Cannabinoid treatment for all EB pain and itch (2024)

This trial tested an oil called Transvamix, containing medical cannabis, to see if it reduced pain in EB. Eight adults (men and women over 16 years old) with EBS, JEB or DDEB completed the study by self-administering an oil under their tongue. They didn’t have to stop other pain medication they were taking and could increase their use of the oil over two weeks until it helped, or they noticed side effects. Some were given Transvamix initially, then swapped to an oil that looked, smelled and tasted identical but didn’t contain the medical cannabis (a placebo). Others were given the placebo oil first then swapped to Transvamix. Neither the people taking part in the study nor the researchers knew, at the time, whether they were receiving Transvamix or the placebo and the order was selected randomly for each person (a randomised, double-blind trial).

The trial lasted seven weeks for each person, during which time they completed questionnaires about their EB symptoms and had MRI scans of their brain. The study finished at the end of 2024 and showed that the Transvamix provided some benefits. It reduced neuropathic pain, and half of those people who were taking other pain medication chose to reduce or stop it altogether while using the Transvamix. All reported side effects resolved on their own without medical attention or intervention. The results will be fully analysed and published.

In November 2023, researchers reported that they were still recruiting for the clinical study. They need at least eight people to take part for the results to be meaningful. Of the seven people taking part so far, more than half have completed the study. They expect to enrol the eighth person early in 2024 and will analyse the results once all eight people have completed the study.

In April 2023, researchers reported that recruitment of patients for this study started in March 2022 but fewer people were suitable than expected because of the MRI scans planned. They changed their plan so people who cannot have MRI scans could participate in the study. Seven patients were expected to complete the study by the end of August 2023.

The researchers published their clinical trial protocol in December 2022 and received several responses. They recommend publishing similar manuscripts to other research teams in the EB field.

An update was shared by the institution in March 2022:

UMCG starts research into the effects of medicinal cannabis oil in EB patients

Prof Dr André Wolff is head of the UMCG Pain Centre, chairs the UMCG Pelvic Pain Centre and has a special interest in the (medical) innovation of chronic pain related patient care. His work concerns pain precision diagnosis by invasive methods in chronic pain patients and identifying neuropathic pain. He is also active in the field of implementation science and quality of care.

Dr Marieke Bolling, MD, PhD, is a dermatologist specialising in EB and other inherited skin diseases and is the medical coordinator for the multidisciplinary EB team at the Centre for Blistering Diseases at the University Medical Centre Groningen. She successfully defended her PhD thesis in 2010 titled: Epidermolysis Bullosa Simplex. Her research experience and oversight will be essential to the successful set-up, implementation and completion of this project.

Dr José Duipmans, has been committed to the improvement of care through active daily communication with patients and the local DEBRA NL branch. A great deal of her time has been focused on understanding patient needs, family expectations and understanding the main problems perceived by children living with EB. José will be involved in the patient centered logistics of this study and provide a key point of contact throughout the study.

Nicholas Schräder, BSc, has been working with EB since 2010 and has taken up active roles in EB-related educational programmes and studies including experience at the Chinese University of Hong Kong Prince of Wales Hospital, EB Research Center University of Freiburg Medical Center, Great Ormond Street Children’s Hospital and University Medical Center of Groningen. Since 2012, Nicholas has been involved in scientific research for EB under the guidance of Prof. Marcel Jonkman, with special regard to symptomatic care and quality of life. Encountering countless anecdotes of medical cannabis-use for an array of EB-related problems, and working within the Dutch healthcare system with an established multidisciplinary EB-center, he was able to further investigate the potential implication of medical cannabis, or cannabinoids, for people suffering from EB.

Prof Dr Marcel Jonkman passed away in January, 2019. He was renowned for his innovative approach to EB scientific and academic research. His work and leadership led to an increasingly in-depth understanding of the numerous dimensions that play a role in the pathophysiology of EB, both in and outside of the clinic.

“The anecdotes, stories and questions from patients have been crucial to our current understanding of the tolerability of cannabinoid medicines used for EB symptoms… It is time to scientifically analyse these favourable anecdotal treatments and work towards a treatment protocol which may significantly alter the quality of life of our life-long suffering patients.”

Grant Titles:

Substantiating the effectiveness of a sublingual phyto-cannabinoid based oil for the treatment of pain and pruritus (itch) in epidermolysis bullosa.

A prospective explorative controlled study on cannabinoids to treat chronic pain in epidermolysis bullosa.

Transvamix (10% THC / 5% CBD) to treat chronic pain in epidermolysis bullosa: An explorative randomized, placebo-controlled and double-blind intervention crossover study.

