1.9 million euros for research into neuropathic pain

The Dutch government is supporting research into the use of medicinal cannabis in the treatment of neuropathic pain with € 1.9 million. The grant has been awarded to a joint project of the Centre for Human Drug Research (CHDR), a Dutch independent institute that specializes in clinical drug research, and the Leiden University Medical Center (LUMC). Neurologist Geert Jan Groeneveld (CSO / CMO at CHDR and professor of Clinical Neuropharmacology at the LUMC) and Albert Dahan (professor of Anesthesiology at the LUMC) will conduct the research.

The research intends to lead to a specific recommendation of an optimal delta-9-tetrahydrocannabinol (THC) –  cannabidiol (CBD) dosage for the treatment of neuropathic pain in a particular subgroup of patients. In addition, it contributes to evidence for the effectiveness of medicinal cannabis. Bedrocan’s raw materials will be used for the production of the research material.

Geert Jan Groeneveld
Management

Innovative

The research does not look at the entire plant, but purely at the pharmacological effect of THC and CBD. Groeneveld: “We want to approach this research exactly as a drug developer would. As a clinical pharmacologist, you extract the proven pharmacological components from a plant and do research with it. That is also innovative in this research”.

The researchers will very accurately measure the pharmacodynamics and pharmacokinetics of THC and CBD, the effects of both substances on pain and brain function and how the substances behave in the human body.

“We are going to isolate the THC and CBD from Bedrocan cannabis and administer them in tablet form in different proportions. We will then look at the influence of CBD on the effects of THC , and investigate which THC-CBD combination is best for the treatment of neuropathic pain”, said Groeneveld.  The Dutch company Echo Pharmaceuticals from Leiden will produce the tablets for the research.

Healthy subjects

The study consists of two parts. In the first part, healthy subjects will be administered the tablets with different THC and CBD ratios. The first part of the research will show whether the adverse effects of THC, such as getting high or feeling anxious, can be reduced by administering CBD simultaneously. According to Groeneveld, the scientific literature has so far provided conflicting results about this: “To be honest, I do not expect much from CBD alone as a treatment for neuropathic pain. From a pharmacological point of view, it is likely that THC affects pain, but this is less the case for CBD. CBD could have an effect on inflammation, but there is no reason  to use CBD as a treatment for inflammatory pain. We already have Ibuprofen for that. It will only become interesting if the adverse effects of THC, such as feelings of anxiety, can be alleviated by administering CBD at the same time. “

Search for the ideal ratio between THC and CBD

THC (9-tetrahydrocannabinol) and CBD (cannabidiol) are the two most studied active ingredients of the cannabis plant. THC is known for its analgesic effect, but it also causes psychoactive side effects. CBD could lead to pain-relieving effects through other mechanisms. It is believed that CBD may also influence the psychotropic effects of THC by modulating THC binding to the CB1 receptor. However, it is still unclear what the ideal ratio of THC to CBD would be to take advantage of the CB1 modulating effects of CBD while preserving the positive effects of THC on pain. In addition, it is still unclear whether the analgesic effects that some patients experience as a result of CBD use are due to a pharmacological action of CBD, or simply because CBD prevents the metabolism of concomitantly used pain killers. The latter will also be investigated in these studies.

Patients with neuropathic pain conditions

The effects on pain in patients will not be investigated until the second part of the study, after the results of the first study are known. This will provide information on which THC:CBD ratio works best. The second part of the study will take place among a diverse group of 200 patients with different neuropathic pain conditions. Groeneveld: “We are going to phenotype this group very well in advance. This means that we want to know exactly how the neuropathic pain manifests itself specifically in this group. Do patients have demonstrable nerve damage, do they have a personality disorder, are they depressed, or do they have sleep disorders? All these are variables that we are going to map.”

Subsequently, the participants in a crossover study will receive placebo for five weeks, and after a wash-out period, they will receive five weeks of cannabinoid treatment or vice versa. Pain will be measured in each treatment period. Groeneveld: “In patients with clear pain relief, we want to further investigate whether there is a correlation between their variables, such as sleeping problems, anxiety or peripheral nerve damage, and the response to treatment with THC.”

The first part of the study will start in the spring of 2021, and Groeneveld expects the first results in the summer. The second part of the study with the pain patients will start in the autumn and will last at least two years.

The problem with CBD oil

The quality of CBD oil, and other CBD products, on the global market varies drastically. From pharmaceutical quality, prescription medicines, to those which are of dubious quality, and in some cases outright dangerous.

There has been a lot of interest, and indeed, investment in cannabidiol (CBD). This is partly because, unlike THC, it is not intoxicating. [1] [2] It has also been re-scheduled in a number of countries, permitting use as a prescription medicine. [3] [4] In the background of regulatory change, CBD has been showcased globally as a wonder drug – almost a panacea.

