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Cannabis Roots: A Traditional Therapy with Future Potential for Treating Inflammation and Pain

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Introduction: The roots of the cannabis plant have a long history of medical use stretching back millennia. However, the therapeutic potential of cannabis roots has been largely ignored in modern times. Discussion: In the first century, Pliny the Elder described in Natural Histories that a decoction of the root in water could be used to relieve stiffness in the joints, gout, and related conditions. By the 17th century, various herbalists were recommending cannabis root to treat inflammation, joint pain, gout, and other conditions. There has been a subsequent paucity of research in this area, with only a few studies examining the composition of cannabis root and its medical potential. Active compounds identified and measured in cannabis roots include triterpenoids, friedelin (12.8 mg/kg) and epifriedelanol (21.3 mg/kg); alkaloids, cannabisativine (2.5 mg/kg) and anhydrocannabisativine (0.3 mg/kg); carvone and dihydrocarvone; N-(p-hydroxy-β-phenylethyl)-p-hydroxy-trans-cinnamamide (1.6 mg/kg); various sterols such as sitosterol (1.5%), campesterol (0.78%), and stigmasterol (0.56%); and other minor compounds, including choline. Of note, cannabis roots are not a significant source of Δ⁹-tetrahydrocannabinol (THC), cannabidiol, or other known phytocannabinoids. Conclusion: The current available data on the pharmacology of cannabis root components provide significant support to the historical and ethnobotanical claims of clinical efficacy. Certainly, this suggests the need for reexamination of whole root preparations on inflammatory and malignant conditions employing modern scientific techniques.
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REVIEW Open Access
Cannabis Roots:
A Traditional Therapy with Future Potential
for Treating Inflammation and Pain
Natasha R. Ryz,
*David J. Remillard,
and Ethan B. Russo
Introduction: The roots of the cannabis plant have a long history of medical use stretching back millennia. How-
ever, the therapeutic potential of cannabis roots has been largely ignored in modern times.
Discussion: In the first century, Pliny the Elder described in Natural Histories that a decoction of the root in water
could be used to relieve stiffness in the joints, gout, and related conditions. By the 17th century, various herbalists
were recommending cannabis root to treat inflammation, joint pain, gout, and other conditions. There has been
a subsequent paucity of research in this area, with only a few studies examining the composition of cannabis root
and its medical potential. Active compounds identified and measured in cannabis roots include triterpenoids,
friedelin (12.8 mg/kg) and epifriedelanol (21.3 mg/kg); alkaloids, cannabisativine (2.5 mg/kg) and anhydrocanna-
bisativine (0.3 mg/kg); carvone and dihydrocarvone; N-( p-hydroxy-b-phenylethyl)-p-hydroxy-trans-cinnamamide
(1.6 mg/kg); various sterols such as sitosterol (1.5%), campesterol (0.78%), and stigmasterol (0.56%); and
other minor compounds, including choline. Of note, cannabis roots are not a significant source of D
tetrahydrocannabinol (THC), cannabidiol, or other known phytocannabinoids.
Conclusion: The current available data on the pharmacology of cannabis root components provide significant
support to the historical and ethnobotanical claims of clinical efficacy. Certainly, this suggests the need for reex-
amination of whole root preparations on inflammatory and malignant conditions employing modern scientific
Keywords: cannabis; friedelin; gout; hemp; inflammation; root
The cannabis plant is known for its multiple uses: the
leaves, flowers, seeds, stalks, and resin glands have all
been exploited for food, fuel, fiber, medicine, and
other uses. One of the first mentions of the medical
use of cannabis root was by the Roman historian,
Pliny the Elder, who wrote in his Natural Histories
that ‘‘a decoction of the root in water relaxes contrac-
tions of the joints and cures gout and similar maladies.’’
By the latter part of 17th century, various physicians and
herbalists recommended cannabis root to treat fever,
gout, arthritis, and joint pain,
as well as skin burns
and hard tumors.
are also accounts of cannabis root being used to treat
postpartum hemorrhage,
difficult child labor,
ally transmitted disease,
and gastrointestinal activi-
and infection.
Despite a long history of
therapeutic use (Table 1), the roots of cannabis plants
have been largely ignored in modern medical research
and practice.
History of Use of Cannabis Roots
Gout, arthritis, and joint pain
In earlier times, cannabis root was used to treat
physician and botanist, wrote in his herbal book
Ryz Re
´mi, Vancouver, Canada.
PHYTECS, Los Angeles, California.
*Address correspondence to: Natasha R. Ryz, PhD, Ryz Re
´mi, 306-8900 Citation Drive, Richmond, BC V6Y 3A3, E-mail:
ªNatasha R. Ryz et al. 2017; Published by Mary Ann Liebert, Inc. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cannabis and Cannabinoid Research
Volume 2.1, 2017
DOI: 10.1089/can.2017.0028
Cannabis and
Cannabinoid Research
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‘‘hemp root, boiled in water, and wrapped—is also
good for gout.’’
Similarly, the French physician
and writer François Rabelais noted ‘‘the root of this
herb, boiled in water, soothes muscles, stiff joints, gout
pains, and rheumatism.’
In 1613, Szymon Syrenski,
the Polish botanist and academic, recorded the uses of
hemp roots boiled in water for ‘‘curved and shrunken
body parts.’’
In 1640, John Parkinson, the English bot-
anist and herbalist, also noted ‘‘the decoction of the
rootes, easeth the paines of the goute, the hard tumours,
or knots of the joynts, the paines and shrinking of
the sinewes, and other the like paines of the hippes.’
In 1710, the English physician Dr. William Salmon
recorded ‘‘the decoction of the root.—it is said .to
ease the pains of the gout, to help hard tumors or knots
in the joints, cramps, and shrinking of the sinews, and
to ease the pains of the hip, or sciatica, being applied
thereto by fomentation, and afterward mixed applied
made up into a cataplasm with barley flower, renewing
of it every day.’’
