Updates

A recent study conducted by the Leiden University Medical Center (LUMC) examined the side effect profiles of the opioid oxycodone and cannabis product Bediol®. The outcomes of the study were published in the scientific journal Frontiers in Pain Research under the title Cannabis Combined with Oxycodone for Pain Relief in Fibromyalgia Pain: A Randomized Clinical Self-titration Trial with a focus on Adverse Events.

The results showed that (i) around one in four participants dropped out of the study, mainly due to the severity of adverse effects experienced from inhaled cannabis; (ii) there were no significant differences in pain scores between treatments; (iii) the drug load increased in patients treated with the combination of oxycodone and cannabis relative to either treatment alone; and (iv) patients titrated their dosing based on adverse effects and pain relief.

Bedrocan’s Chief Scientific Officer, Mikael Kowal, briefly commented on the results: “Unfortunately, the results are not entirely as expected. We hoped that Bediol® would provide clear advantage over oxycodone in terms of the side effect profile and treatment efficacy for fibromyalgia-induced pain. However, due to many patients not tolerating inhaled cannabis well, the study results do not clearly point to a beneficial effect of Bediol®. To be precise, 31% of patients that received cannabis dropped out from the study due to various adverse effects, most notably headaches.”

Cannabis or opioids for pain relief

“On the other hand, the study also demonstrated that Bediol® worked just as well as the opioid oxycodone for pain relief in some patients, despite the many dropouts during the study. Although the study design and findings do not allow us to draw conclusions that the side effect profile of Bediol® is better than that of oxycodone, it is clear that the use of opioids is more dangerous than the use of cannabis. Using opioids can cause respiratory depression, which can lead to death. That is not the case with cannabis.”, Kowal says.

Kowal: “In sum, I think that the most important conclusion from this study is that cannabis may be an effective pain treatment for some patients, but that it is certainly not for everyone. It is therefore crucial to determine which factors contribute to a good response to cannabis treatment.”

Medicinal cannabis may potentially reduce pain intensity. This is the conclusion of the Bedrocan research team, which analysed the results of eleven studies in which the cannabis products Bedrocan® and Bediol® were used to treat various pain-related medical conditions. The results of the literature review have been published in the scientific journal Frontiers in Pharmacology in a special issue about the therapeutic potential of cannabinoids under the title ‘The effects of standardized cannabis products in healthy volunteers and patients: a systematic literature review’.

In total 18 papers investigated the acute effects of standardised cannabis products in different medical conditions. Eleven of these papers assessed subjective pain as the main outcome measure in pain-related medical conditions such as fibromyalgia, chronic pain, and migraine. Cannabis varieties used in these studies included Bedrocan® (22% THC) and/or Bediol® (6.3% THC; 8% CBD), with large differences in the route, dose and frequency of administration.

Nevertheless, all studies demonstrated a significant reduction in pain intensity. Treatment with medicinal cannabis demonstrated a mild safety profile with feeling high, coughing and mental confusion as the most frequently reported side effects. Other studies reported a relief in symptoms of Alzheimer’s Disease, Post Traumatic Stress Disorder, Tourette’s Syndrome, and Attention Deficit Hyperactivity Disorder.

Side effects and drop-out rates

The review team would like to add a footnote to the results. Although all studies demonstrate a decrease in subjective pain intensity, this evidence mainly comes from observational and retrospective studies. Despite a generally mild safety profile for most patients, some cases of discontinuation of cannabis were also observed. These were primarily due to side effects such as confusion. Two possible factors involved in the experience of side effects and drop-out rates were cannabis use history as well as a higher dose of THC-dominant cannabis. For other medical conditions, it is even harder to draw conclusions because of the limited availability of scientific studies. Future research should focus on conducting randomised clinical trials with sufficient sample size to determine whether patients could benefit from treatment with standardised medicinal cannabis.

Systematic literature review

Bedrocan’s research team identified and included a total of sixty papers that conducted research with standardised cannabis products/varieties from Bedrocan in the systematic literature review. Research topics addressed in these papers could be subdivided into the following four categories:

1. pharmacokinetics of THC and CBD
2. acute subjective experiences
3. impact on cognitive assessments
4. influence of CBD:THC ratios on acute outcome measures.

The current systematic literature review is the first review about the acute effects of standardised cannabis products/varieties from Bedrocan in healthy volunteers and patients. Read the full outcome of the review on the Frontiers website.

Bedrocan is returning to the Canadian medicinal cannabis market. The company purchased a facility in Scarborough, the former home of Bedrocan in Canada, and was recently granted a cultivation license by Health Canada. These steps fulfil Bedrocan’s long-held promise of returning to Canada to grow standardised medicinal cannabis for Canadian patients. The company intends to start production in early 2025.

Benefit patients

Bedrocan is solely focused on producing medicinal cannabis and is known for its high-quality cannabis products with consistent levels of THC and CBD. Bedrocan’s CEO Jaap Erkelens on Bedrocan’s attention to patients: “We have had a strictly pharmaceutical approach since our foundation in 2003. We use the knowledge we have acquired in more than twenty years of business to produce cannabis products that benefit patients exclusively. In the same vein as prescribing physicians, patients want a reliable, standardised product with the same therapeutic effect time after time.”

