ArticlePDF Available

History of medical cannabis

Authors:

Abstract and Figures

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.
Content may be subject to copyright.
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.
E-mail: jfriedberg@medreleaf.com
Abstract
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
plant.
Keywords: Cannabis, history of cannabis, medical cannabis,
cannabinoid
Introduction
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.
388
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
389
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.
390
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
391
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.
392
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
consumption
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
anxiety.
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
smoking.
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
393
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
by-products.
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).
Conclusion
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
methodology.
Conflict of interest
The authors are all employees of MedReleaf, an
authorized grower and distributor of medical cannabis
in Canada.
Acknowledgments
We thank Dean Pelkonen for assistance with graphic
design for Figure 1.
References
[1] Hui-Lin L. An archaeological and historical account of
cannabis in China. Econ Bot 1974;28:437-48.
[2] Touw M. The religious and medicinal uses of cannabis
in China India and Tibet. J Psychoactive Drugs 1981;
13:23-34.
[3] Zuardi AW. History of cannabis as a medicine: a
review. Rev Bras Psiquiatr 2006;28:153-7.
[4] Mack A, Joy J. Marijuana as medicine? The science
beyond the controversy. Washington: National
Academy Press, 2001.
[5] Mikuriya TH. Marijuana in medicine: past, present and
future. Calif Med 1969;110:34-40.
[6] 6. Mahdizadeh S, Ghadiri MK, Gorji A. Avicenna's
canon of medicine: a review of analgesics and anti-
inflammatory substances. Avicenna J Phytomed 2015;
5:182-202.
[7] Lozano I. The therapeutic use of cannabis sativa (L.) in
Arabic medicine. J Cannabis Ther 2001;1:63-70.
[8] Whalley B. Cannabis and epilepsy from recreational
abuse to therapeutic use. University of Reading 2007.
URL: http://www.medicinalgenomics.com/wp-content/
uploads/2013/11/Cannabis_Epilepsy_ben-whalley.pdf.
[9] McMeens RR. Report of the Ohio State Medical
Committee on Cannabis Indica. Transactions of the
Fifteenth Annual Meeting of the Ohio State Medical
Society of Ohio White Sulphur Springs 1860. URL:
http://www.onlinepot.org/medical/Dr_Tods_PDFs/s3_1.
pdf
[10] Sajous CE, Sajous LT. Analytic cyclopedia of practical
medicine. Philadelphia: Davis, 1918.
[11] Lee MA. The discovery of the endocannabinoid system.
The Prop 215 Era 2012. URL: http://www.beyondthc
.com/wp-content/uploads/2012/07/eCBSystemLee.pdf.
[12] Munro S, Thomas KL, Abu-Shaar M. Molecular
characterization of a peripheral receptor for
cannabinoids. Nature 1993;365:615.
Andrew Hand, Alexia Blake, Paul Kerrigan et al.
394
[13] De Meijer EPM, Bagatta M, Carboni A, Crucitti P,
Moliterni VMC, Ranallo P, et al. The inheritance of
chemical phenotype in Cannabis Sativa L. Genetics
2003;163:335-46.
[14] De Meijer EPM, Hammon KM. The inheritance of
chemical phenotype in Cannabis sativa L. (II):
Cannabigerol predominant plants. Euphytica 2005;145:
189-98.
[15] Fellermeier M, Eisenreich W, Bacher A, Zenk MH.
Biosynthesis of cannabinoids: incorporation
experiments with 13C-labeled glucoses. FEBS J 2001;
268:1596-604.
[16] Rahajo TJ, Chang WT, Choi YH, Peltenburg-Looman
AMG, Verpoorte R. Olivetol as product of a polyketide
synthase in Cannabis sativa L. Plant Sci 2004;166:381-
5.
[17] De Meijer EPM, Hammond KM, Sutton A. The
inheritance of chemical phenotype in Cannabis sativa L.
(IV): cannabinoid-free plants. Euphytica 2009;168:95-
112.
[18] De Meijer EPM. The chemical phenotypes
(chemotypes) of cannabis. In: Pertwee RG, ed.
Handbook of cannabis. Oxford: Oxford University
Press, 2011:89-110.
