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History of medical cannabis


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Understanding the cultural and medical history of cannabis use is an important component to the successful integration of cannabis in modern clinical practices. This review chronicles over six thousand years of documented cannabis use in cultural practices, medical applications, breeding practices to enhance the pharmacological properties, and the various methods by which people have consumed the plant.
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J Pain Manage 2016;9(4):387-394 ISSN: 1939-5914
© Nova Science Publishers, Inc.
History of medical cannabis
Andrew Hand, MSc, Alexia Blake, MSc,
Paul Kerrigan, BSc, Phineas Samuel,
and Jeremy Friedberg*, PhD
MedReleaf Corp, Markham Industrial Park, Markham,
Ontario, Canada
* Correspondence: Dr. Jeremy Friedberg, MedReleaf Corp.,
Markham Industrial Park, Markham, Ontario, Canada,
L3R 6C4, P.O. Box 3040.
Understanding the cultural and medical history of cannabis
use is an important component to the successful integration
of cannabis in modern clinical practices. This chapter
chronicles over six thousand years of documented cannabis
use in cultural practices, medical applications, breeding
practices to enhance the pharmacological properties, and
the various methods by which people have consumed the
Keywords: Cannabis, history of cannabis, medical cannabis,
Today there is much discussion and debate over
cannabis and its use in healthcare. But what is often
left out of the dialogue is the more than 6000 years of
documented experience people have had with this
plant. Historically, cannabis’ medical applications
appear to have been realized by most cultures,
however, it appears that much of our modern day
cultural perspective on cannabis is based neither on
historical evidence nor recent discovery. As with
many scientific disciplines, much can be learned from
our collective history. To help with our modern
understanding of cannabis, this chapter provides the
reader with a historical account of this plants use, a
perspective into the effects of millennia of selective
breeding, and insight into the many ways in which
cannabis can be administered.
History of cannabis use
The earliest evidence of cannabis cultivation comes
from China in the form of pollen deposits found in the
village site of Pan-p’o dated to 4000 BCE (1). At the
Andrew Hand, Alexia Blake, Paul Kerrigan et al.
time, cannabis was regarded among the ‘five grains’
and was farmed as a major food crop in addition to its
major role in the production of textiles, rope, paper,
and oil (2). The first record of its use in medicine
comes from the Pen-ts’ao ching, the world’s oldest
pharmacopoeia (3). Although compiled between 0-
100 AD, the Pen-ts’ao has been attributed to Emperor
Shen-nung, who ruled during 2700 BCE (3). It
recognizes cannabis as being useful for more than 100
ailments, including rheumatic pain, gout and malaria
(4). The Pen-ts’ao ching also mentions the
psychoactive effects of cannabis stating that ma-fen
(fruit of cannabis), if taken over the long-term, makes
one communicate with spirits and lightens one’s
body” (1). Between 117 and 207 AD, Hua T’o, a
physician of the time and the founder of Chinese
surgery, described cannabis as an analgesic (5). He is
reported to have used a mixture of cannabis and wine
to anesthetize his patients before surgery (1). As
cannabis use increased in China, it spread westward,
reaching India by 1000 BCE (2, 3).
Cannabis spread quickly throughout India and
was used extensively, both recreationally and
medicinally (3). It was also adopted and integrated
into religious practices, earning mention in the
Atharva Veda, one of the Vedic scriptures of
Hinduism, as being among the five sacred plants of
Hinduism, and teaching that a guardian angel lives
within its leaves (3). Cannabis is mentioned within the
Vedas as a “source of happiness,” a “joy-giver,” and a
“bringer of freedom” (2, 3). The Raja Valabba states
that the gods created cannabis out of compassion for
humans (2). In Hinduism, cannabis was smoked
during the daily devotional service (2). Due to
religious use in India, it was possible to explore the
medicinal benefits of cannabis, which led to the
discovery that cannabis can be used to treat a plethora
of diseases and ailments (2). The general uses in
India included use as an analgesic, anticonvulsant,
anesthetic, antibiotic, and anti-inflammatory (3).
These properties allowed for the treatment of many
diseases, including epilepsy, rabies, anxiety,
rheumatism and even respiratory conditions such as
bronchitis and asthma (3). Cannabis use continued to
spread throughout the world and was adopted by
many different cultures (3).
The Assyrians were aware of cannabis’
psychotropic effects since at least 900 BCE (3). By
450 BCE, cannabis had reached the Mediterranean, as
evidenced by a first-hand account from Herodotus (3).
Herodotus writes of a Scythian funeral ceremony,
where cannabis seeds were burned ritually for their
euphoric effects (3). In Tibet, cannabis was
considered to be sacred, used extensively in medicine
and in Tantric Buddhism to facilitate meditation (3).
In Persian medicine, cannabis’ biphasic effects were
clearly noted, emphasizing the distinction between
cannabis’ initial euphoric effects and the dysphoric
effects that follow (2). The Persian physician
Avicenna (980 1037 AD), one of the most
influential medical writers of the medieval period,
published ‘Avicenna’s Canon of Medicine’, a
summary of all medical knowledge of the time (6).
His canon was widely studied in western medicine
from the thirteenth to the nineteenth century, having a
lasting impact on western medicine (6). Avicenna
recorded cannabis as an effective treatment for gout,
edema, infectious wounds and severe headaches (6).
