Oral capsules of tetra-hydro-cannabinol (THC), cannabidiol (CBD) and their combination in peripheral neuropathic pain treatment

Kanita Zubcevic; Merete Petersen; Flemming Winther Bach; Aksel Heinesen; Thomas Peter Enggaard; Thomas Peter Almdal; Jakob Vormstrup Holbech; Lene Vase; Troels Stahelin Jensen; Christian Stevns Hansen; Nanna Brix Finnerup; Søren H. Sindrup

doi:10.1002/ejp.2072

Oral capsules of tetra-hydro-cannabinol (THC), cannabidiol (CBD) and their combination in peripheral neuropathic pain treatment

Kanita Zubcevic, Merete Petersen, Flemming Winther Bach, Aksel Heinesen, Thomas Peter Enggaard, Thomas Peter Almdal, Jakob Vormstrup Holbech, Lene Vase, Troels Stahelin Jensen, Christian Stevns Hansen, Nanna Brix Finnerup, Søren H. Sindrup^*

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

Abstract

Background: Cannabinoids are often prescribed for neuropathic pain, but the evidence-based recommendation is ‘weak against’. Objectives: The aim was to examine the effect of two cannabinoids and their combination in peripheral neuropathic pain. Methods: This was a randomized, double-blind, trial with treatment arms for cannabidiol (CBD), tetra-hydro-cannabinol (THC), CBD and THC combination (CBD/THC), and placebo in a 1:1:1:1 ratio and flexible drug doses (CBD 5–50 mg, THC 2.5–25 mg, and CBD/THC 5 mg/2.5 mg–50 mg/25 mg). Treatment periods of 8-week duration were proceeded by 1 week for baseline observations. Patients with painful polyneuropathy, post-herpetic neuralgia and peripheral nerve injury (traumatic or surgical) failing at least one previous evidence-based pharmacological treatment were eligible for inclusion. The primary outcome was the change in weekly average of daily pain measured with a numeric rating scale (NRS). Trail Making Test (TMT) was used as one of the tests of mental functioning. Results: In all, 145 patients were included in the study of which 118 were randomized and 115 included in the intention-to-treat analysis. None of the treatments reduced pain compared to placebo (p = 0.04–0.60). Effect sizes as estimated in week 8 (positive values worse and negative better than placebo) were CBD mean 1.14 NRS points (95% CI 0.11–2.19), THC 0.38 (CI −0.65 to 1.4) and CBD/THC −0.12 (−1.13 to 0.89). Conclusions: CBD, THC and their combination did not relieve peripheral neuropathic pain in patients failing at least one previous evidence-based treatment for neuropathic pain.

Originalsprog	Engelsk
Tidsskrift	European Journal of Pain (United Kingdom)
Vol/bind	27
Nummer	4
Sider (fra-til)	492-506
Antal sider	15
ISSN	1090-3801
DOI	https://doi.org/10.1002/ejp.2072
Status	Udgivet - apr. 2023

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10.1002/ejp.2072Licens: CC BY-NC-ND

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Zubcevic, K., Petersen, M., Bach, F. W., Heinesen, A., Enggaard, T. P., Almdal, T. P., Holbech, J. V., Vase, L., Jensen, T. S., Hansen, C. S., Finnerup, N. B., & Sindrup, S. H. (2023). Oral capsules of tetra-hydro-cannabinol (THC), cannabidiol (CBD) and their combination in peripheral neuropathic pain treatment. European Journal of Pain (United Kingdom), 27(4), 492-506. https://doi.org/10.1002/ejp.2072

@article{ef94d986a6764192833ea9ec8114a9ab,

title = "Oral capsules of tetra-hydro-cannabinol (THC), cannabidiol (CBD) and their combination in peripheral neuropathic pain treatment",

abstract = "Background: Cannabinoids are often prescribed for neuropathic pain, but the evidence-based recommendation is {\textquoteleft}weak against{\textquoteright}. Objectives: The aim was to examine the effect of two cannabinoids and their combination in peripheral neuropathic pain. Methods: This was a randomized, double-blind, trial with treatment arms for cannabidiol (CBD), tetra-hydro-cannabinol (THC), CBD and THC combination (CBD/THC), and placebo in a 1:1:1:1 ratio and flexible drug doses (CBD 5–50 mg, THC 2.5–25 mg, and CBD/THC 5 mg/2.5 mg–50 mg/25 mg). Treatment periods of 8-week duration were proceeded by 1 week for baseline observations. Patients with painful polyneuropathy, post-herpetic neuralgia and peripheral nerve injury (traumatic or surgical) failing at least one previous evidence-based pharmacological treatment were eligible for inclusion. The primary outcome was the change in weekly average of daily pain measured with a numeric rating scale (NRS). Trail Making Test (TMT) was used as one of the tests of mental functioning. Results: In all, 145 patients were included in the study of which 118 were randomized and 115 included in the intention-to-treat analysis. None of the treatments reduced pain compared to placebo (p = 0.04–0.60). Effect sizes as estimated in week 8 (positive values worse and negative better than placebo) were CBD mean 1.14 NRS points (95% CI 0.11–2.19), THC 0.38 (CI −0.65 to 1.4) and CBD/THC −0.12 (−1.13 to 0.89). Conclusions: CBD, THC and their combination did not relieve peripheral neuropathic pain in patients failing at least one previous evidence-based treatment for neuropathic pain.",

author = "Kanita Zubcevic and Merete Petersen and Bach, {Flemming Winther} and Aksel Heinesen and Enggaard, {Thomas Peter} and Almdal, {Thomas Peter} and Holbech, {Jakob Vormstrup} and Lene Vase and Jensen, {Troels Stahelin} and Hansen, {Christian Stevns} and Finnerup, {Nanna Brix} and Sindrup, {S{\o}ren H.}",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC {\textregistered}.",

