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Plants as medical tools


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Cannabis has been used for centuries for its fiber, food and as medicine. This review highlights the history of cannabis, its uses as a medical tool and the active ingredients found in this versatile plant. Many pain management pharmaceuticals widely accepted and used today, such as opioids and aspirin, contain plant derived extracts. The evolving cannabis story is paralleled to the history of current plant extracts used as pharmaceuticals. Usage, side effects and mortality rates of current pain medications are compared to cannabis and reveal great potential for cannabis as a safe and effective alternative in pain management.
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J Pain Manage 2016;9(4):493-504 ISSN: 1939-5914
© Nova Science Publishers, Inc.
Plants as medical tools
Haleh Hashemi, PhD, Andrew Hand, MSc,
Angelique Florentinus-Mefailoski, MSc,
Paul Kerrigan, BSc, Phineas Samuel, BSc,
and Jeremy Friedberg*, PhD
MedReleaf Corp, Markham Industrial Park, Markham,
Ontario, Canada
* Correspondence: Jeremy Friedberg, PhD, MedReleaf Corp,
Markham Industrial Park, POBox 3040, Markham,
Ontario, L3R 6C4, Canada.
Cannabis has been used for centuries for its fiber, food and
medicinal properties. This review highlights the history of
cannabis, its uses as a medical tool and the active
ingredients found in this versatile plant. Many pain
management pharmaceuticals widely accepted and used
today, such as opioids and aspirin, contain plant-derived
extracts. The evolving cannabis story is paralleled to the
history of current plant extracts used as pharmaceuticals.
Usage, side effects and mortality rates of current pain
medications are compared to cannabis and reveal great
potential for cannabis as a safe and effective alternative in
pain management.
Keywords: Cannabinoids, opioids, aspirin, plant
metabolites, salicylates
One of the primary sources of difficulty for doctors
exploring the use of cannabis as a medical tool stems
from the idea that they are prescribing a “plant” and
not an individual compound. Although this plant
contains a predominant family of active ingredients,
the cannabinoids, it is still a mixture of all the
components in the plant tissue or plant extract. To
compound this apprehension, this particular plant has
had a long and sorted cultural and social-political
history in western civilization that is slowly, yet with
difficulty, on the path to a resolution. However, in the
annals of western medicine, the story of this plant’s
journey is not new or unique, and there is much to
learn from the journey other plants have taken from
obscurity to common use. The purpose of this chapter
is to chronicle two historical plants journeys in
modern medicine and what comparisons and
differences can be drawn to the story of cannabis.
Haleh Hashemi, Andrew Hand, Angelique Florentinus-Mefailoski et al.
Current plant extracts used
as pharmaceuticals and used in
pharmaceutical production
Secondary metabolites, also referred to as
natural products (NP), are organic compounds
that are not directly involved in the natural
growth, development, or reproduction of an
organism, and they typically result from the
activities of biosynthetic pathways. The vast
biodiversity of earth’s flora and fauna have been a
tremendous and variable source of useful and
medically relevant compounds and in many cases
compounds that cannot be synthesized in vitro (1).
The mechanism by which an organism synthesizes
secondary metabolites is often found to be unique to
each organism or it is an expression of the
individuality of a species. They are produced for
different reasons from a result of the organism’s
adapting to its external environment, to acting as a
possible defense mechanism against predators, or
simply in assisting in the survival of the organism
(2, 3).
Medicinal plants
Plants and their extracts have been used as
medicinal compounds for thousands of years.
Their unique properties are the result of their
evolution. This has resulted in the production
of unique and structurally diverse secondary
metabolites. These unique pharmacological properties
and their application by different cultures and
regions made them great candidates for new drug
discovery research (4). According to the World
Health Organization (WHO), 80% of people still
rely on traditional plant-based medicine for
primary health care and 80% of plant-derived drugs
were related to their historical applications (5).
In recent years, advancements in molecular
biology in association with traditional medicine
has promoted further investigations and yielded
new drug candidates for the pharmaceutical market
History of plant extracts used
as pharmaceuticals
The oldest records for the usage of medicinal plants
dates back to 2400 BCE on clay tablets
(Mesopotamia). The Greek physician, Dioscorides
(100 AD), recorded the collection, storage and uses of
medicinal herbs, while the Greek philosopher and
natural scientist, Theophrastus (~300 BCE), collected
similar information in a series of books available to
this day. The monasteries in England, Ireland, France
and Germany preserved this Western knowledge
while scholars in the Middle East preserved the
Greco-Roman knowledge and expanded the uses of
their own resources, together with Chinese and Indian
herbs unfamiliar to the Greco-Roman world during
the Dark and Middle Ages. In the Middle East,
Avicenna, a Persian pharmacist, physician and
philosopher contributed much to the sciences of
pharmacy and medicine through works such as the
Canon Medicine book, which directly aided people in
the Middle East to establish privately owned
pharmacies as early as the 8th century (7).
