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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.

Sean Myles and Sophie Watts at Bedrocan Series

On Friday, November 5, Sean Myles and Sophie Watts of the Dalhousie University research team will be guests at Bedrocan Series. During this webinar they 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

How nice that you found us! Welcome to our website. You were probably looking for information about Reizen Waes. Last summer, presenter Tom Waes visited us in Emmeloord, where he made recordings for the new season of Reizen Waes. This episode will be broadcast on Sunday 31 October at 8.50 pm on NPO 3 and on Monday 06 December on Eén.be.

In the broadcast, you will learn more about our company as our CEO Tjalling Erkelens gives Tom Waes and his film crew a tour.

In the meantime, you can also check out our website. We are the only producer of medicinal cannabis in the Netherlands, and we do this on behalf of the Dutch government. Our medicinal cannabis is prescribed by doctors and is only available at pharmacies.

Click here for an overview of our products or if you want to know more about medicinal cannabis.

For questions about medicinal cannabis as a patient, please go to your personal GP.

If you would like to contact us, you can do so via our online 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 molecule

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 zit als CBD-zuur in trichoom

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?

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

Social Visual Bedrocan Series Renger Witkamp 300x251

Matthijs Bossong: “THC conducts psychotic-like symptoms in healthy people”

Matthijs Bossong is a neuroscientist at the University Medical Center Utrecht, where he conducts scientific research into the effect of cannabinoids (especially THC and CBD) on the human brain. Bossong has been involved in such research for sixteen years, first upon completing his PhD in Utrecht, where he investigated the endocannabinoid system’s role in psychiatric disorders in the human brain. That research focused mainly on the influence of THC in the development of psychosis-like symptoms. Later, Bossong conducted research on CBD and how this cannabinoid works in people at high risk of developing psychosis at the Institute of Psychiatry (King’s College) in London. Bossong subsequently deepened this research at the Department of Psychiatry of the University Medical Center Utrecht with a study into the effect of CBD in patients with a psychotic disorder.

Matthijs Bossong kicks off the second edition of Bedrocan Series with a brief explanation of the endocannabinoid system (ECS). Simply put, the functioning of our brain depends on communication between neurons (nerve cells), and that communication takes place via neurotransmitters. Well-known neurotransmitters include dopamine, glutamate, and gamma-aminobutyric acid (GABA), all of which affect feelings of tension, fear, and anxiety. But cannabinoids are also neurotransmitters. We only knew since the end of the last century that they are not only found in cannabis (phytocannabinoids), for example, but also in the human body (endocannabinoids). It is, therefore, logical to assume that the administration of phytocannabinoids influences communication in the human body. And thus also the brain and how our body is controlled.

Bossong can already share a clear conclusion with more than fifty participants during the webinar. “THC contributes to psychosis-like symptoms in healthy people,” he says. This conclusion follows from research in which a group of healthy people vaporized THC and were subsequently examined using an MRI scanner while performing a number of assignments. “We saw increased activity in certain parts of the brain when THC was administered in these tasks,” Bossong says. “This involved those parts of the brain where you can also see increased activity in psychosis. Everything indicates that THC causes those parts of the brain of healthy people to work harder than normal to carry out certain tasks.” Bossong compares that to a car that suddenly needs more fuel to cover the same distance.

Bedrocan Series met Matthijs Bossongg

In later research, Bossong focused on the effect of CBD. The central question was whether CBD could normalize psychosis or psychosis-like symptoms. In London, it was investigated how people at increased risk of psychosis (but who have not yet been diagnosed) respond to CBD. It became clear that symptoms of psychosis (anxiety, depression) were reduced by using CBD. The study among 31 patients with psychosis that was subsequently conducted in Utrecht seems to confirm this. It also raises questions on whether CBD, like THC, is a psychoactive substance. “That quickly raises a semantic discussion about ‘psychoactive’, but the fact is that CBD also affects certain parts of the brain, at least in people with a psychiatric background. In healthy people, you see that THC has an ‘intoxicating’ effect,” says Bossong.

THC is a risk factor in the development of psychosis, even when using medicinal cannabis, Bossong says when asked. “You can compare that to the role that smoking or eating hamburgers have in developing cardiovascular problems.” So be careful.

