (
a
) and pistillate flowers (
b
) with the trichome structures
as the localization of cannabinoids and terpenes of Kees’ Old School Haze
®
(available at https:
//dutch-passion.com) (c).
Table 1. Dierences between cannabis (marijuana) and hemp.
Characteristics Cannabis (Marijuana) Hemp
Genus Cannabis sativa L. Cannabis sativa L.
Sub variety Indica sativa
Utilized organs leaves, flowers, stems and
seeds containing trichomes stem
Level of psychoactive THC High (>1%/DW) Low
Medicinal CBD Can be high Can be high
Leaf Broad, darker leaf color Thinner and greenish
Content of terpene (Rosin) High (gluey) Low
Three types of glandular trichomes are characterized based upon their surface morphology,
namely bulbous, sessile, and stalked (Figure 4a) [
38
]. Bulbous trichomes are the smallest, while sessile
trichomes appear on the epidermis with a short stalk and 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 [39].
In cannabis, the sessile and stalked trichomes dier not only in morphology, but they also have distinct
fluorescent properties, number of cells in their secretory disc, and terpene profiles [
40
]. 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
less cannabinoids and higher proportions of sesquiterpenes.
To separate the trichomes, the flowers are usually pre-frozen or freeze-dried and then are gently
rubbed on the sieve mesh. The trichomes separated in this process are known as kief, which can be
pressed to make hash. In Nepal, hash is hand-shaped into balls, also known as wax or “Charas” [
41
].
Hash oil, on the other hand, is the concentrated hash that has been dissolved in organic solvents
such as alcohol, propane, or butane [
42
,
43
]. The extraction allows pigments such as chlorophylls and
other contaminants to be extracted along with the terpenes, resulting in a dark green color extract.
After extraction, the solvent is then removed by evaporation either by direct heat or under a vacuum,
resulting in the oil product with high viscosity.
Molecules 2020,25, 5792 5 of 16
Figure 4.
Dierent trichome structures for cannabis plants (
a
); the stalked types that are available on
the floral surface (
b
); and sugar leaf structures with the presences of trichomes of the Cannabis sativa L.
var. Kees’ Old School Haze®(available at https://dutch-passion.com) (c).
4. Terpene Biosynthesis in Cannabis
The energy required for plant growth and development derives from photosynthesis, respiration,
and transpiration with O
2
, CO
2
, 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 or pests and herbivores. Plants then
produce dierent 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 [
44
]. These compounds are produced in
dierent forms and are exploited for their biological functionalities [
45
]; 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 [
46
]. 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 [
47
]. Saponin glycoside in soap nuts can be used as a surfactant [
48
],
and finally, the terpenoids, which are main ingredients found in plants containing essential oils [
49
],
are used as food additives and some depict psychoactive ability and aroma characteristics such as those
found in the cannabis. Terpenes are hydrocarbons with small isoprene units linked to one another to
form chains, while terpenoids are oxygen-containing terpenes. Three types of terpenes/terpenoids
are usually found in the cannabis plant which are (i) monoterpenes (10C) of two isoprene units;
(ii) sesquiterpenes (15C) of three isoprenes; (iii) diterpenes (20C) of four isoprenes; and (iv) triterpenes
(30C) of six isoprenes [
26
]. To date, more than 200 volatiles have been reported from the dierent
cannabis genotypes of which 58 monoterpenes and 38 sesquiterpenes have been characterized [
50
53
].
Figure 5a illustrates a chromatogram of the terpene extract from the floral tissue of cannabis. Among
others, the major monoterpene components are limonene,
β
-myrcene,
α
-pinene, and linalool with
traces of
α
-terpinolene and tran-ocimene [
54
,
55
] (Figure 5b), while predominate sesquiterpenes are
E-caryophyllene, caryophyllene oxide, E-
β
-farnesene, and
β
-caryophyllene [
56
]. The cannabinoids
are biologically synthesized from diterpene structures to form phenol terpenoids, which account for
almost a quarter of all metabolites [
26
]. Thus, the combination of the terpenes provides the unique
aromas to dierent strains.
Molecules 2020,25, 5792 6 of 16
Figure 5.
The gas chromatogram equipped with mass spectrometry (GC-MS) of the cannabis terpene
extract (butanol) from the floral tissue of Cannabis sativa L. (
a
) and predominant terpene chemovars (
b
).
Denotes the dried cannabis flower (0.2 g) extracted with propanol by the ultrasonic assisted method [
36
]
and gas chromatography mass spectrometry (GC-MS) analysis was performed using the protocol
described previously [57].
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 [
8
,
58
]. These pathways regulate the
dierent substrates available for terpene synthesis (TPS). The MEP converts pyruvate and
glyceraldehyde-3-phosphate (G3P) into 5-carbon building blocks, isopentenyl diphosphate (IPP),
and dimethylallyl diphosphate (DMAPP) in the plastids [
59
]. 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) [
58
]. 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 [59,60]. GPP is also a building block of cannabinoid biosynthesis (Figure 6) [61].
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), delta 8-THC, tetrahydrocannabinolic acid (THCA),
and tetrahydrocannabivarin (THCV) [
62
]. These compounds, along with the terpenes, are produced in
the trichome structures available on the female cannabis flower [
40
]. The highest concentration of the
natural cannabinoids in cannabis are cannabidiolic acid (CBDA) and
9-tetra-hydrocannabinoic acid
(
9-THCA). The psychoactive metabolites such as delta 9-THC and the non-psychoactive CBD are
then activated through decarboxylation by heat treatments. It is also favored by several factors such
Molecules 2020,25, 5792 7 of 16
as storage time and the use of alkaline conditions [
63
,
64
]. Below are the important cannabis terpene
groups and their synergistic and functional properties.
Figure 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.
4.1. Cannabis Monoterpene
The
α
-pinene and
β
-pinene inhibits the activity of acetylcholinesterase in the brain. Therefore,
it is claimed to aid memory and minimize cognitive dysfunction induced by THC intoxication [
65
].
The characteristic of pine scent possesses antiseptic activity [
49
,
66
,
67
].
β
-myrcene is known to have
the analgesic eect of THC and CBD by stimulating the release of endogenous opioids through the
α
2-adrenergic receptor dependent mechanism [
68
,
69
]. Thus, if the level of myrcene is >0.5%, it may
result in a “couch lock” eect while low levels of myrcene (>0.5% myrcene) can produce a higher
energy [
26
]. This compound oers the musky or hop-like fragrance with the functions of antioxidant
and anticarcinogens [
28
,
66
]. Even though it has been postulated that limonene of the citrus aroma has a
low anity for cannabinoid receptors, this monoterpene boosts up the level of serotonin and dopamine,
thereby inducing the anxiolytic, anti-stress, and sedative eects of the CBD [
68
,
70
]. The floral fragrance
of linalool could assist with the anxiety through aromatherapy [66].
4.2. Cannabis Sesquiterpenes
β
-Caryophyllene, a spice (pepper) aroma, is the most available sesquiterpenoid in cannabis
plants and extracts, especially after decarboxylation by heat. It is an agonist with the CB2 receptor
without psychoactivity [
52
]. It is also responsible for the cannabis anti-inflammatory eects [
66
].
This sesquiterpene is also proven to give gastroprotective, analgesic, anticancerogenic, antifungal,
antibacterial, antidepressant, anti-inflammatory, antiproliferative, antioxidant, anxiolytic, analgesic,
and neuroprotective eects [
26
]. The caryophyllene oxide that gives the lemon balm-like scent is
proven to have anti-fungal and insecticidal properties [28].
5. The Cannabis Chemovars
Depending on the variable compositions of the terpenes, dierent cannabis ‘strains’ elicit dierent
aromas with a greater link to product quality, retail price, and consumer preference [
8
,
71
]. The terpene
compositions of cannabis are a seasonal variable. The alteration in the proportion of terpenoids in
cannabis are in accordance with the variety of cannabis, plant part, environmental conditions, maturity,
Molecules 2020,25, 5792 8 of 16
and method of analyses [
72
74
]. Dierent growth stages of the cannabis could give considerable
variations in the terpene compositions. The terpene profile of the cannabis at the vegetative stage was
considered to have a much lower proportion of monoterpenes than the flowering stage [
56
]. Aside from
the variations and compositions of terpenes among dierent phenotypes, the modulated molecular
or biological functions of the terpenes are eective only when the concentration of the terpene in the
full-spectrum cannabis extract is above 0.05% v/w [
31
,
68
,
75
]. To characterize the aromatic profile of the
cannabis of dierent chemovars, solid phase microextraction (SPME), which is non-destructive and
non-invasive, was used to collect the volatiles from the samples [
53
,
76
]. This method favors a small
sample size, and eliminates the use of organic solvents and more importantly, it allows for the emission
of hundreds of volatile compounds from the samples [
53
,
77
]. Figure 7shows the chromatograms of the
volatile compounds diusing from the floral tissue of C. sativa var. Northern Light using SPME and
a gas chromatography. As many as 51 volatiles were detected in which caryophyllene was dominant,
while β-myrcene and limonene were among the major monoterpenes identified.