In Arabic medicine, cannabis was regarded as an
effective treatment for epilepsy (7). Recorded first by
al-Mayusi, between 900-1000 AD (13), followed by
al-Badri, in 1464 AD, who wrote of the chamberlain’s
epileptic son who was cured using cannabis leaves
(6). In the 1300s, Arab traders brought cannabis from
India to Africa, where it was used to treat malaria,
fever, asthma and dysentery (3). The 1500s saw
cannabis reach South America via the slave trade,
which transported Africans along with seeds, from
Angola to Brazil (3). In Brazil, cannabis was used
extensively in the African community, including in
religious rituals such as the ‘Catimbo,’ which used
cannabis for magical and medical purposes. From
Brazil, cannabis travelled north to Mexico where it
was used recreationally by individuals of low-
socioeconomic class (3).
Cannabis’ therapeutic uses were first introduced
to Western medicine in 1839, when the Irish
physician William O’Shaughnessy published ‘On the
preparations of Indian hemp, or gunjah’ (3). In the
first paragraph of his work he highlights that “…in
Western Europe, [cannabis’] use either as a
stimulant or as a remedy is equally unknown,”
indicating British unfamiliarity with the drug (3).
O’Shaughnessy first encountered cannabis while
working as a physician in India with the British East
India Company (3). Interested, he studied the existing
History and cannabis
literature on cannabis and conferred with elders and
healers to understand the recreational and medicinal
uses of cannabis in India (3). O’Shaughnessy then
proceeded to test the effects of different forms of
cannabis on animals to evaluate the toxicity of the
drug (3). Confident that the drug was safe, he
provided extracts of cannabis to patients and
discovered it had both analgesic and sedative
properties (5). The immediate results impressed him
enough to begin prescribing the drug and he was
rewarded with positive results (5). His greatest
success came when he managed to calm the muscle
spasms caused by tetanus and rabies (5).
O’Shaughnessy’s initial results, followed by those of
other physicians, led cannabis to spread rapidly
through Western medicine in both Europe and into
North America.
In 1860, the Committee on Cannabis Indica of the
Ohio State Medical Society reported success for the
use of cannabis to treat many ailments including
gonorrhea, asthma, rheumatism and intense stomach
pain (9). Cannabis’ use in medicine continued to
grow, peaking in the late eighteenth/early nineteenth
century when it could be readily found in over-the-
counter pharmaceuticals such as “Piso’s cure” and the
“One day cough cure” (5). This rapidly increasing
popularity of the new medication sparked the
publication of more than 100 papers on its therapeutic
uses (3). In 1924, Sajous’s Analytic Cyclopedia of
Practical Medicine summarized what, at the time,
were believed to be the main therapeutic uses of
cannabis (10). They concluded that cannabis was
useful in the treatment of migraines, coughing and
inflammation, along with diseases such as tetanus,
rabies, and gonorrhea.
Following this rapid rise of use within 1900s
medicine, cannabis use began to decline due to a
variety of factors (3). Vaccines for diseases such as
tetanus made cannabis’ previous role in treating these
diseases obsolete (3). Furthermore, development of
synthetic analgesics such as chloral hydrate,
antipyrine (5) and aspirin filled some of the demand
for analgesics (3). However, it was the development
of the hypodermic needle and its application to
opiates that could be considered the greatest factor to
the decline of cannabis use (3). These factors led to an
overall decrease in the prevalence of cannabis and its
necessity as an analgesic, making it more susceptible
to the political influences to follow.
At the beginning of the 1900s, cannabis’
recreational use in the United States of America was
in large restricted to Mexican and African minority
groups who had immigrated into the country (3). By
the 1930s there was an increase in recreational use
among all US citizens, leading narcotics officers to
push for restrictive legislation on both the recreational
and medicinal use of cannabis (5). The American
Medical Association advised that cannabis remains a
medical agent, citing its medicinal use, low toxicity
and absolutely no evidence “…to show that its
medicinal use is leading to the development of
cannabis addiction” (5). However, despite the
protests, in 1937 the Marijuana Tax Act was enacted,
essentially ending the already diminished use of
cannabis as a therapeutic (5). In 1941, cannabis was
removed entirely from the American pharmacopeia
(5). Over the next couple decades, cannabis use in
medicine was essentially non-existent, and it was not
until the 1970s that medical interests were revived (5).
The prevalence of recreational cannabis use rose
significantly in the early 1970s, spiking from only 5%
of people reporting to have used cannabis in 1967, to
44% in 1971 (3). This massive increase in recreational
use brought cannabis into the spotlight, and with the
discovery of cannabis’ active component (Δ9-THC)
by Gaoni and Mechoulam in 1964, it became possible
to isolate the principle component, making the study
and quantification of its effects possible (3). In 1988,
the receptor CB1 was identified (11). It was found to
be the binding site of THC and to be the most
abundant neurotransmitter receptor in the central
nervous system (11). This discovery was followed by
the identification of a second cannabinoid receptor,
CB2, localized primarily in the peripheral nervous
system and on immune cells (12). The presence of
cannabinoid receptors, concentrated in neural and
immune cells, alluded to a possible mode of action
that could be the source of cannabis’ analgesic,
sedative and immunoregulatory properties.
Over the past few thousand years many different
cultures have been exposed to cannabis and often
realized the medicinal application of cannabis (see
Figure 1). When cannabis was introduced to Western
medicine, its medicinal applications were swiftly
recognized and its use spread rapidly. The decline of
Andrew Hand, Alexia Blake, Paul Kerrigan et al.
cannabis use in the west was due to a variety of
factors and as a result its medicinal use was forgotten.