The rise in use of CBD oils, or any other product containing CBD, reflects a sharp rise in self-medication. The trend is underscored by the population risk of taking high doses of a medicine we still know very little about. [5]

Medicinal cannabis oil

The rise of CBD oils

‘Charlottes Choice’ ignited a storm – the online video and story went viral. ‘CBD oral dosing reduced a young child’s epileptic seizures brought on by Dravet syndrome.’ [6] [7] [8] Media coverage increased CBD oil demand, [9] while political power plays promoted accessibility. [10]

While anecdotal reports sparked interest cannabinoid treatments, the lack of clinical evidence did not support safety or efficacy. Subsequently, GW Pharmaceuticals published solid research supporting the use of CBD in treatment resistant epilepsy (i.e. Dravet syndrome and Lennox-Gastaut Syndrome). Epidiolex™ then received FDA approval. [11]

In the background, rapidly moving away from the epilepsy focus, CBD was gaining momentum in other conditions. With the great promise of its therapeutic potential, combined with the lack of regulatory oversight, a huge, worldwide market for (unregulated) CBD products has emerged. [12]

Unregulated, or poorly regulated products are a problem for consumers and patients alike. The cannabinoid composition may not be correctly disclosed, nor checked by a certified control laboratory. Products may contain no CBD at all, while others may contain high doses of THC. [13] Such dubious products may also include residual manufacturing solvents, and contaminants such as microbes, pesticides, heavy metals or mycotoxins.[14] Besides posing a health threat to consumers, the lack of product consistency makes it difficult to evaluate the therapeutic effects. [15]

The demand for CBD is expected to markedly increase if CBD becomes available for use as wellness products (e.g. lotions, balms, oral drops), and, or is incorporated into consumer products (i.e. beverages and other food stuffs). This trend may be partly driven by the might of the alcohol industry, with the likes of Constellation Brands (an alcohol company) and Canopy Growth Corporation (a Canadian recreational/medicinal cannabis producer) weighing into the market. [16]

Can CDB be harmful?

There seems to be a global concensus that CBD is safe, without harm. Perhaps this is driven by that it is not intoxicating, alongside its relative success certain specific cases.

The FDA are deliberating this very issue “there are many unanswered questions about the science, safety, and quality of products containing CBD”. [17] As such, if CBD is shown to be a risky substance, causing harm such as toxicity to the liver, the entire industry that has invested so heavily in it will fall under heavy scrutiny. Many companies could fail.

CBD is a medicine, so always consult a doctor

Given CBD affects the endocannabinoid system, it can also disrupt that system. There are also many unknowns about CBD, especially about the long term use and in high daily doses. [18] [19]

Some side-effects from CBD might include fatigue, diarrhoea, decreased appetite, and weight loss. [20] [21] Furthermore, CBD is typically an adjunct treatment (taken with other medicines) and is metabolised by the liver cytochrome P450 enzymes (CYP450). When taken together with other medicines metabolised by the CYP450 system, there is the potential for drug-drug interactions. [22] Finally, dose adjustment is recommended in patients with moderate to severe hepatic impairment, to reduce burdening the metabolic process. [23]

Widespread ‘self-medication’ poses risks beyond poor quality products. Consumers or patients should be encouraged to ask about or inform health professionals before trying CBD. Health professionals should suggest using only reliable, safe and standardised products, preferably of pharmaceutical quality. Typically, this would mean accessing products from a pharmacy.

A reputable CBD oil, or any CBD product, will have a Certificate of Analysis (CoA) to confirm the label claimed CBD content (milligrams per millilitre (mg/mL)), and that it is free of contaminants. A CoA is produced by an external, independent contracted laboratory. Ask for this. [24] A quality product is also likely to have online reviews, which can be compared with the CoA.

Quality is the question for the CBD oil market

CBD products can be purchased online, are distributed through informal cannels, or from the drug store. In Europe and the USA, many are sold as a food supplements, with most not having been approved by the European Food Safety Authority (EFSA) or Food and Drug Administration (FDA).

Quality control and standardisation is very important. The use of sub-standard materials and methods to produce CBD medicine, for example, risks batch-to-batch variation and the potential for medicine contamination (i.e. toxicity) [25] [26] [27] [28] [29]. Good quality products are produced by pharmaceutical companies, or a compounding pharmacy. The manufacturing process assures consistent strength, purity and the monitoring of the manufacturing operations. Unregulated producers cannot assure consumers and patients this level quality.

In sum, there is a dire need to confirm the clinical value of CBD, as well as to properly regulate its quality and distribution as a potential medicinal product.

References

[1] Kowal, M., Hazekamp, A., Colzato, L., van Steenbergen, H., Hommel, B.. (2013). Modulation of cognitive and emotional processing by cannabidiol: the role of the anterior cingulate cortex. Frontiers in Human Neuroscience. 7

[2] Mechoulam, R., Parker, L., Gallily, R. (2002). Cannabidiol: An Overview of Some Pharmacological Aspects. The Journal of Clinical Pharmacology. 42(S1):11S-19S

[3] For example, New Zealand currently permits CBD as a prescription medicine, while Australia is currently considering low dose CBD as Pharmacy Only Medicines.