The intention is for Bedrocan to bring several standardised cannabis products to the Canadian market of which the Bedrocan® product is the most well-known. The products will be distributed through a third party via the medical sales channel to registered patients.

Canopy Growth

Bedrocan was previously active in Canada but ceased its activities after a partnership with Canopy Growth was terminated. Bedrocan has always expressed its intention to return to Canada one day. “We are thrilled to be coming back to Canada,” said Erkelens. “We look forward to serving patients in Canada and positively impacting the Canadian healthcare landscape.”

Bedropuur®, a high THC variety, will soon be available for patients in Europe. The variety was previously sold in Canada when Bedrocan was still active in the country. Now, the company plans to grow the variety in its new Danish facility and bring it to the European market. Also, there are plans to reintroduce the product in Canada after it has been off the market for a few years.

Indica-dominant variety

Bedropuur® was introduced to the Canadian market in 2014, but due to Bedrocan’s departure from Canada, the product was also discontinued. Bedropuur® is the brand name for the cultivar Cannabis sativa L. ‘Harmina’. It is an indica-dominant variety with a THC content of 20%. It has a different terpene profile than the cannabis product Bedrocan®.

Cut flos

Bedropuur® is available in flos or as cut flos. The cut flos form has an even more consistent content compared to flos. It has a uniform distribution of cannabinoids, terpenes, flavonoids, and other plant compounds throughout the product – batch-to-batch, dose-to-dose. Both flos and cut flos forms are free of pesticides and heavy metals and irradiated for microbiological purity.

Contract manufacturing

Bedrocan also offers industrial forms, which can be customised to the client’s needs. In addition, Bedrocan offers contract manufacturing services with the option to grow clients’ own cannabis cultivars or Bedrocan cultivars that are not yet on the market. Contact our business team to explore the possibilities. Send us an email business@bedrocan.com or fill in the below form.

Bedrocan is going to commercialise a new cannabis variety with a cannabidiol (CBD) content of 14 per cent. With this, we are  responding to increasing demand for medicinal cannabis with high CBD content. The new variety will be produced primarily at the new facility in Denmark. “The new CBD variety will be available under the brand name Bedrolina®”, CEO Jaap Erkelens reveals.

There is a lot of demand for CBD with high CBD levels. Drug developers usually process the CBD in cannabis into medicinal oils or ointments. Erkelens continues: “Hemp varieties, which are grown in the open field worldwide, often contain a lower CBD percentage, which means that more biomass is needed. In addition, these hemp varieties are not suitable for pharmaceutical applications. Bedrolina®, on the other hand, is grown and packaged entirely under GMCCP / GMP and is free of pesticides and other contaminants.”

Production facility in Denmark

The brand new production facility in Denmark will be operational in Q1, 2025. Erkelens about this project: “The construction took about a year and a half, but we got exactly what we wanted. Everything was set up according to Bedrocan’s method so we can also supply standardised medicinal cannabis from this facility. The advantage of working from Denmark is the possibility to do business without the direct intervention of a government organisation such as in the Netherlands.”

Growing outdoors

Bedrocan also plans to grow Bedrolina® on a large scale outdoors. This is unique because Bedrocan currently only grows indoors. With the outdoor biomass, Bedrocan is targeting primarily the cosmetics industry. The demand for CBD has grown substantially, partially due to the inclusion of naturally-derived cannabidiol in the Cosing (Common cosmetic ingredient ) database that lists all substances authorised in cosmetics.

Med-tech company Syqe has reached an important milestone: The cartridge containing Bedrocan’s standardised cannabis has recently received EU-GMP (good manufacturing practice) certification. This cartridge is a vital component of the advanced SyqeAir Inhaler, a device that delivers metered and consistent doses of THC and cannabinoids from full-spectrum cannabis in aerosol form.

The cartridge includes sixty standardised cannabis units (VaporChips), filled with Bedrocan®, a cannabis product that has been produced under GMP guidelines since 2017. Manufacturers seeking to market products in the European Union must comply with EU-GMP guidelines, which are among the strictest in the world. Bedrocan also follows similar guidelines for medicinal cannabis cultivation, known as Good Medicinal Cannabis Cultivation Practices (GMCCP).

Landmark achievement

Hagit Kamin, CEO of SyqeAir: “Receiving the EU-GMP certification is a landmark achievement for both SyqeAir and the medical cannabis industry. It underscores our unwavering commitment to safety, quality, and efficacy in delivering therapeutic solutions. This certification is a testament to our dedication to providing patients and healthcare professionals with an innovative, clinically validated platform for cannabis-based treatments.”

SyqeAir cartridges are manufactured at the company’s production site in Israel. For Syqe, this milestone is significant as it enables the company to market the device and cartridges in countries that adhere to EU-GMP guidelines.

Previous studies* have indicated gender differences in pain relief and side effects experienced – in particular, women experience more treatment-related side effects.

In a recent study of mostly chronic pain patients, pain reduction was similar for both genders, and no differences in adverse effects (AE) were found. Indeed, the overall rate of AE was relatively low at 10%.