The discovery of the active constituent Δ9-THC, as
well as endogenous receptors for cannabinoids,
stimulated research into the drug shows that cannabis
does, in fact, have a direct effect on the body.
Figure 1. A timeline of cultural and medical milestones in cannabis.
The genetics and selective breeding
of cannabis
Since human cultures first began cultivating cannabis,
selective breeding has been employed to improve wild
cannabis as a source of seeds, fiber and drugs.
However, cannabis is not a very simple plant to breed,
as two primary complications have made controlled
selective breeding a challenge. Firstly, cannabis is
typically a dioecious plant, indicating that individual
plants are distinctly male or female. Therefore,
cannabis plants are predisposed to outcrossing as
opposed to self-pollination, which is the primary
means of fixing desirable traits in other species. In
addition to this, the valuable components of cannabis
are produced and harvested from female plants, and
thus it is a challenge to identify males with favourable
genetically regulated traits. Secondly, cannabis is a
wind-pollinated plant and therefore will very easily
pollinate surrounding females, making selective
crosses difficult to control. Due to the challenges
outlined above, it is typical of cannabis growers to
utilize clonal propagation as opposed to seeds, as this
will produce identical “offspring.” Regardless of these
limitations, cannabis breeders have improved upon
the concentration of psychotropic compounds and
yield, whereas hemp breeders have continuously
worked to improve the textile characteristics of fiber-
type cannabis cultivars. Understanding the inheritance
of chemical phenotype (chemotype) for the most
clinically relevant cannabinoids has been central to
modern medicinal cannabis and hemp breeding.
Modern molecular techniques have allowed for a
History and cannabis
greater ability to screen for elite cultivars, greatly
increasing the rate at which desired traits can be
identified and bred into new cultivated varieties.
Primarily through the research of de Meijer at
HortaPharm B.V., four loci, O, A, B and C, have been
found to genetically regulate cannabinoid content (13,
14). Cannabinoids are terpenophenolic compounds,
produced primarily with the monoterpenoid precursor
geranylpyrophosphate (GPP), and one of two phenolic
precursors, olivetolic acid or divarinolic acid, both of
which are resorcinolic acid homologs produced by the
polyketide pathway (15, 16). Production of the
phenolic precursors can be disrupted by a mutant null
allele o, at locus O. In a homozygous state, synthesis
of either resorcinolic acid precursor is blocked, while
O/o heterozygous phenotypes typically have one-tenth
the cannabinoid content. This indicates that allele o
acts as a dominant repressor of the polyketide
pathway that generates both olivetolic acid and
divarinolic acid (17).
Synthesis of either olivetolic acid or divarinolic
acid is regulated by locus A, which according to de
Meijer (18) is likely polygenic, with the alleles Ape1 to
n encoding olivetolic acid synthase, and alleles Apr1 to n
encoding divarinolic acid synthase. These phenolic
precursors, along with GPP, are utilized by the
enzyme geranylpyrophosphate:olivetolate transferase
to produce either CBGA or CBGVA depending on the
phenolic precursor present (19). The synthesis of the
two most clinically relevant cannabinoids, THC
and CBD, is then controlled by co-dominant
alleles present at Locus B. THCA/THCVA or
CBDA/CBDVA will be produced if alleles BT or BD
is present and functional, respectively, while
homozygous individuals will produce significant
quantities of both metabolites. Variations in the
sequence of BT and BD can lead to enzymes with
reduced function, so THC:CBD ratios are commonly
found to deviate from 1:1 (14). Mutant alleles
BT0 and BD0 significantly reduce THCA and
CBDA production, while leading to considerable
accumulation of the precursor CBGA (14). Lastly, an
independent gene at Locus C produces the enzyme
CBCA synthase, which competes with CBDA
synthase and THCA synthase for CBGA precursor,
producing the cannabinoid CBCA or CBCVA (see
Figure 2).
Figure 2. Cannabinoids biosynthetic pathways.
Andrew Hand, Alexia Blake, Paul Kerrigan et al.
Many of the genes mentioned above have been
sequenced, and molecular markers detectable via PCR
have been developed and validated to correlate with
specific chemotypes. Modern breeders can take
advantage of this simple molecular technique in order
to expedite breeding objectives, while using classical
breeding techniques in order to select for other
favourable traits, such as yield, disease resistance and
flowering time requirements, all aspects that greatly
impact the output of a medical cannabis facility.
In the near future, more advanced molecular
breeding techniques, such as transgenic gene
expression or substitution of gene promoters with
knockdown/overexpression variants could yield
dramatically different chemotypes with potentially
novel medical applications.
Modern methods of cannabis
Most commonly, the flower of the plant is dried,
ground, and smoked. The main benefit of smoking is
that it provides rapid relief on the timescale of
minutes (20). Furthermore, this instant feedback
allows users to adjust their dosing to either increase or
maintain a steady state of relief. This control also
reduces the risk of experiencing adverse effects due to
overconsumption, such as dizziness, paranoia, or
Similarly, vaporization also provides rapid
onset of effects, with the added benefit of being
considered a much safer and more efficient means
of cannabis consumption compared to smoking.
Pyrolysis of cannabis has been shown to generate
more than 2000 new compounds, including
hazardous components such as carbon monoxide
and polycyclic aromatic hydrocarbons (21, 22).
