A primer to

medicinal
cannabis
An introductory text to the therapeutic
use of cannabis
 Access to reliable, evidence-based information
still hinders the prescribing of pharmaceutical
quality cannabis for therapeutic use

Author
Martin Woodbridge | Consultant at Woodbridge Research
Ltd, New Zealand. This booklet was made possible
with funding from Bedrocan International who maintain
copyright.

Acknowledgment
The author would like to thank Professor Jennifer Martin,
chair of the discipline of Clinical Pharmacology in the
School of Medicine and Public Health at the University of
Newcastle (Australia), for her contribution to the review
of content of this booklet. The author would also like to
thank Dr Mikael Kowal for his insights and scientific review
of this booklet.

2
A primer to medicinal cannabis
This booklet discusses the therapeutic use of cannabis. That means we are not talking
about pot, marijuana, grass, or dope for recreational use to get ‘high’. It focusses strictly on
medicinal cannabis. It is meant to give health care professionals, regulators and patients
insights into the medical and scientific aspects of Cannabis sativa L. and how this plant fits
in the chain of therapeutic options.

Cannabis is a complex plant. There are over 500 chemical As early as the 1960s, the major biologically active
components identified; the chemical content of each cannabinoids THC and CBD were identified in the plant.
cannabis variety is different to the next. Globally, and By the late 1980s to early 1990s the cannabinoid receptors
for generations, it has been used recreationally and had been discovered. Both are critical time points for
associated with criminal activity - this has tainted its image identifying the key therapeutic components of the cannabis
as a legitimate medicine. International treaties also make plant and confirming the biological pathway for its action.
its medical use complicated. However, despite illegality, Since that time clinical research demonstrates medicinal
vast numbers of patients across the globe use cannabis in cannabis has potential therapeutic applications in certain
its crude form for symptom relief, while a smaller number conditions.
access pharmaceutical-quality products via their doctors
and pharmacists. Access to reliable, evidence-based With the development and availability of pharmaceutical-
information still hinders the prescribing of pharmaceutical- quality products, reliable clinical data are now being
quality cannabis for therapeutic use. Medicine regulators generated. This knowledge will help determine the place
often do not permit cannabinoids, the active substances in of medicinal cannabis in the therapeutic toolbox and to
cannabis, to be used as a mainstream medicine. separate therapeutic use from recreational.

3
4
Table of contents
1 What a medicine is and where cannabis fits in 7

2 The cannabis plant, its makeup and chemistry 9

3 Our endocannabinoid system 13

4 Quality and standardisation 17

5 Dosage forms and their administration 23

6 How cannabinoids move through the body 27

7 Prescribing medicinal cannabis 29

8 Health professionals perspectives 35

9 Patients perspectives 43

10 Legal perspectives 49

11 Glossary of terms 53

12 Suggested reading 57

5
6
1 What a medicine is and where cannabis fits in
Medicines are central to modern and traditional medical practice. Medicines are tools.
They are used to treat or prevent disease, and to promote health. If misused they can also
cause harm.

Doctors must have access to quality, safe, and effective Medicinal cannabis is a novel class of medicine. It is not a
medicines. They must also use them rationally. Every time panacea or a cure for disease. Currently, in most parts of
the doctor has to make decisions around whether it is the world, it is also not a first line treatment. Rather, eligible
appropriate to a patient’s needs, at the correct dose, for patients have not responded well to other medicines, or
the right length of time, and at an acceptable cost. experience unacceptable side effects. While only few
are officially registered medicines, cannabis products
Doctors also need choice. For patients who do not for medical use are still required to meet certain quality
respond well to one medicine, having an alternative standards. As a result, government medicine regulators
therapeutic option is helpful. Medicine choice allows often are managing a patient and doctor demand for
doctors to find the most appropriate treatment for the medicinal cannabis alongside the requirements of product
patient under their care. safety, quality and efficacy. So, as much as there is a
need for clinical data and prescribing guidance, robust
Over the last decade the number of patients exposed to information to support policy development and decision
medicinal cannabis (the cannabinoids THC and CBD) has making by government officials is just as essential.
increased alongside a variety of conditions where patients
have reported symptomatic benefit. These include, but
are not limited to, chronic pain; multiple sclerosis; nausea,
vomiting and appetite stimulation; epilepsy; and anxiety.
Others include sleep disorders; fibromyalgia; Gilles de la
tourette syndrome; therapy-resistant glaucoma; Crohn’s
disease and ulcerative colitis; Parkinson’s disease;
Medicinal cannabis is a
rheuma­toid arthritis; attention-deficit disorder (ADD); and
posttraumatic stress disorder (PTSD). Each has shown
novel class of medicine
varying degrees of response, and many still require being
confirmed by good clinical science.

7
 A potted history
Cannabis is one of the oldest known medicinal plants.
It is described in ancient handbooks on plant medicine.
Archaeological evidence indicates the plant spread from
Asia to Africa and on to the Middle-East. Eventually it
arrived in Europe around 500 BC. It was later used widely
for industrial purposes and was integral to early shipping
as hemp fibre. History states that the therapeutic use
of cannabis was introduced to Europe in around 1840
by an Irish doctor called William O’Shaughnessy. While
in India he observed its widespread therapeutic use. In
the following decades cannabis gained a short period
of popularity in Europe and the United States. Dozens
of different cannabis preparations were available. These
products were recommended for conditions including
menstrual cramps, asthma, cough, insomnia, labour pains
during birth, migraine, throat infection and withdrawal from
opium use. At the time no tools existed for quality control
and standardised preparations. Patients often received
a dose that was either too low having no effect, or too
high resulting in unwanted side effects. These drawbacks
meant the therapeutic use of cannabis was largely taken
over by standardised opium-based drugs such as codeine
and morphine. Cannabis gradually disappeared from all
Western pharmacopoeias. In the late fifties the World A cannabis extract produced by the pharmaceutical
Health Organisation (WHO) claimed that cannabis and its company Parke Davis & Co.
preparations no longer served any useful medical purpose.

The therapeutic use of cannabis was introduced

to Europe in around 1840 by an Irish doctor called
William O’Shaughnessy

8
2 The cannabis plant, its makeup and chemistry
Like other plants, cannabis is made up of hundreds of chemical compounds. It also comes
in many different types. Some people refer to indica, sativa, or ruderalis types. But all of
these belong to the same species: Cannabis sativa L. – a member of the Cannabaceae
family. Many people are familiar with cannabis by the name hemp. Another of its close
relatives is Humulus lupulus L., better known as hops, a key ingredient of beer.

Cannabis is said to originate in the arid climates of Central

Asia (Eurasian steppe), most likely the Hindu-Kush region.
Straddling the borders of Pakistan and Afghanistan, the
800-kilometre-long mountain range was an integral part of
the ancient Silk Road. The Silk Road provided a network
of trade routes connecting Eurasia. The road and maritime
trading routes moved various goods, including cannabis,
in its various forms (hemp fibers, oil-rich seeds, intoxicants,
and medicines), to the east beyond the Korean peninsula
and west beyond the Mediterranean Sea. Nowadays,
cannabis can be found growing in places all around the
world, except in humid, tropical rain forests.

There are male and female cannabis plants, each with a

distinct way of blooming. The cannabis plant has a lifespan
of one year. The plant typically reaches a height of two to
three meters (seven to 10 feet), after which it blooms and
the growth ceases. After fertilisation, the seeds mature and
the plant dies.

A female cannabis plant

9
 Cannabis by any other name is non-psychoactive (i.e. it does not alter perception or
More than 700 cultivated varieties (cultivars) of cannabis consciousness).
are thought to exist. The difference between distinct
cannabis varieties is not solely determined by the The cannabinoids are biologically active chemicals. The
cannabinoid content, but also the specific terpene content. concentration of cannabinoids varies throughout the plant
These chemical constituents act as distinct biochemical (excluding seeds and roots). The highest concentration is
markers, and can be used to ‘map the current chemical found in the unfertilised female flower.
diversity of cannabis’. By analysing the concentrations
of these compounds, researchers can identify specific The biological activity is mainly linked to the major
cannabis plants with defined chemical profiles. For the cannabinoids THC and CBD. Although THC and CBD have
purposes of medicine development, these particular plants unique activities, it is becoming clear that a wider range of
can be used in clinical trials to determine their specific cannabinoids and other constituents of the cannabis plant
biological actions, and later introduced as new varieties to may be involved in its various therapeutic effects. These
the existing product range. include the cannabinoids tetrahydrocannabivarin (THCV),
cannabichromene (CBC), and cannabigerol (CBG). These
Such analytical insights have led to a better understanding minor cannabinoids are thought to subtly modulate or
of cannabis taxonomy (scientific classification of plants). enhance biological effects when taken therapeutically. This
In the past, the distinction between sativa and indica has effect may be the result of them working on their own, or
presented much debate. The classification was based working together with THC and CBD.
upon differences in chemical composition, especially the
differences in terpene content. However, to date there is The terpenes
no conclusive research displaying distinct ancestral lines The other main compounds in cannabis are the terpenes.
for Cannabis indica or sativa. So, although cannabis plants These are aromatic compounds which give cannabis
can significantly differ from one another, the scientific varieties distinctive smells and tastes. Terpenes may
emphasis has shifted to a hypothesis that all cannabis falls have additive therapeutic action, meaning they may work
under Cannabis sativa. together with cannabinoids to modify or enhance medicinal
effects. To date more than 120 different terpenes have
The cannabinoids been identified in cannabis. Unlike cannabinoids, all major
Over 500 chemical compounds are produced by the terpenes present in cannabis (e.g. myrcene, alpha-pinene,
cannabis plant. Of these, at least 100 are unique to the and beta-caryophyllene) can be found abundantly in
cannabis plant – the cannabinoids. The plant-derived nature.
cannabinoids are termed phytocannabinoids. The major
phytocannabinoids, and those we know most about, It is thought that the terpenes work together with
are delta-9-tetrahydrocannabinol (THC) and cannabidiol cannabinoids to modify or enhance their effects. This is
(CBD). THC possesses psychoactive effects, while CBD known as the ‘entourage effect’.

10
The glandular trichomes The cannabinoids exist mainly in an inactive acid form. The
The cannabinoids and terpenes are produced in the plant’s pharmacologically active cannabinoids (e.g., THC/CBD) are
resin glands. These are called glandular trichomes. The formed when cannabis is heated to a temperature of at
trichomes are located on the surface of the entire plant. least 180°C resulting in ‘decarboxylation’. With the use of a
The largest concentration of the glands are found in the vaporizer, the active cannabinoids are released from the
flowering heads of the female plant. glandular trichomes in a vapour at 230°C which can then
be inhaled into the lungs.

