Cannabinoid use and effects in patients with epidermolysis bullosa: an international cross-sectional survey study

Nicholas H B Schräder, Emily S Gorell, Roy E Stewart, José C Duipmans, Nicole Harris, Victoria A Perez, Jean Y Tang, André P Wolff, Marieke C Bolling, Nicholas H B Schräder, Emily S Gorell, Roy E Stewart, José C Duipmans, Nicole Harris, Victoria A Perez, Jean Y Tang, André P Wolff, Marieke C Bolling

Abstract

Background: Epidermolysis bullosa (EB) patient anecdotes and case reports indicate that cannabinoid-based medicines (CBMs) may alleviate pain and pruritus and improve wound healing. CBM use has not been characterized in the EB patient population.

Objectives: To evaluate CBM use among EB patients, including CBM types, effects on symptoms (e.g., pain and pruritus), disease process (e.g., blistering, wounds, and inflammation), well-being (e.g., sleep, appetite) and concomitant medications.

Methods: English-speaking EB patients or caregivers completed an online international, anonymous, cross-sectional survey regarding CBM use. Respondents reported the types of CBMs, subsequent effects including perceived EB symptom alteration, changes in medication use, and side effects.

Results: Seventy-one EB patients from five continents reported using or having used CBMs to treat their EB. Missing question responses ranged between 0 (0%) and 33 (46%). Most used more than one CBM preparation (mean: 2.4 ± 1.5) and route of administration (mean: 2.1 ± 1.1). Topical and ingested were the most common routes. Pain and pruritus were reported retrospectively to decrease by 3 points (scale: 0-10; p < 0.001 for both) after CBM use. Most reported that CBM use improved their overall EB symptoms (95%), pain (94%), pruritus (91%) and wound healing (81%). Most participants (79%) reported decreased use of pain medications. The most common side-effect was dry mouth (44%).

Conclusions: CBMs improve the perception of pain, pruritus, wound healing, and well-being in EB patients and reduced concomitant medication use. Nevertheless, a direct relation between the use of CBMs and reduction of the above-mentioned symptoms cannot be proven by these data. Therefore, future controlled studies using pharmaceutically standardised CBM preparations in EB are warranted to delineate the risks and benefits of CBMs.

Keywords: Cannabinoid-based medicines; Epidermolysis bullosa; Genodermatoses; Itch; Pain; Patient driven research; Survey; Symptom alleviation; Wounds.

Conflict of interest statement

None to declare.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Boxplot of numeric rating scale (NRS 0–10) scores for pain and pruritus prior to- and after cannabinoid-based medication (CBM) administration. Note the improvement in the perception of both pain and pruritus following CBM use. Significant differences (p prior to CBM-use vs. after CBM-use)
Fig. 2
Fig. 2
Participant-reported effects of cannabinoid-based medicines on epidermolysis bullosa-related A symptoms and disease process, B well-being and C pain types. Data is ordered by frequency of much improved. N = 48 responses are included. Items indicated as not applicable by participants are removed
Fig. 3
Fig. 3
A Reported changes in pain and pruritus treatments due to cannabinoid-based medication administration. B Reported changes in supportive interventions. Note that not all participants answered each question. No participants indicated “A lot more needed” for any responses