In addition, some studies have shown that 30-50%
of THC is lost during burning (23). Since vaporization
involves heating dried cannabis to temperatures
below combustion, the production of smoke is
avoided, and fewer harmful combustion by-products
are created (24, 25). Thus, vaporization is a very
efficient method of consumption that allows for rapid
relief of symptoms, and is overall a superior and
healthier means of consuming cannabis compared to
Oral administration
Oral administration through either ingestion or
sublingual absorption are also popular methods of
cannabis consumption. Similar to vaporization, oral
consumption avoids exposure to smoke and other
hazardous pyrolysis by-products. However, cannabis
must be decarboxylated prior to ingestion.
Oral administration often involves the
consumption of a cannabis extract rather than
the actual plant material. For oral sprays, such as
Sativex, the extract is often mixed with a
diluting/carrier agent, such as propylene glycol (26).
Alcohol, flavouring, and sweeteners may also be
added to adjust the viscosity and taste. Application of
the product under the tongue results in rapid
absorption due to the high vascularity of the
sublingual region. However, taste is obviously a
concern with such products, and a titrated spray
dispenser is required for consistent dosing.
Alternatively, an infusion can be made by
soaking decarboxylated cannabis in butter or edible
oil. This infusion can be used for cooking or baking
applications. However, making this infusion is a time-
consuming and highly tedious process that, if
completed at home, will produce extracts with
unknown and highly variable THC concentrations.
Because of this dosing challenge, capsules may be a
safer and more convenient method of cannabis
administration, resulting in higher patient compliance
and a lower risk of experiencing adverse effects.
Despite being a popular historical method of
consuming cannabis, tea preparations are not very
popular or recommended for several reasons (27).
First, cannabinoid extraction during steeping will be
very low due to the low water solubility of
cannabinoids. However, the addition of cream or non-
skim milk may aid in this. Secondly, water
temperatures may not be sufficient to completely
decarboxylate cannabinoids. Thirdly, the final
concentration of cannabinoids in the tea will be
unknown (and low), making tea a very inefficient way
of consuming cannabis.
Compared to sublingual administration or
inhalation, there is a noticeable delay in the onset of
therapeutic action following ingestion (21, 28). For
this reason, ingestion may not be a preferred means of
consumption if instant relief is desired.
History and cannabis
Other methods of consumption
While inhalation and oral administration are the most
common (and therefore the most studied) methods of
cannabis consumption, rectal, transdermal, and
ophthalmological administration are also possible. All
of these methods are commonly used for drugs that
are not suitable for oral administration, often due
to their potential to irritate the stomach or
gastrointestinal tract, and more commonly due to their
low oral bioavailability (21). For cannabis, these
methods also avoid the generation and consumption
of smoke and other hazardous combustion
Transdermal application may be achieved by
incorporating decarboxylated cannabis oil into topical
products, such as lotions, gels, or transdermal
patches. Such products may be most useful for
individuals seeking to treat localized, physical
pain. Ophthalmological and suppository products
are less common, but animal studies have
demonstrated their potential as alternative methods
of cannabis consumption offering rapid absorption
(24, 28-30).
Cannabis use both culturally and medically has
had a long and well-documented history. Cannabis
has been used medicinally in many different
cultures, and upon exposure to western medicine
in the 19th century, it quickly gained popularity
as an analgesic, anticonvulsive, and hypnotic. These
medical properties are innately part of cannabis
biology, and over time selective breeding projects
have amplified these traits. The medical properties
of this plant combined with an understanding
of the effective methods of consumption help
make cannabis the powerful medication it is
today. Much can be learned from this historical
record, but what is most salient is that the use
of cannabis to treat clinical symptoms is not new.
The challenge is education and policy changes to
incorporate the nature of cannabis’ atypical
consumption requirements into modern clinical
Conflict of interest
The authors are all employees of MedReleaf, an
authorized grower and distributor of medical cannabis
in Canada.
We thank Dean Pelkonen for assistance with graphic
design for Figure 1.
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Submitted: August 01, 2016. Revised: August 25,
2016.Accepted: September 03, 2016.
... Both cannabinoids are metabolized in the liver by cytochrome P450 [32,33]. In the last decade, advocates of medicinal cannabis have demonstrated its potential for the treatment of various diseases, including cancer [34,35]. Cannabinoids are known to have palliative effects on cancer patients [10], helping to reduce the sensations of nausea, pain and vomiting induced by chemotherapy, as well as helping with insomnia and appetite [36]. ...
... This approach has been used to obtain complex mixtures of compounds or essential oils from aromatic plants [39][40][41], and it has been demonstrated that their biological activities depend on the relative concentration of their components [42]. In a similar way, it has been found that cannabis oils exhibit higher activity than isolated compounds, and this synergic effect is known as the entourage effect [34,43]. Therefore, the development of pharmacological and biotechnological applications based on antioxidant and antimycobacterial properties will strongly depend on the extraction procedure [2], which can significantly modify the relative composition of oils obtained from C. sativa L. [22]. ...