Close up: The glandular trichomes containing cannabinoids and terpenes are found over the entire surface of the
cannabis plant.

11
12
3 Our endocannabinoid system
Like in the case of the opioid system reacting to opioids (morphine, codeine), humans have
a distinct receptor system for cannabinoids. The endocannabinoid system (ECS) contains
cannabinoid (CB) receptors and influences the activity of many other body systems. The
phytocannabinoids of the cannabis plant work in a similar way to our naturally produced
endocannabinoids.
The human brain and other organs contain naturally How cannabinoids work
occurring cannabinoid (CB) receptors and the Cannabinoids produce their effects by binding to
chemicals that bind to them. This is called the human specific CB receptors. Cannabinoid receptors are one
endocannabinoid system (ECS). The ECS role is to maintain of the superfamily of G-protein-coupled receptors (see
our body’s ability to function normally by influencing the illustration). So far, two types of cannabinoid receptors (CB1
functioning of other systems. It plays a critical role in our and CB2) have been identified with certainty.
nervous system, and regulates multiple physiological
processes. This includes the adjustment of our response The CB1 receptor is found mainly in the brain and central
to pain, appetite, digestion, sleep, mood, inflammation, nervous system. CB1 is also found in certain tissues and
and memory. The ECS also influences seizure thresholds organs, such as the lungs, liver and kidneys.
(i.e. in epilepsy), coordination, and other processes such
as the immune system, heart function, sensory integration The CB2 receptors are mainly found on certain cells of the
(touch, balance, sense of space), fertility, bone physiology, immune system, the gastrointestinal tract, and in immune-
the central stress response system (the HPAA), neural related organs such as the spleen and tonsils.
development, and eye pressure.
The phytocannabinoid THC activates both CB1 and CB2
Humans produce their own cannabinoids, the receptors, which in turn influences the activity of various
endocannabinoids. These endocannabinoids act on, or physiological systems. CBD, by comparison to THC, has
stimulate, the cannabinoid receptors. These compounds less affinity for the CB receptors, and works to partly block
act in a similar way to phytocannabinoids which also bind receptor activity.
to the receptors.

The plant cannabinoids are called phytocannabinoids.

They are the unique constituents of the cannabis plant.
Tetrahydrocannabinol (THC) and cannabidiol (CBD) are
the main constituents. There are other cannabinoids, but
currently far less is known about them.

13
 Cannabinoid receptors

CB1 receptors CB2 receptors

Found mainly in the brain Found mainly in the organs
(hippocampus, cerebellum and cerebrum) (spleen, tonsils, and immune cells)

CB1 & CB2

G-protein coupled receptors

CB2 / CB1 receptor

Signal

For example, the CB1 receptor is located in a number of As our knowledge of the human ECS develops so will our
regions of the brain which control various physical and understanding of how the phytocannabinoids, THC, CBD
behavioural functions. As a result, cannabinoids influence and other cannabinoids work. This understanding will lead
sensory and motor responsiveness (movement), heart to better medicines.
rate, emotional reactions, appetite and nausea/vomiting,
sensitivity to pain, learning and memory, and high-level
decision making.

14
GPCRs The human
Cannabinoid receptors are G-protein-coupled
receptors (GPCRs). GPCRs are found on the
brain
surface of our cells. These receptors are said
to ‘act like an inbox for messages, talking with
cells and therefore our body’. GPCRs have
a great number of functions in the human
body. As a result, many medicines, including
medicinal cannabis, work on GPCRs. Humans
produce endocannabinoids which interact with
the GPCRs CB1 and CB2. We know the most
about the endocannabinoids anandamide
(AEA) and 2-arachidonoylglycerol (2-AG).

The neural
network
The neurons

Pre-synaptic
Phytocannabinoids neuron
CB1 GPCR

Neuro- Synapse
transmitters
Endocannabinoids
Precursor Receptor
Post-synaptic
neuron
Activity

15
 The different types of cannabinoids are briefly described in the schematic below. This includes those derived from the
cannabis plant, laboratory made, and made in our bodies.

Types of cannabinoids

Cannabinoids
Cannabis sativa L.

Phytocannabinoids Synthetic cannabinoids Endocannabinoids

O Neurotransmitters
OH produced in the brain
OH that bind to the
H (R)

(R)
cannabinoid receptors
H
O O O
HO
N
O H
THC:
Delta-9-tetrahydrocannabinol OH
H (S)
THC is the primary psychoactive
component of cannabis (S)
H
O Anandamide (AEA)

O OH
OH Nabilone
OH
(racemic mixture: cis-trans isomerism) O
A synthetic drug that mimics the effect
HO of the natural cannabinoid THC
2-Arachidonoylglycerol (2-AG)
CBD: Cannabidiol
CBD is the secondary non-
psychoactive component
of cannabis

16
4 Quality and standardisation
The quality of medicinal cannabis can vary greatly. This poses risks and uncertainties to
patients and their prescribers. So, why is quality so important?

Cannabis has been used in human clinical studies and The safest and most reliable products are of
found to be relatively safe for most people, compared pharmaceutical-quality. These products meet good
to other medicines. However, some patients taking manufacturing practice (GMP) standards. GMP is the
cannabis have had worsened symptom control and new highest standard of medicine manufacture. GMP is an
side effects such as sleepiness, abnormal liver function assurance of consistently high-quality products and
and diarrhoea. Absolute safety does not exist for any production processes. For medicinal cannabis, GMP
medicine. All medicines can pose a risk of side effects and practices should start from the very first step, cultivation,
possibly adverse effects (resulting in harms). In particular, right through the entire production process to the finished
large doses of THC and potent synthetic cannabinoids product. It is not just about the packaging of cannabis flos,
have been shown to pose a risk of harm (e.g. postural- or the production of an oil extract. Under GMP, each part
hypotension resulting in a fall, or a mild to severe psychotic of the medicine production and testing process must be
event). clearly documented. Personnel, premises and materials
must meet the highest standards. These processes provide
patients and prescribers with the safest and most reliable
products.

17
 A pharmaceutical-quality product could be, for example, yy The absence/presence of heavy metals – The
cannabis flos for inhalation, a capsule for swallowing or cannabis plant can quickly take up heavy metals from
a spray for the mouth. Each product type will require a soil – termed heavy metal bio-accumulation. Every
slightly different set of tests for quality. These tests are batch must be checked for the presence of harmful
often published. The pharmacopoeia monographs, for heavy metals such as arsenic, cadmium, lead and
example, are the most reliable published methods for mercury.
the analysis of medicines. These monographs explain yy The absence/presence of foreign matter – It is
the standards for potency, quality and so on. Medicinal essential that the final plant material (and the finished
cannabis products are required to be independently product dose form) is free from impurities such as soil,
tested by specialised laboratories. The tests laboratories dust, dirt and other contaminations.
undertake often include: yy The total water content – For cannabis flos which is
intended to be inhaled by vaporization, the final water
yy The identification of cannabis – Medicinal cannabis content is important. The right amount of moisture
products typically must be derived only from the (water content) in dried cannabis flos assures an easy
cannabis plant. An important first step is to test the inhalation process during vaporization.
plant material to confirm it is actually cannabis, and not
an adulterant or substitute.
yy The identification of active ingredients – There are
numerous components of the cannabis plant. This test
typically requires identifying THC and CBD, and often
the terpene content.
yy The absence/presence of microorganisms – During
cultivation the cannabis plant can host harmful
microorganisms like fungi and bacteria which can
end up in the finished product. This may require
decontamination treatment by gamma irradiation to
eliminate microorganisms such as Staphylococcus
Aureus and Escherichia Coli. The process must not
affect the quality of the finished product.
yy The absence/presence of pesticides – Many different
types of pesticides can be used in cannabis cultivation,
but none are approved for use in cannabis. This
test ensures the finished product does not contain
pesticides which are very harmful to patients’ health.

18
The cornerstone of reliability Indoor versus outdoor cultivation
Medicines must have a clearly defined composition. GMP- The discussion around standardisation continues with
certified, fully standardised medicinal cannabis contains a comparing indoor and outdoor cannabis cultivation.
constant composition active ingredients, batch-to-batch. This is because the chemical composition of cannabis is
This means the same dose can be taken each time. determined by the plant’s genetics, and the total content is
Doctors can better monitor dosage, condition progress, most influenced by the plant’s growing conditions.
and reduce the risk of overdose and side effects. These
products are also free of microbial contaminants (moulds, Indoor, fully controlled cultivation allows for fully
fungi, and bacteria), pesticides, and heavy metals. These standardised cannabis flos (the whole dried female flowers)
are qualities which are especially important for people and whole plant extracts (containing cannabinoids and
with weakened immune systems, and which make the terpenes) year-round. Controlling all growing conditions
products safe for vaporization and inhalation into the lungs. and the plant’s genetic composition produces a finished
Finally, standardisation allows the comparison of different product, free of contaminants, and containing an exact
clinical trials and studies across time. It is a critical factor for content of active components. The production of cannabis
building the evidence base of medicinal cannabis. flos, in compliance with pharmaceutical standards of GMP,
is only possible within fully controlled environments and
Batch-to-batch consistency is a challenge. The cannabis using plants with stable genetics.
plant is chemically complex and can vary greatly from
plant-to-plant. Growing standardised cannabis means Outdoor cultivation, including in fields or greenhouses,
consistently achieving a balance of all potential active produces genetically undefined, non-standardised
components (specifically the cannabinoids and terpenes). cannabis. Outdoor cultivation is suitable for single
This must be confirmed batch-to-batch by laboratories who cannabinoid extraction (i.e. THC or CBD). Outdoor
issue Certificates of Analysis. cultivation, from seed, produces plants with a dissimilar
genetic composition and inexact content of active
The most common approach standardisation is to select components. An uncontrolled growing environment
cannabis cultivars with good genetic stability and that is likely to permit cross-pollination which reduces the
originate from one single seed. These plants are then quantity and quality of cannabinoids. It also increases the
grown by multiplying the original plant material. Copying risk of contamination with pesticides, heavy metals, and
a fragment of the mother plant helps to prevent ‘genetic hazardous moulds, bacteria and fungi.
drift’, which can cause major changes and weakness in the
plant over time.

To achieve batch-to-batch consistency in the plant is very

difficult. Indeed, to date, only one company, Bedrocan
in the Netherlands, has been able to achieve fully
standardised cannabis flos with GMP certification.