Current status of natural products (NP)
including medicinal plant extracts
In 2014, the global market for plant-derived drugs
was valued at $23.2 billion. It is expected that this
market will reach $35.4 billion by 2020, representing
a significant share of the global pharmaceutical
market (8). This increase is a result of (1) the interest
expressed by pharmaceutical companies in new and
lower price drugs especially for psychosomatic,
metabolic, and minor disorders and (2) the tendency
of people to use modern traditional medicine.
Traditional medicine has been widely used in
different types of medication, dietary products and
nutritional supplements since ancient times. Many of
them currently are registered pharmaceuticals through
regulatory offices such as the Food and Drug Agency
(FDA) once they surpass clinical trials and
demonstrate efficacy and safety (6, 8, 9). To date,
60,000 species of plants have been screened to yield
the 135 known drugs. Considering the number of
unscreened plant species, (approximately >300,000),
there is a potential to find 540653 new drug
candidates in the years to come (10).
Plants as medical tools
Table 1. Plant-derived natural products approved for therapeutic use in the last thirty years (1984 2014)
Generic name
Scientific name
Trade name
(year of introduction)
(mechanism of action)
Artemisia annua
Artemisinin (1987)
Malaria Treatment
(radical formation)
Artemisia glabella
Arglabin (1999)
Cancer Chemotherapy
Casicum Annum L.,
Qutenza (2010)
Post therapeutic neuralgia
Colichicum SPP
Colcrys (2009)
Gout (tubulin binding)
Cannabis Sativa L,
Sativex (2005)
Chronic neuropathic pain
(CB1 and CB 2Receptor
Galanthus Cancasicus
Razadyne (2001)
Dementia associated with
Alzheimer’s disease
(ligand of human Nicotinic
acetyl choline receptors
Euphorbia peplus L
Picato (2012)
Actinic keratosis
(inducer of cell death)
Table 1. (Continued on next page)
Haleh Hashemi, Andrew Hand, Angelique Florentinus-Mefailoski et al.
Generic name
Scientific name
Trade name
(year of introduction)
(mechanism of action)
Larrea tridentata
Actinex (1992)
Cancer chemotherapy
(lipoxygenase inhibitor)
Omacetaxine mepesuccinate
Synribo (2012)
(protein translation inhibitor)
Taxus brevifolia
Taxol (1993),
Abraxanec (2005),
Nanoxelc (2007)
Cancer chemotherapy
(mitotic inhibitor)
Solanum spp
Curadermd (1989)
Cancer chemotherapy
(apoptosis triggering)
Resources: (Atanas et al, 2015, Butler, 2005, 2008; Butler et al, 2014; Fürst and Zündorf, 2014; Newman and Cragg, 2012),, and
Plant extracts widely used
in pharmaceutical production
The plant extracts utilized as pharmaceuticals vary
greatly from country to country. Due to the rapid
development in the understanding of plant chemistry,
and the advancing ability to isolate and purify natural
compounds, there are now a diversity of plant extracts
on the market, either synthetic or directly derived
from plants. Morphine, purified from opium by
Serturner (1806), was the first alkaloid with high
biological efficacy. This event was subsequently
followed by the isolation of many other alkaloids
including strychinine from Strychnos mux-vomica,
and quinine from Cinchona spp. The most widely
used breast cancer drug is paclitaxel (Taxol®), which
was isolated from the bark of Taxus brevifolia
(Pacific Yew). It is now produced synthetically and is
one of the main tools to treat breast cancer.
Cannabis (Cannabis sativa) was traditionally
used to alleviate severe headaches, as well as to treat
degenerative bone and joint diseases, ophthalmitis,
general edema, infectious wounds, gout, and pelvic
pain. Sativex, a titrated extract containing delta-9-
tetrahydrocannabinol (psychoactive) and cannabidiol
(anti-inflammatory), has been approved in a few
countries (e.g., Canada, The United Kingdom,
Germany and New Zealand) since 2005. This
botanical prescription drug is an oromucosal spray
containing cannabinoid medicine for the treatment of
spasticity due to multiple sclerosis and neuropathic
pain of various origins. Marinol (dronabinol) and
Cesamet (nabilone) are available in North-America
for the treatment of vomiting and nausea associated
with the use of chemotherapy to treat cancer (11).