Full-text available
Currently, much effort is being placed into obtaining extracts and/or essential oils from Cannabis sativa L. for specific therapeutic purposes or pharmacological compositions. These potential applications depend mainly on the phytochemical composition of the oils, which in turn are determined by the type of C. sativa and the extraction method used to obtain the oils. In this work, we have evaluated the contents of secondary metabolites, delta-9-tetrahydrocannabinol (THC), and cannabidiol (CBD), in addition to the total phenolic, flavonoids, and anthraquinone content in oils obtained using solid–liquid extraction (SLE) and supercritical fluid extraction (SCF). Different varieties of C. sativa were chosen by using the ratio of THC to CBD concentrations. Additionally, antioxidant, antifungal and anticancer activities on different cancer cell lines were evaluated in vitro. The results indicate that oils extracted by SLE, with high contents of CBD, flavonoids, and phenolic compounds, exhibit a high antioxidant capacity and induce a high decrease in the cell viability of the tested breast cancer cell line (MCF-7). The observed biological activities are attributed to the entourage effect, in which CBD, phenols and flavonoids play a key role. Therefore, it is concluded that the right selection of C. sativa variety and the solvent for SLE extraction method could be used to obtain the optimal oil composition to develop a natural anticancer agent.
... Scientists Wood, Spivey, and Easterfield discovered one active ingredient of cannabis, which they named "cannabinol"in 1896 (Mills 2003 Hand et al. 2016). ...
... The general use, cultivation, and "smuggling" of cannabis were also evident in British colonies of America, China, Africa, Sri Lanka, and Burma. By global standards, cannabis regulations in Africa were early and rigorous, targeting specific socio-economic and cultural groups (Hand et al. 2016). In Sri Lanka, the Opium and Bhang Ordinance, enacted by the British authority in 1867, limited the selling of cannabis to licensed sellers only. ...
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Background The emergence of colonial medicine in the North-Eastern Frontier witnessed different phases of consistent competition and resistance. Herbs such as cannabis provided native physicians with a coherent power to resist colonial medical intervention. Before British rule, cannabis assumed great significance in the socio-economic, cultural, and religious spheres. The colonizers’ bioprospection of cannabis shifted the production and use of cannabis from a medical and recreational plant to an industrial and commercial commodity. British policies on cannabis caused its ban leading to natives’ reliance on colonial cannabis products. As a result, the native medical practitioners resisted for reviving cannabis in the indigenous therapeutics. This paper mainly aims to investigate the decline of medicinal cannabis in indigenous therapeutics, causing subtle resistance of the native physicians of the North-Eastern Frontier. Methods This paper follows a nomadology method based on primary and secondary sources to understand the impact on native physicians after the ban on private use, cultivation, and sale of cannabis. The primary sources/data have been collected from the Directorate of Archives: Government of Assam and Directorate of State Archives and Research Centre, Kolkata, West Bengal. Secondary sources have been collected from books, articles, and theses accessed from various libraries and websites. Results Ban on cannabis led to dual responses from the indigenous population of the frontier. First is the interest of the native physicians resisting the revival of cannabis in indigenous therapeutics. The second is the interest of the frontier’s elites, who viewed cannabis as a “dangerous drug.” The British policies of control and restrictions on cannabis, the rift of response from the natives, and the over-powering of the indigenous therapeutics by the colonial medical system led to the decline of medicinal uses of cannabis in the North-Eastern Frontier. Discussions Various pre-colonial and colonial factors helped colonial medical practices to get the upper hand over indigenous therapeutics. Such a shift led to the decline of indigenous medicinal cannabis causing native resistance, which was patient and silent. Conclusions British ban on cannabis resulted in a rift of native responses, resistance, and decline of cannabis in the indigenous therapeutics of the North-Eastern Frontier.
... On a historical basis the use of marijuana dates as far as back to six millennia of the common era, when the seeds of the plant were used for edible purpose in mainland China, even though the weaving material drawn from the plant in hemp dates back to four millennia of the pre-Christian era (Monotony, et al., 2021). The earliest recorded use of Cannabis on pharmaceutical grounds was in 2727 of the common eras in mainland China (Hand, et al., 2016). The records suggest that the plant was used in old (TCM) typically for intestinal disorders, jungle fever, joint aches as well as acute pains occurring during labour . ...
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Cannabis sativa, popularly known as "marijuana," poses a problem since it may have both beneficial and harmful effects. Cannabis has long been used for medicinal and recreational purposes, which demonstrates its value as a plant. Instead of this, enough evidence suggests that abusing this wonder herb can have negative effects on a number of organs and organ systems, such as the pulmonary system, the body's defense system, the cardiovascular system, etc. Additionally, it may affect both male and female potency and may also have clastogenic effects. Yet, it cannot be ruled out that there are some benefits to using marijuana responsibly, since it has been shown to be a miraculous treatment for atrophy, acute pain, a loss of muscular tone, motion sickness, and insomnia. This chapter will attempt to provide a thorough understanding of the various health effects of the herb and its extracted active bioactive ingredients.
... On a historical basis the use of marijuana dates as far as back to six millennia of the common era, when the seeds of the plant were used for edible purpose in mainland China, even though the weaving material drawn from the plant in hemp dates back to four millennia of the pre-Christian era (Monotony, et al., 2021). The earliest recorded use of Cannabis on pharmaceutical grounds was in 2727 of the common eras in mainland China (Hand, et al., 2016). The records suggest that the plant was used in old (TCM) typically for intestinal disorders, jungle fever, joint aches as well as acute pains occurring during labour . ...
... Ancak uzun süreli kullanıldığında psikoaktif etkilerinin olduğundan bahsedilmektedir. Çin cerrahisinin kurucusu olan Hua Tou keneviri analjezik olarak tanımlamıştır (10,11). ...