Like many of his colleagues, Matthijs Bossong emphasizes the importance of (more) scientific research. In the coming years, he will be involved in a large, multi-year international study into the effect of CBD among approximately 750 patients, partly people with psychosis and partly people with an increased risk of psychosis. The research, led by King’s College, should provide even more insight into how the endocannabinoid system works and how cannabinoids affect the function of our brain.

Medicinal cannabis or medical marijuana?

The way of referring to cannabis for medicinal use varies across the globe. Is it better to use the word medical or medicinal for cannabis? And what about medical marijuana? Bedrocan has a clear preference for what the correct term is, i.e. which is suitable and which is not. We are quite outspoken about that. In this article, we explain why.

Medical or medicinal

Let’s start with the terms medical or medicinal cannabis. Both are used, but are these two terms interchangeable? Is there a difference in meaning? At Bedrocan, we think so.

We avoid using the term medical next to cannabis. Medical is more applicable to a location or a practice such as a hospital or a dispensary. Its use is also better suited when referred to a condition, problem or treatment.

On the other hand, medicinal is defined, according to the Merriam Webster dictionary, as “tending or used to cure disease or relieve pain.” Unfortunately, cannabis cannot cure any disease, but it can definitely relieve pain and help treat several other medical conditions.

Medicinal cannabis or medical marijuana
Medicinal cannabis or medical marijuana

Bedrocan’s glossary

Medicinal cannabis, n: cannabis, or a product derived from cannabis, that is intended for medicinal use. Also, likely is: (i) prescribed by a trained medical professional; (ii) for a known medical condition or a set of conditions where it has proven to be an effective treatment; (iii) for which there is research demonstrating its efficacy as a treatment and/or where other treatments have been ineffective.

What about the term medical marijuana or weed?

Medical marijuana or marihuana is also being used to refer to medicinal use. In some countries, patients are forced to turn to products meant for the adult recreational market, often from the same outlet or delivered by post. Whereas in the Netherlands and in many other countries where Bedrocan is available, patients can access pharmaceutical-grade medicinal cannabis, not marijuana, through their pharmacy on prescription.

We avoid the term medical marijuana or weed as much as we can because it is linked to recreational use. Bedrocan believes in the strict separation between medicinal cannabis and cannabis for recreational use. We are committed to providing a pharmaceutical product that is only available on prescription for patients who benefit from it. We are entirely focused on this assignment. Besides that, the word cannabis is directly linked to the plant name: Cannabis sativa L. So why look for another term when one is already available. A nice side effect is that this scientific name fits a science driven company like us perfectly.

Cannabis, marijuana or weed?

Cannabis goes by many names. Marijuana, gañjā and hemp being the most well-known. Other less salubrious names include weed, pot or smoke.

Hemp is associated with the fibre-type cannabis plant, low in THC. Marijuana is most used in the Americas, while gañjā and derivations of the word are used in India and South-East Asia. Another well-known word is hash or hashish – a THC-rich resin extracted from the cannabis plant.

Regardless of all these terms and their differentiation by type (Indica, Sativa, Ruderalis), the term is now commonly accepted as simply Cannabis sativa L., or just cannabis. However, when produced pharmaceutically and used for medicinal purposes, the term medicinal cannabis is most appropriate.

Science is shaping how we talk about medicinal cannabis

Today, science shapes how we think and talk about medicinal cannabis. Along with like-minded companies, science is at the heart of Bedrocan. Our research programme focuses on advanced cultivation techniques and the development of unique, standardised cannabis strains for use by patients and the pharmaceutical industry. Other companies are taking steps toward registering cannabis-based medicines and medical devices (e.g. Epidiolex, Syqe). While, at a global level, the United Nations International Narcotics Control Board (INCB) is currently preparing a guideline of good practices. Driven by scientific evaluation, this global regulatory framework aims to achieve greater uniformity in good practices around cultivation, manufacture, distribution and global trade of cannabis for medicinal and scientific use.

All these actions are helping shape the future – including how we talk about cannabis for medicinal use and a broader acceptance of its use in more countries around the world.

Bedrocan proud partner of Institute Medicinal Cannabis

Reliable information about medicinal cannabis and it effects is not always easy to find. For that reason, Dutch pharmacists, doctors, companies and researchers have joined forces and set up a new partnership: the Institute Medicinal Cannabis Netherlands (IMC). Bedrocan is one of the proud partners of this new institute. The IMC aims to improve the provision of information about medicinal cannabis to patients and prescribers and strengthen collaboration in scientific research. Professor Dr. Renger Witkamp, professor of Nutrition and Pharmacology at Wageningen University, is the chairman of the IMC. Ole Heil, director Communications & Government Affairs at Bedrocan, is treasurer.