Figure 7.
The chromatogram of the volatile profiles of Cannabis sativar L. var. Northern Light (https:
//www.seedstockers.com). Denotes terpenes isolated from dried florescence (50 mg) using headspace
solid phase microextraction (SPME) with 50/30
µ
m carbowax-divinylbenzene, CAR-PDMS-DVB
StableFlex fiber (Supelco, Bellefonte, PA, USA) followed by gas chromatography coupled with mass
spectrometry [75,78].
Among the cannabis strains analyzed by Shapira, Berman, Futoran, Guberman, and Meiri [
75
],
five chemotype groups were elucidated according the predominant terpenes: (i)
β
-myrcene, (ii)
α
- and
β
-pinene, (iii)
β
-caryophyllene and limonene, (iv)
β
-caryophyllene, and (v) terpinolene. In the sensory
perception of the terpene profile dierences among cannabis strains, two distinct descriptive clustering
groups were nominated [
71
]. The first group included uniformly earthy, woody, and herbal, and the
other group comprised the most frequent descriptors including citrus, lemon, sweet, and pungent.
Table 3shows the lists of cannabis strains available from the Dutch passion seed company (https:
//dutch-passion.com) classified by the chemotypes and descriptive ategories.
Molecules 2020,25, 5792 9 of 16
Table 2. Terpene profile category of dierent commercial cannabis stains.
Cannabis Family
(Commercial)* Stains (Commercial
Names)
Seed Types Level of Cannabinoid
THC (Max =5)
Chemotypic Catagories 1Descriptive Sensorial Categories 1
(i)
β-myrcene
(ii) α- and
β-pinene
(iii)
β-caryophyllene
and Limonene
(iv)
β-caryophyllene
(v)
Terpinolene
(i) Earthy, Woody
and Herbal
(ii) Citrus, Lemon,
Sweet and Pungent
Afghani Kush
Banana Blaze®F 3
Auto Banana Blaze®F, A 5
Master Kush F 3
Night Queen®F 4
Blue family
Auto Blue Berry®F, A 3
Auto Black Berry Kush®F, A 4
Blue Auto Mazar®F, A 4
CBD rich
CBD Charlotte’s Angel®F 1
CBD Skunk Haze®F 2
Classics
C-vibez®F 5
Mokum’s Tulip®F 4
Auto Ultimate®F, A 4
Think Fast®F 3
Auto Cinderella Jack®F, A 5
Outlaw Amnesia®F 4
Auto Xtreme®F, A 4
Auto White Widow®F, A 4
Molecules 2020,25, 5792 10 of 16
Table 3. Terpene profile category of dierent commercial cannabis stains.
Cannabis Family
(Commercial)* Stains (Commercial
Names)
Seed Types Level of Cannabinoid
THC (Max =5)
Chemotypic Catagories 1Descriptive Sensorial Categories 1
(i)
β-myrcene
(ii) α- and
β-pinene
(iii)
β-caryophyllene
and Limonene
(iv)
β-caryophyllene
(v)
Terpinolene
(i) Earthy, Woody
and Herbal
(ii) Citrus, Lemon,
Sweet and Pungent
Dutch outdoor
Frisian Dew®F 2
Purple N0. 1®R, F 2
Auto Durban Poison®F, A 2
High altitude Snow Bud®F 2
Orange family Passion Fruit®F 4
US special
Sugar Bomb Punch®F 5
Kerosene Krash®F 5
Meringue®F 5
Hifi 4G®F 4
Auto lemon Kix®F, A 5
Bubba island Kush®F 4
Auto Glueberry O.G.®F, A 4
1
The chemotype categories as described by Shapira, Berman, Futoran, Guberman, and Meiri [
75
] and the descriptive sensory group according to Gilbert and DiVerdi [
71
]. F =Feminized;
A=Auto; R =Regular, * available at https://dutch-passion.com. The odor representatives; hop; pine; lime; spice and orange peel were according to Russo [
28
].
Molecules 2020,25, 5792 11 of 16
6. Separation of Cannabis Terpenes and Industrial Importance
In the past, identifying the terpene profile of the cannabis was for the purposes of improving canine
training aids in illicit drug detection [
76
]. In the world of the cannabis industry, however, terpenes
play a vital role in dierentiating the flavor and aroma that are specific to the particular strains [
56
].
Some terpenes can enhance the eect of cannabinoids and synergize the feeling of relaxation, stress relief,
energy boost, and maintaining focus along with their underlying pharmaceutical functions [
54
,
79
].
Thus, a growing number of industries have shown interest in adding either cannabis terpenes or
botanically-derived terpenes to their CBD oils and edibles. The estimated growth in this sector should
reach a 20 billion-market by 2024 [
80
,
81
]. The success in this sector might be challenged by a few
restrains. First, the consumer believes that the functionality and safety are truly related to sources,
perceived novelty, and most importantly, perceived benefits [
82
,
83
]. Additionally, the extraction of the
full-spectrum oil consisting of a full mix of naturally occurring cannabis terpenes is almost impossible.
The most cost-eective way is to selectively separate the terpenes and include them back into the final
products [68,80].
Numerous terpene recovery techniques have been developed by solvent-based or solvent-less.
Essential oils are usually hydro-distillated extracts from the trichomes of cannabis containing mostly
terpenes or terpenoids. Although most of the constituents remain intact during distillation, a few
monoterpenes may undergo chemical changes or are quite often lost due to the nature of the distillation
process [
26
,
56
]. The other possible technique is steam distillation by passing dry steam through the
inflorescences of the cannabis whereby the terpenes are volatilized, condensed, and collected [
84
,
85
].
Moreover, the microwave-assisted extraction (MAE) can enrich bioactive compounds. The MAE
treatment using high irradiation power and relatively long extraction times significantly increased the
content of CBD in the essential oil with considerably high yield when compared with the conventional
hydro-distillation techniques [
86
]. In Canada, for instance, the commercial production of the extract is
achieved by either solvent extraction such as butane or supercritical fluid (SFE) with the restriction
on product purity of no solvent contaminants [
87
]. The later technique is known to give superior
performance in terpene recovery [
88
]. SFE has recently become a much-preferred method for terpene
recovery, largely because it allows using lower temperatures, leading to less deterioration of the
thermally labile components and is free from organic solvents [
88
,
89
]. A supercritical fluid is the
substance at a temperature and pressure above its critical points, with no boundary between the
liquid and gas stage. At these points, the fluid is low in viscosity with high diusion properties to
dissolve chemical molecules from the plant matrix. Carbon dioxide (CO
2
) is generally used because it
is nonflammable, relatively inexpensive, and non-toxic. Large amounts of terpene ingredients were
recovered from this method (i.e., up to 50%, 20% and 10% of caryophyllene, humulene and limonene,
respectively, can be recovered compared to the conventional methods) [64,89].
7. Conclusions
Recreational cannabis as a food ingredient has become more acceptable in a broader public
context in which cannabis terpenes have gained high industrial attention in recent years. The terpene
profiles not only embody the characteristics of cannabis genotypes, but their entourage eect with
cannabinoids could enhance their medicinal functionality. This review highlights the importance
of understanding cannabis terpene chemistry and provide descriptive profile categories of dierent
cannabis commercial strains.
Author Contributions:
Conceptualization, S.R.S.; Validation, S.R.S. and P.J.; Resources, S.R.S.; Data curation,
S.R.S.; Writing—Original draft preparation, S.R.S.; Writing—Review and editing, C.C., W.R., and P.J., Visualization,
S.R.S. and P.J.; Funding acquisition, S.R.S. and W.R. All authors have read and agreed to the published version of
the manuscript.
Funding: This research work was partially supported by Chiang Mai University.
Acknowledgments:
We would like to especially thank Katsuhisa Komiya for his extended knowledge in the topic.
Michael D. Burgett is highly appreciated for his thoughtful language editing of the entire manuscript.
Molecules 2020,25, 5792 12 of 16
Conflicts of Interest: The authors declare no conflict of interest.
References
1.
Cheng, C.; Zang, G.; Zhao, L.; Gao, C.; Tang, Q.; Chen, J.; Guo, X.; Peng, D.; Su, J. A rapid shoot regeneration
protocol from the cotyledons of hemp (Cannabis sativa L.). Ind. Crop. Prod. 2016,83, 61–65. [CrossRef]
2.
Weinberger, A.H.; Zhu, J.; Levin, J.; Barrington-Trimis, J.L.; Copeland, J.; Wyka, K.; Kim, J.H.; Goodwin, R.D.
Cannabis use among US adults with anxiety from 2008 to 2017: The role of state-level cannabis legalization.
Drug Alcohol Depend. 2020,214, 108163. [CrossRef] [PubMed]
3.