Kenevir bitkisi, endüstri ve tıp gibi temel alanlarda kolay, ekonomik ve sağlıklı çözümler sunan bir bitkidir. Başta kannabinoidler olmak üzere çok sayıda kimyasal madde içermektedir ve zengin bir ürün yelpazesi vardır. Endüstriyel kenevir biyobozunur her çeşit plastik madde, kağıt-karton, ısı yalıtım ve inşaat malzemeleri üretiminde, tekstil ve otomotiv sektöründe, gıda ve kozmetik ürünlerin imalatında ve biyodizel üretiminde kullanılmaktadır. Medikal kenevir kemoterapiye bağlı bulantı-kusma, kanser ile ilişkili nöropatik ağrı, multipl skleroz ile ilişkili spastisitede, HIV’li hastalarda kilo alımında ve epilepsi gibi bazı hastalıkların tedavisinde kullanılmaktadır. Bu yazıda, eski uygarlıklar tarafından kullanılmış olup kültürümüzde önemli bir yere sahip olan ve son yıllarda popülerlik kazanan tıbbi ve endüstriyel kenevir bitkisinin dünden bugüne kullanımı, yetiştirilmesi, tıp ve endüstrideki yeri hakkında bilgi verilmesi ve aynı zamanda kenevirin ekonomik potansiyelinin ortaya koyulması amaçlanmıştır.
... Lastly, if the compound occurs in consumable portions of the cannabis plant, that concentration can be used as part of the weight of evidence to determine toxicological risk. Cannabis has been utilized medically, recreationally, and spiritually for millennia with fewer adverse effects identified than tobacco, many pharmaceuticals, and alcohol [34][35][36]. Even though the plant has changed through advanced breeding techniques, serious adverse events remain rare [37][38][39]. ...
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Vaporization is an increasingly prevalent means to consume cannabis, but there is little guidance for manufacturers or regulators to evaluate additive safety. This paper presents a first-tier framework for regulators and cannabis manufacturers without significant toxicological expertise to conduct risk assessments and prioritize additives in cannabis concentrates for acceptance, elimination, or further evaluation. Cannabinoids and contaminants (e.g., solvents, pesticides, etc.) are excluded from this framework because of the complexity involved in their assessment; theirs would not be a first-tier toxicological assessment. Further, several U.S. state regulators have provided guidance for major cannabinoids and contaminants. Toxicological risk assessment of cannabis concentrate additives, like other types of risk assessment, includes hazard assessment, dose–response, exposure assessment, and risk characterization steps. Scarce consumption data has made exposure assessment of cannabis concentrates difficult and variable. Previously unpublished consumption data collected from over 54,000 smart vaporization devices show that 50th and 95th percentile users consume 5 and 57 mg per day on average, respectively. Based on these and published data, we propose assuming 100 mg per day cannabis concentrate consumption for first-tier risk assessment purposes. Herein, we provide regulators, cannabis manufacturers, and consumers a preliminary methodology to evaluate the health risks of cannabis concentrate additives.
Existen tres tipos de cannabinoides, su estudio ha estado íntimamente relacionado entre sí, por lo que en ocasiones es difícil hablar de unos sin mencionar a los otros. Los primeros en ser descubiertos fueron los fitocannabinoides, que vienen de la planta Cannabis spp. (Linneo, 1753). Después de este descubrimiento se identificaron receptores que modulan la respuesta al uso del cannabis, lo cual fue apoyado con el diseño de lo que ahora conocemos como cannabinoides sintéticos. Finalmente se encontraron los endocannabinoides, sustancias parecidas a las dos anteriores, pero producidas por el propio organismo (figura 1). La historia de estas sustancias es amplia y es un proceso que lleva por lo menos 60 años y continúa avanzando.
Study objectives As cannabis is increasingly used to treat sleep disorders, we performed a systematic review to examine the effects of cannabis on sleep and to guide cannabis prescribers in their recommendations to patients, specifically focusing on dosing. Methods We searched EMBASE, Medline, and Web of Science and identified 4,550 studies for screening. 568 studies were selected for full-text review and 31 were included for analysis. Study results were considered positive based on improvements in sleep architecture or subjective sleep quality. Bias in randomised controlled trials was assessed using Cochrane Risk of Bias tool 2.0. Results Sleep improvements were seen in 7 out of 19 randomised studies and in 7 out of 12 uncontrolled trials. There were no significant differences between the effects of tetrahydrocannabinol and cannabidiol. Cannabis showed most promise at improving sleep in patients with pain-related disorders, as compared to those with neurologic, psychiatric, or sleep disorders, and showed no significant effects on healthy participants’ sleep. While subjective improvements in sleep quality were often observed, diagnostic testing showed no improvements in sleep architecture. Adverse events included headaches, sedation, and dizziness, and occurred more frequently at higher doses, though no serious adverse events were observed. Conclusion High-quality evidence to support cannabis use for sleep remains limited. Heterogeneity in cannabis types, doses, timing of administration, and sleep outcome measures limit the ability to make specific dosing recommendations.
