History is made: from flos to cannabis oil

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

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

OMC

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

Cystic fibrosis

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

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

Magistral preparations

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

Other pharmacies

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

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

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

Is medicinal cannabis on the rise in Australia?

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

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

High price

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

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

Professor Iain McGregor

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

General Practitioners

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

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

Research inspired by the Lambert family

Despite the medicinal cannabis programme, parents in Australia are still treating their children who suffer from epilepsy with cannabis products of unknown composition. This often includes severely sick children for whom regular medication barely works or does not work at all.

This is a big concern for the Lambert Initiative because the organisation is closely involved with families with children who suffer from epilepsy. The establishment of the research institute was made possible by a large donation from the prosperous Lambert family. Their grandchild Katelyn suffers from Dravet Syndrome, a rare and severe form of epilepsy affecting young children. Her family fought for years to legalise medicinal cannabis in Australia after discovering that cannabis oil reduced their daughter’s epileptic seizures. Katelyn is currently being treated successfully with approved medicinal cannabis oil. But at one time Katelyn’s father was standing in front of a judge himself because he grew cannabis illegally to treat his daughter.

Katelyn and Barry Lambert

The Lambert Initiative was curious to know if more Australian families were breaking the law to treat their children. In the end they found 65 families who were willing to participate in a study. Most of the parents are using cannabis oil obtained through the illegal circuit. They think they are administering CBD oil to their child. CBD is an active ingredient in cannabis. However, analysis showed that a considerable number of samples also contained THC. Iain McGregor, Academic Director of the Lambert Initiative, was very surprised: “Families were surprised as well. There are a whole lot of families that think that CBD has a fantastic effect. But we found out that there was no or low doses of CBD in their oils, but quite a lot of THC.”

The study was not designed in such way to provide any definitive conclusions on how effective these cannabis extracts are for childhood epilepsy. McGregor: “However, the study does throw a spotlight on the world of families who are resorting to the use of illicit cannabis products to treat their child’s epilepsy when conventional treatments have failed.”

Therapeutic Goods Administration

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

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

Paperwork

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

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

Medicinal cannabis chewing gum in clinical phase

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

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

MedChew Rx

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

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

Lekhram Changoer

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

More clinical trials

AXIM Biotechnologies will be carrying out more clinical research next year. QPS, a medication research company based in Groningen (Netherlands), will conduct a study on chewing gum with synthetic dronabinol (THC). This gum should, among other things, prevent nausea and vomiting (chemotherapy) or stimulate the appetite (anorexia, AIDS). The University of British Columbia in Canada will carry out clinical trials for treating drug-related psychoses with cannabis chewing gum. A double-blind, randomised, phase 2 study with 30 RLS patients will start in Israel next year.

Restless Leg Syndrome

AXIM Biotechnologies developed a chewing gum containing CBD to help patients suffering from Restless Leg Syndrome (RLS). RLS patients suffer from muscle spasms in their lower legs, knees and sometimes arms during the night. This leads to sleep disorders and the condition is also often accompanied by excruciating pain. The gum contains 1,000 milligrams of CBD and gabapentin, an anticonvulsant.

Just like a pill

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

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

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

‘Without doctors and pharmacists cannabis is not medication’

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

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

Photo courtesy of Yuval Landschaft

The Green Book

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

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

How it works

Israeli patients need a medical cannabis license, based on a specialist’s recommendation. This health care professional needs to be specialised in treating the condition for which the cannabis is recommended. This recommendation is examined by the MCA, based on relevant criteria and indications. Upon receiving the approval for a medical cannabis permit for the patient, the permit will be issued and transferred to the supplier. The supplier will contact the patient to coordinate instructions and supply to him or her.

Cannacopia

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

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

This inhaler will increase the acceptance of cannabis as medicine

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

Is that still the case?

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

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

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

What inspired you to start this company?

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

Perry Davidson

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

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

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

Syqe Inhaler

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

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

Clinical trials

Since 2014 Syqe has completed three clinical trials. The first trial was already published – a pharmacokinetic study that demonstrated the technology indeed meets pharmaceutical standards for drug delivery via inhalation. Subsequent trials focused on safety and efficacy for dosing in microgram levels. Outcomes were very positive, and Syqe expects to publish the rest of the clinical data soon. The inhaler has been in use in a hospital setting since 2015, and is expected to be available to patients in Israel later this year, distributed by Teva Pharmaceuticals. But Syqe also has prepared its infrastructures for the international markets, as they has set their sights on Europe, Canada and the United States.

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

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

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

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

New brochure provides more information about medicinal cannabis

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

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

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

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

See link to download a copy.

‘Avoid using sativa/indica terminology’

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

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

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

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

Sean Myles
Sean Myles

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

Cannabis reclassified

Cannabis labelled sativa and indica may not come from distinct ancestries, according to a study performed by the Canadian Dalhousie University in cooperation with Bedrocan on the genetic differences between the two types and their hybrids. In this study 149 Dutch cannabis samples were analysed, correlating the genotype and chemotype to their reported ancestries. Indica- and Sativa-labelled samples were not as distinct as sub species would be assumed to be, but the genetic differences between them do correlate to their terpene profile (resin fragrance), which could explain the variation between them.