Several FDA-approved botanicals like Veregen
(Tea catechins) for the treatment of external genital
and perianal warts (12) and Fulyzaq (extract from the
red sap of Croton lechleri) for the treatment of
Plants as medical tools
diarrhea in HIV patients are currently available in the
global market. In 2012, the Dutch Medicines
Evaluation Board approved a dry extract of Dioscorea
nipponica, a traditional Chinese botanical, to relieve
headache, muscle pain and cramps (12). This was the
first time a Traditional Chinese Medicine (TCM)
product was introduced into a European Union
country. The list of plant species, which are processed
in a relatively large scale, and their respective
bioactive agents have been shown in table 1. A list of
plant-derived products that have been used in clinical
trials is shown in table 2.
Table 2. Plant derived natural products in clinical trials
Generic name and chemical
Number of recruiting clinical trials: indications (potential
mechanism of action)
1 trial: Solid tumors (E2F1 pathway activator)
Curcuma longa L
26 trials: Cognitive impairment, different types of cancer,
familialadenomatous polyposis, schizophrenia, cognition,
psychosis, prostate cancer, radiation therapy, acute kidney
injury, abdominalaortic aneurysm, inflammation, vascular aging,
bipolar disorder, irritable bowel syndrome, neuropathic pain,
depression, somaticneuropathy, autonomic dysfunction,
Alzheimer's disease, plaquepsoriasis, fibromyalgia,
cardiovascular disease (NF-κB inhibition)
Camellia sinensis
14 trials: Epstein-Barr virus reactivation in remission patients
with nasopharyngeal carcinoma, multiple system atrophy,
Alzheimer's disease, cardiac amyloid light-chain amyloidosis,
Duchenne muscular dystrophy, cystic fibrosis, diabetic
nephropathy, hypertension, fragile X syndrome, different types
of cancer, obesity, influenza infection (cell growth arrest and
apoptosis induction
Genista tinctoria
5 trials: Colon cancer, rectal cancer, colorectal cancer,
Alzheimer's disease, non-small cell lung cancer,
adenocarcinoma, osteopenia, osteoporosis (protein-tyrosine
kinase inhibitor, antioxidant)
hirsutum L.
2 trials: B-cell chronic lymphocytic leukemia, refractory chronic
lymphocytic leukemia, stage III chronic lymphocytic leukemia,
stage IV chronic lymphocytic leukemia, non-small cell lung
cancer (Bcl-2 inhibitor)
Royle, replaced
1 trial: Glioblastoma, gliosarcoma, anaplastic astrocytoma,
anaplastic oligodendroglioma, anaplastic oligoastrocytoma,
anaplastic ependymoma (tubulin binding/IGF-1R Inhibitor)
Table 2. (Continued on next page)
Haleh Hashemi, Andrew Hand, Angelique Florentinus-Mefailoski et al.
Generic name and chemical
Number of recruiting clinical trialsa: indications (potential
mechanism of action)
Allium cepa L.
9 trials: Chronic obstructive pulmonary disease, Fanconi
anemia, different types of prostate cancer, diabetes mellitus,
obesity diastolic heart failure, hypertensive heart disease, heart
failure with preserved ejection fraction, hypertension, oxidative
stress, Alzheimer's disease, pancreatic ductal adenocarcinoma,
plaque psoriasis (NF-κB inhibition)
Vitis vinifera L
22 trials: Pre-diabetes, vascular system injuries, lipid
metabolism disorders (including non-alcoholic fatty liver
disease), endothelial dysfunction, gestational diabetes,
cardiovascular disease, type 2 diabetes mellitus, inflammation,
insulin resistance, disorders of bone density and structure,
metabolic syndrome, coronary artery disease, obesity, memory
impairment, mild cognitive impairment, diastolic heart failure,
hypertensive heart disease, heart failure with preserved ejection
fraction, hypertension, oxidative stress, polycystic ovary
syndrome, Alzheimer's disease (NF-κB inhibition)
Resources: (Atanas et al, 2015, Butler, 2005, 2008; Butler et al, 2014; Fürst and Zündorf, 2014; Newman and Cragg, 2012),, and
The opioid story
Opiates have had a long-standing role similar to
Cannabis in both management of disease and
recreational use. The Greek word for juice, “opos,
was chosen due to the latex liquid that seeps from cuts
in immature seed capsules. Modern usage of the word
applies to all alkaloid and peptide compounds that can
bind to opioid receptors (15). It is widely accepted
that opium poppies were first cultivated in lower
Mesopotamia, with the Sumerians referring to it as
“hul gil,” which translates to “joy plant” (16). In the
same geographical region, civilizations such as the
Babylonians, Assyrians and Egyptians all have
documented use of the plant for both pain
management and ritualistic purposes (17). The Ebers
Papyrus, an Egyptian medical document from ca.