In 1758, the French writer M. Marcand-
ier reported in Traite
´du Chanvre, ‘‘its root, boiled in
water, and coated in the form of a cataplasm, mollifies
and softens the joints of the fingers that are shrunken.
Is quite good against the gout, and other inflammations;
it resolves tumors and callosities of the joints.’
In gen-
eral, the historical records indicate that cannabis root is
most often extracted with boiling water
and ap-
plied topically to treat gout and arthritis.
In the 12th century, the Persian Philosopher Ibn Sina
(Avicenna) wrote in the Canon of Medicine that ‘‘the
compress with the boiled roots of cannabis decrease
In Argentina, cannabis root was also recom-
mended for fever due to infection with malaria—‘‘the
root bark, provides a fairly harsh taste mainly due to
the presence of tannin, is used fresh in cooking at the
rate of thirty grams per liter of water, or dry, fifteen
grams, for abbreviating bouts of fever in malaria.’’
From these accounts, cannabis roots were administered
both topically
and orally
for fever.
There are numerous mentions of cannabis root as a
treatment of inflammation.
In the 17th century,
Nicholas Culpeper, an English botanist, herbalist, and
physician, stated in his book Culpeper’s Complete
Herbal that ‘‘the decoction of the root allays inflamma-
tions of the head or any other parts.’’
In 1640, Parkin-
son also noted ‘‘hempe is cold and dry—The decoction,
of the roote is sayd to allay inflammations in the head
or any other part.’’
In 1710, Salmon recorded ‘‘the de-
coction of the root.—it is said to be good against, viz. to
allay inflammations in the head, or any other part.’’
1747, the English physician Robert James wrote in his
book Pharmacopoeia Universalis:or, A New Universal
English Dispensatory, ‘‘the root boil’d, and applied by
way of cataplasm, mitigates inflammations.’’
In the
18th century, M. Husain Khan also wrote in the Persian
medical text Makhzan-al-Adwiya, ‘‘A poultice of the
boiled root and leaves for discussing inflammations,
and cure of erysipelas, and for allaying neuralgic pains.’’
In general, a decoction of the cannabis root
or boiled
water extraction
administered topically
is the pre-
ferred method for using cannabis root to target overac-
tive inflammation.
Skin burns
Cannabis root has also been used topically to treat skin
burns. In 1542, Fuchs recorded ‘‘hemp root .the raw
root, pounded and wrapped, is good for the burn.’’
1640, Parkinson also noted ‘‘hempe is cold and dry—
The decoction, of the roote .it is good to be used,
for any place that hath beene burnt by fire, if the fresh
In 1758,
Marcandier reported that cannabis root ‘‘pounded and
Table 1. Medical History of Cannabis Roots
Medicinal use of
cannabis roots
Methods of
Methods of
Gout, arthritis,
joint pain
Boiled roots,
Fever Boiled roots
Boiled roots,
Skin burns
Raw root,
juice or
with fat (butter)
Hard tumors
Boiled roots
Juice and decoction
Sexually transmitted disease
(Unknown) Eaten
Gastrointestinal activity
To induce
Boiled roots
As a stomach tonic
Pulverized, mixed
with wine
Boiled roots
Toxins and
Pulverized, mixed
with wine
Juice and decoction
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ground fresh, with butter in a mortar, one applies it to
burns, which it soothes infinitely, provided it is often
Overall, cannabis root has been used topically
to soothe skin burns in a variety of ways, including raw
as a juice,
and mixed with fat (butter).
Hard tumors
There are mentions of cannabis root for treating tumors,
however, the term ‘‘tumor’’ may have been used to de-
scribe any kind of ‘‘abscess, sores, ulcers, or swelling,’’
but it is unclear if these tumors included what we con-
sider today to be cancerous tumors. In the 12th century,
Ibn Sina wrote ‘‘the compress with the boiled roots of
cannabis .resolve the indurations if applied on the
hot tumors and hardened places [of the body].’’
1710, Salmon recorded ‘‘the decoction of the root—it is
said .to help hard tumors or knots in the joints.’’
ilarly, in 1747, James wrote ‘‘the root boil’d, and applied
by way of cataplasm, discusses tumors, and dissolves
tophaceous Concretions at the Joints.’’
in 1758, Marcandier reported that cannabis root ‘‘re-
solves tumors and callosities of the joints.’
In general,
topical application of boiled cannabis root is used to
help with hard tumors.
In the ancient Chinese pharmacopeia, the Pe
Ching, it is stated that the juice of the cannabis root
has been used to assist with the cessation of hemorrhage
after childbirth. ‘‘The juice of the root is thought to have
a beneficial action in retained placenta and postpartum
Similarly, other accounts from China re-
port ‘‘Ma gen, Cannabis Radix, cannabis (hemp) root:
This is the root of the cannabis plant. Ma gen dispels sta-
sis and stanches bleeding. It is used in the treatment of
strangury, flooding and spotting, vaginal discharge, dif-
ficult delivery, retention of the placenta, and knocks and
falls. It is taken orally, either as a decoction or crushed
to extract its juice (in its fresh form).’’
to assist with difficult childbirth, cannabis root is admin-
istered orally, either as juice or decoction.
Sexually transmitted disease
There is a report of cannabis root being used to help
treat the sexually transmitted disease gonorrhea.
the 17th century, a German-born botanist employed
by the Dutch East India Company in what is now
known as eastern Indonesia noted ‘‘in Hitu [Ambon
Island, Indonesia] the Moors took the root of the
male or flower-bearing plant (which in European herb-
als are not readily distinguished) from my garden, and
gave it to eat to those who were held fast by unclean
It is unclear from this account how
the cannabis root was prepared to eat.
Gastrointestinal activity
Cannabis root has been used to protect against vomit-
ing (antiemetic) in Re
´union, a French island in the In-
dian Ocean: ‘‘boiled roots were used to reduce infants’
In Chile, hemp roots have also been
used to induce vomiting (purgative).