[19] Fellermeier M, Zenk MH. Prenylation of olivetolate by
a hemp transferase yields cannabigerolic acid, the
precursor of tetrahydrocannabinol. FEBS Lett 1998;
427:283-5.
[20] Grotenhermen, Franjo. Pharmacokinetics and pharmaco
-dynamics of cannabinoids. Anesthesiology. 1997;
86(4):2433.
[21] Huestis MA. Human cannabinoid pharmacokinetics.
Chem Biodivers 2007;4(8):1770804.
[22] Abramovici H. Information for health care
professionals: cannabis (marihuana, marijuana) and the
cannabinoids. Health Canada 2013. URL: http://www.
hc-sc.gc.ca/dhp-mps/alt_formats/pdf/marihuana/med/
infoprof-eng.pdf.
[23] Sharma P, Murthy P, Bharath MMS. Chemistry,
metabolism, and toxicology of cannabis: Clinical
implications. Iran J Psychiatry 2012;7(4):14956.
[24] Gieringer DH. Cannabis “vaporization”: a promising
strategy for smoke harm reduction. J Cannabis Ther
2001;14(9):15370.
[25] College of Family Physicians of Canada. Authorizing
dried cannabis for chronic pain or anxiety: preliminary
guidance from the College of Family Physicians of
Canada. Mississauga, ON: College of Family
Physicians of Canada, 2014.
[26] GW Pharmaceuticals. Product Monograph - Sativex.
GW Pharmaceuticals 2015. URL: http://www.gwpharm
.com/sativex.aspx.
[27] Hazekamp A, Bastola K, Rashidi H, Bender J,
Verpoorte R. Cannabis tea revisited: a systematic
evaluation of the cannabinoid composition of cannabis
tea. J Ethnopharmacol 2007;113(1):85-90.
[28] Ben Amar M. Cannabinoids in medicine: a review of
their therapeutic potential. J Ethnopharmacol 2006;
105:112.
[29] Green K, Kearse E, McIntyre O. Interaction between
Delta-9-tetrahydrocannabinol and indomethacin.
Ophthalmic Res 2001;33(4):21720.
[30] Brenneisen R, Elsohly M. The effect of orally and
rectally administered 9-tetrahydrocannabinol on
spasticity: a pilot study with 2 patients. Int J Clin
Pharmacol Ther 2016;34(10):44652.
Submitted: August 01, 2016. Revised: August 25,
2016.Accepted: September 03, 2016.
... 15 Historically, cannabis medical applications appear to possess been realized by most cultures. 16 This utilization of cannabis continued in the West till the mid-1880s and continues today in parts of Asia. 13 Humans have utilized Cannabis : Joints of Mental Illness C Review Article cannabis products in various forms throughout recorded history. ...
... 12 Cannabis' therapeutic uses were first introduced to Western medicine in 1839. 16 Although cannabis features a long history of therapeutic use, in both traditional and Western medicine, it fell into disuse almost a century ago, when it had been superseded by more stable, reliable and effective new synthetic medications. 15 Over the past few thousand years many different cultures have been exposed to cannabis and often noticed the medicinal application of cannabis. ...
... 15 Over the past few thousand years many different cultures have been exposed to cannabis and often noticed the medicinal application of cannabis. 16 The utility and undertaking of medicinal cannabis pursued to evolve, as manifested by the developing number of states now permitting use for certain medical indications. 14 ...
Article
Full-text available
With the increasing push to legalise cannabis in western nations there is an estimation that the potential impact of this policy change on vulnerable population such as those with mental illness, including schizophrenia, mood and anxiety disorders. Cannabis is the most likely used illicit drug worldwide. Cannabis sativa is an important herbaceous species originating from central Asia which has been used in folk medicine. Despite the widespread use of cannabis among young people little research attention has been given to the development of pscyhometrically sound measures specific to cannabis related problems. The laws governing cannabis are evolving worldwide are associated with changing pattern of use. Patients with a serious mental illness often use cannabis at higher rates than the general population. Cannabis may induce or exaberate a number of mental health problems. The main psychoactive drug in cannabis is ?9 tetrahydrocannabinol (THC). Cannabidiol, a non-toxicating cannabinoid found in some forms of cannabis, may offset some of these acute effects. Chronic use of cannabis is associated with psychiatric, respiratory, cardiovascular and bone effects. It also has oncogenic, teratogenic and mutagenic effects, all of which depend upon dose and duration of use. The present article mainly reviews about the association between cannabis and mental health.