References

    1. Has C, Bauer JW, Bodemer C, Bolling MC, Bruckner-Tuderman L, Diem A, et al. Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility. Br J Dermatol. 2020;183:614–627.
    1. Boeira VLSY, Souza ES, Rocha BO, Oliveira PD, Oliveira MFSP, de Rêgo VRPA, et al. Inherited epidermolysis bullosa: clinical and therapeutic aspects. An Bras Dermatol. 2013;88:185–198.
    1. Mauritz PJ, Jonkman MF, Visser SS, Finkenauer C, Duipmans JC, Hagedoorn M. Impact of painful wound care in epidermolysis bullosa during childhood: an interview study with adult patients and parents. Acta Derm Venereol. 2019;99:783–788.
    1. Goldschneider KR, Good J, Harrop E, Liossi C, Lynch-Jordan A, Martinez AE, et al. Pain care for patients with epidermolysis bullosa: best care practice guidelines. BMC Med. 2014;12:178–201.
    1. Papanikolaou M, Onoufriadis A, Mellerio JE, Nattkemper LA, Yosipovitch G, Steinhoff M, et al. Prevalence, pathophysiology and management of itch in epidermolysis bullosa. Br J Dermatol. 2021;184:816–825.
    1. Danial C, Adeduntan R, Gorell ES, Lucky AW, Paller AS, Bruckner A, et al. Prevalence and characterization of pruritus in epidermolysis bullosa. Pediatr Dermatol. 2015;32:53–59.
    1. Chelliah MP, Zinn Z, Khuu P, Teng JMC. Self-initiated use of topical cannabidiol oil for epidermolysis bullosa. Pediatr Dermatol. 2018;35:e224–e227.
    1. Schräder NHB, Duipmans JC, Molenbuur B, Wolff AP, Jonkman MF. Combined tetrahydrocannabinol and cannabidiol to treat pain in epidermolysis bullosa: a report of three cases. Br J Dermatol. 2019;180:922–924.
    1. Martinez AE. Time to drop the stigma: cannabinoids are drugs that may alleviate pain in people with epidermolysis bullosa. Br J Dermatol. 2019;180:711–712.
    1. Pacher P, Bátkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev. 2006;58:389–462.
    1. Bíró T, Tóth BI, Haskó G, Paus R, Pacher P. The endocannabinoid system of the skin in health and disease: novel perspectives and therapeutic opportunities. Trends Pharmacol Sci. 2009;30:411–420.
    1. Tóth KF, Ádám D, Bíró T, Oláh A. Cannabinoid signaling in the skin: therapeutic potential of the “c(ut)annabinoid” system. Molecules. 2019;24:918.
    1. Andre CM, Hausman JF, Guerriero G. Cannabis sativa: the plant of the thousand and one molecules. Front Plant Sci. 2016;7:19.
    1. MacCallum CA, Russo EB. Practical considerations in medical cannabis administration and dosing. Eur J Intern Med. 2018;49:12–19.
    1. Lynch ME, Ware MA. Cannabinoids for the treatment of chronic non-cancer pain: an updated systematic review of randomized controlled trials. J Neuroimmune Pharmacol. 2015;10:293–301.
    1. Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA. 2015;313:2456–2473.
    1. Wong SSC, Chan WS, Cheung CW. Analgesic effects of cannabinoids for chronic non-cancer pain: a systematic review and meta-analysis with meta-regression. J Neuroimmune Pharmacol. 2020;15:801–829.
    1. Liszewski W, Farah RS. Response to: “The role of cannabinoids in dermatology”. J Am Acad Dermatol. 2017;77:e87–e88.
    1. Mounessa JS, Siegel JA, Dunnick CA, Dellavalle RP. The role of cannabinoids in dermatology. J Am Acad Dermatol. 2017;77:188–190.
    1. Avila C, Massick S, Kaffenberger BH, Kwatra SG, Bechtel M. Cannabinoids for the treatment of chronic pruritus: a review. J Am Acad Dermatol. 2020;82:1205–1212.
    1. Jastrząb A, Gęgotek A, Skrzydlewska E. Cannabidiol regulates the expression of keratinocyte proteins involved in the inflammation process through transcriptional regulation. Cells. 2019;8:827.