[4] Despite its widespread use, CBD remains a controlled drug. The UN Single Convention 1961 lists cannabis and preparations in Schedule I (extracts and tinctures) and IV (cannabis and resin). Given CBD is derived from cannabis, it is a controlled drug.

[5] WHO (2018). Cannabidiol critical review report. WHO Expert Committee on Drug dependence. Geneva; June 2018. . Retrieved online 28 October 2020

[6] Marijuana stops child’s severe seizures. Retrieved online 28 October 2020

[7] Charlotte’s Web CBD products: 2020 review. Retrieved online 28 October 2020

[8] Charlotte’s Web. Retrieved online 28 October 2020

[9] Example. Epilepsy patients flock to Colorado after medical pot gives them hope. Retrieved online 28 October 2020

[10] Example. Medicinal cannabis: Victorian families hopeful as state grows crop to treat children with severe epilepsy. Retrieved online 28 October 2020

[11] FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy.U.S. Food and Drug Administration. Retrieved online 28 October 2020

[12] Dance, a. (2019).  As CBD skyrockets in popularity, scientists scramble to understand how it’s metabolized. Nature magazine on November 14, 2019. Retrieved online 28 October 2020

[13] Hazekamp, A. (2018). The trouble with CBD oil. Med Cannabis Cannabinoids;1:65–72

[14] Romano, L & Hazekamp A. (2013). Cannabis Oil: chemical evaluation of an upcoming cannabis-based medicine. Cannabinoids;1(1):1-11

[15] Freeman, T., et al. (2019). Medicinal use of cannabis based products and cannabinoids. BMJ 2019;365:l1141

[16] What Constellation Brands’ massive investment in Canopy Growth Corp. means for both companies. Retrieved online 28 October 2020.

[17] FDA consumer updates. What you need to know (and what we’re working to find out) About Products Containing Cannabis or Cannabis-derived Compounds, Including CBD. Retrieved online 28 October 2020

[18] Ibid.

[19] Huestis, M., et al. (2019). Cannabidiol adverse effects and toxicity. Curr Neuropharmacol. 2019 Oct; 17(10): 974–989

[20] Epidiolex. Highlights of prescribing information. Retrieved online 28 October 2020

[21] Iffland, K., & Grotenhermen, F. (2019). An update on safety and side effects of cannabidiol: A review of clinical data and relevant animal studies. Cannabis Cannabinoid Res. 2017; 2(1): 139–154.

[22] Lucus, C., et al. (2018). The pharmacokinetics and the pharmacodynamics of cannabinoids. Br J Clin Pharmacol (2018) 84 2477–2482 2477

[23] Ibid

[24] See this reference for advice. Chesak, J., (2019). Reading a CBD label: How to find a quality product. Retrieved online 28 October 2020

[25] Hazekamp, A. An evaluation of the quality of medicinal grade cannabis in the Netherlands. Cannabinoids 2006;1(1):1-9

Compared to pharmaceutical cannabis, non-pharmaceutical cannabis has been found to contain less cannabinoids, is contaminated with bacteria and fungi, and often will contain the pesticides, fungicides or heavy metals.

[26] Bettiol et al. (2019). Galenic preparations of therapeutic Cannabis sativa differ in cannabinoids concentration: A quantitative analysis of variability and possible clinical implications. Front. Pharmacol., 17 January 2019 |

[27] Calvi, L., et al. (2018). Comprehensive quality evaluation of medical Cannabis sativa L. inflorescence and macerated oils based on HS-SPME coupled to GC-MS and LC-HRMS (q-exactive orbitrap®) approach. J Pharm Biomed Anal. 2018 Feb 20;150:208-219

[28] Hazekamp, A. (2018). The trouble with CBD oil. Med Cannabis Cannabinoids;1:65–72

[29] Romano, L & Hazekamp A. (2013). Cannabis Oil: chemical evaluation of an upcoming cannabis-based medicine. Cannabinoids;1(1):1-11

Study finds: Medicinal cannabis oil can reduce migraine attacks

Medicinal cannabis oil, based on the raw materials Bediol and Bedica, may have a positive effect on the severity and frequency of migraine attacks. This is evident from a cross-sectional retrospective study, in which patients completed a questionnaire about their experiences with the use of cannabis oil. The patients were approached by the Transvaal Pharmacy in The Hague. According to the researchers, medicinal cannabis oil could serve as a possible alternative for migraine attacks from a pharmacological point of view.

Strongest decline

Bediol oil was the most prescribed in the participating patients and showed the strongest decrease in the number of migraine attacks per month and their severity. Bedica oil also showed a significant decrease in the number and severity of the migraine attacks. Bedrocan cannabis oil does not appear to have an effect on the frequency and severity of the migraine attacks.