19
 From cannabis cultivation to cannabis flos
Below is a pictorial illustration of an indoor cultivation growth cycle and production of standardised, GMP-certified
pharmaceutical-quality cannabis flos.

A cutting is obtained

Plants are placed into Rockwool The plants are placed in a growing room

20
The harvested cannabis plant is dried The stems and leaves are removed

The cannabis flos is packaged

21
22
5 Dosage forms and their administration
Like other medicines, medicinal cannabis is available in different dose forms (e.g.,
inhalation, oral, transdermal) to meet different patient requirements. How medicinal
cannabis is administered or taken depends on its dose form.

In this section we talk about the most common ways Inhalation – by the lung
medicinal cannabis is taken by patients across the world. In
the next section we talk about how cannabis is absorbed,
Dose form
distributed, metabolised and then excreted (removed) from
Using a vaporizer or inhalation medical device,
our body.
cannabinoids are inhaled (from cannabis flos) as a
vapour which then enter the bloodstream from the
lungs.
The dose form is really important. It can influence
patient behaviour in different ways, including:
yy If patients actually take their medicine, and Inhalation has proven to be an efficient administration
adhere to their daily regimen route. The inhaled vapour is quickly absorbed by the
yy When they take it (the time of day) lungs. The immediate onset of action means it is the
yy How often they take it (the frequency of use) preferred choice for many patients. The vapour contains
yy How much they have to take (total daily dosage) cannabinoids and terpenes in consistent, measurable
yy The side effects and how these are tolerated quantities. The speed of onset simplifies titration - the
ability to achieve the correct dose without side effects
- and achieve fast relief from symptoms. The amount of
cannabinoids delivered depends on the depth of inhalation
and breath hold. While inhalation results in higher blood
levels of cannabinoids, their effects compared to oral
administration is shorter in duration.

Medical vaporizer
Given the risks from smoking, patients nowadays seek
reliable, affordable and portable vaporizers or inhalation
devices. Research dedicated to advancing vaporizer and
inhalation technology has seen major developments in
device quality.

23
 Medical vaporizers for the administration of cannabis flos - Oral – by the mouth
instantly we think of e-cigarettes or vape-pens - are in fact
quite different. The vapour does not contain nicotine, liquid
propylene glycol, glycerol nor synthetic flavours. There is Dose form
also no large, socially intrusive, toxic vapour cloud. These Cannabinoids (whole plant extracts or individual
vaporizers (or inhalation devices) offer patients an effective, cannabinoids) taken by mouth and either swallowed
safe, and easy to use delivery system. (oral), or absorbed from under the tongue
(sublingual). When swallowed, the medicine enters
Smoking into the bloodstream via the stomach, intestines and
Ultimately, smoking medicinal cannabis is harmful to the liver. When absorbed from under the tongue,
patients’ health and is therefore not recommended. the medicine bypasses the liver and enters into the
Toxic pyrolytic compounds are produced when the plant bloodstream directly.
material is smoked (i.e. combustion). Typically cannabis
flos is rolled into a ‘joint’ cigarette, and cannabinoids are
inhaled as smoke into the lungs. The medicine enters Oral preparations are familiar dose forms. They are similar
into the bloodstream from the lungs. Smoking cannabis to other medicines patients already take, and are easy to
results a rapid onset of action. The effect is noticed within administer. As a result, concentrated cannabis extracts are
minutes. While smoking results in higher blood levels of becoming increasingly popular.
cannabinoids, their effects compared to oral administration
is shorter in duration. Furthermore, unless it is fully Oils
standardised, the amount of THC and CBD in cannabis flos An increasing number of patients are using extracts of
can vary greatly between batches. The amount of THC cannabis flos. Whole plant cannabis extracts contain
delivered also depends on the depth of inhalation, puff cannabinoids and terpenes in a concentrated dose
volume and duration, and breath hold. form. Often they are called ‘oil’ because of their dark
viscous appearance. The extract is dissolved in an oil
(e.g., olive, sunflower, peanut) to act as a carrier and ease
Pharmaceutical quality cannabis flos administration.
For vaporization to deliver consistent therapeutic
levels of cannabinoids, the product must be A single dose can be dispensed from a dropper and
of pharmaceutical quality. This cannabis flos is placed under the tongue. It is absorbed from the lining of
genetically and chemically standardised according the mouth (termed sublingual absorption) where upon it
to pharmaceutical standards. From a patient safety enters the bloodstream.
perspective, it is free of microbial contaminants,
pesticides, impurities and heavy metals. These are Sublingual delivery increases total available dose. This
qualities that make the vapour safer for inhalation means smaller doses are required for the same effect,
into the lungs. compared to swallowing capsules or drinking tea.

24
Sublingual dose forms can provide a reliable uniform dose. Furthermore, tea typically has a low concentration of
cannabinoids, the tea composition is effected by boiling
Sprays time, volume of tea prepared, and the length of time in
Sprays are also administered under the tongue just as oils. storage. This means dosing by tea can provide a less
An example is Sativex™, a standardised (oromucosal) dose certain therapeutic effect.
form of a pharmaceutical product, made from two strains of
cannabis. One strain produces mainly THC and the other Edibles
mainly CBD. Exacting proportions of the active compounds Other whole plant dose forms include edibles such as
THC and CBD are dissolved in an alcohol solution. This is cookies/brownies. It is difficult to obtain a consistent
placed in a metered-dose bottle which is sprayed under cannabinoid composition in edibles. Patients can easily
the tongue. overdose, particularly as the time to effect may be
2-3 hours and patients may ingest a second dose if they
Capsules are awaiting effects.
An alternative oral dose form are capsules. These typically
contain exacting concentrations of single cannabinoids The therapeutic effect is less certain than standardised oral
(i.e. THC and CBD) dissolved in a carrier oil. The capsule products and it usually takes longer to achieve. As a result,
is swallowed, breaks open, the drug is released and finally edibles are not considered a therapeutic product.
absorbed in the stomach and intestines. The rate (time) of
absorption can be unpredictable, and varies depending
on, for example, if food is present, and if the patient is
mobile (able to exercise/walk freely). Interestingly, THC The importance of standardisation
itself slows the rate of gastric emptying (from the stomach There are numerous oil products available on the
to intestine). Oral administration (by swallowing) results in market. Their quality and reliability relies on the
slower onset of action, lower total blood concentration, quality of the starting material, cannabis flos.
and a longer duration of effects compared to inhalation. Because most extraction companies don’t use fully
Total cannabinoid content is affected by liver metabolism standardised cannabis flos, the total cannabinoid
and stomach contents. This means oral dosing can be less content of the extract often is different to the
unreliable and unpredictable. medicine label. Some companies’ medicine labels
show a ‘target’ cannabinoid concentration. This
Tea or infusion is because the cannabinoid concentrations in the
A proportion of patients consume medicinal cannabis as a cannabis starting material varies from batch-to-
tea (cannabis flos infused in hot water). Teas are swallowed batch. Unpredictable medicine concentrations are a
and the cannabinoids are absorbed in the stomach and concern for patient safety. This is because the quality
small intestine. Similar to oral dosing, the total cannabinoid of a medicine is partly determined by ‘accuracy of
content is affected by liver metabolism and stomach dosing’ and ‘reproducibility’ of the dose.
contents. This means dosing by tea may be unreliable and
unpredictable.

25
 Transdermal – by the skin

Dose form
Transdermal literally means across the skin. The
typical dose forms include creams which are applied
to the skin surface or a mucous membrane; and,
transdermal patches which are a medicated adhesive
patch applied directly on the skin. A specific dose is
then administered gradually over a set time.

The importance of form

Transdermal dose forms are being investigated for their The form in which medicinal cannabis is administered
clinical use and application. Currently they are being used determines the onset, intensity, and duration of
to treat certain skin conditions and for localised muscular effects (how it moves and works in our body). The
or joint pain. major factors which determine the selection of dose
form include:
Given that most cannabinoids dislike water (are highly yy Accuracy of dosing – how precise the dosing
hydrophobic), it can be difficult to achieve a reliable method is to reach the desired dose, to avoid
dose form that is applied to the skin and can achieve under-dosing, over-dosing and side effects.
appropriate blood concentrations. However, novel yy Bioavailability – the fraction of the dose that
nanotechnology may overcome this. Dose forms such as reaches the bloodstream to provide a therapeutic
creams are intended for local application and action. These effect. Typically, intravenous injections have the
do not require achieving penetration through the skin into greatest bioavailability (direct to bloodstream),
the blood stream. then inhalation, sublingual, buccal oral mucosal,
rectal and oral and transdermal dose forms.
yy Onset of action – the amount of time before the
effects of the medicine are felt.
yy Duration of effect – the length of time the
medicine is active.
yy Reproducibility – the degree to which the
medicine can be given to achieve repeated
effects, preferably with good precision.
yy Safety – the dose form is easy to use, is of good
quality and does not cause harm or intolerable
side effects.

26
6 How cannabinoids move through the body
Determining how a medicine is going to work for an individual patient is very important
to medicine safety and efficacy. The way the cannabinoids THC and CBD move through
the body (pharmacokinetics) varies depending upon how it is taken. The duration of their
action is influenced by dose size, dose form, and the route of administration - the lungs,
mouth, gut or the skin.

Absorption and distribution Pharmacokinetics

THC and CBD are mainly found in cannabis in their Pharmacokinetics is abbreviated as PK. It is the study
inactive acid form. To activate THC and CBD a carboxyl of the movement of medicine within the body. The
group must be removed by heat. In practice, this so called acronym ADME is used to describe a medicine’s
‘decarboxylation’ occurs by heating cannabis flos in a Absorption, its Distribution, Metabolism, and final
vaporizer, or heating the cannabis flos extracts before Excretion from our body.
being placed into a solution.

The absorption of inhaled cannabinoids results in a

maximum (peak) blood concentration within minutes (see
figure). Effects in the brain start within seconds to a few Plasma drug concentration Time of maximum
drug concentration
minutes, and reach a maximum after 15-30 minutes. They
Maximum (peak)
taper off within 2-3 hours. drug concentration

Absorption is slower when cannabinoids are ingested.

Lower, more-delayed peak concentrations occur with oral
ingestion. The effects in the brain are delayed for 30-90
minutes, and reach their maximum after 2-3 hours. They
last for about 4-12 hours. Time

Bioavailability describes the proportion of a medicine The pharmacokinetic profile of a medicine is described as
entering blood circulation after administration. The the medicines blood plasma concentration over a period
bioavailability of oral THC and CBD is low. By comparison, of time.
the inhalation of cannabinoids has been shown to be more
effective and reliable compared to oral administration.