People with epidermolysis bullosa (EB) face constant, debilitating symptoms, such as pain and itch. Anecdotal reports from EB patients suggest that cannabinoid-based medicines (CBMs) are effective for symptom control.

Everybody has an endocannabinoid system of molecules and receptors that play a role in the various functions of the body, including the signalling of pain and itch – making the brain aware of those symptoms.

Evidence for numerous painful and itchy diseases, as well as EB patient experiences, suggest that CBMs, produced outside of the body (such as from the Cannabis plant) reach comparable levels of symptom relief to mainstream medicines. Often more than one medicine is used for a single goal (e.g. for pain, opiates & anti-inflammatories are used) which may lead to unwanted or unnecessary side effects. Recent anecdotal reports from patients with EB around the world, detailing their experience with CBMs, both prescribed and self-obtained, have been overwhelming, and call for scientific research to assess the safety and effectiveness of CBMs. CBMs are available in a growing number of countries, including the Netherlands, however EB specific knowledge and guidelines are lacking.
Therefore, in researching this potential treatment, this project aims to gain an insight as to whether it can ultimately improve the quality of life in patients with EB.

Globally, researchers are currently looking into various CBM formulations and administration forms for numerous diseases. In the Netherlands recent advances have led to the standardisation of cannabis plants for therapeutic use by Dutch patients. With regard to the CBM choice for this study, these “phytocannabinoids” (plant-based cannabinoids) are extracted from the plants and incorporated into an oil which is administered as droplets under the tongue (sublingually). The final product is a pharmaceutical – grade CBM oil, and is currently distributed to patients in the Netherlands who have obtained a prescription from their registered physician.

The use of plant-based CBMs is not physically addictive, and has not been associated with life threatening or debilitating complications. As there is currently not enough information about the long term effects of cannabinoid use on the developing nervous system in children, this study is only for patients over 18 years old. Specific inclusion criteria will take into account pre-existing psychiatric conditions as these can be affected by CBM use.

The research will investigate if additional treatment with this sublingual oil can improve the quality of life of adults with EB suffering from pain and/or itch. The effects of the CBM oil can last 4-8 hours and will therefore need to be taken 4 times daily to maintain blood levels. Patients will report pain, itch and changes in their quality of life monthly over 6 months. Quality of life, pain and itch will be measured by the use of patient questionnaires or patient reported outcome measurements. A number of these will be used to also identify which measurements are most sensitive to changes in patients with EB.
Stopping current medication is not required as a study participant, during the course of the research, the research team will monitor the change in medication-use of each patient (such as a reduction in opiate use), and at the end scrutinize whether this correlates with CBM oil use.

This study is considered a prospective, open label, proof of concept study – testing a new medicine in a small number of patients, where everyone takes the new medicine to see what benefits can be identified. Therefore, in researching this potential treatment, this project aims to gain an insight as to whether it can ultimately improve the quality of life in patients with EB.

Positive experiences shared by clinicians and patients with EB with cannabinoids used as therapeutic agents, have significantly contributed to our understanding. This study will start the process of scientifically analysing these anecdotes and work towards a treatment protocol and evidence-based guidelines which may significantly alter the quality of life of EB patients. As this study involves the use of a sublingually administered CBM oil, the results and conclusions will be largely relevant to this CBM formulation and administration form, as other formulations and administration forms are processed by the human body through different mechanisms.

A prospective explorative controlled study on cannabinoids to treat chronic pain in epidermolysis bullosa.

Transvamix (10% THC / 5% CBD) to treat chronic pain in epidermolysis bullosa: An explorative randomized, placebo-controlled and double-blind intervention crossover study.

Preparatory and regulatory work for the clinical trial has been completed. In addition to ethical approval, logistics for study medication coordination, radiographic imaging and online case report forms (database) have been set up and approved. As of 15-03-2022 recruitment for participation has started. The expected inclusion period is 6 months. The expected closure followed by data analysis is Q4 2022.

The research team encountered significant delays due to the ethical vetting process. This in turn resulted in a reformulated clinical trial methodology improving the quality and power of the study – with specific regard to objective data parameters (fMRI-use, placebo control, cross-over design). In addition, all issues around the COVID pandemic, and the consequent regulations, provided additional delay. As noted above, changes to methodology minimize burden of participation, and allow for robust collection and analysis of results. Since the approval to commence research activities, media attention has increased, DEBRA-UK are noted as grant distributors. (From 2022 progress report).

