Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstract
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Addendum
Announcement
Art & Psychiatry
Article
Articles
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Commentary
Conference Oration
Conference Summary
Continuing Medical Education
Correspondence
Corrigendum
Cosmetic Dermatology
Cosmetology
Current Best Evidence
Current Issue
Current View
Derma Quest
Dermato Surgery
Dermatopathology
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
e-IJDVL
Editor Speaks
Editorial
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Errata
Erratum
Focus
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
General
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
History
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL AWARDS 2015
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
In Memorium
Inaugural Address
Index
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
LETTER TO THE EDITOR - LETTERS IN RESPONSE TO PUBLISHED ARTICLES
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Medicolegal Window
Messages
Miscellaneous Letter
Musings
Net Case
Net case report
Net Image
Net Letter
Net Quiz
Net Study
New Preparations
News
News & Views
Obituary
Observation Letter
Observation Letters
Oration
Original Article
ORIGINAL CONTRIBUTION
Original Contributions
Pattern of Skin Diseases
Pearls
Pediatric Dermatology
Pediatric Rounds
Perspective
Presedential Address
Presidential Address
Presidents Remarks
Quiz
Recommendations
Regret
Report
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Retraction
Review
Review Article
Review Articles
Revision Corner
Self Assessment Programme
SEMINAR
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Snippets
Special Article
Specialty Interface
Studies
Study Letter
Study Letters
Supplement-Photoprotection
Supplement-Psoriasis
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
SYMPOSIUM - VITILIGO
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Review and Meta-Analysis
Systematic Reviews and Meta-analyses
Systematic Reviews and Meta-analysis
Tables
Technology
Therapeutic Guideline-IADVL
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapeutics
Therapy
Therapy Letter
View Point
Viewpoint
What’s new in Dermatology
View/Download PDF

Translate this page into:

Therapy Letter
88 (
4
); 551-552
doi:
10.25259/IJDVL_71_2021
pmid:
35593277

Purified oral cannabidiol for pain management in severe recessive dystrophic epidermolysis bullosa

Department of Dermatology and Allergology and EB House, University Hospital of the Paracelsus Medical University, Salzburg, Austria
Clinical Investigation Support GmbH, Vienna, Austria
Corresponding author: Dr. Tobias Welponer, Department of Dermatology and Allergology and EB House Austria, University Hospital of the Paracelsus Medical University, Salzburg, Austria. t.welponer@salk.at
Licence
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Welponer T, Diem A, Nahler G, Laimer M. Purified oral cannabidiol for pain management in severe recessive dystrophic epidermolysis bullosa. Indian J Dermatol Venereol Leprol 2022;88:551-2.

Sir,

Severe recessive dystrophic epidermolysis bullosa is a rare, genetically inherited skin fragility disorder. It is an autosomal recessive condition caused due to mutations in the COL7A1 gene that codes for collagen VII, the main constituent of anchoring fibrils within the basement membrane zone. Clinical hallmarks of recessive dystrophic epidermolysis bullosa include blister formation, chronic wounding and scarring of the skin and mucous membranes upon minor mechanical stress, thereby causing significant morbidity.1

We report a 21-year-old woman suffering from recessive dystrophic epidermolysis bullosa due to heterozygous COL7A1 mutations (344insG, 487delT) which lead to a frameshift and biallelic preterminal stop-codons. Oro-oesophageal blisters, erosions and strictures caused significant odynophagia, dysphagia and dystrophy resulting in undernourishment (body mass index 14.2 kg/m2). Although clinically indicated, a gastrostomy was refused by the patient because of tomophobia. Neither topical therapy (application of budesonide with 2% lidocaine gel twice daily on the mucous membrane) nor surgical interventions (including two oesophageal dilatations) provided any relief to the patient. Attempts to provide systemic analgesia with metamizole 500 mg up to four times daily and ibuprofen 400 mg up to three times daily could not mitigate disease progression or provide satisfactory symptomatic relief. As long-term analgesic therapy was indicated, the patient refused morphine as well as other analgesic treatments (tramadol hydrochloride, gabapentin, pregabalin, amitriptyline, etc) because of concerns about opiate/drug dependence and their potential side effects. Her general condition thus progressively worsened, resulting in significant restriction in daily life activities and causing severe depression.

As a palliative approach to improve pain control and quality of life, we started administration of oral cannabidiol drops containing 20% phyto-cannabidiol (purity <99.8%, without delta-9-tetrahydrocannabinol) produced according to good manufacturing practice standards. Lacking clinical experience with purified cannabidiol in epidermolysis bullosa, the initial dose of 62 mg (10 drops, 1.6 mg/kg body weight) twice daily was prescribed according to the manufacturer’s (Trigal Pharma GmbH, Austria, Vienna) standard dosage recommendations and was maintained for six weeks. As there was an excellent tolerability, the dosage was thereafter increased to 124 mg (20 drops, 3.1 mg/kg body weight) twice daily. This regimen resulted in a clinically relevant symptomatic improvement reflected by a mean pain reduction by three points on a visual analogue scale from baseline range of 4–8 to (range of 1–5 by week 6, (visual analogue scale: 0 = no pain, 10 = worst pain imaginable). In addition, pain peaks of ≥8 which were reported multiple times per week before initiating the treatment were experienced only once during the 92 weeks treatment period. Pain reduction was associated with improved swallowing, thereby ameliorating the patient’s self-reported health status, quality of life and emotional state. The self-reported frequency and duration of depressive episodes decreased consistently, from twice a month prior intervention to once a month during the treatment period and from about two weeks to less than five days, respectively. After 36 weeks of treatment, the patient’s mother decided to reduce the cannabidiol dose to 93 mg (15 drops, 2.3 mg/kg body weight) twice daily without informing her daughter, in order to determine whether the striking pain reduction would be dose-dependent on cannabidiol intake. Indeed, the patient reported worsening of symptoms within one week after tapering, while a subsequent re-introduction of 124 mg twice daily dose (corresponding to 6.2 mg/kg body weight daily) led to a symptomatic alleviation within two weeks, suggestive of an individual threshold dose for maintenance therapy.

Apart from a macrogol-containing laxative given daily to prevent obstipation, the patient did not take any comedication. Notably, the beneficial effects of cannabidiol were observed in an add-on setting to the analgesic premedication with metamizole and ibuprofen.

Legal access to medicinal cannabis products, including purified good manufacturing practice-grade cannabidiol, is limited in European and non-European countries. However, pharmaceutical grade phyto-cannabidiol had received marketing authorization in the United States already in June 2018 and in the European Community in September 2019.2 Cannabidiol can be legally prescribed in several countries, including Austria, Australia, Canada, Germany, New Zealand and Switzerland. Nevertheless, the use of cannabinoids in dermatology is still at an experimental stage.3 Cannabidiol and other cannabinoids are known to have anti-inflammatory and analgesic effects.4 Data also suggests that they foster wound healing and re-epithelialization by increased expression of platelet-derived growth factor -A and -B,5 enhancement of keratinocyte migration as well as immunomodulation through downregulation of interleukin-1β, interleukin-6, tumour necrosis factor-α, transforming growth factor-β1 and up-regulation of interferon-γ after activation of the cannabinoid receptor type 2.6 The literature-based evidence for use of cannabidiol in epidermolysis bullosa, however, is sparse and of rather low quality. For instance, a topical, yet not further specified “cannabidiol-oil” was reported to improve pain and wound healing in three children with epidermolysis bullosa simplex.7 Another case series comprising three adult epidermolysis bullosa patients - two with intermediate junctional epidermolysis bullosa and one with severe recessive dystrophic epidermolysis bullosa - revealed a considerable reduction of pain and itch after sublingual ingestion of a cannabinoid-based oil, containing cannabidiol and tewtrahydrocannabinol.8

The therapeutic impact of cannabidiol, in particular on patients with epidermolysis bullosa, remains rather elusive. For a critical appraisal, the heterogeneous quality of many cannabidiol-oils is a major limitation. This refers to the purity and concentration of the two main cannabinoids, i.e., non-psychotomimetic cannabidiol and psychotomimetic tetrahydrocannabinol. The latter exerts psychoactive side effects including dependence and potentially detrimental effects on the developing brain.9,10

In addition, the content of cannabinoids and terpenes may show considerable variations, creating an unpredictable “entourage effect” on the therapeutic outcome.11 Finally, many of the over-the-counter cannabidiol products are mislabelled and their composition ill-defined and contaminated by pesticides and microbial toxins.12 Considering these significant shortcomings as well as the limitations of our single-case observation, large-scale, controlled clinical trials are warranted to more comprehensively assess the potential of highly purified cannabidiol to improve pain and overall quality of life alongside an acceptable safety profile in patients with recessive dystrophic epidermolysis bullosa.

Acknowledgements

We thank the patient and her family for providing the information and giving permission to publish this manuscript.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship

The study was supported by Trigal Pharma GmbH. The company provided cannabidiol for the patient for 4 months. Cannabidiol for the remaining 19 months was sponsored by the non-profit support group DEBRA Austria. There was no other support.

Conflicts of interest

Gerhard Nahler, MD, Ph.D. is an independent consultant. Among others, he consults physicians, the non-profit NGO International Institute for Cannabinoids (ICANNA), the European Industrial Hemp Association (EIHA) and a number of pharmaceutical companies.

References

  1. , , , , , , et al. Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility. Br J Dermatol. 2020;183:614-27.
    [CrossRef] [PubMed] [Google Scholar]
  2. , . Regulatory status of cannabidiol in the United States: A perspective. Cannabis Cannabinoid Res. 2018;3:190-4.
    [CrossRef] [PubMed] [Google Scholar]
  3. , , . Knowledge, attitudes, and perceptions of cannabinoids in the Dermatology Community. J Drugs Dermatol. 2018;17:1273-8.
    [PubMed] [Google Scholar]
  4. . Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress. Free Radic Biol Med. 2011;51:1054-61.
    [CrossRef] [PubMed] [Google Scholar]
  5. , , , , , , et al. Beta-caryophyllene enhances wound healing through multiple routes. PLoS One. 2019;14:e0216104.
    [CrossRef] [PubMed] [Google Scholar]
  6. , , , , , , et al. Pharmacological activation of cannabinoid 2 receptor attenuates inflammation, fibrogenesis, and promotes re-epithelialization during skin wound healing. Eur J Pharmacol. 2016;786:128-36.
    [CrossRef] [PubMed] [Google Scholar]
  7. , , , . Self-initiated use of topical cannabidiol oil for epidermolysis bullosa. Pediatr Dermatol. 2018;35:e224-e7.
    [CrossRef] [PubMed] [Google Scholar]
  8. , , , , . Combined tetrahydrocannabinol and cannabidiol to treat pain in epidermolysis bullosa: A report of three cases. Br J Dermatol. 2019;180:922-4.
    [CrossRef] [PubMed] [Google Scholar]
  9. , , . Association of Cannabis use with adolescent psychotic symptoms. JAMA Psychiatry. 2018;75:864-6.
    [CrossRef] [PubMed] [Google Scholar]
  10. , , , . Cannabidiol drugs clinical trial outcomes and adverse effects. Front Pharmacol. 2020;11:63.
    [CrossRef] [PubMed] [Google Scholar]
  11. , , , , , , et al. Quality traits of “Cannabidiol Oils”: Cannabinoids content, terpene fingerprint and oxidation stability of European commercially available preparations. Molecules. 2018;23:1230.
    [CrossRef] [PubMed] [Google Scholar]
  12. , , , , , . Labeling accuracy of cannabidiol extracts sold online. JAMA. 2017;318:1708-9.
    [CrossRef] [PubMed] [Google Scholar]

Fulltext Views
3,792

PDF downloads
179
View/Download PDF
Download Citations
BibTeX
RIS
Show Sections