Medicinal cannabis oil is administered sublingually drop by drop. Medicinal cannabis flos, the dried version, is used in evaporated and edible forms, among others.

Migraine & Menopause

The average age of the consulted patients was 54 years old. Of these, about 80% were women, and most women were around the menopause age. According to the researchers, this may have played a role in the positive results with women. Studies show that most women who suffer from migraines see improvement after menopause. However, other studies suggest that migraines seem to worsen in women after menopause. According to the researchers, it is therefore not possible to affirm with certainty that menopause had a positive effect on the results with women.

Side effects

Furthermore, the questionnaire asked about five direct side effects, namely: nausea, drowsiness, nervousness, nightmares and memory loss. With the use of medicinal cannabis oil, nausea and drowsiness were mainly reported as side effects.

However, there were more patients with a decrease in nausea than with an increase. According to the researchers, this can be considered a therapeutic effect rather than a side effect. This decrease was mainly due to the use of Bedica oil. As a result of this study, Bedica oil could be recommended for patients who suffer from nausea during a migraine attack.

To confirm this study’s findings and to include medicinal cannabis oil in current migraine treatment guidelines, the researchers argue that randomized, controlled clinical trials with a larger study population are desirable.

Cannabis studies with Bedrocan products

Over the years, Bedrocan cannabis has been used in many scientific studies. Initially, research focused on a better understanding of the pharmacology of cannabis and its components. However, many cannabis studies involving human subjects also investigated the psychopharmacological effects of Bedrocan products. While more recent research has aimed at exploring the clinical applications of cannabis in patients.

When possible, Bedrocan supports independent research, and we are open for collaboration with academic and medical institutions, such as the LUMC.

We believe that supporting scientific research contributes to our mission to bridge the gap between patients’ needs and the regulatory demands of modern medicine.

Please check the updated list for an overview of published researches with the use of Bedrocan cannabis.

Smoking cannabis vs vaporization

Around the world, people administer medicinal cannabis in various ways. Inhalation is one option. While vaporization continues to be a notable mode of consumption, it is smoking cannabis that remains number one. But why smoke cannabis when vaporization is an option?

Why would you smoke cannabis?

Imagine smoking. Inhale… Exhale… Big inhale! Cough, cough, cough! Lungs filled with smoke, tar, toxins.

We have been warned off about smoking for years, mainly from our collective knowledge of the risks of smoking tobacco. But we know smoking cannabis brandishes harms, too. [1]

Looking at Canada, among survey respondents who used cannabis in the past year, the majority used cannabis flower. Despite over half (53%) being exposed to health warnings, increasing their knowledge of the harms related to cannabis use, the majority continued to smoke. Indeed, smoking (84%) was the most common method of consumption in Canada among non-medical users. While not identical, there are similar trends for Canadian medical users (using on average 1.5 gram/day cannabis flower). [2] And, indeed, this use profile is mirrored among respondents in previous ‘use’ surveys. [3]

So, why are people not vaporizing?

Is it the cost? Is accessing and using a vaporizer prohibitive? Is it people not being used to vaporizing technology? Is it faster to roll and smoke a joint? [4]

The benefits of vaporizing cannabis

We know that the use of a high-quality vaporizer device avoids the respiratory disadvantages of smoking. [5]

A vaporizing medical device, compared to smoking cannabis, dramatically lowers concentrations of toxic compounds such as carbon monoxide, ammonia and polyaromatic carbohydrates (PACs). Compared to smoking, higher therapeutic levels of THC and consistent, reproducible THC extraction and delivery is possible. [6] [7]

It has been established that inhalation via a vaporizer is an efficient route of administration. The vapour is quickly absorbed by the lungs, resulting in measurable cannabinoid serum levels rapidly (reaching Tmax within minutes). [8]

The rapid onset of effects of vaporized and inhaled cannabinoids allows easier titration of the dose based upon symptom severity, tolerability and avoidance of side-effects. [9] While fully standardised, pharmaceutical-quality cannabis flos enables the administration of an exact dose – assured dose composition and dose repeatability. It also means it is free of contaminants such as microbes, pesticides, heavy metals and other toxic compounds. From a patient safety perspective, these qualities make the vapour safer for inhalation into the lungs.

Over the past years, more and more patients have vaporized cannabis flos without reports of serious adverse reactions. It is now time to start exploring ways to move patients away from smoking toward less harmful modes of administration.

Given patients seek a reliable, affordable and portable vaporizer for administering cannabis flos, perhaps more attention is required here?

Is adept, well-timed policy the way forward?

Future thinking – policy angles

Given patients indicate a preference for vaporizers, sensible policy and practical education might be the way to usher in positive change.

With regard to administration, the future policy must be clear and obvious. For example, in Germany, Australia, New Zealand, and The Netherlands smoking cannabis flos is not permitted and/or actively discouraged. The clinical guidelines only support cannabis flos for inhalation administered by vaporization. These types of policies need support from the health sector, industry, and must achieve buy-in from patients and their careers.

