Cannabisbureau.nl

Ministry of Health, Welfare and Sports
Office of Medicinal Cannabis
P.O. Box 16144
2500 BC The Hague
The Netherlands

Medicinal Cannabis

Information for Health Care Professionals
Date of revision of the text: October 2013

1. Name of the medicinal product
Cannabis, dried flowers (Cannabis flos) There are four varieties: Variety
2. Qualitative and quantitative composition
Cannabis consists of the dried inflorescences of the female Cannabis sativa L. plant, and is cultivated and processed under standardised conditions in order to obtain a consistent product. Cannabis contains several constituents including substances that belong to the cannabinoids, such as dronabinol (delta-9-tetrahydrocannabinol, THC) and cannabidiol (CBD). The content of cannabinoids depends on the type of cannabis.
3. Pharmaceutical form
Dried female flowers (gamma-irradiated)

4. Clinical particulars

4.1 Therapeutic indications
There is adequate information available now, which proves medicinal cannabis can be
effective in the treatment of:
- disorders that involve spasticity with pain (multiple sclerosis, spinal cord injuries) - nausea and vomiting (resulting from chemotherapy, radiotherapy, and HIV combination therapy and medication by hepatitis C) - chronic pain (in particular neurogenic pain) - palliative treatment of cancer and AIDS especially to stimulate the appetite to decrease pain and to avoid weight loss and nausea If medical treatment with registered medicines is disappointing or there are too many side-effects with registered medicines, cannabis can be considered. Experiences of patients and doctors also mention a significant number of other indications. Ministry of Health, Welfare and Sports Office of Medicinal Cannabis
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Medicinal Cannabis can’t cure above-mentioned disorders. Cannabis can ease the
symptoms of the disorders or reduce the side-effects of medicines. It is up to a doctor to
decide when a patient can benefit from medicinal cannabis. The doctor isn’t bound by a
list of disorders.
Inhaling cannabis with a high content of dronabinol increases the risk of psychological
side-effects. This can be avoided by choosing a variety with a low content of dronabinol
or through oral administration (tea) when cannabis is used for the first time.

4.2 Posology and method of administration
The required amount of cannabis per day should be determined on an individual basis.
The starting dosage must be low. The dosage, which is necessary to achieve the desired
effects is often different/ lower than the dosage, which causes psychological side-effects
(get high). If a patient benefits from a higher dose, the cannabis can be increased
slowly.
Two methods of administration are recommended: oral administration or administration
through inhalation. Inhaling cannabis exhibits a stronger and faster therapeutic effect.
Oral (tea): (see also 6.6)
Drink 1 cup (0.2 litre) of tea in the evening, hot or cold.
When using this method, keep in mind that it will take an average of two weeks before
the maximum effect is achieved. If after roughly two weeks the result is too limited or
unsatisfactory, the patient can drink one extra cup (0.2 litre) in the morning.
Inhalation (vaporizer): (see also 6.6.)
The recommended starting dose is 1-2 times a day. Inhale a few times until the desired
effect is reached or until psychological side-effects occur. Wait 5-15 minutes after the
first inhalation and wait between inhalations. When using the inhalation method, the
strength of the cannabis must be kept in mind. Be careful about the dosage when you
switch from one variety of cannabis to another, especially if you use cannabis with a
higher content of dronabinol. With repeated administration of cannabis, it will take 2
weeks to get the steady-state concentrations of dronabinol. This must be kept in mind in
deciding the activity of the drug.

4.3 Contra indications
Patients with a tendency to get psychotic illnesses would definitely advised not to use
cannabis. Exercise great restraint to patients with underlying psychological problems.