Conference Paper
Thirty bacterial strains, isolated from soils or endophytes to diverse plant species, belonging to the genera Bacillus, Pseudomonas, Paenibacillus and Kokuria were tested by inoculating potted hemp (Cannabis sativa L) indoors cultures of the cannabidiol (CBD) variety Silver Haze V1. Plants were grown for four week and growth assessment allowed to select the best biostimulant candidates. Parameters measured were chlorophyll content, crown diameter, shoot fresh and dry weights and internodes lengths. After this first selection round, five bacterial strains were retained for evaluation on growth, flower yield and cannabinoids contents of hemp after 12 weeks- culture until flowering and harvest. These strains were Paenibacillus sp. GDS96 UASWS1643, Priestia aryabhattai B29 UASWS1812, Bacillus simplex B33 UASWS1816, B. amyloliquefaciens BA5 UASWS1607 and Pseudomonas koreensis UASWS1668. Inoculations of Paenibacillus sp. GDS96 UASWS1643, P. aryabhattai B29 UASWS1812 and B. amyloliquefaciens BA5 UASWS1607 induced statistically significant increase (11-18%) in crown diameter, when compared to non-fertilised plants. Paenibacillus sp. GDS96 UASWS1643 even induced 14.5% increase in crown diameter, if compared to the positive fertilized control. Paenibacillus sp. GDS96 UASWS1643, B. amyloliquefaciens BA5 UASWS1607 and B. simplex B33 UASWS1816 induced higher chlorophyll contents. In terms of increase in dry flowers yields, all inoculations produced more dry flowers weight than the negative control, but Paenibacillus sp. GDS96 UASWS1643 and P. aryabhattai B29 UASWS1812 yielded 20.6% and 24.7 % more flowers weight than the negative control and 8.5% and 12.5% more than the positive control. They also yielded more CBD content.
The general use of “medical cannabis” and “cannabis-based drugs” in the treatment of cancer patients cannot be recommended due to the currently, still insufficient amount of data available. However, taking into account the legal framework, it is possible to consider its use in selected cases. Patients must be informed in detail about treatment goals, relevant side effects to be expected, and the character of a “therapy attempt”. Further the effectiveness and safety of the treatment should be critically re-evaluated after a few weeks and, if necessary, be terminated in the event of insufficient clinical improvement or if intolerable side effects occur. Smoking cannabis should be avoided and oral or oromucosal preparations should be used. Due to the narrow therapeutic range, the lowest possible starting dose is recommended, particularly for older patients, in the case of comorbidities, or in patients taking centrally acting drugs. Little is known about the clinically relevant interaction risks of cannabis. Especially in the context of modern cancer treatment, increased attention is required.
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Naturally occurring substances mentioned in medieval medical literatures currently have, and will continue to have, a crucial place in drug discovery. Avicenna was a Persian physician who is known as the most influential medical writers in the Middle ages.Avicennàs Canon of Medicine, the most famous books in the history of medicine, presents a clear and organized summary of all the medical knowledge of the time, including a long list of drugs. Several hundred substances and receipts from different sources are mentioned for treatment of different illnesses in this book. The aim of the present study was to provide a descriptive review of all anti-inflammatory and analgesic drugs presented in this comprehensive encyclopedia of medicine. Data for this review were provided by searches of different sections of this book. Long lists of anti-inflammatory and analgesic substances used in the treatment of various diseases are provided. The efficacy of some of these drugs, such as opium, willow oil, curcuma, and garlic, was investigated by modern medicine; pointed to their potent anti-inflammatory and analgesic properties. This review will help further research into the clinical benefits of new drugs for treatment of inflammatory diseases and pain. Please cite this paper as: Mahdizadeh SH, Khaleghi Ghadiri M, Gorji A. Avicenna's Canon of Medicine: a review of analgesics and anti-inflammatory substances. Avicenna J Phytomed, 2015; 5 (3): 182-202.
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Cannabis is one of the most widely abused substances throughout the world. The primary psychoactive constituent of cannabis, delta 9-tetrahydrocannabinol (▵9_THC), produces a myriad of pharmacological effects in animals and humans. Although it is used as a recreational drug, it can potentially lead to dependence and behavioral disturbances and its heavy use may increase the risk for psychotic disorders. Many studies that endeavor to understand the mechanism of action of cannabis concentrate on pharmacokinetics and pharmacodynamics of cannabinoids in humans. However, there is limited research on the chronic adverse effects and retention of cannabinoids in human subjects. Cannabis can be detected in body fluids following exposure through active/passive inhalation and exposure through breastfeeding. Cannabis detection is directly dependent on accurate analytical procedures for detection of metabolites and verification of recent use. In this review, an attempt has been made to summarize the properties of cannabis and its derivatives, and to discuss the implications of its use with emphasis on bioavailability, limit of detection, carry over period and passive inhalation, important factors for detection and diagnosis.
