The Italian pharmacist Dr Marco Ternelli received so many requests from doctors and patients about how to prescribe medicinal cannabis that he decided to put all the information together. Prescribing in Italy is not an easy matter. Doctors have little knowledge, do not know how to dose cannabis, and there are complicated forms a doctor should fill in to prescribe.

By now his clients come from all over Italy, albeit mainly from north and central Italy. For over three years, he saw 10,000 to 15,000 prescriptions for medicinal cannabis (oils, capsules, suppositories, eye drops and creams) pass through his hands for the most wide ranging conditions. He incorporated all those data in a comprehensive brochure (only available in Italian). It contains an overview of all the cannabis prescriptions he has handled over the years. ”It is a sort of personal statistics I decided to share. Reporting the strains prescribed by Italian doctors and what conditions they prescribe them for.”

Besides doctors, other pharmacists and patients benefit from the information in his blog. Dr Ternelli continued “Pharmacies and pharmacists understand how a prescription for medicinal cannabis has to be completed by doctors to be accepted and for them to be permitted to proceed with the compounding preparation. In other words, what pharmacists need to check to consider the prescription as valid.”

Our brochure ‘A primer to medicinal cannabis’ has been revised by adding the latest research in the area of medicinal cannabis. Ideal for healthcare providers, policy makers and patients who would like to have more insight into the medical and scientific aspects.

The Leiden University Medical Center (LUMC) is looking for fibromyalgia patients who wish to participate in a new study into the effects of medicinal cannabis on the medication oxycodon. Patients may register through a special website of the Anaesthesiology Department. Lead researcher Professor Albert Dahan aims to demonstrate that medicinal cannabis in combination with the opiate product oxycodon may have added value in pain relief.

The main purpose of the study is to assess whether co-medication with Bediol reduces the side effects of oxycodon in patients with chronic pain. The study will run for several years. According to the Professor it will be a complex study, because the patients may determine the dose they take. “We will give a maximum, but within that limit patients may determine what they use.” Furthermore, the study takes place in patients’ homes. They will be given a vaporiser that can be used to take the cannabis. “This set-up will definitely succeed, because our researcher will be in continuous contact with the patients.”

“Even in a country like America, where a form of cannabis is legalised in most States, pain specialists do not know how to prescribe or dose medicinal cannabis. I know I cannot make any recommendations on the basis of this experimental study, but I can set them on their way.”

If you are interested in participating in the LUMC study, you can register with the online form on the Dutch website Samen tegen Pijn.

The Dutch Ministry of Health, Welfare and Sport (VWS) has made 1.9 million Euro available for research into the effectiveness of medicinal cannabis for neuropathic pain. The Ministry instructed ZonMw, a Dutch stimulus fund for healthcare, to look for suitable research. The subsidy will be awarded to one Dutch research organisation, knowledge institute or other type of organisation.

A maximum of 1.9 million Euro is available for the entire project over a maximum period of four years.

Bedrocan was able to answer many questions from international pharmaceutical companies at the world’s largest pharmaceutical trade fair CPhI Worldwide in Frankfurt, Germany. There was a significant amount of interest from companies that aim to use cannabis as raw material for medication.

From November 31 to November 2, Berlin is the setting for the Cannabinoid 2019 conference. The conference, organized by the International Association for Cannabinoid Medicines (IACM) aims – just like the IACM itself – to advance the knowledge on cannabis, cannabinoids, the endocannabinoid system and their therapeutic potential.

In Italy, access to cannabis-based medicines is complicated because of the ‘excess of bureaucracy’, according to Dr Marco Bertolotto, an Italian pain specialist. Dr Bertolotto is an experienced prescriber of cannabis-based medicines, having already treated more than 2500 patients. While other Italian doctors do not even consider prescribing. Dr Bertolotto points out: “Every step is complex and insidious. A serious error can be punishable by law. Every step has a trap inside.” Limited prescribing means few patients access medicines they could benefit from. “It is a recurrent story. Patients suffer from the disease and from the lack of therapy.”

Dr Bertolotto runs a regional pain clinic and palliative care centre ASL2 in Liguria, Italy. At the end of 2018 he launched a personal website with information about the use of cannabinoids as a medicine. Due to a special Bedrocan cannabis Masterclass in December 2015 in the Netherlands, Dr Bertolotto and a small group of Italian medical experts were trained in depth on the use of medicinal cannabis according to Bedrocan standards. He now considers himself an expert and an Italian pioneer in the field. “My experience started five years ago, at the start of the Italian medical cannabis programme. I found out that there was a group of patients that were suffering and had tried so many drugs, without efficacy. They were looking for an alternative and an expert doctor who could help them.”

Despite the maze of rules, Bertolotto’s motto to doctors starting out prescribing is ‘not to be afraid. Throw away your bias, your preconceptions and try. Choose the dosage by starting low, and continue going slow. Follow the patient day by day.” Bertolotto also provides advice with regards to which administration form to use. “It depends of the patient and the disease. I normally prefer to use oil, because the titration with drops is easy, but I also prescribe cannabis dried flower by vaporization.” As Western medicine is entirely based on scientific evidence that requires randomised, double-blind studies there is unfortunately still not enough evidence. Bertolotto about this issue: “This is a big problem as doctors are therefore reluctant to prescribe. Evidence based medicine is not adapted to studying cannabis-based medicine. We need a different approach. My personal approach, that I will present later this week at the Italian Cannabis Business conference, is called Personalised Medicine. We collect and analyse a lot of data until we have an algorithm to help doctors.”

On 22 and 23 October, Warsaw will see the first Central European Cannabis Forum Conference in Poland. Bedrocan will be presenting the company and the latest news on its clinical research. We spoke to the man behind this first time event, Andrew de Roy, to find out why he decided to organise this event in Poland and the goals he wants to achieve.

Andrew de Roy has been a risk consultant and corporate investigation specialist. He has built over the past twelve years Bearstone Global, a risk consultancy with offices in Poland, Berlin and opening in London. Over this time they have increasingly been working in the space of medical cannabis as the industry has developed at such great speed over the past few years.

‘The industry is not only fast moving but obviously also controversial, as the industry goes from Black to White, most visibly in North America, but also in greater frequency in Europe. As the industry has developed, Poland is one of the more interesting countries in Europe in terms of progressive laws and numbers of registered patients. The industry requires the development of a more organised ecosystem and the ability to speak with one voice on issues which are key for the whole industry in general,’ De Roy explains.

‘Patients are the most important here’

He organises the event in order to educate, network and help the industry to speak with one voice in Poland, and to help regional integration within the industry. De Roy: ‘I am convinced that Poland has huge potential to develop businesses, as well as be a leader in an industry which still has such a significant room for innovation and development. We hope that the conference will result in a Memorandum of Understanding for a Polish Medical Cannabis Association. We hope that a more collaborative approach will assist everyone within the ecosystem, from cultivators to companies, and of course right through to the patients, who are the most important here.’

‘Future is promising, but process is difficult’

Looking at the future, De Roy sees huge potential in Poland, but it is not easy: ‘The election on October the 13th will likely show a lot! We have just had four new products registered in Poland raising the overall number to five, and there is a significant pipeline of products in line. There are rumors that all registrations have been halted, but this has not been verified officially, and there is much confusion about this. What is certain is that at present the process is cumbersome and difficult. We also have issues in terms of access for patients and cost, which is very much in line with many others in Europe.’

There has been a lot of talk in the media about the risks of vaping. This article discusses the differences between vaping and the administering cannabis flos by vaporization.

Not all vaporizers are the same

Many of us have heard of vaporizers, and instantly we think of ‘e-cigarettes’ or ‘vape-pens’. However, these are not the only types of devices available. Vaporizers (as medical devices) for the administration of cannabis flos [1] are in fact quite different from ‘vape-pens’ or ‘e-cigarettes’.

The vaporizer vapour does not contain nicotine, or carrier agents such as liquid propylene glycol, glycerol, or vitamins and synthetic flavours. [i] [ii] [iii] The large, socially intrusive vapour clouds of ‘e-cigarettes’ do not apply for the medicinal use of cannabis flos by vaporization.

Vaporization devices do not include liquids, rather dry cannabis is heated by precise temperature control, efficiently releasing active ingredients without toxic by-products.

Vaporization devices offer patients an effective, safe, and easy to use delivery system for cannabis flos. [iv] [v] The inhaled vapour contains THC, CBD, and terpenes [2] in consistent, measurable quantities. The use of a high quality vaporizer device avoids the respiratory disadvantages of smoking, [vi] and of the inhalation of compounds from liquid vape-pens.

An efficient administration route

The most efficient administration route of medicinal cannabis is by inhalation. Indeed, administration by inhalation is a rapid way to induce measurable serum levels of cannabinoids. [vii]

A vaporizing medical device, compared to smoking or vaping, [3] dramatically lowers concentrations of toxic compounds such as carbon monoxide, ammonia and polyaromatic carbohydrates (PACs). Compared to smoking, higher therapeutic levels of THC and consistent, reproducible THC extraction and delivery is possible. [viii] [ix]

The vapour is quickly absorbed by the lungs, permitting patients to effectively titrate to optimise their dose based upon symptom severity, tolerability and avoidance of side-effects. The rapid onset of effects of inhaled cannabinoid use allows easier titration of dose, while standardised cannabis products enable patients to administer an exact dose. [vi] [x][xi][xii]

Patient perspectives and providing therapeutic options

Prescribers, pharmacists and patients should be aware of this differences between ‘vaping cannabinoids’ and ‘vaporising cannabis flos’.

The importance of vaporization is underlined in patient use surveys. The majority of survey respondents report higher satisfaction (approval) scores with the inhalation route. In general, whole plant, herbal cannabis-based medicines received higher scores than other products containing isolated cannabinoids. [viii][xiv]

Patients seek a reliable, affordable and portable vaporizer for administering cannabis flos. Presently there is research dedicated to advancing administration technology. Some examples of major developments in vaporizer devices, using standardised cannabis flos, include the Volcano® and Mighty Medic vaporizer (Storz & Bickel) [xv] [xvi] [xvii], and the Syqe® Inhaler [xviii] [xiv].  All devices have relied on Bedrocan standardised cannabis flos for their quality testing and clinical trials.

Vaporizer medical devices, delivering standardised doses, underline quality assurance, safety, and efficacy. With these administration technical advancements, smoking of cannabis flos can soon be a thing of the past. Backed by proper scientific studies, cannabis flos will become an acceptable therapeutic among patients, prescribers, and regulatory authorities. [xx]

Future thinking – critical policy decisions

It should be recognised that vape-pens for inhalation of cannabinoids often are not subjected to any technical or clinical testing. While, by comparison, a number of the devices for administering cannabis flos by vaporisation have robust supporting clinical and technical studies.

With regard to administration, future policy must be clear and obvious. For example, in the Netherlands, Germany, Australia and New Zealand, smoking cannabis flos is actively discouraged and/or not permitted, respectively. While the clinical guidelines support cannabis flos for inhalation administered by vaporization.

While there are similarities between the administration methods – vaping vs vaporisation – a blanket ban on inhalation or on vaporizer devices for administering cannabis flos would be nonsensical. This would have implications for administration options and prescriber-patient choice. It would also impact on their valid use in hospitals and hospices, rest-homes, and home settings.

[1] Fully-standardised, pharmaceutical-quality cannabis flos is the whole, dried flowers of the cannabis plant which is genetically and chemically standardised according to pharmaceutical standards with a defined cannabinoid and terpene composition. Also, it is free of contaminants such as microbial contaminants (molds, fungi, and bacteria) pesticides (residues), aflatoxins, impurities and heavy metals.

[2] Terpenes are a major component of Cannabis sativa. Responsible for the plant’s aroma, terpenes may also act synergistically with the cannabinoids. ^x

[3] When administering pharmaceutical quality cannabis flos.

References

[i] Douglas, H., Hall, W., Gartner, C. (2015). E-cigarettes and the law in Australia. Australian Family Physician. 44 (6): 415-418.

[ii] Jensen, P., Luo, W., Pankow, J., Strongin, R., Peyton, D. Hidden formaldehyde in e-cigarette aerosols. New England Journal of Medicine. 372 (4): 392-393.

[iii] Editorial and Review (2019). E-Cigarettes and Vaping-Related Disease. New England Journal of Medicine. Online: https://www.nejm.org/vaping

[iv] Eisenberg, E., Ogintz, M., Almog, S. (2014). The pharmacokinetics, efficacy, safety, and ease of use of a novel portable metered-dose cannabis inhaler in patients with chronic neuropathic pain: A Phase 1a study. Journal of Pain & Palliative Care Pharmacotherapy. 28:216–225.

[v] Hazekamp, A., Ruhaak, R., Zuurman, L., van Gerven, J., Verpoorte, R. (2006). Evaluation of a vaporizing device (Volcano) for the pulmonary administration of tetrahydrocannabinol. Journal of Pharmaceutical Sciences. 95(6):1308-17.

[vi] Pomaahcova, B., Van der Kooy, F., Verpoorte, R. (2009). Cannabis smoke condensate III: the cannabinoid content of vaporised Cannabis sativa. Inhalation Toxicology. 21(13): 1108-12.

[vii] Grotenhermen, F. (2003). Pharmacokinetics and pharmacodynamics of cannabinoids. Clinical Pharmacokinetics. 42: 327-360. Also, Grotenhermen, F. (2004). Clinical pharmacodynamics of cannabinoids. Journal of Cannabis Therapeutics. 4(1): 29-78.

[viii] Abrams, D., Vizoso, H., Shade, S., et al. (2007) Vaporization as a smokeless cannabis delivery system: a pilot study. Clinical Pharmacology and Therapeutics. 82 (5): 572 – 8.

[ix] Gieringer, D., Laurent, J., Goodrich. (2004). Cannabis Vaporizer Combines Efficient Delivery of THC with Effective Suppression of Pyrolytic Compounds. Journal of Cannabis Therapeutics. 4(1)

[x] Hazekamp and Heerdink (2013). The prevalence and incidence of medicinal cannabis on prescription in The Netherlands. The European Journal of Clinical Pharmacology.

[xi] Van de Donk, T., Niesters, M., Kowal, M., Olofsen, E., Dahan, A., Van Velzen, M. (2019). An experimental randomized study on the analgesic effects of pharmaceutical-grade cannabis in chronic pain patients with fibromyalgia. Pain; 160: 860–869.

[xii] Russo, E. (2011). Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. British Journal of Pharmacology. 163: 1344–1364.

[xiii] Hazekamp, A., Ware, M., Muller-Vahl, K., Abrams, D., Grotenhermen, F. (2013). The medicinal use of cannabis and cannabinoids: An international cross-sectional survey on administration forms. Journal of Psychoactive Drugs. 45 (3), 199–210.

[xiv] de Hoop, B., Hazekamp, A., Kopsky, D., Wijnkoop, L. (2016). Experiences and motives of medicinal cannabis patients: A cross-sectional questionnaire. Radboud Universiteit Nijengen, the Netherlands. (Unpublished work)

[xv] The Volcano® Medic vaporizer medical device is listed on the Medical Devices Active Licences Listing (Health Canada), licence No.: 82405.

[xvi] Hazekamp, A., Ruhaak, R., Zuurman, L., van Gerven, J., Verpoorte, R. (2006). Evaluation of a vaporizing device (Volcano) for the pulmonary administration of tetrahydrocannabinol. Journal of Pharmaceutical Sciences. 95(6):1308-17.

[xvii] Pomahacova, B., Van der Kooy, F., Verpoorte, R. (2009). Cannabis smoke condensate III: the cannabinoid content of vaporised Cannabis sativa. Inhalation Toxicology. 21(13):1108-12.

[xviii] Eisenberg, E., Ogintz, M., Almog, S. (2014). The pharmacokinetics, efficacy, safety, and ease of use of a novel portable metered-dose cannabis inhaler in patients with chronic neuropathic pain: A Phase 1a study. Journal of Pain & Palliative Care Pharmacotherapy. 28:216–225.

[xix]  Vulfsons S, Ognitz M, Bar-Sela G, Raz-Pasteur A, Eisenberg E (2019). Cannabis treatment in hospitalized patients using the SYQE inhaler: Results of a pilot open-label study. Palliative and Supportive Care, 1–6.

[xx] Van de Donk, T., Niesters, M., Kowal, M., Olofsen, E., Dahan, A., Van Velzen, M. (2019). An experimental randomized study on the analgesic effects of pharmaceutical-grade cannabis in chronic pain patients with fibromyalgia. Pain; 160: 860–869.

Bedrocan will be present at the world’s largest pharmaceutical exhibition, CPhI Worldwide. At the fair we will present ourselves as the first GMP supplier of plant-based full-spectrum cannabis APIs. CPhI gathers over 45,000 pharma professionals from around the globe with more than 2,500 international exhibitors. It is the place for Bedrocan to network and meet pharmaceutical companies that are interested in cannabis as an active pharmaceutical ingredient. (API).

Global trend

A global trend has arisen: Prescribers are becoming more familiar with cannabis-based medicines and prescribing them. The increasing demand for pharmaceutical quality cannabis-based medicines has resulted in greater need for reliable and consistent APIs.

Text continues below the announcement.

In their quest for a reliable source of API, pharmaceutical companies are increasingly finding their way to Bedrocan.

This is unsurprising given Bedrocan is the only fully GMP-certified producer of standardised medicinal cannabis in the world. Founder and CEO Tjalling Erkelens talks about standardised pharmaceutical quality medicinal cannabis.

Can you define standardised medicinal cannabis?
“It refers to cannabis products that are consistent in terms of its active ingredients – the cannabinoids tetrahydrocannabinol (THC) and cannabidiol (CBD), but also the terpenes which are the aromatic compounds. Bedrocan produces five different varieties of medicinal cannabis. They are produced in accordance with pharmaceutical quality requirements, because our production sites comply with the requirements imposed by GMP – from cultivation to packaging. Each variety shows a constant composition of cannabinoids and terpenes; batch-to-batch, year after year. That’s what we call standardised medicinal cannabis. We have been doing this for over two and a half decades now. And we’re only getting better.”

Why standardisation?
“To us standardisation is a core concept. It is the essence of our mission and vision that were defined years ago but that are still relevant today. The patient is at the heart of all this. Prescribers, pharmacies and patients expect a safe product that works. They expect a product that complies with all the pharmaceutical production requirements, and that starts with high quality starting materials. The pharmaceutical industry needs an API that is consistent in its composition to develop and manufacture novel cannabis-based medicines.”

How do you achieve pharmaceutical standardisation with cannabis?
“Over the past 25 years we have developed and refined a unique method that has taken cannabis to the level of a pharmaceutical API. It starts with stable plant genetics, followed by a series of processes that are fully standardised and controlled. Our cannabis is produced under climate-controlled conditions, with minimised external influences. Furthermore, Bedrocan was the first medicinal cannabis producer to be compliant with the European Medicines Agency’s GMP standards, covering the whole production process.”

How does the pharmaceutical industry benefit from this?
“Bedrocan is the world’s first GMP producer of standardised, full-flower medicinal cannabis. Consequently, our API offers seamless GMP finished product manufacturing. We offer both blended and genetically distinct herbal preparations suitable to develop novel, cannabis-based medicines.”

Unlike other medication, cannabis does not have a fixed chemical/molecular composition. A cannabis plant contains hundreds of different substances and each individual plant is different in terms of its composition. THC and CBD are the best-known substances, but there are dozens to hundreds of other known and unknown substances in the plant that may have an effect. No two cannabis plants are the same. Even if the levels of THC and CBD are the same, the substances around them can produce a different effect for the patient; this known as the ‘entourage effect’. There have been various studies of this entourage effect. Ultimately, the complete ‘fingerprint’ of the plant determines its effect.

Four crucial reasons why medicinal cannabis should be standardised

In the Netherlands, there are now five medicinal cannabis varieties available. Each variety has a unique, fully standardised genetic composition that is and remains the same each time, for every batch, year in, year out, because of the unique production process. The result is that the CBD and THC levels are always the same, but the other substances are also always present in the same ratio. The reproducible chemical profile enables doctors to monitor the dose and the effect on the disorder in the same way as for other certified medication. Furthermore, it makes these varieties suitable for carrying out scientific medical research.

1. PATIENTS

Constant availability of a standardised product is extremely important to the patient

Just like ‘normal’ medication, all patients are ‘set’ on a certain variety. Sometimes it can take a long time to get patients on the right variety with exactly the right dose on the basis of the existing five varieties. The same applies to the use of cannabis oil. Changing the dose or administering medication with a different genetic composition can have adverse consequences for individual patients. In some cases medicinal cannabis oil is used for children and adults with serious epilepsy. The Dutch Epilepsy Fund and doctors recommend changing brands as little as possible for epilepsy medication, because somebody can end up with a seizure after changing medication.

2. DOCTORS

Constant availability of a standardised product is extremely important to the doctor

Quite rightly, doctors want to know exactly what they give to their patients and what its effects are. It takes a lot of time and effort for doctors to become used to prescribing cannabis. The reproducible chemical profile of standardised medicinal cannabis enables doctors to monitor the dose and the effectiveness in the same way as for other certified medication. As this medicinal cannabis is also produced in accordance with pharmaceutical standards (GMP), quality and safety are guaranteed as much as possible. As doctors have prescribed the same products from the Office of Medicinal Cannabis for years, they know what it does and they feel comfortable with it. The same applies to the pharmacists who ultimately hand over the product.

3. RESEARCHERS

Constant availability of a standardised product is extremely important to researchers and clinical research

For the first time, there is now larger scale serious clinical research into the effect of medicinal cannabis. In December 2018, the first results were published of a placebo-controlled, comparative study of 3 of the 5 varieties available in the Netherlands, carried out by the University Medical Centre Leiden. Different doctors, pharmacists, and study groups are now preparing further clinical research. They prefer to work with standardised medicinal cannabis that has a guaranteed quality, safety and availability.

In order to obtain permission for medical scientific research with humans, you need a detailed statement of the product that is studied. At the end of the study, the outcomes only say something about the specific plant, and its unique genetic composition, that was used in the study. Clinical research that is carried out with the existing Bediol variety, can only be carried out with that plant. Changing variety in the meantime is not possible from a substantive point of view, it is legally impossible, and certainly not desirable. If there were to be a change to a plant with only comparable THC and CBD levels, permission for the research would have to be applied for again. THC and CBD may well be comparable, but the chemical and genetic composition of the plant and the presence of other substances changes. So therefore, in essence the product used for the research changes too. It means the outcomes that were gathered up to that point are no longer usable, because they do not apply to this new, different plant.

4. MEDICINE DEVELOPERS

Constant availability of a standardised product is extremely important to developers of medication and medical devices

At the moment, medicinal cannabis only applies as a medical raw material, i.e. an API or Active Pharmaceutical Ingredient. Various companies around the world are working on developing medication or medical devices on the basis of this active pharmaceutical ingredient. One example is an extremely advanced inhaler, which was developed by using standardised products from the Netherlands from the beginning. This inhaler is so advanced that it detects even the slightest change in the form and composition of the product to be administered. For the device to work correctly, the same percentage of THC and CBD and exactly the same genetic and chemical composition of the product are important. Any change in plant will produce high modification costs and months, if not years, of delay in its further development.

CBD can have a strengthening effect on the THC level in the blood. This was observed in data from a clinical study with fibromyalgia patients. A poster presentation about this matter gathered a large and engaged group of researchers and regulators at the ICRS congress last June. The ICRS congress is a leading scientific conference where international scientists present their findings in the field of cannabinoid research.

Previous research has shown that administering THC together with CBD can help reducing the undesirable side effects of THC, especially those related to increased anxiety. However, recent clinical and psychopharmacological research shows that co-administration of THC and CBD can lead to additional, unexpected effects.

Specifically, a recently published clinical study conducted at the Leiden University Medical Center, with the support of Bedrocan, compared the blood levels of THC in chronic pain patients after the administration of three cannabis chemovars (varieties): Bedrocan® (THC 22% | CBD <1.0%), Bediol® (THC 6.3% | CBD 8%), and Bedrolite® (THC <1.0% | CBD 9%).

Bedrocan’s research coordinator Mikael Kowal presented the results at the ICRS congress and there was great interest in his analyses. “The findings from our clinical study regarding the complex interactions between THC and CBD in the body are novel and were surprising to many.”

Knowledge

“Apparently, the effect of CBD increasing THC concentrations in the blood was discovered by one researcher in the early days of creating the formulation of Sativex. However, at that time this finding was difficult to explain, due to lack of sufficient knowledge on the workings of CBD. Currently, we seem to be the first to have this data published and similar results are being found in animal research.”

In the case of Bediol, the mixed THC/CBD cannabis chemovar, the blood levels of THC were about 50% higher than expected from the administered THC dose. Moreover, a similar effect was observed in a psychopharmacological study conducted with healthy cannabis users at the University of Sydney, in which higher THC levels were found in the blood of subjects who received cannabis containing equal amounts of THC and CBD, than in the case of cannabis containing an equal dose of THC, but without CBD.

The exact mechanism by which this effect occurs is still not clear. Possible explanations include an increased absorption of THC in the lungs or the inhibition of THC metabolism, both induced by CBD, or the conversion of CBD into THC. In any case, knowledge of these pharmacokinetic THC-CBD interactions can help physicians and patients in establishing a proper therapeutic dose of cannabis to treat their symptoms. Further research is needed to confirm this, however it is possible that lower doses of THC are required when co-administering it with CBD, in order to achieve symptom control of a particular disease.

What are we talking about when we talk about medicinal cannabis?

The term ‘medicinal cannabis’ leads often to faulty assumptions and misconceptions. That’s why we think it’s important to make clear what medicinal cannabis actually is. In a series of short articles we present the most common misconceptions about medicinal cannabis, in order to speak the same language in discussions, news articles and so on.

All cannabis is suitable for medicinal use

There is a great difference between ‘medicinal cannabis’ and ‘cannabis for medicinal use’. That difference is all about the manner in which and the purpose for which the cannabis is produced. Medicinal cannabis is intended solely for patients and the production process is fully attuned to that purpose.

Production takes place in a fully standardised manner, in a pharmaceutical environment, and is subject to those stringent quality and safety standards. The production processes are designed so that the cannabis is genetically consistent, the proportion of active ingredients is consistent, and there is minimum risk of contamination (microorganisms, heavy metals, and no pesticides). The cannabis quality is tested by an independent laboratory. This way quality is guaranteed. Both the patient and doctor clearly know what is being prescribed.

Industrial hemp is medicinal too

Hemp belongs to the family of Cannabis sativa L. It contains cannabinoids and is sometimes used for ‘recreational’ or ‘medicinal’ purposes, although it is never produced under pharmaceutical conditions. When referring to hemp, this typically concerns ‘industrial hemp’; a sturdy agricultural crop with long, strong fibres.

It differs genetically from the medicinal cannabis species. Mainly used in clothing, paper, (animal) feed, and automobile industries, industrial hemp contains negligible or zero levels of THC (the psychoactive component of cannabis). This is why it may be legally grown in many countries under more relaxed regulations. Industrial hemp does however contain CBD. As a result it is sometimes also used for the production of CBD rich oils which are not for medical use.

Medicinal cannabis is expensive

The production of medicinal cannabis requires considerable investment. The production process must continuously comply with the applicable quality and safety requirements of medicines. Nonetheless, in the Netherlands – a programme designed to provide patients with acceptably priced pharmaceutical quality medicines was initiated in 2003 – it has proven possible to gradually reduce the price.

Indeed, the price for one gram of medicinal cannabis has remained below the average price for recreational cannabis in the Netherlands for some time. This was made possible due to industrial efficiencies, scalable production process, and – in more recent years – income from exports.

In 2018, the Minister for Public Health, Welfare and Sport – who is ultimately responsible for the Dutch medicinal cannabis programme – further reduced the price per gram. A patient today pays € 5.80 (net) at the pharmacy.

Dr. Timna Naftali, Gastroenterologist at the University of Tel Aviv, was the first person to research the effect of medicinal cannabis on inflammatory bowel disease (IBD). While she received great criticism, one patient always inspired her not to give up. Scientific evidence is crucial for Naftali, and she is therefore devoted to the cause. She is determined to supply proof that medicinal cannabis works for IBD sufferers.

Ten years ago, a young patient walked into Dr Naftali’s surgery for her initial consultation. She had not been back for a check-up for a year. Naftali was surprised to see her again and wondered why she had never made a follow-up appointment.

“She had something to confess,” says Naftali. “The patient explained she had been using cannabis for the last year. All pain had disappeared, and had therefore felt no need to come back. In the meantime the patient had married, was trying to get pregnant, and had therefore stopped using cannabis. Her situation had once again deteriorated.”

The positive effect of cannabis on this young woman triggered many questions for Naftali. Would it not be fantastic to help more patients suffering from Crohn’s disease and colitis ulcerosa?

Lecture

In the end, it was a lecture by Dr. Yehuda Baruch, former head of the Israeli medicinal cannabis programme that was the deciding factor to look for answers. “To my amazement, he informed me that medicinal cannabis could be prescribed for patients in Israel suffering from Crohn’s disease. I was surprised that as a doctor, I was unaware of this.”

With total dedication, Naftali searched for clinical studies that supported the policy of the Israeli government. Finally, she concluded there was nothing to be found. “Nothing at all. Not a scrap of scientific evidence.” In the end, it was Naftali herself who took up the challenge to produce the much-needed scientific evidence. But where to start the research?

Dispensaries

Israel has special cannabis dispensaries where patients with a government permit may source their medicinal cannabis. “I approached a local cannabis producer and supplier and they put me in contact with thirty Crohn’s disease patients. Their experience with medicinal cannabis was impressive.

Patients required less (typical prescription) medication, suffered less pain, retained a healthy weight. Some patient no longer needed hospitalisation. Their quality of life had visibly improved because of their medical use of cannabis.”

That research was published in the Israel Medical Association Journal (2011) and promptly received criticism. The small retrospective observational study asked patients about their experience. It did not include patients who experienced little or no improvement. However, the positive consequences made Naftali more convinced of the necessity of continuing her research. She was determined to undertake a randomised, double-blind study. “A proper study”, as she herself refers to it, complete with a placebo, so that patients would not know what they were taking.

The research took around two years and the results were nothing less than spectacular. “Nearly half of the patients (45%) felt completely healthy after using medicinal cannabis. As if their disease had disappeared. In the placebo group on the other hand, a mere 10% experienced a complete remission. Once again, Naftali research was criticised within her professional field. Apparently, the study was not objective enough and there was insufficient clarity on the effect in the bowel after the use of cannabis. A justifiable observation, Naftali believes with hindsight: “We all know that cannabis can give a sense of euphoria. Was that why these patients felt better or was it the condition of their digestive tract and an actual solution for the disease?” She had also deployed an unhealthy method of application, namely smoking. A new study therefore proved to be essential. The latest study used a different administration method (cannabis oil for oral use). Patients received endoscopic intestinal examinations before and after the use of medicinal cannabis, in order to detect any improvement in inflammation levels.

Latest study

The results, published in October 2018 at the annual United European Gastroenterology congress, received positive reactions. Naftali herself was not satisfied. “Although patients felt much better after consuming the cannabis, no improvement was visible in the digestive tracts during the endoscopy. What does that mean? Either cannabis has no influence or there was not enough time between administration and the intestinal examination. It was only an eight-week period after all. Perhaps an interval of three months would have been more useful.”

Naftali also encountered another problem: “There are many types of cannabis, and as a researcher you have no idea which will work best. I still genuinely wonder what type of cannabis to administer, for how long and in what form.” In other words, her work is not finished yet.

Naftali is in the early stages of a new study designed to show the effects of purely synthetic CBD. CBD is known to have few side effects and is therefore considered safe. “It could serve as a supplement to further medication. But we first need to know whether it actually works.”

Naftali would appreciate being able to cooperate with researchers outside of Israel. Although the Meir Medical Centre in the Israeli city of Kefar Sava, where Naftali works, treats a thousand IBD patients, she believes this population to be too limited. The main obstacle to international cooperation however is that all researchers must be able to use the same cannabis. “The product I use here in Israel is not the same as that available in the Netherlands. We would therefore need to export the product, which has not exactly proved simple so far.”

By now, the patient who revisited Dr. Naftali ten years ago, has married and moved away to a different region of Israel. Naftali no longer has contact with her, but it is thanks to this patient that she remains convinced of the usefulness of medicinal cannabis for a majority of patients.

If you are interested in further research by Dr Timna Naftali, check out PubMed.

Bedrocan’s CEO Tjalling Erkelens has been featured on the Cannabis Economy podcast a significant number of times over the past few years. For the first time, Cannabis Economy’s Digital Workshop will take place on July 30^th and 31^st, bringing together leaders in policy, science and business. American events moderator Seth Adler is the driving force behind these podcasts. We discussed his background and the reasoning behind the podcast.

Who are you?

I’m a host, moderator, producer and unlicensed anthropologist. I’ve spent over 20 years producing international events, podcasts, video, and the written word. I am responsible for bringing “The greatest show on earth Ringling Bros and Barnum & Bailey”, the former American traveling circus, to town. I have also produced music showcases at the historic – now closed – New York City music club CBGB. I’m currently focused on the societally significant industries of legal cannabis and artificial intelligence through the production and hosting of Cannabis Economy and the AI & Intelligent Automation Network.

I procured a network of leaders in the space, including Catherine Sandvos of the Netherlands’ Office of Medicinal Cannabis’, and began running events. A six month gap between events is too long, and so I launched the Cannabis Economy podcast. The podcast has now reached the 850K downloads milestone and over 400 episodes have aired.

What is the digital workshop about?

The Digital Workshop brings global leaders from across the cannabis space together on one platform. Experts include elected officials, regulators, scientists, business leaders, advocates and activists discussing cannabis as a medicine, wellness and economic opportunity.

Why do you organise it? And why digital?

While the global cannabis economy has experienced dynamic growth, 2019 is specifically a year of sea-change with the World Health Organization setting guidelines, Israel exporting, EU members taking action, Asia-Pacific diving in, the first full year of legal cannabis in Canada and actual federal legislation receiving votes in the United States.

With a huge variety of cannabis events specialising in global policy, science and business, the Cannabis Economy Digital Workshop supplements this extensive calendar and provides parties the opportunity to learn from leading experts without blocking up schedules.

What do you want to achieve?

The goal of the Cannabis Economy Digital Workshop is to connect best-in-class thought-leadership and information-sharing in order to identify standard sensible regulations, safe patient access and industry advancement within the cannabis space.

How, where and when can people join?

While the content is designed for leaders in business, policy and science, attendance is free thanks to our sponsor’s support. Please register at the Cannabis Economy website.

Cannabis Europa has grown to become the foremost arena to share knowledge and shape the future of medicinal cannabis in Europe. The 2019 event hosts more than eighty expert speakers – ranging from politicians, policy-makers, scientists,  health care professionals, patients and industry. Bedrocan will be there.

Tjalling Erkelens, founder and CEO of Bedrocan, has been invited to speak about business leadership and global business development. It is indeed an interesting subject. Working within highly fragmented regulatory environments and often immature markets, the challenges facing industry leaders are numerous.

Cannabis Europa
Date: 24 & 25 June 2019
Location: Southbank Centre
London, United Kingdom

Programme Highlights

Monday 24 June – 15.30 – 16.30

Strong and Stable | Business Leadership
Nicholas Vita – Columbia Care
Tjalling Erkelens – Bedrocan
Nick Davis – Memery Crystal
Sabah Meddings – Sunday Times (Chair)

Tuesday 25 June – 10:00 – 11:00

Seizing the Initiative | Political Opportunity
Dr Ricardo Baptista Leite MP – Assembly of the Republic of Portugal
Delano Seiveright – Cannabis Licensing Authority Jamaica
Dr Marco van de Velde – Office for Medicinal Cannabis of the Netherlands
Andrea Paine – Aurora (Chair)

Can medicinal cannabis reduce the use of opiates? In order to answer that question, Leiden University Medical Centre (LUMC) is starting a study into the use of medicinal cannabis as an opiate-saving product among chronic pain patients. The product Bediol®, which contains both the cannabinoids THC and CBD, is used for this purpose. The study is carried out by the Anaesthesiology Department and is partly supported by Bedrocan, the world’s most experienced producer of legal medicinal cannabis.

The principal investigator, Prof. Albert Dahan, previously did research into the effect of medicinal cannabis in the treatment of chronic pain caused by fibromyalgia. An article about this was published in the journal PAIN at the end of 2018. Results of that research were positive and Dahan will now start a follow-up study. The main purpose of the study is to assess whether comedication with Bediol (6.3% THC and 8% CBD) will reduce the side effects of opioids among chronic pain patients.

Opiates are painkillers based on the natural substance opium. Examples of opiates are morphine, oxycodone and fentanyl. Prof Dahan said “Long-term use of these painkillers is addictive and causes unpleasant side effects like drowsiness, nausea and constipation. We believe that you can reduce the amount of oxycodone prescribed if you give people the option to use medicinal cannabis.”

The research team is currently working on the study’s preparatory phase. It is expected that the first patients will participate this year. From then on the study will take about two years to complete.

Facts and myths – the MJBizDaily factbook ‘Medical Cannabis in Europe: The Markets & Opportunities’ provides a clear picture of the European medicinal cannabis for the first time. What does the European market for medicinal cannabis look like? Which regulations apply to which country, who produces, who imports and which producers make the largest contribution?

Those questions and many more are answered factually and in detail for the first time by a special edition of Marijuana Business Daily, an American news outlet on the global cannabis industry. What transpires? Bedrocan is the clear market leader in Europe. More than 61% of the medicinal cannabis that is used by patients in Europe comes from our sites in Emmeloord and Veendam.

A special team of journalists and researchers analysed the European market for medicinal cannabis. It produced a diverse picture, both in terms of regulation and figures. Just three countries – the Netherlands, Germany and Italy – have a significant domestic market, whilst all other countries together account for just 3% of the market. Furthermore, the Netherlands is the only country that is able to meet the needs of patients internally, as all other countries depend on import. In contrast to a popular argument, this import does not come from Canada.

Besides the general European figures, the report also provides a good overview of the market and the regulations in more than 20 individual countries. If you are interested, you can download the MJBizDaily factbook free of charge.

Developing new medication is a long and expensive process, marred by uncertainty. On average it takes 10 years before medication is registered officially, but in the world of cannabis it works the other way around. Cannabis and cannabis products are on the market already, be that legal or illegal. “It’s time for governments to get into gear”, argued Bedrocan’s CEO Tjalling Erkelens in a guest article he wrote for the German Hanf Magazine. Politicians and policy makers need to come up with universal regulations that are meaningful to the cannabis industry, the healthcare professional and the patient.

By: Tjalling Erkelens – CEO Bedrocan
Published in Hanf Magazin

No, this title is not an error. However, it certainly has to do with “confusion” and more in particular about confusion surrounding cannabis these days. Aside of all ‘big money’, ‘big pot’ and ‘big pharma’ discussions I do see an immense amount of confusion among doctors, patients, pharmacists, but also scientists, regulators and politicians.

Since cannabis has become ‘hot’ everybody is trying to jump on the bandwagon and be part of the current ride that cannabis is taking in the world. Even worse, everybody nowadays also has an opinion on cannabis. At the numerous conferences and meetings that are now being held on this subject we see so much information either lacking, being false or at least incorrect and certainly not patient-focused.

I am working in the world of cannabis since 1992. So that started only 16 years after fellow Dutchman Harm Dost, was arrested in Kleve (as a tourist). Harm Dost was known for his sales of cannabis in Arnhem, also to German people who he, at that time, treated as patients, calling himself a caregiver. In 1977, after having spent 18 months in a German prison, he was extradited to The Netherlands. In 1986 he was again sentenced in Germany, now to 10 years in prison. In 1987, on appeal the sentence was diminished such way that he was released from prison immediately. Twenty-two years later (2008) Germany imported its’ first medicinal cannabis from The Netherlands and sales through pharmacies, on prescription of a medical doctor started.

So, I have seen the world of cannabis change from a full illicit/grey product and industry, basically without any surrounding scientific knowledge, into one in which science, industry and regulators / politicians have started to see the added (medical) value of cannabis. That doesn’t mean that everything now is perfectly right and ok. As said in the intro, there is still a lot of confusion among many stakeholders. Even today, a lot of politicians and regulators don’t see the difference between cannabis for medical use or recreational use. At the least they are struggling with it. Although the amount of positive scientific evidence is more and more piling up these days, the acceptance of cannabis as a medicine is still highly driven by emotions and (contra-)activism. Lack of consensus among scientists, lack of coherence and harmonization of regulations and an un-unified industry are frustrating development of proper cannabis-based medications, let alone proper access for patients globally.

To unravel this relative complex problem, we have to start with a very basic question: ‘What is cannabis?’ Even till 5 years ago, the general answer was: ‘A plant, well-known for its’ healing, though psychotropic effects due to its’ main constituent THC.’ If you will ask today, a majority will tell you: ‘A plant, well-known for its’ healing and non-psychotropic effect due to its’ main constituent CBD.’ In between you will find people talking about terpenes, minor-cannabinoids, flavonoids, entourage-effect. But in the end, nobody is able to provide all the right answers. The only thing we do know is that cannabis works well for a lot of people in all kinds of suffering and diseases. However, from that point on, we all got stuck in a swamp of so-called expert-opinions, testimonies, n=1 studies and even hearsay.

Solving this problem is not an effort that can be put on the shoulders of industry, research institutions or NGO’s only. The consequences of more than 60 years of global prohibition will have to be borne by the politicians who made that decisions back in the early sixties of last century. So actually, that means all of us, represented by our politicians. If we want proper research, proper products and proper access for patients and that way allow cannabis to become the medicine we all think it is, this is a bigger task than making industry responsible in the traditional pharmaceutical way. Such would have worked 60 years ago, just like it did with other controlled substances producing plants (poppies and coca mainly). Some then would say legalize all cannabis use and thus have the recreational user contribute to the development of cannabis medicines. That is what I call: mixing apples and pears. The 60 years of prohibition were not caused by recreational users or activists and patients neither of course…

Now a number of governments is telling the newly arising cannabis industry to follow the well-known track of pharmaceutical drug development. That would mean in very broad strokes: develop your product, perform your (clinical) research, register your product, get market authorization and have your product into the patient’s hand hopefully reimbursed partially or in full. Following that track will mean another 10 – 20 years of waiting because that is what this ‘royal route’ brings with it. However, that time is not really available. Cannabis and cannabis derive products already are in the market (licit or illicit); efficacy is shown by means of the numbers and experiences. If you can show a 100.000 times or more positive N=1 (research on 1 person) results, is a result that cannot be ignored.

In the end it means that the ‘royal route’ is not available, simply because we’re already far beyond that point. The combination of allowing cannabis to the market but having no proper or sometimes very ‘creative’ regulations in place is not good for patients, nor their caregivers. It has become time now for regulators on a global, or at least multi-national level, to come together and unify regulations on the basis of safety and efficacy on one hand and immediate, proper and responsible access on the other. Germany (although still struggling as we all know) is a good example of allowing and regulating at least that combination of factors to happen. Maybe instead of all those business conferences, the industry should focus on more regulator conferences. Let’s make 2019 “Year Of The Regulator”.

At the end of last year, the rules for using medicinal cannabis in United Kingdom were relaxed substantially, but many patients are still looking for ways to obtain medicinal cannabis or derived products in a lawful, affordable and responsible way. Healthcare professionals are extremely cautious with prescriptions, because of the attached ‘clear published evidence of benefit’ condition. According to Hannah Deacon, mother of epilepsy patient Alfie Dingley, time is of the essence. “There is much more awareness in the UK and important steps have been taken, but the procedures are too bureaucratic and time consuming. Patients can’t wait for those.”

In 2018, the UK government took significant steps in terms of the use of medicinal cannabis. Since the 1st of November 2018, medical specialists have been permitted to prescribe medicinal cannabis in specific situations. For a while, it seemed like the icing on the cake for a large group of patients and supporters in the UK who worked tirelessly to put medicinal cannabis on the political agenda and for the rules to be amended. Young patients Alfie Dingley (7) and Billy Caldwell (13) became the figureheads. Both boys suffer from a serious type of epilepsy, but it had become evident that medicinal cannabis could make an enormous difference to them. After Charlotte Caldwell, mother of Billy, was arrested at Heathrow Airport in June 2018 after purchasing medicinal cannabis oil in Canada, they were given an emergency license so Billy could continue taking his oil. Hannah Deacon, Alfie’s mother, also made the news on a regular basis. She started a campaign, personally met PM Theresa May and asked her to change the rules and allow a license to be issued to Alfie to use the oil he had used so succesfully in Holland. Among other things, they also managed to win actor Patrick Stewart for Alfie’s case. Alfie’s doctors recieved the first medicical cannabis license which was issued on 19th of June 2018 and then they could import and use medicinal cannabis from Holland. Hannah was the first person in the UK to bring in THC oil legally through customs in July 2018.

‘Sensible’ approach

In addition, in June 2018, Home Secretary Sajid Javid announced that the use of medicinal cannabis would be reviewed. He made it clear from the start that this review would not lead to a full legalisation of cannabis, ensuring a clear distinction between recreational use and medicinal applications. The outcome was a strict set of rules that became effective as of the 1st of November. Medicinal cannabis was also moved to a category of drugs (Schedule 2) that is still controlled, but that may be prescribed in certain situations. For example, only specialists in a hospital may issue prescriptions for a limited number of disorders. This concerns children with rare and serious types of epilepsy, adults who are undergoing chemotherapy and adult MS patients. Furthermore, treatment with medicinal cannabis may only start when all the other options have been exhausted, whilst the NHS argues that the treatment method needs to be proven to be effective too. Dr Michael Bloomfield, a leading research fellow in psychiatry at University College London was able to accept this ‘sensible’ approach as, like many other healthcare professionals, he is waiting for scientific evidence. “When we don’t have very strong evidence for any medicine, then it should be hard to prescribe something because we should be prescribing medicines when there’s a very strong evidence base for them”, he told BBC News.

New phenomenon

Hannah Deacon understands that perfectly well, but also sees the practical issues for the nearly 25,000 young patients in the UK with refractory epilepsy who, like Alfie and Billy,  could benefit from medicinal cannabis. “We are of course extremely grateful that the responsible bodies acted and that we received permission to import the oil for Alfie. We also understand that healthcare professionals have responsibilities and want scientific evidence, but in practice the new rules mean that many patients still don’t have access to medicinal cannabis. Medicinal cannabis is a new phenomenon for doctors and everyone is waiting for the outcome of clinical trials. Patients simply don’t have that amount of time to spare. More to the point, the rules are limited and complicated and manu clinicians do not understand them. Or they do not understand medicinal cannabis and how to prescribe it.”

Availability

Yet it cannot be denied that the UK is taking steps in line with other countries in Europe. Up to the 1st of November 2018, Billy, Alfie and many other English patients did not have access to medicinal cannabis at all without a special license. Nearly all medicinal products based on cannabis were Schedule One drugs, that were assigned no medicinal or therapeutic value and the use of which was prohibited. MS patients were allowed to use Sativex®, whilst Nabilone® was given to cancer patients. However, the use of these registered products was subject to conditions. Availability was a general problem for patients for whom regular treatment methods no longer worked, as was the case with Alfie Dingley. So in September 2017, Hannah and Alfie crossed the Channel to the Netherlands to find out whether medicinal cannabis provided relief; in the Netherlands medicinal cannabis has been available on prescription since 2001. Time was of the essence for Alfie.

Responsible product

Alfie suffers from PCDH19 epilepsy, which is caused by a mutation in the PCDH19 gene that disturbs the production of the protein protocadherin and disrupts the communication between brain cells. This is a serious form of epilepsy that produced clusters of seizures in Alfie; sometimes as many as 30 seizures a day or 150 per cluster. “Initially, the cluster attacks occurred every eight months, but when Alfie was five years old he was in hospital every week”, remembered Ms Deacon. “In the meantime we tried all sorts of different medication, but nothing worked. The situation became more serious as Alfie grew older, so something had to be done.”

Hannah and her husband Drew Dingley explored the possibilities of medicinal cannabis. “There is a lot of anecdotal evidence. In consultation with our GP we went to the Hague, where a specialist was prepared to treat Alfie and where the Transvaal Apotheek produced oil from medicinal cannabis in a responsible manner”, said Ms Deacon who is familiar with stories about illegal and often contaminated cannabis products. “When it comes to health, a little scepticism is a good thing. We were convinced that we needed to look for a legal, standardised and pharmaceutically responsible product. In the Netherlands that is available on prescription.”

After five weeks of treatment in the Netherlands, Alfie started to respond positively to an oil with a low THC content. After adding another oil (with more THC), Alfie’s situation improved enormously. Ms Deacon said: “After five months we were fairly certain that we had found good medication for Alfie. We returned to the UK and started the campaign that enabled Alfie to be given the license after a fair number of setbacks and other patients taking action. In the end, that license led to a prescription from the National Health Service (NHS), ensuring that Alfie can have lawful access to medicinal cannabis. The only problem is that we need to travel to the Netherlands on a regular basis, because the oil used by Alfie is not yet available in the UK.”

Savior

“All things concerned, Alfie is doing well”, continued Hannah Deacon. “The number of attacks has been reduced to just a handful. When they come, they are also far easier to deal with and Alfie recovers far quicker. He goes to school, rides a bike, rides a horse and is developing like any other child. Previous medication worked less well and made him aggressive too. We can truly say that medicinal cannabis has been a savior for us all. Alfie and the people around him have their life back.”

Unfortunately, this is still not true for all patients in the UK. It is with good reason that Hannah Deacon is concerned. “We did not campaign for Alfie alone. There are so many other patients – with different disorders – who could benefit from medicinal cannabis. Now the government has given consent, the availability of medicinal cannabis should be improved rapidly.”

It is often reported that cannabis strains which are high in CBD are less impairing than those with equivalent THC but low levels of CBD. However, a recent study carried out by the Lambert Initiative at the University of Sydney and led by Australian researcher Thomas Arkell suggests that CBD might actually exacerbate some of the impairing effects of THC on driving and cognition.

It has already been established that cannabis can negatively impact the ability to safely drive a car. The effects can vary substantially between individuals; however, cannabis is generally thought to have a mild to moderate effect on driving. This is a point of concern for patients who often use medicinal cannabis as a last resort in dealing with their illness.

Driving performance

Driving is a complex activity that requires many cognitive skills – looking, changing gear, assessing, planning, judging etc. PhD student Thomas Arkell recently ran a randomised, double-blind and placebo-controlled crossover study to investigate the effects of vaporized THC and CBD on driving with the support of the Australian research institute the Lambert Initiative. He was surprised by their findings: “We found that cannabis containing both THC and CBD had a worse effect on driving performance than cannabis with only THC”. Further, when participants received both THC and CBD, they had slightly higher levels of THC in their blood compared with when they had just received THC.

“These results therefore suggest that CBD does not mitigate or reduce the effects of THC, and that it may in fact exacerbate these effects.”

Patients

According to Mr Arkell, patients in particular will benefit from this new information. “Cannabis patients who are using high CBD products which also contain THC (such as Bediol or Sativex) need to be made aware CBD could potentially elevate the amount of THC in your blood and may under some circumstances actually increase the effects of THC.”

Generalised advice

So should patients not be allowed to drive after they take their medication? It continues to be difficult to issue general advice to patients who use medicinal cannabis. The effect of cannabis differs from patient to patient. Mr Arkell continued: “Cannabis is not as straightforward as alcohol. Each person metabolises the drug and responds to its effects in a different way which makes it hard to say whether a certain amount of THC in your blood or saliva will have a particular effect”.

In the study, participants were still impaired 3.5 – 4 hours even though they felt much less ‘high’ at this time. According to Mr Arkell these results suggest that patients should probably avoid driving for at least 3-4 hours after taking their medication.

Arkell: “With more research, we can hopefully provide better guidelines for patients who may be unsure how long they need to wait before driving.”  A follow-up study led by Dutch Professor Johannes Ramaekers of Maastricht University is currently being developed and will begin this year. The follow-up study will use the Bedrocan and Bedrolite products as well as a placebo and will incorporate an on-road driving test.

What is considered to be impaired driving?

Thomas Arkell said: “To measure impairment we look at something called standard deviation of lateral position. This is a measure of lane weaving, or how much people are moving around on the road. Normally, people are pretty good at maintaining a steady position in their lane. When people are impaired due to alcohol or other drugs, however, they are unable to control this as well and so their standard deviation of lateral position goes up. We can use this same measure to detect the effects of cannabis on driving.”

SDLP – Standard Deviation of Lateral Position

Placebo
(e.g. SDLP = 16 cm)

Sedating drug
(SDLP = increases)

An arbitration tribunal rules that the Dutch medicinal cannabis producer Bedrocan International (“Bedrocan”) is allowed to resume commercial activities in Canada as of September 11, 2019, and allowed to engage the same in South America (retroactively) as of March 14, 2019.

A legal settlement agreement containing a moratorium on commercial activities between Canopy Growth Corporation and Bedrocan, prohibited Bedrocan from operating in Canada until 1 January 2020, with the same prohibition applying to South America until 7 June 2019. This moratorium was enforced by Canopy in June 2018 after both parties agreed to terminate their joint licensing agreement.

The arbitrator has now reduced the duration of this moratorium due to Canopy not meeting all the conditions set out for the termination in the license agreement. The arbitrator concluded that the mere fact that Canopy was seriously prejudiced by a reduction of the moratorium is for the account of Canopy and Canopy only. He concluded as well that Canopy could have prevented any damage (i.e. reduction of moratorium) themselves had they simply adhered to the terms of settlement in a timely fashion. Following this ruling Bedrocan will be announcing its next steps within these markets some time later this year.

Bedrocan CEO, Tjalling Erkelens believes that “lifting of the moratorium not only results in an important milestone for Bedrocan as a company, but is also very good news for Canadian and South American patients who rely on the use of medicinal cannabis and who already used medicinal cannabis from Bedrocan before the moratorium commenced.”

While cannabis was historically used in traditional medicine, its use promptly ceased with the Narcotics Control Act 1976. Given previous staunch drug policies, it came as a surprise to many that Thailand moved to re-introduce cannabis-based medicines. However, “the evidence from many countries, in particular Europe, has shown that it is useful for the treatment of specific diseases. Quality science and good policy examples now presents the opportunity for Thailand to move ahead.”

Chairman of the Board of Directors
The Government Pharmaceutical Organisation (GPO), Thailand

Governing committee

In moving ahead, Thailand has established a governing committee which covers production and extraction, medical indications, regulation, clinical trials and knowledge development. This executive committee has now explored ‘best practice’, having visited multiple countries where the medicinal use of cannabis is already underway.

“It is the committee’s responsibility to ensure that appropriate quality standards, licencing and clinical research underlines the introduction of these medicines into Thailand. Ensuring medicine efficacy and safety for patients is paramount. It is a step-by-step process. This means introducing cannabis-based medicines into select prescribing populations, assessing risks, altering aspects where necessary and scaling up to cover the whole country in time.”

Chairman of the Board of Directors, GPO

Aging population

Thailand has an aging population and is exploring new ways to deal with and treat aging related disease. The rapid development of the palliative care sector is one tactic. However, in this setting, currently, access to and the use of opioids is complicated. There remains stigma and concern for safety from use in this population of patients. “Thai patients understand what an opioid is and the role of opioids to control pain and suffering at the end of life. However, for most Thai patients, there is the need to clarify some misconceptions. Often there are concerns, for example, about the risk of addiction to opioids, the hastening of death, or even disease progression. These medicines can actually improve quality of life.”

Thai Palliative Care Professional   

Scientific basis

Like for opioids, there will be a need for educating patients and family about the risks and benefits of cannabis-based medicines. Equally, there will be a need to moderate expectations about cannabis-based medicines, given the media hype about them being a ‘panacea’.

Like in the Netherlands in early 2000’s, Thailand is approaching this matter from an objective, scientific basis. The health and wellbeing of the population are dominant concerns. Making cannabis-based medicines affordable is also essential. The GPO is responsible for delivering essential medicines to the population at an affordable price. It is likely that the GPO will also lead the advancement of cannabis-based medicines for Thailand.

Thailand is a respected thought leader in the ASEAN community. It is likely that neighbouring countries will watch the developments closely as Thailand progresses toward the re-introduction of cannabis-based medicines.

Infinity Pharma in Helmond, the Netherlands, is a pharmacy that works with regular medication as well as ‘new’ medicinal products, such as cannabis oil. It is one of the four pharmacies that compounds medicinal oil from standardised medicinal cannabis under the supervision of the Dutch government, and in accordance with GMP guidelines. The Office for Medicinal Cannabis in the Netherlands oversees the whole process. “The demand for cannabis oil is high and we like to meet it. But it has to be produced responsibly.

Until the 8th of August 2018, Infinity Pharma was known as GMP Apotheek Mierlo-Hout, a well-respected pharmacy with advanced medicinal knowledge and a strong dialogue between prescribers and patients allowing for ‘personalised medicine’. This led to a desire to produce cannabis oil in-house which could be issued to patients on the basis of a prescription. “We saw an increase in the interest in cannabis oil and we did not want to ignore that”, says Key Account Manager Loes Haast.

Medicinal cannabis

“We followed the developments around medicinal cannabis closely and trusted our own knowledge to be able to compound the oil responsibly. The fact that the Dutch government has made medicinal cannabis that is highly standardised and produced under GMP available for some years now provides a responsible basis. On top of that, Transvaal Apotheek in The Hague helped us with setting up the production. They already had the experience and we weren’t looking to reinvent the wheel. Furthermore, it is important to patients and prescribers that the products we offer are of the highest quality with minimum risks.”

Fagron Group

The Helmond pharmacy Infinity Pharma is part of the Fagron Group that has 200 pharmacists in more than 50 sites on 5 continents. Rafael Padilla, CEO of Fagron, used to be a pharmacist and aims to roll out the Infinity Pharma concept in Europe. The site in Helmond is the first of its kind and serves patients and consumers from the Netherlands, Belgium and Germany.

Fully in line with the history of the pharmacy in Helmond and the mission and vision of the parent company, Infinity Pharma offers regular medication alongside ‘personalised’ products. The pharmacy strives to have customised products for each patient and uses its own system of medication control to avoid risks.

Portfolio

The portfolio has been subdivided into the product groups: ‘pharmaceuticals’, ‘nutriceuticals’ and ‘cosmeceuticals’. Digital Transformation Manager Dimitri Lambrecht informs us that all are produced state of the art and are offered in clearly recognisable packaging. “We keep our eyes open for new products to serve patients and consumers in the best possible way. We make a clear distinction between products that may only be issued on prescription and products that may be sold over the counter or online. That distinction is reflected in the packaging. Under the flag of nutraceuticals we also offer a self-care product based on CBD. This oil can be produced responsibly and in contrast to most CBD oils, the consumer can check the ingredients exactly. Cannabis oils are of the product group pharmaceuticals, thus available on prescription, and are produced using Bediol®, Bedica®, Bedrocan® and Bedrolite®, the latter exists in two versions.”

FTO module

Apart from serving patients and consumers, Infinity Pharma also aims to share knowledge. This happens at the pharmacotherapeutic meeting (FTO), with one module solely focussed on medicinal cannabis and cannabis oil. During the FTO, doctors and colleagues receive comprehensive information from pharmacist Joris Cornelissen. “We base ourselves on scientific facts and not on anecdotal evidence”, said Loes Haast. “Our profession requires an enormous amount of responsibility and we take that extremely seriously. That applies to the information we provide to patients, doctors and colleagues, but also to the parties we work with, such as the suppliers of raw materials and equipment.”

Although he has retired, Rudolf Brenneisen’s mission – the re-medicalisation of cannabis – has not come to an end. Mr Brenneisen gives lectures, talks to the press and leads the Swiss Taskforce for Cannabinoids in Medicine (STCM), for which he himself organises a biannual congress. His motto is to develop, interpret and share scientific knowledge. “We must bring the plant to the physician.”

“This is the last time I’ll be doing this on my own”, said Rudolf Brenneisen on the eve of third STCM congress around the middle of January.

“I really enjoy organising a congress and the previous ones demonstrated that scientific meetings about medicinal cannabis meet a need, but it is too much work for one person.

Furthermore, I’m retired and need to focus on my hobbies. There is more to life than cannabis.”

That wasn’t always the case. The curriculum of Rudolf Brenneisen (Bern, 1949) comes down to nearly 40 years of acquiring and sharing knowledge of the medicinal potential of cannabis. It began and ended at the University of Bern, where he started as a researcher at the Institute of Pharmacy in 1975 and where he retired as Professor of Phytochemistry and Pharmacognosy of the Department of Research in 2014. Not surprising, because Mr Brenneisen’s country of birth has a rich tradition in the area of phytotherapy and cannabis was one of the plants that was offered as being beneficial way back in the last century.  “My first research was focused on the pharmaceutical potential of blueberries”, remembers Mr Brenneisen. “At some point in my Pharmacy study I was allowed to compose a cannabis preparation for corns and that generated my interest in the cannabis plant. I wondered whether the qualities of this ‘folk medicine’ could be translated to pharmacy. At the same time, I was extremely aware of the controversy surrounding cannabis and the risks of excess consumption. It became clear to me that you to have maintain a strict separation between medicinal and recreational use of cannabis – and the discussion about it.”

From forensic to medical

In the 1970s, Mr Brenneisen took his first steps as a cannabis scientist, but in the forensic sphere. On the instructions of the Swiss Drogenpolizei he was at the cradle of a reliable method for determining the THC content of cannabis, and then moved to the Research Institute of Pharmaceutical Sciences in Oxford Mississippi, where together with Professor Mahmoud ElSohly he worked on the chemical fingerprint (terpenoids profiling) of the cannabis plant and its active components (cannabinoids). This knowledge brought Mr Brenneisen to the laboratory of the Drug Enforcement Administration (DEA) in McLean, Virginia around the middle of the 1980s. A beautifully framed certificate on the wall in Mr Brenneisen’s office in Bern serves as a daily reminder of that period. In the end, a pilot study with muscle-spasm patients brought the Swiss cannabis specialist back to his country of birth.

“That was a definite move from forensic to medical science”, said Mr Brenneisen. “That study, where initially two patients were treated with THC, proved to be a milestone in cannabis research. The study was scaled up to several patients and actually opened the door to clinical studies of cannabis in Switzerland. Perhaps even in the rest of the world, because after that many trials were started up in the area of neurological disorders, such as Amyotrophic Lateral Sclerosis (ALS) and pain.”

Remedicalisation

With nearly 40 years of forensic and medical-scientific research, Rudolf Brenneisen has been referred to as the ‘cannabis papst’ (cannabis pope) more than once. Perhaps because he has fervently expressed his belief in the medicinal potential of cannabis, albeit a little unorthodox at times. Perhaps because he had an unchanging mission; making sure that cannabis returned to the pharmacies, where it deserves a place alongside all other prescription medication. Therefore Mr Brenneisen prefers to talk about the ‘re-medicalisation’ of cannabis. “It cannot be right that patients who benefit from cannabis have to go to the street or the internet to buy their ‘medication’ from the illegal circuit. For patients, who suffer enough as it is, it constitutes a possible criminal offence as well as a health risk. Practice has demonstrated time and again that you simply do not know what you are using. In my view, quality and safety are paramount and therefore a scientific, pharmaceutical approach is essential. I’m not a ‘cannabis pope’. I do not belong to the group of people who believe that everything from nature is good for your health by definition. And I’m not a catholic either (laughs). However, I do believe in medicinal cannabis and by now there is scientific information to support that belief.”

Clinical facts

There continues to be a massive call for scientific evidence. Not just for patients and doctors, but for health insurance companies, regulatory bodies and politicians – they are all waiting. Mr Brenneisen commented “It starts with patients. Over the years, plenty of anecdotal evidence has been gathered and although that is promising, ultimately the doctor or specialist need to understand it and believe in it, because they are closest to the patient. Therefore we need hard, clinical facts and everybody knows that is not easy because it costs time and money. Back to me; whether I will live to see the actual re-medicalisation of cannabis remains to be seen, but steps are being taken across the globe.”

Mystification

The attention for the medicinal use of cannabis has taken flight worldwide, and more and more countries are considering legal use by patients or are working on setting up a programme. The European Parliament recently made some statements, the World Health Organisation formulated recommendations, and medical-scientific research of cannabis has taken off. The retired Swiss Professor turns 70 this year and according to pension law he no longer has to worry, but he still does. “I simply still find it absolutely incredible to see how versatile a cannabis plant is and how many scientific questions medicinal cannabis produces, although I do struggle with the wholesale mystification that is taking place. That has been the case for CBD for quite some time. It is marketed aggressively as a food supplement or lifestyle product, and consumers go for it en masse. That is simply the result of a lack of knowledge. Cannabis – and I’m talking about the entire plant here – is a natural product with medicinal potential, it is not a panacea. We also know it carries risks. We need to get rid of stigmatization, but also of glorification. At the same time there are so many questions to answer, and that demands a scientific approach. What is the ideal formula of cannabis as medication and what does the endocannabinoid system do? Should we be looking for medication with an isolated active substance or is it actually the combination of cannabinoids that is making the difference? What is the ideal administration method? There is plenty of research of all those questions and I still find it fascinating and useful to bring all that knowledge together and to share it with the world.”

Stay involved

In order to stay involved Rudolf Brenneisen is still linked with the Swiss Task Force for Cannabinoids in Medicine (STCM) and the Schweizerische Akademie der Pharmazeutischen Wissenschaften, for which he organises the biannual scientific congress himself. This year (2019) is the third congress and is quite a job, barely leaving time for other hobbies, such as exploring the American highways on a Harley Davidson or listening to the famous twelve bar blues of the English rock band Status Quo. “On one Saturday we try to get as many healthcare professionals, scientists, patients, politicians and other stakeholders together and this year they come from 19 different countries. It underlines massive global interest,” said Mr Brenneisen. “Continuing to develop, interpret, and share objective, scientific knowledge of real importance is something I like to contribute to. This also motivated me to act as editor in chief of the new open access journal ‘Medical Cannabis and Cannabinoids’.”

Some countries permit products containing CBD either as food supplements or by turning a blind eye, but the reverse applies in Austria. The country recently prohibited CBD because the government believes that the product is uncontrolled and sales are out of hand. The Austrian Ministry of Health is of the opinion that patients need to be protected, but according to the patients organisation Arge Canna, this measure will only harm patients’ interests.

The CBD prohibition in Austria became effective at the end of 2018, just before the recent recommendation from the World Health Council (WHO) to deregulate CBD. CBD, together with THC, is one of the most important active components of cannabis, whereby THC being known particularly for its psychoactive effect.

Advice WHO

The WHO recently recognised the therapeutic benefits of cannabis, and no longer considers the plant as dangerous, recently proposing to move cannabis from the strict schedule 4 to the more permissive schedule 1 in the Single Convention on Narcotic Drugs from 1961.

According to the Austrian patient organisation Arge Canna, patients do not benefit from a prohibition on its own. There has to be more regulation and improved quality control of CBD products.

Spokesperson Klaus Hübner of Arge Canna commented on the prohibition by saying “In Austria you can still buy cannabis flowers, extracts and hash with CBD and less than 0.3% THC. They’re just no longer sold as a food supplement or medication, but as an aroma product or as raw plant material extract, because that is still allowed.” According to Mr Hübner, there is absolutely no quality control from the government, even though these CBD products are used by patients. It is a thorn in the side of the patients organisation, who call themselves a quality guard. “We now have the worst of both worlds – CBD is not permitted for medicinal use and there are no controls of any kind. Patients are in danger because of it.”

Due to the lack of quality control, Arge Canna, a non-profit NGO, has been testing various Austrian CBD products on their content substances since 2016, through an independent laboratory. On request of the manufacturer they check every product for the presence of cannabinoids, the active ingredients of cannabis (THC content must not exceed 0.3%), as well as whether the product contains heavy metals, pesticides, micro-organisms (fungi), residual solvents or PAHs (polycyclic aromatic hydrocarbons). Hübner: “Products that pass the test receive a mark of approval from us and the product gets the predicate safe. We do not publish bad results, they just do not get our seal of approval and they will not be listed on our website.” There are now five companies that have their products tested and approved.

Arge Canna mainly certifies CBD oil. This year cannabis flos, sprays and crystals have been added.

Reimbursement

Despite the CBD prohibition, you don’t hear many complaints from Austrian patients. It is standard practice for the Austrian government to reimburse medicinal cannabis, and that is something the average European patient can only dream of. However, there are downsides. Cannabis flos containing THC, the dried cannabis flowers, are not permitted in Austria, a doctor may only prescribe THC in the form of dronabinol concentrate where the THC is processed by the chemist into a tablet, oil or cream. This is just one active component. For patients who benefit from THC and CBD, this is far from ideal. It is presumed that those patients now collect their uncontrolled CBD product from the aforementioned aroma shops.

Experts see no benefits

Briefly it seemed like the law might be amended at the end of 2018 and that dried cannabis flowers with THC could be used as an alternative medication. However, following expert advice from the Austrian Health Council (Oberster Sanitätsrat) and the association of chemists and doctors (Apothekerkammer and Ärztekammer) the status quo remains. There is insufficient scientific evidence that cannabis flos works better than the dronabinol that is already available. Furthermore, with cannabis-based drugs it is possible to produce exact doses, whilst it is believed that this cannot be achieved with flos. In Austria, Sativex® has been the only other approved cannabis-based medication since 2012, not including synthetic cannabinoids like Nabilone.

Exception

Despite the prohibition of CBD, the Austrian government makes an exception for a small group of patients. Children with a rare type of epilepsy may be administered CBD to suppress seizures and they are reimbursed. Mr Hübner said “This CBD-containing juice is only prepared by the pharmacist, is of pharmaceutical quality, and cannot be compared to the CBD that is available for sale in the aroma shops.” However, adult epilepsy patients miss the boat, as do people who suffer from Parkinson’s disease because they are not eligible for reimbursement. Patient organisation Arge Canna, which is now active in four Austrian cities, provides the answer in those cases. “Our network of patients and our knowledge of scientific studies is enormous. We help until reimbursement has been organised”, continued Mr Hübner.

As the global cannabis market continues to grow so does the number of conferences about this subject. Bedrocan has selected the following conferences to speak. Our message during these events will always be our focus on the company’s core values: separation of markets (medical vs recreational), global harmonisation of laws and regulations to ease patient access, and allow for easier transfer of products around the world.

The World Economic Forum in Davos starts today and for the first time (medicinal) cannabis is part of the discussions being held there. Our founder and CEO Tjalling Erkelens will join these discussions for the rest of this week. His message will focus on the company’s core values: separation of markets (medical vs recreational) and global harmonisation of laws and regulations in order ease patient access and allow for easier transfer of products around the world.

Cannabis Conclave
This Thursday Tjalling Erkelens will also attend the Cannabis Conclave in Davos to discuss the global cannabis movement with other cannabis leaders and investors.

Pharmaceutical-grade cannabis with THC relieves pain in fibromyalgia

A recent study shows that Bedrocan’s standardised pharmaceutical-grade cannabis with a high tetrahydrocannabinol (THC) content is effective in treating pain in fibromyalgia. However, cannabis with only cannabidiol (CBD) did not show relief at all. The study was conducted by the Dutch Leiden University Medical Centre (LUMC) in cooperation with Bedrocan International BV, world’s most experienced producer of legal medicinal cannabis. Principal Investigator, Professor Albert Dahan, head of the Anaesthesia & Pain Research Unit of the Department of Anaesthesiology at the LUMC, believes this is the first real scientific proof that at least two of Bedrocan’s products are effective for fibromyalgia.

Reimbursement

It is the first time a randomised, placebo-controlled four-way cross-over study is conducted into the therapeutic effects of inhaling Bedrocan’s medicinal cannabis products. Tjalling Erkelens, founder and CEO of Bedrocan is especially delighted for patients: “The outcome is very important for patients who suffer from fibromyalgia. Now we have the serious clinical evidence that medical doctors are asking for when prescribing our products and that health insurance companies want to have, to legitimise reimbursement.”

A total of twenty patients participated in the study. They were treated at four distinct moments. Administration of three different cannabis products (Bedrocan®, Bediol®, Bedrolite®) and placebo (cannabis without the main active substances THC and CBD) was done by means of a vaporizer.

All subjects were exposed to externally inflicted pain by applying increasing pressure. With the Bedrocan and Bediol products, patients experienced significantly less pressure pain compared to the placebo. Furthermore, many respondents noted they experienced relief in their spontaneous pain after using Bediol.

Furthermore, the Principal Investigator, Professor Dahan, reached the following conclusion about THC: “Fibromyalgia patients experience pressure pain on muscles and tendons especially. Because only Bediol and Bedrocan show good results and the CBD product Bedrolite not at all, it means that especially THC is effective in this specific condition.”

Investigators conducted a series of measurements and tests before and after the cannabis was administered in order to systematize the variables. In one test, a weight was placed on the muscle between the thumb and forefinger. Dahan: “Healthy people can handle ten kilograms. For a fibromyalgia patient, one kilogram is already painful. But after administering Bedrocan products with THC, we saw that the same patient could suddenly bear ten kilos.”

Both Bedrocan and the Principal Investigator believe that investigation is now required to determine whether the same results on pain relief can be reproduced in a long-term study with fibromyalgia patients. “The next study takes place with patients at home. I want to investigate whether THC can be used as an opiate-saving drug. Many people use, and abuse opiates, such as oxycodone. We think that you do not have to prescribe much oxycodone if you also allow patients to use THC,” said Professor Dahan.

Overview of used products and their THC and CBD levels

A decade ago, under the previous Labour Government, New Zealand introduced policy to permit eligible patients to access cannabis-based medicines. This was accompanied by clinical guidance for a range of indications, reviewed by New Zealand’s medicines regulator, Medsafe, and specialists in palliative care, general practice, oncology and pain. At that time, Sativex™ was considered most appropriate, as it was high quality and offered standardised dosing. However, cost was a big barrier to patient access.

Ten years on, under a new Labour Government, New Zealand is intent on making great strides to increase access. The emphasis is terminally ill patients and seriously ill patients needing palliative relief where the focus of treatment is on improving quality of life. Like before, a medicines framework will remain in place. This means access to pharmaceutical-quality medicines, via a doctor’s prescription and pharmacy dispensing.

The Misuse of Drugs (Medicinal Cannabis) Amendment Bill will require new regulations, licensing rules and quality standards. Now being drafted, these will establish the foundation of a regulated market. The legislation will also permit products to be manufactured in New Zealand for the global marketplace.

The groundswell support for the Bill, in Parliament and across society, was focussed on increasing access for those in need. That includes making medicines more affordable.

Like in other jurisdictions, the wider access to pharmaceutical-quality medicines requires a well-considered health professional education curriculum. A robust pharmacovigilance programme to enhance the safety of these medicines is also vital.

The Bill passed its third reading in Parliament and now requires Royal Assent to become part of New Zealand legislation. Regulations, licensing rules and quality standards will be concluded in 2019.

Scientific Committee gives green light to medicinal cannabis

Like most other European countries, France is considering a programme for medicinal cannabis, to ensure patients have legal access to a product that can improve their quality of life. On Thursday the 13th of December, the temporary scientific Committee CSST submitted its advice and findings to the ANSM, the French National Agency for Medicines and Health Products Safety. The preliminary conclusion is that ‘It would be “appropriate to authorise the use of therapeutic cannabis […] in certain clinical situations and in cases where [existing] therapies provide insufficient relief or are not well tolerated”.

CSST

According to the French media, that means the temporary Committee gives the ‘green light’ for medicinal cannabis in France, even though this Comité Scientifique Spécialisé Temporaire (CSST) – which started under the Chairmanship of the psychiatrist Dr Nicolas Authier on the 10th of September 2018 – does impose some prerequisites. Next, the Agence Nationale de Sécurité du Médicament et des produits de santé (ANSM) will take a decision about the Committee’s advice. This decision is expected shortly.

Important steps

The Belgian pharmacist and adviser Igna Huyghe has been closely tracking the process in France and she believes that important steps have been taken over the past few months. Certainly since June this year. “It has been a long time coming, but now there is real movement and it is clear that signals about the potential of medicinal cannabis are taken seriously at the highest level. Over a short period of time, the CSST Committee interviewed a large number of stakeholders in France and beyond and appears to be following the lead of many other European countries. Although the Committee quite rightfully acknowledges that large amounts of scientific research are required, it also recognises that cannabis provision for medicinal purposes meets a major need.”

French patients

France has an estimated 300,000 to 1 million patients that could benefit from medicinal cannabis. The country has permitted use of two products based on cannabinoids, but one is only prescribed to patients with neuropathic pain in extremely specific conditions (Marinol®), whilst the other (Sativex®) is still not available in pharmacies due to discussions about the price.

It is a well-known fact that a large number of French patients has discovered cannabis as medication, but need to enter the illegal circuit and are not guaranteed a consistent or safe product. There is an urgent need to regulate cannabis for medicinal use in France, and the Minister for Public Health Agnès Buzyn has said that she will not exclude cannabis as a legal medicinal product for patients.

Medicinal cannabis

As in many other countries, the concept of ‘medicinal cannabis’ leaves plenty of room for discussion. “The problem is that the concept of ‘medicinal cannabis’ is not clear to many people, including patients, healthcare professionals or politicians”, concludes Ms Huyghe. “There is a demand for a standardised full-spectrum product that is produced in accordance with pharmaceutical standards, i.e. that is GMP compliant. A product that is of consistent quality, guaranteed safe as much as possible, affordable and still available in the future. A product that is tested carefully and ends up with patients through the healthcare systems – doctors and pharmacists – and where there are options to monitor the patients and consequently the product. Such a standardised product is also the only basis for scientific research.”

Round table in Paris

Ms Huyghe, who provides information about medicinal cannabis to patients in Belgium and France was in Paris on the 5th of December, when the temporary CSST Committee shared the first findings of its study with the public during a round table. “On that day we actually heard the recommendations from the report”, she said. “They want to make medicinal cannabis available for chronic pain, certain types of epilepsy, palliative care, supportive care in oncology and for multiple sclerosis. Smoking cannabis is not an option, but the Committee sees possibilities for vaporizing or oral administration.”
The Committee also recommends that patients are monitored to ensure that the effectiveness and any side effects of medicinal cannabis are charted. There will be special attention for the assessment of the benefits of treatment and any risk of addiction. The Committee also aims to promote scientific and other research. When the ANSM adopts the Committee’s recommendations, the second phase of the research starts. That will determine the most appropriate administration method, how the distribution of medicinal cannabis can be organised and whether there can be any reimbursement. The final advice from the temporary Committee is expected in September 2019 and it would seem logical that the French programme for medicinal cannabis will not start before 2020.

Agricultural country

Aside from the discussion about the contribution that medicinal cannabis makes to public health, France also has a discussion about the economic impulse promised by the cultivation of medicinal cannabis. Traditionally, France is an agricultural country and in some départements and régions farmers are struggling to keep their heads above water. It is not surprising that the agricultural sector is considering the opportunities provided by medicinal cannabis with interest and espoir (hope). Hemp is grown in many parts of France and the country is already able to deal with cultivating controlled substances; France harvests more than 100 tonnes of opium poppies, which accounts for 21% of total global production, per year. Ms Huyghe continued “It is logical that the French wish to study how they can control the production of medicinal cannabis themselves, but for patients we hope that the economic interests will not undermine the medicinal importance. I have the distinct impression that they are well aware of this in France.”

The Dutch Transvaal Apotheek is a pharmacy with a history. The library contains books from 1889 and according to the website one of the clients has been coming here for more than seventy years. Under the leadership of Paul Lebbink and Arwin Ramcharan, in 2015 they made medicinal cannabis oil available in the Netherlands for the first time.

With this, the pharmacy from The Hague made headlines both in the Netherlands and abroad, much to the surprise of the Transvaal Apotheek staff. “The impact was larger than expected”, Arwin Ramcharan, chemist and QA at Transvaal Apotheek, remembers.

OMC

Since 2003 Dutch patients have access to medicinal cannabis flos. The cannabis programme is run by the Office for Medicinal Cannabis (OMC) on behalf of the Dutch government. Ramcharan about this time: “As pharmaceutical chemist we were already well acquainted with the dried product and many of the users. But once we had refined the production process and the oil was released onto the market, the demand proved to be much greater than expected.” The pharmacy currently serves patients throughout the Netherlands and sometimes even abroad. The oil, which is available in five different varieties, is used for a multitude of conditions, with pain, epilepsy, glaucoma, migraines, nausea, infections, restlessness and insomnia, spasms and decreased appetite being the most common.

Cystic fibrosis

The Dutch pharmacist made history again in 2017. The Transvaal Apotheek started to fight big pharma with their own cost-effective alternative to exorbitantly priced medication for cystic fibrosis.

Patients in the Netherlands can only get the oil on doctor’s prescription. They can obtain it at the counter or have it delivered to their home by ‘medical post’. The number of patients who come to The Hague from neighbouring countries to take home oil is gradually increasing. They need a doctor’s prescription and – of course – permission to bring the cannabis oil home. Ramcharan: “We mainly see patients who have tried all other types of medication and who have become more or less therapy resistant. They have heard of medicinal cannabis, but they also want a product with known contents and a traceable origin. And they often appreciate receiving guidance from their physician and the chemist. The price of the oil is sometimes the subject of a debate, but most patients understand that the production requires investing in equipment and knowledge and that this is a labour-intensive and strictly-controlled pharmaceutical production process.”

Magistral preparations

Cannabis oil is a commonly used form among patients who administer their medication themselves because it is easy to dose. Transvaal Apotheek is one of the last Dutch pharmacies that still make magistral preparations so it came as no surprise that Ramcharan and his colleagues were asked to produce cannabis oil. “The request for oil came from the BMC and was initially aimed at young patients”, Ramcharan says. “In approximately nine months time we, in collaboration with (then still) pharamcist-in-training Svenja Laarhuis and researcher Arno Hazekamp, created a standardised process for the preparation of oil with mainly CBD, based on the then new Bedrolite® brand. After a large number of trial runs and tests we were able to start supplying oil to our patients in 2015. We were lucky to have good active pharmaceutical ingredient.” Bedrocan products are being used for the production of the oils. Ramcharan: “The medicinal cannabis available through pharmacies in the Netherlands is standardised and extensively tested on contents and the absence of contamination. It is also produced in compliance with GMP which prevents unnecessary discussions. And… our oil is also extensively tested. Because if you supply a medicinal product while being unsure about its quality and safety, you are on the wrong track, to put it mildly. The responsibility is simply too great.”

Other pharmacies

Transvaal Apotheek is no longer the only pharmacist in the Netherlands that is allowed to produce cannabis oil. Three other chemists also received permission and have started production and deliveries in the last few years. Two of these received guidance from Ramcharan and his colleagues. “These pharmacies thought it was unnecessary to re-invent the wheel and wanted to start production of medicinal cannabis oil as quickly as possible, while also assuring top quality”, Ramcharan says, who thinks a standardised way of working is important. “We think it is important to work in a standardised way and to use the same ingredients. This way you produce the exact same product every time, which means you can make statements about the effects and possible side effects in the long run.”

In the meantime the pharmacists exchange information and thus collect clinically relevant information. Ramcharan says: “Especially in the case of medicinal cannabis, everyone is waiting for clinically relevant information. Collaborating with other dispensers can also reveal information about the application of medicinal cannabis for other conditions. We therefore have collected information about migraine patients.”

According to Ramcharan, more patients can be followed by the collaboration: “In collaboration with a specialist, our chemist is currently monitoring a group of approximately 20 epilepsy patients. We are seeing, for example, positive effects from the administration of CBD. But we can now also provide information about possible side effects. As soon as we are able to broaden and deepen the scope of this type of research, we will gain access to incredibly valuable data. Not just for patients and professional care providers, but also for researchers.”

Medicinal use of cannabis has been legal in Australia since 2016. There are currently an estimated one thousand patients who have been granted permission. That is a very small number in a population of 24 million. Indeed,  it is assumed that one hundred thousand patients still obtain their medicine from illegal sources. How is that possible? We talked about this with Professor Iain McGregor, Academic Director of the Lambert Initiative for Cannabinoid Therapeutics, an Australian research institute within the University of Sydney.

Since its establishment in 2015, McGregor and his team have been researching the effects of medicinal cannabis, among other things. This year they published the results of two surveys from both physicians and patients. This was the first time both target groups were surveyed about the medicinal use of cannabis. And it showed hidden populations.

High price

According to McGregor, the high price of medicinal cannabis is a major reason why Australian patients still depend on the black market: “Most of the people are extremely poor because they live on social welfare or pensions. People cannot afford pharmaceutical products that are on offer in the federal scheme. It would cost 60,000 Australian dollars a year to treat an epileptic child with 1,000 milligrams of CBD a day.”

Medicinal cannabis is not covered by health insurance or government pharmaceutical subsidies in Australia. Therefore, McGregor is not surprised that patients are looking for cheaper alternatives. “Our research even shows that a quarter of the patients sometimes don’t pay anything at all for their cannabis. They get it for free or grow it themselves.”

The same research shows that Australian patients do not want it to be this way. “The same as with other medications, patients want a standardised product of pharmaceutical quality that is available at the chemist. This wish does not comply with the current programme”, says McGregor.

General Practitioners

The Australian GP is not to blame. The majority of GPs think that medicinal cannabis should be available on prescription. The Lambert Initiative surveyed 640 General Practitioners (family physicians) last year and the results astounded even researcher McGregor: “We knew pain doctors and specialists are very negative about medicinal cannabis. But the majority of the GPs, the family doctors, are in fact in favour of medicinal cannabis. This was quite surprising.”

GPs also say they support the use of cannabis for conditions such as chronic pain, epilepsy (intractable epilepsy) and palliative care, but less for depression or anxiety disorders. According to McGregor, the problem with the Australian system is that GPs are not allowed to prescribe medicinal cannabis, although they would like to. This task is reserved for specialist physicians (neurologists, oncologists and palliative care physicians) only. McGregor: “In Australia it is very difficult to get access to specialised medical care, let alone to find a specialist who is interested in cannabis-based medication.”

Therapeutic Goods Administration

Over the past two years the Australian drug agency the Therapeutic Goods Administration (TGA) has approved 1,442 applications. The number of patients who actually use cannabis is lower than the number of applications because some physicians submit multiple applications for the same patient. McGregor and his team estimate there are about one thousand patients who actually make use of the programme legally. But he thinks there could be many more: “Our opinion is that people that are suffering should have the benefit of medicinal cannabis if it is going to have a favourable effect. It is very simple: if the doctor wants to prescribe it and the patient wants it then the politicians and regulations should probably get out of the way.”

Another obstacle is the complex application procedure for the Australian medicinal cannabis programme. The physician must first submit an application to the Federal Department of Health. This application must clearly show that alternative treatments are not effective and that an extensive literary study has been carried out.

Paperwork

Until recently the same application also had to be sent to the Department of Health in the state where the patient lives. McGregor: “The paperwork was just terrible. There were also a lot of refusals because both the state health and federal departments were really looking for evidence that cannabis products were better than existing medication.”

The procedure has been adapted so physicians only have to fill out one online form and most applications are now assessed within 48 hours. Still McGregor is not satisfied and advocates for expanding the number of permitted conditions: “Patients are using cannabis for quite different conditions to the ones that you can get an approval for from the government. Most of the conditions are not acknowledged by the Therapeutic Goods Administration. For example, fifty percent of the patients are using cannabis for controlling their back pain and back pain is not on the TGA list. There is no evidence or clinical study that shows back pain is a condition that cannabis treats. But people are doing it anyway.”

For more information about the studies mentioned in this article, see:

Nicotine gum is probably the most well-known medicinal application. But chewing gum containing medicinal cannabis is something new. So new that the first batch has not even been made yet. AXIM Biotechnologies developed the product and is waiting to start the first clinical trials in the Netherlands, Israel and Canada.

Earlier this month they uncorked the champagne bottles at both the American head office in New York and in the Netherlands. The company that is listed on the American stock market (AXIM U.S.: OTC) received a GMP certificate from the Dutch government to produce samples for clinical trials. This test medication may now be used worldwide as a research resource. This is a huge milestone for the company that has been trying to bring medicinal cannabis gum onto the market since 2007.

MedChew Rx

MedChew Rx, a type of gum produced by AXIM looks very promising. It contains 5 milligrams of CBD – a non-psychoactive component of cannabis – and 5 milligrams of THC – a psychoactive cannabinoid. The cannabis for this chewing gum is supplied by Bedrocan. The medication was developed to treat pain and spasms in Multiple Sclerosis (MS) patients. The Dutch VU University Medical Center in Amsterdam will carry out the clinical trials.

Motion sickness, pain, quitting smoking, dental decay and middle ear infections are all well-known or lesser-known medical conditions for which medicinal chewing gum is available. AXIM consciously chose chewing gum as a method of administration.

According to Lekhram Changoer, Chief Technology Officer, it is a socially accepted and user-friendly method. Much more so than smoking or inhaling cannabis. And does it work? Changoer: “Chewing has a considerable effect. Chewing activates your brain. Scientists at the Vrije Universiteit in Amsterdam have proven that the medication has a greater effect when chewed, especially for pain.”

Just like a pill

According to Changoer, physicians have responded positively to this administration method: “It is not entirely new. They are already familiar with nicotine gum. Physicians don’t want their patients to smoke cannabis because it is unhealthy. Some physicians are also weary of inhaling. Not all patients can or want to use a vaporizer. Chewing gum is easy to take with you, just like a pill.”

The goal is to have the gum officially registered as medication. This way a physician can prescribe it and determine the dose. But clinical trials must first show that the product works.

Changoer: ”Preliminary studies paint a positive picture of the implementation of CBD and THC. Research will provide us with more insight into dosage. The approach is that the patient will calmly chew on one piece of gum for about twenty minutes. The absorption of the active chemicals will then take place via the mucous membranes in the cheek.” Changoer expects it will take at least another three years before the chewing gum will be available on the market.

Friday the 20th of April 2018 was a momentous day in Israel – a number of pharmacies are now permitted to issue medicinal cannabis to patients. This also marked the start of a pilot programme, charting the course to a regulated and properly documented system for issuing medicinal cannabis in Israel once and for all. For Yuval Landschaft, head of the Israeli Medical Cannabis Unit (MCA), this is a dream come true. “We wanted a system where the entire chain – from research and cultivation to diagnosis and distribution – is carefully regulated. We call that the medicalisation of cannabis. That system is now in place.”

Since 2013, Yuval Landschaft has been on top of Israel’s cannabis programme. The programme intends to provide medicinal cannabis for patients in Israel, but over time it will also deal with the export of medicinal cannabis abroad. Compliant with quality and safety requirements, the starting point was ‘medicalisation’; the use of cannabis for medicinal purposes based on scientific knowledge. Landschaft recollects that “all the available knowledge of medicinal cannabis in Israel was brought together and was used to develop this programme. It makes medicalisation something quite different from decriminalisation or legalisation, because our programme is focused on patients.”

The Green Book

The Israeli programme – recorded as ‘The Green Book’ – covers medicalisation, the standardisation of cannabis products, the training of doctors and pharmacists and the organisation of agro-technical and medical research and development. That provides for a clear chain – from product development to the patient. It goes without saying that growers are selected carefully and that requirements are imposed on the distribution side (prescribers, pharmacists). The National Center for Cannabis, part of the Ministry of Agriculture and the Ministry of Health, maintains tight control.

Whilst in Israel the medicinal use of cannabis has been permitted for some time, a controlled programme for ‘medicalisation’ proved difficult to get off the ground. Setting up the MCA paved the way for a programme for medicinal cannabis. Yuval Landschaft was appointed to lead the unit. “There was a system where growers worked in a ‘traditional’ way and played a role in the distribution and information provision to patients”, remembers Landschaft. “But you can’t call that a medicinal programme, because it didn’t involve any healthcare professionals. In other countries, including the Netherlands, they were much further ahead. We obtained comprehensive information from the Dutch government and were impressed by the achievements; a clear programme focused on medicinal use and pharmaceutically responsible products. That was exactly what we had in mind.”

Cannacopia

The MCA – which has representatives from the Ministries of Agriculture, Health, Justice and National Security – summarised the chain for production and distribution into five chapters, which Yuval Landschaft refers to, in jest, as the ‘Cannacopia’ or ‘the Torah of cannabis’. “We have a clinical approach that is focused on collecting and distributing scientific knowledge, identifying indications, designing a treatment protocol, defining products and their potential, administration and risk of abuse and addiction. Furthermore the entire chain – from cultivation to distribution – is covered by quality protocols based on the familiar and recognised good practices at agricultural, clinical, delivery, manufacturing and security level. We are aiming high, but it is the only way to properly regulate the availability of medicinal cannabis for patients.”

Landschaft believes that Israel has now joined a small group of countries where the production and distribution of medicinal cannabis is organised by the book. “In Israel we have paved the way to a thorough system. The patient is always the starting point and the only route is that of safe, standardised products, prescribed and issued by healthcare professionals. They have the medical knowledge required to determine a diagnosis, to prescribe medication and to support patients. Without doctors and pharmacists cannabis is not medication.”

It took him seven years and tens of millions of dollars to transform a raw plant into a mainstream medical drug. Perry Davidson is the creator of the Syqe Inhaler – a new technology that allows doctors and patients to precisely dose pharmaceutical quality ‘cannabis flos’ by inhalation. After all these years of hard work, according to Davidson ‘it is still something worthwhile waking up each morning for’.

Is that still the case?

‘Yes. What’s really driving everyone at Syqe is the realisation that what we achieved with cannabis can and should be replicated with other medicinal plants. Plants that pharma has shied away from for so many years. A technology that from one end takes a raw plant, and from the other end produces a pharmaceutical grade product, will have a profound impact on health.’

You founded Syqe Medical seven years ago and you are running the business. How does a usual business day look like?

‘A usual business day in a medical start-up is relentless. Add to that the fact that the Syqe Inhaler is the first product of its kind, designed for an industry which is still in its infancy. This forces us to innovate in practically every frontier, be it technological, clinical, regulatory or legislative. Therefore a usual business day in Syqe is an interaction between the multiple dedicated teams – biology, chemistry, mechanics, electronics, software, design, product, engineering, operations, clinical, pharmacology, QA/RA, legal and of course the standard teams of HR, finance, business development, marketing and IP.’

What inspired you to start this company?

‘What drove me to start Syqe was sheer frustration. In 2006, I co-founded the first cannabis company in Israel and while I was the CEO I interacted with nearly 2,000 patients and of course the medical community at large. I experienced first-hand the hardships of introducing a plant into a western health system and offering patients a predictable and safe treatment. I did not accept the fact that cannabis had such a significant therapeutic role, but not a single pharmaceutical company was able to transform it into an acceptable and efficacious mainstream drug.’

What makes the Syqe Inhaler different from all other ‘vaporizers’ on the market?

‘For the cannabis industry, Syqe is the first and only metered dose cannabis inhaler meeting pharmaceutical standards, a strong emphasis on meeting pharmaceutical level drug delivery precision.

For the pharmaceutical industry, Syqe is the first and only drug delivery platform able to administer whole plants within pharmaceutical standards, and also the first that allows changing dose levels in real time – the first Selective Dose Inhaler.’

How did you manage to put the whole cannabis plant into a small cartridge that’s is not larger than a biscuit?

‘Syqe’s selective-dose inhaler consists of a cartridge that holds 75 VaporChips^TM. Each chip is loaded with an exact amount of fully-standardised whole-plant cannabis, ground in a unique process that preserves the medicinal properties of the plant in their entirety. Real-time thermal and airflow controls enable the inhalation of precise amounts of naturally-occurring molecules directly from the cannabis plant.’

You are using Bedrocan’s standardised raw plant material for the micro dosed cartridges. Why have you chosen for Bedrocan as a supplier?

‘Quite simply Bedrocan was able to provide us with pharmaceutical-grade GMP starting material. The standardisation levels Bedrocan has achieved is unparalleled, allowing us to guarantee the pharmaceutical precision levels which are so needed for this industry.’

Do you think this device can contribute to a better acceptance of cannabis as a medicine? 

‘Any technology that takes the cannabis plant as a whole and transforms it into a pharmaceutical product will immediately increase the acceptance of cannabis as medicine.’

Bedrocan recently funded the publication of a booklet explaining the effects of medicinal cannabis in clear language.

This booklet covers key information on the cannabis plant, cannabinoids, the biological pathway for their action, and the quality requirements of modern medicines. It also takes a forward step to consider the perspectives of experienced health professionals, and insights from patients.

The booklet is intended as an introductory text to the therapeutic use of cannabis. For now it is an English publication intended for the health sector, policymakers, and patient groups.

The booklets official release was at the International Cannabinoid Research Society 2018 conference; this coincided with its New Zealand release, by the author, at Medsafe, the Ministry of Health.

See link to download a copy.

There is perhaps no debate in the world of cannabis more contentious than that of species. The genus Cannabis sativa L. is the only official species, but the cannabis industry is using other terms as indica and hybrid to promote their varieties. Associate Professor Sean Myles from the Canadian Dalhousie University recommends avoiding the use of these terms as a recent study has demonstrated that current labelling of varieties as sativa and indica does not reflect any meaningful genetic identity.

Myles, who supervised the study on the genetic differences between the two cannabis types and their hybrids, will present his results on the International Cannabinoid Research Society (ICRS) conference in Leiden, Netherlands, from 1 – 4 July 2018. In the run-up to the conference, Bedrocan asked him a few questions.

Do you consider the results as ground-breaking?
‘No, I don’t. Any professional in breeding or genetics with even peripheral knowledge of the cannabis industry would have bet that the ‘sativa’ and ‘indica’ labelling in the current cannabis market was unlikely to reflect genetic reality. It just took some data to demonstrate the degree to which this is the case, which we have done and continue to do.’

How did you come up to study cannabis?
‘Our laboratory developed an interest in cannabis because we do similar research in genetic ancestry deconvolution in other species, like grapes and apples. It made a lot of sense to extend our expertise to cannabis since it is an economically valuable agricultural species, little was known about its genetic structure, and there was widespread use of a dichotomy (i.e. ‘sativa’ vs. ‘indica’) that was believed to reflect ancestry. For the study together with Bedrocan, we benefited from their expertise in chemical profiling and paired it with our expertise in genomics and bioinformatics. The result has been fruitful in terms of insights into the question of variety identity.’

What are the reactions to your research results so far?
‘Overall, the public has taken a strong interest in our results, which suggest that the manner in which the labels ‘sativa’ and ‘indica’ are currently being used do not reflect meaningful genetic identities. Many of those in the cannabis industry, both medical and recreational, have also headed our advice to avoid using these terms until there is a consensus about what they mean. In the end, I believe our results have contributed to a shift whereby varieties are being increasingly described by their measurable chemical content rather than by their purported ancestry.’

What were the responses from companies that sell cannabis?
‘There are those in the recreational cannabis market who are unlikely to abandon the terms ‘sativa’ and ‘indica’ because they are useful terms for marketing their products. This is especially the case for companies selling seeds online. Their discontent is acknowledged, but the evidence speaks for itself and I’m hopeful that, in the end, labelling of cannabis products will be based on empirical data rather than marketing tricks.’

Some people claim to be able to smell the difference between an indica or sativa type. What would you like to say to them?
‘Our results do in fact suggest that the labelling of strains as ‘sativa’ vs. ‘indica’ may have more to do with their aromas than their genetic ancestry. Thus, in this case, these people may in fact be partially correct – they can associate a smell with a label. However, this still does not mean that the labels are capturing meaningful genetic information.’

What would be your recommendation to medicinal cannabis producers? Whether or not to make the distinction?
‘Our recommendation is to avoid the use of ‘indica’ and ‘sativa’ as it’s likely to create confusion in the marketplace.  So far, there is no evidence to support this dichotomy as a useful tool for describing ancestry or chemical composition.  We advise producers to describe the content of their product empirically with regards to cannabinoid and terpenoid content.’

Cannabis has been on the worldwide list of banned substances since 1961 and according to the World Health Organization (WHO) has hardly any medical value. This view could very well be coming to an end. Last week the ECDD, a special WHO drug committee, met for the first time to discuss exclusively the pros and cons of cannabis for health. Various parties from the field – doctors, patients and experts – were invited to the hearing to give their advice to the committee.

At the ECDD meeting the International Association for Cannabinoid Medicines (IACM) showed a video message with the intention of giving doctors and patients more opportunities to prescribe medicinal cannabis. According to IACM director Franjo Grotenhermen, it is a good sign that his organisation was allowed to speak. The positions of the selected speakers say a lot about the possible outcome of the meeting. Grotenhermen: “For the first time in history speakers had the opportunity to say the current situation is no longer justified. The committee will probably use these statements in their own recommendations. Otherwise they would have invited parties which are more focused on the dangers of cannabis use.”

Michael Krawitz of the FAAAT, an international think-tank on drug addiction, calls the meeting of historical importance. Krawitz, an expert in the field of international drug policy for over twenty years, was in Geneva at the fortieth meeting of the ECDD to submit an advisory report. “It was a great meeting. Their recommendations are likely to change international law,” is the high expectation of Krawitz. “It is the very first time the medicinal use of cannabis is on the ECDD’s agenda. In 1961, cannabis ended up as a prohibited drug in the UN treaty without ever being officially reviewed by experts. A genuine formal scientific evaluation of cannabis as a medicine has never been done. That is now being put right.”

The Dutch Harm Hids was one of the individual speakers. “The meeting was very well set up. You would expect everyone to be against cannabis, but that was certainly not the case.“ Hids has a son with Crohn’s disease, a chronic inflammation of the intestine.

His son has successfully used CBD capsules and THC oil for years, which locally counteracts inflammation. Hids: “He is given a maximum of 12 mg of THC per day. He does not get high and can just go to school and study.”

During the meeting of the World Health Organization, it became clear that the committee is struggling with recreational cannabis use. In order not to blur the market, according to Hids, the medicinal cannabis industry must remain far away from recreational use. “As long as the product remains smokable, then you know for certain that people will also use it for recreational purposes. You prevent abuse by transforming cannabis to forms that are totally uninspiring for recreational use. That was my message to the committee.”

The final report and recommendations from the meeting will be available on the ECDD website by the end of July 2018.  After approval from the WHO the recommendations will then be put to a vote with the 53 member states of the Commission on Narcotic Drugs. This body must eventually reach agreement on whether the current UN treaties may be amended.

There is nothing Chelsea Leyland (30) would like more than for her older sister to have access to medicinal cannabis too to curb the daily epileptic seizures. But…her sister lives in the UK and medicinal cannabis is not permitted in that country. Leyland, an epilepsy patient herself, is currently working on a documentary about her own life and that of her sister, who has sustained irreparable brain damage as a result of the many seizures. The documentary Separating The Strains is aimed at providing more insight into the effects of medicinal cannabis and at fostering understanding and empathy amongst doctors and politicians in the UK.

The film, which is set to be released at the end of this year, will show a world of contradictions. Chelsea Leyland is a young successful DJ and model, lives in New York and travels around the world to attend the best parties. Her fascinating life is in stark contrast with that of her older sister Tamsin (35), who lives permanently in a full time care because of her illness.

Chelsea Leyland has access to medicinal cannabis, her sister does not. At the moment British-born Leyland lives in America, where medicinal cannabis has been legalised in 29 States. “People ask me why I don’t take my sister to New York, but she is too ill to fly. She has 20 to 30 seizures a day and needs 24/7 care.”

According to figures from the British epilepsy association, more than half a million Brits suffer from epilepsy. Since her early teens, Leyland has had a type known as juvenile myoclonic epilepsy. Two years ago, she stopped her regular medication and gradually moved over to CBD oil. Leyland had serious sleeping issues that were caused by her epilepsy medication. A nasty side effect, because a lack of sleep only increased the frequency of the epileptic seizures.

It was never Leyland’s intention to stop her epilepsy medication. She went to her neurologist for advice. He was very dismissive about her wish to learn more about medicinal cannabis. “I was so angry with my doctor. I felt totally unsupported. I expected supervision and involvement, but what I got was a narrow-minded response. The trust and confidence in my doctor was gone, and I decided to find out for myself.”

On the advice of an acquaintance, she started with CBD oil, which she bought from an online shop in England. As in most other countries, this oil is offered as a food supplement and consequently it is freely available. However, CBD is one of many substances in a cannabis plant and because cannabis is on the list of prohibited substances worldwide, CBD oil should really be illegal too. Yet most authorities turn a blind eye. Chelsea Leyland commented “The shops are everywhere. We have actually created an uncontrolled industry where patients use food supplements as medication without any real knowledge. They’ve read somewhere that CBD can cure cancer or can help treatment of MS or epilepsy and they buy a bottle of CBD from their local health store to be cured.”

Leyland argues for regulation and recognition of cannabis as official medication. ”You cannot stop patients. Look at me. I did the same and that’s a major issue. Patients buy cannabis on the internet, from the health store or on the black market. Those are not the right channels. They need support from a doctor. Patients are entitled to that.”

Her decision to reduce her medication herself was really dangerous – she realises that now – and she does not recommend it to anyone. Leyland said “I was stubborn and I was lucky. There is no guarantee that cannabis use will work well for everybody.” She is a strong ambassador for open and honest discussions between patients and their doctors. She also thinks that healthcare professionals should seek better information “More doctors should become involved with the subject of medicinal cannabis. There needs to be investment in education to ensure that medicinal cannabis can be used as normal medication and not as a food supplement.”

However, she does not regret her decision, because since she made the transition she no longer suffers from epileptic seizures. She recalls the first time she took the oil. “It was a real sensation. For the first time I hit the ground with both feet. As an epilepsy patient you feel like your head is full of individual pieces that you cannot connect. Your brain is out of kilter. Your memory does not work well and it is difficult to find the right words. It’s like a chest pain when you’ve got a cold, but in your head. After my first use I felt calm in my head for the first time. I was able to think clearly. I thought ‘Gosh, this is what it feels like for normal people, who don’t have epilepsy’.“

To the question what’s to happen to her sister, she answers with hope “The frontal lobe of her brain is completely damaged by the seizures and that damage will not repair, ever. But it is not too late to help her move to cannabis. It would be wonderful if we could improve the quality of her life by just a fraction and if we could half the number of seizures.”

Leyland firmly believes that the documentary, which is still in the making, will change the way in which doctors and politicians view cannabis. “I want to appeal to people’s empathy, including that of politicians and doctors. The power of my film is in the stories of the patients. Like that of a mother of a child that has 100 seizures a day. The viewer sees the health improve enormously when the child is administered medicinal cannabis. You don’t need any more proof.“

Chelsea Leyland also realises that success stories are not enough. “We need scientific evidence”, she continues her argument. “Cannabis is an extremely complexed medicine that contains many active components. We need more research and people need to receive the right information. We’re not talking about recreational use here, but about real medication. Let’s be clear about that.”

There are more and more cannabis-related conferences worldwide. Bedrocan chooses only meetings about the medicinal use of cannabis or where we can tell our story about GMP-quality medicinal cannabis. The ICRS symposiums is close to our heart.

This year it will be held in Leiden, the Netherlands (30 June to 5 July). ICRS, the peak International Cannabinoid Research Society, is an independent organisation promoting scientific research in cannabinoids, the most important components of cannabis.

ICRS provides impartial information about cannabis and cannabinoids. It is also provides a forum for research discourse, and a platform to share scientific the latest studies. This year the global scientific community meet in Leiden where Bedrocan is one of the principal sponsors.

During the year, you can catch up with Bedrocan, when we present at the following international conferences:

When a science student stepped into his office and explained about the medicinal use of cannabis, Dr Radovan Hřib developed a serious interest in cannabis as a medicine in the Sint Anna University Hospital, Brno city of Czech Republic. Prescribing since May 2015 under state registration, he currently treats around 80 patients experiencing pain of different origin. Dr Hřib has a message for reluctant doctors: “Do not be afraid about cannabis for medicinal use. It will surprise you pleasantly.”

According to Dr Hřib there are three types of patients in his hospital. The first already has some good experience with cannabis, and wants to the use it under his medical supervision. The second patient type is already taking a number of analgesics such as non-steroidals, paracetamol, anti-rheumatics and opioids. They only receive partial response. With the third type, current treatment using classical medications hardly work and cannabis is their last hope.

He prescribes fully standardised cannabis flos, the whole dried flower, as it is the only pharmaceutical-quality product available in the Czech Republic. His patients take their medicine either prepared by the hospital pharmacy, as capsules containing a single dose of cannabis flos and are taken by mouth, or are dispensed cannabis flos for inhalation by vaporization. Just recently the Sint Anna Hospital has set up a special area where pain and cancer patients learn how to operate a vaporizer.

Why do you prescribe medicinal cannabis to patients? Is there a personal motivation?

I prescribe medicinal cannabis to patients for one simple reason: because it is helping them. This is driven by my professional curiosity and the intention to provide the best outcomes for my patients. An overwhelming majority of patients are actively interested in possibility using it as a treatment for pain. However, there will always be a few patients with strong opinions against its use.

What are the key benefits of medicinal cannabis?

I still have many benefits to discover. However, the longer I prescribe it, the more I am fascinated. In the treatment of pain, cannabinoids act in several modalities, apart from a

good analgesic effect, it significantly improves sleep and its use is accompanied by a reduction in anxiety. In this way, the so called vicious circle of chronic pain can be broken in several places.

What are the risks of prescribing medicinal cannabis?

The very individual character of dosing poses a disadvantage for many physicians. In Czech Republic we prescribe cannabis as an individually prepared medical product. Therefore you need a collaborating pharmacist who understands what is needed. I am lucky that I can rely on the great support of our hospital pharmacist Monika Pecháčková. As a prescribing doctor I would like to point out that my work with medicinal cannabis would not be possible without the support and tolerance of my faculty superiors, my family, colleagues and co-workers at the workplace and in the hospital.

Why is that?

There is great stigma around medicinal use of cannabis and this is also present in the Czech medical community. It is still tightly regulated, it is risky because there are still unknowns. As opposed to other work places, the hospital I work at has been openly supporting me from the very beginning.

How do you decide the best dose for individual patients?

Mostly, this being specific for the Czech Republic, I use oral administration through capsules. Mainly for financial reasons as patients appreciate that this method does not significantly increase the price of already expensive plant material. The body is offered the whole herb, and we let the human organism to choose what to absorb from it.

At the moment, I am using two dosing schemes for capsules. First one is according to my own empirical experience. We start at a dose of 0.125 gram of cannabis decarboxylated by heat, presented in a gelatine capsule, per night (which makes up to 18 – 25 mg THC depending on variety). If the patient experiences difficulties, the patient can call me immediately, at any time of the day. Within 7 days I want to hear from the patient, also if they only benefit from the treatment. When there are significant side effects, usually it is dizziness, we reduce the dose or we try to encourage the patient to keep trying. The dose is increased at the earliest after one month from the beginning of the therapy.

I also started using the second scheme according to neurologist Ethan Russo. Starting with a dose of 2.5 mg THC per night. After about 5 days we gradually increase the dose by 2.5 mg THC.

When vaporizing, I teach the patient about gradual titration. In the near future, I would like to combine oral capsule administration with vaporization. Now that we have opened our user centre, we will try to introduce the gradual titration directly in the hospital, or during hospitalisation.

Do you encounter diversion for misuse or the abuse of medicinal cannabis?

So far, I was lucky to have disciplined patients, and I did not have to deal with this problem with regards to medicinal cannabis.

How do you identify this issue in your practice?

Given the fact that I have been prescribing highly addictive opioids to my patients for over 18 years, I have quite a lot of experience with diversion for misuse or the abuse. Fortunately, with patients experiencing chronic pain, this problem is minimal. Mostly, patients with this problem identify themselves. For example, they often “lose” medications, are not disciplined in treatment or check-ups, and so on. I believe that the best way to prevent and deal with abuse is to have an individual and personal approach to the patient.

If a doctor wants to know more about prescribing medicinal cannabis, what would be a good information source?

I recommend two basic resources to doctors.

• The publication An Introduction to Medicinal Cannabis by Arno Hazekamp. It is also translated in Czech and can be downloaded from Bedrocan’s Czech website.
• The retrospective analysis by the authors Zábranský, Hanuš, Rokyta: “An overview of the current knowledge about the healing effects of cannabis and its products and its perspectives“, published in the Czech language in the Bulletin of the Association of Practical Doctors 2016 and 2017.

Furthermore I recommend the following websites:

• IPVZ – the Institute of Post Gradual Education in Healthcare. They are holding already a third training seminar on cannabis.
• ICCI – International Cannabis and Cannabinoids Institute based in the Czech capital Prague. Our hospital is also now offering the opportunity to organize seminars in cooperation with ICCI.
• SAKL – State Institute of Cannabis for medicinal use
• KOPAC – Czech Patient Association

As the doctor’s experience grows, they can much more rely on their own experience, and only use the internet occasionally.

Do you have any advice for doctors starting out prescribing?

Do not be afraid of medicinal cannabis and try it in your therapeutic practice.

What would you like to say to doctors that are reluctant to prescribe cannabis because there is not enough clinical evidence that medicinal cannabis actually works?

I will only repeat myself. Do not be afraid about cannabis for medicinal use. It will surprise you pleasantly. On the contrary, you will be able to contribute to the creation of scientific evidence. And I mean this as criticism towards the almost exclusively strict use of evidence-based medicine, which is well described, and the tendency to adhere to prescribing only this, rather than being open to new methods and treatments. Trying out new treatments and creating your own opinion… only then you will discover yourself what the real art of medicine is.

The average daily dosage for prescribed medicinal cannabis among Dutch patients has remained remarkably stable over the past years. The average daily dose has risen slightly from 0.64 to 0.73 gram of cannabis per day during two study periods. This can be concluded from a recent study carried out by researcher Bas de Hoop. We asked him why is this important?

Where does the data for this study come from?

The Dutch Foundation for Pharmaceutical Statistics (SFK). SFK is an independent organisation who collects 90% of all prescription data from Dutch pharmacies. This includes the prescriptions for medicinal cannabis, but excludes pharmacies that are located in care homes or hospitals.

All manner of information can be collected from these prescription details. For example, the issue date, the amount of cannabis dispensed, the specialty of the prescribing doctor, and importantly the age and gender of the patient. On the basis of this raw data we produced calculations that provide an approximation, such as patients’ average daily dose and the total duration of use.

Is there an increase in the number of users in the Netherlands?

Certainly, you can observe a gigantic increase in users between the study periods 2003-2010 and 2011-2016. During the first eight years we identified 5,601 people. Six years later we identified 10,826. That is only for prescriptions of cannabis flos. In 2015, cannabis oil became available as a dosage form. In the year after Transvaal Apotheek in The Hague introduced cannabis oil, there are now 6.720 patient prescribed the oral dose form.

We also calculated how many patients there were in relation to the total Dutch population. Those figures are spectacular. In 2003, 6.4 patients per 100,000 inhabitants used a medicinal cannabis product. By 2010,this had moved up to 6.9, which is not exactly a gigantic leap in use. However, by 2016 we note that 24.6 patients per 100,000 inhabitants are prescribed medicinal cannabis, either as cannabis flos or oil.

The introduction of cannabis oil at the end of 2015 had a significant impact on the figures? 

The availability produced an enormous increase. In 2016 alone, the number of patients prescribed oil was much higher than for cannabis flos. Unfortunately, cannabis oil was introduced too recently to provide reliable data on the average daily use or other interesting aspects. However, those data demonstrate that patients prescribed oil were often older and more often female compared to patients who prescribed cannabis flos.

What do the figures say about the age structure and gender distribution of the average patient?

The largest group of patients is over 40 years of age. Eighty percent of the flos users are older than forty years, and this number is 88 percent for the patients who are prescribed cannabis oil. About the same number of men and women are prescribed cannabis flos. In relation to oil, women have a slight majority (60%). Most prescriptions are among patients aged between 41 and 60 years old (42.9%), followed by the category of 61-80 year olds (30.9%). So they are an older group, on average.

In this study we compared the current data with previously published material. The age distribution of patients remained virtually the same for the two study periods. However, there was a slight shift in the gender split – the percentage of female patients fell from 57.1%  to 51.4%.

Why should we care about these figures?

We have been gathering data about medicinal cannabis use in the Netherlands for more than 15 years. We can learn a lot about actual usage. As far as I know, there is nowhere else in the world where these figures are collected centrally. Not even in Canada, which was the first country in the world to start with a medicinal cannabis programme. In other words, these figures are fairly unique and, particularly when it concerns a daily dose of 0.7 gram. The Netherlands has a prescriber-pharmacy model, where guidance for using medicinal cannabis is actively provided. This is important because not every patient has the same course of treatment meaning a doctor and patient and pharmacy work together to find the correct dose and improve patient safety.

This data provides a framework for a doctor to take into account when considering prescribing for their patient.

Can you say something about the duration of use?

The figures demonstrate that as the patient gets older, the number of days they use medicinal cannabis reduces. While it is possible to calculate an average duration, but it is difficult to interpret, given the average duration of use is likely to be affected by deaths in the highest age category.

The daily dose in the Netherlands has been around 0.7 gram for more than 10 years. What does that tell us?

This shows clearly that there is no increase in the consumption of medicinal cannabis in the Netherlands. Policymakers may have fears that the introduction of medicinal cannabis will lead to an increased patient tolerance, physical addiction and dependency. In the Netherlands, policymakers fears are laid to rest with these figures; over a period of 10 years we cannot find an indication for unwarranted increased in medicinal cannabis use.

Can you say something about what conditions Bedrocan products are prescribed?

Unfortunately I cannot provide an accurate answer to this question. The reason is that we do not have the right information. The disease or complaint of the patient is not stated on the prescription, it just says who prescribed it. More than half of the prescribing doctors are GPs (59.2%), followed by specialists (27.1%). The data refer to specialisations, but when it says surgery, cardiology, or internal medicine you don’t know enough to identify the complaint.

Bedrocan has donated ten medical vaporizers to two Czech hospitals. They concern the Volcano Medic®, and they are used in the Sint Anna University Hospital and the Masaryk Cancer Institute in the Czech city of Brno. Under the guidance of trained personnel, pain and cancer patients learn how to operate and dose the device. The Sint Anna Hospital has set up a special area for this purpose, which was put into use officially on 17 April.

The Czech Republic has had a medical cannabis programme for many years. However, as in the Netherlands, cannabis and expensive vaporizers are no longer reimbursed by health insurance policies, causing a major problem for patients with low incomes in particular. Bedrocan hopes that by donating the vaporizers, patients are able to familiarize themselves with vaporization as a method of administration before they purchase the vaporizers. Vaporizing is generally regarded as the most efficient dosage form because the active substances are absorbed quickly into the body. It is also safer than smoking because there is no release of toxic substances, such as carbon monoxide, ammonia or polycyclic aromatic hydrocarbons (PAHs).

Capsules

Bedrocan has been working with one of the doctors of the St. Anna hospital, doctor Radovan Hřib, for many years. As a pain specialist, he prescribes medicinal cannabis for patients with chronic or acute pain. The special user space was his idea.

Doctor Hřib commented “Now patients often have to rely on capsules that are compounded by the pharmacy, but it is not the best dosage form in pain management. Vaporizing is preferable above all else, because the vapour is absorbed immediately into the bloodstream and the effect is felt immediately. ”

In addition to his work in the hospital, Dr Hřib is associated with the Czech patient organization KOPAC. In the Czech Republic he is regarded as the medical expert in the field of medicinal cannabis. He cooperates with government bodies to increase the availability of cannabis for medicinal use to the patients and to simplify administration for doctors.

He was also involved with the registration of medical vaporizers in the Czech Republic. The user area with the vaporizers is intended to teach patients to dose. Doctor Hřib said “Unfortunately there is no universal dosage. Every patient reacts differently to cannabis. Here they learn which dosage suits them best. Under expert guidance, they also discover any possible side effects occur and how to deal with those.”

Recently the Dutch Transvaal Apotheek in The Hague started marketing cannabis cream alongside cannabis oil. This cream is a new dosage form for patients. It is based on the cannabis variety Bediol and is intended for treating skin conditions.

According to Arwin Ramcharan, pharmacists QA of Transvaal Apotheek, the cream was developed at the request of a dermatologist in The Hague. “I won’t mention names, but it is a dermatologist with whom we have worked before. He was already familiar with the cannabis oil we have been preparing on the basis of the Bedrocan varieties since 2015 and which he prescribes from time to time. He wanted to try out a cream based on Bediol for group of approximately 40 patients. If the trial is positive, the group of patients will be expanded. For the time being, other patients can buy the cream from us on prescription.”

With the cream, for which a patient pays 60 Euro (per 20 gram), a new dosage form has been added to the range of cannabis products based on Bedrocan varieties. The Transvaal Apotheek will leave it at that for the time being. Ramcharan: “Occasionally we receive requests for capsules, but they are more difficult to make. Furthermore, it is a significantly different administration method as capsules go via the stomach where substances are broken down; it means you need to increase the dose.”

Clinical Cannabis Care in Breukelen, which prepares oil from Bedrocan varieties, also has a cream available for various skin conditions. However, this Cannabinoid Cream is made on the basis of CBD crystals.

Hospital staff or researchers are at low risk of exposure to patient’s exhaled cannabis vapour. An Australian study demonstrated staff who administer vaporized cannabinoid medication to patients in a clinical environment will not be exposed to THC. The active substance THC was not found in the blood after staff had been exposed to environmental vapours.

A vaporizer medical device is considered to be a safe administration method for patients. There is no exposure to harmful substances like from smoking. The medicinal effects occur sooner with vaporizing than with other administration forms, because the cannabinoids are absorbed into the blood almost immediately after inhalation. It is also a user-friendly method for patients who struggle with swallowing. However, until recently there was little or no knowledge of whether the exhaled vapour would be harmful to other people in the same environment. In other words, could someone else be exposed to THC?

The conclusion is therefore that vaporizing is safe for staff who administer medicinal cannabis to patients. However, a more comprehensive study of this subject is warranted. A study including more participants, room sizes, cannabis varieties, and types of vaporizers would be beneficial.

Since 1st January 2018, cannabis for medicinal use is permitted in Denmark. How did the first weeks work out? If we are to believe the stories in the media, Denmark will be cultivating cannabis on a major scale next year. Doctors on the other hand are sceptical, because there is insufficient scientific evidence. Meanwhile, a public pain clinic is unable to meet demand and patients are on a one-year waiting list.

Odense, the third largest city in Denmark, aims to become the European capital of cannabis cultivation. That was the heading of a newspaper article from early 2018 about the developments in what is known as the centre of Danish horticulture. At the end of last year, a local tomato grower and a hemp grower entered into cooperation with two major Canadian cannabis producers. The Canadians bring money and knowledge, whilst the growers supply the greenhouses and the land. Peppers and orchids are being exchanged for ‘green gold’ and thousands of square metres of old greenhouses are transformed into high-tech businesses.

Cannabis cultivation

According to the Danish medicines agency, which issues licences for cannabis cultivation, 12 Danish businesses have received permission to start cultivating. They may only do so within the context of a four-year pilot project. After two years there will be an interim evaluation and the Danish government will decide whether to continue the project or not. According to Henrik Uth of the company CannGros, currently the only importer of medicinal cannabis in Denmark, obtaining a growers licence does not mean you can start selling medicinal cannabis. “In principle, you just need to present a plan to the authorities. You don’t even need facilities. It will be interesting to see how the production, and the regulation on quality control on Danish grown medicinal cannabis, will come together. There is still little clarity on that point.”

Either way, government rules prescribe that the new growers must be able to produce standardised and consistent cannabis. The levels of active substances must be the same for every harvest. This has been Bedrocan’s speciality for years, and for doctors who wish to prescribe medicinal cannabis it is simply essential. Pain specialist Tina Horsted is familiar with the issue. She runs a pain clinic in Copenhagen where she treats 90 patients a day. Tina Horsted comments:  “Standardisation is essential. Patients must have the guarantee that with every inhalation, drop of cannabis oil or capsule they receive the same amount of THC or CBD. It is about safety and quality. That makes the difference between going to a doctor or obtaining cannabis on the black market.”

In Denmark, Tina Horsted is the only doctor who specialises in prescribing medicinal cannabis. Two years ago, she started the public pain clinic Min Smerte. A loophole in the law enabled her to prescribe cannabis to patients, because cannabis was considered to be a natural medicine. “It had to be a hand-written prescription and the end product had to be compounded by a pharmacist”, commented Horsted. She found one pharmacist who was prepared to produce oil and capsules with cannabis components. He lawfully obtained the CBD-containing cannabis from Austria and the THC was added separately.

At the moment, she treats 1,200 patients in her clinic who suffer from chronic pain, MS, RA and cancer. The change in legislation now enables her to prescribe Bedrocan products lawfully and everything is done electronically. In principle, a patient can take a valid prescription to any Danish pharmacy. At the moment, the Danish government has permitted two products – Bedrocan® and Bediol®, which are the most commonly prescribed cannabis products in the world.

Danish doctors

However, a majority of Danish doctors opposes the change in legislation. They argue there is insufficient scientific evidence to support the effect of cannabis. There is also little known about the correct dose, side effects and possible risks of combining cannabis with other medication. Danish patients are struggling to find a doctor who is prepared to write the prescription. Jens Thau is in charge of Clinic Horsted that is privately run and he is confronted with the doctors’ reluctance on a daily basis. “Each day we receive some 20 calls from patients all over the country who do not receive any assistance from their own doctor.” These patients, except for terminal cancer patients, end up on a one-year waiting list because of the high demand. “According to Danish rules we may only employ one doctor in our clinic and that is Tina.” The costs of treatment in the public clinic are reimbursed in full by the Danish government. Patients who do not want to wait, or who cannot wait, can attend the private clinic that has an open surgery every Friday. Patients pay for their treatment themselves or have it reimbursed by additional insurance. Thau comments: “Most pain patients do not have insurance, they are 65 or older and often did heavy labour. That is the saddest part of the story.”

Book

The couple Hosted and Thau are  convinced of the beneficial effect of cannabis and in their evenings they travel around the country to convince Danish doctors and parliamentarians. A book about their experiences with prescribing medicinal cannabis, which will be published this year, is also intended to contribute to more knowledge transfer. Until then doctors will have to make do with the guidelines of the Danish medicines agency, which are available online. Information about the two Bedrocan products that have been included in the trial, comes from importer Uth. “We are bound by rules and may not provide information that encourages the sales of the cannabis product. The only thing that is permitted is a general leaflet with advice about administration and doses. It is in high demand.” As in the Netherlands, the recommendation is vaporizing with a vaporizer or drinking tea. Smoking is not recommended due to the ‘risk of lung and airways infections’ according to Danish guidelines. It is also recommended to start with a low dose. According to the Danish government, it is ultimately the doctor who decides on the dose and the correct usage method.

Read more about this topic

• Odense aims to become the European capital of cannabis (Swedish)
• Pain doctor opens cannabis clinics in Denmark and abroad (Danish)
• The tomato king from Funen wants to grow cannabis in style (Danish)

Websites

• Private pain clinic Clinic Hosted
• Public pain clinic Min Smerte
• CannGros
• Danish medicines agency

Before the turn of the millennium ‘producing cannabis of pharmaceutical quality’ was a self-imposed task. Today it is nothing less than a tour de force for Bedrocan. Operating across the globe, Bedrocan is keeping abreast of the growing demand for the highest quality medicinal cannabis.

The will to move cannabis to the level of a licensed medicine came from Tjalling Erkelens, founder and chairman/CEO of Bedrocan. From the start he envisaged a specialised cultivation process. He made a three-fold promise to the Dutch government (in 2003 – ed.) – to be patient inspired, science driven, and regulatory compliant. Since then, Bedrocan has been the sole supplier to the Dutch prescriber-pharmacy medicinal cannabis programme.

“The cannabis varieties we supply now are based on years of knowledge and experience, and on patient need,” clarifies Erkelens. “In conjunction with our client, the Dutch government, we translated that into a number of standardised varieties of cannabis flos (the whole dried flower). These days there is more and more scientific research into the effect of the active substances in cannabis on the human body, to ensure the approach to medicinal cannabis moves from empirical and anecdotal to scientifically sound. We support this development wholeheartedly. Bedrocan continues to undertake and support scientific research. The same applies to studies of administration methods, such as our patient-friendly vaporizer. Input from patients continues to be essential, because they are the reason for our efforts. We have now come to a point where we initiate and support clinical trials. If your aim is to have cannabis registered as medicine, you can only achieve that on the basis of scientific evidence.”

Recreational use

In the area of compliance, Bedrocan has always taken a clear course. Erkelens continues: “From the start we have worked in accordance with applicable legislation and regulations. That is beyond dispute as far as we’re concerned.

Outside the Netherlands, we only wish to focus on countries where the production and use of medicinal cannabis is enshrined in law. We continue to focus on the medicinal application of cannabis; intended for patients.

We are never party to the global discussion about legalisation, we stay away from recreational use, and only seek to cooperate with partners that share our vision of compliance.”

This choice means that Bedrocan and its licensees are bound by increasingly stringent requirements in the area of quality and safety. Compliance, again. This time a commitment to pharmaceutical requirements. “Fair enough”, says Erkelens. “We are a pharmaceutical company. So you need to comply with strict requirements and be tested for those. That is why we were the first manufacturer to have the entire production process – including cultivation – good manufacturing practice (GMP) certified. It is why we invest in people, equipment and processes in that area.”

Cannabinoid therapeutic products

Globally there is increasing interest in the medicinal application of cannabis. Not only as pharmaceutical cannabis flos for vaporization, but also as an active ingredient for cannabinoid therapeutic products. Bedrocan keeps pace with those developments.

In 2016, we started with controlled cultivation, and that led to a larger, more streamlined organisation, where botany joins forces with pharmaceutical knowledge. In 2017, a new state of the art production site was commissioned. “This enables us to meet the growing demand in the Netherlands and abroad”, continues Erkelens, who realises that the interest in medicinal cannabis will increase across the world.

“The number of countries that are active in the area is increasing and that is all to the good. However, it is important that we express clearly who we are, what we do, and why we do it this way. Anyone can address us on that.”

A group of some 20 Dutch patients is about to test the new Bedrocan vaporizer. Recently, a call was made in the Dutch media and through patient associations. More than 70 patients have said they would like to participate. The purpose of the study is to collect feedback about, among other things, the user-friendliness of this medical device. The vaporizer will be marketed under the name Bedromedic®.

With a Bedromedic it is possible to inhale Bedrocan’s medicinal cannabis products safely. Heating cannabis releases vapours with active components. The vapour is inhaled by means of a mouthpiece and absorbed into the body via the lungs. It does not involve any tobacco. Temperatures are lower than during smoking, which prevents the release of harmful substances that are produced during burning.

The study is carried out by Bedrocan’s own research department, which screens patients in advance. Participants must have medicinal cannabis from Bedrocan prescribed by a doctor. It is also important that a participant has at least six months of experience with using cannabis as medication. Experience with using vaporizers is not necessary. Participants have the Bedromedic® vaporizer sent to their home and can try it out in their home environment. Afterwards, they complete a comprehensive online questionnaire.

Insights from experienced health professionals prescribing cannabinoids.

There is a place for cannabinoids in the therapeutic toolbox. So how should they be prescribed? Discourse with doctors is a series of interviews with experienced doctors prescribing cannabinoids. This article highlights prescribing realities and strategies to improve patient safety, dispels some myths, and aims to encourage self-driven inquiry.

Do you have any advice for doctors starting out prescribing?

My advice for clinicians who are starting to prescribe cannabinoids is to stick to specific indications where there is a solid foundation of evidence for its use, e.g. multiple sclerosis, patients experiencing central neuropathic pain, or cancer patients. This allows us to gain experience with the effects of this medication in a specific patient population.

Recreational cannabis users are, in my opinion, not a good patient category to start with. They may put considerable pressure on the clinician to prescribe for dubious indications.

Prescribing experience

How long have you prescribed cannabinoid therapeutics?

I have prescribed cannabinoids, mainly for patients with cancer, since I started working here in Holland ten years ago.

Can you describe a typical patient who you would prescribe products containing cannabinoids?

There are two typical types of patients where I would initiate cannabinoid therapeutics. These are in patients with:

• advanced cancer experiencing loss of appetite and possibly nausea and vomiting. Often many other medications have been tried before.
• central neuropathic pain (after unsuccessful trials of more common medications).

Prescribing cannabinoid therapeutics

How is prescribing cannabinoid therapeutics different to prescribing other medicines?

They are like any other medicine. However, many patients will have an opinion about cannabis [and cannabinoid products]. For some it has a rather negative connotation as being a substance of abuse.

What are the key benefits of cannabinoids as a therapeutic product?

There are three main advantages of cannabinoid therapeutics in general over other medicines used in my field of pain medicine, these include that:

• 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.
• there are no known organ damaging side effects in the adult patient. As compared to, for example, those linked with using NSAID’s.
• some cannabis flos variants have a soothing effect, which some patients greatly appreciate.

What do you think are prescribing practices that improve patient outcomes?

For patients with no experience using cannabinoid products, the possible psychological side effects can be distressing. In order to avoid this we advise patients’ to start with low dosage and use the medicine in a quiet and relaxing environment.

In our experience, it is advantageous to prescribe cannabis flos as an inhalational agent, administered by vaporization, as it creates more rapid analgesic effects and has a more reliable absorption profile.

Are there any special considerations you make when prescribing a ‘herbal’ medicine (cannabis flos)?

With cannabis flos, the prescribing clinician needs to be aware that in many countries the standards are different with respect to ‘regular’ medicines: concerning the quality control of the active ingredient, and toxicological contamination.

What is cannabinoid therapeutics?

Medicinal cannabis is a term used to describe the use of cannabis to treat or manage illness. It hails from a time when the products used where typically marijuana and patients smoked joints. Since that time, there have been major developments in cultivation techniques, product quality and controls. Today, the sympathetic regulatory environment favours standardised products (e.g., Bedrocan cannabis flos, Sativex) and safer modes of administration (sublingual, oral and vaporization). A prescriber-pharmacy model now offers patients better communication of risks and benefits, and the safety of health professional oversight. Standardised products and clinical research means plant-based products are closer to achieving full medicine registration. The use of the term ‘medicinal cannabis’ in these circumstances seems redundant.

In this article, we talk about the therapeutic use of cannabinoids. The class of medicines containing cannabinoids (e.g., THC and CBD) and other chemical compounds secreted by cannabis plant (e.g., terpenes) that are intended to be used in, or on human beings for a therapeutic purpose. This change in terminology from ‘medicinal cannabis’ to ‘cannabinoid therapeutics’ reflects our knowledge and understanding of the endocannabinoid system, the cannabinoid receptors, endogenous (human) cannabinoids, and exogenous (plant) cannabinoids.

Using cannabis flos originating from controlled producers means patients are assured there is no biological or toxicological contamination.

In the Netherlands cannabis flos is produced under strict quality conditions by the government licenced company Bedrocan.

Administration by vaporization

Aside from eliminating the harms from smoking, what are the benefits of administration by vaporization?

With vaporization cannabis flos is heated to a specific temperature without burning it. Cannabinoids and terpenes are released in a vapour which is directly inhaled.

There are three main advantages of administration by vaporization is that it:

• allows for exact dosing,
• leads to a rapid effect, and
• avoids the disadvantages of smoking (i.e., no tar, ammonia, carbon monoxide).

What do patients say about the administration of cannabis flos by vaporization?

Using vaporized cannabis flos is the preferred means of use by most patients, especially when compared with an oral application. This is due to the more rapid effect by inhalation.

For some years the vaporizers where reimbursed by Dutch health insurance, thereby eliminating the threshold of a financial burden for the patient.

Patient considerations

Thinking about a first consultation with a patient, how do you start a conversation about cannabinoid therapeutics?

There are two types of discussion around the use of cannabinoids:

The elderly, cannabis naive patient:

An elderly cancer patient may be hesitant to use cannabis as a medication. This likely is related to prejudices about cannabis being a product for ‘recreational’ use. With these patients, I rarely discuss the use of these medicines during a first consult. If the patient is eligible and several other therapies did not provide sufficient pain relief, I then mention cannabinoid therapeutics as a possible option. This allows the patient and his/her family to contemplate that treatment option until the next appointment.

The experienced patient:

There may be patients who have extensive experience using cannabis recreationally. They may be actively looking into cannabinoid therapeutics as a potential adjunct to their pain therapy. These patients emphasise the ineffectiveness or side effects of other therapies, and may push clinicians towards prescribing a cannabis product. 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 cannabinoid products.

Are you aware of patients experiencing interactions with cannabinoid therapeutics and other medicines?

Indeed, we do see patients who experience drug interactions using cannabinoids alongside other CNS depressant medications (e.g. opioids).

Sedative effects can be enhanced especially in the geriatric population. Severe drowsiness and hallucinations can also be provoked.

Aside from drug interactions, the smoking of cannabis is related to an increased risk of myocardial infarction and 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.

Do you encounter diversion for misuse or the abuse of cannabinoids? How do you identify this issue in 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 it as a cheap way to get a ‘recreational drug’ which they were already abusing.

How do you deal with diversion for misuse or abuse in your practice?

This patient group can be quite challenging. They may put pressure on clinicians to prescribe cannabinoids as the only means to relieve their pain. Mentioning misuse and abuse can provoke abrupt reactions.

Clinicians should be coherent in prescribing cannabinoids only for indications with enough evidence for beneficial effects (e.g. analgesic for neuropathic pain, appetite stimulation etc). Misuse and abuse should be discussed openly if they become apparent.

Bedrocan has for decades been a household name as a brand and company when it comes to the development and production of standardised, medicinal cannabis of pharmaceutical quality. Based on the knowledge that a picture is worth a thousand words, a short film has been made showing the unique combination of growing, harvesting and production (in accordance with good manufacturing practice) and research & development. The film explains in just three minutes and thirty one seconds precisely what we mean by ‘beyond pioneering’.

As of November 2017, the new Dutch Bedrocan production facility officially manufactures in accordance with good manufacturing practice (GMP). This guarantees that Bedrocan meets international pharmaceutical quality and safety requirements.

It is the second time that a Bedrocan production site has been made compliant with the GMP requirements for an active pharmaceutical ingredient. Earlier this year, the manufacturer of standardised medicinal cannabis acquired a GMP certificate for the existing Dutch production site. This made Bedrocan the first manufacturer in the world where the entire production process – including cultivation – complies with the international requirements imposed on the production of pharmaceutical raw materials and end products.

On 15 September 2017, the new Bedrocan production site harvested the first batch of standardised medicinal cannabis and handed it over to the Office for Medicinal Cannabis. The new site, outfitted with state-of-the-art finishings and fittings, has a surface area of 10,000 m2, half of which is in use at the moment. With this significant increase in production capacity, Bedrocan meets the growing demand for standardised medicinal cannabis of pharmaceutical quality.

Cannabis labelled ‘Sativa’ and ‘Indica’ may not come from distinct ancestries, according to a study performed by the Canadian Dalhousie University in cooperation with Bedrocan on the genetic differences between the two types and their hybrids. In this study 149 Dutch cannabis samples were analysed, correlating the genotype and chemotype to their reported ancestries. Indica- and Sativa-labelled samples were not as distinct as sub species would be assumed to be, but the genetic differences between them do correlate to their terpene profile (resin fragrance), which could explain the variation between them. Results of this new study have been presented on the International Association for Cannabis as Medicine (IACM) congress in Cologne, Germany, September 2017.

There is perhaps no debate in the world of cannabis more contentious than that of species. The genus Cannabis sativa L. is the only official species, but the terms ‘Sativa’, ‘Indica’ and ‘Hybrid’ have been widely adopted by cannabis breeders and cultivators as a way of advertising their product’s effects, aromas or purported pedigree. The degree to which these labels correspond to their actual ancestry, however, is dubious, and how this informal classification scheme relates to genotype or phenotype has been largely unexplored.

In the study an analysis of 149 cannabis samples was performed, correlating the genotype and chemotype (based on terpene and cannabinoid content of the flowers) to their reported ‘ancestry’.  The researchers then compared the reported labels to new scales they generated by reclassifying the samples based on their genetic and chemical similarity.

The Indica/Sativa classification of Dutch cannabis does not correspond to distinct genetic lineages or to cannabinoid type, but there are genetic and chemical similarities that explain the variation between the groups. Deconvolution of the Indica-Sativa ancestry showed a strong relationship between the chemical and genetic profiles, suggesting that the distinct terpene contents of the types are heritable and important to the identity of these two groups. It is likely that strains are classified by their distinct aromas, and not their lineages, which has a direct impact on the genetics of this crop.

Bedrocan, worldwide producer of standardised medicinal cannabis, is already working on the terpene profiles that are associated with the current Bedrocan products. Hugo Maassen, head of the phyto engineering department at Bedrocan: “This study shows that the Indica/Sativa differences could be largely based on terpene content, which instead of the current Indica/Sativa labelling might require for more insight in the terpene profiles related to the Bedrocan products available for patient use.”

The terpene profiles of the Bedrocan products are expected to be announced in the near future.

Used by patients in the Netherlands since 2003, Bedrocan® standardised cannabis flos is now available for patients in Australia. This includes the same cannabis flos currently used in the NSW palliative care clinical trial.

Administered by vaporization, the consistent chemical profile of the flos better allows doctors to monitor dosage, condition progress, and reduce the risk of overdosing and unwanted side effects.

Being free of microbial contaminants (molds, fungi, and bacteria), pesticides, and heavy metals, Bedrocan cannabis flos is safe for vaporization and inhalation into the lungs. These qualities are especially important for people with weakened immune systems.

The recently published Prescribing Bedrocan provides information to assist health professionals on dosing, safety, and side effects. Our portal now allows doctors to report adverse events online.

Novachem, a specialist import and distribution agent, will supply flos and vaporization technology to licensed pharmacies in Australia.

The first of its kind in Australia, Bedrocan’s cannabis flos and placebo will be used in a cancer palliative care clinical trial. Led by Professor Meera Agar, the double-blind randomised controlled trial will explore whether vaporized medicinal cannabis flos can promote appetite and improve quality of life. For people with cancer, the pathways that promote appetite are disrupted. Their quality of life is reduced due to fatigue, low mood, nausea and insomnia – aspects critical to health and wellbeing.

Researchers are now recruiting patients. Approximately 30 adult patients with advanced cancer will be included in the trials undertaken at Sydney’s St Vincent’s Sacred Heart Health Service and Newcastle’s Calvary Mater Hospital. The results may lead to a further trial, enrolling up to 250 patients from metropolitan and regional hospitals across the state.

The New South Wales Minister for Medical Research, the Hon. Pru Goward, fully supports the trial as part of the state Government’s $21 million funding commitment to medicinal cannabis clinical trials and reforms. To learn about the NSW Government’s Centre for Medicinal Cannabis Research and Innovation and the trial see www.medicinalcannabis.nsw.gov.au.

For more on vaporization as a way of administering cannabis flos, read our article Not all vaporizers are the same.

Patient perspectives and providing options

The importance of vaporization is underlined in patient use surveys. The majority of survey respondents report higher satisfaction (approval) scores with the inhalation route. In general, whole plant, herbal cannabis-based medicines received higher scores than other products containing isolated cannabinoids.

While smoking may be a popular administration method internationally, it is evident patients are looking for alternatives to smoking. Patients seek a reliable, affordable and portable vaporizer for administering cannabis flos. Presently there is research dedicated to advancing administration technology. An example of major developments in vaporizer medical devices, using standardised cannabis flos, include the Syqe® Inhaler (Syqe Medical).  This device has relied on Bedrocan standardised cannabis flos for its quality testing and clinical trials.