    1. Cintosun A, Lara-Corrales I, Pope E. Mechanisms of cannabinoids and potential applicability to skin diseases. Clin Drug Investig. 2020;40:293–304.
    1. Baswan SM, Klosner AE, Glynn K, Rajgopal A, Malik K, Yim S, et al. Therapeutic potential of cannabidiol (CBD) for skin health and disorders. Clin Cosmet Investig Dermatol. 2020;13:927–942.
    1. Kimel M, Zeidler C, Kwon P, Revicki D, Ständer S. Validation of psychometric properties of the itch numeric rating scale for pruritus associated with prurigo nodularis: a secondary analysis of a randomized clinical trial. JAMA Dermatol. 2020;156:1354–1358.
    1. Garra G, Singer AJ, Domingo A, Thode HC. The wong-baker pain FACES scale measures pain, not fear. Pediatr Emerg Care. 2013;29:17–20.
    1. Prodinger C, Diem A, Ude-Schoder K, Piñón-Hofbauer J, Kitzmueller S, Bauer JW, et al. Profiling trial burden and patients’ attitudes to improve clinical research in epidermolysis bullosa. Orphanet J Rare Dis. 2020;15:182.
    1. Bridgeman MB, Abazia DT. Medicinal cannabis: history, pharmacology, and implications for the acute care setting. P T. 2017;42:180–188.
    1. Ko GD, Bober SL, Mindra S, Moreau JM. Medical cannabis—the Canadian perspective. J Pain Res. 2016;9:735–744.
    1. Bruckner AL, Losow M, Wisk J, Patel N, Reha A, Lagast H, et al. The challenges of living with and managing epidermolysis bullosa: Insights from patients and caregivers. Orphanet J Rare Dis. 2020;15:1.
    1. Gorell ES, Wolstencroft PW, de Souza MP, Murrell DF, Linos E, Tang JY. Financial burden of epidermolysis bullosa on patients in the United States. Pediatr Dermatol. 2020;37:1198–1201.
    1. Angelis A, Kanavos P, López-Bastida J, Linertová R, Oliva-Moreno J, Serrano-Aguilar P, et al. Social/economic costs and health-related quality of life in patients with epidermolysis bullosa in Europe. Eur J Heal Econ. 2016;17:31–42.
    1. Karschner EL, Darwin WD, Goodwin RS, Wright S, Huestis MA. Plasma cannabinoid pharmacokinetics following controlled oral Δ9-tetrahydrocannabinol and oromucosal cannabis extract administration. Clin Chem. 2011;57:66–75.
    1. Lucas CJ, Galettis P, Schneider J. The pharmacokinetics and the pharmacodynamics of cannabinoids. Br J Clin Pharmacol. 2018;84:2477–2482.
    1. Huestis MA. Human cannabinoid pharmacokinetics. Chem Biodivers. 2007;4:1770–1804.
    1. De Hoop B, Heerdink ER, Hazekamp A. Medicinal cannabis on prescription in the Netherlands: statistics for 2003–2016. Cannabis Cannabinoid Res. 2018;3:54–55.
    1. Ramaekers JG, Van Wel JH, Spronk DB, Toennes SW, Kuypers KPC, Theunissen EL, et al. Cannabis and tolerance: acute drug impairment as a function of cannabis use history. Sci Rep. 2016;6:26843.
    1. Serpell MG, Notcutt W, Collin C. Sativex long-term use: an open-label trial in patients with spasticity due to multiple sclerosis. J Neurol. 2013;260:285–295.
    1. Russo EB. Current therapeutic cannabis controversies and clinical trial design issues. Front Pharmacol. 2016;7:309.
    1. Colizzi M, Bhattacharyya S. Cannabis use and the development of tolerance: a systematic review of human evidence. Neurosci Biobehav Rev. 2018;93:1–25.
    1. Solis DC, Teng C, Gorell ES, Barriga M, Nazaroff J, Li S, et al. Classification of two distinct wound types in recessive dystrophic epidermolysis bullosa: a retrospective and cohort natural history study. J Am Acad Dermatol [Internet]. 2020;Online ahead of print.