27
 THC and CBD are fat soluble (highly lipophilic) compounds The slow elimination of cannabinoids and their metabolites
which are rapidly absorbed by the lungs. As a result, is due to their slow movement out of our body fat and
inhalation is a convenient and fast-acting method of other tissues back into the bloodstream.
administration, allowing easier titration to the desired
dosage and biological effect. About 25% of inhaled THC
enters the blood circulation.

The distribution of cannabinoids in the body are ruled by

their lipophilicity (their fat solubility) and binding to blood
proteins. THC is distributed widely throughout the body,
particularly to fatty tissues. The body storage of THC
increases with increasing frequency and duration of use.

Metabolism and elimination

The cannabinoids are mainly metabolised by a collection
of liver enzymes called cytochrome P450 (CYP450). The
same as many other medicines, these enzymes chemically
alter the cannabinoids to remove them from our body
(excretion). Besides the liver, other tissues like the heart First-pass metabolism and THC
and lungs are also able to metabolise cannabinoids, albeit A metabolite is a substance formed during
to a lesser degree. THC and CBD metabolism follows a metabolism – a breakdown product. After swallowing
similar metabolic route. a medicine it is then absorbed in the small intestine
and carried to the liver and metabolised. This is
Elimination of medicines means their complete removal called first-pass metabolism. First-pass metabolism
from our body. Metabolism is the major route for the greatly reduces the medicine concentration,
removal of THC. Unlike THC, a large proportion of CBD is meaning only a proportion of the original medicine
excreted unchanged. Within 5 days of taking a single dose, reaches the blood circulation. In some cases, the
a total of 80−90% of THC is excreted. The elimination metabolite can be potent and long acting. For THC,
of THC and its metabolites occurs via the faeces and the metabolite 11-hydroxy-THC (11-OH-THC) is about
urine. After inhalation, about 25% of the absorbed dose is twice as psychoactive as THC itself. When THC is
excreted in the urine; about 65% is eliminated via faeces. inhaled, it avoids first-pass metabolism and its rapid
Only very small amounts of THC are excreted unchanged. conversion to 11-OH-THC.
Less than 5% of an oral dose is found unchanged in the
faeces. THC metabolites can be found in the urine and
faeces for several weeks.

28
7 Prescribing medicinal cannabis
When used rationally and correctly, medicines can be effective in treating or preventing
disease. If misused, they can cause harm. This includes medicinal cannabis. In this section
we discuss the prescribing of medicinal cannabis.

Medicinal cannabis is a rapidly changing field of medicine, For other conditions there is less available or negative
with new products, scientific and clinical data emerging. In clinical data. These include, epilepsy (particularly the
the last decade, clinical research has mainly focused on drug resistant childhood epilepsies), Gilles de la Tourette
the therapeutic effects of cannabinoids as an analgesic syndrome, therapy-resistant glaucoma, fibromyalgia;
in chronic neuropathic pain, as an appetite stimulant post-traumatic stress disorder, sleep disorders, bladder
in cancer, and in the treatment of spasticity in multiple dysfunction, some symptoms of Parkinson’s disease,
sclerosis. Other indications include for example in anxiety, and depression. While existing scientific evidence does
psychosis, and fibromyalgia. More recently, cannabidiol not fully support a specific condition, a paucity of clinical
(CBD) has emerged as a single cannabinoid with plausible research does not necessarily reflect the potential of
therapeutic action in childhood epilepsy. Clinical trial medicinal cannabis in a given disease for a particular
reviews provide insight to relevant conditions and dosing, patient.
while newly published supporting information on plant
chemistry, cultivation, quality analysis, and administration The next summary covers clinical insights for areas of
adds value to knowledge of product safety and prescribing interest to most readers. These include chronic pain;
practice. nausea, vomiting and appetite; multiple sclerosis; and
epilepsy.
Conditions which show promise
There is clinical research supporting the use of medicinal Chronic pain
cannabis in certain conditions including: Severe chronic pain seems to be the major reason for
yy Chronic pain, particularly pain associated with the which patients use medicinal cannabis. There are many
nervous system, caused for example by a damaged types of pain, and cannabinoids do not influence each
nerve, phantom pain and facial neuralgia pain type identically. To date, the therapeutic benefit of
yy Nausea, loss of appetite, weight loss, and vomiting medicinal cannabis has only been seen in neuropathic
associated with chemotherapy or radiotherapy used in pain studies – the pain originating from injury or disease
the treatment of cancer, and anorexia and cachexia in that affects the sensory nerves. By comparison, studies
HIV/AIDS measuring the effects on acute pain (e.g. postoperative
yy Pain and muscle spasms or cramps associated with pain) often show no beneficial effects. Most likely, this
multiple sclerosis or spinal cord damage difference is related to the role endocannabinoids play in
both types of pain. However, the mechanism behind this
difference is not yet fully understood.

29
 Chronic neuropathic pain is common, difficult to treat, Cannabinoids have been shown to stimulate appetite,
and has limited treatment options. Consequently, even described as a strong desire for foods with high fat or
the modest effects of cannabinoids may be important for sugar content. For example, since the 1980’s, Marinol®
patients. Patient preference studies show the side effects has been used as an appetite stimulant for weight loss in
from cannabinoids are better tolerated than strong opioid patients with HIV/AIDS. For patients experiencing loss of
medications. Indeed, medicinal cannabis has often been appetite, a high caloric intake may contribute to weight
studied in combination with other medicines, including for gain and to the absorption of nutrients. Often this is crucial
example morphine. It has been found that cannabinoids in managing medical conditions such as wasting syndrome
and opioids work together with a strong combined effect. (cachexia).

Although other drugs are available to treat nausea,

vomiting, or reduced appetite, the combined effect of
cannabinoids on all these symptoms at once makes it a
unique option for contributing to improving a patient’s
quality of life.

Multiple sclerosis
Together with chronic pain, multiple sclerosis (MS) is
the other medical condition in which long-term effects
of cannabinoids have been extensively studied. The
research show patients do not develop a tolerance for the
medicinal effects, nor increase their doses over time to
achieve the same therapeutic result. Although the medical
evidence supporting cannabis use for MS is still limited, it
Nausea, vomiting and appetite is important to note the same is true for most conventional
Cannabinoids can have strong effects on nausea MS medications.
and vomiting resulting from cancer chemotherapy or
radiotherapy, hepatitis C and HIV/AIDS treatments. A As a result, patients suffering from MS have historically
synthetic THC dose form (as Marinol®) has been widely experimented with alternative therapies, including
used as an antiemetic for cancer patients undergoing cannabis, to improve their quality of life. Standard therapies
chemotherapy. Supporting studies suggest that the often provide inadequate relief and can be limited by
addition of THC directly before and after chemotherapy medication side effects. Existing scientific evidence
offer more benefit than using older antiemetic medications. supports the use of medicinal cannabis to treat disease-
However these have not been compared against the related pain, bladder symptoms, tremor, and spasticity.
latest antiemetic medications which are significantly more Additionally, for many patients cannabinoids improves
effective in this setting than the older ones. sleep, resulting in both deeper and longer sleep.

30
Epilepsy A treatment protocol provides patients with advice on:
Epilepsy is typically well-controlled by existing medications. yy An appropriate starting dose
However, a significant number of people with epilepsy do yy How to increase their dose (minimum and maximum
not have adequate control of their seizures. As early as dose)
in 1979, laboratory studies confirmed the anti­convulsant yy How to find an optimal daily dosage based the severity
effects of (pure) CBD. In various subsequent animal and of the patient’s condition, and changes in their other
(small-scale) human studies, CBD was able to reduce the medication
frequency and severity of seizures. Combined with an yy How to maintain their daily dosage
absence of psychoactive effects, these results show the yy Medicine and food interactions
potential of CBD as a treatment for human epilepsy. yy Ways to reduce the risk of side effects or adverse
reactions occurring
Unfortunately, the low quality of most the reported scientific yy A plan to stop treatment if there is a poor response
data does not allow for making definite conclusions on
the potential of cannabinoids as a treatment for epilepsy. Safety
In addition, the safety and tolerability of cannabinoid
preparations in a paediatric population is not fully clear. Potential medicine interactions
Although CBD appears to be effective in reducing seizures Medicines can interact with each other. The risk increases
in epilepsy patients, more controlled research is needed to if a patient is taking lots of medicines at once. Indeed,
understand the full clinical value of these types of products. patients’ who are prescribed medicinal cannabis often
have complex conditions and take multiple medicines.
Dose, dosage and titration
Like with other medicines, individual patients will respond There are a number of medicines medicinal cannabis may
differently to medicinal cannabis. Their response depends interact with. Care should be taken when co-prescribing
on the cannabis product used, the condition being treated, medicines with sedating effects, which also includes
the duration of treatment, how it is administered, and drinking alcohol. The combination of cannabinoids and
genetic predispositions. Certain ratios of cannabinoids sedatives can affect response time, co-ordination, and
have so far emerged to be the basis of specific effects; concentration. Cannabinoids may also interact with heart
and appear to be better tolerated than single compounds and circulation medicines (e.g. adrenaline, beta-blockers,
(especially high doses of THC). and diuretics). Also, THC appears to enhance the action of
opioids (e.g. codeine, morphine).
A patient’s doctor generally provides advice regarding
dose titration (dose adjustments to a desired effect) to The above list is not exhaustive. A full review should
achieve an optimal daily dosage. This helps patients to be undertaken before co-prescribing, including those
obtain the desired therapeutic effects and to minimise medicines which interact with the CYP-450 metabolic
undesired effects. enzymes.