4.4 Special warnings and precautions
Inexperienced users can be frightened by the psychological effects of cannabis. It is
advised to administer cannabis for the first time in a quiet and familiar setting, and in
the presence of another person who can calm down the patient if necessary.
Smoking is not recommended. Cannabis smoke contains harmful combustion products, including carcinogens and carbon monoxide. As a result, frequent use of smoked cannabis over a long period of time presumably exposes users to health risks associated with smoking. Smoking cannabis can impair pulmonary function (histopathological Ministry of Health, Welfare and Sports Office of Medicinal Cannabis
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changes in the mucous membranes) and reduce resistance to infection. Regular cannabis smokers can develop pharyngitis, rhinitis and COPD (Chronic Obstructive Pulmonary Disease). To limit the damage caused by combustion products, cannabis can be inhaled by a vaporizer. Patients with heart diseases (heart arrhythmias, angina pectoris) should avoid high doses of cannabis because of the cardiovascular side-effects (in particular tachycardia). Tolerance to these effects develops within a few days to weeks. The dosage may only be increased slowly as indicated by the effects on the heart. 4.5 Interactions with other drugs and other forms of interaction
It is known that the use of cannabis at the same time with other tranquillizing
substances such as alcohol, benzodiazepines and opiates cause cumulative effects. If
there is a combination of cannabis with an opiate, the dose of the opiate can often be
decreased. Provided that the analgetic effect improves or stays the same, the opiate can
also give less side-effects. There hasn’t carried out research to interactions with other
drugs.
Because of the high first-pass effect in the liver, particularly in the case of oral
administration of cannabis, it is possible that pharmacokinetic interactions could occur
with drugs, which are broken down by the isoenzymes CYP2C9 and CYP3A4 in the
cytochrome P450 system. Drugs that inhibit these isoenzymes are macrolides (in
particular claritromycin and erythromycin), antimycotics (itraconazole, fluconazole,
ketoconazole and miconazole), calcium antagonists (in particular diltiazem and
verapamil), HIV protease inhibitors (in particular ritonavir), amiodarone and isoniazid.
Simultaneous use of the enzyme inhibitors mentioned above can increase the
bioavailability of dronabinol and with that, the possibility of additional side-effects.
Drugs that accelerate the breakdown of dronabinol via the isoenzymes mentioned are
rifampicin, carbamazepine, phenobarbital, phenytoin, primidone, rifabutin, troglitazone
and Saint John’s Wort. If a patient stops taking one of these drugs, there can be an
increase in the bioavailability of dronabinol.
Interactions are also possible with drugs which (like dronabinol) are strongly bound to
plasma proteins.
4.6 Pregnancy and breastfeeding
Use of cannabis during pregnancy should be avoided. It is known that dronabinol reaches
the fetus via the umbilical cord. Research indicates growth retardation when cannabis is
used during pregnancy. School-aged children who were exposed to cannabis while in
utero have a normal overall IQ but score lower on certain aspects (in particular, in their
ability for abstract-visual reasoning, memory function, and the executive function, which
is the ability to demonstrate flexible, purposeful behaviour). Hyperactivity, concentration
problems and impulsivity are also reported in 10-year olds. Dronabinol is detected in
breast milk. Therefore, the use of cannabis while breastfeeding is not recommended.


Ministry of Health, Welfare and Sports Office of Medicinal Cannabis
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4.7 Effects on ability to drive and use machines
The use of cannabis can reduce the ability to react and can cause a lower concentration.
This may create problems in carrying out everyday activities. Participating in traffic and
operating machines are not recommended.
4.8 Side-effects
The psychological side-effects of cannabis can vary widely, and depend on several
factors: the amount of cannabis which is used, the method of administration, the
patient’s experience with cannabis and personal constitution, such as the person’s state
of mind at the time of use and how impressionable the user is to experiencing the
effects. A person can become “high” after using cannabis. This is a feeling of euphoria
that slowly changes into a pleasant sensation of calmness and tranquility. Users can also
experience other effects while they are “high”, such as sedation, cheerfulness with fits of
laughter, hunger, a heightened sensitivity to perceptions of colour and music, a
disrupted sense of time and space, and lethargy. This altered perception can give rise to
a sense of anxiety, panic and confusion. Restlessness and insomnia are also reported.
Cannabis can sometimes provoke a psychotic reaction, characterized by delusions and
hallucinations. A genetic relationship between cannabis use and schizophrenia has been
established, although it is not clear whether the relationshop is causal.
Physical side-effects of cannabis are:
- sense of hot or cold in hands and feet - in cannabis smokers (and after inhaling): irritation of the bronchial tubes These effects are temporary and disappear a few hours after use. Long term and intensive use of cannabis is presumed to have an effect on cognition, but this is reversible. In some cases, cannabis use can result in cannabis dependence and cannabis excess. Chronic users who use high doses can experience physical withdrawal symptoms such as mild forms of restlessness, irritability, insomnia and nausea if they stop. 4.9 Overdose
An overdose of cannabis may cause depression or feelings of fear, even feelings of panic
and fainting are possible. In general the symptoms disappear spontaneously in a few
hours. In case of overdose, benzodiazepines (diazepam IV) can be administered.
Tachycardia can be treated with a beta blocker (propranolol IV).
Ministry of Health, Welfare and Sports Office of Medicinal Cannabis
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5. Pharmacological properties