Rabiee, R.; Lundin, A.; Agardh, E.; Hensing, G.; Allebeck, P.; Danielsson, A.-K. Cannabis use and the risk of
anxiety and depression in women: A comparison of three Swedish cohorts. Drug Alcohol Depend.
2020
,216,
108332. [CrossRef] [PubMed]
4.
Lloyd, S.L.; Lopez-Quintero, C.; Striley, C.W. Sex dierences in driving under the influence of cannabis:
The role of medical and recreational cannabis use. Addict. Behav. 2020,110, 106525. [CrossRef] [PubMed]
5.
Turna, J.; Balodis, I.; Munn, C.; Van Ameringen, M.; Busse, J.; MacKillop, J. Overlapping patterns of
recreational and medical cannabis use in a large community sample of cannabis users. Compr. Psychiatry
2020,102, 152188. [CrossRef] [PubMed]
6.
Theparat, C. New Rule Makes It Legal to Grow Hemp. Available online: https://www.bangkokpost.com/
thailand/general/1845714/new-rule-makes-it- legal-to-grow-hemp (accessed on 2 October 2020).
7.
Koltai, H.; Namdar, D. Cannabis Phytomolecule ‘Entourage’: From Domestication to Medical Use.
Trends Plant Sci. 2020,25, 976. [CrossRef] [PubMed]
8.
Booth, J.K.; Bohlmann, J. Terpenes in Cannabis sativa—From plant genome to humans. Plant Sci.
2019
,
284, 67. [CrossRef]
9.
Clarke, R.; Merlin, M.D. History of Cannabis Use for Fiber. In Cannabis; University of California Press:
Berkeley, CA, USA, 2019.
10.
Fleming, M.; Clarke, R. Physical evidence for the antiquity of Cannabis sativa L. J. Int. Hemp Assoc.
1998,5, 80–95.
11.
Li, H.-L. An archaeological and historical account of cannabis in China. Econ. Bot.
1973
,28, 437–448. [CrossRef]
12.
Li, H.-L. The origin and use of cannabis in Eastern Asia linguistic-cultural implications. Econ. Bot.
1974
,
28, 293–301. [CrossRef]
13.
Hillig, K.W. A chemotaxonomic analysis of terpenoid variation in Cannabis. Biochem. Syst. Ecol.
2004
,
32, 875–891. [CrossRef]
14.
Aluko, R.E. Chapter 7—Hemp Seed (Cannabis sativa L.) Proteins: Composition, Structure, Enzymatic
Modification, and Functional or Bioactive Properties. In Sustainable Protein Sources; Nadathur, S.R.,
Wanasundara, J.P.D., Scanlin, L., Eds.; Academic Press: San Diego, CA, USA, 2017. [CrossRef]
15.
Abel, E.L. Cannabis in the Ancient World. In Marihuana; Springer: Berlin/Heidelberg, Germany, 1980;
pp. 3–35.
16.
Bonini, S.A.; Premoli, M.; Tambaro, S.; Kumar, A.; Maccarinelli, G.; Memo, M.; Mastinu, A. Cannabis sativa:
A comprehensive ethnopharmacological review of a medicinal plant with a long history. J. Ethnopharmacol.
2018,227, 300. [CrossRef] [PubMed]
17.
Mediavilla, V.; Leupin, M.; Keller, A. Influence of the growth stage of industrial hemp on the yield formation
in relation to certain fibre quality traits. Ind. Crop. Prod. 2001,13, 49–56. [CrossRef]
18.
Cosentino, S.L.; Riggi, E.; Testa, G.; Scordia, D.; Copani, V. Evaluation of European developed fibre
hemp genotypes (Cannabis sativa L.) in semi-arid Mediterranean environment. Ind. Crop. Prod.
2013
,
50, 312–324. [CrossRef]
19.
Bewley-Taylor, D.; Blickman, T.; Jelsma, M. The Rise and Decline of Cannabis Prohibition, the History of
Cannabis in the UN Drug Control System and Options for Reform; Transnational Institute (TNI): Amsterdam,
The Netherlands, 2014.
20.
Gaoni, Y.; Mechoulam, R. Isolation, structure, and partial synthesis of an active constituent of Hashish. J. Am.
Chem. Soc. 1964,86, 1646–1647. [CrossRef]
21.
Mudr, P.; Et, S.; Facultatis, M. Compounds. In Acta Universitatis Palackianae Olomucensis-TOM.35;
Facultatis, M., Ed.; PalackýUniversity Olomouc: Olomouc, Czech Republic, 1964.
Molecules 2020,25, 5792 13 of 16
22.
Adams, R.; Pease, D.C.; Cain, C.K.; Baker, B.R.; Clark, J.H.; Wol, H.; Wearn, R.B. Conversion of cannabidiol
to a product with marihuana activity. A type reaction for synthesis of analogous substances. conversion of
cannabidiol to cannabinol. J. Am. Chem. Soc. 1940,62, 2245–2246. [CrossRef]
23.
Devane, W.A.; Dysarz, F.A., 3rd; Johnson, M.R.; Melvin, L.S.; Howlett, A.C. Determination and
characterization of a cannabinoid receptor in rat brain. Mol. Pharmacol. 1988,34, 605–613. [PubMed]
24.
Devane, A.W.; Hanus, L.; Breuer, A.; Pertwee, R.G.; Stevenson, A.L.; Grin, G.; Gibson, D.; Mandelbaum, A.;
Etinger, A.; Mechoulam, R. Isolation and structure of a brain constituent that binds to the cannabinoid receptor.
Science 1992,258, 1946–1949. [CrossRef]
25.
Simonsen, J.L.; Todd, A.R. 32. Cannabis indica. Part X. The essential oil from Egyptian hashish. J. Chem. Soc.
1942,10, 188. [CrossRef]
26.
Hanuš, L.O.; Hod, Y. Terpenes/Terpenoids in Cannabis: Are They Important? Med. Cannabis Cannabinoids
2020,3, 25–60. [CrossRef]
27.
Ben-Shabat, S.; Fride, E.; Sheskin, T.; Tamiri, T.; Rhee, M.-H.; Vogel, Z.; Bisogno, T.; De Petrocellis, L.;
Di Marzo, V.; Mechoulam, R. An entourage eect: Inactive endogenous fatty acid glycerol esters enhance
2-arachidonoyl-glycerol cannabinoid activity. Eur. J. Pharmacol. 1998,353, 23–31. [CrossRef]
28.
Russo, E.B. Taming THC: Potential cannabis synergy and phytocannabinoid-terpenoid entourage eects.
Br. J. Pharmacol. 2011,163, 1344–1364. [CrossRef]
29.
Gallily, R.; Yekhtin, Z.; Hanuš, L.O. The Anti-Inflammatory Properties of Terpenoids from Cannabis.
Cannabis Cannabinoid Res. 2018,3, 282. [CrossRef] [PubMed]
30.
Baron, E.P. Medicinal properties of cannabinoids, terpenes, and flavonoids in cannabis, and benefits in
migraine, headache, and pain: An update on current evidence and cannabis science. Headache J. Head
Face Pain 2018,58, 1139. [CrossRef] [PubMed]
31.
Lewis, M.A.; Russo, E.B.; Smith, K.M. Pharmacological foundations of cannabis chemovars. Planta Med.
2017,84, 225. [CrossRef] [PubMed]
32.
Horne, M.R.L. 5B-Bast fibres: Hemp cultivation and production. In Handbook of Natural Fibres, 2nd ed.;
Kozłowski, R.M., Mackiewicz-Talarczyk, M., Eds.; Woodhead Publishing: Cambridge, UK, 2020. [CrossRef]
33.
R
é
quil
é
, S.; Le Duigou, A.; Bourmaud, A.; Baley, C. Peeling experiments for hemp retting characterization
targeting biocomposites. Ind. Crop. Prod. 2018,123, 573. [CrossRef]
34.
Anderson, L.C. Leaf variation among cannabis species from a controlled garden. Bot. Mus. Leafl. Harv. Univ.
1980,28, 61–69.
35.
Schultes, R.E.; Klein, W.M.; Plowman, T.; Lockwood, T.E. 35. In Cannabis: An Example of Taxonomic Neglect;
Walter de Gruyter GmbH: Berlin, Germany, 1975; Volume 23, pp. 21–38.
36.
Cai, C.; Yu, W.; Wang, C.; Liu, L.; Li, F.; Tan, Z. Green extraction of cannabidiol from industrial
hemp (Cannabis sativa L.) using deep eutectic solvents coupled with further enrichment and recovery
by macroporous resin. J. Mol. Liq. 2019,287, 110957. [CrossRef]
37.
Wiebelhaus, N.; Hamblin, D.; Kreitals, N.M.; Almirall, J.R. Dierentiation of marijuana headspace volatiles
from other plants and hemp products using capillary microextraction of volatiles (CMV) coupled to
gas-chromatography-mass spectrometry (GC-MS). Forensic Chem. 2016,2, 1–8. [CrossRef]
38.
Hammond, C.T.; Mahlberg, P.G. Morphogenesis of capitate glandular hairs of Cannabis sativa (Cannabaceae).
Am. J. Bot. 1977,64, 1023–1031. [CrossRef]
39.
Potter, D. The Propagation, Characterisation and Optimisation of Cannabis sativa L. as a Phytopharmaceutical;
King’s College London: London, UK, 2009.
40.
Livingston, S.J.; Quilichini, T.D.; Booth, J.K.; Wong, D.C.J.; Rensing, K.H.; Laflamme-Yonkman, J.;
Castellarin, S.D.; Bohlmann, J.; Page, J.E.; Samuels, A.L. Cannabis glandular trichomes alter morphology and
metabolite content during flower maturation. Plant J. 2019,101, 37. [CrossRef] [PubMed]
41.
Gupta, A.K.; Jain, A.; Roy, P.; Singh, R. Pharmacological evaluation of Cannabis indica for their
aphrodisiac potential. Int. J. Ayurvedic Med. 2020,11, 399. [CrossRef]
42.
Ahmed, A.; Shapiro, D.; Su, J.; Nelson, L.P. Vaping Cannabis Butane Hash Oil Leads to Severe Acute
Respiratory Distress Syndrome—A case of EVALI in a teenager with hypertrophic cardiomyopathy. J. Intensiv.
Care Med. 2020. [CrossRef] [PubMed]
43.
Stephens, D.; Patel, J.K.; Angelo, D.; Frunzi, J. Cannabis butane hash oil dabbing induced lung injury
mimicking atypical pneumonia. Cureus 2020,12, e7033. [CrossRef] [PubMed]
Molecules 2020,25, 5792 14 of 16
44.
Schwachtje, J.; Baldwin, I.T. Why does herbivore attack reconfigure primary metabolism? Plant Physiol.
2008
,
146, 845–851. [CrossRef] [PubMed]
45.
Sommano, S. Eect of Food Processing on Bioactive Compounds. In Advances in Food Science and Nutrition,
2nd ed.; Visakh, M.P., Iturriaga, L.B., Ribotta, P.D., Eds.; Scrivener Publishing LLC: Beverly, MA, USA, 2013;
pp. 361–390. [CrossRef]
46.
Sommano, S.R.; Can, N.; Kerven, G. Screening for antioxidant activity, phenolic content, and flavonoids
from Australian native food plants. Int. J. Food Prop. 2012,16, 1394–1406. [CrossRef]
47.
Sunanta, P.; Chung, H.-H.; Kunasakdakul, K.; Ruksiriwanich, W.; Jantrawut, P.; Hongsibsong, S.;
Sommano, S.R. Genomic relationship and physiochemical properties among raw materials used for Thai
black garlic processing. Food Sci. Nutr. 2020,8, 4534–4545. [CrossRef]
48.
Wisetkomolmat, J.; Suppakittpaisarn, P.; Sommano, S.R. Detergent plants of northern Thailand: Potential
sources of natural saponins. Resources 2019,8, 10. [CrossRef]
49.
Tangpao, T.; Chung, H.-H.; Sommano, S.R. Aromatic profiles of essential oils from five commonly used
Thai basils. Foods 2018,7, 175. [CrossRef]
50.
Ross, S.A.; ElSohly, M.A. The volatile oil composition of fresh and air-dried buds of Cannabis sativa.J. Nat. Prod.
1996,59, 49–51. [CrossRef]
51.
Turner, C.E.; ElSohly, M.A.; Boeren, E.G. Constituents of Cannabis sativa L. XVII. A review of the
natural constituents. J. Nat. Prod. 1980,43, 169–234. [CrossRef] [PubMed]
52.
Wanas, A.S.; Radwan, M.M.; Chandra, S.; Lata, H.; Mehmedic, Z.; Ali, A.; Baser, K.; Demirci, B.; ElSohly, M.A.
Chemical composition of volatile oils of fresh and air-dried buds of cannabis chemovars, their insecticidal
and repellent activities. Nat. Prod. Commun. 2020,15, 1934578X20926729. [CrossRef]
53.
Rice, S.; Koziel, J.A. Characterizing the smell of marijuana by odor impact of volatile compounds:
An application of simultaneous chemical and sensory analysis. PLoS ONE 2015,10, e0144160. [CrossRef]
54.
Ternelli, M.; Brighenti, V.; Anceschi, L.; Poto, M.; Bertelli, D.; Licata, M.; Pellati, F. Innovative methods for
the preparation of medical cannabis oils with a high content of both cannabinoids and terpenes. J. Pharm.
Biomed. Anal. 2020,186, 113296. [CrossRef] [PubMed]
55.
Wang, C.-T.; Ashworth, K.; Wiedinmyer, C.; Ortega, J.; Harley, P.C.; Rasool, Q.Z.; Vizuete, W.
Ambient measurements of monoterpenes near Cannabis cultivation facilities in Denver, Colorado.
Atmos. Environ. 2020,232, 117510. [CrossRef]
56.
Abdollahi, M.; Sefidkon, F.; Calagari, M.; Mousavi, A.; Mahomoodally, M.F. Impact of four hemp
(Cannabis sativa L.) varieties and stage of plant growth on yield and composition of essential oils. Ind. Crop. Prod.
2020,155, 112793. [CrossRef]
57.
Sriwichai, T.; Junmahasathien, T.; Sookwong, P.; Potapohn, N.; Sommano, S.R. Evaluation of the optimum
harvesting maturity of makhwaen fruit for the perfumery industry. Agriculture 2019,9, 78. [CrossRef]
58.
Booth, J.K.; Page, J.E.; Bohlmann, J. Terpene synthases from Cannabis sativa.PLoS ONE
2017
,
12, e0173911. [CrossRef]
59.
Nagegowda, D.A.; Gupta, P. Advances in biosynthesis, regulation, and metabolic engineering of plant
specialized terpenoids. Plant Sci. 2020,294, 110457. [CrossRef]
60.
Chen, F.; Tholl, D.; Bohlmann, J.; Pichersky, E. The family of terpene synthases in plants: A mid-size
family of genes for specialized metabolism that is highly diversified throughout the kingdom. Plant J.
2011
,
66, 212–229. [CrossRef]
61.
Fellermeier, M.; Eisenreich, W.; Bacher, A.; Zenk, M.H. Biosynthesis of cannabinoids Incorporation
experiments with 13C-labeled glucoses. JBIC J. Biol. Inorg. Chem.
2001
,268, 1596–1604. [CrossRef] [PubMed]
62.
Aliferis, K.A.; Bernard-Perron, D. Cannabinomics: Application of metabolomics in cannabis (Cannabis sativa L.)
research and development. Front. Plant Sci. 2020,11, 11. [CrossRef] [PubMed]
63.
Masoud, A.N.; Doorenbos, N.J. Mississippi-Grown Cannabis sativa L. III: Cannabinoid and cannabinoid
acid content. J. Pharm. Sci. 1973,62, 313–315. [CrossRef]
64.
Grij
ó
, D.R.; Osorio, I.A.V.; Cardozo-Filho, L. Supercritical extraction strategies using CO2 and ethanol to
obtain cannabinoid compounds from Cannabis hybrid flowers. J. CO2 Util. 2018,28, 174. [CrossRef]
65. Miyazawa, M.; Yamafuji, C. Inhibition of acetylcholinesterase activity by bicyclic monoterpenoids. J. Agric.
Food Chem. 2005,53, 1765–1768. [CrossRef] [PubMed]
Molecules 2020,25, 5792 15 of 16
66.
Gaggiotti, S.; Palmieri, S.; Pelle, F.D.; Sergi, M.; Cichelli, A.; Mascini, M.; Compagnone, D.
Piezoelectric peptide-hpDNA based electronic nose for the detection of terpenes; Evaluation of the aroma
profile in dierent Cannabis sativa L. (hemp) samples. Sens. Actuators B Chem.
2020
,308, 127697. [CrossRef]
67.
Sriwichai, T.; Sookwong, P.; Siddiqui, M.W.; Sommano, S.R. Aromatic profiling of Zanthoxylum myriacanthum
(makwhaen) essential oils from dried fruits using dierent initial drying techniques. Ind. Crop. Prod.
2019
,
133, 284. [CrossRef]
68.
Maayah, Z.H.; Takahara, S.; Ferdaoussi, M.; Dyck, J.R. The molecular mechanisms that underpin the
biological benefits of full-spectrum cannabis extract in the treatment of neuropathic pain and inflammation.
Biochim. Biophys. Acta (BBA) Mol. Basis Dis. 2020,1866, 165771. [CrossRef]
69.
Rao, V.S.N.; Menezes, A.M.S.; Viana, G.S.B. Eect of myrcene on nociception in mice. J. Pharm. Pharmacol.
1990,42, 877–878. [CrossRef]
70.
Meschler, J. Thujone exhibits low anity for cannabinoid receptors but fails to evoke
cannabimimetic responses. Pharmacol. Biochem. Behav. 1999,62, 473–480. [CrossRef]
71.
Gilbert, A.N.; DiVerdi, J.A. Consumer perceptions of strain dierences in Cannabis aroma. PLoS ONE
2018
,
13, e0192247. [CrossRef] [PubMed]
72.
Brenneisen, R. Chemistry and Analysis of Phytocannabinoids and Other Cannabis Constituents. In Marijuana
and the Cannabinoids; ElSohly, M.A., Ed.; Humana Press: Totowa, NJ, USA, 2007. [CrossRef]
73.
Fischedick, J.T.; Hazekamp, A.; Erkelens, T.; Choi, Y.H.; Verpoorte, R. Metabolic fingerprinting of
Cannabis sativa L., cannabinoids and terpenoids for chemotaxonomic and drug standardization purposes.
Phytochemistry 2010,71, 2058–2073. [CrossRef] [PubMed]
74.
Brown, A.K.; Xia, Z.; Bulloch, P.; Idowu, I.; Francisco, O.; Stetefeld, J.; Stout, J.; Zimmer, J.;
Marvin, C.; Letcher, R.J.; et al. Validated quantitative cannabis profiling for Canadian regulatory
compliance—Cannabinoids, aflatoxins, and terpenes. Anal. Chim. Acta
2019
,1088, 79. [CrossRef] [PubMed]
75.
Shapira, A.; Berman, P.; Futoran, K.; Guberman, O.; Meiri, D. Tandem Mass Spectrometric Quantification of
93 terpenoids in cannabis using static headspace injections. Anal. Chem. 2019,91, 11425. [CrossRef]
76.
Rice, S.; Koziel, J.A. The relationship between chemical concentration and odor activity value explains
the inconsistency in making a comprehensive surrogate scent training tool representative of illicit drugs.
Forensic Sci. Int. 2015,257, 257–270. [CrossRef]
77.
Kabir, A.; Holness, H.; Furton, K.G.; Almirall, J.R. Recent advances in micro-sample preparation with
forensic applications. TrAC Trends Anal. Chem. 2013,45, 264–279. [CrossRef]
78.
Calvi, L.; Pentimalli, D.; Panseri, S.; Giupponi, L.; Gelmini, F.; Beretta, G.; Vitali, D.; Bruno, M.; Zilio, E.;
Pavlovic, R.; et al. Comprehensive quality evaluation of medical Cannabis sativa L. inflorescence and
macerated oils based on HS-SPME coupled to GC–MS and LC-HRMS (q-exactive orbitrap
®
) approach.
J. Pharm. Biomed. Anal. 2018,150, 208. [CrossRef]
79.
Koltai, H.; Poulin, P.; Namdar, D. Promoting cannabis products to pharmaceutical drugs. Eur. J. Pharm. Sci.
2019,132, 118. [CrossRef]
80.
Koby, M. How Terpenes Could Revolutionize the Cannabis Industry as We Know It in Innovators; Entrepreneur Media,
Inc.: Irvine, CA, USA, 2020.
81.
King, J.W. The relationship between cannabis/hemp use in foods and processing methodology. Curr. Opin.
Food Sci. 2019,28, 32. [CrossRef]
82.
Charlebois, S.; Somogyi, S.; Sterling, B. Cannabis-infused food and Canadian consumers’ willingness to
consider “recreational” cannabis as a food ingredient. Trends Food Sci. Technol. 2018,74, 112. [CrossRef]
83.
Khan, R.S.; Grigor, J.V.; Winger, R.; Win, A. Functional food product development—Opportunities and
challenges for food manufacturers. Trends Food Sci. Technol. 2013,30, 27–37. [CrossRef]
84.
Benelli, G.; Pavela, R.; Petrelli, R.; Cappellacci, L.; Santini, G.; Fiorini, D.; Sut, S.; Dall’Acqua, S.; Canale, A.;
Maggi, F. The essential oil from industrial hemp (Cannabis sativa L.) by-products as an eective tool for insect
pest management in organic crops. Ind. Crop. Prod. 2018,122, 308. [CrossRef]
85.
Hanif, M.A.; Nawaz, H.; Naz, S.; Mukhtar, R.; Rashid, N.; Bhatti, I.A.; Saleem, M. Raman spectroscopy for the
characterization of dierent fractions of hemp essential oil extracted at 130
C using steam distillation method.
Spectrochim. Acta Part A Mol. Biomol. Spectrosc. 2017,182, 168. [CrossRef] [PubMed]
86.
Fiorini, D.; Scortichini, S.; Bonacucina, G.; Greco, N.G.; Mazzara, E.; Petrelli, R.; Torresi, J.; Maggi, F.; Cespi, M.
Cannabidiol-enriched hemp essential oil obtained by an optimized microwave-assisted extraction using a
central composite design. Ind. Crop. Prod. 2020,154, 112688. [CrossRef]
Molecules 2020,25, 5792 16 of 16
87.
Blake, A.; Nahtigal, I. The evolving landscape of cannabis edibles. Curr. Opin. FoodSci.
2019
,28, 25. [CrossRef]
88.
Baldino, L.; Scognamiglio, M.; Reverchon, E. Supercritical fluid technologies applied to the extraction of
compounds of industrial interest from Cannabis sativa L. and to their pharmaceutical formulations: A review.
J. Supercrit. Fluids 2020,165, 104960. [CrossRef]
89.
Naz, S.; Hanif, M.A.; Bhatti, H.N.; Ansari, T.M. Impact of supercritical fluid extraction and traditional
distillation on the isolation of aromatic compounds from Cannabis indica and Cannabis sativa.J. Essent. Oil
Bear. Plants 2017,20, 175. [CrossRef]
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... 16,17 b-Caryophyllene possesses gastroprotective, analgesic, anticancerogenic, antifungal, antibacterial, antidepressant, anti-inflammatory, antiproliferative, antioxidant, anxiolytic, analgesic, and neuroprotective effects. 18,19 b-Myrcene has analgesic effects similar to THC and CBD by stimulating the release of endogenous opioids through the a2-adrenergic receptor dependent mechanism. 19 Pinene is known to aid memory and minimize cognitive dysfunction, as well as being used for its antiseptic properties. ...
... 18,19 b-Myrcene has analgesic effects similar to THC and CBD by stimulating the release of endogenous opioids through the a2-adrenergic receptor dependent mechanism. 19 Pinene is known to aid memory and minimize cognitive dysfunction, as well as being used for its antiseptic properties. 19 It has been used to treat respiratory tract infections for centuries. ...
... 19 Pinene is known to aid memory and minimize cognitive dysfunction, as well as being used for its antiseptic properties. 19 It has been used to treat respiratory tract infections for centuries. 20 Endourage, Formula CÔ, the focus of this study, is a CBD-rich, hemp-derived, whole-flower preparation with trace amounts of THC and other minor cannabinoids and a robust terpene profile. ...
Article
Introduction: Coronavirus Disease 2019 (COVID-19) causes a wide range of symptoms, including death. As persons recover, some continue to experience symptoms described as Post-Acute COVID-19 Syndrome (PACS). The objectives of this study were to measure the efficacy of Formula C™, a cannabidiol (CBD)-rich, whole-flower terpene-rich preparation in managing PACS symptoms. Materials and Methods: This randomized, placebo-controlled, single-blind, open-label crossover study was conducted in 2021. Informed consent was obtained from participants, and they were randomized to two treatment groups. Group 1 (n=15) received blinded active product for 28 days, and Group 2 (n=16) received blinded placebo for 28 days (Treatment Period 1). Both groups crossed over to open-label active product for 28 days (Treatment Period 2) with a safety assessment at day 70. Patient-Reported Outcomes Measurement Information System (PROMIS®) scores and the Patient Global Impression of Change (PGIC) score were used to assess primary and secondary objectives. Safety assessments were also done at each visit. Results: Twenty-four participants completed study, with 8 withdrawals, none related to study product. PGIC and PROMIS scores improved across both groups at day 28. This raised questions about the placebo. A reanalysis of the placebo confirmed absence of CBD and unexpected medical concentration of terpenes. The study continued despite no longer having a true placebo. The improved scores on outcome measures were maintained across the open label treatment period. There were no safety events reported throughout the study. Discussion: For persons with PACS who are nonresponsive to conventional therapies, this study demonstrated symptom improvement for participants utilizing Formula C. In addition, the benefits seen in Group 2 suggest the possibility that non-CBD formulations rich in antioxidants, omega-3, and omega-6 fatty acids, gamma-linoleic acid, and terpenes may also have contributed to the overall improvement of the partial active group through the study. Conclusion: Given that both groups demonstrated improvement, both formulations may be contributing to these findings. Limitations include the small number of participants, the lack of a true placebo, and limited time on study products. Additional studies are warranted to explore both CBD-rich hemp products and hempseed oil as treatment options for PACS. Trial Registration ClinicalTrials.gov Identifier: NCT04828668.