Thousands of patients

In the Netherlands, medicinal cannabis has been available to patients on a doctor’s prescription through pharmacies since 2003. Currently, about 10,000 people, with various conditions, make use of it every year. It is used, among other things, as a painkiller and as a symptom reliever in certain forms of epilepsy, MS and palliative care. Nevertheless, it appears to be difficult to find good and reliable information about the use and application of medicinal cannabis.

Bedrocan proud partner of the Institute Medicinal Cannabis

Renger Witkamp: “Unfortunately, we see a lot of incorrect information about medicinal cannabis. Many patients who may benefit from the product end up unnecessarily in the coffee shop or with illegal providers. Or worse, some doctors even actively refer their patients to this. The IMC aims to change this through good information. The IMC promotes that the treatment of patients who may benefit from medicinal cannabis takes place under the medical supervision of a doctor and pharmacist.”

Coordination of research

In recent years, more and more research has been conducted into the effect and application of medicinal cannabis. This is also the case in the Netherlands. Researchers are working on this at almost every university in our country. Because the research area is still in its infancy, there is still little collaboration and coordination. The IMC provides a platform to bring researchers together and join forces where possible.

Dr. Monique van Velzen, research manager of the Anesthesiology department of the Leiden University Medical Center (LUMC), is a board member of the IMC, in charge of research: “I notice that there is a great need for collaboration in the field of medicinal cannabis scientific research. Many studies, sometimes even within the same institution, overlap. And it is also difficult for researchers to find out what is and what is not allowed when it comes to cannabis, with many delays as a result. That is a shame, and we will soon change that with the IMC. By connecting researchers, we can learn from each other and streamline, coordinate and structure research.”

Substantive experts

The IMC is a foundation to which various partners and substantive experts have joined. In addition to a number of companies from the medicinal cannabis chain in the Netherlands, including pharmacies, these are doctors and researchers from the LUMC, UMC Utrecht, University Medical Center Groningen and Wageningen University & Research.

More information and contact details are available on the IMC website.

UMCG starts scientific research into cannabis oil and liver-cancer

The University Medical Center Groningen (UMCG) will start this year, 2021, a study on the effect of cannabis oil on liver-cancer patients who have exhausted all the avenues of treatment. The purpose of the pilot study, which will have 20 participants, is to see whether cannabis oil can reduce liver-cancer tumours. This is unique, as this type of study has not been carried out before. “It is pioneering in many ways”, said surgeon and lead researcher Maarten Nijkamp.

In three years from now, Nijkamp and his colleague Frederik Hoogwater, oncologist Derk Jan de Groot and gastroenterologist Frans van der Heide would like to be able to say whether medicinal cannabis oil has an impact on the growth, or rather the regression, of liver-cancer tumours. In this study twenty patients will be enrolled who all have come to the end of their standard treatment but still have a good liver function. The latter is important, because a functioning liver will ‘process’ cannabis oil on the basis of natural processes. As soon as the correct dose of cannabis oil has been determined and administration has started, a liver scan will be performed for every participant after three, six and nine months. Blood samples will also be taken to study the liver function and to check the presence of tumour markers. No later than in 2024 – or as much sooner as possible – the research team aims to present a clear conclusion.

UMCG starts scientific research into cannabis oil and liver-cancer

Anecdotal evidence

The idea for this clinical trial came up more than three years ago, when an UMCG patient with advanced liver cancer showed remarkable results upon using cannabis oil. The tumours in his liver started to disappear gradually after he started taking cannabis oil and now – five years following the diagnosis – he has been given the ‘all clear’. When comparable results were seen in a second patient, Nijkamp and his colleagues started to become excited. “We would have been equally excited if the patients had used fish oil”, tempers Nijkamp.

“However, cannabis and cannabis products are unusual. You only need to go on the internet to find a fair amount of anecdotal evidence for cannabinoids as a weapon in the fight against cancer. However, it is incidental and you do not know in how many patients the use of cannabinoid-based products did not have the desired effects. Then there is laboratory research that demonstrates that cannabis can have an inhibiting effect on the growth of liver-cancer cells. However, if you pour hot water or chlorine on cancer cells in a laboratory, you will see a comparable effect. In other words, you cannot state that cannabinoid-based medicines are able to cure cancer – in this case liver cancer – because there is no scientific proof. That requires a clinical trial with real patients. These two patients gave the topic ‘cannabis oil and liver cancer’ ‘meaning’ for my colleagues and me, because we are scientists as well as specialists. From a scientific point of view, we felt compelled to start up a trial. At the same time, we knew that it would be pioneering in many respects.”