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

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

What Bedrocan does

Bedrocan takes the advice into account and will reconsider how the differences can be classified better in the future.

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

‘WHO recommendations are likely to change international law’

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

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

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

ECDD

The Expert Committee on Drug Dependence (ECDD) is a WHO committee and is composed of independent experts in the field of drugs and medicines. The committee is convened by the WHO about once a year to assess the impact of psychoactive substances on public health and to make recommendations to the international community. This year the fortieth meeting was completely dominated by cannabis. This being the first time after the foundation of the WHO in 1948.

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

UN treaties

The Commission on Narcotic Drugs is a UN body that determines which drugs fall under international control. The committee comes to these decisions based on recommendations from the World Health Organization (WHO).

There are three major UN treaties that regulate drugs around the world:

  • The Single Convention on Narcotic Drugs (1961)
  • The Convention on Psychotropic Substances (1971)
  • Illegal trafficking in narcotic drugs and psychotropic substances (1988)

The 1961 treaty states that cannabis and cannabis preparations are out of date and there is no reason for their medical use. That treaty is what the proponents of medicinal cannabis use would like to see adapted.

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

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

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

Cannabis documentary about epilepsy to foster more understanding

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

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

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

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

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

CBD oil

Over time, the popularity of CBD oil has increased enormously. It is sold as a food supplement in the form of oil or capsules, and as a component of other products, such as care products for skin problems. Many people use the oil to calm down or to sleep better. The oil does not contain THC, a substance from cannabis that can make you high.

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

Regulation in the UK

In the United Kingdom, cannabis is on the list of classified drugs.  The UK uses three different classes, where a class A drug is more harmful than a class C drug and the punishments for misuse are higher. The cannabis plant, but also extracts such as oil and resin, are classified as Class B. Cocaine, LSD and ecstasy on the other hand are Class A.

Possession of cannabis is punishable with 5 years of imprisonment, supply with 14 years. The British Home Office may issue a licence in exceptional cases, generally for research purposes.  Since 2016, the United Kingdom has had an Act that states that all substances that contain psychoactive substances are illegal.

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

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

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

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

Chelsea Leyland ( right) and her sister Tamsin
Chelsea Leyland ( right) and her sister Tamsin

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

Alfie Dingley

This year, there was wider interest in medicinal cannabis in the United Kingdom following recent press articles about young epilepsy patients who are administered cannabis oil. One of those patients is six-year old Alfie Dingley, whose seizures reduced dramatically after being administered cannabis oil from the Netherlands. The use is illegal and to date import is not possible. The parents submitted an import application to the Home Office.

Mother Hannah Deacon is hopeful. In a recent video message on Facebook she said that the authorities are ‘extremely helpful’, and she calls it a ‘fantastic result’ that the British government is processing the application at all. “We need to stay positive and hopefully we will have a positive decision in four weeks time. If not, we will start another campaign, but I want to give the Home Office the opportunity to do something good.” Meanwhile Alfie is doing well.

Public opinion in the UK appears to be changing too. A petition asking permission for Alfie to use medicinal cannabis produced more than 370,000 signatures. Today three quarters of Brits think that doctors should be able to prescribe cannabis for medicinal purposes.

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

Bedrocan sponsors ICRS scientific congress

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

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

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

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

What Where When
Cannabis Europe Cannabis Europe London, United Kingdom 22 May
World Cannabis Congres World Cannabis Congress New Brunswick, Canada 10 – 12 June
Medical Cannabis Medical Cannabis ‘Controversies in Cannabis-Based Medicines’ Vienna, Austria 24 & 25 June
ICRS ICRS Leiden, the Netherlands 30 June – 5 July

Dr Hřib: ‘Don’t be afraid of medicinal cannabis’

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

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

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

Dr Hřib

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

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

What are the key benefits of medicinal cannabis?

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

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

What are the risks of prescribing medicinal cannabis?

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

Why is that?

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

How do you decide the best dose for individual patients?

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

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

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

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

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

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

How do you identify this issue in your practice?

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

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

I recommend two basic resources to doctors.

Furthermore I recommend the following websites:

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

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

Do you have any advice for doctors starting out prescribing?

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

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

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

Dutch patients’ daily cannabis dose remains stable

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

Where does the data for this study come from?

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

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

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

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

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

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

OMC

Dutch patients have been able to obtain medicinal cannabis on prescription from their GP for 15 years. The medicinal cannabis programme is supervised by the Dutch Ministry of Health’s Office for Medicinal Cannabis (OMC) . A programme which supplies pharmaceutical-quality medicinal cannabis. Since the start of the programme in 2003, medicinal cannabis has been prescribed a total of 170,000 times to more than 15,000 patients.

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

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

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

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

Why should we care about these figures?

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

On prescription

In the Netherlands, medicinal cannabis is only available on prescription and can be issued by any pharmacy in the country. Currently, only Bedrocan products are available. Five different products of pharmaceutical quality and standardised composition are available.

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

Can you say something about the duration of use?

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

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

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

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

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

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