1500 BCE, also mentions the use of opium-soaked
sponges for the management of pain during surgery
and for the prevention of excessive crying from
children. From there, opium spread through the
Eastern world, with documented evidence of opium
use by Greek culture in the third century BCE and in
both India and China in the eighth century AD (18).
With the introduction of opium came addiction and
abuse, particularly in China during the seventeenth
century after the ban on smoking tobacco led to an
increased rate in the smoking of opium.
Pharmacist Friedrich Sertürner first isolated
morphine from opium poppies in 1806, the name
being derived from Morpheus, the Greek God of
dreams (19). Morphine saw regular use in the
nineteenth century for pain and other ailments such as
respiratory problems and anxiety (20). With the
invention of the hypodermic needle in 1853, use of
morphine for minor surgical procedures, management
of chronic pain and as an anesthesia during operations
increased (16, 20). During the American Civil War,
many soldiers were given morphine for injuries
sustained during battle, and thus many suffered from
opiate addiction after the war ended (21). To help
combat morphine addiction, heroin was synthesized in
1898 as a more effective, less addictive and generally
safer alternative. Saint James Society even provided
free heroin through the mail to morphine addicts in an
attempt to curb their usage. Between 1898 and 1910,
Bayer marketed heroin as an analgesic and cough
suppressant before discovering that the drug did
Plants as medical tools
indeed induce considerable dependence in users and
was very hazardous (22).
All opioids act by interacting with opioid
receptors, which are distributed throughout both the
central and peripheral nervous systems, as well as
some other organs such as the heart, liver and kidney
(23). Multiple opioid receptors classifications exist- μ,
κ, σ, nociception receptor, each with similar but
different tissue location and function (24). Opioid
receptors, located on sensory nerves in the peripheral
nervous system, regulate analgesia and inflammation,
the latter due to cytokines produced during
inflammation inducing the release of endogenous
compounds that interact with opioid receptors. Similar
to the endocannabinoids endogenously produced by
the human body, endo-opioids such as endorphins and
enkephalins interact with the same opioid receptors as
plant-derived opioids (25).
The aspirin story
Humans have benefitted from the use of plant-derived
salicylates for millennia. Recommendations for
treatment are described among the Ebers papyrus in
Egypt (1500-3000 BCE) and also in Greece (500 BC)
by the physicians Hippocrates and Galen (26).
Patients would be treated with a preparation including
the leaves or bark of the willow tree, Salix alba,
which alleviated inflammation, fever, and pain.
To test historical observations, scientific
validation is needed to confirm true relationships. In
1763, the first scientific description of Salix alba as a
treatment for malarial fever in 50 patients was
performed by Reverend Edward Stone (27). At the
end of his account, Stone states his hopes “that it
(Salix alba bark powder) may have a fair and full trial
in all its variety of circumstances and situations, and
that the world may reap the benefits accruing from it”
Advances in organic chemistry in the 1820s
allowed for the isolation of Salicin from willow bark
(28). Salicin was used successfully to treat rheumatic
fever, notably by TJ Maclagan and Sir William Osler,
until the end of the 19th century (29).
In 1838, salicylic acid was derived from Salicin.
Pharmaceutical chemists began to investigate the
useful derivatives of salicylic acid, which reduced
such side effects as gastrointestinal irritation, resulting
in over a dozen such compounds being synthesized
by 1908 (26). In 1897, acetylsalicylic acid was
synthesized in pure form and by 1899 was being sold
worldwide as Aspirin by Bayer. Current worldwide
production of acetylsalicylic acid is estimated to be
40,000 tons per year, and the number of clinical trials
involving the drug is estimated to be 700-1000
annually (30). Certainly, the powdered bark of Salix
alba has had its advantages and many people continue
to reap benefits from its acetylated and pure cousin,
acetylsalicylic acid.
The evolving cannabis story
In the Western world, cannabis was used only as a
fiber source until the mid-1800s. However, once
introduced for its pharmacological benefits, it quickly
played an important role in medicine as early as the
20th century (31). Early in its introduction, cannabis
was included in numerous over-the-counter and
prescription drugs and referenced in many medical
texts (32). However, in the mid-20th century, a major
cultural shift labeled cannabis as an illicit drug, and
its therapeutic applications became deterred as a result
of changes in the law. (33).
As a medication, cannabis had many strengths
and potential applications. One of the main reasons
behind its initial decline was the growing use of
alternative analgesics (33). Initially, the decline in
the medicinal use of cannabis was practical: it was
insoluble, which made it incompatible with
hypodermic needles, and its delayed onset of at least
an hour when consumed posed a challenge compared
to new quick-acting analgesics (32). Another
significant practical dilemma involved the sizable
variation in effects induced both between different
batches of cannabis and from person to person.