In Argentina,
hemp root was recommended, ‘‘the bark should be col-
lected in the early spring, when it is also a good tonic,
successfully administered pulverized and mixed with
wine for weakness and pains of the stomach. It tones
at the same time the entire digestive apparatus, removes
toxins and infections caused by the weakness of them.
Its same fruits [seeds] can replace the root.’’
There are several mentions of cannabis root for treat-
ing infection. In the Persian medical text Makhzan-
al-Adwiya, ‘‘a poultice of the boiled root and leaves
for .cure of erysipelas,’’
which is a bacterial infection
of the upper skin layer. In modern Argentina, hemp
root was recommended ‘‘to remove toxins and infec-
Marcandier also noted in 1758 that ‘‘its juice
and decoction placed in the buttocks [anus] of horses,
in fact, also brings out the vermin.’’
To assist with in-
fection, cannabis root has been administered topically,
and intrarectally.
Active Compounds in Cannabis Roots
Cannabis roots contain many different active com-
pounds, including triterpenoids, friedelin and epi-
friedelanol (Table 2).
Friedelin is found in many
plants, including Aesculus,Cannabis,Citrus,Diospyros,
Quercus,Rhododendron, and Vaccinium, as well as
algae, lichen, mosses, peat, coal, and mineral wax.
Epifriedelanol is also abundant in nature.
The con-
centration of friedelin and epifriedelanol in cannabis
root samples from Mexico, calculated by Slatkin et al.,
was 12.8 and 21.3 mg/kg, respectively.
There is cur-
rently no research available about the activity of
friedelin or epifriedelanol specifically isolated from
cannabis roots.
Sethi et al.
collected wild cannabis roots from
dered roots, the extraction assay revealed 15 mg of friede-
lin, 29 mg epifriedelanol, and 30 mg of beta-sitosterol.
Interestingly, the researchers also isolated a 2.3 g oil
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fraction (extracted with n-hexane) from the root extract
and noted a characteristic odor. The oil fraction was
identified by gas liquid chromatography as containing
77.7% carvone and 23.3% dihydrocarvone.
and dihydrocarvone are monoterpenes found in Mentha
spicata (spearmint) and Anethum graveolens (dill) and
are responsible for its distinctive minty aroma.
Other compounds identified in cannabis roots include
cannabisativine (2.5 mg/kg)
and anhydrocannabi-
sativine (0.3 mg/kg),
surprisingly, no pharmacological
information is available on either alkaloid. Canna-
bis roots contain various sterols, including sitosterol
(1.5%), campesterol (0.78%), and stigmasterol (0.56%).
Cannabis roots have also been shown to contain N-( p-
at calculated concentration of 1.6 mg/kg.
roots also reportedly contain choline.
Interestingly, cannabis roots do not contain a
significant amount of cannabinoids.
The D
tetrahydrocannabinol (THC) content of dried seeds,
roots, stems, leaves, and flowers was found to be
0.0%, 0.0%, 0.3%, 0.8%, and 15.2% w/w, respectively.
Cannabinoids, including THC, are formed from the
short-chain fatty acyl-coenzyme A (CoA) precursor
hexanoyl-CoA. The quantity of hexanoyl-CoA content
of roots, stems, leaves, and flowers was found to be
1.5, 2.2, 4.0, and 15.5 pmol/g, respectively.
This pattern
was similarfor the accumulation of the end product can-
nabinoid, cannabidiolic (CBA) acid, and levels in the
roots, stems, leaves, and flowers were found to be
0.004, 0.05, 0.5, and 2.4 pmol/g, respectively.
Modern Studies on Biochemical Activity
of Compounds Found in Cannabis Roots
Inflammation, fever, and pain
There are several compounds in cannabis root with
potential anti-inflammatory activity, including alka-
N-( p-hydroxy-b-phenylethyl)-
and friedelin.
lin isolated from Azima tetracantha Lam. was previously
investigated in murine models for its anti-inflammatory,
antipyretic, and analgesic effects.
In adult Wistar al-
bino rats, friedelin showed potent anti-inflammatory
activity in numerous in vivo tests: (1) friedelin mark-
edly reduced carrageenan-induced hind paw edema,
persisting for 6 h; effects of friedelin at 40 mg/kg
dose were comparable with indomethacin 10 mg/kg,
(2) friedelin at doses of 2 or 4 mg markedly reduced
ear edema after croton oil administration, (3) friedelin
inhibited peritoneal capillary permeability after acetic
acid administration in a dose-related manner, (4) frie-
delin inhibited granuloma formation after placement
of cotton pellets subcutaneously in the axilla, and (5)
friedelin significantly ( p<0.05) inhibited paw swelling
after Freund’s adjuvant injection.
Friedelin may also
help with fever: friedelin administered orally showed
significant reduction in rectal temperature ( p<0.05)
after yeast injection in adult Wistar albino rats. Results
were comparable with the antipyretic effect of parace-
tamol (acetaminophen).
Friedelin significantly ( p<
0.05) reduced abdominal constrictions and stretching
after acetic acid injection in adult Wistar albino rats.
The effect was less on first phase (0–5 min) neurogenic
pain than on second phase (20–30 min) inflammatory
pain. However, friedelin showed no significant effect
versus control on pain threshold in the hot plate test
in adult Wistar albino rats.
Cannabis roots have also been shown to contain N-( p-
at calculated concentration of 1.6 mg/kg, with analge-
sic activity in the mouse tail flick test at 25, 50, and
100 mg/kg via subcutaneous injection.
Carvone, as
identified in cannabis root from India by Sethi et al.,
also has antinociceptive activity.
In the acetic acid-
induced writhing test, carvone-treated mice exhibited a
significant decrease in the number of writhes when
100 and 200 mg/kg were administered through intraper-
itoneal (IP) injection. It was also demonstrated that car-
vone inhibited the licking response of the injected paw
when 100 and 200 mg/kg were administered through
IP injection to mice in the first and second phases of
the formalin test.