Review

The set-up up of the trial presented a number of practical issues for Nijkamp and his team. First of all, the trial topic had to be approved and reviewed by various bodies, including the Medical Research Ethics Committee. Nijkamp: “Cannabis oil is not a registered drug and there are many unknowns. The wildest stories do the rounds, and we certainly did not want to fuel any fires with this trial. The review committee made sure that our trial complies with all the requirements imposed on such scientific research. At the same time, we needed answers to a number of questions. Such as: What are the substances that make cannabis effective? In what ratio are they required in the oil? Which dose is most suitable? Both patients used cannabis oil that contained THC and CBD, so that was our starting point.”

Good foundations

Then the team had to look for a manufacturer and supplier of the oil. “It is not difficult to obtain cannabis oil, but medicinal cannabis oil is a different story. For a trial like this one, the bar has been raised as high as possible”, said Nijkamp. “It goes without saying that the review bodies do the same. You need to have solid foundations: you need to procure material from a party with the right certificates for the production of your trial material. That is part of the requirements imposed on such a trial. You need to be sure that the trial material has a consistent composition, because otherwise you cannot make any statements about the results of the study. We knew that since a few years the Transvaal Pharmacy specialised in the responsible production of medicinal cannabis oil. They prepare that on the basis of standardised medicinal cannabis that is produced by Bedrocan under a contract with the Ministry of Health. The oil of Transvaal Apotheek is of a consistent quality and is tested by an independent laboratory. We knew that Transvaal Apotheek was working on obtaining certificates for the production of trial materials. That requires a significant amount of prior testing and review, and we had to wait for that to be completed. Then it was a case of selecting the right cannabis oil for the trial.”

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Transvamix®

For this pilot study, a medicinal cannabis oil that was already part of the range of Transvaal Apotheek has been chosen. Nijkamp: “We used the composition of the oils that were used by both patients as the starting point. That was oil with a relative high THC content. Transvaal Apotheek makes the oil on the basis of the standardised plant varieties Bedrocan® and Bedrolite®; it contains 10 percent THC and 5 percent CBD and is known as ‘Transvamix®’. We will use that oil as the material for the clinical trial.”

Dosage

The dosage was another point of attention, because in that sense cannabis oil is not comparable to regular medication. According to Nijkamp it may well be a reason why there have been very few clinical trials with cannabis or cannabis oil thus far. “Again, we were pioneering. With regular medication – like painkillers for example – there is a set dose; you know what the medication will do at a certain dose”, says Nijkamp. “Cannabis or cannabis oil is another story. Every patient responds differently to the product and the amount of oil that is required to be effective, may differ from patient to patient. That makes a trial much more complicated. For every patient we will raise the dose on a daily basis until there are side effects. Then we go down to the dose without side effects. In theory that would give you the highest possible dose without side effects.”

Pilot study

As far as we know, the UMCG is the first research institute in the world to carry out a study of cannabis oil for liver cancer. “In this form anyway”, said Nijkamp. “There are various laboratory studies into the effect of cannabis on tumours. We know about studies about cannabis oil for brain tumours, but as far as we know there has been no follow up. It goes without saying that cannabis is also used by cancer patients for a positive effect on the quality of life during treatment. So, this is a real pilot study. The study will only tell something about the effect of cannabis on patients with liver cancer who still have a functional liver. As soon as we know that it works in one patient, we will have taken one step forward and we can start thinking seriously about further research. Patients with liver cancer and liver damage, for example and other types of cancer. We might be able to observe that cannabinoids – in this ratio and for these patients – make a positive contribution to the quality of life. On that basis, cannabis-based products could play a set role in oncology in the future.
The outcome could also be that there is no response in any of the twenty people. Then, to that point, we have done what was required from a medical-scientific point of view, but would still be faced with a mystery in terms of why both patients were cured.”

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Bedrocan at the Australian United in Compassion Medicinal Cannabis Symposium
€1.4 million for research into medicinal cannabis in epilepsy