Ultimately, physicians found it difficult to work
around these issues and analgesics such as aspirin,
heroin and chloral hydrate, which were easily
administered, fast-acting and consistent, began to
phase out cannabis (33).
Though there where legitimate reasons for
physicians to move towards other analgesics, cannabis
had major advantages that were lost as a result: the
reduced risks of developing physical dependence
Haleh Hashemi, Andrew Hand, Angelique Florentinus-Mefailoski et al.
associated with cannabis, its low toxicity, and its
limited disturbance of vegetative functions (32).
These advantages over other analgesics warrant
efforts to solve the practical obstacles to the medical
uses of cannabis in modern day approaches. The main
issue of inconsistency with cannabis can be addressed
far more effectively in modern day medicine than it
could have been in the past. The main method used to
determine the strength of a dose during the late 1800s
was to administer cannabis to animals and observe the
reaction (33). Today, laboratory analysis can be far
more precise in measurement, using modern chemical
analysis techniques to determine the exact chemical
composition of the plant. By providing this
information to physicians, it is now possible for them
to gauge the dose they are prescribing the patient (34).
Another cause of inconsistency was that cannabis was
most likely obtained from many sources growing
different plants (32). Even if the source was the same,
each plant would have a different potency due to
genetic variation between seeds and, as a result, it was
nearly impossible to acquire a supply of cannabis that
was consistent in composition (35). Today, this issue
can be addressed through the application of clonal
propagation and the production of many daughter
plants using prunings from a single mother plant. The
advantage of this method is that all daughter plants
will be genetically identical, so patients can continue
to have access to consistent and identical medication
In light of these developments and based off
growing evidence of the medical application of
cannabis, the perception of cannabis is once again
changing. We are seeing a general trend towards
cannabis once again becoming a part of Western
medicine as evidenced by its legal status for
medicinal use in Canada (37). Use of Cannabis as a
medicine should be re-evaluated using modern
approaches of science and medicine to determine its
true value as a therapeutic agent.
Comparison of current pain
The use of prescription pain medications such as
opioids, corticosteroids and anticonvulsants has
dramatically increased over the past decades. These
prescription pain medications provide effective pain
management but often come with risk of abuse,
physical dependence, addiction and other serious side
effects and are routinely used in combination with
other medications (38-44) (see table 3).
Opioids, including morphine, codeine and
oxycodone, are the most commonly used prescribed
medications to treat acute or chronic moderate to
severe pain. Opioids are used to control pain in
cancer, neuropathy, fibromyalgia and other
conditions. Patients taking prescription opioids need
to be observed closely to monitor pain management
and the physical reaction to the medication
prescribed. Long-term use brings adverse effects such
as tolerance, risk of overdose, dependence and
addiction and even death. Other side effects
associated with short- or long-time use include brain
damage, heart disease, liver disease, breathing
problems and psychiatric effects (45).
In the United States, 47,000 people died of drug
overdose in 2014 and 61% of deaths associated with
drug overdose involved prescription opioids, of which
oxycodone and hydrocodone were most frequently
prescribed (45-47). Every year, the number of people
who die from drug poisoning increases exponentially.
There is a large demand for an effective and safer
alternative for pain relief.
Cannabis has been used for centuries to treat
pain, neurological disorders, immunity, metabolism,
and mood and behavioural disorders (see table 3)
(48, 49). Side effects of cannabis use are often
mild and reversible with low acute toxicity and
no recorded deaths by the Centers for Disease
Control and Prevention (50). Common side effects
of cannabis use include euphoria and temporary
cognitive and memory impairment. Hypotension
might also be caused, which could pose a
risk for patients with cardiovascular diseases (51).
In recent studies, data was obtained from
patients using medical cannabis and/or prescription
pain medication (PPM) for pain management.
Patients using PPM found medical cannabis to be
more efficient in controlling pain than PPM.
Patients on PPM used medical cannabis to
significantly reduce opioid intake and improve
their quality of life (52). Overall, cannabis offers a
low-risk profile and effective alternative in pain
Table 3. Comparison of current pain medications
Medication Utility Common drugs Target
Side effects Mortality rate
Cannabis Cancer, HIV Cannabis Sativa
Rare Cognitive and memory impairment 0
Neurologi cal disorders Cannabis Indica
Increased heart rate, fluctuation in blood pressure.