M. spicata (spearmint) oil contains
Table 2. Active Compounds in Cannabis Roots
Active compounds in cannabis root Amount/concentration
7.5–12.8 mg/kg
14.5–21.3 mg/kg
Monoterpenes From initial 2 kg sample of
dried powdered roots,
2.3 g oil fraction (extracted
with n-hexane) from the
root extract was identified
as 77.7% carvone and
23.3% dihydrocarvone.
2.5 mg/kg
0.3 mg/kg
N-( p-hydroxy-b-phenylethyl)-
1.6 mg/kg
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up to 60–70% carvone and is being investigated as a
treatment for osteoarthritis.
Estrogenic activity
Friedelin may have estrogenic activity. Cissus quadran-
gularis (Vitaceae) is an edible plant found in hotter
parts of India, Sri Lanka, Malaya, Java, and West
Africa. The plant has been documented in Ayurveda
for its medicinal uses in gout, syphilis, venereal disease,
and as an aphrodisiac.
A friedelin-rich fraction iso-
lated from C. quadrangularis has been shown to have
estrogenic activity in ovariectomized female Wistar
Treating rats with the friedelin-rich fraction
(75 and 100 mg/kg per os) improved sexual behavior
parameters and estrogenic activity as indicated by vag-
inal cornification, increase in uterine weight, and rise in
serum estrogen.
Maytenus ilicifolia also contains frie-
and is reported to have estrogenic activity.
Antioxidant, liver protectant, and anticancer activity
Friedelin isolated from A. tetracantha Lam. leaves
showed strong antioxidant activity in vitro and liver
protectant properties in vivo, and pretreatment with
40 mg/kg friedelin reduced carbon tetrachloride (CCl
induced liver function elevations due to hepatic damage
(p<0.005), comparable with silymarin extract of Sily-
bum marianum (milk thistle).
It should be noted that
friedelin isolated from the leaves of M. ilicifolia did not
decrease gastric ulcers when tested on indometacine-
induced ulcer model in rats.
Friedelin from the stem
bark of Mesua daphnifolia had weak cytotoxic activity
against four cancer cell lines, including MDA-MB-231
(human estrogen receptor-negative breast cancer),
HeLa (human cervical carcinoma), CEM-SS (human
T-lymphoblastic leukemia), and CaOV3 (human ovar-
ian cancer).
Friedelin and epifriedelanol isolated from
the stem bark of Elaeocarpus floribundus also had weak
anticancer activity against CEM-SS and HeLa cell lines.
However, friedelin and epifriedelanol isolated from var-
ious other plants had no activity against a variety of can-
cer cell lines.
Cardiac activity?
Throughout history, the ancients did not record any car-
diac activity of cannabis roots. In 1971, Rodger pub-
lished an account in the Journal of the American
Medical Associated (JAMA), recollecting his physician
uncle using Indian hemp roots to treat dropsy
(edema) in 1931.
This prompted an investigation by
Ham Ten, who infused cannabis roots with whiskey
into guinea pig hearts with resultant bradycardia—the
heart rates dropped from 240 to 60 beats/min. A quick
recovery was seen when administration was stopped.
Similarly, Mole et al. tested cardiac activities of cannabis
root and showed minimal bradycardia.
It should
be noted that in 1939, Indian hemp was the common
name applied to Apocynum cannabinum, a known car-
diotoxin, used to treat dropsy in folk medicine (p. 346)
and also by the Meskwaki Native Americans of the Mid-
It appears that Rodger may have mistaken the
Cannabis sativa root for Indian hemp, that is, A. canna-
binum. As such, Rodger’s report is likely spurious and
has no relationship to actual toxicity of cannabis roots.
This sort of confusion is totally avoidable through ap-
propriate utilization of Latin binomials and voucher
specimens for authentication of the samples.
Summary and Future Directions
There is renewed interest in pharmacotherapy with
cannabis flowers and their extracts, stems, and leaves.
The roots, however, are still largely ignored in scholar-
ship and in medical practice, where historically, they
were valued as medicinal agents for treating a vari-
ety of conditions, including fever,
gout, arthritis, and joint pain.
The phytocan-
nabinoids, including THC and CBD, have been the
major focus of attention for medicine and are found
in the glandular resin heads, which are most con-
centrated in flowers and bracts, and also contain
terpenes such as limonene, alpha-pinene, and beta-
Interestingly, cannabis roots are not
a significant source of cannabinoids or the aforemen-
tioned terpenes, but are rich in other compounds,
including the triterpenoids, friedelin and epifriedela-
; alkaloids, cannabisativine
and anhydro-
; and other compounds that may
have therapeutic applications. It is important to note
that past studies have included analysis of roots of C.
sativa from various regions of the world, including
and India.
The plant genus Cannabis
is a member of the family Cannabaceae, and while
some botanists argue for cannabis as a single species,
others describe up to four, including C. sativa,Canna-
bis indica,Cannabis ruderalis, and Cannabis afghanica
(or kafiristanica).
It is clear there are many dif-
ferent chemotypes of cannabis, including THC pre-
dominant, CBD predominant, and mixed types.
Future research should compare the phytochemistry
of hemp roots with those from various drug chemo-
vars to determine if there are differences in active
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compounds. Furthermore, reports of carvone and
dihydrocarvone in significant amounts
and other
potential monoterpenes in cannabis roots must be
confirmed. Modern studies using the same terpe-
noids found in cannabis roots have shown anti-
inflammatory and pain-relieving activities.
there is no pharmacological information available
about the alkaloids found in cannabis roots. Further
research is required to study the active compounds
in cannabis roots and explore their potential thera-
peutic applications.
There are various traditional methods of preparing
cannabis root for therapeutic use. The raw cannabis
roots can be prepared by pounding and crushing the
fresh root to extract its juices.
There are numerous
mentions of cannabis root preparations in water, espe-
cially boiling water,
which suggest that early
formulators were attempting to extract the water-soluble
compounds in the roots. Throughout the 17th and 18th
centuries, there are also many mentions of using canna-
bis root decoctions.