... The nonfunctional allele B 0 does not allow for the conversion of the precursor CBGA into THCA or CBDA, and is sometimes referred to as Type IV chemovar, which is CBGApredominant. An independent gene at locus C codes for CBCA synthase that produces CBCA from CBGA (Hand et al., 2016). Studies showed that type I chemovar dominates the markets, but often it is not as beneficial as the other chemovars in achieving the desired symptom relief (Lewis et al., 2018;Aviram et al., 2020a;Aviram et al., 2021b). ...
Article
Full-text available
Medical Cannabis and its major cannabinoids (−)-trans-Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are gaining momentum for various medical purposes as their therapeutic qualities are becoming better established. However, studies regarding their efficacy are oftentimes inconclusive. This is chiefly because Cannabis is a versatile plant rather than a single drug and its effects do not depend only on the amount of THC and CBD. Hundreds of Cannabis cultivars and hybrids exist worldwide, each with a unique and distinct chemical profile. Most studies focus on THC and CBD, but these are just two of over 140 phytocannabinoids found in the plant in addition to a milieu of terpenoids, flavonoids and other compounds with potential therapeutic activities. Different plants contain a very different array of these metabolites in varying relative ratios, and it is the interplay between these molecules from the plant and the endocannabinoid system in the body that determines the ultimate therapeutic response and associated adverse effects. Here, we discuss how phytocannabinoid profiles differ between plants depending on the chemovar types, review the major factors that affect secondary metabolite accumulation in the plant including the genotype, growth conditions, processing, storage and the delivery route; and highlight how these factors make Cannabis treatment highly complex.
... The utilization of cannabis for medicinal purposes is well-documented since ancient times (Zuardi, 2006;Russo, 2014) but its breakthrough into the modern pharmacopoeia occurred only during the 19th century, when western physicians recognized its therapeutic potential (Mikuriya, 1969;Small, 2017a). However, due to advances in medicinal technology and alternative medication during the first half of the 20th century, the popularity of cannabis dwindled (Mikuriya, 1969;Hand et al., 2016;Small, 2017a) but concurrently, its recreational consumption became more prevalent . Over this period, international prohibition of cannabis and cannabis trafficking was initiated, labeling the cannabis plant and its products as narcotics (Erkelens and Hazekamp, 2014;Pain, 2015;Pisanti and Bifulco, 2017). ...
Article
Full-text available
In recent decades with the reacknowledgment of the medicinal properties of Cannabis sativa L. (cannabis) plants, there is an increased demand for high performing cultivars that can deliver quality products for various applications. However, scientific knowledge that can facilitate the generation of advanced cannabis cultivars is scarce. In order to improve cannabis breeding and optimize cultivation techniques, the current study aimed to examine the morphological attributes of cannabis inflorescences using novel image analysis practices. The investigated plant population comprises 478 plants ascribed to 119 genotypes of high−THC or blended THC−CBD ratio that was cultivated under a controlled environment facility. Following harvest, all plants were manually processed and an image of the trimmed and refined inflorescences extracted from each plant was captured. Image analysis was then performed using in-house custom-made software which extracted 8 morphological features (such as size, shape and perimeter) for each of the 127,000 extracted inflorescences. Our findings suggest that environmental factors play an important role in the determination of inflorescences’ morphology. Therefore, further studies that focus on genotype X environment interactions are required in order to generate inflorescences with desired characteristics. An examination of the intra-plant inflorescences weight distribution revealed that processing 75% of the plant’s largest inflorescences will gain 90% of its overall yield weight. Therefore, for the optimization of post-harvest tasks, it is suggested to evaluate if the benefits from extracting and processing the plant’s smaller inflorescences outweigh its operational costs. To advance selection efficacy for breeding purposes, a prediction equation for forecasting the plant’s production biomass through width measurements of specific inflorescences, formed under the current experimental methodology, was generated. Thus, it is anticipated that findings from the current study will contribute to the field of medicinal cannabis by improving targeted breeding programs, advancing crop productivity and enhancing the efficacy of post-harvest procedures.