Rare: Stroke, heart infarct
Immunity Anxie ty, panic, depressi on, hormonal imbalance
Mood and behaviour
Suppressed immune system, growth disorde rs, apathy,
mood/personali ty changes, hormonal changes
Appetite and metabolism
Opioids Neuropathy Morphine Opioid receptor Yes Addiction, brain damage, ove rdose, death <28,000 (9 per 100,000 persons) in USA in 2014
Pain (dental, injury, surgery) Codeine
Weakened immune systetm, hallucinations, coma,
breathing problems
Cancer Oxycodone
Sedation, anxi ety, hormonal inbal ance, drug interaction,
Fybromyalgia Tramadol
Anxie ty Fentanyl
Cough, serious diarrhea Methadone
Headache, migrane Hydromorphone
Sickle cel l disease
Corticosteroids Cancer Dexamethasone
Steroid hormone
Liver disease , inferti lity, heart attack, high blood
pressure, cancer, depression, psychiatric effe cts, damage
to gonads
Prednisone : 666 of 5626 RA patients in USA over 25
Arthritis Cortisone Insomnia, muscle weakness, suppress immune system
Glaucoma, osteoporosis, hormonal inbalance, drug
interaction, withdrawal
Anti-convulsant Seizures Carbamazepine GABA receptor Yes Dizziness, suicidal thoughts/actions, depression Carbamazepine: 16 per 100,000 cases per year
Neuropathy Ethosuximi de PPAR receptor
Liver problems, kidney dise ase, drug interactions,
fatigue, drowsi ness, nausea, rash, tremor, wei ght gain
Gabapentin: 14 of 725 cases in France 1995-2009
Personality disorders Gabapentin
Heart disease, depression, confusi on, anxiety,
constipation, mania
Mood Pregesterone Hormonal inbalance, drug interaction, withdrawal
Brain disorders (bipol ar, mania,
Haleh Hashemi, Andrew Hand, Angelique Florentinus-Mefailoski et al.
The medical and cultural apprehension surrounding
the use of cannabis in clinical practice is
understandable. Parallels to the stories of other plant
extracts becoming pharmaceuticals, as well as a
consideration of the associated benefits compared to
risks, explains the state of cannabis acceptance today.
Many of these stories have evolved without
controversy, while others have been fraught with
social and cultural challenges as well as significant
health risks. In the case of cannabis, history is
showing us a reasonable and feasible path forward.
The difference in the cannabis story, however, is that
the final clinical utility resides in the plant itself and
not just a single compound. Cannabis will continue to
be a viable and beneficial clinical tool. With ongoing
education and research, there is great potential for
discovering further applications of cannabis in
Conflict of interest
The authors are all employees or consultants of
MedReleaf, an authorized grower and distributor of
medical cannabis in Canada. The authors report no
other conflicts of interest.
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... Furthermore, numerous records, documents, and recollections from various ancient societies contain some of the oldest medicinal remedies known today [3], [4], [7], [9], [40], [105], [161]. The [6], [8], [94], [100], [102], [110], [118], [120], [147], [152], [233], [13], [29], [37], [38], [45], [79], [87], [88]. ...
... Furthermore, although ancient Egyptian medicine has been traced back to 2,900 BCE, one of the most prolific of their ancient medicinal texts is a pharmaceutical treatise called the Ebers Papyrus (1500 BCE) which documents the functions and usage of over 800 different plant medicines [1], [2], [33], [38]- [40], [43], [45], [64], [72], [84], [86], [5], [87], [88], [102], [105], [109], [110], [118], [119], [133], [147], [8], [152], [161], [184], [196], [9], [11]- [13], [21], [29]. ...
... Additionally, the neurotransmitters are what interact with the signal receiver and transducer, which in turn relays the rest of the information the brain is processing [41], [138], [265], [331], [332], [366], [368]- [370]. As stated previously, humans have always sought out the healing properties of botanics to address pathological illnesses, this includes mental illness [2], [9], [190], [63], [64], [67], [84], [100], [124], [144], [147]. Abnormal psychological behaviour was considered to be an actual affliction throughout parts of the world and history, as such people have often sought to try and remedy the symptoms that are associated with MDD and anxiety disorders through the use of medicinal plants [2], [9], [190], [63], [64], [67], [84], [100], [124], [144], [147]. ...
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Mental illness has long been a part of human history; however, not as long as humans have been using plants for medicinal purposes. Medicinal plants are the source of over 50% of our medications today. Several countries integrate traditional systems of medicine (homeopathic medicine) with international systems of medicine. However, the presence of medicinal plants for anxiolytic and anti-depressant medications is sorely lacking. This is despite a 30-year gap between the last new medications for anxiety and depressive disorders and the availability of ketamine in 2019. Several gaps and lack of access to research regarding the potential benefits of using medicinal plants as anxiolytic and antidepressant solutions create even more difficulties for researchers. In addition to this, the cost of development associated with creating new medications within this field of medicine is incredibly resource and time-intensive. Despite this level of stagnation pharmaceutical companies are still hesitant to approach medicinal plants and phytochemicals as potential sources of pharmaceutical interest. A hesitancy that seems to be echoed by several nations despite the vast amounts of money lost due to symptoms caused by anxiety and depressive disorders. This paper takes an in-depth look at all the issues listed above and more, analyzing the merit of researching/using medicinal plants for anxiolytic and antidepressant purposes, in the past, present, and potentially the future.