31
 Potential side effects Risks
In general, patients seem to tolerate medicinal cannabis Like any other medicine, medicinal cannabis is certainly not
well. Typical side effects last a short time, are mostly without risks. The known risk factors and precautions are
benign, and resolve as tolerance builds. Side effects mainly briefly described in the non-exhaustive list below.
occur after taking high doses, or when used in combination
with other substances. These tend to occur quickly after Prescribing for the elderly
use. Signs of side effects include: Elderly patients are more sensitive to the neurological,
psychoactive and postural-hypotensive (feeling dizzy or
yy Dry mouth lightheaded) effects of medicinal cannabis (particularly
yy Redness of the eyes THC). This is especially so for elderly patients who are
yy Heightened appetite (which may be desirable) prone to falls and those with dementia. If considered
yy Mild euphoria appropriate, elderly patients should start at the low end of
yy Reduction of alertness of the user, especially in the few the dosing range.
hours directly after consumption
yy Increased heart rate
yy Lowering of blood pressure and dizziness
Cannabinoids can have
In general, all side effects will slowly decrease and then a significant effect on
disappear within a few hours. This depends upon the dose
taken and mode of administration. heart rate and blood
Overdosing pressure
Overdose can usually be prevented by preparing a
treatment protocol. When using too large doses containing Psychosis or other psychiatric conditions
THC, a patient may experience intoxication. This is often Medicinal cannabis should not be used in patients with a
described as a mild euphoria or results in sedation and family history or previous episode of psychosis, psychiatric
somnolence. In some cases, this can be experienced as a conditions or major depression because THC may bring on
distortion of reality, mild anxiety, changes in heart rate and psychotic symptoms.
blood pressure. In these cases, most often, it is sufficient
for patients to sit or lay down in a calm and comfortable Heart disease cardiac/coronary conditions
location, preferably with someone familiar to talk to. Cannabinoids can have a significant effect on heart
Overdosing with very high doses may result in a psychotic rate (hypertension, tachycardia) and blood pressure
state or other psychiatric conditions, particularly in those (vascular constriction) which can cause cardiac ischaemia.
with a pre-existing genetic vulnerability (see below). Patients with a history of heart disease or receiving heart
medication should avoid use, or only use medicinal
cannabis under careful supervision by their doctor.

32
Pregnancy and lactation Driving and operating machinery
The use of medicinal cannabis during pregnancy is likely At therapeutic doses, cannabis may produce undesirable
to affect the development of the fetus and should not be effects such as dizziness and drowsiness which may impair
prescribed. Because certain cannabinoids – including THC judgement and performance. Patients should not drive,
– are excreted in breast milk, use is also not advised while operate machinery or engage in any potentially hazardous
breastfeeding. activity under the influence of medicinal cannabis or
cannabinoid therapeutic products that contain THC.
Liver disease
After administration, the liver is the main organ involved in
chemically altering the cannabinoids to remove them from
our body (metabolism). Patients with liver disease should What is pharmacovigilance?
be monitored to make sure the dosage does not exceed Pharmacovigilance is the collection and evaluation of
the liver’s ability to remove it (metabolic capacity). information from healthcare providers and patients
on the adverse effects of medicines. Monitoring the
Addiction and aberrant prescribing use of medicines in everyday use helps to identify
The evidence suggests that the risk of developing an previously unrecognised adverse effects or changes
addiction to cannabis when taken as a medicine is not in the patterns of adverse effects.
common. Nonetheless, particular care should be taken
if patients have prior problematic substance use. High Medicine quality and safety relies on patients,
doses of medicinal cannabis, taken over long periods, their carers, and healthcare professionals to report
could lead to dose escalation, misuse and harm. Abrupt problems with medicines and administration devices
ending of treatment may cause withdrawal symptoms, (droppers, syringes, vaporizers, transdermal patches).
such as restlessness, irritability, insomnia, vivid dreams and Pharmaceutical companies and regulatory agencies
decreased appetite. can then investigate reports, identify the specific
cause, and determine any necessary regulatory
Diversion and misuse action to resolve the problem.
Cannabinoid therapeutic products containing THC are
often considered desirable psychoactive substances. Most importantly, understanding why a medicine is
Like other controlled drugs, medicinal cannabis requires causing harm can lead to improvements. This is for
the same guidance and considerations by doctors and the benefit of patients.
pharmacists to limit diversion and misuse.

33
34
8 Health professional perspectives
Who can prescribe and dispense medicinal cannabis depends on country specific policy.
Most often health professionals are the gatekeepers to patient access. In particular,
prescribers and pharmacists have an important role to play. In a prescriber-pharmacy
model, patients are offered more objective communication of risks and benefits, and the
safety of health professional guidance.

However, many health professionals do not know how

medicinal cannabis should be prescribed and dispensed.
This is not surprising given that medicinal cannabis is a
new class of medicine. The traditional approach to drug
discovery and development, including clinical trials, have
not been undertaken on most products. Clinicians are now
rapidly trying to understand how they work.

We have talked about the potential place of medicinal

cannabis in the medical toolbox. So how should it be
prescribed and dispensed? This section presents two case
studies: one from the perspective of a pain specialist, and
the other from a community pharmacist. They highlight
prescribing and dispensing realities, and strategies to
improve patient safety. The information shared in these
case studies are context-specific and not intended to
support decision making by prescribers and pharmacists.

This section focuses on the Netherlands. It has the longest Many health
running medicinal cannabis programme (since 2003) and
provides fully standardised medicines under the guidance professionals do not
of prescribers and pharmacists. This is the same guidance
patients receive with traditional medicines. The insights know how medicinal
below are drawn from two professionals with extensive
experience working with standardised oral an inhalation cannabis should be
dose forms.
prescribed
35
 Prescribing medicinal cannabis Prescribing
Trained as an anaesthesiologist in Germany, Do you have any advice for doctors starting out
Dr Jürgen Fleisch then undertook a fellow­ship prescribing?
in pain medicine (Portland, Oregon). He now “My advice for clinicians who are starting to prescribe
practices anaesthesiology and pain therapy in medicinal cannabis is to stick to specific indications
the Netherlands at the Leiden University Medical where there is a solid foundation of evidence for its use.
Centre. For the last decade, his close cooperation This allows us to gain experience with the effects of this
with the Department of Oncology means he medication in a specific adult patient population.
regularly treats symptoms in cancer patients using
medicinal cannabis. In both settings, he typically Recreational cannabis users are, in my opinion, not a good
encounters two types of patients. Those with patient category to start with. They may put considerable
advanced cancer experiencing loss of appetite pressure on the clinician to prescribe for dubious
and possibly nausea and vomiting, and often indications.”
many other medications have been tried before.
And, those that experience central neuropathic How is prescribing medicinal cannabis different to
pain after unsuccessful trials of more common prescribing other medicines?
medications. “They are like any other medicine. However, many patients
will have an opinion about cannabis. For some it has
With a focus on safe prescribing practices, a rather negative connotation as being a substance of
prescribers play a pivotal role in managing patient abuse.”
therapy. This is especially important when patients
take multiple medicines. What are the key benefits of cannabinoids as a
therapeutic product?
“There are three main advantages of medicinal cannabis
in general over other medicines used in my field of pain
medicine, as follows:
yy There are analgesic effects on neuropathic pain
syndromes and, depending on the medicine type,
anti-emetic and appetite stimulating effects. This is
especially important for cancer patients with pain.
yy There are no known organ damaging side effects in
the adult patient, aside from the potential risk to mental
health. As compared to, for example, those linked with
using NSAIDs when used inappropriately.
yy Some cannabis flos variants have a soothing effect,
which some patients greatly appreciate.”

36
What do you think are prescribing practices that There are three main advantages of administration by
improve patient outcomes? vaporization is that it:
“For patients with no experience using cannabis products, yy Allows for exact dosing,
the possible psychological side effects can be distressing. yy Leads to a rapid effect, and
In order to avoid this we advise patients to start with low yy Avoids the disadvantages of smoking (i.e., no tar,
dosage and use the medicine in a quiet and relaxing ammonia, carbon monoxide).”
environment.
Patient considerations
In our experience, it is advantageous to prescribe Thinking about a first consultation with a patient, how
cannabis flos as an inhalational agent, administered by do you start a conversation about medicinal cannabis?
vaporization, as it creates more rapid analgesic effects “There are two types of discussion around the use of
and has a more reliable absorption profile. medicinal cannabis:

With cannabis flos, the prescribing clinician needs to be The elderly, cannabis naive patient:
aware that in many countries the standards are different An elderly cancer patient may be hesitant to use cannabis
with respect to “regular” medicines: concerning the as a medication. This likely is related to prejudices about
quality control of the active ingredient, and toxicological cannabis being a product for ‘recreational’ use. With
contamination. Using cannabis flos originating from these patients, I rarely discuss the use of these medicines
controlled producers means patients are assured there is during a first consult. If the patient is eligible and several
no biological or toxicological contamination.” other therapies did not provide sufficient pain relief, I then
mention medicinal cannabis as a possible option. This
Aside from eliminating the harms from smoking, what allows the patient and his/her family to contemplate that
are the benefits of administration by vaporization? treatment option until the next appointment.
“Using vaporized cannabis flos is the preferred means of
use by most patients, especially when compared with an The experienced patient:
oral application. This is due to the more rapid effect by There may be patients who have extensive experience
inhalation. using cannabis recreationally. They may be actively
looking into medicinal cannabis as a potential adjunct
With vaporization cannabis flos is heated to a specific to their pain therapy. These patients emphasise the
temperature without burning it. Cannabinoids and ineffectiveness or side effects of other therapies, and may
terpenes are released in a vapour which is directly push clinicians towards prescribing a cannabis product.
inhaled. With these patients the topic must be discussed fully
during a first consult. The main question during this consult
is ‘are they at all eligible to receive medicinal cannabis?’.”

37
 Are you aware of patients experiencing interactions with How do you deal with diversion for misuse or abuse in
medicinal cannabis and other medicines? your practice?
“Indeed, we do see patients who experience drug “This patient group can be quite challenging. They may
interactions using cannabinoid therapeutics alongside put pressure on clinicians to prescribe medicinal cannabis
other CNS depressant medications (e.g. opioids). as the only means to relieve their pain. Mentioning misuse
and abuse can provoke abrupt reactions.
Sedative effects can be enhanced especially in the
geriatric population. Severe drowsiness and hallucinations Clinicians should be coherent in prescribing medicinal
can also be provoked. cannabis only for indications with enough evidence for
beneficial effects (e.g. analgesic for neuropathic pain,
Aside from drug interactions, the smoking of cannabis is appetite stimulation). Misuse and abuse should be
related to an increased risk of myocardial infarction and discussed openly if they become apparent.”
stroke. Cannabis as a trigger of myocardial infarction
is plausible, given its cardio-stimulatory effects, which
may cause ischemia in susceptible hearts. Carboxy-
hemoglobinemia from the smoking of cannabis may also
contribute to ischemia. Smoking is never recommended.”
Smoking is never
Do you encounter diversion for misuse or the abuse of
medicinal cannabis? How do you identify this issue in recommended
your practice?
“During the period when Dutch health insurers widely
reimbursed medicinal cannabis, we had frequent
discussions with patients, best described as ‘recreational
users’, about their eligibility.