    1. Russo EB. The case for the entourage effect and conventional breeding of clinical cannabis: no “Strain”, no gain. Front Plant Sci. 2019;9:1969.
    1. Fischer B, Russell C, Sabioni P, Van Den Brink W, Le Foll B, Hall W, et al. Lower-risk cannabis use guidelines: a comprehensive update of evidence and recommendations. Am J Public Health. 2017;107:e1–12.
    1. Casarett DJ, Beliveau JN, Arbus MS. Benefit of tetrahydrocannabinol versus cannabidiol for common palliative care symptoms. J Palliat Med. 2019;22:1180–1184.
    1. Banerjee S, McCormack S. Medical cannabis for the treatment of chronic pain: a review of clinical effectiveness and guidelines. CADTH (Canadian Agency Drugs Technol Heal Rapid Response Reports [Internet]. 2019;1–43.
    1. Mücke M, Phillips T, Radbruch L, Petzke F, Häuser W. Cannabis-based medicines for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2018;3:CD012182.
    1. Dworkin RH, Bruehl S, Fillingim RB, Loeser JD, Terman GW, Turk DC. Multidimensional diagnostic criteria for chronic pain: introduction to the ACTTION–American Pain society pain taxonomy (AAPT) J Pain. 2016;17:T1–9.
    1. Snauwaert JJLL, Yuen WY, Jonkman MF, Moons P, Naulaers G, Morren MA. Burden of itch in epidermolysis bullosa. Br J Dermatol. 2014;171:73–78.
    1. Van Scheppingen C, Lettinga AT, Duipmans JC, Maathuis CGB, Jonkman MF. Main problems experienced by children with epidermolysis bullosa: a qualitative study with semi-structured interviews. Acta Derm Venereol. 2008;88:143–150.
    1. Danial C, Adeduntan R, Gorell ES, Lucky AW, Paller AS, Bruckner AL, et al. Evaluation of treatments for pruritus in epidermolysis bullosa. Pediatr Dermatol. 2015;32:628–634.
    1. Roh YS, Sutaria N, Biles NF, Kwatra SG. Treatment of chronic pruritus with medical Marijuana. JAMA Dermatol. [Internet]. 2021;Online ahead of print.
    1. El Hachem M, Zambruno G, Bourdon-Lanoy E, Ciasulli A, Buisson C, Hadj-Rabia S, et al. Multicentre consensus recommendations for skin care in inherited epidermolysis bullosa. Orphanet J Rare Dis. 2014;9:76.
    1. Maida V, Shi RB, Fazzari FGT, Zomparelli L. Topical cannabis-based medicines—a novel paradigm and treatment for non-uremic calciphylaxis leg ulcers: an open label trial. Int Wound J. 2020;17:1508–1516.
    1. Weigelt MA, Sivamani R, Lev-Tov H. The therapeutic potential of cannabinoids for integumentary wound management. Exp Dermatol. 2021;30:201–211.
    1. Nagarkatti P, Pandey R, Rieder SA, Hegde VL, Nagarkatti M. Cannabinoids as novel anti-inflammatory drugs. Future Med Chem. 2009;1:1333–1349. doi: 10.4155/fmc.09.93.
    1. Solis D, Nazaroff J, Dutt-Singkh Y, Choi S, Barriga M, Bailey-Healy I, et al. 219 Natural history of chronic wounds in patients with recessive dystrophic epidermolysis bullosa. J Invest Dermatol. 2017;137:S37.
    1. Goloff N, Dahl J. Successful opioid de-escalation with dexmedetomidine in a 1 year old with worsening pain and opioid-induced neurotoxicity. Pediatrics. 2018;142:meeting abstract 665.
    1. Davila-Seijo P, Hernández-Martín A, Morcillo-Makow E, De LR, Domínguez E, Romero N, et al. Prioritization of therapy uncertainties in dystrophic epidermolysis bullosa: where should research direct to? An example of priority setting partnership in very rare disorders. Orphanet J Rare Dis. 2013;8:61.