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Context: The liver, one of the most important organs of the body, is known to be responsible for several functions. The functional contribution of the liver to the metabolism of carbohydrates, protein, drugs and toxins, fats and cholesterol and many other biological processes are still unknown. Liver disorders are classified into two types: acute and chronic. Different drugs are used in liver diseases to treat and control pain. Most pain relief medications such as opioids are metabolized via the liver; therefore, the adverse reactions of drugs are probably higher for patients with liver disease. The current study aimed to evaluate the effects of opioid drugs on patients with liver disease; therefore, it is necessary to select suitable opioids for such patients. Evidence acquisition: This review was written by referring to research literature including 70 articles and four textbooks published from 1958 to 2015 on various reputable sites. Searches were carried out on the key phrases of narcotic pain relievers (opioids), acute and chronic hepatic failure, opioid adverse drug reactions, drug-induced liver injury (DILI) and other similar keywords. References included a variety of research papers (descriptive and analytical), intervention and review articles. Results: In patients with liver disease, administration of opioid analgesics should be observed, accurately. As a general rule, lower doses of drugs should be administered at regular intervals based on the signs of drug accumulation. Secondly, the interactions of opioid drugs with different levels of substrates of the P450 cytochrome enzyme should be considered. Conclusions: Pain management in patients with liver dysfunction is always challenging to physicians because of the adverse reactions of drugs, especially opioids. Opioids should be used cautiously since they can cause sedation, constipation and sudden encephalopathy effects. Since the clearance of these drugs in patients with hepatic insufficiency is decreased, the initial dose must be decreased, the intervals between doses should be increased and some patients need to be continuously assessed.
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Unlabelled: Opioids are commonly used to treat patients with chronic pain (CP), though there is little evidence that they are effective for long term CP treatment. Previous studies reported strong associations between passage of medical cannabis laws and decrease in opioid overdose statewide. Our aim was to examine whether using medical cannabis for CP changed individual patterns of opioid use. Using an online questionnaire, we conducted a cross-sectional retrospective survey of 244 medical cannabis patients with CP who patronized a medical cannabis dispensary in Michigan between November 2013 and February 2015. Data collected included demographic information, changes in opioid use, quality of life, medication classes used, and medication side effects before and after initiation of cannabis usage. Among study participants, medical cannabis use was associated with a 64% decrease in opioid use (n = 118), decreased number and side effects of medications, and an improved quality of life (45%). This study suggests that many CP patients are essentially substituting medical cannabis for opioids and other medications for CP treatment, and finding the benefit and side effect profile of cannabis to be greater than these other classes of medications. More research is needed to validate this finding. Perspective: This article suggests that using medical cannabis for CP treatment may benefit some CP patients. The reported improvement in quality of life, better side effect profile, and decreased opioid use should be confirmed by rigorous, longitudinal studies that also assess how CP patients use medical cannabis for pain management.
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What is already known on this topic? The rate for drug overdose deaths has increased approximately 140% since 2000, driven largely by opioid overdose deaths. After increasing since the 1990s, deaths involving the most commonly prescribed opioid pain relievers (i.e., natural and semisynthetic opioids) declined slightly in 2012 and remained steady in 2013, showing some signs of progress. Heroin overdose deaths have been sharply increasing since 2010. What is added by this report? Drug overdose deaths increased significantly from 2013 to 2014. Increases in opioid overdose deaths were the main factor in the increase in drug overdose deaths. The death rate from the most commonly prescribed opioid pain relievers (natural and semisynthetic opioids) increased 9%, the death rate from heroin increased 26%, and the death rate from synthetic opioids, a category that includes illicitly manufactured fentanyl and synthetic opioid pain relievers other than methadone, increased 80%. Nearly every aspect of the opioid overdose death epidemic worsened in 2014. What are the implications for public health practice? Efforts to encourage safer prescribing of opioid pain relievers should be strengthened. Other key prevention strategies include expanding availability and access to naloxone (an antidote for all opioid-related overdoses), increasing access to medication-assisted treatment in combination with behavioral therapies, and increasing access to syringe service programs to prevent the spread of hepatitis C virus infection and human immunodeficiency virus infections. Public health agencies, medical examiners and coroners, and law enforcement agencies can work collaboratively to improve detection of and response to outbreaks associated with drug overdoses related to illicit opioids. © 2016, Department of Health and Human Services. All rights reserved.
