Combined Tetrahydrocannabinol and Cannabidiol to Treat Pain in Epidermolysis Bullosa

A Report of Three Cases

N.H.B. Schräder; J.C. Duipmans; B. Molenbuur; A.P. Wolff; M.F. Jonkman

Disclosures

The British Journal of Dermatology. 2019;180(4):922-924. 

In This Article

Case Report

Case 1

A 64-year-old woman (EB012-01) diagnosed with junctional EB generalized intermediate (JEB-gen intermed) suffered from refractory pain for over 20 years, reporting 9/10 for pain on the visual analogue scale (VAS). Her daily pain therapy included 3 × 1000 mg paracetamol, 2 × 10 mg oxycodone extended release (ER), 1 × 10 mg codeine-phosphate, 2 × 25 mg amitriptyline and 1 × 5 mg g−1 topical morphine (applied to the painful right heel). However, this regimen could not provide satisfactory analgesia. Ten years prior, she attempted treatment with an inhaled CBM; however, she experienced only short-lived analgesia (< 45 min), and the presence of euphoria and dizziness. Subsequently an orally administered CBM tea was prescribed with no adequate pain relief.

Sublingual CBM oil (20 mg mL−1 CBD, 13 mg mL−1 THC) was started at 0·5 mg CBD and 0·325 mg THC, 4 × daily and increased stepwise up to 2·5 mg CBD and 1·625 mg THC, 4 × daily. She reported VAS scores ranging between 1/10 and 4/10. At 3 months, she was weaned off oxycodone-ER and at 6 months, oxycodone immediate-release (IR) was used for dressing changes only. During the following 2 years, treatment with topical morphine was replaced with 1 mg CBD and 0·65 mg THC CBM oil, applied daily to her painful heel; she was also weaned off amitriptyline. Notably, she also reported a moderate reduction of pruritus expressed by a lower pruritus frequency and reduced urges to scratch. An increased appetite was the only side-effect reported from the CBM, and she currently maintains that this treatment provides adequate pain relief.

Case 2

A 41-year-old man (EB132-01) diagnosed with JEB-gen intermed was treated for pain, for over 10 years, with 1000 mg paracetamol, 4 × 200 mg ibuprofen, 20 mg oxycodone-IR and 5 mg g−1 topical morphine, daily. He reported a VAS for pain of 9/10 and sought alternative analgesic modalities. He was therefore started on treatment with a sublingual CBM (20 mg mL−1 CBD, 13 mg mL−1 THC). At 1 month he reached a dose of 3 mg CBD and 1·95 mg THC, 4 × daily and reported a VAS for pain of 3/10. He was weaned off oxycodone-IR and topical morphine was stopped. Additionally, after commencing the CBM treatment, he reported a reduction in the frequency and intensity of his pruritus, as well as a reduced urge to scratch. At 6 months, due to an increase of wound pain, supplementary treatment was started with 5 mg oxycodone-IR 3 × daily, subsequently inducing a self-reported distorted sense of time and delayed reaction time. On the grounds of a drug–drug interaction, the CBM was reduced to nocturnal doses only, which alleviated these symptoms and his pain relief was maintained. He stopped CBM treatment 2 months later as his health insurance withdrew reimbursement of the sublingual CBM oil, which he could not afford (€200 per month). He was admitted to hospital after a subsequent exacerbation of skin ulcerations and pain, whereby his clinical team resorted to treatment with prednisolone 15 mg daily for 2 weeks, which provided only moderate analgesia. His pain treatment remains unresolved.

Case 3

A 36-year-old man (EB015-01) diagnosed with recessive dystrophic EB generalized severe (RDEB-gen sev), had a history of complications including chronic pain, pruritus, obstipation, pseudosyndactyly, squamous cell carcinoma (SCC) of his hands, and multiple amputations. His pain treatment consisted of topical morphine, oxycodone-ER, oxycodone-IR, amitriptyline, paracetamol, etoricoxib and locally injected dexamethasone. He experienced sedative side-effects from amitriptyline, delayed wound healing by topical morphine, and obstipation due to oxycodone-ER, oxycodone-IR and etoricoxib. Unable to tolerate these side-effects, he experimented with CBM-flos (the dried flower of the female cannabis plant) by way of combustion and inhalation. During routine clinical follow-up he reported an improvement of pain treated with paracetamol and inhaled CBM-flos and his opioid-induced obstipation resolved.

After 6 months, worsening tumour pain in both hands required supplementary analgesia. As EB pain recommendations indicated the use of strong opioids, which were contraindicated due to his susceptibility to side-effects, a sublingual CBM oil (20 mg mL−1 CBD, 13 mg mL−1THC) was started. At 1 week he reported a 40% reduction in pain intensity. Both the sublingual CBM and intrapulmonary CBM were continued for 2 years. The combination of intrapulmonary and sublingual CBMs surpassed previous pain treatments, and additionally reduced the severity of pruritus and his urge to scratch.

Later, he entered terminal care as a sequela of metastasized cutaneous SCC and persisted to continue both intrapulmonary and sublingual CBM administration, combined with 10 mg amitriptyline and 10 mg prednisolone, daily. He died at 38 years of age.

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