The fresh ground root, juice, or
cannabis root decoction has also been mixed with fat (oil
or butter).
There is also an account of mixing pulver-
ized cannabis root with wine.
Interestingly, topical ap-
plications of cannabis root-based preparations are most
often described.
Modern cannabis dispensaries
in the United States now stock preparations made from
hemp and cannabis root, including body lotions, salves,
lip balms, massage oil, and pet sprays.
It should be
noted, if cannabis roots are being used therapeutically,
the source of the roots must be carefully considered
since cannabis roots can be used for phytoremediation
and can accumulate heavy metals from the soil, includ-
ing iron, chromium, and cadmium.
Future studies will
also have to determine the best methods of preparing
cannabis roots and best methods to administer cannabis
roots for various conditions.
Author Disclosure Statement
No competing financial interests exist.
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Cite this article as: Ryz NR, Remillard DJ, Russo EB (2017) Cannabis
roots: a traditional therapy with future potential for treating inflam-
mation and pain, Cannabis and Cannabinoid Research 2:1, 210–216,
DOI: 10.1089/can.2017.0028.
Abbreviations Used
CBD ¼cannabidiol
CoA ¼coenzyme A
IP ¼intraperitoneal
Publish in Cannabis and Cannabinoid Research
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... Traditional Chinese medicine was the first to use hemp roots to treat symptoms such as mouth ulcers in indigenous peoples of southwestern China. Over time, even herbalists recommended cannabis root to treat fever, inflammation, gout, joint pain and hard tumors (Ryz et al., 2017). Subsequent studies reported that cannabis root extracts exerted various pharmacological effects including anti-inflammatory, hantiasthmatic and spasmolytic activity (Huang et al., 2023;Nascimento Meneze et al., 2021;Bezerra Lima et al., 2021). ...
... In particular, ethanol extracts obtained from inflorescences of different cannabis cultivars have also proved to be particularly effective thanks to their mixed content of cannabinoids and terpenes (Janatova et al., 2022). On the other hand, cannabis roots do not represent a significant source of cannabinoids, therefore, to date, based on the available compositional information, their potential use is mainly oriented towards an anti-inflammatory and painrelieving effect (Ryz et al., 2017). ...
... Since acidic substances are highly toxic to plant cells, the final stage of their synthesis takes place outside the cells of the trichosomes [72]. The roots of C. sativa also contain triterpenoids' active compounds [73].The high concentrations of monoterpenoids occur in capitate glandular trichomes in bracts; cannabinoids are also stored in the glandular trichome secretory cavity, but they are found predominantly in female flowers [24]. In T. media, taxol exhibits special mechanisms for synthesis and storage to prevent toxic effects on its source plant. ...
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Terpenoids are the broadest and richest group of chemicals obtained from plants. These plant-derived terpenoids have been extensively utilized in various industries, including food and pharmaceuticals. Several specific terpenoids have been identified and isolated from medicinal plants, emphasizing the diversity of biosynthesis and specific functionality of terpenoids. With advances in the technology of sequencing, the genomes of certain important medicinal plants have been assembled. This has improved our knowledge of the biosynthesis and regulatory molecular functions of terpenoids with medicinal functions. In this review, we introduce several notable medicinal plants that produce distinct terpenoids (e.g., Cannabis sativa, Artemisia annua, Salvia miltiorrhiza, Ginkgo biloba, and Taxus media). We summarize the specialized roles of these terpenoids in plant-environment interactions as well as their significance in the pharmaceutical and food industries. Additionally, we highlight recent findings in the fields of molecular regulation mechanisms involved in these distinct terpenoids biosynthesis, and propose future opportunities in terpenoid research, including biology seeding, and genetic engineering in medicinal plants.
... [111,112] Many researchers have argued that sitosterol could reduce the expression of chemokines and inflammatory cytokines, and promote the production of the anti-inflammatory cytokine, such as TNF-α, IL-1β, IL-6, IL-8, IL-12, IL-17, MMP-2/9, and IL-10. [113][114][115] Moreover, there is a consensus among de Souza et al [116] and Ryz et al [117] that the symptoms of GA could be alleviated by sitosterol, such as foot edema. However, very little is known about these combinations, so further experimental investigations are needed to verify molecular docking results. ...
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Background Guizhi-Shaoyao-Zhimu decoction (GSZD) is a Chinese herb formula. Previous studies have reported that the clinical symptoms and laboratory indicators of gouty arthritis patients could be improved by GSZD. However, no previous study has evaluated and analyzed its efficacy, safety, underlying mechanisms, and the relationship between related ingredients of herbs and targets of gouty arthritis. Methods Randomized controlled trials of GSZD for gouty arthritis were retrieved from various databases. Meta-analysis was performed by Stata 17 software. Galbraith plot was used to find studies with possible heterogeneity. Publication bias was assessed by Egger test and funnel plot. The related ingredients of herbs and the targets of herbs and gouty arthritis were obtained from several databases, such as TCMSP, HERB, and DrugBank. The protein-protein interaction network was conducted by the STRING platform. DAVID database was used to perform GO and KEGG analysis. Molecular docking and visualization of docking results were carried out by AutoDock and PyMOL software. Results Twenty studies with 1633 patients were included. Meta-analysis indicated that GSZD could better improve the clinical efficiency and visual analogue scale score, and reduce the level of blood uric acid and inflammatory biomarkers (including C-reactive protein, erythrocyte sedimentation rate, interleukin 6, interleukin 8, and tumor necrosis factor-α) than conventional treatment. In addition, we retrieved 157 active compounds, 517 herb target genes, 3082 disease targets, and 295 intersection targets of herb and disease. The results of network pharmacology analysis showed that the core related ingredients included quercetin, kaempferol, sitosterol, luteolin, catechin, etc. The core intersection targets contained AKT1, TNF-α, TP53, IL6, etc. And the critical signaling pathways included IL-17, HIF-1, TNF, PI3K-Akt, etc. Among the 56 molecular docking results, only 8 results had binding energy values greater than −5.0 kcal/mol. Conclusion GSZD could be a satisfactory complementary and alternative therapy for treating gouty arthritis. However, it should be verified by further studies. Future research on gouty arthritis could be conducted from the active components including beta-sitosterol and sitosterol, the targets including TNF-1, IL1B, and ESR1, and the signaling pathways including IL-17 and HIF-1.