    1. Davila-Seijo P, Hernández-Martín Á, Morcillo-Makow E, Rajan C, García-Doval I. Current dystrophic epidermolysis bullosa research does not match research needs perceived by patients and clinicians. J Am Acad Dermatol. 2014; 1008–11.
    1. Brun J, Chiaverini C, Devos C, Leclerc-Mercier S, Mazereeuw J, Bourrat E, et al. Pain and quality of life evaluation in patients with localized epidermolysis bullosa simplex. Orphanet J Rare Dis. 2017;12:119.
    1. Okusanya BO, Asaolu IO, Ehiri JE, Kimaru LJ, Okechukwu A, Rosales C. Medical cannabis for the reduction of opioid dosage in the treatment of non-cancer chronic pain: a systematic review. Syst Rev. 2020;9:1–8.
    1. Befort K. Interactions of the opioid and cannabinoid systems in reward: Insights from knockout studies. Front Pharmacol. 2015;6:6.
    1. Abrams DI, Couey P, Shade SB, Kelly ME, Benowitz NL. Cannabinoid-opioid interaction in chronic pain. Clin Pharmacol Ther. 2011;90:844–851.
    1. Chen JSC, Yang A, Murrell DF. Prevalence and pathogenesis of osteopenia and osteoporosis in epidermolysis bullosa: an evidence-based review. Exp Dermatol. 2019;28:1122–1130.
    1. Hubbard LD, Mayre-Chilton K. Retrospective longitudinal study of osteoporosis in adults with recessive dystrophic epidermolysis bullosa. Clin Case Reports. 2019;7:58–63.
    1. Martinez AE, Mellerio JE. Osteopenia and osteoporosis in epidermolysis bullosa. Dermatol Clin. 2010;28:353–355.
    1. Milando R, Friedman A. Cannabinoids: potential role in inflammatory and neoplastic skin diseases. Am J Clin Dermatol. 2019;20:167–180.
    1. Blake A, Wan BA, Malek L, DeAngelis C, Diaz P, Lao N, et al. A selective review of medical cannabis in cancer pain management. Ann Palliat Med. 2017;6:S215–S222.
    1. Martin K, Geuens S, Asche JK, Bodan R, Browne F, Downe A, et al. Psychosocial recommendations for the care of children and adults with epidermolysis bullosa and their family: evidence based guidelines. Orphanet J Rare Dis. 2019;14:133.
    1. Prestifilippo JP, Fernández-Solari J, De La Cal C, Iribarne M, Suburo AM, Rettori V, et al. Inhibition of salivary secretion by activation of cannabinoid receptors. Exp Biol Med. 2006;231:1421–1429.
    1. Fine JD, Johnson LB, Weiner M, Stein A, Cash S, Deleoz J, et al. Eye involvement in inherited epidermolysis bullosa: experience of the national epidermolysis bullosa registry. Am J Ophthalmol. 2004;138:254–262.
    1. Fitzcharles MA, Baerwald C, Ablin J, Häuser W. Efficacy, tolerability and safety of cannabinoids in chronic pain associated with rheumatic diseases (fibromyalgia syndrome, back pain, osteoarthritis, rheumatoid arthritis): a systematic review of randomized controlled trials. Schmerz. 2016;30:47–61.
    1. Lopez-Quintero C, de Cobos JP, Hasin DS, Okuda M, Wang S, Grant BF, et al. Probability and predictors of transition from first use to dependence on nicotine, alcohol, cannabis, and cocaine: Results of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) Drug Alcohol Depend. 2011;115:120–130.
    1. Zehra A, Burns J, Liu CK, Manza P, Wiers CE, Volkow ND, et al. Cannabis addiction and the brain: a review. J Neuroimmune Pharmacol. 2018;13:438–452.
    1. Hazekamp A. The trouble with CBD oil. Med Cannabis Cannabinoids. 2018;1:65–72.
    1. Pavlovic R, Nenna G, Calvi L, Panseri S, Borgonovo G, Giupponi L, et al. Quality traits of “cannabidiol oils”: Cannabinoids content, terpene fingerprint and oxidation stability of european commercially available preparations. Molecules. 2018;23:1230.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir