Updates

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Bedrocan and adult-use cannabis legalization in Germany

The new German government is set to legalize some form of adult-use cannabis. Bedrocan has been supplying cannabis to German patients for years. Lately, we have often been asked: ‘Will you soon also be supplying German recreational users?’ That is a very understandable question. However, the answer is simple: No.

Bedrocan does not supply cannabis for recreational use. We do not do that anywhere in the world, not even in the Netherlands, and soon also not in Germany.

Why does Bedrocan not want to enter the recreational market?

Bedrocan believes in a strict separation of medicinal cannabis and cannabis for recreational use. We are committed to providing a pharmaceutical product that is available on prescription to patients who benefit from it. We want to focus one hundred per cent on this assignment. This means that we cannot and do not want to be involved with cannabis for recreational use.

In other countries, we have (unfortunately) seen patients that use medicinal cannabis become the victims of the legalization of recreational use. Not so much because of the legalization itself, but because of the fact that producers were tempted to jump into this market. The quality requirements are lower, the rules are easier, controls are less strict, and yields (they hoped) higher. Result: medicinal cannabis received less (or no) attention, and patients were left without the product. We want to avoid that at all costs.

Moreover, it is true that there can indeed be adverse effects from the use of cannabis. That’s why we want our products to be available only to patients who use them with a prescription and under the supervision of a pharmacist. We also only want to use our many years of knowledge and experience in the field of cannabis cultivation for this purpose.

Are you approached by companies or users who would like to work with Bedrocan towards the recreational market?

Yes, very often, in fact. The answer is and will always be ‘no.’ At first, that may sound strange. But change the resource and the players. Suppose the government legalizes Ecstasy pills. Would a pharmaceutical company that now makes antidepressants or rheumatism drugs show up there? No, of course not. They would stay far from it. The same goes for us. Medicinal cannabis and cannabis for recreational use are two different products with completely different target groups. You shouldn’t want to mix them up.

Will you continue to supply German patients?

The current supply system via the Dutch Office of Medicinal Cannabis (OMC) will not be impacted. Therefore, German patients will continue to have access to our pharmaceutical-grade products.

Bedrocan shows pharmaceutical API at CPhI 2021

Last week world’s largest pharmaceutical API & raw materials fair: CPhI Worldwide in Milan, Italy. Bedrocan was, of course, present this year again. Our team met a lot of interesting parties during the event who were curious about our standardised medicinal cannabis API. The team had a very fruitful event and spread our message on the importance of pharmaceutical quality standards for medicinal cannabis products.

Bedrocan op CPhI Worldwide 2021
Andrew Kraszewski, Karolina Ostapenko & Varun Arora

Varun Arora represented our organisation and our cannabis products together with Key Account Manager Karolina Ostapenko. In addition, our Director of Product Development & Compliance Naiem Hakiemie, our Manager Legal Affairs Robert Rademaker and our Corporate Strategy Analyst Andrew Kraszewski strengthened the team.

Promoting our products

The last time Bedrocan participated in CPhI in 2019, we focused mainly on presenting our five varieties of standardised cannabis as an API. This time, Bedrocan could also introduce the trichome powder and placebo product forms. Many pharmaceutical companies showed interest in these products. Although there is no production line for these products yet, this interest certainly encourages Bedrocan to produce them on a larger scale in the future. Especially for companies from countries in which the import of cannabis flos is not allowed, having our products in a different form that can be used as raw material would be very valuable. The placebo also called the attention of those parties involved in clinical trials, as currently, there is no placebo for medicinal cannabis in the form of flos/granulate.

Additionally, Bedrocan team also promoted our unique cultivation techniques and excellent quality management system, which could also be applied to the production of other medicinal plant products.

Next year, we will be present again in CPhI Frankfurt and hope to have another successful event.

IMC Nederland to Copenhagen at the invitation of the Danish government

Together with the Danish Technology Institute, Invest in Denmark recently held the symposium: Medicinal Cannabis, from plant to patient. Invest in Denmark is part of the Danish Ministry of Foreign Affairs and is committed to attracting foreign companies to Denmark. Medicinal cannabis has recently become one of their spearheads. This edition was all about collaboration and partnership. To explain how the Institute for Medicinal Cannabis (IMC) in the Netherlands promotes cooperation and partnership, IMC board member Ole Heil, also director of Communication & Government Affairs at Bedrocan, spoke at this symposium at the invitation of the Danish government.

IMC good example

Heil: “Since 2018, dozens of new companies have started up in Denmark, and research has really taken off. This is largely due to the favorable regulations, but also due to the efforts of the government. It actively supports parties in the sector, which is bearing fruit with dozens of new companies and research projects.”

Bedrocan proud partner of the IMC

Bedrocan has joined the IMC because it allows us to contribute to the knowledge about medicinal cannabis among doctors, pharmacists and patients in the Netherlands and to facilitate medical research.

“Something the Danish government would like to see more of is mutual cooperation. It aims to create a sustainable ecosystem of companies, doctors and researchers. At the moment the cooperation is still relatively limited.”

“We had the same situation in the Netherlands, but within the IMC, Dutch medical researchers, pharmacists, universities and companies, including Bedrocan, are now working together in the field of information and coordination of investigations. The IMC does this independently and on a non-profit basis. We also serve the interests of parties in the medicinal cannabis chain.”

Medicinal cannabis in Denmark

On January 1, 2018, a trial program with medicinal cannabis started in Denmark. This program makes it possible for doctors to prescribe medicinal cannabis and for companies to develop commercial activities with medicinal cannabis. The pilot was extended by the Danish Parliament for a further four years for doctors and patients in March 2021. The commercial activities have even been made possible on a permanent basis. Medical cannabis has rapidly developed into a major industry in Denmark in those four years. Since the start of a trial period, a vibrant sector has emerged in the chain of breeding, production, processing and development of medicinal cannabis products.