SyqeAir inhaler

Patients received inhaled doses of Δ-9-THC administered by SyqeAir, a metered dose inhaler that contains Bedrocan® cut flos, at 22% Δ-9-THC, alongside all other cannabis components in the aerosol, such as minor cannabinoids and terpenes. Treatment using the SyqeAir inhaler with its pre-filled cartridges showed similar overall Δ-9-THC plasma levels, heart rate, and blood pressure. A similar significant improvement in sleep latency, duration, and quality was also observed for both genders.

Irregularities from dosing

“In other studies, only the Δ⁹-THC concentration of the raw plant material was known. The SyqeAir Inhaler clinical research demonstrates the previously reported differences were likely irregularities from dosing with non-standardised cannabis flos. The SyqeAir Inhaler administers an exact Δ-9-THC dose as an aerosol to the patients’ lungs. This is a major advance in inhaled cannabis medicine clinical research,” says Dr. Joshua (Shuki) Aviram, Director of Clinical Affairs at Syqe Medical. “This study provides the highest quality evidence on the safety and efficacy, driven by the SyqeAir Inhaler technology and its cartridges which deliver standardised cannabis flos produced by Bedrocan.”

These findings demonstrate the importance of standardised cannabis flos and the technological advances in the SyqeAir metered dose inhaler.

*) References

• Tseng, A.H.; Harding, J.W.; Craft, R.M. Pharmacokinetic factors in sex differences in -tetrahydrocannabinol-induced behavioral effects in rats. Behav. Brain Res. 2004, 154, 77–83.
• Aviram, J.; Lewitus, G.; Vysotski, Y.; Berman, P.; Shapira, A.; Procaccia, S.; Meiri, D. Sex Differences in Medical Cannabis Related Adverse Effects. Pain 2021, 163, 975–983.
• Cooper, Z.D.; Haney, M. Sex-dependent effects of cannabis-induced analgesia. Drug Alcohol Depend. 2016, 167, 112–120. [CrossRef]
• Fogel, J.S.; Kelly, T.H.; Westgate, P.M.; Lile, J.A. Pharmacology, Biochemistry, and Behavior Sex differences in the subjective effects of oral ∆-9-THC in cannabis users. Pharmacol. Biochem. Behav. 2017, 152, 44–51.
• Rademaker, M. Do Women Have More Adverse Drug Reactions? Am. J. Clin. Dermatol. 2001, 2, 349–351. [CrossRef]

Italy is one of few countries where reimbursement of costs for medicinal cannabis is possible. But how does it work in each Italian region? As an experienced patient, Founder Isabella Palazzo of the Italian Patient Association Tutela Pazienti Cannabis Medica is working hard to raise awareness about access to medicinal cannabis in Italy. The association organises workshops for healthcare professionals and spreads information to patients on how to access medicinal cannabis and how the costs can be covered by the Italian National Health Service (Servizio Sanitario Nazionale; SSN).

Patient-driven

Isabella Palazzo is the president of the association. She has several pathologies, which combined generate a lot of pain. She started using medicinal cannabis because conventional medicines did not help relieve her symptoms. As a medicinal cannabis patient, she experienced first-hand the challenges patients face to access medicinal cannabis in Italy. That is why she decided to set up the patient association: “I was driven by the need of sick Italian citizens, who found themselves abandoned to their own luck when it comes to medicinal cannabis.” According to Isabella, despite being legal in Italy since 2006, Italian doctors still have strong prejudices towards cannabis: “Patients are often denigrated by doctors when they ask for treatment with cannabis.”

Free cannabis

Out of the twelve years as a patient, Isabella has been able to get her medicinal cannabis for free for ten years. Currently, the Italian government allows the costs of medicinal cannabis to be reimbursed by the National Health Service (SNN). However, there is a maximum cap for the costs, and only specific health conditions are covered. Additionally, Italian regions have the autonomy to determine for which conditions the costs can be covered and can designate eligible doctors that can prescribe, which varies a lot between regions. Isabella: “Unfortunately, barriers for patients to access medicinal cannabis remain. The regional laws are not helpful as there are many discrepancies. For example, in the Molise region, they have no regional law and patients who want access to this treatment are forced to pay for the costs themselves.”

Workshops

The patient association has been offering workshops to doctors and pharmacists in different regions of Italy. During the workshops, they provide a comprehensive overview of cannabis research, how to prescribe medicinal cannabis in Italy and more information about pharmaceutical preparations. The first workshop was held in Milan in February this year. Another workshop took place on 16 May in the city of Ferrara in the region of Emilia-Romagna. According to Isabella, the association is focused on raising awareness among doctors throughout Italy: “Rather than raising awareness among patients, who sometimes know more than doctors in this regard, we want to raise awareness among doctors, as they are really reluctant to prescribe cannabis.”

On 5 July, the association is hosting a webinar on “Prescription, use and reimbursement in the various regions”. Other two workshops are planned until the end of 2024:

• 12 September in Macerata, Le Marche
• 12 December in Rome

Doctors and pharmacists can register for the webinar and future workshops through the association’s website.