Prescription opioid use has increased in recent decades. Although opioids provide effective pain control, their use may be associated with the risk of misuse. Opioid misuse (OM) is prevalent among adolescents and young adults (AYAs). Opioids are necessary to treat cancer-related pain; however, oncology patients are not immune to medication misuse. Research examining OM among AYAs with cancer is scarce. This article examines the risk factors described in the general adult and adolescent medication abuse literature and aims to provide recommendations for practice in the AYA oncology population. The following risk factors should be examined in AYA oncology patients to determine their relevance: age, sex, behavioral and academic problems, psychological conditions, and a history of illicit drug use/abuse. To maintain the delicate balance of providing adequate pain relief while protecting patients from the risk of OM, clinicians must consider potential risk factors, motivating factors, and individual behaviors. Placing these challenges in perspective, this review provides clinical considerations, recommendations, and intervention strategies for OM prevention in AYA oncology patients.
Painful diabetic peripheral neuropathy occurs in approximately 25% of patients with diabetes mellitus who are treated in the office setting and significantly affects quality of life. It typically causes burning pain, paresthesias, and numbness in a stocking-glove pattern that progresses proximally from the feet and hands. Clinicians should carefully consider the patient’s goals and functional status and potential adverse effects of medication when choosing a treatment for painful diabetic peripheral neuropathy. Pregabalin and duloxetine are the only medications approved by the U.S. Food and Drug Administration for treating this disorder. Based on current practice guidelines, these medications, with gabapentin and amitriptyline, should be considered for the initial treatment. Second-line therapy includes opioid-like medications (tramadol and tapentadol), venlafaxine, desvenlafaxine, and topical agents (lidocaine patches and capsaicin cream). Isosorbide dinitrate spray and transcutaneous electrical nerve stimulation may provide relief in some patients and can be considered at any point during therapy. Opioids and selective serotonin reuptake inhibitors are optional third-line medications. Acupuncture, traditional Chinese medicine, alpha lipoic acid, acetyl-l-carnitine, primrose oil, and electromagnetic field application lack high-quality evidence to support their use.
Background and objectives: The misuse and abuse of opioids has increased across the United States in recent years, associated with a rise in opioid-related overdose deaths. Physicians report having difficulty discerning substance abuse or drug diversion, which can lead to over- or under-prescribing of opioids and poor pain management. Additionally, research suggests that patient characteristics (eg, sex, ethnicity/race, age) may unduly influence the pain management decisions of health care providers. This investigation aimed to assist in physicians' prescribing decisions and reduce prescribing bias through the assistance of mental health professionals. Methods: This study utilized 151 chronic pain patients being considered for chronic opioid therapy to determine if a psychological opioid-risk evaluation influenced physicians' opioid prescribing. The evaluation resulted in an opioid-risk level (ie, low, moderate, high) being assigned to each patient representing their potential risk for misusing or abusing opioid medication. A record review was conducted on each patient, abstracting information about opioid prescribing, and several other factors, which were included in logistic regression analyses. Results: Risk status and substance abuse history significantly predicted opioid prescribing, with a lower risk status associated with greater likelihood of opioid prescribing and those with a history of substance abuse being less likely to be prescribed an opioid; however, substance abuse did not significantly improve the overall model and was removed. Demographic variables were not significant predictors of prescribing contrary to findings in other studies. Conclusions: These findings suggest that providing physicians with additional information about their patients' opioid abuse potential aids in prescribing decisions and may reduce prescribing bias based on demographic factors.
Introduction: The benefits of opioid therapy must be balanced by any adverse effects. In recent years, prescription opioids have been increasingly prescribed, but have also been associated with increased abuse, overdose and death. Areas Covered: This review will categorize the common risks of opioid administration. Recognized adverse effects of opioid therapy include constipation, tolerance, endocrinopathies, sleep disorders, cognitive effects, respiratory depression, overdose and addiction. Studies have shown that there is increased risk of overdose and death with higher daily opioid doses, particularly above a morphine equivalent oral daily dose of 100 milligrams. Extended-release/long acting (ER/LA) opioid formulations may be beneficial for the compliant patient, yet may expose a higher risk for abuse if used inappropriately since each tablet carries a larger dose of medication. Expert Opinion: Prospective, controlled one-year trials are needed to establish the efficacy and safety profile of chronic opioid therapy. In addition to the well known side effects of chronic opioid therapy, the influence and serious effect of opioids on sleep and central sleep apnea is only recently being investigated. The lowest possible daily opioid must be used to manage chronic pain, and all clinicians should be cautious in the use of daily morphine equivalent doses above 50-100 milligrams.