Some other approaches might include:

  • Setting a positive regulatory environment, focusing on and enabling rapid developments in the vaporizer industry. The aim is to usher in vaporizers which are more affordable, portable, easy to use, environmentally and consumer friendly.
  • Ensuring that a blanket ban on inhalation is not pushed into law. Excluding quality vaporizer devices from the market would be nonsensical. It would:
    • Eliminate their valid use in hospitals and hospices, rest-homes, and home settings.
    • Have implications for administration options; limiting therapeutic options and prescriber-patient choice.
    • Confine administration to oral dosing only (i.e. excluding the inhalation option).

Policy focused to support education is another, including:

  • Educating prescribers, pharmacists and patients to be aware of the differences between ‘vaping cannabinoids’ and ‘vaporising cannabis flos’, and fully understand why smoking should be avoided.
  • Educating the consumer (i.e. patients) on the benefits of using a vaporizer, compared with smoking. This requires really clever social-advertising – getting people to change, often embedded, behaviours and the accepted culture of smoking a joint.
  • Educating the consumer (i.e. patients) on what makes a good vaporizer – what quality aspects to look for.

For more on administration, see the article The risks of vaping cannabis.

References

[1] Tashkin, D. P. (2013). Effects of marijuana smoking on the lung. Annals of the American Thoracic Society, 10(3), 239-247.

Tetrault, J. M., Crothers, K., Moore, B. A., Mehra, R., Concato, J., & Fiellin, D. A. (2007). Effects of marijuana smoking on pulmonary function and respiratory complications: a systematic review. Archives of Internal Medicine, 167(3), 221-228.

[2] Health Canada (2019). The Canadian Cannabis Survey 2019.

[3] Sexton, M., Cuttler, C., Finnell, J., Mischley, L. (2016). A cross-sectional survey of medical cannabis users: Patterns of use and perceived efficacy. Cannabis and Cannabinoid Research; 1: 131-138.

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

[4] Aston, E., Scott, B., and Farris, S. (2019). A qualitative analysis of cannabis vaporization among medical users. Exp Clin Psychopharmacol. 2019 Aug; 27(4): 301–308.

[5] Loflin, M., and Earleywine, M. (2015). No smoke, no fire: What the initial literature suggests regarding vapourized cannabis and respiratory risk Can J Respir Ther. 2015 Winter; 51(1): 7–9.

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

[6] When administering pharmaceutical quality cannabis flos.

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

Gieringer, D., Laurent, J., Goodrich. (2004). Cannabis vaporizer combines efficient delivery of THC with effective suppression of pyrolytic compounds. Journal of Cannabis Therapeutics. 4(1)

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

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

[8] Tmax: the time it takes to reach the maximum concentration (Cmax) of an exogenous compound or drug in the plasma or a tissue after a dose is administered.

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

Marie Arena, a strong voice bringing the topic of medicinal cannabis into European politics

Bedrocan has always been a strong advocate for internationally harmonised regulations on medicinal cannabis. A woman with the same cause is a Belgian Member of the European Parliament (MEP) Marie Arena (PS). Last December, she organised a large event in the European Parliament in Brussels named ‘Cannabis Renaissance.’ She chose this name on purpose to represent the revival of the cannabis plant: ‘The cannabis plant is part of a long history that is currently revived across Europe, in traditional and medicinal use and scientific research.’

Bedrocan spoke with Marie Arena and asked her what her plans are for medicinal cannabis in Europe.

As a MEP, you have been quite active on the topic of medicinal cannabis. Why?

This will obviously be a lengthy process, but our goal is to have a new EU legal framework on the use of cannabinoids in medicinal products and the marketing of these products to ensure access of patients to these products.

An even further step would also be to make progress on the legislation of CBD beyond medicinal uses but this is not our main goal yet.

Marie Arena
Marie Arena

You promote a clear distinction between medicinal cannabis and cannabis for recreational purposes. Why do you think that separation is important?

I think this clear distinction is important for two reasons. First, there is still a strong misconception and taboo when talking about cannabis. Many people still see cannabis in the illegal drug context and not for its medicinal properties. So I think separating the two is a way to reassure these people and to include them in the dialogue around this topic.

The second reason this is important is from a legal point of view. There is already a European framework that enables Member states to develop medicinal cannabis programs. So the base is already here for us to build upon and go further. When it comes to recreational purposes, this is a much more sensitive topic that lies with the Member states. And this also serves the first aspect I was talking about regarding the taboo around cannabis. The strong legal framework around the use of cannabis for medicinal purposes will help reassure and talk to people that have understandable concerns about this.

Marie Arena

Marie Arena, born and raised in Belgium, comes from an Italian migrant family. Her father worked in the Belgium mines and the glass and steel industry. From this background, Arena got her commitment to work hard for a fairer society in which citizens are protected and their rights respected.

After her studies in economic sciences, she held various jobs, eventually becoming a Minister for employment and training in Wallonia’s government.