... As such, little information about the constituents and biological activities of hemp roots is available in the literature. Hemp roots have been historically used to treat inflammation, fever, gout, arthritis, joint pain, and skin burn (Ryz et al., 2017). Furthermore, the aqueous extract of the roots of C. sativa exhibited anti-inflammatory and anti-asthmatic activity in mice (Lima et al., 2021;Menezes et al., 2021). ...
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Cannabis sativa L. (hemp) has a global distribution and social impact, and it is widely used as a medicinal plant, food ingredient, and textile fiber. Its roots have received less attention than other parts, especially the inflorescence, leaves, and shoots. Triterpenoids, including friedelin and epifriedelanol, have been found in hemp roots, and their anti-inflammatory effects have been reported. In this study, the potential enhancement of triterpenoid accumulation in the roots of C. sativa by elicitation was examined. Hairy roots were successfully established, and they contained 2.02-fold higher triterpenoid levels than natural roots. Furthermore, hairy roots treated with 75 μM salicylic acid had 1.95-fold higher friedelin levels (0.963 mg/g DW) and 1.4-fold higher epifriedelanol levels (0.685 mg/g DW) than untreated hairy roots. These results suggested that the elucidation of hairy root cultures using an optimized elicitor could represent an alternative strategy to produce the valuable triterpenoids friedelin and epifriedelanol.
... A natural remedy known for millennia, the cannabis plant has tranquilizing, hypnotic and aphrodisiac effects, used since ancient times to treat various conditions. The root, was recommended for treating inflammation, gout, arthritis, fever, skin burns, infections, postpartum hemorrhage, gastrointestinal diseases and tumors (Ryz et al., 2017). Cannabis inflorescence and leaves have also been used to treat epilepsy, glaucoma, insomnia, and pain (Brunetti et al., 2020;Jin et al., 2020). ...
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Cannabis enjoyed a “golden age” as a medicinal product in the late 19th, early 20th century, but the increased risk of overdose and abuse led to its criminalization. However, the 21st century have witnessed a resurgence of interest and a large body of literature regarding the benefits of cannabinoids have emerged. As legalization and decriminalization have spread around the world, cancer patients are increasingly interested in the potential utility of cannabinoids. Although eager to discuss cannabis use with their oncologist, patients often find them to be reluctant, mainly because clinicians are still not convinced by the existing evidence-based data to guide their treatment plans. Physicians should prescribe cannabis only if a careful explanation can be provided and follow up response evaluation ensured, making it mandatory for them to be up to date with the positive and also negative aspects of the cannabis in the case of cancer patients. Consequently, this article aims to bring some clarifications to clinicians regarding the sometimes-confusing various nomenclature under which this plant is mentioned, current legislation and the existing evidence (both preclinical and clinical) for the utility of cannabinoids in cancer patients, for either palliation of the associated symptoms or even the potential antitumor effects that cannabinoids may have.
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Friedelin and epifriedelanol are pentacyclic triterpenoids that preferentially accumulate in the roots of hemp (Cannabis sativa L.) and are valued for their antidiabetic, hypolipidemic, antioxidant, liver protective, anti-ulcer, anti-inflammatory, antimicrobial, anticancer, and antisenescence properties. The aim of the present study was to investigate the influence of media, carbon sources, and elicitation on the production of C. sativa hairy root biomass and these metabolites. The MS liquid medium promoted the highest fresh weight (9.45 ± 0.00 g/100 mL flask) biomass production in hairy root cultures after 28 days. The highest levels of epifriedelanol (3.79-fold) and friedelin (3.25-fold) were found at the end of the exponential phase. The presence of 3% sucrose provided the highest accumulation of epifriedelanol ( 0.930 ± 0.013 mg/g DW) and friedelin (0.574 ± 0.024 mg/g DW) in the roots. The effects of methyl jasmonate (MJ) and salicylic acid (SA) on the enhancement of friedelin and epifriedelanol in C. sativa hairy root cultures were investigated. Between the two elicitors, SA showed the highest production of epifriedelanol (up to 5.018 ± 0.35 mg/g DW) and friedelin up to 1.56 ± 0.34 mg/g DW in 28-day-old stationary phase hairy roots. These represented 5.22- and 2.88-fold increase over the control (0.96 ± 0.01 mg/g DW and 0.54 ± 0.03 mg/g DW) after 96 h of treatment, respectively. The maximum accumulations of epifriedelanol (3.59 ± 0.12 mg/g DW) and friedelin (1.31 ± 0.01 mg/g DW) were observed in the treatment with MJ (100 µM) after 24 h of exposure and were 3.73- and 2.44-fold higher than the control, respectively. These findings suggest that elicitation is an effective technique for enhancing the yields of these valuable bioactive pentacyclic triterpenoids in C. sativa hairy root cultures in a relatively short period of time.
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Introduction_Cannabis sativa L. is an annual, dioecious, herbaceous, monotypic genus of blooming plants, synthetically rich in the natural constituents of complex compounds including terpenophenolic chemicals such as phytocannabinoids. Thus, cannabis is gaining a distinct fascination in the pharmaceutical research under its medicinal properties despite being prohibited in many countries. This study aims to provide overview of cannabis's phytochemical and pharmacological qualities as well as its cannabinoids synthesis. Methods_Between 2011 and April 2022, the literature was reviewed by searching Medline, Scopus, Google Scholar, ScienceDirect, Web of Knowledge, PubMed, and SpringerLink databases. The accompanying vital terms were utilized: ‘Cannabis sativa L.’, ‘Chemical constituents’, ‘Biosynthesis’, ‘Pharmacological aspects’, ‘Phytocannabinoids’, and ‘Terpenes’. Results_More than 588 bioactive compounds have been extracted and characterized into various classes of cannabinoids and non-cannabinoids (i.e., terpenes, alkaloids, hydrocarbons etc.). Overall, 20 studies show to exhibit diversified implications of cannabis in arrays of diseases, especially cancer and neurological disorders, because of its analgesic, antidiabetic, antioxidant, anti-inflammatory, anticancer, sedative, spasmolytic, antimicrobial, and expectorant effects. Conclusion_This investigation suggests that the cannabinoids from Cannabis sativus can be employed to treat different serious ailments.
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Is Cannabis a boon or bane? Cannabis sativa has long been a versatile crop for fiber extraction (industrial hemp), traditional Chinese medicine (hemp seeds), and recreational drugs (marijuana). Cannabis faced global prohibition in the 20th century because of the psychoactive properties of ∆9-tetrahydrocannabinol; however, recently, the perspective has changed with the recognition of additional therapeutic values, particularly the pharmacological potential of cannabidiol. A comprehensive understanding of underlying mechanism of cannabinoid biosynthesis is necessary to cultivate and promote globally the medicinal application of Cannabis resources. Here, we comprehensively review the historical usage of Cannabis, biosynthesis of trichome-specific cannabinoids, regulatory network of trichome development, and synthetic biology of cannabinoids. This review provides valuable insights into the efficient biosynthesis and green production of cannabinoids, and the development and utilization of novel Cannabis varieties.
Ethnopharmacological relevance: Although the root of Cannabis sativa L. has been mentioned in some regions, such as the Vale do São Francisco, for its potential traditional medicinal use as an anti-inflammatory, anti-asthmatic, and against gastrointestinal diseases, it has received little exploration and discussion. Aim of the study: This study aimed to perform a chemical analysis of an aqueous extract of Cannabis sativa roots (AqECsR) and evaluate its pharmacological effects against uterine disorders, in vivo and ex vivo, in rodents. Materials and methods: The roots were provided by the Brazilian Federal Police, and the freeze-dried extract was used for the chemical analysis of the AqECsR by high performance liquid chromatography coupled with mass spectrometry (HPLC-MS). The sample was subsequently used in three doses for pharmacological assays (12.5, 25, and 50 mg/kg), which included the spasmolytic activity test and the primary dysmenorrhea test. The primary dysmenorrhea test aimed to verify the effect of AqECsR on induced abdominal contortions in female mice in vivo and to perform a morphometric analysis of the organs. Association tests at subtherapeutic doses of AqECsR with antidysmenorrheic drugs were also performed. Results: The data obtained by HPLC-MS suggested the presence of four substances: cannabisativine, anhydrocannabisativine, feruloyltyramine, and p-coumaroyltyramine. In the pharmacological assays, the AqECsR showed no spasmolytic effect. However, in the antidysmenorrheal activity test, AqECsR demonstrated a significant in vivo effect of reducing oxytocin-induced abdominal contortions. Morphometric analysis of the uterus showed no significant organ enlargement effect, and the association of AqECsR with subtherapeutic doses of three drugs used in antidysmenorrheal therapy (mefenamic acid, scopolamine, and nifedipine) showed an effect in reducing abdominal contortions. Conclusions: In conclusion, AqECsR contains four chemical compounds and exhibits an antidysmenorrheic effect both alone and in association with drugs, reducing abdominal contortions in female mice without generating organ enlargement in the animals. Further studies are needed to prove the mechanism of action by which AqECsR promotes its effect on primary dysmenorrhea and to explore its associations.
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Cannabis: Evolution and Ethnobotany is a comprehensive, interdisciplinary exploration of the natural origins and early evolution of this famous plant, highlighting its historic role in the development of human societies. Cannabis has long been prized for the strong and durable fiber in its stalks, its edible and oil-rich seeds, and the psychoactive and medicinal compounds produced by its female flowers. The culturally valuable and often irreplaceable goods derived from cannabis deeply influenced the commercial, medical, ritual, and religious practices of cultures throughout the ages, and human desire for these commodities directed the evolution of the plant toward its contemporary varieties. As interest in cannabis grows and public debate over its many uses rises, this book will help us understand why humanity continues to rely on this plant and adapts it to suit our needs.
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Multiple sclerosis (MS) is a chronic and debilitating autoimmune disease, characterized by chronic inflammatory demyelination in the nervous tissue and subsequent neurological dysfunction. Spermidine, a natural polyamine, has been shown to affect inflammation in some experimental models. We show here that spermidine could alleviate experimental autoimmune encephalomyelitis (EAE), a model for MS, through regulating the infiltration of CD4⁺ T cells and macrophages in central nervous system. Unexpectedly, we found that spermidine treatment of MOG-specific T cells did not affect their pathogenic potency upon adaptive transfer; however, spermidine diminished the ability of macrophages in activating MOG-specific T cells ex vivo. Depletion of macrophages in diseased mice completely abolished the therapeutic effect of spermidine, indicating a critical role of spermidine-activated macrophages. Mechanistically, spermidine was found to specifically suppress the expression of interleukin-1beta (IL-1β), IL-12 and CD80 while enhance the expression of arginase 1 in macrophages. Interestingly, macrophages from spermidine-treated mice could also reverse EAE progression, while pretreatment of those macrophages with the arginase 1 inhibitor abrogated the therapeutic effect. Therefore, our studies revealed a critical role of macrophages in spermidine-mediated treatment on EAE and provided novel information for better management of MS.Cell Death and Differentiation advance online publication, 22 July 2016; doi:10.1038/cdd.2016.71.