... Historically, the usage of marijuana could be found during 6000 BC when the seeds of Cannabis were used as food material in China, while in 4000 BC, Chinese designed textile material from hemp (Monthony et al., 2021). The first record found for the association of Cannabis with the field of medicine was in 2727 BC in China (Hand et al., 2016). In Traditional Chinese Medicine (TCM) it was usually used to treat constipation, malaria, rheumatic pains as well as pain during childbirth (Anand et al., 2019). ...
Article
Full-text available
Cannabis sativa, widely known as ‘Marijuana’ poses a dilemma for being a blend of both good and bad medicinal effects. The historical use of Cannabis for both medicinal and recreational purposes suggests it to be a friendly plant. However, whether the misuse of Cannabis and the cannabinoids derived from it can hamper normal body physiology is a focus of ongoing research. On the one hand, there is enough evidence to suggest that misuse of marijuana can cause deleterious effects on various organs like the lungs, immune system, cardiovascular system, etc. and also influence fertility and cause teratogenic effects. However, on the other hand, marijuana has been found to offer a magical cure for anorexia, chronic pain, muscle spasticity, nausea, and disturbed sleep. Indeed, most recently, the United Nations has given its verdict in favour of Cannabis declaring it as a non-dangerous narcotic. This review provides insights into the various health effects of Cannabis and its specialized metabolites and indicates how wise steps can be taken to promote good use and prevent misuse of the metabolites derived from this plant.
... Today, more healthcare patients are not only requesting but also advocating for the use of medical cannabis (Crocq 2020). This presents healthcare professionals with many challenges, not least because they may not feel they have adequate knowledge to prescribe effectively (Gardiner et al. 2019), but also because there is still significant stigma around the legalised (and recreational) use of cannabis (Hand et al. 2016). ...
Article
Full-text available
Aim This scoping review aims to examine what determinants of behaviours, beyond knowledge, are used as per the theoretical domains framework (TDF) in relation to the research design and findings in the selected studies related to healthcare professionals and medical cannabis (MC). Subject and methods The use of MC has been legalized in various countries and states over the last 10 years. This rapid change of a stigmatised ‘drug’ to a modern ‘medicine’ and contradictory laws have undermined the consistent implementation of MC in healthcare. Data synthesis of the evidence base in the selected studies used the TDF to examine the enablers and barriers influencing implementation of medical cannabis. The TDF was developed to support the implementation of change with healthcare professionals (Cane et al. Implement Sci 7:37, 2012). The TDF is comprised of 14 theoretical domains taken from 33 psychological change theories and 128 constructs. Results Using the preferred reporting items for systematic reviews, 34 publications were identified that met the inclusion criteria. The domains most frequently identified as influencing behaviours were ‘knowledge’ and ‘beliefs about consequences’. Through a focus on knowledge in the studies, findings showed that improving education is required. However, multiple factors influencing behaviours of professional healthcare groups must also be considered to support consistent implementation of MC. Conclusion Examining broader determinants of behaviour, beyond knowledge is required, such as environmental influences and the norms of healthcare professionals for consistent MC implementation. Use of the TDF to ensure multiple domains are included in future research and educative programs would support this aim.
... Despite the lack of scientific means to profile and quantify the plant's medicinal agents (cannabinoids), cannabis breeding goals continued to be progressively implemented, with breeder's considerations founded mainly on perceived and sensorial parameter estimations such as inebriant potency, yield production and preference for certain aromatic blends [30,31]. Using this approach, cannabis breeders had a dramatic effect on shaping the physiological and chemical profile of recreational cultivars, as evidenced by the significant growth of THC content in cannabis plants over the last few decades [32][33][34][35] and the continued popularity of indoor cultivation methods for recreational consumption [5,36]. ...
