Combined tetrahydrocannabinol and cannabidiol to treat pain in epidermolysis bullosa: a report of three cases

Schräder, Nicholas H. B.; Duipmans, José C.; Molenbuur, Bouwe; Wolff, André; Jonkman, Marcel F.

doi:10.1111/bjd.17341

Cited by 34 publications

(36 citation statements)

References 16 publications

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“…Curiously however, whereas the SFN-mediated induction of keratin 16 partly depends on NRF2, the induction of keratin 17 is NRF2-independent [53]. Since topical and oral CBD have been used by EBS patients with promising results [22,54] our results provide a mechanistic explanation and support CBD as a promising option for the prevention of the pathological skin fragility occurring in EBS and for improving wound closure.…”

Section: Discussionmentioning

confidence: 64%

Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1

et al. 2020

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Cannabidiol (CBD) is a major non-psychotropic phytocannabinoid that attracted a great attention for its therapeutic potential against different pathologies including skin diseases. However, although the efficacy in preclinical models and the clinical benefits of CBD in humans have been extensively demonstrated, the molecular mechanism(s) and targets responsible for these effects are as yet unknown. Herein we characterized at the molecular level the effects of CBD on primary human keratinocytes using a combination of RNA sequencing (RNA-Seq) and sequential window acquisition of all theoretical mass spectrometry (SWATH-MS). Functional analysis revealed that CBD regulated pathways involved in keratinocyte differentiation, skin development and epidermal cell differentiation among other processes. In addition, CBD induced the expression of several NRF2 target genes, with heme oxygenase 1 (HMOX1) being the gene and the protein most upregulated by CBD. CRISPR/Cas9-mediated genome editing, RNA interference and biochemical studies demonstrated that the induction of HMOX1 mediated by CBD, involved nuclear export and proteasomal degradation of the transcriptional repressor BACH1. Notably, we showed that the effect of BACH1 on HMOX1 expression in keratinocytes is independent of NRF2. In vivo studies showed that topical CBD increased the levels of HMOX1 and of the proliferation and wound-repair associated keratins 16 and 17 in the skin of mice. Altogether, our study identifies BACH1 as a molecular target for CBD in keratinocytes and sets the basis for the use of topical CBD for the treatment of different skin diseases including atopic dermatitis and keratin disorders.

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Section: Discussionmentioning

confidence: 64%

Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1

et al. 2020

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“…The authors concluded that the effects might have been due to the anti-inflammatory activity of CBD, but in light of the above data, one can speculate that CBD might have beneficially modulated the keratin expression profile as well [ 183 ]. Likewise, in another small pilot study, three EB patients, who were prescribed pharmaceutical-grade sublingually administered cannabinoid-based medicine (CBM) comprising THC and CBD, reported improved pain scores, reduced pruritus and decreased overall analgesic drug intake [ 184 ]. Further studies are therefore invited to exploit putative therapeutic potential of the (endo)cannabinoid signaling in the clinical management of keratin diseases.…”

Section: Translational Potential Of the Cutaneous Cannabinoid Signmentioning

confidence: 99%

Cannabinoid Signaling in the Skin: Therapeutic Potential of the “C(ut)annabinoid” System

et al. 2019

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The endocannabinoid system (ECS) has lately been proven to be an important, multifaceted homeostatic regulator, which influences a wide-variety of physiological processes all over the body. Its members, the endocannabinoids (eCBs; e.g., anandamide), the eCB-responsive receptors (e.g., CB1, CB2), as well as the complex enzyme and transporter apparatus involved in the metabolism of the ligands were shown to be expressed in several tissues, including the skin. Although the best studied functions over the ECS are related to the central nervous system and to immune processes, experimental efforts over the last two decades have unambiguously confirmed that cutaneous cannabinoid (“c[ut]annabinoid”) signaling is deeply involved in the maintenance of skin homeostasis, barrier formation and regeneration, and its dysregulation was implicated to contribute to several highly prevalent diseases and disorders, e.g., atopic dermatitis, psoriasis, scleroderma, acne, hair growth and pigmentation disorders, keratin diseases, various tumors, and itch. The current review aims to give an overview of the available skin-relevant endo- and phytocannabinoid literature with a special emphasis on the putative translational potential, and to highlight promising future research directions as well as existing challenges.

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“…Research performed with adults with all subtypes of EB have shown pharmaceutical grade CBD-based medicines can improve pain scores, reduce pruritus and reduce overall analgesic drug intake. 35,36 There is no current recommendation for CBD use in paediatric patients with JEB.…”

Section: Novel Therapiesmentioning

confidence: 99%

<p>Optimal Management Of Chronic Wounds In Paediatric Junctional Epidermolysis Bullosa Patients</p>

McDonald¹,

Plevey²,

Petrof³

et al. 2019

CWCMR

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Epidermolysis bullosa (EB) is a group of rare genetic mucocutaneous fragility disorders. Patients with EB can experience blister formation following minor skin trauma, which can progress to chronic wounds. These wounds can be painful and difficult to manage. There are four major types of EB which are defined by the defective protein and the layer within the skin this protein is located. Junctional epidermolysis bullosa (JEB) is caused by mutations within the lamina lucida proteins which are located at the dermoepidermal junction. The prognosis of JEB varies considerably between the different subtypes of JEB, with JEB generalised severe being the most severe, with high mortality within the first 2 years of life. On the opposite end, patients with JEB localised would be expected to have normal life expectancy. In this review, we discuss the management of chronic wounds in paediatric patients with JEB, including suitable wound cleansing, recommended dressings and topical preparations for chronic wound treatments. We include chronic wounds over specific anatomical sites which are frequent in patients with JEB and their recommended management. Important differences between the subtypes of JEB, and specifics on dressings suitable in the neonatal and infancy period are highlighted. Symptom care of wounds in these children, such as pain, infection, pruritus and overgranulation are also addressed. Finally, we highlight the changes to practice which have occurred in recent years and novel treatments which have been trialled and can be considered.

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Combined tetrahydrocannabinol and cannabidiol to treat pain in epidermolysis bullosa: a report of three cases

Abstract: This summary relates to https://doi.

Cited by 34 publications

References 16 publications

Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1

Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1

Cannabinoid Signaling in the Skin: Therapeutic Potential of the “C(ut)annabinoid” System

<p>Optimal Management Of Chronic Wounds In Paediatric Junctional Epidermolysis Bullosa Patients</p>

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