UMCG starts scientific research into cannabis oil for chronic pain in Epidermolysis Bullosa

The Dutch University Medical Center Groningen (UMCG) has recently started a study into the effect of cannabis oil in patients with Epidermolysis Bullosa (EB). EB is a serious hereditary blister disease in which patients experience different types of pain. The study is an exploratory, randomised, placebo-controlled and double-blind crossover intervention study, in which 16 patients participate. Within a year, the chief physician of EB patients at the UMCG, Dr Marieke Bolling, and Prof. Dr André Wolff, medical head of the UMCG Pain Center, both principal researchers, want to be able to tell whether medicinal cannabis oil has an influence on the pain experience of these patients.

Together with fellow physician-researcher Nic Schräder from the UMCG, they are working on this unique study: “We are the first in the world to clinically investigate the effect of cannabinoids in EB patients in this way.”

Epidermolysis Bullosa

Epidermolysis bullosa (EB) is an inherited blistering disease of the skin and mucous membranes often associated with intense pain, chronic wounds and scarring. EB patients are treated according to the usual WHO pain ladder, a step-by-step plan developed by the World Health Organization (WHO). Lead researcher Dr Bolling: “What we as doctors have available to fight pain in EB patients is actually not sufficient. The pain starts at birth and lasts for a lifetime because the blisters and wounds keep coming. So, there is no cure. Many pain interventions are not intended to be used for years, but unfortunately, that is necessary for EB patients.”

It is therefore not surprising that patients themselves are looking for methods to fight their pain: “Cannabinoid-based medicines, such as cannabis oil, are of course an example of this. We know that patients use medicinal cannabis with or without medical supervision.”

Since 2015, a cannabinoid-based drug oil (CBM) containing Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) has been prescribed to Dutch patients with Epidermolysis Bullosa with reported relief of pain, itching and reduction in the concomitant use of other medications for these patients’ symptoms.

The idea for the study originated in 2014. Nic Schräder, the driving force behind the research trajectory, became unintentionally involved in the subject as a former medical student. “I went to EB patients’ homes for a small-scale wound examination to test a new kind of bandage. During small talks, it kept coming up that these people were using cannabis to treat pain. As a tea or joint, or in a vaporiser, but also on the wound itself.” His interest was piqued, as the use of cannabis was, even then, a controversial topic. After consultation with Prof. Dr. Marcel Jonkman, head of the dermatology department of the UMCG then, Schräder prepared three case reports. After that, a subsidy application for a placebo-controlled follow-up study was the next step.

cannabisolie voor chronische pijn bij epidermolysis bullosa

Patient association DEBRA

The financial resources for the study were obtained from, among others, the patient organisations DEBRA-UK and Debra Nederland. However, the most challenging obstacle was the methodological exchange between the Medical Ethics Review Committee (METC) and the research team, which took three years. “There are so many variables when you do research with cannabis; which form of administration should you investigate, which cannabinoid composition suits the clinical picture, which dosage is the right one, and which effects do you want to measure as reliably as possible?” Schräder explains.

By involving other specialists from the UMCG and the German Oldenburg, including an epidemiologist, we finally succeeded in drawing up an ethically sound, thorough research protocol. “Epidemiologists are methodologically very well versed. This helped us design the study, and it will help us process statistics and make the right choices,” said Prof. Dr Wolff about this special choice. The knowledge exchange within the UMCG has also borne fruit. Doctors and researchers from the UMCG, who are involved or interested in cannabinoids within a scientific and clinical context, meet regularly in Round Table meetings to exchange knowledge and discuss the subject. It is the second time in a short time that the UMCG has started an investigation into the effect of cannabis oil. Schräder: “We have exchanged a lot of knowledge in this area with the Hepato-pancreato-biliary Surgery Department, who have previously started a study into liver cancer.”

Transvamix®

Medicinal cannabis oil that contains sufficient CBD is used for the study. Schräder: “The literature shows that CBD theoretically suppresses the adverse side effects of THC.” This Transvamix® contains 10 per cent THC and 5 per cent CBD and is prepared by the Dutch Transvaal Pharmacy. This uses the standardised plant varieties Bedrocan® and Bedrolite® as raw materials for the oil. This oil is also used in another scientific study by the UMCG, a study into the effects of cannabis oil in liver cancer.

Crossover design

A crossover design was chosen for the study, a setup in which the participant is administered the cannabis oil, as well as the placebo. So there is no separate control group. Schräder “There is a limited number of patients with EB who are willing and able to participate, and who meet the strict criteria for participation.” In the Netherlands, there are about 500 patients with EB, of which about 90 per cent are registered in the treatment centre for blisters of the UMCG. Sixteen patients were selected to participate in the study. According to Prof. Dr Wolff, the number is less important because the design of the study determines whether something has statistical value. “You have to be able to demonstrate an effect. The right method, that’s what matters.”

Nociplastic pain

The study focuses solely on the experience of pain and not on blistering. Pain in Epidermolysis Bullosa is chronic and difficult to treat and is often experienced as ‘unpleasant’ by patients. This concerns wound and care pain, neuropathic and nociplastic pain, whereby the latter form of pain can appear in various places in the body without being anatomically explained. Prof. Dr Wolff: Pain often has a negative impact on people’s mental state, behaviour and interaction with the people around them. People are often anxious, depressed or unable to work and become socially isolated.”

It remains difficult for science to determine someone’s experience of pain objectively. A scale of 0-10 is often used for this, but the outcome is still a subjective score. A new way to measure objective pain is the use of a functional MRI (fMRI). fMRI creates a 3D image of the brain. The areas, the brain activity, that are responsible for processing pain become visible. Schräder: “For the first time, this gives us a picture of what the pain circuit looks like in EB patients before and after treatment with cannabis oil. We do these scans in addition to the patients’ self-reported pain scores. If you put all that data side by side, you should get a better picture of the pain experience.”

If this combined fMRI method works, it could be of interest for other studies of pain. But according to Prof. Dr Wolff, the primary goal of the study is to demonstrate effectiveness: “You want to show whether cannabis can make a difference and is effective in EB patients with pain because that is not yet clear. The studies on the effect of cannabinoids on other pain syndromes are not always conclusive.”

Bedrocan at CPhI Worldwide 2021 in Milan

Bedrocan will be present at the world’s largest pharmaceutical exhibition, CPhI Worldwide. A pioneer in the medicinal cannabis industry, Bedrocan began its journey more than three decades ago. The company has been a reliable supplier of pharmaceutical-grade cannabis to the medicinal cannabis programme in the Netherlands since its inception in 2003. Over the last five years, the industry has grown exponentially and there is increasing interest from pharmaceutical companies seeking high quality cannabis raw material and APIs for drug development.

At CPhI, Bedrocan is looking to engage with some of these companies and also share its vast knowledge about the industry and regulations.

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.

Meet us in Milan

CPhI Worldwide 2021 will be held in Milan from Tuesday November 9th until Thursday November 11th.

You can visit our booth and meet our Business Development team at stand number 18H24.

 

In their quest for a reliable source of API, pharmaceutical companies are increasingly finding their way to Bedrocan. This is unsurprising given Bedrocan was the first EU GMP-certified producer of standardised medicinal cannabis in the world. Varun Arora (Advisor Strategy & Development) and Karolina Ostapenko (Key Account Manager) will be present at CPhI Worldwide. We talk to them about the medicinal cannabis industry and Bedrocan’s product offerings.

Meet the Bedrocan CPhI Team

Varun Arora & Karolina Ostapenko

CPhI Worldwide

Karolina

I began my journey at Bedrocan in February 2019. I am a pharmacist by trade. As Key Account Manager, I am the point of contact at Bedrocan with regards to the Dutch medicinal cannabis system and possibilities of ordering Bedrocan products from the Office of Medicinal Cannabis. I am well-versed with the regulatory aspects of medicinal cannabis worldwide and can provide detailed information on Bedrocan products and the manufacturing process, which is compliant with EU GMP guidelines for pharmaceutical products.

Varun

I joined Bedrocan a little over three years ago in what can be described as an interesting moment for the medicinal cannabis industry in Europe. My background is actually in investment research. I worked as an equity research analyst for almost seven years, with three of those focused on the life sciences industry. Since joining Bedrocan, I have focused mainly on formulating the company’s commercial strategy and taking the lead with regard to commercial development.

Feel free to contact Varun Arora and Karolina Ostapenko via the Meet Bedrocan page.

Tell us about the Dutch medicinal cannabis program

Varun: “The Netherlands began a cannabis program more than two decades ago. The need for such a program was driven by the fact that there were a large number of self-medicating patients in the Netherlands and the Dutch government ‘s intent was to bring them under prescriber/pharmacist supervision and move them away from the illicit market to procure their medicines. In line with the requirements under the UN Single Convention, the Dutch set up a cannabis agency, the OMC, which then tendered out different parts of the supply chain to different companies. For the last nearly twenty years, Bedrocan has been handling cultivation, with the entire harvest sold to the OMC, which has monopoly over trade of cannabis in the Netherlands. The programme has largely been successful, with around 9,000 patients in the Netherlands and around 90% of our total capacity of approximately 5.4 tons is actually exported through the OMC.”

Karolina: “Interestingly, the programme was never set up with the intent to export, a mistake that several countries in Europe that legalised medicinal cannabis in the last few years made. Because the Netherlands implemented a cannabis programme many years before the hype in the industry, its interpretation of the Single Convention is quite strict. Under the current framework in the Netherlands, the actual vendor of Bedrocan products is the OMC. We are essentially a contract manufacturing organisation, or CMO. However, regulators in the country have obviously noticed the changes in the industry, especially since Germany, one of biggest medicinal cannabis market outside North America, legalised access to medicinal cannabis in March 2017. And given these changes, a review of the Dutch cannabis policy began in the summer of 2020 and some changes are expected in the coming years that would provide more freedom, especially when it comes to product development activities and engaging in business-to-business supplies.”

What are your current product offerings?

Karolina: “As noted above, the actual vendor of all Bedrocan products is the OMC. Through the OMC, Bedrocan currently offers five different strains of dried cannabis flowers, with the Bedrocan variety accounting for almost 80% of our total production. Current regulations in the Netherlands do not allow manufacturing cannabis extracts for commercial purposes but in anticipation of a change in regulation down the line, we have stepped up our product development activities and one of the pipeline products is the trichome powder or dry extract. We have developed a technique to separate trichomes from the plant material. Trichomes have the highest concentration of cannabinoids. By separating trichomes from plant material, what you get is a much cleaner product. Moreover, no solvents are used in the extraction process and this is important as it means the integrity of the product is maintained and what we offer in the end is a true herbal product. We have done proof-of-concept work with our Bedrocan variety and the THC concentration for this variety goes up to 45% (from 22%).”

Varun: “There are two ways to look at our product offering. One as Karolina explained is the five standardised varieties that are currently supplied through the OMC and their derivatives such as the solventless extract, which subject to regulatory changes we would be able to offer commercially. But as a CMO and an accomplished cannabis raw material producer, what we are essentially offering is three things; our unmatched capabilities when it comes to cultivation techniques, our quality management system and finally stable genetics. The first two can be replicated for other cannabis cultivars and as a CMO we are always open to such opportunities. In fact, our cultivation techniques and QMS can even be replicated for other medicinal plants and this is the company’s mid-to long-term goal in terms of expanding product offerings.”

Can you define standardised medicinal cannabis?

Varun: “Standardised medicinal cannabis is consistent in terms of its active ingredients – the cannabinoids tetrahydrocannabinol (THC) and cannabidiol (CBD), but also the terpenes. which are the aromatic compoundsAll our products are produced in accordance with pharmaceutical quality requirements, because our production sites comply with the requirements imposed by EU GMP.”

Karolina: “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.”

Why standardisation?

Karolina: “Standardisation is the essence of our mission and vision. The patient is at the heart of all this. Prescribers, pharmacies and patients expect a safe product that works. The same applies to pharmaceutical companies, which do not want a discussion about the composition of their raw materials. The industry needs an API that is consistent in its composition to develop and manufacture novel cannabis-based medicines. So, from pharma to patient; they all expect a product that complies with all the pharmaceutical production requirements, and that starts with high quality starting materials.”

How do you achieve pharmaceutical standardisation with cannabis?

Varun: “Over the past 27 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. Furthermore, Bedrocan was the first medicinal cannabis producer to be compliant with the European Medicines Agency’s GMP standards. We set the bar high.”

Can you tell us more about your cannabis placebo product?

Karolina: “Cannabis placebo is of particular interest to researchers. A high-quality placebo is essential for thorough scientific research. We already had a placebo product for years. This has served science well, but is no longer available. Work is currently underway on a new, improved placebo product.”

International research shows: No genetic distinction between ‘Sativa’ and ‘Indica’ cannabis

The cannabis industry needs to look more critically at its own disclosures. According to researchers at Canada’s Dalhousie University and the Wageningen University & Research, the Indica and Sativa labels on cannabis are often wrong and misleading. Patients and consumers would benefit from a more scientific approach. The researchers analysed hundreds of cannabis samples. The study shows that the genetic and chemical composition of the cannabis tested often does not correspond to the typical cannabis label Indica or Sativa.

Cannabis labels are often wrong and misleading

The results were recently published in the leading international journal Nature Plants. Robin van Velzen, plant expert scientist at Wageningen University and also affiliated with Bedrocan, contributed to the research.

The terms Indica and Sativa are often used to categorise cannabis. These different strains are generally believed to be associated with certain psychoactive effects. Often the effect of a Sativa strain is described as mentally stimulating and energising, while that of an Indica strain is described as relaxing and soothing. In addition, it is often suggested that the labels say something about the genetic background.

However, the research shows that plants with the Sativa label are no more genetically similar than plants with an Indica label. Also, chemically there is mainly overlap between these two labels.

“Growers worldwide label their cannabis strains quite subjectively with the terms ‘Indica’ and ‘Sativa’. There’s nothing scientific about that. Unfortunately, retailers and consumers cannot rely on the labels that are stuck to the jars,” says Dr Sean Myles, Associate Professor at Dalhousie University‘s Faculty of Agriculture and lead author of the study.

“There is now a broad scientific consensus that the current use of the Indica and Sativa labelling is misleading: these labels do not provide reliable information about the genetic or chemical makeup of the plant,” Myles continues.

Terpenes

The research shows that genetically it is impossible to prove whether a cannabis plant is an Indica or Sativa. There is no difference in the genes. “What our study mainly shows is that you should not just rely on those labels, but that you should look at the specific terpene profile,” says Van Velzen. “For example, cannabis labelled as Sativa often contains higher concentrations of single terpenes with tea-like and fruity aromas, while Indica samples generally contain higher concentrations of terpenes with an earthy smell such as myrcene, guaiol, gamma-elemene and gamma-eudesmol.”

But the distinction that the researchers found is not convincing: “It really is about these specific, individual terpenes that make the difference. The overall chemical profile, like the genetics, shows no apparent difference between the labels. We also found only a small number of regions in the cannabis genome that likely contribute to the earthy aroma associated with the Indica label,” said Van Velzen.

It is also striking that different cannabis samples sold under the same name such as ‘Lemon Haze’ or ‘OG Kush’ could be genetically just as different from each other as samples with different names.

Van Velzen: ‘Unlike other valuable plant species, the labeling of cannabis is very unreliable. This is particularly undesirable for patients who use cannabis as a medicinal product”.

Indica variant Bedica

Bedrocan shows the terpene profiles per product on the website and makes a distinction between Indica and Sativa per cannabis product because many patients need this information. The product Bedica is marketed as an Indica variant. Van Velzen: “The typical terpenes such as myrcene and gamma-eudesmol are also found in Bedica. In that respect, the labelling is therefore in line with our findings.”

According to the researchers, the industry should be more open about the chemical composition. “Show the terpene profiles for real instead of an unreliable name like Indica or Sativa. Fortunately, a number of companies already do this, but a standardised measurement and naming convention is still lacking. Reliable information is of great importance; certainly for medicinal applications,” concludes Van Velzen.

Sophie Watts at Bedrocan Series

On Friday, November 5,  Sophie Watts of the Dalhousie University research team will be our guests at Bedrocan Series. During this webinar she will explain more about the research and its results.
Do you want to know more? Or already reserve a spot at the webinar? Click here.

Well-known Belgian travel program ‘Reizen Waes’ visiting Bedrocan

Welcome to our website. You probably found us as a result of the Travel program Reizen Waes.

Last summer, presenter Tom Waes filmed us in Emmeloord for the new season of Reizen Waes. This episode was shown on Sunday 31 October at 8.50 pm on NPO 3 and will be broadcast on Monday 06 December on Eén.be.

Missed the broadcast? Then watch it again via this link.

In this broadcast, you get a first look at our company while our CEO Tjalling Erkelens takes Tom Waes and his film crew for a tour.

