Cannabinoid treatment for all EB pain and itch

A significant challenge for people with all types of EB is lifelong pain and itch. This research seeks to prove that this can be reduced with cannabinoid-based medicine.

Dr Marieke Bolling works with Prof André P. Wolff at the Center for Blistering Disease at the University Medical Center, Groningen, Netherlands on the pain and itch that people with EB experience. Because some EB patients have said that cannabinoid-based medicines (CBMs) help with pain and itch, this project will look for evidence of this in EB patients who take drops of oil containing tetrahydrocannabinol (THC) and cannabidiol (CBD) under their tongues several times each day for 6 months. Evidence that this treatment is effective will help to produce guidelines for using it more widely to treat pain and itch in EB.

Read more in our researchers' blogs by Dr Bolling and Dr Schräder.

About our funding:

Research leader	Prof Dr André Wolff and Dr Marieke Bolling
Institution	Center for Blistering Diseases, Department of Dermatology, University Medical Center Groningen
Type of EB	All types of EB
Patient involvement	Adults with EB will trial a cannabinoid medicine
Funding amount	€177,200
Project length	3 years (extended due to Covid)
Start date	August 2018
DEBRA internal ID	Jonkman1

Latest progress summary (2023):

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

Treating pain and itch in adults with EB

About our researchers:

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.

Treating pain and itch in adults with EB Prof Jonkman (left) with Nic Schräder

Why this research is important:

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.

Back to contents

Researcher's abstract:

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.

Researcher’s progress update:

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).