Introduction

The C4EB study concluded at the end of 2024. This project was initiated by our research team at the University Medical Centre of Groningen, with a focus on research that improves daily life. The team included a diverse group of experts: José Duipmans (Nurse Practitioner), Marieke Bolling (Dermatologist), André Wolff (Pain Specialist), Roy Stewart (Epidemiologist), Karin Vermeulen (Methodologist), Peter Söros (Neurologist/Neurophysiologist), and Nicholas Schräder (Physician/PhD Researcher).

The C4EB study aimed to investigate whether a cannabinoid-based medicine, Transvamix (medical cannabis in the form of an oil applied under the tongue), could help reduce pain in patients with Epidermolysis Bullosa (EB). The study drug was prepared by a research pharmacy and contained two cannabinoids: THC and CBD. Over recent years, research has highlighted the potential benefits of cannabinoids for managing pain and itch in various conditions, including EB. While patients often report positive effects, it is crucial to study these medications under controlled conditions to understand how they work and how effective they are.

Since this study involved a medical treatment, strict criteria were in place for who could participate and which assessments they would undergo. Participants had to be adults aged 16 or older, and they needed to experience pain as a symptom of EB at the time of inclusion. The study lasted 7 weeks for each participant, during which they received both Transvamix and a placebo oil (which looked, smelled, and tasted identical to the study drug). To ensure reliable results, neither the participants nor the researchers knew the order in which Transvamix or placebo was given.

Participants gradually increased their dosage over two weeks until they either experienced relief from their symptoms or noticed side effects. In addition to completing surveys about pain and how they coped with it, participants also underwent MRI scans. These scans helped researchers observe how the brain processes pain signals, similar to creating a “video recording” of brain activity. Throughout the study, participants were allowed to continue their usual pain medications and adjust their doses as needed.

Results

A total of 9 patients with EB participated in the study. Unfortunately, one participant dropped out early, though this was unrelated to Transvamix or the placebo. The remaining participants represented various types of EB, including EB Simplex, Junctional EB, and Dominant Dystrophic EB.

The primary focus of the study was a pain survey that categorized pain into four types. For three of these types—continuous pain, intermittent pain, and affective pain (emotional processing of pain)—there was no significant difference in relief between the placebo and Transvamix. However, for neuropathic pain (pain linked to nerve dysfunction), participants reported more relief when using Transvamix compared to the placebo.

Additionally, among participants who were taking pain medication during the study, half were able to reduce their dosage or stop their medication altogether while using Transvamix. Importantly, both participants and researchers reported any side effects (adverse events) that occurred during the study, whether related to the placebo or Transvamix. All reported side effects were considered mild or moderate and resolved on their own, typically within a few hours, without requiring medical attention or intervention.

Data to be Processed

The MRI data collected during the study requires complex calculations and detailed analysis, which is still underway. Over the next few weeks, our team will finalize the results and prepare a comprehensive summary for publication in a scientific journal, allowing EB and non-EB researchers around the world to learn from our findings.

Conclusions

This study is the first to formally evaluate the use of cannabinoid-based medicines to manage pain in patients with EB. While the results may not be considered groundbreaking, they provide valuable insights. Transvamix, when used in a controlled and safe environment, showed potential benefits for some patients with EB, particularly in managing neuropathic pain. The reduction in the use of other pain medications and the mild nature of reported side effects further support the potential of cannabinoid-based treatments for EB-related pain.

Future Prospects

Through this study, we hope to inspire other researchers and clinicians to undertake similar investigations, both in clinical practice and research. Every patient with EB is unique, and there are many promising avenues for exploring cannabinoid-based treatments. These include variations in cannabinoids (CBD vs. THC), forms of administration (oil, cream, vapor), and addressing other challenges faced by patients, such as itch, chronic wounds, and scarring. Additionally, this study’s methodology—using a small group of participants and incorporating a placebo—provides a promising framework for future research. Our team is currently working on the COSEB project (Core Outcome Set for EB), which aims to standardize the tools and measurements used in EB research. We are happy to answer any questions you might have about this research. Please bear with us as we prepare to publish the complete data as soon as possible. Please see the links below, news articles referring to our work.

Links:

UMCG starts scientific research into cannabis oil for chronic pain in Epidermolysis Bullosa November 2021

The effectiveness of cannabis oil in pain management for EB-patients

UMCG starts research into the effects of medicinal cannabis oil in EB patients March 2022

UMCG starts research into medicinal cannabis for Epidermolysis Bullosa March 2022

UMCG starts research into the effects of medicinal cannabis oil March 2022

(From 2024 final progress report.)