Tom makes it seem as it is very exciting to visit Bedrocan. Of course, you can’t just walk into our facilities, that’s not allowed at other production companies either, but we don’t want to call ourselves a secret. Commissioned by the Dutch Ministry of Health, we have been the only producer of medicinal cannabis in the Netherlands for almost 20 years. Our medicinal cannabis is prescribed to thousands of patients at home and abroad by doctors and is only available at pharmacies.

Medicinal cannabis is subject to very strict guidelines, just like other pharmaceutical companies are. Tom notes that Tjalling is very strict about the hygiene guidelines in order to prevent possible contamination of the plants. This is not without reason. Bedrocan is GMP certified by the Health and Youth Care Inspectorate (IGJ). GMP stands for Good Manufacturing Practice. This is a quality assurance system for the pharmaceutical industry that guarantees the quality of medicine or raw material. Medicines and active substances for use in medicines may only be produced by companies that have such a GMP certificate. Bedrocan was the first cannabis company in the world to receive such a certificate, and we are still proud of it. Since then, we are actually no longer a cannabis grower but a pharmaceutical raw material producer.

Tjalling is not alone in producing and monitoring our quality. Together with a high-quality team of almost 100 professionals and the necessary quality systems, we turn a vegetable product into a reliable medicinal product.

Do you want to know more about Bedrocan? Take a look around our website.

Here you can read more about our method, the GMP certificate and the people behind the company. If you want to know more about medicinal cannabis and an overview of our products, click here.

If you are a patient and have questions about the use of medicinal cannabis, please contact your GP or pharmacist.

If you have a question that is not answered on our website, please contact us using this form.

Tom Waes van het bekende reisprogramma bezoekt Bedrocan

Monique van Velzen on chronic pain and medicinal cannabis

Research into chronic pain and its treatment is urgent, because the burden of disease is high. According to researcher Monique van Velzen, one in five adults suffers from some form of chronic pain. Van Velzen was (and is) involved in different scientific studies into medicinal cannabis and chronic pain. On August 12, she was a guest during the third webinar of the Bedrocan Series.

Monique van Velzen is an assistant professor and research coordinator at the Leiden University Medical Center. She conducts team research into chronic pain and – ultimately – the most appropriate way to treat people with chronic pain. She is also a board member of the Institute for Medicinal Cannabis (see below).

Research into chronic pain and its treatment is urgent, because the burden of disease is high. According to Van Velzen, in the Netherlands alone, one in five adults suffers from some form of chronic pain, and this is no different in other countries.

Impact

In addition, chronic pain is a difficult condition to describe, says Van Velzen: “In a sense, pain is an emotion; it is often dependent on the situation of the moment and therefore subjective. This does not detract from the seriousness of the complaints, because many patients with chronic pain suffer from this in daily life; work is made more difficult, sleep is sometimes bad, people become depressed and/or become socially isolated. That makes chronic pain a very serious condition with a lot of impacts.”

Bedrocan Series - Cannabis as a medicine, chronic pain and opiates

The treatment of chronic pain is not easy either. Van Velzen: “There are medicines, such as anti-epileptics, anticonvulsants and opioids, but they all have serious side effects. You have to ask yourself whether this is desirable in long-term treatment because in some cases, the remedy is ultimately worse than the disease.”

Cannabis

That was also the reason for the LUMC Anasthesia & Pain Research Unit, led by Van Velzen and Professor Albert Dahan, to investigate whether medicinal cannabis could be an alternative or addition. “We chose fibromyalgia patients, a large group of patients with pain complaints throughout their body. Pain complaints that are also difficult to treat” says Van Velzen. “We know through various channels that many of those patients turn to cannabis as a pain reliever.”

That’s why we wanted to know if it is effective and what the side effects are. We have done a proof of concept study, a so-called randomized, double-blind, placebo-controlled four-way cross-over study. We wanted to use cannabis varieties whose composition – also in the longer term – is always the same so that you can make statements about effect and side effect. This is how we arrived at standardised medicinal cannabis, which is available on prescription from Dutch pharmacies. These were administered to the subjects by vaporizing.”

Two varieties

The study revealed that fibromyalgia patients might benefit from medicinal cannabis, especially the varieties Bedrocan and Bediol. “We saw the most effect with varieties that were slightly higher in THC. But we also saw that those varieties produced the most side effects. This was already expected as some doses were given to people who are not used to using cannabis. In the long run, however, these two varieties seem to work best for fibromyalgia patients.”

Side effects

The study, which was completed in 2018, was followed up fairly quickly. “Chronic pain requires chronic treatment, so we restarted a study that focuses on side effects. We use the Bediol variety, which is used by patients for a period of six weeks. We look at how these patients tolerate the drug. Are there any side effects? Does the use of this drug fit in their lives, also in the longer term? And how does that compare to the use of oxycodone, which is widely prescribed but also has many side effects and is therefore not ideal in the long term?”

Difference

That study is currently underway, and conclusions cannot yet be drawn, although Van Velzen indicates that some expected side effects of both medicinal cannabis and opiates have now been noted. “We see the typical side effects, with oxycodone and with Bediol. We do not yet know whether there is a difference between the groups.”

The final result of the study is expected in the course of 2022, and in the meantime the Leiden Anesthesia & Pain Research Unit, together with the Centre for Human Drug Research (CHDR), will conduct research into medicinal cannabis in patients with neuropathic pain. The research group has received a subsidy of 1.9 million euros from the Dutch government to research the most optimal ratio of THC and CBD for pain relief. And here, too, side effects will be looked at. In addition, the research group wants to further investigate patients’ processing of pain in the brain so that treatment – ​​with an appropriate dose of THC/CBD – can be tailored to this. These are lengthy studies, but the progress can be followed on the Dutch website Samentegenpijn.nl.

You can watch Bedrocan Series with Monique van Velzen here.