5.1 Pharmacodynamic properties
Cannabinoids act on the cannabinoid receptors. At least two different receptors (G-
protein coupled receptors) are identified: CB and CB receptors. CB receptors are found
particularly in the central nervous system, while the CB type occures peripheral especially in the immune system and gastrointestinal tract. 5.2 Pharmacokinetic properties
Absorption
The absorption of cannabinoids in the body is determined by the method of
administration. When cannabis is inhaled, the cannabinoids are absorbed into the blood
within minutes via the lungs and are transported to the brain. The concentration of
cannabinoids in the brain reaches a maximum within 15 minutes, which coincides with
the peak of the psychological and physiological effects. Absorption differs per individual
and depends on various factors, including the heating of the cannabis, the number of
inhalations, the waiting time between two inhalations, the inhalation time and lung
capacity.
When cannabis is taken orally, absorption of cannabinoids in the blood is slow and more
unpredictable. This results in the psychoactive effect being delayed 30 to 90 minutes
with the maximum effect being experienced two or three hours later. The effect lasts
four to eight hours. The result of dronabinol concentration in the blood with oral intake is
25-30% in relation to inhalation. This is partly caused by the large first-pass effect in the
liver.
Distribution
After being absorbed, the cannabis constituents are distributed through-out the body.
The concentration of cannabinoids rises the quickist in the tissues with large blood
supply: such as brains, lungs, liver and kidneys. A substantial portion of the dronabinol is
stored in fatty tissue. Dronabinol and its metabolites are strongly bound to plasma
proteins. The distribution volume of dronabinol is 10 liter per kilogram of body weight.
Elimination
In the liver, isoenzymes CYP2C9 and CYP3A4 of the cytochrome P450 system initially
convert dronabinol to 11-hydroxy-THC (11-OH-THC), a metabolite that is biologically
active. This connection probably contributes to some of the effects of cannabis. The
metabolite 11-OH-THC is further converted to 9-carboxy-THC (THC-COOH), which is
biologically inactive. A range of other inactive metabolites are also formed. The
elimination half-time of dronabinol and 11-OH-THC is 25-36 hours. Dronabinol
metabolites can be detected in the urine up to several weeks after the last use of
cannabis.
Ministry of Health, Welfare and Sports Office of Medicinal Cannabis
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6 Pharmaceutical information

6.1 List of excipients
Not applicable.
6.2 Cases of incompatibility
Not applicable.
6.3 Shelf life
Cannabis can decompose under the influence of light and moisture. Cannabis can be
stored in the original packaging until the expiry date indicated on the package.
6.4 Special precautions for storage
Store in the original package at room temperature (15-25 C).
6.5 Type and content of the packaging
Cannabis is available for pharmacies in 5-gram packages.
6.6 Instructions for use and processing
In cannabis, the cannabinoids are primarily present as pharmacologically inactive acids
(for example, THC acid). Heating gives rise to free molecules through decarboxylation.
Therefore, a heating step must always be carried out before administration.
Using the vaporizer
See the instructions enclosed with the device. The active ingredients of cannabis can be
evaporated if the cannabis is heated. Subsequently, they can be inhaled without
combustion. The right temperature has been reached when a vapour is just visible (a
light mist) but no smoke has formed (thick clouds). When the vaporizer has a
thermostat, the temperature must be set at 180-195 C. It is possible to re-use the same cannabis 2-3 times in the inhaler. Making tea Boil half a gram of cannabis for 15 minutes in half a litre of water in a covered pan. Before using, strain the solid ingredients from the tea. Sweeten the tea as desired with honey or sugar. If you want to consume the tea, which is left, the same day, you can keep it in a thermos flask. When the tea is made for several days it is possible to store it in the refrigerator for 5 days. A fatty substance such as milkpowder must be added to the tea to keep the concentration of active ingredients in balance. Ministry of Health, Welfare and Sports Office of Medicinal Cannabis
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7. Particulars
In the Netherlands cannabis is mentioned in the Opiumact (list II). Cannabis is regarded as dope by the International Olympic Committee (section III: list of forbidden drugs under special conditions) In the Netherlands it is possible to cross the border with cannabis in the same way as other narcotic drugs: 1. If a Dutch citizen goes to a country that signed the Treaty of Schengen, the person can get a certificate at the Dutch Health Inspectorate. 2. If a Dutch citizen goes to a country outside the Schengen countries, the person has to go to the embassy of that country for a certificate. There is always a risk of prosecution when you cross the border with cannabis without a certificate. Many countries punish severely in case of importing cannabis or using/possessing cannabis. Cannabis is placed on the market as Cannabis flos by the Office of Medicianal Cannabis. The OMC is a department of the Ministry of Health, Welfare and Sports in the Netherlands
Import
A foreign company or pharmacy can import medicinal cannabis.
The Office of Medicinal Cannabis needs official documents for an import procedure: 2 original import licences A letter with the amount of medicinal cannabis, which is needed, and the indication of After the OMC has received those documents it will apply for an export licence at the Dutch Health Inspectorate. The OMC draws up a contract and will send the contract with an invoice together to the applicant. If the OMC receives the signed contract and the invoice has been paid, the OMC will export the medicinal cannabis to the applicant.

Source: http://www.cannabisbureau.nl/en/doc/pdf/Information%20for%20Health%20Care%20Professionals%20(version%20October%202013)_18980.pdf