Patients of this group, who were already using large

amounts of cannabis, were requesting access for rather
dubious indications. Some patients were seeing medicinal
cannabis as a cheap way to get a ‘recreational drug’
which they were already abusing.”

38
Dispensing medicinal cannabis Administration
As a pharmacist at Transvaal Apotheek, Oral dose forms (oil extracts) are an increasingly
Salma Boudhan dispenses cannabis flos, and popular, what advice do you give patients on safe use?
oil extracts for named patients through­out the “In accordance with their doctor’s prescription, we suggest
Netherlands. Based in The Hague, Transvaal that patients start low and go slow. As a starting dose
Apotheek has been meeting patient needs for oil, we recommend to use 2 drops (0,05ml) under the
since the late 1800’s. A patient recently said she tongue, 3 times a day and increase the dose until the
had been coming there for more than 70 years. desired effect is achieved. The maximum dosage is 10
Transvaal has dispensed medicinal cannabis (flos) drops (0,25ml), 3 times a day.
since it was legalised in 2003, and high quality
whole cannabis oil extracts for sublingual use The ‘steady state’ concentration of THC/CBD and the
since 2015. A typical patient arriving at Transvaal active metabolite is reached after 1-2 weeks. This time
are those suffering from cancer pain, nausea and span should be taken into account for the assessment of
vomiting; neuropathic pain; or epilepsy. the medicines effectiveness for the patient.”

The role of pharmacists is just as important as Vaporization is a popular mode of administration, what
prescribers. Pharmacists support prescribers with advice do you give patients on safe use?
patient medicine reviews, and talk with patients “We recommend patients inhale 1-2 times a day until the
about a medicine’s risks and benefits. They help desired effect is achieved or until (psychotropic) side
to minimise medicine misuse and harm, and seek effects occur. This means they have had too much. Per
feedback on safety, effectiveness and adverse inhalation, we recommend patients wait at least 5 minutes
reactions. between the inhalations.

Patients should take into account that inhaling cannabis

results in a higher uptake than when using other
administration routes. Patients have to dose carefully
when changing to a different variety, especially if they
have previously used cannabis with a lower content of
THC/CBD.

The ‘steady state’ concentration of THC/CBD and the

active metabolite is reached after one to two weeks. Like
oral dosing, this time span should be taken into account
for the assessment of the medicines effectiveness for the
patient.”

39
 Safety From a pharmacist’s point of view, what are the actual
What do you tell patients about the safe and effective and potential complications with medicinal cannabis?
use of medicinal cannabis? “The biggest risk is getting high and triggering psychoses
“First we ask the patient what they already know about (especially with psychiatric patients) or worsening current
medicinal cannabis. Then we inform them about the depression. There are risks in prescribing in the elderly,
mechanism of action, how to use it, the dosage regimen, and the potential long-term effects on children are still
possible side-effects, how to safely store it. Finally we unknown.”
make sure that the patient takes notice of possible
interactions with other medicines or contra-indications What is the role of the pharmacy profession in ensuring
(certain conditions where medicinal cannabis should not patient safety with the use of these medicines?
be used). “Pharmacovigilance is an important role of a pharmacist.
We seek feedback from patients on the safety,
In a follow-up discussion we ask the patient about their effectiveness and adverse reactions they experience
experience with the use of medicinal cannabis, with extra from their medicine use. We are also required to provide
attention to side-effects and effectiveness.” adequate instructions and honest information to patients
about the benefits and risk of their medicines.”
What are the key risks of using cannabis as a
therapeutic product? Do you encounter diversion for misuse, or the abuse of
“The only known contra-indications include schizophrenia, medicinal cannabis?
arrhythmia and other heart conditions. We work closely “Not often. We identify this issue by monitoring the
with prescribing doctors and also provide adequate quantities dispensed and the frequency of dispensing.
instructions to patients about the benefits and risk of their We make an agreement with the patient to avoid further
medicines.” misuse. If this doesn’t help, we consult the prescribing
doctor and find solutions to the problem.”
Are you aware of any patients that have experienced
cannabis interactions with other medicines? Do you have any good advice (tips) for pharmacists
“We know that cannabis is metabolised by CYP450 starting out?
enzymes. When taken together with other medicines “Get training or read a lot into the subject, because
metabolised by the same enzymes, there may be patients are generally quite well informed but also
the potential for drug-drug interactions. We discuss misinformed.”
with patients about the risk of using such medicines
concurrently, or recommend alternative medications.”

40
41
42
9 Patient perspectives
The future of healthcare is in understanding and responding to patients’ needs and
wants. This is called patient centred healthcare. For medicines, this means gaining patient
perspectives throughout the medicine’s life cycle. In particular, patient satisfaction with their
medicine is very important. This might include understanding if the dose form is acceptable,
if the treatment is adhered to, and if there are real improvements in quality of life.

We have talked about all aspects of medicinal cannabis. yy It is considered healthier than other medication as it is
So, what does this all mean from a patient perspective? ‘natural’, and as a ‘herbal’ medicine is perceived to be
This section talks about who uses medicinal cannabis, for less harmful than other ‘chemical’ medications.
what conditions, how they used it, and their relationship yy Patients are often searching for alternatives for their
with health professionals. usual medicines due to unbearable side effects (e.g.
gastrointestinal problems, drowsiness, numbness,
Insights from patients allergic reactions).
A Belgian-based social researcher, Frederique Bawin looks yy Conventional medicine side effects are considered
at medicinal cannabis from the patients’ perspective. Bawin problematic – patients become emotionless,
explores the legal and illegal use of medicinal cannabis depressed or apathetic. Patients had experienced
among self-reported patients. While not the experience significant adverse events caused by conventional
of every patient, findings from this cohort provides new medicines.
insights into uses, behaviours, relationships and risks
surrounding medicinal cannabis. Most patients found that medicinal cannabis was an
effective treatment for their conditions, often mentioning
Reasons for use that other people noticed improvements.
Why do patients use medicinal cannabis? Patients use
medicinal cannabis for multiple reasons, including the Patients used it for symptom management, to relieve
following: symptom complaints. Patient state it suppresses symptoms
but it did not cause them to disappear. It is not seen as
yy It is perceived to be more effective than other providing a solution to everything, and generally is not
medicines or it was the only effective drug for regarded as a cure. Indeed, some patients reported
certain symptoms (e.g. cramps, pain, inflammations, medicating with medicinal cannabis to cope with certain
chemotherapy induced nausea and vomiting). symptoms for which it turned out to be unsuccessful or
only partially successful (e.g. bladder problems due to MS,
acute headache).

43
 Medicinal cannabis was mainly used as a treatment for Health professional relationships
pain. While their pain had not completely disappeared,
it had lessened and became bearable as a result of Are their doctor and pharmacist actively
their medicinal cannabis use. While higher doses were involved in their treatment?
seen to be more effective in relieving pain, patients Sativex® is the only registered product in Belgium,
balanced this against possible side effects including mild however, doctors are allowed to prescribe unlicensed
intoxication. Similarly, while typical medicines were more medicines* which are available in Dutch pharmacies. This
effective in alleviating pain, patients preferred medicinal puts doctors in a difficult position. Most doctors’ response
cannabis because of the adverse effects associated with to patient requests were that they did not want themselves
conventional pain medications. or their patient to face legal problems because of illegal
cannabis, they were not allowed to prescribe by the
Treatment response National Medical Association and so on. Patients therefore
searched for doctors who were willing to prescribe
How did they respond to treatment? medicinal cannabis.
Overall, patients report very few or no side effects from
medicinal cannabis. Most adverse effects were perceived Medical support for medicinal cannabis use was very
to be less severe than their conventional medicines. The diverse among patients. Some patients reported that their
side effects that were not considered highly problematic doctors accepted their use and were supportive, whereas
or negative include: dry mouth, laughing, feeling happy, others had negative experiences. Numerous patients
increased appetite, increased heart rate, dizziness and indicated their doctors were sceptical, disapproved, not
being easily distracted. Some patients, however, did report interested, or silent about this subject.
experiencing negative side effects such as dry mouth,
feeling high, increased appetite, memory problems, bad For patients who were provided medical guidance, it
taste, blackouts, multitasking problems and increased heart differed significantly from instructions and advice they
rate. received for their other medicines. Most of the time their
doctor wrote a prescription and provided very general
Side effects from medicine use are subjective. A side effect advice. Patients had to experiment with their patterns of
reported by one person is not necessarily considered use. Typically those doctors were not willing to supervise
a side effect by another. For example, several patients use because of a lack of expertise, and the possible harms
dealing with insomnia did not regard drowsiness as and legal consequences arising from using medicinal
an adverse effect. While a craving for ‘sweets’ was a cannabis.
complication for patients who are attentive to maintaining
their weight, it was viewed by others as important given * In Belgium, physicians are allowed to prescribe unlicensed
medicines because of the so-called ‘therapy freedom’.
their condition meant they were dealing with weight loss.
As written in law, practitioners cannot be subject to regulatory
limitations in the choice of the medicines being used, either
for making a diagnosis, for setting up a treatment and its
execution, or for the execution of magisterial preparations.

44
Most patients sourced their own medicinal cannabis
and did not discuss this with their general practitioner
(family doctor) because of a lack of interest or a lack of
knowledge. As a result, these patients are not supervised
by a doctor. Patients therefore self-selected the cannabis
product, the dosage, the method of administration, and
when they took it.

Patients prefer to be supervised by a doctor however, and

regretted that few doctors had experience or knowledge
in medicinal cannabis. Often, it was the patient providing
insights and advice, turning the doctor-patient relationship
upside down.

Social cultural issues

What did their family or caregivers think?

For most patients, their use of medicinal cannabis was
accepted and supported by family and caregivers. They
noticed the difference medicinal cannabis made and
were glad the cannabis product appeared to relieve their
symptoms. Patients often explained the purpose of using
medicinal cannabis in order to gain acceptance.

Although most experience social support, some had to

deal with teasing comments, or stereotypical or negative
reactions because others were not pleased about a
patient’s ‘cannabis use’. Some patients deal with serious
consequences including conflicts in the home and at work. The future of healthcare
Most patients believe disapproval of medicinal cannabis is
because people are ill-informed and have a wrong image is in understanding and
of medicinal cannabis.
responding to patients’
needs and wants

45
 Insights from surveys
The table below compares findings from patient use surveys drawing on a global and Dutch perspective. The purposes of
both surveys were slightly different, but still provide useful insights.