... Similarly deficient are clinical trials of oils specified by the strain used to form them, assuming that this strain's properties are retained in the formed extract [43][44][45]. As the composition of terpenes in extracts varies with cultivation conditions and depends on the extraction and thermal process steps used [4,33,42,46,47], no reproducibility is guaranteed for different extracts of the same plant source, unless directly analyzed and corrected. It is worth noting that Sativex ® and Cannador ® , the intensively studied and used cannabis extracts, are defined by their THC and CBD content, with no data on the other extracted ingredients [40,48]. ...
... Some publications suggest collecting the lost terpenes and adding them back to the produced oil [33,47]. Given the number of steps wherein terpenes evaporate and given the need to separate terpene vapors from other gaseous components (e.g., solvent vapors), such collection is practically infeasible in industrial production, processing dozens of kilograms of inflorescence per batch. ...
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Differences between therapeutic effects of medical cannabis inflorescences and those of their extracts are generally attributed to the differences in administration form and in the resultant pharmacokinetics. We hypothesized that difference may further extend to the composition of the actually consumed drug. Cannabinoid and terpene contents were compared between commercial cannabis inflorescences (n = 19) and decarboxylated extracts (n = 12), and between inflorescences and decarboxylated extracts produced from them (n = 10). While cannabinoid content was preserved in the extracts, a significant loss of terpenes was evident, mainly in the more volatile monoterpenes and monoterpenoids (representing a loss of about 90%). This loss changes the total terpene content, the proportion of monoterpenes out of the total terpenes, and the monoterpene/cannabinoid ratio. Terpene deficiency might impair extracts’ pharmacological efficacy and might contribute to the patients’ preference to inflorescences-smoking. This argues against the validity of terms such as “whole plant” and “full spectrum” extracts and creates a misleading assumption that extracts represent the pharmacological profile of the sourced inflorescences. Furthermore, it reduces the diversity in extracts, such as loss of differences between sativa-type and indica-type. Enriching cannabis extracts with selected terpenes may provide a suitable solution, generating a safe, precise, and reproducible drug with tailored cannabinoid and terpene contents. Careful selection of terpenes to be added enables tailor-made extracts, adjusted for various medicinal aims and for different populations.
... The diverse classes of secondary metabolites are different parts of the plant with a wide range of applications (nutraceuticals, cosmetics, aromatherapy, and pharmacotherapy) that are beneficial to humans. However, in the past, they focused the studies mainly on the two most abundant phytocannabinoids: THC and CBD, which resulted in greater knowledge about their pharmacological activities, increasing interest in the numerous possibilities of medicinal actions of the plant [88][89][90][91][92] Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 7 November 2022 doi:10.20944/preprints202211.0122.v1 Figure 07. ...
Preprint
The endocannabinoid system (eCB) began to be studied from the identification of the molecular structures present in the cannabis sativa plant. The ECS is constituted of cannabinoid receptors, endogenous ligands and all the associated enzymatic apparatus responsible for maintaining homeostasis. Several physiological effects of cannabinoids are exerted through interaction with various receptors such as CB1 and CB2 receptors, vanilloid receptors, and the recently discovered [GPCRs (GPR55, GPR3, GPR6, GPR12 and GPR19). Endogenous ligands such anandamide and 2-arachidonoylglycerol might modulate these receptors. eCB has proved to play a critical role in some human diseases and has been extensively studied due to its wide therapeutic potential and because it is a promising target for the development of new drugs. Phytocannabinoids and synthetic cannabinoids have shown varied affinities to eCB, which are relevant to the treatment of various diseases. They may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases. Furthermore, Integrative and Complementary Health Practices (ICHP) appear to influence the endocannabinoid system through modulation. This review will show a description of ECS components and discuss how phytocannabinoids, other exogenous compounds, and PICS may operate the eCB balance.
... Therefore, the behavioral effects of whole-plant cannabis use result from complex interactions between an array of cannabis components. Recent research suggests that terpenes [54], another group of cannabis compounds, may also have anxiolytic effects [14 ••, 55]. Therefore, future research is needed to elucidate how THC interacts with other cannabinoids to impact anxiety, as well as to better understand how these effects change with extended cannabis exposure. ...
Article
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Purpose of Review In the context of ongoing decriminalization and legalization of cannabis, a better understanding of how THC and CBD impact anxiety is critical to elucidate the risks of recreational cannabis use as well as to establish the therapeutic potential of cannabis products for anxiety-related applications. Recent Findings Recent literature supports anxiogenic effects of THC administration, which may be attenuated among regular cannabis users. Data regarding anxiolytic effects of CBD administration are mixed. Most newer studies contradict earlier findings in reporting no effects of CBD on anxiety in healthy participants, whereas inconsistent results have been reported among individuals with anxiety disorders, substance use disorders, and other clinical populations. Summary Future research is needed to reconcile heterogenous findings, explore sex differences in the effects of THC and CBD on anxiety, and to assess how effects change with extended exposure; the impact of different CBD doses, and the interactions between THC, CBD, and other cannabis compounds.
... There are several types of C. sativa strains, which provide incredibly different aromas (Sommano et al., 2020). To date, there have been very few trials to quantify these compounds which provide aromatic profiles (Gilbert & DiVerdi, 2018 ). ...
Chapter
This chapter is concerned with the sensory analysis, aroma compounds, and world regulations applied to Cannabis sativa (C. sativa). The chapter includes: (1) definitions and concepts related to sensory analysis; (2) the biosynthesis of the volatiles and the main chemical families found in this crop; (3) instrumental analysis; (4) scientific production related to C. sativa sensory quality and aroma compounds; (5) EU, USA and world regulations on its use and consumption; and (6) relevant findings in terms of sensory analysis and aroma compounds of C. sativa. Sensory analysis is the scientific discipline used to measure analyze and interpret the human reaction to products characteristics. Despite de developments already done in the instrumental analysis regarding food quality determination, the flavor sensations perceived by humans can be measured only by sensory tests. Within C. sativa, this scientific discipline can provide information about how its sensory characteristics are related to perceived quality and consumer liking, as hemp is widely used in food and cosmetics. The sensory analysis is always combined with analytical instruments to evaluate the aroma compounds. Among all these tools, for C. sativa, instrumental color, gas- and liquid- chromatography are the most used. The first one, to evaluate the color, the second one to determine terpenoids (the main chemical family of aroma compounds of hemp), and the third one is mainly used for the cannabinoids determination (compounds highly valued for their pharmacologically effect and worldwide regulated due to their psychoactive effect on humans). Finally, both sensory and instrumental analysis are required for the elucidation of C. sativa composition, as well as for their use as ingredients in food or other goods. Because instrumental analysis can help to determine the aromatic profile specific to each cultivar, while sensory analysis helps to detect which of those cultivars are more accepted in terms of flavor by the consumers. Last, both techniques might help in the optimization of hemp processing.
... Cannabidiolic acid (CBDA) has antimicrobial and antinausea properties, while cannabigerol (CBG) has anti-inflammatory, antimicrobial, and analgesic activities. Thanks to its lack of psychoactivity, CBD is one of the most interesting compounds, with many reported pharmacological effects in various models of pathologies, from inflammatory and neurodegenerative diseases to epilepsy, autoimmune disorders like multiple sclerosis, arthritis, schizophrenia, and cancer (Sommano et al., 2020). Concerning other phenolics present in C. sativa, several flavonoids have been identified, belonging mainly to flavones and flavonols, together with cannflavins A and B, which are C. sativa typical methylated isoprenoid flavones. ...
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The growing interest on the therapeutic potential against neurodegeneration of Cannabis sativa extracts, and of phytocannabinoids in particular, is paralleled by a limited understanding of the undergoing biochemical pathways in which these natural compounds may be involved. Computational tools are nowadays commonly enrolled in the drug discovery workflow and can guide the investigation of macromolecular targets for such molecules. In this contribution, in silico techniques have been applied to the study of C. sativa constituents at various extents, and a total of 7 phytocannabinoids and 4 terpenes were considered. On the side of ligand‐based virtual screening, physico‐chemical descriptors were computed and evaluated, highlighting the phytocannabinoids possessing suitable drug‐like properties to potentially target the central nervous system. Our previous findings and literature data prompted us to investigate the interaction of these molecules with phosphodiesterases (PDEs), a family of enzymes being studied for the development of therapeutic agents against neurodegeneration. Among the compounds, structure‐based techniques such as docking and molecular dynamics (MD), highlighted cannabidiol (CBD) as a potential and selective PDE9 ligand, since a promising calculated binding energy value (‐9.1 kcal/mol) and a stable interaction in the MD simulation timeframe were predicted. Additionally, PDE9 inhibition assay confirmed the computational results, and showed that CBD inhibits the enzyme in the nanomolar range in vitro, paving the way for further development of this phytocannabinoid as a therapeutic option against neurodegeneration.