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Cannabis sativa L. is an important herbaceous species originating from Central Asia, which has been used in folk medicine and as a source of textile fibre since the dawn of times. This fast-growing plant has recently seen a resurgence of interest because of its multi-purpose applications: it is indeed a treasure trove of phytochemicals and a rich source of both cellulosic and woody fibres. Equally highly interested in this plant are the pharmaceutical and construction sectors, since its metabolites show potent bioactivities on human health and its outer and inner stem tissues can be used to make bioplastics and concrete-like material, respectively. In this review, the rich spectrum of hemp phytochemicals is discussed by putting a special emphasis on molecules of industrial interest, including cannabinoids, terpenoids and phenolic compounds, and their biosynthetic routes. Cannabinoids represent the most studied group of compounds, mainly due to their wide range of pharmaceutical effects in humans, including psychotropic activities. The therapeutic and commercial interests of some terpenoids and phenolic compounds, and in particular stilbenoids and lignans, are also highlighted in view of the most recent literature data. Biotechnological avenues to enhance the production and bioactivity of hemp secondary metabolites are proposed by discussing the power of plant genetic engineering and tissue culture. In particular two systems are reviewed, i.e. cell suspension and hairy root cultures. Additionally, an entire section is devoted to hemp trichomes, in the light of their importance as phytochemical factories. Ultimately, prospects on the benefits linked to the use of the -omics technologies, such as metabolomics and transcriptomics to speed up the identification and the large-scale production of lead agents from bioengineered Cannabis cell culture, are presented.
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Dr. Ethan Russo, MD, is a board-certified neurologist, psychopharmacology researcher, and Medical Director of PHYTECS, a biotechnology company researching and developing innovative approaches targeting the human endocannabinoid system. Previously, from 2003 to 2014, he served as Senior Medical Advisor and study physician to GW Pharmaceuticals for three Phase III clinical trials of Sativex® for alleviation of cancer pain unresponsive to optimized opioid treatment and studies of Epidiolex® for intractable epilepsy. He has held faculty appointments in Pharmaceutical Sciences at the University of Montana, in Medicine at the University of Washington, and as visiting Professor, Chinese Academy of Sciences. He is a past President of the International Cannabinoid Research Society and former Chairman of the International Association for Cannabinoid Medicines. He serves on the Scientific Advisory Board for the American Botanical Council. He is the author of numerous books, book chapters, and articles on Cannabis, ethnobotany, and herbal medicine. His research interests have included correlations of historical uses of Cannabis with modern pharmacological mechanisms, phytopharmaceutical treatment of migraine and chronic pain, and phytocannabinoid/terpenoid/serotonergic/vanilloid interactions.
The golden age of cannabis pharmacology began in the 1960s as Raphael Mechoulam and his colleagues in Israel isolated and synthesized cannabidiol, tetrahydrocannabinol, and other phytocannabinoids. Initially, THC garnered most research interest with sporadic attention to cannabidiol, which has only rekindled in the last 15 years through a demonstration of its remarkably versatile pharmacology and synergy with THC. Gradually a cognizance of the potential of other phytocannabinoids has developed. Contemporaneous assessment of cannabis pharmacology must be even far more inclusive. Medical and recreational consumers alike have long believed in unique attributes of certain cannabis chemovars despite their similarity in cannabinoid profiles. This has focused additional research on the pharmacological contributions of mono- and sesquiterpenoids to the effects of cannabis flower preparations. Investigation reveals these aromatic compounds to contribute modulatory and therapeutic roles in the cannabis entourage far beyond expectations considering their modest concentrations in the plant. Synergistic relationships of the terpenoids to cannabinoids will be highlighted and include many complementary roles to boost therapeutic efficacy in treatment of pain, psychiatric disorders, cancer, and numerous other areas. Additional parts of the cannabis plant provide a wide and distinct variety of other compounds of pharmacological interest, including the triterpenoid friedelin from the roots, canniprene from the fan leaves, cannabisin from seed coats, and cannflavin A from seed sprouts. This chapter will explore the unique attributes of these agents and demonstrate how cannabis may yet fulfil its potential as Mechoulam's professed “pharmacological treasure trove.”
Osteoarthritis, as the major cause of chronic musculoskeletal pain, impacts people aged 45 and above. The first line analgesic treatments have reported minimal short term effects. The use of essential oils as pain killer has increased, recently. Mentha spicata, or spearmint essential oil is famous due to its anti-flatulence effects, but one less known biological activity of spearmint is its analgesic activity. The aim of our study was to confirm the analgesic effects of M. spicata essential oil. In this review, we evaluated the articles on analgesic activities of M. spicata essential oil from different relevant databases (PubMed, Science Direct, Wiley, Taylor & Francis, and Springer) without limitation up to April 30, 2016. Different animal studies have reported the analgesic effects of M. spicata essential oil and its main abundant compounds such as carvone, limonene and menthol, also, the efficacy and safety of spearmint oil in reducing of pain severity were confirmed in osteoarthritis patients. In spite of the beneficial effects of spearmint oil in reducing of pain, other large clinical trials are required to confirm the efficacy and safety of M. spicata oil.
The present study was aimed to evaluate the anti-diarrhoeal activity of friedelin isolated from leaves of Azima tetracantha Lam. The anti-diarrhoeal effect of friedelin was studied by using castor oil-induced diarrhoea, gastrointestinal motility test, magnesium sulphate-induced diarrhea and castor oil-induced enteropooling in rats. Friedelin (20 mg/kg) showed significant (P < 0.0001) reduction of intestinal transit and gastric emptying which were similar to the anti- motility activity as known compound atropine (0.1 mg/kg). Friedelin (20 mg/kg) also exerted significant anti-enteropooling effects, against castor oil-induced enteropooling in rats. The defaecation frequencies and the faecal droppings wetness were significantly (P < 0.0001) reduced. Additionally, friedelin (20 mg/kg) revealed significant (P < 0.0001) inhibition (89.64%) of castor oil-induced diarrhea. The overall results elucidated that the anti-diarrhoeal activity of friedelin may be due to its anti-secretory and anti-motility properties, which consequently provide evidence for the traditional claim.