A global perspective A Dutch perspective

General

In 2010, The International Association for Cannabinoid In 2016, a Dutch patient survey provided a snap shot of a
Medicines (IACM) surveyed patients from 31 countries. It is a group of patients. It is a large study of 582 participants (17% on
large study of 953 participants. These findings likely reflect the prescription). These findings likely reflect the total Dutch patient
diversity of the current global patient population. population receiving a prescription for cannabis.

Patients and the conditions being treated

Few patients had sourced their medication from a pharmacy Patients were prescribed medicinal cannabis for the treatment
(10%) or received a pharmaceutical product. This is not of conditions from pain through to severe mental illness.
surprising, considering in most countries the medical use of The top ten indications are spread across physical and
cannabis is illegal. The results therefore tend to reflect the use psychological disease states. These included pain, insomnia/
of herbal cannabis. sleeping disorder, nerve pain, spasms, stress, MS, depression,
anxiety, appetite, nausea and cancer.

Patients used medicinal cannabis to treat various conditions. The average daily dose was reported to be 0.67 grams/day for
The most common conditions were back pain, sleeping cannabis flos and 0.3 mL/day for oil.
disorders, depression, pain resulting from injury or accident, and
multiple sclerosis.

An average daily dose of 3.0 grams was reported for vaporizing At these doses, the majority (80+ %) patients reported some to
and smoking (median dose was 2.0 g/day and 1.5, respectively). substantial improvements in their quality of life and a reduction
in complaints resulting from their illness.

46
A global perspective A Dutch perspective

The mode of administration

The advantages and disadvantages of different administration There are various routes of administration for medicinal
forms were identified. Patients described their experience cannabis. Cannabis oil was the most commonly prescribed,
using different modes of delivery by the: dose needed, onset followed by vaporization and tea as popular modes of
of effect, duration of effect, ease of dose finding, ease of exact administration.
dosing, ease of preparation and intake, irritation of lungs, side-
effects and cost.

Patients reported high satisfaction (approval) scores with While smoking was also popular, it is evident that, like in other
the inhalation route. In general, whole plant cannabis based countries, patients look for alternatives to smoking. Patient use
medicines received higher appreciation scores than products of oil, or a move to administration by vaporization is evident.
containing isolated or single cannabinoids. The duration of effects and ease of dosing reported by study
respondents by the mode of administration were approximately
equivalent.

Study limitations

Most survey participants had experience with herbal cannabis The quasi-legal status of cannabis in the Netherlands means
and the results may be biased towards the use of herbal some cannabis may have been sourced outside of the
cannabis. pharmacy by patients also receiving prescriptions.

47
48
10 Legal perspectives
We have talked about the place of medicinal cannabis in the medical toolbox. This section
discusses why cannabis is treated differently from other medicines.

Marijuana or medicinal cannabis From medicinal cannabis to cannabinoid

The idea of what medicinal cannabis is varies across the therapeutics
globe. The number of patients with access to or having Medicinal cannabis is an old term used to describe the use
used pharmaceutical products is low, compared with illegal of cannabis to treat or manage illness. In recent years there
cannabis. have been major developments in cultivation techniques,
product quality and controls. Today, government regulators
Cannabis is the most commonly used illegal or quasi-legal seek the use of standardised products (e.g., Sativex®,
recreational drug worldwide. The recreational cannabis Marinol®, Bedrocan®) and safer modes of administration
economy is enormous. It supplies a large group of patients (sublingual, oral and inhalation by vaporization).
who otherwise do not have access to pharmaceutical-
quality cannabis products. However the quality of This change in focus from ‘medicinal cannabis’ to
recreational cannabis is often unreliable and unpredictable. ‘cannabinoid therapeutics’ reflects our knowledge and
Cannabis from this market has varying potency and is at understanding of the endocannabinoid system, the
risk of adulteration (for example, the addition of synthetic cannabinoid receptors, endogenous (human) cannabinoids,
cannabinoids, or other illegal drug substances). It likely also and exogenous (plant) phytocannabinoids. The future
contains fungi, bacteria and other microbial content, heavy appears to be about the therapeutic use of cannabinoids.
metals and foreign particles. The risk to patients is high, The class of medicines containing cannabinoids (e.g., THC
especially patients with weakened immune systems as we and CBD) and other chemical compounds secreted by
see with cancer. cannabis plant (e.g., terpenes) intended to be used for a
therapeutic purpose.
Today, across the globe, there are various ways in which
cannabis is supplied to patients. Put simply, two distinct A prescriber-pharmacy model
sources exist: the informal illegal/quasi-legal market, and Government regulators have to make tough calls on
the formal medical market under the control of medicine managing patient and health professional demand for
regulators. Under a formal model, medicinal cannabis products, alongside the need to ensure safety and efficacy
is often a last-resort medication, prescribed when other of products on the market. This is ruled by country specific
options have failed. regulations on controlled drugs and medicines.

49
 Two approaches exist. One is often described as an Typically, individual countries develop drug laws which
office of medicinal cannabis, controlling access to interact with medicines legislation and regulations. For
cannabis products separate to other medicines. The medicinal cannabis, a country’s regulatory and other
other is a medicine regulatory pathway, which treats control measures aim to:
medicinal cannabis the same as any other medicine. Both yy Control legal access and use of medicinal cannabis
approaches expect high levels of product quality, safety yy Allow access to adequate supplies of pharmaceutically
and efficacy. derived cannabis for medical purposes, in certain cases
yy Permit the cultivation and manufacture of cannabis for
Who can prescribe and dispense medicinal cannabis that purpose
depends on country specific policies and regulations. Most
often, health professionals are the gatekeepers to patient Signatory nations are obliged to carefully control the
access. In particular, doctors are allowed to prescribe import, export, and wholesale of cannabis and its
medicinal cannabis to treat a defined set of conditions preparations. This is most often the responsibility of a
and pharmacists can store and dispense reliable and safe country’s Ministry of Health who work closely with the
products for patients. International Narcotics Control Board (INCB) in Vienna.

Typically, a prescriber-pharmacy model offers patients All nations are required to facilitate a working relationship
better communication of risks and benefits, and the safety with the INCB. The INCB controls the global flow of
of health professional guidance. In some countries the cannabis and other controlled drugs intended for medical
therapeutic use of cannabis is well advanced. However, use. Individual countries provide an annual estimate of
in other countries medicinal cannabis is a new class of the national requirements for medicinal cannabis. These
medicines. In both situations health professionals will have estimates limit the amount of cannabis able to be accessed
variable knowledge, skills, abilities and attitudes. This is each year. This is to ensure that the legal manufacture
because, it is a topic which is not often talked about in of, trade in and use of cannabis is adequate for national
their medical training. And often practical, evidence-based medical and scientific requirements, with negligible
guidance and evaluation tools are not available to support diversion to the ‘black market’.
decision making by health professionals.
These are binding requirements. The idea is that limiting
The objectives of the UN Conventions access to controlled drugs makes them difficult to
The United Nations International Drug Control Conventions obtain and then be misused. It is the responsibility of the
are the pinnacle international agreement on the control of government regulators, health profession and patients to
narcotic drugs, such as cannabis. The Conventions require ensure there is no risk of diversion for misuse.
a global shared responsibility to control manufacture, trade
and use of controlled drugs.

50
Opium to opioids
The UN Conventions and country specific legislation permits the cultivation of opium
in Tasmania Australia, its shipment to global pharmaceutical manufacturing sites, its
distribution on the global medicine market, and the ability for a hospital or community
pharmacy to fill a patients codeine, morphine, or oxycodone prescription.

The cultivation, manufacture, distribution, and dispensing of opioids is carefully

controlled. These are the same requirements for cannabis, when used for therapeutic
purposes.

51
52
11 Glossary of terms Endocannabinoid system: the endocannabinoid system
is critical to the bodies overall homeostasis, and influences
all of our main organ and tissues systems. This is a unique
biological system; its mechanisms are responsive and
Cannabis terms capable of adaptation and thus allows for a biological
response aligned to system demand or environmental
Cannabinoids: naturally occurring or synthetic chemicals conditions.
that act on the cannabinoid receptors.
Endogenous: produced by the body, not delivered from
Cannabis: Cannabis sativa L. – a member of the external sources. The endogenous cannabinoids are
Cannabaceae family – contains a number of active called endocannabinoids.
elements. The main active constituents include THC (delta-
9-tetrahydrocannabinol) and CBD (cannabidiol). Entourage effect: suspected synergistic interactions
between cannabinoids and terpenes that lead to modifying
Cannabis flos: the whole dried flower of the cannabis or enhancing the therapeutic effects of cannabinoids
plant. in different ways. Terpenes are a major component of
Cannabis sativa L, responsible for the plant’s aroma and
Cannabinoid receptors: cell membrane receptors found taste. The therapeutic synergy between cannabinoids and
in the brain, the peripheral nervous system, and many terpenes has not yet been confirmed in clinical research.
organs and tissues. These receptors recognise our own
endocannabinoids and phytocannabinoids (i.e., THC, CBD) Medicinal cannabis: cannabis that is intended for thera­
from the cannabis plant. They are typically inclusive of the peutic use. Is prescribed by a trained medical professional,
CB1 and CB2 receptors, but also include other receptors for a known medical condition or a set of conditions where
that cannabinoids bind to. it has proven to be an effective treatment.

Decarboxylation: the cannabinoids exist mainly in Phytocannabinoids: cannabinoids that occur naturally in
an inactive acid form. The pharmacologically active cannabis and are derived from the cannabis plant. There
cannabinoids (e.g., THC/CBD) are formed when cannabis a number of known cannabinoids. The most studied
is heated to a temperature of at least 180°C resulting phytocannabinoids are delta-9-tetrahydrocannabinol (THC)
in ‘decarboxylation’. Specifically, decarboxylation is a and cannabidiol (CBD):
chemical reaction that removes a carboxyl group and
releases carbon dioxide (CO2). yy THC is the most well-known cannabinoid. THC is
responsible for many of the medicinal effects of
Endocannabinoids: the cannabinoids (endogenous cannabis. These may include, among others, reduction
neurotransmitters) produced naturally in the bodies of of nausea, vomiting, pain and muscle spasms, and
humans and animals that bind to cannabinoid receptors. improvement of sleep and appetite.