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Cannabis is well established as possessing immune modulating activity. The objective of this study was to evaluate the anti-inflammatory properties of selected cannabis-derived terpenes and cannabinoids. Based on their activity in cannabis-chemovar studies, α-pinene, trans-nerolidol, D-limonene, linalool and phytol were the selected terpenes evaluated. The cannabinoid compounds evaluated included cannabidivarin, cannabidiol, cannabinol, cannabichromene, cannabigerol and delta-9-tetrahydrocannabinol. Human PBMC were pretreated with each compound, individually, at concentrations extending from 0.001 to 10 μM and then stimulated with CpG (plasmacytoid dendritic cell), LPS (monocytes), or anti-CD3/CD28 (T cells). Proliferation, activation marker expression, cytokine production and phagocytosis, were quantified. Of the 21 responses assayed for each compound, cannabinoids showed the greatest immune modulating activity compared to their vehicle control. Delta-9-tetrahydrocannabinol possessed the greatest activity affecting 11 immune parameters followed by cannabidivarin, cannabigerol, cannabichromene, cannabinol and cannabidiol. α-Pinene showed the greatest immune modulating activity from the selected group of terpenes, followed by linalool, phytol, trans-nerolidol. Limonene had no effect on any of the parameters tested. Overall, these studies suggest that selected cannabis-derived terpenes displayed minimal immunological activity, while cannabinoids exhibited a broader range of activity. Compounds possessing anti-inflammatory effects may be useful in decreasing inflammation associated with a range of disorders, including neurodegenerative disorders.
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Terpenes possess a wide range of medicinal properties and are potential therapeutics for a variety of pathological conditions. This study investigated the acute effects of two cannabis terpenes, β-caryophyllene and α-pinene, on zebrafish locomotion, anxiety-like, and boldness behaviour using the open field exploration and novel object approach tests. β-caryophyllene was administered in 0.02%, 0.2%, 2.0%, and 4% doses. α-pinene was administered in 0.01%, 0.02%, and 0.1% doses. As α-pinene is a racemic compound, we also tested its (+) and (−) enantiomers to observe any differential effects. β-caryophyllene had only a sedative effect at the highest dose tested. α-pinene had differing dose-dependent effects on anxiety-like and motor variables. Specifically, (+)-α-pinene and (−)-α-pinene had significant effects on anxiety measures, time spent in the thigmotaxis (outer) or center zone, in the open field test, as well as locomotor variables, swimming velocity and immobility. (+ /−)-α-pinene showed only a small effect on the open field test on immobility at the 0.1% dose. This study demonstrates that α-pinene can have a sedative or anxiolytic effect in zebrafish and may have different medicinal properties when isolated into its (+) or (−) enantiomers.
Article
Background Neurodegenerative diseases and dementia pose a global health challenge in an aging population, exemplified by the increasing incidence and prevalence of its most common form, Alzheimer's disease. Although several approved treatments exist for Alzheimer's disease, they only afford transient symptomatic improvements and are not considered disease-modifying. The psychoactive properties of Cannabis sativa L. have been recognized for thousands of years and now with burgeoning access to medicinal formulations globally, research has turned to re-evaluate cannabis and its myriad phytochemicals as a potential treatment and adjunctive agent for neurodegenerative diseases. Purpose This review evaluated the neuroprotective potential of C. sativa’s active constituents for potential therapeutic use in dementia and Alzheimer's disease, based on published studies demonstrating efficacy in experimental preclinical settings associated with neurodegeneration. Study Design Relevant information on the neuroprotective potential of the C. sativa’s phytoconstituents in preclinical studies (in vitro, in vivo) were included. The collated information on C. sativa’s component bioactivity was organized for therapeutic applications against neurodegenerative diseases. Methods The therapeutic use of C. sativa related to Alzheimer's disease relative to known phytocannabinoids and other phytochemical constituents were derived from online databases, including PubMed, Elsevier, The Plant List (TPL, www.theplantlist.org), Science Direct, as well as relevant information on the known pharmacological actions of the listed phytochemicals. Results Numerous C. sativa -prevalent phytochemicals were evidenced in the body of literature as having efficacy in the treatment of neurodegenerative conditions exemplified by Alzheimer's disease. Several phytocannabinoids, terpenes and select flavonoids demonstrated neuroprotection through a myriad of cellular and molecular pathways, including cannabinoid receptor-mediated, antioxidant and direct anti-aggregatory actions against the pathological toxic hallmark protein in Alzheimer's disease, amyloid β. Conclusions These findings provide strong evidence for a role of cannabis constituents, individually or in combination, as potential neuroprotectants timely to the emergent use of medicinal cannabis as a novel treatment for neurodegenerative diseases. Future randomized and controlled clinical studies are required to substantiate the bioactivities of phytocannabinoids and terpenes and their likely synergies.
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Background: The associations between cannabis use and anxiety or depression remain unclear. If cannabis affects these conditions, it is of interest to examine possible changes in cannabis use over time, in relation to anxiety and depression, as cannabis potency has increased in recent decades. Methods: Cohorts from the Women and Alcohol in Gothenburg study (n= 1 100), from three time periods were used to examine associations over time between cannabis use and anxiety and depression. Logistic regression analyses were used and relative excess risk due to interaction (RERI) was calculated to examine potential additive interactions between period of cannabis use, cannabis use, and anxiety or depression. Findings: Cannabis use was associated with anxiety in the oldest cohort (examined 1986–1992, born 1955/65), OR = 5.14 (1.67–15.80, 95% CI), and with both anxiety and depression in the youngest cohort (examined 2000–2015, born 1980/93), OR = 1.66 (1.00–2.74, 95% CI) and 2.37 (1.45–3.86, 95% CI), respectively. RERI was significant between cannabis use and depression in the youngest cohort when compared with older cohorts (1.68 (0.45–2.92, 95% CI)). Limitations: Cross-sectional data prevent statements on causality, though between-cohort comparisons are possible. Conclusion: The association between cannabis use and depression becomes more pronounced when adding the effect of period of use rather than looking at the effect of cannabis use itself. This study provides clinicians and public health workers with scientifically underpinned knowledge regarding the link between cannabis use and depression, of particular importance given increasing cannabis potency.
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Cannabis sativa plant has not only cannabinoids as crucial compounds but also the other compounds that play important role as synergistic and/or entourage compound. Cannabis/hemp plant materials and essential oils were analyzed with the help of gas chromatography/mass spectrometry detector for the content of terpenes and terpenoids. The main terpenes/terpenoids and their abundance in the samples were evaluated. Results of this study will be helpful in the next evaluation of these compound in mixture with cannabinoids and their importance in medical treatment.
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Raw materials used for black garlic (BG) processing were collected from the major garlic production areas in Northern Thailand. Five of those were identified as of Thai origin (accession G1–G5), and accession G6 was of the Chinese variety. They were initially analyzed for varietal differences using morphological characteristics and genetic variation. Fresh materials from each accession were dried to the same moisture content (55%–60%) and BG processed at 75°C, 90% relative humidity (RH) for 15 days. Thereafter, physiochemical and chemical profiles were analyzed and compared. The dendrogram from random amplified polymorphic DNA fingerprints grouped G2, G3, G4, and G5 as closely related while G1 and G6 were out‐groups. Prior to BG processing, the pH of fresh garlic was approximately 6.3 and decreased to 3.7, thereafter. The contents of chemical properties were independent with genotypes. BG processing improved phenolic, flavonoid, and antioxidant but the content of thiosulfinate was minimized in all BG samples. Overall, result indicated that garlics grown in Northern Thailand were genotypically variable. BG processing altered physical and chemical appearance, and these changes were independent with the genotypes. Raw materials used for black garlic (BG) processing were collected. They were initially analyzed for varietal differences using genetic variation, physicochemical, and chemical properties.
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Objective: The plant Cannabis indica is a very popular and well known plant across the globe since thousands of years. In India also it is even more popular as bhang or marijuna from ancient time. A quite descriptions of this plant is written in various ancient books like the granths, vedas, puranas, ayurvedic books, dravyaguna, etc.. Number of medicinal properties have been described for different parts of the plant like flower buds(Ganja), Leaf(Bhang) & Leaf wax(Charas). All the parts of this plant have potent and complex psychotropic properties along with some additional therapeutic actions on different body systems. Here we have fond some opportunities to evaluate herbal extracts of leaves for having aphrodisiac potential. Method: The aphrodisiac activity of Cannabis indicaleaf extracts (Pet.ether, methenol & aqueous) were evaluated in male albino rats. Extracts were administered at a dose of 150mg/kg body weight. At a interval of 0,7,14,21 & 28 day several sexual behavior parameters were determined. At the end serum testosterone and FSH level were also determined. Results: This study also contributes to the pharmacology of aphrodisiacs as the plant Cannabis indica leaf extracts has significant effects on sexual physiology. It has shown effects on sexual behaviors as well as significant change in gonadotropin hormone labels in animal blood serum. Conclusion: This study provides a strong experimental evidence for its aphrodisiac use.