Since then, she served both as a federal minister in the Verhofstadt II government and the prime minister of the Cabinet of the French Community in Belgium. Arena was first elected in the European Parliament in 2014, and since then, she has worked tirelessly to promote her values and ideals, among which are the public interest and her commitment to a social, transparent, and united Europe. Besides she is advocating for European harmonisation in medicinal cannabis legislation she is also a member of a new special commission on cancer.

 

Many countries have their own system for getting medicinal cannabis to patients. Do you believe European harmonisation in legislation is necessary?

This is true that several countries already have medicinal cannabis programs, but the lack of harmonisation at the European level is detrimental to patients first. If we want to make the European framework on medicinal cannabis evolve, our main focus must be patients’ access to their medicine. We know that even in countries with such programs, patients often have difficulties to have access to these treatments. There is also the issue of cross-border healthcare. Directive 2011/24, which sets the right of patients when traveling in another Member states to receive healthcare. We must make sure that patients’ rights are ensured and that they can  have access to their medication across all of the EU.

 As of now, the products patients can find from one country to another can have different properties due to the differences in THC and CBD concentration from one Member States to another. This is another reason for which we need a harmonised legislation.

Do you think harmonisation is possible?

I do believe that we can achieve at least some level of harmonisation. More and more countries are launching their own medicinal cannabis program, such as France which just launched a very ambitious experimentation program. So I believe there is a momentum that can make things move in the right direction.

There is also the vote, that has unfortunately been postponed, of the United Nations’ Commission on Narcotic Drugs (CND) on six recommendations following a critical review of cannabis-related substances. If these substances are taken out of the list of Narcotic drugs and this is supported by a number of EU member states, this would be an important political message for us to go further.

What steps will you be taking next to achieve your goals?

We are in the process of contacting interested Members of European Parliament to create a working group in the parliament on the topic. We really want to be a cross-party committee. This working group will work as a forum to discuss and have exchanges with all the relevant stakeholders, experts, NGOs, patients association, and the European Commission.

From all this consultation, we will try to work on a common position we could defend in the Parliament.

If it all goes to plan, a further step, maybe for the second semester 2020, would be to have an initiative report on the topic at the Environment and Health Committee. This will be important in order to have a strong position on the topic and to get the Commission involved.

The risks of vaping cannabis

A year ago, there was a lot of talk about the risks of vaping cannabis (THC containing liquids) – media reporting ‘vaping-related lung illnesses’ across America. Vaping was mistaken for vaporization, a medical device for administering cannabis flos, [1] and was considered dangerous. In our 2019 article, we discussed the risks of using ‘vape-pens’, [2] their diluents or carrier agents, [3] [4] and the accompanying socially intrusive vapour clouds. None of which are a feature of the medicinal use of cannabis flos by vaporization. [5]

So, what has happened since then?

The vaping saga

To recap. Vaping works by heating a liquid (i.e. cannabinoids and diluents) to produce an aerosol that is inhaled into the lungs. [6] In 2019, a surge of people with vaping associated pulmonary injury, some cases fatal, had many scratching their heads looking for answers.

The serious incidents in the United States of ‘E-cigarette, or Vaping, product use-Associated Lung Injury’ (EVALI) were investigated by the US Centres for Disease Control and Prevention (CDC), Food and Drug Administration (FDA) and clinical partners. [7]  Their investigations continue into 2020.

Informal sources

The CDC goes on to state that, “informal sources are linked to most EVALI cases and play a major role in the outbreak”. Indeed, the link to Informal sources, likely illegal and counterfeit products, produced and distributed without regulatory oversight, is substantiated by a report by Anresco Laboratories (California, USA). Anresco tested legal and illegal samples in the state. They discovered no evidence of vitamin E acetate adulteration in the regulated-market products, and a high degree of vitamin E acetate contamination in illicit market samples. [9]

Toxic by-products

In response to the EVALI incident, the ASTM D-37 subcommittee, a cannabis industry standards-setting organisation, discussed vaping concentrates (February 2020, Atlanta, GA, USA). The dialogue included that diluents used in formulating liquids for vaping should be exposed to high temperatures and screened for toxic by-products. This would help assure that no harmful constituents are incorporated into regulated cannabis vape products, now and into the future.

Clearly, industry engagement, robust regulatory processes, and active enforcement remain the backstop to challenge illegal activity in any market.

Various risks of vaping cannabis

Nonetheless, while the legal cannabis market appears sound, there remain various risks of vaping cannabis. There is money made in illegal sales. Counterfeit vape materials and packaging have entered the legal market, at least in California (USA). [10] [11] The unregulated cannabis flower used to produce concentrates is often found to contain higher levels of pesticides, heavy metals, and other contaminants.[12] And, importantly, the process of producing cannabinoid concentrates will logically lead to exposing consumers to higher concentrations of a wide range of toxins.