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Absorption and metabolism of tetrahydrocannabinol (THC) vary as a function of route of administration. Pulmonary assimilation of in-haled THC causes a maximum plasma concentration within minutes, while psychotropic effects start within seconds to a few minutes, reach a maxi-mum after 15 to 30 minutes, and taper off within 2 to 3 hours. Following oral ingestion, psychotropic effects set in with a delay of 30 to 90 minutes, reach their maximum after 2 to 3 hours, and last for about 4 to 12 hours, de-pending on dose and specific effect. The initial volume of distribution of THC is small for a lipophilic drug, equivalent to the plasma volume of about 2.5-3 L, reflecting high protein binding of 95-99%. The steady state volume of distribution has been esti-mated to be about 100 times larger, in the range of about 3.5 L per kg of body weight. The lipophility of THC with high binding to tissue and in par-ticular to fat, the major long-term storage site, causes a change of distribu-tion pattern over time. Only about 1% of THC administered IV is found in the brain at the time of peak psychoactivity. THC crosses the placenta and small amounts penetrate into the breast milk. Metabolism of THC occurs mainly in the liver by microsomal hydroxylation and oxidation catalyzed by enzymes of the cytochrome P-450 complex. In man, the C-11 carbon is the major site attacked. Hydroxylation results in 11-hydroxy-THC (11-OH-THC) and further oxi-dation to 11-nor-9-carboxy-THC (THC-COOH), which may be glucuronated to THC-COOH beta-glucuronide. Pharmacologically, 11-OH-THC shows a similar profile as THC while THC-COOH is devoid of psychotropic ef-fects. With oral administration higher amounts of 11-OH-THC are formed than with inhalation, reaching similar plasma levels as its parent drug, and contributing significantly to the overall effects of THC. Franjo Grotenhermen, MD, is affiliated with nova-Institut, Metabolic interaction between THC and the non-psychotropic canna-bidiol (CBD) is based on inhibition of the cytochrome P-450-3A enzyme by CBD. Repeated administration of all cannabinoids causes induction of some cytochrome P-450 isoenzymes which may result in interactions with other medical and non-medical drugs that are using the same enzymes for metabolism. [Article copies available for a fee from The Haworth Document De-livery Service: 1-800-HAWORTH.
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A polyketide synthase (PKS) was suggested to catalyze the first step of cannabinoid biosynthesis, leading to olivetolic acid. An activity of a PKS was detected in the protein extract of Cannabis sativa flowering top. The enzyme converts one molecule of n-hexanoyl-CoA and three molecules of malonyl-CoA to olivetol. The product was identified by its UV-spectrum, mass spectrometry analysis and comparison with reference compound. The activity of the enzyme was also found in the upper leaves, but the activity occurring there is lesser than in the one occurring in the flowers. The activity of chalcone synthase (CHS), another PKS enzyme, was also found in the protein extract.
Recent studies suggest an important role for the skeletal endocannabinoid system in the regulation of bone mass in both physiological and pathological conditions. Both major endocannabinoids (anandamid and 2-arachidonoylglycerol), endocannabinoid receptors - CB1-receptor (CB1R) a CB2-receptor (CB2R) and the endocannabinoid metabolizing enzymes are present or expressed in osteoblasts and osteoclasts. Previous studies identified multiple risk and protective variants of CNR2 gene dealing with the relationship to bone density and/or osteoporosis. Selective CB1R/ CB2R-inverse agonists/antagonists and CB2R-inverse agonists/antagonists are candidates for prevention of bone mass loss and combined antiresorptive and anabolic therapy for osteoporosis.Key words: cannabinoid receptors - endocannabinoids - marijuana - osteoporosis.
A genetic factor that blocks the cannabinoid biosynthesis in Cannabis sativa has been investigated. Crosses between cannabinoid-free material and high content, pharmaceutical clones were performed. F1s were uniform and had cannabinoid contents much lower than the mean parental value. Inbred F2 progenies segregated into discrete groups: a cannabinoid-free chemotype, a chemotype with relatively low cannabinoid content and one with relatively high content, in a monogenic 1:2:1 ratio. In our model the cannabinoid knockout factor is indicated as a recessive allele o, situated at locus O, which segregates independently from previously presented chemotype loci. The genotype o/o underlies the cannabinoid-free chemotype, O/o is expressed as an intermediate, low content chemotype, and O/O is the genotype of the high content chemotype. The data suggests that locus O governs a reaction in the pathway towards the phenolic cannabinoid precursors. The composition of terpenoids and various other compound classes of cannabinoid-free segregants remains unaffected. Backcrossing produced cannabinoid-free homologues of pharmaceutical production clones with potential applications in pharmacological research. A new variant of the previously presented allele ‘B 0’, that almost completely obstructs the conversion of CBG into CBD, was also selected from the source population of the cannabinoid knockout factor.
Arab scientists were several centuries ahead of our current knowledge of the curative power of hemp (Cannabis sativaL., Cannabaceae). Modern Western scientific literature ignores their contribution on the subject. We review in this paper the therapeutic uses of the plant in Arabic medicine from the 8th to the 18th century. Arab physicians knew and used its diuretic, anti-emetic, anti-epileptic, anti-inflammatory, painkilling and antipyretic properties, among others.
This paper aims to clarify the genetic mechanism that is responsible for the accumulation of cannabigerol (CBG) in certain phenotypes of Cannabis sativa L. CBG is the direct precursor of the cannabinoids CBD, THC and CBC. Plants strongly predominant in CBG have been found in different fibre hemp accessions. Inbred offspring derived from one such individual were crossed with true breeding THC predominant- and CBD predominant plants, respectively. The segregations in the cross progenies indicate that CBG accumulation is due to the homozygous presence of a minimally functional allele, tentatively called B0, at the single locus B that normally controls the conversion of CBG into THC (allele BT) and/or CBD (allele BD). The fact that CBG accumulating plants have so far been found in European fibre hemp populations that are generally composed of BD/BD plants, and the observation that the here investigated B0 allele possesses a residual ability to convert small amounts of CBG into CBD, make it plausible that this B0 is a mutation of normally functional BD. Therefore, B0 is considered as a member of the BD allelic series encoding a CBD synthase isoform with greatly weakened substrate affinity and/or catalytic capacity.