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Essential oil of Cannabis sativa L. is a valuable bio-product due to its versatility, particularly in terms of its commercial values and potential applications in medicine, cosmetics and bio-pesticide. In this study, the effect of different stages of plant growth on essential oil yield and composition of four hemp varieties, (two monoecious non-native (Fedora 17 and its progeny) and two dioecious native (Fars and Yazd) samples) were investigated. The plant materials, consist of foliage in vegetative stage, inflorescent of flower in flowering stage and inflorescent of seeds in seeding stage were subjected to hydro-distillation. The essential oils were analyzed by GC and GC/MS. The oil yields varied from 0.40 % (Fedora17) to 0.65 % (Yazd). Interaction of cultivar and growth stage showed Fed17−2 at vegetative (0.86 %) and Fed17 at flowering stage (0.20 %), had the most and least oil content, respectively. Twenty-nine compounds were identified representing 81.9%–99.5% of the essential oils. The most abundant sesquiterpenes in the oils were E-caryophyllene (16.40 %–44.70 %), α-humulene (4.1 %–15.1 %) and Z-caryophyllene (2.4 %–10.7 %), while the major monoterpenes were (0.4–24.9 %), β-pinene (4.6–24.3 %) and 1,8-cineole (0.8 %–9.3 %) in all growth stages and cultivars. The ratio of sesquiterpenes to monoterpenes were found to decrease during the developing plants. In conclusion, there was no significant difference between mean oil yields of native and non-native samples, but non-native samples produced the highest oil yield in vegetative stage. E-caryophyllene was found at the highest percentage in the oils of non-native samples at vegetative stage. For all samples, the essential oils at vegetative stage contained much lower production of monoterpenes than flowering stage. In addition, to obtain the highest amount of β-pinene and 1,8-cineole, the flowering and seeding stages of hemp are recommended.
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A 17-year-old with severe hypertrophic cardiomyopathy (HCM) presented to the emergency department with symptoms of cough, shortness of breath, chest pain, and tactile fevers. She was initially admitted to the cardiac floor, and later transferred to the cardiothoracic intensive care unit on day 5 of illness with deterioration over the next week from BiLevel positive airway pressure to endotracheal intubation. The patient met criteria for severe acute respiratory distress syndrome (ARDS). Standard ARDS lung-protective strategies were refined in consideration of complications caused by her HCM. Such complications included dynamic cardiac outflow obstruction, myocardial ischemia with tachycardia, elevated pulmonary vascular resistance from diastolic dysfunction, and narrow fluid balance window to reduce pulmonary edema while maintaining adequate left ventricular preload. The patient remained refractory despite broad-spectrum antibiotics requiring multiple vasoactive medications, aggressive ventilator management, and inhaled nitric oxide. Social history revealed “vaping” cannabis with butane hash oil prior to symptom onset. Corticosteroids were initiated 2 weeks after initial presentation (day 9 of mechanical ventilation) with rapid recovery and resolution of illness. Acute respiratory distress syndrome is an aggressive disease in the intensive care unit. E-cigarette or vaping product use–associated lung injury is increasingly recognized as a cause of ARDS in adolescents and adults. A complete social history is essential and must be obtained early in all such patients presenting with symptoms of acute respiratory distress and revisited throughout the hospital stay if no other reason for the ARDS is discovered. Disease progression may be subacute with a long interval between onset of symptoms and peak symptoms. The risk of barotrauma is high despite lung-protective ventilation strategies. Management is supportive with resolution over days to weeks. However, other clinical factors may considerably complicate management in cases of underlying comorbidities.
Article
Background Cannabis use is more common among adults with anxiety. Cannabis legalization is occurring rapidly across the United States (US) and individuals may use cannabis to cope with anxiety. This study investigated whether cannabis use across the US has changed differentially by anxiety status and by state cannabis legalization for medical (MML) and/or recreational use (RML). Methods Public and restricted-use data from the 2004-2017 National Survey on Drug Use and Health, an annual cross-sectional, nationally representative survey of US individuals, were analyzed. The prevalence of past-30-day cannabis use by anxiety status in 2017 was estimated among respondents ages ≥18 (n = 42,554) by sociodemographics and state-level cannabis law. Weighted logistic regressions with continuous year as the predictor for the linear time trend were used to examine the time trends in cannabis use by anxiety and cannabis law status from 2004 to 2017 (total combined analytic sample n = 398,967). Results Cannabis use was consistently two to three times higher among those with high anxiety compared to those with some or no anxiety and was higher in states with RML compared to MML or no MML/RML. Cannabis use has increased over time among those with and without anxiety overall, in MML states, and in states without MML/RML; with a faster increase in cannabis use among those with high anxiety compared to lower anxiety in states with MML. Conclusions Cannabis use is increasing among American adults overall, yet is disproportionately common among Americans with anxiety especially among those residing in states where cannabis has been legalized.
Article
Background Existing evidence suggest that cannabis may impair driving and is the most prevalent drug identified in drivers. Males exhibit an excess risk for driving under the influence of drugs or alcohol compared to females. We assessed sex differences in the association between the reason for cannabis use (medical, recreational, or both) and driving under the influence of cannabis (DUIC). Methods A sample of 17,405 past 12-month cannabis users (18+ years old) were analyzed from the 2016-17 National Survey on Drug Use and Health. Multivariable logistic regression was used to assess the interaction of sex and reason for cannabis use on DUIC using predicted probabilities. Results Among cannabis users in the sample, 88.1% used for recreational reasons, 7.8% used for medical reasons, and 4.1% used for medical and recreational reasons. The probability of DUIC was as low as 20% among female medical only users, and as high as 40% among male combined medical and recreational users. Females showed more similar probabilities of DUIC across reasons of use (range 20% to 25%s) than males (range 28% to 40%). The difference in the probability of DUIC between combined medical and recreational users and recreational only users was significantly greater among males than among females (Δ0.1, p<0.05). Conclusions The observed effects of sex and reasons for cannabis use on DUIC suggests a need for targeted educational interventions, particularly among males reporting combined medical and recreational marijuana use.
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In this work is proposed a critical review of the scientific literature about the extraction of products of industrial interest from Cannabis sativa L., like cannabinoids, essential oil and seed oil, using supercritical and subcritical CO2. Traditional techniques are also reviewed and critically discussed to evidence the advantages of CO2 processing. The extracts can be also used in pharmaceutical and biomedical formulations, in form of co-precipitates and capsules, to improve active compounds bioavailability and performance. Further studies can be required, mainly based on the analysis of mass transfer resistances during extraction and on solubility data of the compounds to be extracted, to improve process selectivity and the purity of the extracts obtained.
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The increase of cultivation of industrial hemp (Cannabis sativa L.) all over the world offers new opportunities for the industry to manufacture innovative products from this multipurpose crop. In this regard, the hemp essential oil represents a niche product with potential interest for the pharmaceutical, nutraceutical, cosmeceutical and agrochemical companies. On this basis, in the present work we used the microwave-assisted extraction (MAE) to get an essential oil enriched in bioactive compounds, especially cannabidiol (CBD), from the dry inflorescences of the Italian variety CS (Carmagnola Selezionata). For this purpose, the operative conditions to increase the essential oil yield and CBD concentration in terms of microwave irradiation power (W/g), extraction time (min) and water added to the plant matrix after moistening (%), were optimized using a central composite design (CCD) approach using a Milestone ETHOS X device. The conventional hydrodistillation (HD) performed for 240 min was used for comparative purposes. The qualitative compositions of essential oils obtained by MAE and HD were analysed by GC-MS, whereas the quantitative detection of CBD and main terpenoids (α-pinene, β-pinene, myrcene, limonene, terpinolene, (E)-caryophyllene, α-humulene and caryophyllene oxide) was achieved by GC-FID. Furthermore, the enantiomeric distribution of the chiral constituents (α-pinene, β-pinene, limonene, (E)-caryophyllene and caryophyllene oxide) was determined using chiral chromatography. Results showed that the MAE treatment, using high irradiation power and relatively long extraction times, increased significantly the content of CBD in the essential oil while maintaining high oil yield values when compared with conventional HD. The enantiomeric excess of three chiral monoterpenes (α-pinene, β-pinene and limonene) was determined, with the (+)-enantiomers being predominant, whereas (E)-caryophyllene and caryophyllene oxide were enantiomerically pure. In conclusion, the MAE was successfully applied to hemp dry inflorescences in order to obtain a CBD-rich essential oil which may be exploited in several industrial applications.