Given the pace of development in regulated markets, we may see a sizable proportion of consumers continue to source products from unregulated sources. At least in the short term. This is evident even in Canada, a nationally regulated market, where not everyone obtains their cannabis from legal, quality-assured sources. [13] In this frame, harm caused by the consumption of unregulated products will continue and so will the risks of vaping cannabis.

So, the issue of vaping associated pulmonary injury is by no means resolved. The black market appears to be at fault. Meanwhile, the various regulators remain vigilant. And, the industry appears resolute in upholding obligatory quality standards. 

References

[1] Fully-standardised, pharmaceutical-quality cannabis flos is the whole, dried flowers/inflorescence of the cannabis plant, which is genetically and chemically standardised according to pharmaceutical standards. It is free of contaminants such as microbial contaminants (molds, fungi, and bacteria) pesticides (residues), aflatoxins, impurities and heavy metals.

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

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

Editorial and Review (2019). E-Cigarettes and vaping-related disease. New England Journal of Medicine.

[3] A variety of diluents, which act as carrier agents, have been used in vape pens, including Polypropylene Glycol (PPG), Propylene Glycol (PG), Polyethylene Glycol (PEG), Vegetable Glycerin (VG), and Ethylene Glycol (EG).

Given the associated health risks with the consumption of the above-noted diluents, vaporizer cartridge producers seem to be moving towards using terpenes, or alternative extraction methods which produce a less viscous cannabis concentrate, eliminating the need for diluents altogether.

[4] Troutt, W., and DiDonato, M. (2017). Carbonyl compounds produced by vaporizing cannabis oil thinning agents. J Altern Complement Med. 2017 Nov;23(11):879-884.

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

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

[6] A vape pen (an atomiser vaporiser) is a device typically containing an electronic heating system and a cartridge (containing a cannabis-based liquid (i.e. decarboxylated cannabinoids and excipients (a diluent or carrier agent)). The liquid is heated, creating an aerosol vapour which is inhaled via a mouthpiece.

[7] CDC update (25 February 2020). ‘Outbreak of Lung Injury Associated with the Use of E-Cigarette, or Vaping, Products

[8] Blount, B., Karwowski, M., Shields, P., et al. (2020). Vitamin E acetate in bronchoalveolar-lavage fluid associated with EVALI. N Engl J Med 2020; 382:697-705.

[9] Eisenberg, Z., Moy, D., Lam, V., Cheng, C., Richard, J., Burack, B. (26 October 2019). Contaminant analysis of illicit vs regulated market extracts. Anresco Laboratories.

[10] Queally, J. (2019). Counterfeit cannabis products stoke black market for California weed. Los Angeles Times; 26 August, 2019.

[11] Eisenberg, Z., Moy, D., Lam, V., Cheng, C., Richard, J., Burack, B. (26 October 2019). Contaminant Analysis Of Illicit Vs Regulated Market Extracts; Anresco Laboratories.

[12] Dryburgh, L., Bolan, N., Grof, C., Galettis, P., Schneider, J., Lucas, C., Martin, J. (2018). Cannabis contaminants: sources, distribution, human toxicity and pharmacologic effects. Br J Clin Pharmacol. 2018 Nov; 84(11): 2468–2476.

[13] Health Canada (2019). The Canadian Cannabis Survey 2019

Health care professionals and COVID-19

In Europe, many healthcare professionals are involved in the production, prescription and delivery of medicinal cannabis products. A number of them have been portrayed in this place. How did they survive the first months of the COVID-19 crisis?

Italy: home delivery spiked tremendously

Dr. Marco Ternelli – Farmagalenica SRL

Dr Marco Ternelli runs an Italian pharmacy,  and he is specialised in compounding medication, among which is medicinal cannabis.

“In Italy we saw an increase in home delivery including medical cannabis. Because home delivery has taken a tremendous spike, patients need to have more patience than before as pharmaceuticals couriers take much longer to deliver than usual. In Italy, a medicinal cannabis prescription lasts only 30 days. So patients shouldn’t wait too long to contact their doctor to apply for a renewal. Otherwise, you’ll surely run out of medication before the pharmacy can deliver it to you.

During the lockdown, pharmacies in Italy were one of the very few activities left open, so we kept seeing people directly.  We were continuously explaining and reassuring patients of what was going on.

They used to say ‘Biggest improvements come in hard times’. I have to admit I have seen some. In order to avoid people gathering at the doctor’s waiting room, all reimbursed medicines have been digitized. This means that the patient simply has to go to the pharmacy, show his medical ID or fiscal code and the pharmacist is able to digitally download all the prescriptions. We are waiting and hoping the same to happen for medical cannabis prescriptions. Unfortunately, being a controlled substance, it didn’t take part in the digital transformation.”

The Netherlands: “We stayed close to the patient, literally”

Paul Lebbink – Transvaal Apotheek

Paul Lebbink heads the Transvaal pharmacy in The Hague with eight other pharmacists. The Transvaal Apotheek was the first pharmacy in the Netherlands to produce and supply various varieties of cannabis oil, in line with the Dutch medicinal cannabis program.