Institute for Medicinal Cannabis

In addition to her work for the LUMC, Monique van Velzen is also a board member of the Institute for Medicinal Cannabis. There, she is responsible for ‘scientific research’. “We see that scientific research into medicinal cannabis is taking place in various places — research on the plant itself, but also in relation to various diseases or symptoms. The IMC wants to be a platform where all scientific knowledge of medicinal cannabis comes together. We want to connect researchers in the Netherlands – but also beyond – so that we can exchange knowledge, support each other and streamline scientific research across the board.”

Instituut Medicinale Cannabis

Cannabidiol, the popular component of cannabis

Cannabidiol, abbreviated as CBD, is getting a lot of attention these days, and everyone knows someone who uses it. But what is CBD, and how does it compare to THC?

CBD is a cannabinoid and is only found in the cannabis plant. There are currently more than 100 different identified cannabinoids, of which THC is the best known. These two substances are very similar in their chemical structure but have very different effects.

CBD has medicinal properties but cannot make the user feel ‘high’. THC can. Some studies suggest that CBD may be effective in treating symptoms of rheumatoid arthritisdiabetes, PTSD, anxiety disorder, and antibiotic-resistant infections, among others.

CBD and epilepsy

More recently, CBD has been used in children with treatment-resistant epilepsy, and a subsidy has been made available by the Dutch government for further research. This study will not only look at CBD, but cannabis products in general, including THC.

CBD ist ein Cannabinoid

THC is more likely to be used to reduce nausea, vomiting, pain and muscle spasms and improve sleep and appetite and the scientific evidence for its effectiveness in these conditions is more sound than the one available for CBD.

Ideal THC:CBD ratio

It has been shown that CBD can influence the effects of THC. However, it is still difficult to say which THC:CBD ratio is the most ideal for a specific medical condition. As an example, a study into the pain experienced by fibromyalgia patients showed that the combination of CBD and THC had a better effect on pain reduction than a product with THC alone. Conversly, CBD alone had no effect on pain. In a follow-up study, the researchers are now looking if a THC:CBD balanced ratio cannabis is better than opiates in reducing  fibromyalgia pain.

However, the ultimate medicinal effect of cannabis does not depend solely on CBD or THC.

CBD and driving

When using CBD and driving it is important to avoid combining CBD with THC. A study of the effects of THC on driving ability showed 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. CBD alone and driving, on the other hand, do go together. No evidence has been found that CBD negatively affects driving behaviour on its own.

Terpenes refine the therapeutic effect

Terpenes are the substances that give cannabis its characteristic smell and taste. So far, over 120 different terpenes have been found in cannabis, with unusual names such as myrcene, alpha-pinene and beta-caryophyllene.

Unlike cannabinoids, terpenes can be found everywhere in nature. For example, they are present in lavender, roses and pine trees. Some studies suggest that terpenes may counteract certain undesirable effects of THC, such as feelings of restlessness or loss of short-term memory, although thorough research on this topic is still lacking.

Certain terpenes may also have medicinal properties of their own: some are antibiotics, while others have analgesic or anti-inflammatory effects. Terpenes are therefore often used in aromatherapy.

Because there are many different terpenes, there are also many different combinations in which they can occur in a cannabis plant. As with cannabinoids, each specific mix of terpenes can lead to a unique medicinal effect. The terpenes are suspected to work with cannabinoids to modify or amplify their effects. This is known as the ‘entourage effect’.

Trichomes

CBD, like other ingredients, is produced by tiny glandular hairs that are present all over the cannabis plant. Also known as trichomes, these hairs produce a sticky resin that accumulates as tiny droplets at the end of each glandular hair. Trichomes are so small that you can only see them with a magnifying glass.

CBD ist in Trichom als CBD-Säure enthalten

Trichomes are found on both male and female plants, but they are particularly concentrated in the tips of the female flower.

Acidic and neutral cannabinoids

THC and CBD are not present in the cannabis plant in ready-to-use form but must first be heated to a temperature of at least 180°C.

The plant only contains ‘acidic’ cannabinoids. THC is, therefore, primarily THC acid (THCA), and CBD from the plant is CBD acid (CBDA, also known as cannabidiolic acid). When these substances are sufficiently heated, the cannabinoid acids are converted into a neutral form known as THC and CBD. This chemical process is called decarboxylation.

Decarboxylation also occurs spontaneously in cannabis as a result of exposure to light and room temperature, although at a slower pace. However, cannabis can be kept for a very long time in the freezer.

CBD acid

Until recently, scientists thought that the acidic cannabinoids had no medicinal properties. However, these substances can indeed be interesting as medicines. For example, it appears that CBDA bactericidal properties and seems promising as an anti-inflammatory substance. Additionally, THC acid seems to have a strong effect on the human immune system.

 

 

Who is involved in the Dutch cannabis supply chain?

Bedrocan is the only company in the Netherlands that produces medicinal cannabis, but that does not mean that we are the only company involved in the production process. There is a long way before the Dutch cannabis products reaches the pharmacy in jars. All these companies contribute.

The route starts with the Dutch government.

Office of Medicinal Cannabis

The Office of Medicinal Cannabis (OMC) has a special role to play. On behalf of the Ministry of Health, Welfare and Sport, this government institution is responsible for making medicinal cannabis available to Dutch pharmacists and for export.

Who is involved in the Dutch cannabis supply chain?
Niederländischer Regierungsangestellter entnimmt eine Probe von medizinischem Cannabis von Bedrocan

They commissioned Bedrocan for the cultivation. The packaging and distribution of the cannabis product are in the hands of other parties. Bedrocan has a long-term contract. In addition, we only grow what is ordered by the OMC.

Although the cannabis product bears the name “Bedrocan”, the OMC is the official producer. They oversee all steps in the production process, from cultivation to delivery to the pharmacy.