53
 yy CBD is another major cannabinoid. It has medicinal Harm: anything that impairs or negatively affects the
effects, but does not induce a psychotropic state (i.e. safety of patients. Medicine harms include adverse drug
its use does not result in feelings of intoxication). CBD reactions, treatment side-effects, and other undesirable
may be effective in conditions such as epilepsy, post- consequences from a health intervention. Medicine quality,
traumatic stress disorder (PTSD), and anxiety disorder. frequency of use and mode of administration modify the
Standardisation: pharmaceutical-quality cannabis flos type and severity of drug-related harms.
is the whole, dried flowers of the cannabis plant which
is genetically and chemically standardised according to Illegal: not according to or authorised by law (unlawful and
pharmaceutical standards, with a defined cannabinoid illicit); not permitted.
composition. Also, it is free of contaminants such as
microbial contaminants (moulds, fungi, and bacteria) Ligand: a ligand binds to a specific receptor. The ligands
pesticides (residues), aflatoxins, impurities and heavy of the cannabinoid receptor are called cannabinoids. The
metals. endogenous ligands of the cannabinoid receptor are
called endocannabinoids, while exogenous ligands are the
Synthetic cannabinoids: a class of man-made chemicals phytocannabinoids.
that bind to cannabinoid receptors, (typically) mimicking the
effects of THC. Medicine: the branch of medicine concerned with the
nonsurgical treatment of disease, and/or the alternative
Terpenes: the aromatic compounds which give cannabis its name for pharmaceuticals.
smell and taste. Each distinct cannabis variety has a unique
composition of terpenes. The terpenes are suspected to Misuse (of pharmaceuticals): to use a pharmaceutical
be involved in different interactions with cannabinoids. incorrectly; taking medication where the dose is increased
or used with the intention of achieving an intoxicating
Medical terms effect.

Dose: the specified amount of a medicine taken at one Oral: a medicine is taken by mouth; to be taken orally.
time.
Risk (factor): an aspect of personal behaviour or lifestyle,
Dosage regimen (therapeutic regimen): the number of an environmental exposure, or an inborn or inherited
doses in a given time period, and the time between doses, characteristic that is associated with an increased risk of a
that is chosen to reach the therapeutic objective (i.e., to person developing a disease.
treat the symptoms of a disease). This depends on the
drug used, the condition being treated, and the patient’s Route (administration of a drug): how a medicine is taken
characteristics. into the body, including the location it is applied. Common
examples include oral, inhalation, sublingual, and topical
administration.

54
Sublingual: ‘under the tongue’; referring to the route of Manufacture: the production of medicines or any part of
administration by which a medicine diffuse into the blood the process of producing medicines or bringing the goods
through tissues under the tongue. to their final state, including the processing, assembling,
packaging, labelling, storage, sterilising, testing or
Therapeutic terms releasing for supply of the goods or of any component or
Active ingredient: the therapeutically active component ingredient of the goods as part of that process.
in a medicine’s final formulation that is responsible for its
physiological action. Pharmacokinetics: the branch of pharmacology
concerned with the movement of drugs within the body;
Administration (mode of drug use): describes the way describing how a medicine is absorbed, distributed,
in which a drug is taken or used, includes for example metabolised and excreted from the body.
inhalation (vaporisation), ingestion or taking orally, and the
injecting of a drug substance. Pharmacovigilance: the collection and evaluation of
information from healthcare providers and patients on the
Batch: a quantity of a product that is (i) uniform in adverse effects of medicines.
composition, method of manufacture and probability of
chemical or microbial contamination; and (ii) made in one Therapeutics: the branch of medicine concerned with
cycle of manufacture and, if required, sterilised or freeze the treatment of disease and the action of medicines. A
dried in one cycle. treatment, therapy or drug.

Certificate of Analysis (CoA): a document of quality Therapeutic option: the idea that expanding medicine
assurance that confirms that a product meets its options for a disease provides the prescribing doctor with
specifications, and results of quality control test on the options to search for a more appropriate treatment for
individual batch of a product. their patient. This may be to reduce the number, frequency
or severity of side-effects, and also the total number of
Formulation (of a therapeutic product): the different medicines taken by the patient in their daily regimen.
chemical substances, including the active drug substance,
which are combined to produce a specific dose form.

Good manufacturing practice (GMP): the acronym GMP

is used internationally to describe a set of principles and
procedures for the manufacturer of medicines; it helps
ensure that the products manufactured are of a certain
quality.

55
56
12 Suggested reading

Administration and dose forms Clinical research reviews

Eisenberg, E., Ogintz, M., Almog, S. (2014). The Aviram, J. & Samuelly-Leichtag, G. (2017). Efficacy of
pharmacokinetics, efficacy, safety, and ease of use of a cannabis-based medicines for pain management: A
novel portable metered-dose cannabis inhaler in patients systematic review and meta-analysis of randomized
with chronic neuropathic pain: A phase 1a study. Journal of controlled trials. Pain Physician; 20:E755-E796.
Pain & Palliative Care Pharmacotherapy. 28: 3.
Ben Amar, M. (2006). Cannabinoids in medicine:
Pomaahcova, B., Van der Kooy, F., Verpoorte, R. (2009). A review of their therapeutic potential. Journal of
Cannabis smoke condensate III: the cannabinoid content of Ethnopharmacology; 105(1-2), 1-25.
vaporised Cannabis sativa L. Inhalation Toxicology.
21(13): 1108-12. Hazekamp, A., and Grotenhermen, F. (2010). Review on
clinical studies with cannabis and cannabinoids 2005-
Romano, L. and Hazekamp, A. (2013). Cannabis Oil: 2009. Cannabinoids; 5 (special issue):1-21.
Chemical evaluation of an upcoming cannabis-based
medicine. Cannabinoids; 1(1): 1-11. Kowal, M., Hazekamp, A., Grotenhermen, F. (2016). Review
on clinical studies with cannabis and cannabinoids 2010-
Chemistry 2014. Cannabinoids; 11 (special issue):1-18.
Hazekamp, A. (2006). An evaluation of the quality
of medicinal grade cannabis in the Netherlands. Nugent, N., Morasco, B., O’Neil, M., et al. (2017). The
Cannabinoids, 1(1), 1-9. effects of cannabis among adults with chronic pain and an
overview of general harms: A systematic review. Annals of
Hazekamp, A., Tejkalova´, K., Papadimitriou, S. (2016). Internal Medicine.
Cannabis: From cultivar to chemovar II - A metabolomics
approach to cannabis classification. Cannabis and Whiting, P., Wolff, R., Deshpande, S., et al. (2015).
Cannabinoid Research; 1.1. Cannabinoids for medical use: A systematic review and
meta-analysis. JAMA; 313(24):2456-2473.
Izzo, A., Borrelli, F., Capasso, R., Di Marzo, V., Mechoulam,
R. (2009). Non-psychotropic plant cannabinoids: New Patient use surveys
therapeutic opportunities from an ancient herb. Trends in de Hoop, B., Hazekamp, A., Kopsky, D., Wijnkoop, L. (2016).
Pharmacological Sciences; 30(10), 515-527. Experiences and motives of medicinal cannabis patients:
A cross-sectional questionnaire. Radbound Universiteit
Nijmegan. Sociologie BA3 – Stage: Arbeidsmarktoriëntatie.

57
 Hazekamp, A., Ware, M., Muller-Vahl, K., Abrams, D., Zuurman, L., Roy, C., Schoemaker, R., Hazekamp, A.,
Grotenhermen, F. (2013). The medicinal use of cannabis den Hartigh, J., Bender, J., Verpoorte, R., Pinquier, J.,
and cannabinoids: An international cross-sectional survey Cohen, A., van Gerven, J. (2008). Effect of intrapulmonary
on administration forms. Journal of Psychoactive Drugs. tetrahydrocannabinol administration in humans. Journal of
45 (3), 199–210. Psychopharmacology. 22(7):707-716.

Sexton, M., Cuttler, C., Finnell, J., Mischley, L. (2016). A

cross-sectional survey of medical cannabis users: Patterns
of use and perceived efficacy. Cannabis and Cannabinoid
Research; 1: 131-138.

Pharmacology
Fischedick. (2010). Cannabinoid receptor 1 binding activity
and quantitative analysis of Cannabis sativa L. smoke and
vapor. Chemical and Pharmaceutical Bulletin;
58(2): 201-207.

Mackie, K. (2008). Cannabinoid receptors: Where they are

and what they do. Journal of Neuroendocrinology,
20(s1), 10–14.

Pertwee, R. (2008). The diverse CB1 and CB2

receptor pharmacology of three plant cannabinoids:
Δ9-tetrahydrocannabinol, cannabidiol and Δ9-
tetrahydrocannabivarin. British Journal of Pharmacology.
153(2):199–215.

Russo, E. (2011). Taming THC: Potential cannabis synergy

and phytocannabinoid-terpenoid entourage effects. British
Journal of Pharmacology, 163, 1344-1364.

Skaper, S. and Di Marzo, V. (2012). Endocannabinoids in

nervous system health and disease: the big picture in a
nutshell. Philos Trans R Soc Lond B Biol Sci,
367(1607): 3193-3200.

58
 Disclaimer
This booklet reflects published data, information and clinical
insights as at June 2018. It mainly considers the use of medicinal
cannabis as a therapeutic product within a prescriber-pharmacy
model which is governed by traditional medicine frameworks.

This booklet is intended for information purposes only. It is

not intended to support decision making by prescribers and
pharmacists on the safe and effective use of medicinal cannabis
or cannabinoids. It should not be relied upon as a definitive text.

While all efforts have been made to ensure the accuracy and
scientific nature of information at the time of its production, the
author make no representations, implied or otherwise, as to the
safety and efficacy of medicinal cannabis or cannabinoids and
the methods of administration, until such time that reliable clinical
data is provided, nor to the contents of this booklet as certain
information may have become outdated due to rapid scientific
and clinical developments in this field.

Both the author and publisher accept no liability for any damage
that may result from the use of the information contained in
this booklet, and do not give any guarantees with regard to the
nature and the contents thereof. The author is not responsible for
any liability for damage of any kind, caused by third party content
Photo’s: Shutterstock and Bedrocan attached to, written or printed in or on this booklet.

59
 A primer to medicinal cannabis discusses the
therapeutic use of cannabis. That means we are
not talking about pot, marijuana, grass, or dope for
recreational use to get ‘high’. It focusses strictly on
medicinal cannabis. It is meant to give health care
professionals, regulators and patients insights into
the medical and scientific aspects of Cannabis
sativa L. and how this plant fits in the chain of
therapeutic options.

Date of preparation Copyright © 2018 by Bedrocan

June 2018
All rights reserved. No part of this document may be reproduced, distributed or transmitted in
any form or by any means, including printing, without the prior written consent of Bedrocan.