“We see about 200 patients on average every day. Locking the pharmacy was not an option, because those people need medication. We immediately took measures to ensure that both patients and staff could be as safe as possible in our pharmacy. Plastic screens, possibilities for disinfection, a maximum of five patients who could be inside at the same time and of course the ‘one and a half meter rule’, to name just a few. And although the latter measure in particular is not easy with a limited floor space and a relatively large number of people, it has been possible to create a COVID-safe environment. In addition, we increased the number of deliveries in March and April. Every day, five couriers drove around to serve patients, which enabled us to reduce waiting times in the pharmacy.

The delivery of medicinal cannabis and medicinal cannabis oil has proceeded normally; In the Dutch medical cannabis chain, the organisations responsible for production and distribution have proven to be COVID-proof. As always, we were able to serve patients on time. Our own production and supply of cannabis oil has also been carried out according to plan. We also have not had any questions from patients about the alleged effect of medicinal cannabis in COVID. We would have reacted cautiously, because of course we only base ourselves on scientific evidence.

In the meantime, the rules in the Netherlands have relaxed somewhat again. The same goes for the rules in our pharmacy, because a ‘1,5 metre society’ is not what we want. We want to be close to the patients, literally.”

Denmark: “Online video consultation kept us open”

Dr. Tina Horsted – Pain Clinic Horsted

Dr. Tina Horsted runs a public clinic. She is the only doctor in Denmark who is specialised in prescribing medicinal cannabis, mainly to chronic pain patients.

“We have been open during the lockdown. We had a continuous steady flow through the crisis, as we developed a video-based online application to help new patients and keep up with ongoing medical controls. And it’s been working very satisfying, both for the patients and the clinic. The video format has more or less forced the patient and us to discuss the actual problem straight away. Patients, therefore, get more value out of their time. For the future, we will keep on doing more medical controls or lighter consultations via this application. Patients are relieved that they do not have to travel for each check-up. But of course, it can and will never replace an in-person consultation if this is required. In the clinic, we have well-designed glass panels, in the waiting room we have removed half of the chairs and all magazines, and there is no coffee. But people are now used to these percussions.  

The Norwegian patients are starting to come back, but the Swedes have been coming to the clinical psychically during the whole period. With a special letter, provided by the clinic, they were able to cross the border.”

Metered dose cannabis inhaler enables precise cannabis treatment

Precise cannabis treatment dosing remains a major challenge, leading to physicians’ reluctance to prescribe medical cannabis. A recent feasibility trial demonstrates that a metered dose cannabis inhaler, produced by Syqe Medical and containing processed Bedrocan cannabis, enables individualisation of medicinal cannabis regimens. “This study is the first to show that human sensitivity to THC is significantly greater than previously assumed, indicating that if we can treat patients with much higher precision, lower quantities of drug will be needed, resulting in fewer side effects and an overall more effective treatment. The Syqe drug delivery technology is also applicable to opioids and other compounds that, while potentially effective, are notoriously associated with dangerous side effects. The introduction of a tool to prescribe medications at such low doses with such high resolution may allow us to achieve treatment outcomes that previously were not possible,” said Perry Davidson, Syqe Medical CEO.

According to dr. Mikael Kowal – Clinical Research Coordinator at Bedrocan International – this outcome is an important step for developing cannabis as an effective treatment for pain. “Syqe Medical’s randomized placebo-controlled clinical trial demonstrated that a metered-dose cannabis inhaler containing processed Bedrocan cannabis was able to dose-dependently produce analgesia in 24 patients with neuropathic pain/complex-regional pain syndrome (CRPS),” says Kowal. “As such, the results indicated that the inhaler can effectively be used to deliver precise doses of pharmaceutical-grade cannabis that can produce an analgesic effect with lower amounts of THC, than in the case of other administration methods. It remains very interesting to see if the pain-reduction resulting from inhaling low and precise doses of THC will remain stable in the long-term. That is definitely a question for future research with this promising device.”

Syqe Inhaler
Syqe inhaler

Listen now… ‘European Cannabis. A Dutch view’

A podcast episode featuring Bedrocan CEO Tjalling Erkelens

Today’s episode of the Cannabis Conversation was recorded at the Central European Cannabis Forum, earlier this June. Host Anuj Desai and Tjalling Erkelens, Co-Founder and CEO of Bedrocan, examine attitudes towards CBD, medical, and recreational cannabis in The Netherlands, alongside discussing the importance of consistency and standardisation of medical cannabis.
The Cannabis Conversation is a weekly podcast exploring the emerging legal cannabis industry from a European perspective. The podcast hosts a wide variety of guests helping to shape the emerging legal cannabis industry including patients, lawyers, doctors, scientists, entrepreneurs, investors and many more.
You can find the Cannabis Conversation on iTunes, Spotify  YouTube and Stitcher. Of course, there is a website too.

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