Opium Act

Because cannabis is classified as a controlled substance in the Dutch Opium Act, Bedrocan is not allowed to trade freely. That has also been agreed upon internationally. The OMC is the only one in the Netherlands that is allowed to buy, sell and export Dutch cannabis. Therefore, all our products are exclusively purchased by the OMC before they are sent to a pharmacy or a pharmaceutical company. This also applies if the cannabis product is used for medical or scientific purposes. With this, the government wants to rule out abuses and control where cannabis comes from and goes to.

Before the medicinal cannabis leaves our facility in large airtight bags, an OMC employee checks the product and all bags are weighted. A control sample is also made and sent to an independent laboratory.

About Bedrocan

Bedrocan has two GMP-certified production locations in the Netherlands, one research facility and its own laboratory in Amsterdam. The cultivation of cannabis is not done outdoors or in greenhouses but indoors in special culture cells. This allows us to fully control the conditions under which the plants grow. This is important so that each plant ultimately has the exact right composition.

Bedrocan currently produces five different standardised cannabis varieties, each with its own composition of THC and CBD, the best-known ingredients.

Independent laboratory

From each batch of medicinal cannabis grown, a sample is sent to an independent laboratory: Ofichem Labs. They test the cannabis for the absence of heavy metals, pesticides, fungi and other contaminants. It is also checked whether the product contains exactly the right amount of ingredients. After all, this cannabis is used as a medicine. A doctor or patient must be able to trust that it contains what should be in it. Only when the test results are satisfactory will OMC release the batch, and the pharmaceutical packer can get started.

Irradiation

Once the cannabis has left our facility, it is then irradiated first. That is how the Dutch government has decided. Irradiation with gamma radiation is a method of making products sterile and more durable. This method is often used in the pharmaceutical industry. It is an extra precaution to kill any micro-organisms such as bacteria and fungi and slow down spoilage. The radiation has no negative consequences for the quality of the cannabis product and the health of patients. The product does not become radioactive, as some may think. The company Steris specializes in gamma irradiation and carries out the work on behalf of the Dutch government.

Dutch Model En

The packer

After irradiation, the medicinal cannabis is taken to the packaging and distribution company. Fagron is the party contracted for this by the Dutch government. The cannabis is supplied in 5-gram jars or bulk packaging to pharmacists or pharmaceutical companies. An inspection is also carried out at Fagron by an OMC employee. This process checks whether the jars have been properly weighted and the total packaged weight of medicinal cannabis.

Distribution

In addition to being a packer, Fagron is also a pharmaceutical wholesaler. Pharmacies can order their medicinal cannabis directly here. Fagron then takes care of the delivery to the pharmacy.

€1.4 million for research into medicinal cannabis in epilepsy

The Dutch Ministry of Health has made a grant of 1.4 million euros available for research into the effectiveness of medicinal cannabis in children with treatment-resistant epilepsy. The question to be answered is whether medicinal cannabis reduces the frequency and/or severity of epileptic seizures in children. Researchers who want to be considered for the grant have until September 28, 2021, to submit their applications. Medical cannabis from the Office of Medicinal Cannabis (OMC) must be used for the research. Bedrocan produces this cannabis on behalf of the OMC.

Second round

This subsidy is the second made available by the Ministry of Health. Last year an initial subsidy of 1.9 million was awarded. This study focuses on the effect of medicinal cannabis on neuropathic pain.  Both studies are financed from the proceeds of the medicinal cannabis sold by the OMC in the Netherlands and abroad. The fact that this round of research is being conducted into epilepsy in children follows directly from a question from the House of Representatives. A motion by Vera Bergkamp (D66) calling for this was adopted in 2018.

Medicinal cannabis in epilepsy

Cannabidiol from the pharmacy can be prescribed according to the Epilepsy guideline from June 2020 in children (from 2 to 18 years old) with a treatment-resistant Dravet syndrome or patients (from 2 years old) with a treatment-resistant Lennox Gastaut syndrome.

In the Netherlands and several other countries, oil is made from the pharmaceutical CBD-containing cannabis product Bedrolite and prescribed to these patients. At the beginning of this year, the Medicines Evaluation Board (MEB) put cannabidiol, used by patients with epilepsy, on the list of medicines for which switching manufacturers is not advisable. This concerns medicines where incorrect intake leads to serious problems.

Renger Witkamp: “Cannabis is constantly making fun of us”

Biologist and pharmacologist Renger Witkamp is a professor of Nutritional Biology at Wageningen University & Research (WUR). Since 2005, he has also been professionally interested in the (im)possibilities of cannabis as a medicine. He has been involved in research into the medicinal effect of cannabis for over twenty years and also chairs the Institute for Medicinal Cannabis (IMC) in the Netherlands since spring 2021. As he notes, “the development and sharing of scientific knowledge about cannabis is a priority.”

Renger Witkamp constantly balances his work at the intersection of food and pharmaceuticals. He once described his field as ‘the field of science concerned with studying the effects of biologically active substances in food, with the aim of achieving a health-promoting or curative effect.’ According to Witkamp, ​​the key to a good and healthy life is a ‘healthy lifestyle’ and it is now generally known that nutrition plays a crucial role in this. But sometimes adjustments are necessary and pharmacology can offer a solution. And Witkamp and his team look further than just regular medication, because the department also focuses on herbs with a proven or alleged medicinal effect. Cannabis is one of them.

No panacea

Witkamp’s interest in the medicinal use of cannabis does not come out of the blue. “I was trained as a pharmacist, I studied biology, and I have always been interested in medicinal herbs. Precisely because the medicinal use of some herbs has been known worldwide for centuries, but often no scientific explanation has yet been found. Cannabis is definitely one of the most interesting plants, especially when you look back in history. The plant has been used for medicinal purposes for centuries and since the late last century, when the endocannabinoid system (“ECS”) was discovered, interest has been rekindled – and rightly so. But cannabis is certainly not a panacea and we still need a lot of scientific evidence to make well-founded statements about how it works.