year = "2023",

month = apr,

doi = "10.1002/ejp.2072",

language = "English",

volume = "27",

pages = "492--506",

journal = "European Journal of Pain (United Kingdom)",

issn = "1090-3801",

publisher = "JohnWiley & Sons Ltd.",

number = "4",

}

Zubcevic, K, Petersen, M, Bach, FW, Heinesen, A, Enggaard, TP, Almdal, TP, Holbech, JV, Vase, L, Jensen, TS, Hansen, CS, Finnerup, NB & Sindrup, SH 2023, 'Oral capsules of tetra-hydro-cannabinol (THC), cannabidiol (CBD) and their combination in peripheral neuropathic pain treatment', European Journal of Pain (United Kingdom), bind 27, nr. 4, s. 492-506. https://doi.org/10.1002/ejp.2072

Oral capsules of tetra-hydro-cannabinol (THC), cannabidiol (CBD) and their combination in peripheral neuropathic pain treatment. / Zubcevic, Kanita; Petersen, Merete; Bach, Flemming Winther et al.
I: European Journal of Pain (United Kingdom), Bind 27, Nr. 4, 04.2023, s. 492-506.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - Oral capsules of tetra-hydro-cannabinol (THC), cannabidiol (CBD) and their combination in peripheral neuropathic pain treatment

AU - Zubcevic, Kanita

AU - Petersen, Merete

AU - Bach, Flemming Winther

AU - Heinesen, Aksel

AU - Enggaard, Thomas Peter

AU - Almdal, Thomas Peter

AU - Holbech, Jakob Vormstrup

AU - Vase, Lene

AU - Jensen, Troels Stahelin

AU - Hansen, Christian Stevns

AU - Finnerup, Nanna Brix

AU - Sindrup, Søren H.

PY - 2023/4

Y1 - 2023/4

N2 - Background: Cannabinoids are often prescribed for neuropathic pain, but the evidence-based recommendation is ‘weak against’. Objectives: The aim was to examine the effect of two cannabinoids and their combination in peripheral neuropathic pain. Methods: This was a randomized, double-blind, trial with treatment arms for cannabidiol (CBD), tetra-hydro-cannabinol (THC), CBD and THC combination (CBD/THC), and placebo in a 1:1:1:1 ratio and flexible drug doses (CBD 5–50 mg, THC 2.5–25 mg, and CBD/THC 5 mg/2.5 mg–50 mg/25 mg). Treatment periods of 8-week duration were proceeded by 1 week for baseline observations. Patients with painful polyneuropathy, post-herpetic neuralgia and peripheral nerve injury (traumatic or surgical) failing at least one previous evidence-based pharmacological treatment were eligible for inclusion. The primary outcome was the change in weekly average of daily pain measured with a numeric rating scale (NRS). Trail Making Test (TMT) was used as one of the tests of mental functioning. Results: In all, 145 patients were included in the study of which 118 were randomized and 115 included in the intention-to-treat analysis. None of the treatments reduced pain compared to placebo (p = 0.04–0.60). Effect sizes as estimated in week 8 (positive values worse and negative better than placebo) were CBD mean 1.14 NRS points (95% CI 0.11–2.19), THC 0.38 (CI −0.65 to 1.4) and CBD/THC −0.12 (−1.13 to 0.89). Conclusions: CBD, THC and their combination did not relieve peripheral neuropathic pain in patients failing at least one previous evidence-based treatment for neuropathic pain.

AB - Background: Cannabinoids are often prescribed for neuropathic pain, but the evidence-based recommendation is ‘weak against’. Objectives: The aim was to examine the effect of two cannabinoids and their combination in peripheral neuropathic pain. Methods: This was a randomized, double-blind, trial with treatment arms for cannabidiol (CBD), tetra-hydro-cannabinol (THC), CBD and THC combination (CBD/THC), and placebo in a 1:1:1:1 ratio and flexible drug doses (CBD 5–50 mg, THC 2.5–25 mg, and CBD/THC 5 mg/2.5 mg–50 mg/25 mg). Treatment periods of 8-week duration were proceeded by 1 week for baseline observations. Patients with painful polyneuropathy, post-herpetic neuralgia and peripheral nerve injury (traumatic or surgical) failing at least one previous evidence-based pharmacological treatment were eligible for inclusion. The primary outcome was the change in weekly average of daily pain measured with a numeric rating scale (NRS). Trail Making Test (TMT) was used as one of the tests of mental functioning. Results: In all, 145 patients were included in the study of which 118 were randomized and 115 included in the intention-to-treat analysis. None of the treatments reduced pain compared to placebo (p = 0.04–0.60). Effect sizes as estimated in week 8 (positive values worse and negative better than placebo) were CBD mean 1.14 NRS points (95% CI 0.11–2.19), THC 0.38 (CI −0.65 to 1.4) and CBD/THC −0.12 (−1.13 to 0.89). Conclusions: CBD, THC and their combination did not relieve peripheral neuropathic pain in patients failing at least one previous evidence-based treatment for neuropathic pain.

UR - http://www.scopus.com/inward/record.url?scp=85146346915&partnerID=8YFLogxK

U2 - 10.1002/ejp.2072

DO - 10.1002/ejp.2072

M3 - Journal article

C2 - 36571471

AN - SCOPUS:85146346915

SN - 1090-3801

VL - 27

SP - 492

EP - 506

JO - European Journal of Pain (United Kingdom)

JF - European Journal of Pain (United Kingdom)

IS - 4

ER -

Oral capsules of tetra-hydro-cannabinol (THC), cannabidiol (CBD) and their combination in peripheral neuropathic pain treatment

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