Article
Full-text available
Background For millennia, drug-type cannabis strains were extensively used for various medicinal, ritual, and inebriant applications. However, cannabis prohibition during the last century led to cultivation and breeding activities being conducted under clandestine conditions, while scientific development of the crop ceased. Recently, the potential of medicinal cannabis has been reacknowledged and the now expanding industry requires optimal and scientifically characterized varieties. However, scientific knowledge that can propel this advancement is sorely lacking. To address this issue, the current study aims to provide a better understanding of key physiological and phenological traits that can facilitate the breeding of advanced cultivars. Results A diverse population of 121 genotypes of high-THC or balanced THC-CBD ratio was cultivated under a controlled environment facility and 13 plant parameters were measured. No physiological association across genotypes attributed to the same vernacular classification was observed. Floral bud dry weight was found to be positively associated with plant height and stem diameter but not with days to maturation. Furthermore, the heritability of both plant height and days to maturation was relatively high, but for plant height it decreased during the vegetative growth phase. To advance breeding efficacy, a prediction equation for forecasting floral bud dry weight was generated, driven by parameters that can be detected during the vegetative growth phase solely. Conclusions Our findings suggest that selection for taller and fast-growing genotypes is likely to lead to an increase in floral bud productivity. It was also found that the final plant height and stem diameter are determined by 5 independent factors that can be used to maximize productivity through cultivation adjustments. The proposed prediction equation can facilitate the selection of prolific genotypes without the completion of a full cultivation cycle. Future studies that will associate genome-wide variation with plants morphological traits and cannabinoid profile will enable precise and accelerated breeding through genomic selection approaches.
... Hingga akhirnya Shaughnessy mendapatkan bahwa ekstrak ganja memiliki sifat analgesik dan dapat bertindak sebagai obat penenang. Shaughnessy menggunakan ekstrak ganja untuk menenangkan kejang otot pada pasiennya yang terkena tetanus dan rabies (Hand, Blake, Kerrigan, Samuel, & Friedberg, 2017). ...
Article
Full-text available
Kebijakan terkait penggunaan ganja untuk pengobatan, meredakan, atau mengurangi gejala penyakit masih menjadi perdebatan di banyak negara, termasuk Indonesia. Artikel ini bertujuan untuk mengetahui narasi yang dibangun oleh pemerintah terkait dengan kebijakan ganja medis di Indonesia, menganalisis hambatan dari narasi kebijakan ganja medis, dan merumuskan alternatif strategi yang dapat dilakukan oleh pemerintah untuk menguatkan kebijakan ganja medis di Indonesia. Penelitian ini menggunakan Analisis Naratif Kebijakan (Narrative Policy Analysis/NPA) untuk menganalisis disparitas naratif dari kebijakan pemerintah tentang ganja medis dan menentukan bentuk naratifnya seperti tingkat analisis, setting, karakter, plot, dan moral dari narasi kebijakan. Data dikumpulkan dari dokumen online terpercaya seperti data publik, pemberitaan media, atau transkrip pidato yang relevan dengan masalah penelitian dari Januari 2019 s/d Desember 2020. Kesimpulan dari penelitian ini adalah 1) Pemerintah tetap melarang adanya pemanfaatan ganja untuk kepentingan medis dengan tujuan untuk melindungi seluruh masyarakat Indonesia dari masalah baru yang berisiko muncul; 2) Hambatan dari narasi kebijakan yang dibangun oleh pemerintah yaitu adanya perbedaan belief system terhadap tanaman ganja serta belum adanya kajian empiris tentang pemanfaatan ganja untuk kepentingan medis di Indonesia; 3) Rekomendasi strategi untuk memperkuat narasi kebijakan pemerintah terkait dengan pemanfaatan ganja medis di antaranya membuka ruang diskusi dengan kelompok masyarakat yang kontra narasi, melakukan uji empiris dengan melibatkan akademisi untuk memperkuat argumen dan narasi kebijakan pemerintah, serta mensosialisasikan kebijakan ganja medis ke berbagai stakeholder terkait.
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.
Article
Full-text available
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.
Article
Full-text available
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.
Article
Full-text available
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.
Article
Full-text available
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.
Article
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.
Article
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.
Article
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.
Article
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.