Renger Witkamp

The problem is that cannabis – with all its different substances – is not an easy ‘product’ to research scientifically. The plant is constantly making fun of us. Cannabis is full of all kinds of substances, of which we only know a small part of what they do. And if we want to conduct research, which condition should we choose? In addition, we are not yet sure which formulation, which dosage form, and which dosage is best. In short, there is still a lot of scientific work to be done.”

Research

Witkamp has certainly contributed to scientific research. Since 2005, when he worked at TNO Pharma, he was involved in the analysis of THC in preparations and research into cannabinoids as a painkiller and appetite-stimulating or – inversely –inhibiting substance. “We already knew that there are cannabinoids (phytocannabinoids) in the plant, but now we also knew that similar substances (endocannabinoids) exist in the human body. Incidentally, also in many other organisms; we even found them in worms…

Like other researchers, we want to know how these phytocannabinoids affect the ECS. I remember that around 2006 all eyes were on the function of CB1 receptors in the body, which are involved in, amongst other things, the regulation of appetite and the development of diabetes. Many researchers – including Big Pharma – went in search of a suitable new CB1 blocker in cannabis, because that would mean a breakthrough in the search for the ‘new generation of drugs’. The idea behind such a synthetic blocker of the CB1 receptor was that it seemed to not only inhibit appetite, but such drugs also seemed to work in other ways against diabetes and its associated complications (collectively referred to as ‘metabolic syndrome’).

Ultimately, this was not successful, because such substances turned out to have serious side effects, precisely because the ECS is so complex and plays a role in so many processes in the body. Interestingly, the cannabis plant also contains a CB1 blocker, in amounts depending on the variety, which may seem more interesting in this regard. This is THCV. Big Pharma subsequently dropped out, but the indications that the ECS offers in the field of appetite and pain and other disorders are still there. Meanwhile, research in the field of phytocannabinoids in many different disorders continues, so that has not stopped. We are also continuing research at WUR, as we recently started in collaboration with the National MS Fund. Together with them, and a number of other parties, we will investigate what CBD can do for MS patients with sleeping problems. But we also see interesting research programs in, for example, Leiden (chronic pain, replacement of supplemental opioids) and Groningen (liver cancer).”

Dutch program

Renger Witkamp also witnessed first-hand the introduction of the Dutch medicinal cannabis programme, which, from 2003, has provided patients with medical prescription cannabis that has been standardised and produced to pharmaceutical grade. “That was an important step, which has also been taken in several other countries. Especially because strict demands were placed on the product from the start. In addition, the way in which patients can obtain it is well regulated. The route via prescriber and pharmacy is the most appropriate for patients, because both the doctor and pharmacist are watching, while the quality of the medicinal cannabis is guaranteed. This brings me to another important point of attention, and that is pharmacovigilance. It is extremely important that any side effects are documented, because we now know that cannabis is not necessarily harmless. For top fit people that may not matter that much, but for people with a reduced resistance – patients, that is – vigilance is required. In addition, priority will have to be given to smart formulations of cannabis-based medicines and, as mentioned, we must continue with scientific research.”

The right route

In the past plus twenty years, Witkamp has seen the world of medicinal cannabis constantly change, but in 2021 he can draw up a balance. “Cannabis is still loaded. Governments are cautious, and so are prescribers. There is still a lot of activism and often the dividing line between medicinal and recreational use is razor thin. All kinds of things are said about the plant, without there being any evidence for it. That’s fine, because traditionally a lot of knowledge comes from the ‘recreational’ angle. But sometimes things are said that could be dangerous for patients, because cannabis, as I said, is not necessarily harmless. I want patients to choose the right route; that they do not start ‘doing’ themselves, but get information and help in the right place; with their doctor, specialist, and pharmacist. But I also want to focus on prescribers because we know that knowledge about medicinal cannabis is sometimes lacking and patients are referred to the coffee shop.”

Share knowledge

With that in mind, Witkamp said ‘yes’ earlier this year when he was asked to become chairman of the IMC, a Dutch foundation that combines all scientific, medical, and production technical knowledge and experience in the field of medicinal cannabis. The foundation, which officially started on 1 March, consists of various organisations, including pharmacists, scientific institutions, universities, and manufacturers. And all affiliated organizations have a common DNA, according to Witkamp: “We are all legally active with medicinal cannabis. All participating organizations have an exemption to work with or conduct research on medicinal cannabis. In addition, we put the patient and the prescriber at the center of all our activities. Combining and expanding the knowledge about medicinal cannabis, and good scientifically based information and discussion about it are matters that are close to my heart and that is exactly what we want to do with the IMC.”

Renger Witkamp

Renger Witkamp (1959) studied Biology and Pharmacy at Utrecht University. After his pharmacy exam and PhD, he continued his work at Utrecht University as an associate professor of pharmacology. In 1996 he transferred to TNO Pharma, where he held various scientific and managerial positions. In 2006, he was appointed professor at WUR, where he currently leads the Nutritional Biology group. This group mainly focuses on the role of nutrition, whether or not in combination with other lifestyle factors and medicines, in aging and (recovery after) chronic diseases.

Since 2005, he has also been involved in research in the field of cannabis and the functioning of the ECS. In addition to his role in education and research, and as chairman of the IMC, he is also active at the Nutrition Lives Foundation, where he is involved in the application of lifestyle intervention as therapy. He is also a board member of the Alliantie Voeding in de Zorg and of the European Nutrition Leadership Platform.
Renger Witkamp was the first guest at Bedrocan Series (see picture). You can view the half hour webinar here.

source: Instituut Medicinale Cannabis

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